key: cord- -nqc pduk authors: dahal, sushma; mizumoto, kenji; bolin, bob; viboud, cécile; chowell, gerardo title: natality decline and spatial variation in excess death rates during the – influenza pandemic in arizona, united states date: - - journal: am j epidemiol doi: . /aje/kwy sha: doc_id: cord_uid: nqc pduk a large body of epidemiologic research has concentrated on the influenza pandemic, but more work is needed to understand spatial variation in pandemic mortality and its effects on natality. we collected and analyzed , death records from arizona for – and , birth records from maricopa county for – . we estimated the number of excess deaths and births before, during, and after the pandemic period, and we found a significant decline in the number of births occurring – months after peak pandemic mortality. moreover, excess mortality rates were highest in northern arizona counties, where native americans were historically concentrated, suggesting a link between ethnic and/or sociodemographic factors and risk of pandemic-related death. the relationship between birth patterns and pandemic mortality risk should be further studied at different spatial scales and in different ethnic groups. initially submitted april , ; accepted for publication july , . a large body of epidemiologic research has concentrated on the influenza pandemic, but more work is needed to understand spatial variation in pandemic mortality and its effects on natality. we collected and analyzed , death records from arizona for - and , birth records from maricopa county for [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . we estimated the number of excess deaths and births before, during, and after the pandemic period, and we found a significant decline in the number of births occurring - months after peak pandemic mortality. moreover, excess mortality rates were highest in northern arizona counties, where native americans were historically concentrated, suggesting a link between ethnic and/or sociodemographic factors and risk of pandemic-related death. the relationship between birth patterns and pandemic mortality risk should be further studied at different spatial scales and in different ethnic groups. - ; arizona; birth; excess mortality; influenza pandemic; maricopa county; natality abbreviation: p&i, pneumonia and influenza. the spanish flu of - was called "the mother of all pandemics" due to its devastating global mortality impact, estimated at million deaths, or %- % of the world population at the time ( , ) . the case fatality rate of this pandemic is estimated at approximately . %-several-fold higher than that of typical seasonal influenza epidemics ( ) . another salient feature of this pandemic is the atypical peak of mortality among young adults ( ) . multiple pandemic waves occurred during - , and areas in the northern hemisphere were more likely to experience a "herald wave" in early ( , ( ) ( ) ( ) . while our understanding of the mortality impact of this pandemic has improved in recent years, much less is known about the pandemic impact on natality. this is important given that influenza vaccination during pregnancy is currently being promoted. further, more work is needed to disentangle the local circumstances that shaped pandemic mortality rates across different populations ( ) . a lethal influenza pandemic may influence birth rate patterns ( - ) because pregnancy leads to physiological, hormonal, and immunologic changes that are known to heighten the risk of illness and death associated with influenza infection ( , ) . for instance, a cross-sectional study of pregnant women hospitalized during the influenza pandemic in maryland, in the united states, found that about half of the pregnant women developed pneumonia, of whom % succumbed, with a case fatality rate of % ( ) . also, a influenza pandemic study from minnesota documented that about % of deaths among women of reproductive age occurred among pregnant women ( ) . furthermore, recent studies have suggested a link between influenza infection in early pregnancy and an increased risk of fetal death ( ) . accordingly, us and scandinavian populations experienced a %- % drop in natality rate - months after the pandemic, suggesting an increased risk of miscarriage in the first trimester ( ). a similar association was reported during the pandemic ( , ) . however, prior studies of the pandemic have focused on highly aggregated national birth statistics, rather than detailed information available from individual birth certificates; further, no study has explored birth patterns in particularly hard hit and low-income populations. increasing epidemiologic evidence indicates that the pandemic was far from a "democratic disease." indeed, differences in socioeconomic conditions or residual immunity acquired from prior exposure to related influenza viruses have been hypothesized to drive mortality differences ( ) ( ) ( ) ( ) . a seminal study proposed that national income differences could in part explain an approximately -fold variation in pandemic mortality rates across countries ( ) . further work is needed to better understand the spatial heterogeneity in pandemic mortality impact at finer spatial scales. in this paper we harness information from , individual death certificates to analyze differences in pandemic-related excess mortality rates across counties of arizona. prior work has shown that the - pandemic killed about . % of the population in arizona ( ) , which is one of the highest pandemic mortality rates reported in the united states ( , ) . we also analyzed , individual birth certificates to quantify the impact of the - influenza pandemic on natality fluctuations in maricopa county, the most populous county in arizona state. arizona became a us state in , a few years prior to the influenza pandemic, and did not become a us vital registration state until ( ); therefore, alternative data sources have to be queried to explore mortality and natality during the pandemic period. maricopa county is the largest county in this state. in , maricopa county represented . % of the arizona population ( ) . between and the population of maricopa county increased from , to , (see figure for a county map of arizona). arizona is unique because of its large population of native americans and its historical concentration of tuberculosis sanatoriums, due to a dry and arid climate ( ) . arizona is one of states with more than , native americans ( ) . wellknown native american tribes in arizona include apache, hopi, maricopa, navajo, papago, pima, yavapai, and yuma. more than native american reservations have covered one-fourth of the state's surface area. of these, the navajo and the tohono o'odham are the largest reservations in the united states ( ) . the navajo reservation include areas in the apache, navajo, and coconino counties, whereas the tohono o'odham reservation lies in central pima and includes southwestern pinal and southeastern maricopa counties. overall, the northeastern part of arizona has a higher residence of native americans ( , ) . the state of arizona had one of the highest tuberculosis death rates ( ) , the highest infant mortality rate, and, in its capital city (phoenix), some of the "worst slums" in the country ( , ) . during - , many minority households relied on irrigation canals for drinking water and for bathing ( ) . infant mortality rates among black persons, hispanics, and native americans were - times higher than among white persons ( , ) . the arizona genealogy database (http://genealogy.az.gov/) is a freely available online resource of all birth records generated during the years - and all death certificates recorded during the years - for the state of arizona. we manually retrieved a total of , birth records from january to december for maricopa county, arizona, from this database. for each birth record, we retrieved the date of birth and compiled monthly birth time series, as in a previous study (see chandra and yu ( ) ). similarly, to assess the timing and mortality impact of the - influenza pandemic, we manually retrieved a total of , individual death records from january to december for arizona. for each death record, we compiled date of death, county of death, cause of death, and age at death. we then created weekly and monthly time series of deaths attributed to pneumonia and influenza (p&i) and to all causes, which are traditionally used to monitor the impact of influenza. we also derived the overall and age-specific population estimates of the arizona counties from to by linear interpolation of estimates available for decennial censuses in , , and ( , ) . two counties, greenlee and lapaz, were excluded from analysis due to lack of population data. pandemic period and excess deaths. to define the pandemic period, we determined the most likely period of pandemic influenza activity from the time series of weekly p&i death rates, the most specific indicator of influenza. we first estimated baseline mortality levels by fitting cyclical serfling regression models to p&i deaths in noninfluenza weeks as in previous studies ( , ) . periods of pandemic influenza circulation corresponded to those weeks in - where the observed total p&i mortality rate exceeded the upper % confidence limit of the baseline level ( , , ) . these pandemic periods were used to assess mortality and natality estimation for different counties, sexes, age groups, and causes of death ( ) . for each county, we estimated excess mortality rates for total population as well as children (< years) during the main pandemic wave (october to december) of . we also classified our study period into categories-before the pandemic, during the pandemic, and after the pandemic-based on observed p&i mortality patterns (we return to this later). we added months to the pandemic period to account for the duration of pregnancy, in line with the expected delay between pandemic activity and birth outcomes ( ). estimation of seasonally and trend-adjusted excess births and deaths. after removing the seasonality and long-term trend components using moving averages, the residual components of the birth and death time series were extracted to capture the corresponding birth and death counts associated with the pandemic. we then estimated the cross-correlation coefficients of p&i deaths and births to identify temporal associations between pandemic influenza and natality at different lags, as in previous studies ( , , ) . we estimated these coefficients to identify temporal associations between monthly deaths and births during the pandemic period. the following definition of cross-correlation coefficient was used ( ): table ) . seasonally and trend-adjusted excess births and deaths, maricopa county figure displays the time series of seasonally and trendadjusted excess births and deaths for maricopa county, arizona, between and , stratified by sex. a small peak in births was observed immediately after pandemic mortality peaked in males and females, while deep troughs in births occurred about months after the peak in pandemic mortality. to formally test the time scale of the association between pandemic activity and births, we calculated the cross-correlation between excess births and sex-specific p&i deaths in individuals aged - years. we found a significant negative association between influenza deaths in males at time t and births - months later, and - months later for female deaths (figure ) . a natality dip of approximately % was observed in july ; dips of this size were not seen at any other time point during - . the total excess mortality rates according to mortality outcomes, sex, and pandemic waves are shown in table . for the total pandemic period, total p&i excess death rates per , population were . for males and . for females. for both males and females, the highest p&i and all-cause death rates were recorded during the main pandemic wave in fall . in relative terms, during the pandemic period the observed p&i mortality rates were about times and times above the baseline for males and females, respectively ( table ). the mortality rate ratio of male to female deaths was . . we also estimated county-specific excess mortality rates for all ages and for children aged < years for counties in arizona that provided appropriately stratified data (table ) . we found that northern counties had higher excess p&i and all-cause mortality overall and for children aged < years. northern counties apache, coconino, mohave, and navajo had significantly higher excess p&i mortality for children aged < years (mean rank = . ) compared with other counties (all other counties categorized as "others"; mean rank = . ) (mann-whitney u test, p < . ). however, there was no statistically significant mortality in this study, we investigated the impact of the influenza pandemic on natality fluctuations as well as on county-level mortality in the state of arizona. we expected a natality decline in the months following peak pandemic activity, as observed in a previous study set in the united states ( ) . although the time series of excess/deficit births fluctuated over time in maricopa county, arizona, we found a statistically significant dip of approximately % in births - months after peak pandemic mortality. while smaller natality drops were seen in earlier years, a drop of this magnitude was unique to the period after the pandemic, suggesting an effect of the pandemic on natality. we also found higher pandemic-related death rates in northern arizona counties, where native americans were historically concentrated. indigenous populations have been disproportionately affected during past influenza pandemics ( , ) . for example, in new zealand, the death rate among the maori was at least . times higher than the corresponding death rate for the rest of the population ( ) . similarly, the mortality ratios for indigenous populations relative to european populations in the continental united states and canada were found to be . and . during the pandemic, respectively ( ) . likewise, our results suggest that northern counties in arizona with high native american population density (e.g., apache, coconino, and navajo) experienced higher excess pandemic death rates compared with other counties in the state. anecdotal evidence recorded in the arizona bulletin of indicated that northern cities with a significant proportion of native americans ( , ) (winslow, holbrook, and flagstaff) required assistance in confronting the pandemic ( ) . we note that quantitative data on the proportion of native americans by county was not available; further work should focus on exploring the association between influenza death rates and ethnicity in a more quantitative manner. we also found high excess mortality rates in the southern mining counties of cochise and yuma. cochise county was one of the counties that had operating copper mines and smelters, and yuma county had one of the oldest silver and lead mines in the state. mining activity could be a proxy for lower socioeconomic conditions. we cannot rule out additional within-county variability in socioeconomic factors, including, nutritional status, overall baseline health, and access to hospital care. for instance, some of the lowest pandemic mortality rates were observed in maricopa county, within which south phoenix was a rather stigmatized and degraded minority district ( ) . the study of within-county variation in pandemic mortality calls for more spatially resolved data sets. it is important to highlight that at the time of the pandemic, the state of arizona was characterized by significant contamination issues, lack of potable water, crowding, substandard housing, and a lack of health care for minorities ( , ) . on one hand, the state was advertised as a privileged location for health seekers due to its dry climate and pure air, but on the other hand many lived in ill-ventilated buildings and were at high risk of contracting infectious diseases ( ) . many minority families in phoenix were found to be eating and sleeping in a single room, and children were found living in the same room with persons afflicted with tuberculosis ( ) . arizona had the highest infant mortality rate of all us states, particularly among minorities ( , ) . in this context, perhaps it is not surprising that the influenza pandemic disproportionately affected lower socioeconomic groups, including native american populations geographically concentrated in northern counties. our study is subject to several limitations. first, due to lack of laboratory confirmation of influenza infection in the era before virology, our excess mortality approach would not have been able to distinguish elevation in mortality rates associated with noninfluenza respiratory causes and coinciding with the pandemic period. second, we did not model other factors associated with world war i that could have influenced fertility rates ( ) . third, a more refined analysis at the neighborhood level could have revealed more clearly the association of specific risk factors, including tuberculosis, income, occupation, and ethnicity ( ) . in summary, we report a significant dip in excess births about - months following the peak in excess pandemic mortality. this period surpasses the expected months of pregnancy and may be due to delays in reporting births or a stronger impact of influenza on pregnancy in the later part of the fall pandemic wave. our results also show significant county-level variation in excess mortality rates during the influenza pandemic. for instance, we found that arizona counties with relatively higher native american population located in northern arizona were disproportionately affected by the pandemic. future research is needed to disentangle spatial variation in excess mortality and birth rates at finer spatial resolutions (e.g., neighborhood) in relation to demographic and socioeconomic indicators. s.d. acknowledges support from the fulbright program. influenza: the mother of all pandemics updating the accounts: global mortality of the - "spanish" influenza pandemic the signature features of influenza pandemics-implications for policy the influenza pandemic: insights for the st century a review of herald pandemic waves in : importance for contemporary pandemic response strategies regional patterns of mortality during the influenza pandemic in newfoundland estimation of potential global pandemic influenza mortality on the basis of vital registry data from the - pandemic: a quantitative analysis can the spanish influenza pandemic of explain the baby boom of in neutral norway? natality decline and miscarriages associated with the influenza pandemic: the scandinavian and united states experiences fertility decline and the influenza pandemic in taiwan pandemic influenza and pregnant women effects of influenza on pregnant women and infants influenza occurring in pregnant women: a statistical study of thirteen hundred and fifty cases deaths from asian influenza associated with pregnancy seasonal influenza a (h n ) infection in early pregnancy and second trimester fetal demise the effect of asian influenza on the outcome of pregnancy spatial-temporal excess mortality patterns of the - influenza pandemic in spain the influenza epidemic's effects on sex differentials in mortality in the united states excess mortality patterns during - influenza pandemic in the state of arizona, usa pandemic morbidity: the first wave hits the poor, the second wave hits the rich. influenza other respir viruses age-and sex-specific mortality associated with the - influenza pandemic in kentucky epidemiological evidence of an early wave of the influenza pandemic in new york city vital statistics rates in the united states - population of states and counties of the united states tuberculosis and urban growth: class, race and disease in early phoenix the growing american indian population, - : beyond demography top indian reservations arizona tribal and federal lands arizona state board of health the geography of despair: environmental racism and the making of south people's padre: an autobiography a survey of public health in arizona united states census bureau. census of population and housing death patterns during the influenza pandemic in chile time series analysis and forecasting by example on time series analysis of public health and biomedical data geography may explain adult mortality from the - influenza pandemic differential mortality rates by ethnicity in influenza pandemics over a century fertility fluctuations in times of war and pandemic influenza disparities in influenza mortality and transmission related to sociodemographic factors within chicago in the pandemic of this work does not represent the views of the us government or the national institutes of health.conflict of interest: none declared. key: cord- -hxjxczyr authors: rello, jordi; pop-vicas, aurora title: clinical review: primary influenza viral pneumonia date: - - journal: crit care doi: . /cc sha: doc_id: cord_uid: hxjxczyr primary influenza pneumonia has a high mortality rate during pandemics, not only in immunocompromised individuals and patients with underlying comorbid conditions, but also in young healthy adults. clinicians should maintain a high index of suspicion for this diagnosis in patients presenting with influenza-like symptoms that progress quickly ( to days) to respiratory distress and extensive pulmonary involvement. the sensitivity of rapid diagnostic techniques in identifying infections with the pandemic h n v influenza strain is currently suboptimal. the most reliable real-time reverse transcriptase-polymerase chain reaction molecular testing is available in limited clinical settings. despite months of pandemic circulation, most novel h n v pandemic strains remain susceptible to oseltamivir. ensuring an appropriate oxygenation and ventilation strategy, as well as prompt initiation of antiviral therapy, is essential in management. as the novel swine-origin influenza a (h n )v global pandemic is under way, the medical community has already experienced an increase in hospitalizations from influenzarelated complications in many geographic regions. primary viral pneumonia is recognized as the most severe pulmonary manifestation of influenza. while uncommon during seasonal epidemics, the syndrome has been well documented during the h n pandemic of - and is thought to be responsible for much of the mortality associated with the young healthy adult population during the h n pandemic [ ] . this paper reviews the clinical aspects of influenza and primary influenza pneumonia that may be of most interest to the practicing physician in the pandemic environment. seasonal influenza epidemics occur each year as a result of minor changes in the antigenic characteristics of the hemagglutinin and neuraminidase glycoproteins of the influenza viruses (antigenic drift) [ ] . the morbidity and mortality associated with seasonal influenza outbreaks are significant, especially in older patients, who incur more than % of the influenza-related mortality each year [ ] . factors contributing to their increased vulnerability include a decline in cellmediated and humoral immune responses, a reduction in lung compliance and respiratory muscle strength, a diminished cough reflex associated with normal aging, the frequent presence of multiple comorbid conditions, nutritional deficiencies, and in the case of residents of long-term care facilities, greater exposure risk due to close living quarters and shared caregivers [ , ] . influenza pandemics occur less frequently, as a result of major changes in the surface glycoproteins of the virus (antigenic shift). the emerging novel influenza strain then easily spreads into an immunologically susceptible population. consequently, pandemics are characterized by a shift in mortality toward the otherwise young and healthy to -year-old adults, with relative sparing of older patients, as evidenced by epidemiological analyses of the influenza a pandemic [ ] . this is likely due to the persistence of immunological memory in older patients after previous exposures to h -type viruses similar to the pandemic strain [ , ] . the virulence of the pandemic strain may also play a role, as demonstrated by recent experiments with the highly fatal influenza strain [ ] . preliminary data from the h n pandemic suggest a similar shift in age-related mortality. an analysis of cases of pandemic h n influenza a in the us, for example, has revealed that % of the cases occurred in patients not older than years of age and that only % occurred in patients older than years [ ] . in the cohorts recently tested, the modest extent of immunological memory in older patients was confirmed by the presence of serum crossreactive antibodies to the pandemic h n influenza a strain found in % of the adults older than years of age versus % to % of the adults to years of age and none of the children [ ] . influenza attack rates during seasonal epidemics vary between % and % but can be much higher during pandemics. for example, an analysis of the pandemic h n influenza a outbreak in la gloria, veracruz, found clinical attack rates of % in adults older than years and % in children younger than years of age [ ] . however, these rates may be different in geographic areas of low population density. groups at high risk for severe disease and complications secondary to pandemic h n influenza a include patients with underlying pulmonary (asthma) and cardiac comorbid conditions, some immunosuppressive states, pregnancy and post-partum states, diabetes mellitus, obesity [ , ] , and, in children, prior neurological disabilities [ ] . severe primary h n influenza pneumonia can also affect young adults without any underlying comorbidities [ ] . person-to-person transmission occurs primarily through droplet spread via small particle-sized aerosols generated by coughing, sneezing, or talking [ ] . airborne transmission should be considered in those patients exposed to aerosolgenerating techniques, such as intubation or mechanical ventilation. the incubation period is usually to hours. in the absence of antiviral treatment, viral shedding starts within hours before the onset of symptoms and continues for approximately days in healthy adults [ ] . viral shedding can last longer in children, patients with extensive comorbidities, older patients, patients who undergo mechanical ventilation, and immunocompromised hosts [ ] [ ] [ ] . the infectious period can be significantly reduced by the use of antiviral medications within the first to hours of illness [ ] . after inhalation, the virus is deposited onto the respiratory tract epithelium, where it attaches to ciliated columnar epithelial cells via its surface hemagglutinin. local host defenses, such as mucociliary clearance, or secretion of specific secretory iga antibodies can remove some of the virus particles. however, if mucociliary clearance is impaired (as in smokers [ ] or older patients [ ] ) or secretory antiinfluenza iga antibodies are absent (as in no antecedent exposure to the virus), infection continues unabated [ ] . respiratory epithelial cells are invaded, and viral replication occurs. newer viruses then infect larger numbers of epithelial cells, shut off the synthesis of critical proteins, and ultimately lead to host cell death [ ] . in patients with uncomplicated influenza, bronchoscopy typically reveals diffuse inflammation and edema of the larynx, trachea, and bronchi, and biopsy may show cellular infiltration with lymphocytes and histocytes and desquamation of the ciliated columnar epithelium [ ] . in patients with severe influenza infections that progress to primary viral pneumonia, the involvement of the respiratory tree is extensive, with necrotizing tracheobronchitis, ulceration and sloughing of the bronchial mucosa [ ] , hyperemic alveolar capillaries with intra-alveolar hemorrhage, infiltration of alveolar spaces with fluid, fibrin, and cellular exudates, and lining of the alveoli with acellular hyaline membranes [ ] . autopsies from patients with primary influenza pneumonia confirmed bilateral severe hemorrhagic pneumonitis with interstitial inflammation, diffuse alveolar damage, and heavy viral loads observed in the periphery of the lungs. the clinical features of uncomplicated influenza are virtually indistinguishable from those of other respiratory viral infections. influenza is classically characterized by an abrupt onset of headache, high-grade fever, chills, dry cough, pharyngeal irritation, myalgias, malaise, and anorexia. the fever lasts an average of days (range of to days). the cough, initially nonproductive and nonpurulent, may persist for weeks. bronchial hyper-reactivity and small-airway dysfunction are often present in influenza virus infection. in the presence of asthma or structural lung disease, wheezing may be a prominent manifestation [ ] . vomiting and diarrhea, while rare in seasonal influenza, have been frequently reported in infections with the pandemic influenza a h n v strain [ ] , particularly in children. the clinical presentation of influenza in the immunocompromised host may be more subtle and manifest only as coryza; similarly, the classic fever symptom may be absent in the older patient, who may present only with lethargy, confusion, anorexia, and cough [ ] . influenza pneumonia and respiratory complications in patients with th defects, such as hiv infection, are uncommon. pneumonia and the acute respiratory distress syndrome (ards) account for the majority of severe morbidity and mortality that accompany pandemic influenza infection [ ] . pneumonia may occur as a continuum of the acute influenza syndrome when caused by the virus alone (primary pneumonia) or as a mixed viral and bacterial infection after a delay of a few days (secondary pneumonia) [ ] . identifying patients who are more likely to develop severe complications from influenza pneumonia requires a high clinical vigilance. commonly used pneumonia severity assessment tools, such as the pneumonia severity index [ ] or curb [ ] , are not useful in deciding which patients to hospitalize in the context of primary influenza pneumonia since these tools have not been developed and validated during a pandemic scenario. thus, careful triage in the emergency department and early identification of young patients with decreased oxygen saturation, respiratory rate above , concomitant diarrhea, or hypotension are crucial. elevated lactate dehydrogenase, creatine phosphokinase, and creatinine at hospital admission may also serve as prognostic indicators of severe disease [ ] . c-reactive protein and procalcitonin are increased during this acute lung injury stage of early fibroproliferation. the most ominous cases are those infections that progress rapidly to ards and multilobar alveolar opacification. these patients usually present with gradually increasing dyspnea and severe hypoxemia after an antecedent of to days of typical influenza symptoms [ ] . the cough is usually productive of thin, often bloody, sputum with few cells. hypoxemia increases progressively to the point of respiratory failure requiring intubation and mechanical ventilation, often after only one day of hospitalization [ ] . the radiological appearance of primary influenza pneumonia can be difficult to distinguish on chest x-ray from pulmonary edema, given the presence of perihiliar congestion and hazy opacification, at least in the lower lobes (figure a,b) . pleural effusions may also be present. computed tomography scans ( figure ) can add further diagnostic insight and may be useful to differentiate primary viral pneumonia from bronchiolitis and interstitial pneumonias, which occur frequently in children and young adults but have a benign outcome. concomitant myopericarditis should be excluded by echocardiography. concurrent pulmonary emboli, as suggested by early case reports from hospitalized patients with pandemic influenza a h n v in the us [ ] , may further contribute to clinical deterioration in some patients. however, the occurrence of concomitant pulmonary emboli has not been reproduced in other geographic regions so far. bacterial co-infection, though uncommonly reported in the early stages of the h n pandemic, may be more prevalent than initially thought. a recent analysis of lung specimens from fatal cases of pandemic h n v infection found a prevalence of concurrent bacterial pneumonia in % of these patients [ ] . the most common coinfecting bacterial pathogens were pneumococcus, staphylococcus aureus, and streptococcus pyogenes, with a median duration of illness of days [ ] . the real-time reverse transcriptase-polymerase chain reaction (rrt-pcr) swine flu panel for detection of pandemic h n influenza, developed by the centers for disease control and prevention (atlanta, ga, usa) and distributed to many laboratories in us and worldwide, is a reliable and timely method of diagnosing the pandemic strain [ , ] . the viral culture, while the gold standard in influenza diagnostics, takes several days before the results are known [ ] . the direct fluorescent antigen influenza test was recently reported to have a sensitivity of % compared with the rrt-pcr [ ] , but the test requires considerable technical expertise in addition to a fluorescent microscope. the commonly used point-of-care rapid influenza tests provide results in less than hour but are of only modest sensitivity for seasonal influenza viruses ( %) [ ] and unacceptably insensitive for the detection of pandemic h n influenza [ , ] . thus, for the majority of clinicians practicing during the - influenza pandemic, the access to a reliable and timely diagnostic modality may still be limited. as such, it is chest x-rays of a patient with primary h n (swine-origin influenza a) influenza pneumonia on day (a) and day (b) of hospitalization. reassuring to know that the patients presenting during influenza epidemics with both cough and fever within the first hours of symptom onset are very likely to have actual influenza ( % positive predictive value) [ ] . the majority of patients with primary influenza pneumonia require ventilatory support. mortality is high but can be decreased with an optimal protective ventilatory strategy (tidal volume of not more than ml per kilogram of predicted body weight, with a plateau airway pressure goal of not more than cm h o), as shown in acute respiratory distress syndrome network clinical trials; this strategy is therefore recommended in acute lung injury [ , ] . maintaining an adequate fluid balance is also important for survival in acute lung injury. the hemodynamic status should be optimized by appropriate repletion of intravascular volume deficits during the early systemic inflammatory stage [ ] . once acute lung injury has become established, a conservative fluid management protocol, which was associated with beneficial effects in clinical trials, should be considered [ , ] . in severe refractory cases of primary influenza pneumonia, some patients require venovenous extracorporeal membrane oxygenation support and continuous renal replacement for acute renal failure. antiviral treatment should be initiated as soon as possible, particularly in patients at high risk of complications. the majority of treatment benefits are derived when antivirals are initiated within the first hours from onset of symptoms. unfortunately, most patients with primary viral pneumonia receive oseltamivir after to days of influenza onset [ ] . however, the experience with seasonal influenza suggests that a reduction in mortality for hospitalized patients has been documented even when oseltamivir was initiated after the first hours following illness onset [ ] . thus, being out of the ideal therapeutic window should not be a reason to withhold antiviral treatment at any stage of active disease. both neuraminidase inhibitors (oseltamivir and zanamivir) are active against the novel h n v pandemic influenza a strain. the recommended adult dose for oseltamivir, considered the first-line therapy for h n influenza infection, is mg orally twice a day for a total of days [ ] . dose adjustment may be required in the presence of reduced creatinine clearance, but the dosage should be maintained for patients undergoing continuous venovenous hemodialysis. a recent world health organization treatment guideline for pharmacological management of pandemic h n v influenza a recommends the consideration of higher doses of oseltamivir ( mg twice a day) and longer duration of treatment for patients with severe influenza pneumonia or clinical deterioration [ ] . since hospitalized patients can shed influenza virus for prolonged periods of time, extending antiviral treatment beyond the first days of treatment in cases of persistent influenza symptoms may be necessary. however, clear guidelines for these circumstances have not been established, and clinical trials examining the appropriate treatment dose and duration for severe h n influenza in various patient populations are acutely needed. development of oseltamivir resistance in novel h n influenza, though still exceedingly rare, has been reported from several countries [ ] . it should be suspected in patients who remain symptomatic or have evidence of viral shedding despite a full treatment course of oseltamivir. immunosuppression and prior exposure to oseltamivir, such as receipt of prolonged post-exposure prophylaxis, increase the risk for oseltamivir resistance [ ] . zanamivir remains an effective therapeutic option for these cases. zanamavir is also indicated in the rare circumstance when an oral route for oseltamivir administration is not available for critically ill patients in the intensive care unit. the risk of bronchospam rarely associated with zanamivir, particularly in patients with underlying reactive airway disease, can be minimized by concurrent bronchodilator administration. adamantanes (amantadine and rimantadine) have no activity against the influenza a h n v pandemic strain. they are effective for seasonal h n influenza strains, which are % resistant to oseltamivir. therefore, for patients presenting with primary influenza pneumonia in geographic regions where seasonal h n strains are circulating in addition to the novel h n pandemic strain, amantadine or computed tomography scan of the patient with primary h n (swineorigin influenza a) influenza pneumonia whose chest x-rays appear in figure . rimantadine should be added to oseltamivir [ ] . rimantadine is also associated with immunomodulatory effects. patients presenting with severe influenza pneumonia who may have concurrent bacterial superinfection should also receive antibacterial agents effective against the most common etiologic pathogens, such as streptococcus pneumoniae, streptococcus pyogenes, and staphylococcus aureus, including methicillin-resistant staphylococcus aureus, according to published guidelines in the management of communityacquired pneumonia [ ] . corticosteroids remain controversial in persistent ards and are not routinely recommended [ ] . further research is required to clarify their impact on outcome. whether other adjunctive immunomodulatory therapies such as statins, chloroquine, and fibrates could prove useful in the context of an influenza pandemic [ ] remains to be determined. primary influenza pneumonia caused by the pandemic influenza a h n v strain, though rare, carries a high mortality. the rapid progression from initial typical influenza symptoms to extensive pulmonary involvement, with acute lung injury, can occur both in patients with underlying respiratory or cardiac morbidities and in young healthy adults, especially if obese or pregnant. prompt initiation of effective antiviral treatment, appropriate oxygenation and ventilation support, and antibacterial treatment in the case of concurrent bacterial pneumonia are critical for survival. the most reliable and timely diagnostic method for pandemic influenza a h n v infection is the rrt-pcr developed by the centers for disease control and prevention. common 'point-of-care' rapid influenza tests are very insensitive. a negative test result in a patient with clinical symptoms compatible with influenza pneumonia does not accurately rule out influenza and should not be a deterrent to prompt oseltamivir treatment during this current pandemic. further research is needed in order to identify the immunological dysfunction and determine the most effective dose and duration of oseltamivir as well as the role of potential adjunctive agents in the treatment of primary influenza pneumonia. studies on influenza in the pandemic of - . ii. pulmonary complications of influenza genetic variation of influenza a viruses as studied by recombinant dna techniques mortality associated with influenza and respiratory syncytial virus in the united states the immunopathogenesis of sepsis in elderly patients viral pneumonia in older adults pandemic versus epidemic influenza mortality: a pattern of changing age distribution observations on mortality during the influenza pandemic protective immunity and susceptibility to infectious diseases: lessons from the influenza pandemic enhanced virulence of influenza a viruses with the haemagglutinin of the pandemic virus emergence of a novel swine-origin influenza a (h n ) virus in humans serum cross-reactive antibody response to a novel influenza a (h n ) virus after vaccination with seasonal influenza vaccine who rapid pandemic assessment collaboration: pandemic potential of a strain of influenza a (h n ): early findings hospitalized patients with novel influenza a (h n ) virus infection -california león-gil c; h n semicyuc working group: intensive care adult patients with severe respiratory failure caused by influenza a (h n )v in spain swine-origin influenza virus h n , seasonal influenza virus, and critical illness in children prevention and control of influenza: recommendations of the advisory committee on immunization practices (acip) time lines of infection and disease in human influenza: a review of volunteer challenge studies duration of influenza a virus shedding in hospitalized patients and implications for infection control prolonged shedding of amantadine-resistant influenzae a viruses by immunodeficient patients: detection by polymerase chain reaction-restriction analysis viral loads and duration of viral shedding in adult patients hospitalized with influenza effects of cigarette smoke on epithelial cells of the respiratory tract influence of age on bronchial mucociliary transport influenza: pathogenesis and host defense influenza virus bronchotracheal response in human influenza. type a, asian strain, as studied by light and electron microscopic examination of bronchoscopic biopsies clinicopathologic study of thirty-three fatal cases of asian influenza clinical features of influenza a virus infection in older hospitalized persons complications of viral influenza a prediction rule to identify low-risk patients with community-acquired pneumonia defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study bacterial coinfections in lung tissue specimens from fatal cases of pandemic influenza a (h n ) -united states us centers for disease control and prevention: interim guidance on specimen collection, processing, and testing for patients with suspected swine-origin influenza a (h n ) virus infection the weekly epidemiological record (wer) ruling out novel h n influenza virus infection with direct fluorescent antigen testing rapid-test sensitivity for novel swine-origin influenza a (h n ) virus in humans evaluation of rapid influenza diagnostic tests for detection of novel influenza a (h n ) virus -united states clinical signs and symptoms predicting influenza infection surviving sepsis campaign management guidelines committee: surviving sepsis campaign guidelines for management of severe sepsis and septic shock ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. the acute respiratory distress syndrome network zanotti-cavazzoni s: practice parameters for hemodynamic support of sepsis in adult patients: update comparison of two fluid-management strategies in acute lung injury fluid-management strategies in acute lung injuryliberal, conservative, or both? influenza in hospitalized adults: gaining insight into a significant problem world health organization: who guidelines for pharmacological management of pandemic (h n ) influenza and other influenza viruses. publication date world health organization: antiviral use and the risk of drug resistance pandemic (h n ) briefing note advisory committee on immunization practices (acip): prevention and control of influenza: recommendations of the advisory committee on immunization practices (acip) infectious diseases society of america: update of practice guidelines for the management of communityacquired pneumonia in immunocompetent adults ancukiewicz m; national heart, lung, and blood institute acute respiratory distress syndrome (ards) clinical trials network: efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome confronting an influenza pandemic with inexpensive generic agents: can it be done? the patient whose radiological images appear in figures and has given written consent for their publication. the authors declare that they have no competing interests.this article is part of a review series on influenza, edited by steven opal.other articles in the series can be found online at http://ccforum.com/series/influenza key: cord- -xofwk a authors: davis, mark title: uncertainty and immunity in public communications on pandemics date: - - journal: pandemics, publics, and politics doi: . / - - - - _ sha: doc_id: cord_uid: xofwk a this chapter examines uncertainty in the expert advice on pandemics given to members of the general public. the chapter draws on research conducted in australia and scotland on public engagements with the influenza (swine flu) pandemic and discusses implications for communications on more recent infectious disease outbreaks, including ebola and zika. it shows how public health messages aim to achieve a workable balance of warning and reassurance and deflect problems of trust in experts and science. the chapter considers how uncertainties which prevail in pandemics reinforce the personalization of responses to pandemic risk, in ways that undermine the cooperation and collective action which are also needed to respond effectively to pandemics. uncertainty is a central challenge for public communications on matters pandemic. recent efforts to respond to outbreaks of infectious diseases, such as pandemic (swine flu) influenza (world health organization ), ebola (green ; world health organization ) and zika virus (world health organization ) have been marked by the limits of what can be known ahead of time and the challenges of responding to the particular turnings of outbreaks as they happen. the pandemic influenza-the topic of research i conducted with colleagues in australia and scotland-is a pivotal example of this problem of responding to a pandemic in real time. the pandemic put huge strain on global, national and local health systems, affecting many individuals and especially pregnant women and people with specific vulnerabilities to respiratory infections. it was a prominent, perhaps dominant, health news story of the period. but the pandemic turned out to be nothing like as severe as it was first thought to be. moreover, there was insufficient take-up of the h n vaccine (bone et al. ; galarce et al. ; white et al. ; yi et al. ) and it was observed that only minorities or small majorities reported that they intended to, or did, enact recommended social isolation to avoid transmission of the virus (kiviniemi et al. ; mitchell et al. ; rubin et al. ; van et al. ) . like the "swine flu affair" of the s in the united states (fineberg ) , the pandemic raised questions for the public health system of how to shape public action in light of the significant uncertainties which are particular to influenza, and without jeopardizing trust in government and the scientific knowledge on which is built public policy. central, too, was immunity, in its medical and social senses. immunity is not simply an object of biomedicine, it is also deeply entwined with collective life and the interrelations that come with, specifically, contagious diseases. it is also important to recognize that these issues are by no means settled; how individuals conduct themselves in relation to others in time of pandemic is a central and enduring concern for public health systems. in in the uk, for example, advertisements featured images of travellers on public transport and the following text: if you could see flu germs, you'd see how quickly they spread. cold and flu germs can live on some surfaces for hours. always carry tissues with you and use them to catch your cough or sneeze. bin the tissue, and to kill the germs, wash your hands with soap and water, or use a sanitiser gel. this is the best way to help slow the spread of flu. protect yourself and others (nhs swine flu information). this advice addresses responsible individuals and asks them to help limit the spread of infection. the final part of the message 'protect yourself and others' captures the idea that an easily spread influenza virus requires significant cooperation and the internalization of the idea of action on health for the collective good, as well as for oneself. this reference to altruistic action on health indicated that the social response to the pandemic exemplified biopolitics (rose ) . individuals are expected and encouraged to internalize the idea that they can take action on themselves to sustain and better their health and reproductive futures. this self-subjectification applies to the advice given to members of the general public on the influenza pandemic. in addition to the advice noted above, individuals were encouraged to arrange a network of "flu friends" who could be called upon in the case of illness, to stay abreast of developments in the media, and adopt expert advice (national health service ). publics were also advised to stay home if they suspected they were ill and to contact nhs services online or by telephone and to not attend gp surgeries of a&e, unless instructed to do so. in this view, the communications of hailed pandemic citizenship fashioned around the imperatives of action to avoid and contain the spread of infection and to make oneself available to expert advice. in what follows i explore pandemic communications under conditions of uncertainty, as exemplified by the influenza pandemic and its resonances with other recent contagions. as we will see, uncertainty has the effect of accentuating personalized responses to expert advice. it also sponsors communicative action figured around seeking the "just right" balance of warning and reassurance and related implications for trust in expert knowledge and authority to govern. the events of foregrounded many of the strengths and weaknesses of public health systems across the globe. key among these was preparedness and capacity to cope with large scale containment strategies which were used to manage the emerging pandemic. the pandemic preparedness plans in place in required that in the early phases of the pandemic, efforts should be made to sequester infected individuals and to trace their contacts so that the spreading infection could be tracked down and curbed (world health organization ). probably a central lesson of was that such efforts were costly and apparently ineffective. in some settings public health professionals were asked to continue this method even when they were aware that the virus was spreading quickly despite their best efforts . the pandemic therefore revealed the importance of being able to quickly assess the biological characteristics and severity of the infection so as to be able to modify the application of resources. since , public health systems have attended to the development of evidence-based measures to assess seriousness and the development of local and viable responses to a global pandemic threat (australian department of the prime minister and cabinet ). pandemic preparedness, therefore, has demonstrated a marked shift away from uniformity and top-down governance towards local, evidence-based, approaches. for example, australia's version of its preparedness plan adopted a traditional method of top-down transmission of expert knowledge and advice to publics. government in this view was mandated to: deliver consistent and accurate public messages nationwide in the event of a pandemic. governments will make every effort to provide timely and reliable advice to the public, media, businesses and industries. (australian department of health and ageing : ) by , however, the australian pandemic policy instrument referred to the need for public communications which were "two-way" and "listening" to publics (australian department of health : ). this approach to feedback on the transmission of information was said to depend on in vivo market research, the monitoring of social media, and a q&a website where publics can pose questions and air their opinions (australian department of health : ). the policy also made reference to the need for specific and tailored messages for vulnerable groups. however, during pandemic public communications faced significant challenges, not all of which are obviously addressed in the revised policies and their emphasis on feedback loops, market research and social media. surveys conducted at the time of the onset of the pandemic in show that while publics largely endorsed government action on the pandemic, they underestimated risk of infection and only minorities reported that they had adopted recommended behaviours such as social isolation and coughing and sneezing etiquette (rubin et al. ). the findings suggest that individuals interpreted public health advice with some scepticism. research shows also that espoused trust in government was associated with self-reported compliance with public health advice (lin et al. ; rubin et al. ). as noted, populations across the globe adopted vaccination only in small proportions, insufficient to protect the entire population. this indication of weak public engagement with the pandemic may be explained by a more general effect of risk management. it is surmised that the repetition of warnings over the last few decades-for example, hiv, bse, avian influenza, hospital superbugs, sars, h n , ebola and zika, to name a few-leads to weariness on the part of publics (joffe ) . diminishment in public engagement with risk is also thought to be an effect of risk society preoccupation with the forecasting and management of risks (giddens ) . public weariness can be thought of as a manufactured risk in the sense that it arises through attempts to manage risk. it is also evident that news on current risks are often framed by established patterns of meaning used to depict previous or contiguous risks (ungar ) . it is possible, therefore, that publics have learned to screen out global health alerts and treat media on the topic with a degree of scepticism, a perspective supported by our own davis ) and similar research (hilton and smith ; holland and blood ) . implied also is that repeated global health alerts coupled with some scepticism on the part of publics may lead them to fall back on personal knowledge and resources. the individualization of responses to pandemic risk communications was supported by our own research. individuals in our interviews and focus groups endorsed expert advice regarding coughing and sneezing etiquette and social isolation, but they did not think that these strategies would be viable in the long run . some of our respondents did adopt forms of social isolation, but they also saw in these strategies some flaws and inadequacies. they appeared, in general, to recognize the ease with which infection could occur. for these reasons, many of the people we spoke with resorted to discourse on immunity as a means of coping with a more than likely infection. almost absent was discourse on personal action as a means of protecting all, apart from among those with severe respiratory illness who were used to dealing with the threat of infection posed by others. our respondents focused on matters such as the building of immunity through consumer products, rest and exercise, and spoke of the need to cultivate and educate their personal immune system, with some reference to childhood experiences of exposure to infection. individuals seemed to accept that interaction with microbial life was inevitable and important to health and that their immune systems were shaped by their own actions. this "choice immunity" was spoken of as managing one's body and those of dependent others in ways that resonated with the well-known notion of "choice biography" which is said to characterize reflexive modernization (beck and beck-gernsheim ) . there are other implications of this resort to choice immunity. ed cohen has shown how immunity is a conceptual framing of subjectivity that preceded modern day microbiology ( ). with its root in the latin munis-also the root for municipal and remuneration, for example-immunity referred to the suspension of one's civic and pecuniary obligation to collective life. cohen gave examples which include, duty, gift, tax, tribute, sacrifice, and public office ( ). immunity suspends the "bond of requirement," but also, therefore, reinscribes it (p. ). it always and necessarily marks the power of the social obligation it refuses, including in matters of health. as cohen showed, microbiology, and specifically germ theory, appropriated and reconfigured the metaphor of immunity to help narrate the emerging science of cells, microbes and pathogenesis. in particular, the idea of immunity helped to explain how the immune system destroyed cells colonized by alien microbial life and bypassed uninfected cells of the body, although autoimmunity and microchimerism complicate this understanding of biological immunity (martin ) . combined with germ theory, immunity operates to produce a "milieu interieur;" an imaginary of the battle with microbial invaders inside the body (cohen : ), a metaphor which accentuates the emphasis on the individual in relation to contagious health threats. emily martin has made a similar point that media depictions of immunity have often referred to the war within the body ( ). it is therefore no surprise that individuals resort to the practical and metaphorical properties of immunity when they are asked to contend with the risk of pandemic influenza, which creates uncertainties over which they otherwise have very little apparent control. these issues are reflected in consumer products, for example, the commercial marketing of probiotic foods and supplements (burges watson et al. ; koteyko ; nerlich and koteyko ) , which address individual consumers in terms of "choice immunity." probiotics also raise the idea that it is important to replace bacteria that have been killed off due to antibiotic treatment and/or the idea that "good" bacteria will outcompete illness producing bacteria. the scientific underpinning and marketing of probiotics, then, depend on a division of "good" and "friendly" bacteria from disease-producing bacteria. it is against this backdrop of immunity culture that public health institutions have to shape and circulate messages on how individuals ought to conduct themselves. as with the pandemic, agencies such as the who, regional who offices, and lead national public health agencies such as the cdc and public health scotland implement communication strategies and are key sources of expert commentary in worldwide news media. a central communication challenge is how to shape messages so that they are productive of desired action on the part of members of the general public, when it cannot be known absolutely how matters will transpire. it is clear from our research with public health professionals in australia and the uk that finding a balance of motivation and reassurance was paramount (davis et al. (davis et al. , . in this context, public health experts were concerned that publics should be advised and asked to prepare for the pandemic but not in ways that promoted anxiety or promoted panic, as reflected in, for example, runs on supermarkets, pharmacies and clinics. this meant that messages also had to be reassuring but not in a way that led publics to ignore advice, or worse, to become complacent. as briggs and nichter have pointed out, pandemic messaging was carefully styled around the notion of "be alert, not alarmed" ( ). they have identified this approach as the "just right" goldilocks method, that is, the production of alert, but not panicky, reassured, but not complacent publics. for example, in a newspaper article published on april , in the first few days of the pandemic alert, the chief health officer of australia was quoted to have said: we should be aware but i'm not overly alarmed at this point. we don't have confirmed cases in australia but i think there will be some cases in the future. we think the population should be alert, should be aware of travellers in their midst who have the flu. but not alarmed at this point, just aware. (robotham and pearlman ) in this way, pandemic communications help to constitute the expert-informed, life choices of individuals. less obvious are obligations to others which also make immunity possible, such as herd immunity and the related practice of altruistic vaccination to protect vulnerable others. it is also important to recognize that explicit reference to immunity is rarely a feature of this public health advice; it is nearly always implied. the pandemic raised some other problems related to the eventual character of the pandemic as mild for most, but not all. as noted, the pandemic was quickly found to be less severe than early indications portended, though some groups faced elevated risks and the pattern of morbidity differed from that typical for seasonal influenza (presanis et al. ) . it therefore became necessary to manage the communications turn away from alert, but without the cessation of cautionary messaging and continued advice for those who did face higher risk of severe disease. influenza is known to return, on occasion, in a second wave which has the potential to be more severe for all or some of those affected (presanis et al. ) . uncertainties like these meant that it was imperative to sustain a kind of watchful, just in case, attitude, until such time as an effective vaccine became available. this particular situation of a global alert followed by revisions of preparedness and response and growing evidence of a significantly less dangerous pandemic led to new communications challenges to do with explaining to publics what was happening and how they should therefore conduct themselves. this shifting in messaging across the period of the pandemic implied "the boy who cried wolf " parable (nerlich and koteyko ) , which teaches in narrative form the jeopardy of trust faced by raising a false alarm, too often. one effect of false alarm is that it may amplify the importance of choice immunity, that is, recourse to the self-reliant management of the body as the means to contend with an uncertain health threat. sociological perspectives on choice biography point out that under the conditions of neo-liberal economic and political order, individuals are forced to rely on themselves and their own decision-making capacities, since there is in the end, nowhere else for them to go (beck and beck-gernsheim ) . they nevertheless are bound to depend on expert advice, since no one person can be expert in all the considerations that pertain to health or any other of the major life decisions (ungar ) . false alarm destabilizes expert authority and leaves people doubly reliant on themselves. in this view, the tendency for individuals to fall back on their immunity is a rational response to the requirement to take action and because, in the face of the uncertainties which preside in the case of influenza, the body is one apposite arena in which people are able to exercise some control. our research shows also that the communication on the pandemic had the potential to divide publics according to their vulnerability, another way in which knowledge and questions played out in the pandemic. they showed awareness of the "boy who cried wolf" dilemma but also recognized the invidious situation in which public health experts found themselves. they spoke of the needless hype of the media on the pandemic, by which they meant the extent of the reporting on the progress of the pandemic (davis and lohm forthcoming). it is important to remember, also, that some groups and individuals were affected and profoundly so, for example, women who were pregnant in . public communications on the risk of pandemic influenza, therefore, had a schismatic quality in the sense that the mildness of the virus needed to be explained to publics, while some remained at risk. like the universalism of pandemic preparedness, communications were also faced with the need for nuance and provisionality. this splitting of publics according to their vulnerability , was suggestive also of the coexistence of different modes of pandemic subjectivity. the "not at risk and in general unconcerned" could look upon news media and public communications as needless and hyped, particularly as the pandemic progressed. vulnerable groups, as we have suggested , at times had trouble recognizing themselves in these messages and once they had established for themselves awareness of their immunological vulnerability, they looked upon the hype as masking what for them was a real and visceral anxiety and set of practical issues of infection control and vaccination. this schism in public engagement accentuates the sense in which people have to make up their own mind on how to act in the context of what our vulnerable interviewees suggested were confusing, mixed messages. the communications challenges of emerging, changing pandemics are considerable. messages have to, at first, inform publics without frightening them, but also reassure them without producing complacency. as the example of the pandemic indicates, as the infection progressed and evidence emerged of the health effects of the h n virus, public health systems had to explain that the pandemic was mild, though this situation could change. they also had to embed in this more general message information for minorities that they remained at serious risk. this changing, complex message risked provoking accusations of false alarm and therefore mistrust, as has happened in previous outbreak situations (fineberg ) . as i argued, too, the mixing of a general message of a mild pandemic which might change with messages that also some particular kinds of people were at risk, placed vulnerable people in the difficult situation of having to identify themselves in these messages and take action when others were sceptical and unlikely to be acting to protect themselves and those around them. when we asked people in our research to talk about h n and specifically if it could be prevented, people acknowledged that infection was unlikely to be avoided and, accordingly, they were forced to reflect on the capacity of their body to cope with infection. as indicated, this resort to personal immunity was not quite the same as the science of cellular immunity discussed by cohen and others. it more closely resembled an acceptance of the possibility of the presence of the virus in the body and fashions an arena for volitional action on the body when other forms of action seem to have less practical value, as was the case in . for example, social isolation and possibly vaccination, were endorsed but by and large not extensively taken up, particularly given that the virus was in general mild and easy to catch. because the h n virus was observed to be so easily transmitted, the resort to personal immunity had doubled value. it may be for this reason that publics endorsed expert advice to self-isolate and vaccinate, but did not do so, that is, they fended for themselves and the pandemic turned into a mild one, anyway, though not for everyone. appeals to the collective good and altruistic vaccination on which depend public health efforts concerning pandemics, may miss the point that individuals are led to think of their personal immunity as an arena within which they can sustain themselves in the face of deeply uncertain threats which arise in communal life. if as cohen has suggested, immunity is fused with ideas of cellular action on microbial pathogens but it is also a metaphor for freedom from obligation. it seems, then, that a key lesson from was that freedom from the dangers of infection found in personal action on immunity also implied freedom from having to act in the interest of others; the more free one is from the dangers of infection-the stronger one's immunity-the less one needs to consider the dangers which others face, particularly under conditions of uncertainty. individualized ideas of immunity in connection with uncertainties may limit the effectiveness of public health communications on influenza pandemics and other contagious threats. australian health management plan for pandemic influenza australian health management plan for pandemic influenza: important information for all australians. canberra: australian government, department of health and ageing australian department of the prime minister and cabinet individualisation: institutionalised individualism and its social and political consequences population and risk group uptake of h n influenza vaccine in mainland france - : results of a national vaccination campaign biocommunicability and the biopolitics of pandemic threats little bottles and the promise of probiotics a body worth defending: immunity, biopolitics and the apotheosis of the modern body is it going to be real?' narrative and media on a pandemic forthcoming. pandemics, publics and narrative we had to do what we thought was right at the time': retrospective discourse on the h n pandemic in the uk compliant, complacent or panicked? investigating the problematisation of the australian general public in pandemic influenza control we became sceptics': fear and media hype in general public narrative on the advent of pandemic influenza biopolitics and pandemics: public and individual responses to the threat to life preparing for avian influenza: lessons from the 'swine flu affiar socioeconomic status, demographics, beliefs and a(h n ) vaccine uptake in the united states risk society: the context of british politics west africa struggles to contain ebola outbreak public views of the uk media and government reaction to the swine flu pandemic public responses and reflexivity during the swine flu pandemic in australia public apprehension of emerging infectious diseases: are changes afoot? perceptions of and willingness to engage in public health precautions to prevent h n influenza transmission i am a very happy, lucky lady, and i am full of vitality!' analysis of promotional strategies on the websites of probiotic yoghurt producers what have we learned about communication inequalities during the h n pandemic: a systematic review of the literature flexible bodies: tracking immunity in american culture from the days of polio to the age of aids microchimerism in the mother(land): blurring the borders of body and nation non-pharmaceutical interventions during an outbreak of pandemic influenza a (h n ) virus infection at a large public university important information about swine flu balancing food risks and food benefits: the coverage of probiotics in the uk national press crying wolf ? biosecurity and metacommunication in the context of the severity of pandemic a/h n influenza in england: a bayesian evidence synthesis global alarm as killer swine flu spreads. the sydney morning herald the politics of life itself: biomedicine, power and subjectivity in the twenty-first century public perceptions, anxiety, and behaviour change in relation to the swine flu outbreak: cross sectional telephone survey mobilising 'vulnerability' in the public health response to pandemic influenza misplaced metaphor: a critical analysis of the 'knowledge society global bird flu communication: hot crisis and media reassurance university life and pandemic influenza: attitudes and intended behaviour of staff and students towards pandemic (h n ) australia's pandemic influenza 'protect' phase: emerging out of the fog of pandemic influenza vaccine uptake in pregnant women entering the influenza season in western australia world now at the start of influenza pandemic report of the review committee on the functioning of the international health regulations ( ) in relation to pandemic (h n ) statement on the st meeting of the ihr emergency committee on the ebola outbreak in west africa world health organization predictors of the uptake of a (h n ) influenza vaccine: findings from a population-based longitudinal study in tokyo acknowledgements this chapter is based on research funded by an australian research council discovery project grant on pandemic influenza (dp ). i would like to acknowledge the assistance of my colleagues from the pandemic influenza project, niamh stephenson, paul flowers, emily waller, casimir macgregor and davina lohm. i am also very grateful for the time and efforts of those who participated in the interviews and focus groups for the research. key: cord- -zvb bxix authors: connolly, john title: the “wicked problems” of governing uk health security disaster prevention: the case of pandemic influenza date: - - journal: disaster prev manag doi: . /dpm- - - sha: doc_id: cord_uid: zvb bxix purpose: the purpose of this paper is to examine the governance and policy-making challenges in the context of “wicked problems” based on the case of pandemic influenza. design/methodology/approach: the case study research is based on an analysis of official documentation and interviews with policy elites at multiple levels of uk governance. findings: results of this study show that policy actors regard risk communication, the dynamics of international public policy and uk territorial governance as the main governance challenges in the management of influenza at a macro-level. the paper also serves to identify that although contingencies management for epidemiological issues require technical and scientific considerations to feature in governance arrangements, equally there are key “wicked problems” in the context public policy that pervade the health security sector. practical implications: the study indicates the need to build in resources at a national level to plan for policy coordination challenges in areas that might at first be seen as devoid of political machinations (such as technical areas of public policy that might be underpinned by epidemiological processes). the identification of the major governance challenges that emerge from the pandemic influenza case study is a springboard for a research agenda in relation to the analysis of the parallels and paradoxes of governance challenges for health security across eu member states. originality/value: this paper provides a novel interrogation of the pandemic influenza case study in the context of uk governance and public policy by providing a strategic policy lens from perspective of elites. in april the british public were reminded that pandemic influenza (flu), in the context of health security, continues to be a major concern for uk policy-makers. there is recognition by the uk government that a pandemic remains the top health risk for the population (nhs england, ) . the risk of pandemic flu has come into the spotlight recently due to the fact that key measures to prevent such a diseaseinduced disaster may not be effective. a review of the effectiveness of tamiflu [ ] (the main contingencies measure to manage a pandemic) produced by the cochrane collaboration ( jefferson et al., ) , referred to in the rest of this paper as "cochrane review", in the uk concluded that tamiflu had no significant impact on reducing hospital admissions and does not serve to prevent the person to person spread of influenza. this led to pharmaceutical companies retorting by questioning the reliability and validity of the review. uk health authorities responded by insisting that investing in tamiflu remained "a good insurance policy for the population" . the debates around the cochrane review (which are often scientific and epidemiological in nature) also served to highlight the public policy-orientated challenges to managing health security threats such as a pandemic. this paper seeks to delve into the public policy aspects of contingencies management for disease threats from the perspective of policy elites based on the case study of the influenza pandemic in the uk. the paper addresses a lacuna in uk disaster and crisis management literature by contributing to the "governance" aspects managing health security. there are studies which consider crisis management, resilience and risk in the context of uk public policy (e.g. mcconnell, ; drennan and mcconnell, ; brassett et al., ) , however, there are very few case-based research studies which illustrate crisis and disaster governance challenges from the perspective of those institutions and policy actors that are responsible for managing such "wicked problems" from a macro-level policy position. from a public policy point of view, pandemics represent challenges that are unstructured, relentless and cross-cuttingall hallmarks of a wicked problem (weber and khademian, , p. ) . first, as weber and khademian ( , p. ) note, issues that can be viewed in this way are unstructured given that there are high informational demands, there is not always a clear solution to the problem and they have multiple ripple effects. second, the relentlessness of such problems emerges as a result of the fact that the fight is never over and a line cannot be drawn under themthere is no finality. third, cross-cutting refers to the fact that wicked problems involve multiple stakeholders who have a range of views and knowledge within a complex political and economic context. the complexities of disease threats and their transcendence of systems elucidates the fact that health security and pandemic prevention involves trade-offs, require flexibility, resource sharing and collaboration to ensure policy success (durant and legge, ) . other examples of wicked problems include responding and managing climate change, social justice, drug trafficking, immigration, and epidemics. pandemic influenza fits with the notion of a wicked problem given that they call for multi-level and multi-actor responses across territories requiring a high degree of resilience to deal with the contours of the disease (unstructured and cross-cutting). at a population level the risk of a pandemic endures over time as a result of the mutation of disease strains and the impact of pandemics can traced over many years (relentless). indeed, policy-makers are well aware that in the last century alone the , and influenza pandemics have contributed to millions of fatalities as well as vast economic and social disruption (kamradt-scott and mcinnes, , pp. - ) . the case of pandemic influenza is a "way in" to understanding the policy dynamics of the health security sector in the context of disaster research. the issues to emerge from pandemic influenza are likely to have consequences for the governance of other diseases (and, naturally, reference to other diseases will be made in this paper given policy responses to specific diseases do not exist in a vacuum). the question that underpins the paper, therefore, is: what does the case study of pandemic influenza tell us about what policy elites regard as the key "wicked problems" of contingencies management in the context of uk governance? the case study has been interrogated by deploying mixed qualitative methods. the case study method is effective in public policy research for exploring, assessing, conceptualising, and refining explanations for the characteristics and dynamics of social realities or events (lowi, , p. ; eckstein, , pp. - ; flyvbjerg, , p. ) . the approach included a thematic analysis of secondary sources and official government documentationincluding the and house of lords reports into pandemic influenza (hl- , ; hl- , ), the department of health (doh) national framework for responding to an influenza pandemic (doh, ) , the independent review of the influenza pandemic (cabinet office, ), the uk influenza pandemic preparedness strategy (doh, ) and reports of the european commission. the research also involved undertaking in-depth semi-structured elite interviews with policy actors who occupy strategic-level governmental positions in scotland, the uk and in the european commission (the commission being the main policy initiator at the eu level). the analysis of documentation served to support the identification of interviewees and contributed to the themes that structured interview schedules. the interviewees were purposely sampled due to their positions at different tiers of government in the health security policy area. the interview breakdown is as follows: scottish government ¼ interviews (subnational/devolved level); uk government (national) level: public health england (phe) (agency of the uk civil service) ¼ ; westminster/uk parliament ¼ ; uk cabinet office (central ministerial department/headquarters for government) ¼ ; and european commission (health threats unit: ). interviews lasted on average . to hours in length. the scottish and uk level interviews were face-to-face in governmental or parliamentary premises and the interviews with european commission officials took place via teleconference facilities (with the interviewer being present on university premises). there were inconsistencies in terms of the medium by which the interviews were conducted and the necessity for teleconference interviewing was borne out of resource limitations for travel (particularly the high costs for travel between scotland and luxembourg -where the officials were based in the commission). however, these inconsistencies should not necessarily been seen as limitations given that the interviews conducted via teleconference were equally rich in depth and exploratory. interviews were also sought from individuals who work in the area of public health and disease risk management in the doh, however, there was a lack of preparation by such individuals to engage with this research via an interview. the position of the department was that their institutional approach had been detailed sufficiently in strategy documentation (cited earlier in this paper). digital recordings of all the interviews were fully transcribed within hours of the interviews taking place. the interview data was thematically coded around the most significant strategic policy challenges to emerge from the data. it should be noted that the majority of the interviewees felt it to be impossible to "rank" the extent of whether one challenge outweighs another but regarded these challenges to be equally placed on a continuum of policy challenges that were present in the case of pandemic influenza. the quality of the interviews is borne out of the fact that the individuals are situated in strategic-level positions within the institutional environment under investigation (less senior officials, of which there would likely be higher numbers, would be less able to discuss strategic relations across territories). in this respect the quality of the interviews outweighs the need for quantity given the low number of individuals that are in such senior positions in this policy sector (i.e. ten interviews represents a strong sample from a small pool of available data). this approach also serves to highlight the uk health security contribution that emerges from the study in that the interviewees where able to discuss matters of macro, strategic level concern from their perspectives. the interviewees were made up of a senior uk parliamentarian (with a remit for health security) and senior officials working within the areas of contingencies and crisis management for public health at multiple levels of governance (the european commission, uk government departments/agencies and in the scottish government). in short, the paper seeks to identify where the "politics" fits in the area of contingencies and crises management from the perspective of elites in relation to health security within a multilevel governance context. the study accommodates all study protocols which were approved by the author's university ethics committee and by the funding body for the research (carnegie trust, scotland). viewing health security in the context of "disaster" in a similar vein to "crisis", no definition of disaster has been agreed upon in the literature (hood and jackson, ; perry and quarantelli, ) . alexander ( , p. ) has described disaster research as being embedded in a "definitional minefield". analyses have ranged from explaining disasters as the collapse of cultural protections (carr, ) , unique events (rubin and popkin, ), a form of collective stress (barton, ) , systemic events, and a form of a social catalyst (kreps, ) . disasters tend to be events which lead to large-scale damage to human life, damage to the physical environment and have vast economic and social costs. there is a considerable body of literature that has focused on the impact that physical (sometimes expressed as environmental) disasters have had on human activities (alexander, ; steinberg, ) . indeed, human vulnerabilities have been an important defining factor in the classification of an event as a disaster (smith, ) . again, however, there is an analytical grey area between what constitutes a crisis or disaster due to shifting identities and contextual change. for example, analyses have described a shift from threats to disasters (rijpma and van duin, ) and from crises to disasters (davies and walters, ) . the definition(s) applied to analyses seem to be dependent on the discipline using the term and the aims of the researcher because "actors create a definition with different ends in mind" (perry, , p. ) . in this respect, the "securitisation" of health, particularly around pandemic disaster prevention and management in the context of global governance, is now generally accepted by key supranational authorities (who, ; european commission, ) and in the academic literature in the context of global governance (kay and williams, ; connolly, ) . it is argued that health security can be studied and framed in the context of disaster research given that if threats of disease pandemics are not managed effectively, and safeguards are weakened, then a pandemic, and thus pandemonium, will ensueleading to far-reaching damage to human life and produce vast economic social and environmental costs on a global scale. the case of pandemic influenza in the uk the implications of pandemic influenza are "feared by politicians, health practitioners and security experts alike" (kamradt-scott and mcinnes, , p. ). significant concern of a pandemic occurring was heightened as a result of the threat of the avian flu virus in asian countries (h n virus) in and . more recently, fear about human to human transmission of influenza was particularly acute as a result of the h n "swine flu" virus. the threat emerged when the world health organisation (who) declared that there was an outbreak of swine flu following confirmation of human cases in the usa and mexico in april . two confirmed cases of pandemic influenza subsequently emerged which involved a couple who had returned to scotland from mexico (connolly, ) . this led the uk government to increase their stockpile of antivirals (tamiflu) to million (from million). the government's approach was to maintain the policy of containment e.g. through contract tracing and antiviral treatment (cabinet office, , pp. - ) . by june/july the cases of swine flu has reached almost , in countries. the cases of swine flu in the uk reached , and there were pockets of concentration of the disease in birmingham and greater glasgow (cabinet office, , p. ). the who declared the outbreak had moved to pandemic levels which triggered the uk government to procure vaccines to cover per cent of the population. in late november modellers concluded that the pandemic had peaked and a gradual reduction in cases followed (cabinet office, , p. ) . the pandemic led to [ ] deaths during the pandemic in the uk (cabinet office, , p. ). the uk response to the pandemic relied on cooperation between supranational, national and subnational jurisdictions (with uk state level being the "core" crisis management actor through the department of health phe and the uk cabinet office). following the pandemic the government produced a uk influenza pandemic preparedness strategy (doh, ) which, building on the "national framework" for responding to an influenza pandemic (doh, ) , sets out in some detail the key planning assumptions and presumptions for planning for a pandemicincluding a summary of the key roles of government departments and agencies as well as the control strategies in order to mitigate against the impact of a pandemic influenza crisis. an important point, made rather passively in the strategy, is that preparedness and response to the threat is coordinated at local, national and international levels (doh, , pp. - ; connolly, ) . the case of pandemic influenza in highlighted that disease threats, such as pandemic influenza are trans-boundary which can penetrate integrated political and economic systems (such as the european union) and, therefore, call for a large number of organisational actors, at different governance levels, to be engaged in crisis management processes (allison, ; 't hart et al., ) . the resilience literature recognises the importance of considering the implications of when crises outweigh local capacity and there is a need for a multi-level response across borders and tiers of governance (see, e.g. brassett et al., ) . there is general agreement in the literature that local-or state-centric studies of crisis, emergency management, security and risk ('t hart et al., ) need to adapt their analytical frames to consider multi-level systems (coaffee, , p. ). the study "resilience" is characterised by its inexactitude given that, as anderson ( , p. ) , notes it has been referred to in academic circles, amongst other things, as "ethos", "programme", "ideology", "concept", "term", "governing rationality", "doctrine", "discourse", "epistemic field", "logic", "buzzword", "normative or ideal concept", and "strategy of power". however, in the context of health security, we are reminded by the - global ebola outbreaks of the need for international systems to be resilient in terms of being flexible and multi-partnership focused whilst, at the same time, having clarity over institutional roles and responsibilities. this is in order to avoid disorganised and belated responses (as demonstrated by the global response to ebola). in this regard, successful resilience is dependent on being able to navigate complexity given the context of interdependences between governmental and non-state actors across multi-level uk health security and cross-cutting jurisdictional boundaries (bevir, , p. ) which necessitate inter-organisational coordination (perry and lindell, ) . as a result, this warrants the need for contingency planning needs to take place at multiple levels of governance given that internal failures can have implications for the integrated system and have disastrous consequences (see turner and pidgeon, ; boin and mcconnell, ) . these requirements are not always matched by the characteristics of bureaucratic contexts which are known for their conservatism when it comes to institutional change. what is more, conflictual and political behaviours can manifest at different levels or governance and, as a result, a lack of contestation between political and bureaucratic actors cannot be assumed (rosenthal et al., , pp. - ) . yet evidence of this is often masked by the tendency of official governmental documents (such as strategies and contingency planning documents) to be read as if contingency processes (particularly for scientific or epidemiological issues) are in some way non-political in that such documents tend to focus on a range of "manual-like" sequential steps that should be taken in the event of an incident. clarke ( ) discusses the symbolic and political nature of such crisis contingency planning by the use of "fantasy documents". it is the contention that governmental documents that attempt to tame crises or disasters are "little more than vague hopes for remote futures and have virtually no known connection with human capacity or will" (clarke, , p. ) . it is within this context that questions about the "politics" of contingencies and crisis management functions across multiple levels of governance are pursued and, specifically, how this relates to the issue of health security. the case study data indicates that balancing the activities of risk communication with pharmaceutical interests is a major governance challenge in policy-making for pandemic flu (and, arguably, for other diseases). the conclusions of the aforementioned cochrane review questioned whether government investment in a stockpile of "tamiflu" as a contingency measure to safeguard the population matched any potential benefits of taking the medication. the evidence presented by jefferson et al. ( ) suggested that tamiflu moderately reduced the period that individuals would have flu symptoms. this led to pointed media reporting of the issue which included headlines such as "drugs given for swine flu were waste of £ million" (knapton, ) and "what the tamiflu saga tells us about drug trials and big pharmaceuticals" (goldacre, ) . the response from the industry was that the review underestimated the benefits of tamiflu and that they disagreed with the statistical analyses and therefore disagreed with all of the conclusions (gallagher, ) . the uk department of health confirmed that they would not change their public health advice in relation to the use of tamiflu as part of its preparedness planning despite the findings of the cochrane review. it is with key reference to the issue of tamiflu that elite actors suggest that there are challenges with regards to risk communication and, revealingly, the chief medical officer (cmo) for scotland pointed out that "we are not very good in government at conveying the full arguments and why we have decided to continue with the current policy" (keel, ) . for policy-makers the former secretary of state for health, and latterly the chair of the uk parliamentary committee for health, highlighted the difficulties in "communicating the subtleties" of scientific evidence (dorrell, ) . this chimes with the perspectives of the cmo for scotland and the chair of phe who considered that the challenges of "coordinating and digesting advice" (keel, ) that is "unadulterated, clear, properly analysed and packaged for the policy-makers" ) are significant. the wider point here is that scientific evidence is just one consideration by policy-makers and it would almost be impossible for this to not be the case in a politically driven society . a further challenge in terms of risk communication is getting across the message that it will take at least four to six months after a novel virus has been identified and isolated before pharmaceutical manufacturers can make an effective vaccine available (doh, , p. ) . although it could be said that the provision of scientific products by pharmaceutical companies are essential, because they are the only place where new drugs and vaccines and biotechnologies are being developed, the risk for many politicians is that because they are profit-making organisations "it is easy to be accused of favouring a pharmaceutical company because of vested interests" . however, contingency planning for health security requires the need for a stockpile of drugs and vaccines but this undoubtedly remains a political decision because the opportunity cost would be that policy-makers could be accused, in the event of a crisis, of not having appropriate measures in place thus endangering the health of the public (dorrell, ) . pandemic flu served to highlight that risk communication, coupled with industry interests, need to be taken into account when it comes to the management of science-or medical-based areas of public policy. political leaders can have their fate determined by how they respond to crises (boin et al., ) , and investing in a stockpile (even if they are never used), symbolises government readiness ('t hart, ) . the uk department of health has highlighted that in a globalised world it is not possible to prevent, manage and eradicate a new virus in neither the country of origin nor when it penetrates uk borders (doh, , p. ) . it is for this reason that the current chair of ohe, writing back in , noted that reporting and responding to infectious diseases requires collaboration across territories (heymann, , p. ) . heymann ( , p. ) suggested that "[t]his phenomenon is a potential infringement on national sovereignty that compromises the concept that states reign supreme over their territories and peoples". the twin threats of sars and avian influenza served to seal a new approach to health security for disease threats within a globalised world whereby the norms to responding to public health threats are such that reporting is much more the norm in order to eradicate diseases as efficiently and effectively as possible. the rise of surveillance using the internet and international standards and agreements, such as the global influenza surveillance network (of which there are member states), overseen organisations such as the who, has now replaced a situation whereby individual states provide information on disease threats and outbreaks on a voluntary basis (heymann, , p. ) . the relationship between state actors and international policy regimes in the process of contingencies management for health security becomes ever more apparent in the context of eu public policy. the legislative competence of the eu in coordinating contingencies and crisis management arrangements for public health threats has increased after a series of serious disease episodes, such as sars, avian flu and pandemic influenza, which have presented opportunities for closer policy integration and europeanisation (ryan, ) . health security within the eu is coordinated by the directorate general for health and consumer protection of the european commission. the role of the commission has become legally enshrined since the sars outbreak which ended the voluntary arrangement in place for member states to provide data to supranational institutions uk health security (as was the case in terms of providing national level information to the who). there is now a system in place for eu level surveillance in that member states are legally required to statistically report on cases of communicable diseases through the eu health security committee on an annual basis and second, states are obliged to inform each other using an electronic system of outbreaks of one of these communicable disease which could have effects on other member states. yet, enthusiasm for closer integration between states cannot be taken for granted given that given that larger member states (such as the uk, france and germany) have their own systems of contingencies management that have strengthened over time and, therefore, "carrying smaller member states" can be a distraction (phe official, ) . there have also been difficult tensions (which is a key hallmark of "wicked problem") when it comes of the sharing of what some member states would describe as "sensitive data" with each other through the route of the health security committee when it comes to contingency planning. the reason for this is articulated by a senior european commission official: we have member states that plan to vaccinate percent of their population in the event of a pandemic. in other words, percent will not be vaccinated and then you have countries that are providing for percent. clearly if this information becomes public the citizens of the concerned countries -the percent who won't get the vaccine might have some questions to ask of their politicians. the health security committee does not oblige member states to vaccinate everybodythat's not the purpose of the exercisethis is a national decision for how many people they consider suitable or requiring a vaccination. for example it could be public service workers, it could be medical personnel, the armed services, it could be the security services. in germany it was the politicians for some reason. so this is a very political and national decision. what we have done is to take the figures from each member state and formulate a joint tender. so we now have the figures for the different member states which are quite confidential i can tell you and we will make a tender to industry and the industry will be able to apply to supply this vaccine. for senior policy-makers, the governance challenges are grouped around managing public policy dynamics around ensuring closer integration and europeanisation in the knowledge that diseases transcend borders and therefore requires collaboration across territories. however, the complexities come from the politics of using resources to support "weaker" member states and the sensitivities around sharing classified information about who will be prioritised when it comes to implementing a vaccination programme in the event of a pandemic. the wicked problem of uk territorial governance uk policy actors (i.e. in scottish and uk governments) in the area of health security have highlighted the domestic state-level challenges of managing planning for pandemic disease within uk borders and the political dimensions to this process. the uk constitutional arrangements are such that we have devolved governments (with limited powers) in scotland, wales and northern ireland. the governance challenges are complex and this is partly due to the fact that control over health policy in the uk is not straightforward. for example, in the case of scotland public health (i.e. nhs and wider healthcare) is a devolved matter, however, matters of health security that have public health implications (such as bio-terrorism) are reserved matters for the uk government. such challenges are exacerbated when administrations are headed by different political parties at different tiers of governance. for example, the scottish government is headed up by a different political administration to the uk level (the scottish nationalist party) and the case study data has shown there to be evidence that nationalist politics has impacted on approaches to multi-level contingencies management for health security (although, for pandemic influenza specifically, both uk and scottish level elites highlighted that there were strong relationships between public health officials). a scottish government official indicated how the nationalist public health minister, michael matheson, was concerned that documentation on cross-border contingencies management pertaining to health (such as radiation protection and nuclear monitoring) had the word "england" in the title as a result of the creation of "phe" as an executive agency of the uk department of health at uk level in april . this had serious implications for civil servants in scotland in that they had to research and scope out the reasons why there is not the capacity to undertake this type of work at the subnational level in scotland: the current policy arrangements are such that the devolved administrations in the uk contribute to national strategies for preparedness planning and crisis simulations, however, as one senior scottish government official noted, "it is not always the case that the devolved administrations are there and creating plans with the uk government" (scottish government official, ). interviewees from different triers of uk governance agreed that there is mutual interest in maintaining strong relationships across levels of governance both in terms of managing the spread of diseases and ensuring that clear communication channels are in place. this is not to say, however, that there are no political tensions when it comes to multi-level contingencies management for national health and security. a senior official in scottish government gives the example of counterterrorism efforts as part of the operations of the commonwealth games in glasgow . as noted above although counter-terrorism measures have implications for public health, contingencies management arrangements for terrorism are a reserved issue for westminster. this leads to multi-level tensions in terms of information sharing (even to the officials of the host country of the games) given the sensitivities around responses to terrorism: we had an exercise for the commonwealth games and cobra [of the uk cabinet office] was involved. one of the issues that people mentioned quite a lot was the counter-terrorism aspect as that is a big issue. there is an issue in terms of sharing information between parts of the administration. it is clear from such insider perspectives that there are political interests that infiltrate the approach of policy-makers even when it comes to so-called "technical" areas of contingencies and crisis management. the cmo was clear about the fact that there are interests on both sides of the border between scotland and england in terms of maintaining the current arrangements even if the devolution of more powers continues given that diseases and organisms do not stop at the border (keel, ) . in terms of the experience of managing the influenza pandemic the independent review of crisis noted that strong sub-national and national relations were not taken for granted given that "the h n pandemic was the first uk-wide crisis in a devolved policy area, and therefore there could have been inconsistencies and disagreements between the four uk nations during the response" (cabinet office, , p. ). yet the report concluded that "the willingness of the devolved administrations and the department of health to work closely together within a common uk framework was fundamental to the overall success of the response" (cabinet office, , p. ). notwithstanding this encouraging narrative, as noted above, there have been examples of nationalist fervour impacting on the public policy process in scotland which have placed demands on civil servants north of the border. there are also intriguing inter-institutional dynamics here if one considers the fact that reserved areas of public policy (which have health security implications) are legislated for in england (such as counter-terrorism policy which include measures to manage biosecurity) and the uk government can become protectionist when it comes to sharing information with subnational government despite public health being fully devolved to scotland. this serves to demonstrate that the case of public health threats fit with the perspectives of those who consider there to be an "unequal plurality" and a "predominantly asymmetric imbalance" (marsh et al., , p. ) in uk governance. this is certainly the case for the context of contingencies management processes for uk health security. the paper has provided key insights into strategic-level relationships across multiple levels of governance in relation to contingencies management policy-making for health security. it has sought to unpack some of the political multi-level policy complexities associated with managing pandemic influenza as a "wicked problem". contingency management processes in relation to this case study highlights the considerable public policy and political challenges, articulated by for policy elites, in terms of risk communication, the internationalisation and europeanisation of national contingencies management processes and uk national-subnational relations. the lens adopted by this paper, in terms of identifying the perspectives of policy elites, has emerged out of the desire to address a lacuna in uk disaster and crisis research in that there is a dearth of case-based analyses of the challenges and paradoxes of contingencies management processes from a "macro" governance position. by interrogating the case of pandemic influenza the paper highlights that the recent high profile debates over the efficacy of tamiflu instigated by the cochrane review is but one example of the governance challenges that face policy elites. from a practical point of view it is important that risk management registers (i.e. organisational systems for identifying levels of risks and countermeasures) at different tiers of governance address the management of policy and political relations across such levels and that this is continually evaluated as a result of bureaucratic coordination and conflict challenges (which are likely to emerge, in part, by constitutional reforms). this research also presents opportunities for comparative research in terms of the multi-level governance processes for contingencies management in the context of health security. this includes whether the findings of the uk experience are translatable to other state contexts with regards to the management of "wicked problems" from an elite perspective. tamiflu is the antiviral drug stockpiled by uk government to be taken in the event of a pandemic in order to alleviate symptoms and complications of influenza such as pneumonia england related to h n had been recorded, in scotland, in wales and in northern ireland confronting catastrophe: new perspectives on natural disaster towards the development of a standard in emergency planning essence of decision: explaining the cuban missile crisis what kind of thing is resilience key concepts in governance preparing for critical infrastructure breakdowns: the limits of crisis management and the need for resilience the politics of crisis management: public leadership under pressure introduction: an agenda for resilience research in politics and international relations the influenza pandemic -an independent review of the uk response to the influenza pandemic disasters and the sequence-pattern concept of social change mission improbable: using fantasy documents to tame disasters rescaling and responsibilising the politics of urban resilience: from national security to local place-making pandemic influenza in the uk and eu competence in health security policy do all crises have to become disasters? risk and risk mitigation national framework for responding to an influenza pandemic and supporting guidance uk pandemic preparedness strategy interview with the author mission impossible? planning and preparing for crisis wicked problems,' public policy, and administrative theory: lessons from the gm food regulatory arena the handbook of political science: strategies of inquiry global health security initiative five misunderstandings about case study research tamiflu: millions wasted on flu drug, claims major report what tamiflu tells us about drug trials and big pharma symbols, rituals and power: the lost dimensions of crisis management crisis decision making: the centralization thesis revisited sars and emerging infectious diseases: a challenge to place global solidarity above national sovereignty interview with the author the new public management: a recipe for disaster? neuraminidase inhibitors for preventing and treating influenza in healthy adults and children (review) the securitisation of pandemic influenza: framing, security and public policy global health governance: crisis, institutions and political economy interview with the author drugs given for swine flu were waste of £ m disaster as systemic event and social catalyst american business, public policy, case studies, and political theory overview: crisis management, influences, responses and evaluation unequal plurality: towards an asymmetric power model of british politics pandemic influenza remains the top risk for england and the uk definitions and the development of a theoretical superstructure for disaster research preparedness for emergency response: guidelines for the emergency planning process what is a disaster? new answers to old questions from accident to disaster: the response to the hercules crash the bureau-politics of crisis management disaster recovery after hurricane hugo in south carolina, natural hazards research and applications information center interview with the author in the eyes of the beholder? making sense of the systems(s) of disaster(s) acts of god: the unusual history of natural disasters in america man-made disasters wicked problems, knowledge challenges, and collaborative capacity builders in network settings foreign policy and health security an economic theory of democracy uk devolution and the european union: a tale of cooperative asymmetry pandemic influenza preparedness in the asia-pacific region serious cross-border threats to health risk and crisis management in the public sector crises and crisis management: toward comprehensive government decision making the changing world of crises and crisis management about the author the project, funded by the economic and social research council, concerned analysing the dynamics of policy and organisational change in relation to the uk animal health security sector (with particular emphasis on foot and mouth disease and avian flu). the doctoral thesis was awarded the sir walter bagehot prize by the uk political studies association for its contribution to research in public policy and administration. after completing his phd dr connolly worked as a policy adviser in the scottish public sector (nhs health scotland) and returned to academia on a full-time basis in for instructions on how to order reprints of this article, please visit our website: www.emeraldgrouppublishing.com/licensing/reprints.htm or contact us for further details: permissions@emeraldinsight key: cord- -b s es authors: kelso, joel k; halder, nilimesh; postma, maarten j; milne, george j title: economic analysis of pandemic influenza mitigation strategies for five pandemic severity categories date: - - journal: bmc public health doi: . / - - - sha: doc_id: cord_uid: b s es background: the threat of emergence of a human-to-human transmissible strain of highly pathogenic influenza a(h n ) is very real, and is reinforced by recent results showing that genetically modified a(h n ) may be readily transmitted between ferrets. public health authorities are hesitant in introducing social distancing interventions due to societal disruption and productivity losses. this study estimates the effectiveness and total cost (from a societal perspective, with a lifespan time horizon) of a comprehensive range of social distancing and antiviral drug strategies, under a range of pandemic severity categories. methods: an economic analysis was conducted using a simulation model of a community of ~ , in australia. data from the pandemic was used to derive relationships between the case fatality rate (cfr) and hospitalization rates for each of five pandemic severity categories, with cfr ranging from . % to . %. results: for a pandemic with basic reproduction number r( ) = . , adopting no interventions resulted in total costs ranging from $ per person for a pandemic at category (cfr . %) to $ , per person at category (cfr . %). for severe pandemics of category (cfr . %) and greater, a strategy combining antiviral treatment and prophylaxis, extended school closure and community contact reduction resulted in the lowest total cost of any strategy, costing $ , per person at category . this strategy was highly effective, reducing the attack rate to %. with low severity pandemics costs are dominated by productivity losses due to illness and social distancing interventions, whereas higher severity pandemic costs are dominated by healthcare costs and costs arising from productivity losses due to death. conclusions: for pandemics in high severity categories the strategies with the lowest total cost to society involve rigorous, sustained social distancing, which are considered unacceptable for low severity pandemics due to societal disruption and cost. results: for a pandemic with basic reproduction number r = . , adopting no interventions resulted in total costs ranging from $ per person for a pandemic at category (cfr . %) to $ , per person at category (cfr . %). for severe pandemics of category (cfr . %) and greater, a strategy combining antiviral treatment and prophylaxis, extended school closure and community contact reduction resulted in the lowest total cost of any strategy, costing $ , per person at category . this strategy was highly effective, reducing the attack rate to %. with low severity pandemics costs are dominated by productivity losses due to illness and social distancing interventions, whereas higher severity pandemic costs are dominated by healthcare costs and costs arising from productivity losses due to death. conclusions: for pandemics in high severity categories the strategies with the lowest total cost to society involve rigorous, sustained social distancing, which are considered unacceptable for low severity pandemics due to societal disruption and cost. keywords: pandemic influenza, economic analysis, antiviral medication, social distancing, pandemic severity, case fatality ratio background while the h n virus spread world-wide and was classed as a pandemic, the severity of resulting symptoms, as quantified by morbidity and mortality rates, was lower than that which had previously occurred in many seasonal epidemics [ ] [ ] [ ] . the pandemic thus highlighted a further factor which must be considered when determining which public health intervention strategies to recommend, namely the severity of symptoms arising from a given emergent influenza strain. the mild symptoms of h n resulted in a reluctance of public health authorities to use rigorous social distancing interventions due to their disruptive effects, even though modelling has previously suggested that they could be highly effective in reducing the illness attack rate [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . had the h n influenza strain been highly pathogenic, more timely and rigorous responses would have been necessary to mitigate the resultant adverse health outcomes. furthermore, there is continuing concern that a highly pathogenic avian influenza a(h n ) strain may become transmissible between humans. this scenario is highlighted by the large reservoir of influenza a(h n ) in poultry in south-east asia [ ] , and recent experimental results which have shown that the a (h n ) virus may be genetically modified to become readily transmissible between ferrets, a commonly used animal model for human influenza transmission studies [ ] [ ] [ ] . the severity of a particular influenza strain directly impacts on the cost of any pandemic; increased severity increases health care costs and escalates productivity losses due to a) absenteeism arising from increased illness and b) increased mortality rates. in this study, the role which pandemic severity has on the total cost of a pandemic for a range of potential intervention strategies is analysed, and for highly pathogenic influenza strains inducing significant morbidity and mortality, as occurred during the pandemic [ , ] , the results suggest which intervention strategies are warranted in terms of reduction of illness and total pandemic cost. this study adopts a societal perspective on the cost of a pandemic, with the time horizon being the lifetime of individuals experiencing the pandemic. we used a detailed, individual-based simulation model of a real community in the south-west of western australia, the town of albany with a population of approximately , , to simulate the dynamics of an influenza pandemic. comparing simulations with and without interventions in place allowed us to analyse the effect which a range of interventions have on reducing the attack rate and on the health of each individual in the modelled community. epidemic outcome data produced by the simulation model were used to determine health outcomes involving hospitalisation, icu treatment, and death. in turn, these healthcare outcomes, together with productivity losses due to removal from the workforce, were used to estimate the overall cost of interventions. figure provides an overview of this analysis methodology, showing each of the processes that make up the methodology, their input parameters and the resulting data generated by the process. the simulation model captures the contact dynamics of the population of albany, western australia using census and state and local government data [ ] . these data allowed us to replicate the individual age and household structure of all households in this town of approximately , individuals, and also allowed for the construction of an explicit contact network linking households, schools, workplaces and other meeting places by allocating individuals to workplaces and schools. the modelled community was chosen so as to be representative of a developed world population, and selfcontained in the sense that all major locales for interpersonal mixing were represented within the community. the model includes both urban and rural components, a central commercial core, a complete set of schools (covering all age groups), and a mix of large and small employers. the community is also of a size where public health interventions could be uniformly implemented based on local information. the model captures explicit person-to-person contact with the contact network describing population mobility occurring between households, schools, workplaces and the wider community as shown in figure . the virus spreads through the community due to this mobility, as transmission occurs between individuals when they are co-located, possibly following a move from one location to another. for figure overview of pandemic cost analysis methodology. input parameters are shown on the left in boxes with blue text, with arrows indicating to which part of the cost analysis methodology they apply. boxes with white text represent different processes of the methodologyeach process is described in the methods section under a subsection of the same name. boxes with green text appearing at the bottom and on the right represent results generated by the analysis. example, an infectious child moves from household to school on a given day, and infects two further children; they return to households and and, following virus incubation, become infectious and may infect other household members in their households. note that these households may be geographically separate, but are connected via contact of children at school. each household contains uniquely identified individuals. children and adults were assigned by an allocation algorithm to school classes and workplaces, respectively. the assignment of children to classes was based on age, school class size data, and proximity between schools and households; the assignment of adults to workplaces was based on workplace size and commuter survey data. in addition to contact occurring in households and mixing hubs, community contact was introduced to capture mixing which occurs outwith these locales and in the wider community. the number of contacts made by each individual each day in school, work and community settings were adjusted to reproduce the proportion of cases occurring in different settings as reported by empirical studies, specifically % of infections occurred in households, % in schools and workplaces, and % in the wider community [ ] [ ] [ ] . contacts within schools and workplaces occurred in fixed-size mixing groups of maximum size . within mixing groups contact was assumed to be homogeneous. community contacts occurred between randomly selected individuals, weighted toward pairs of individuals located in neighbouring households. a simulation algorithm, realised in the c++ programming language, manipulates the underlying demographic model and captures both population mobility and the time-changing infectivity profile of each individual. each individual has their infectivity status denoted by one of the four (susceptible, exposed, infectious, recovered) states at any time point during the duration of the simulated period. the simulation algorithm captures the state of the whole population twice per day, a daytime pointin-time snapshot and an evening snapshot, with individuals (possibly) moving locations between successive day or night periods, such as household to school or workplace for the day phase, returning to home for the night period. individuals come into contact with other individuals on a one-to-one basis in each location, with possible influenza transmission then occurring. individuals in each household and contact hub make contacts within a close-contact mixing group, taken to be the entire household or a subset of larger hubs, and also make additional non hub-based random community contacts. the attributes of the various locations in which individuals come into potentially infectious contact are summarized in table . using the contact, mobility and transmission features described above, stochastic simulations of influenza spread were conducted. all simulations were repeated times with random numbers controlling the outcome of stochastic events (the locality of seeded infected individuals and the probability of transmission) and the results were averaged. analysis of this simulation model has shown that the -run mean attack rate is highly unlikely ( % confidence) to differ by more than . % from the mean attack rate of a much larger set of experiment repeats. one new infection per day was introduced into the population during the whole period of the simulations, and randomly allocated to a household. this seeding assumption of case per day was chosen to reliably begin a local epidemic in every stochastic simulation. for the transmission characteristics described above, analysis shows that seeding at this rate for days results in a sustained epidemic in > % of the simulation runs and % with two weeks of seeding, with higher percentages for the higher transmissibility scenarios. seeding at this rate is continued throughout the simulation in order to capture the case where an epidemic may be initially suppressed by a rigorous intervention strategy, but may subsequently break out if intervention measures are relaxed. after the beginning of a sustained local epidemic, any subsequent variation in the amount of seeding has very little effect on the progress of the local epidemic, as the number of imported cases is much smaller than those generated by the local epidemic. preliminary analyses using the present model have shown that even if the seeding rate is increased to infections per day, after days the number of infections generated from the selfsustained local epidemic is twice the number of imported infections, and by days local infections outnumber imported infections by a factor of . the simulation period was divided into hour day/ night periods and during each period a nominal location for each individual was determined. this took into consideration the cycle type (day/night, weekday/weekend), infection state of each individual and whether child supervision was needed to look after a child at home. individuals occupying the same location during the same time period were assumed to come into potential infective contact. details of the simulation procedure are presented in [ ] . in the simulation model, we assumed that infectious transmission could occur when an infectious and susceptible individual came into contact during a simulation cycle. following each contact a new infection state for the susceptible individual (either to remain susceptible or to become infected) was randomly chosen via a bernoulli trail [ ] . once infected, an individual progressed through a series of infection states according to a fixed timeline. the probability that a susceptible individual would be infected by an infectious individual was calculated according to the following transmission function, which takes into account the disease infectivity of the infectious individual i i and the susceptibility of susceptible individual i s at the time of contact. maximum group size is . tertiary and vocational education institutions, number and size determined from state education department data. weekdays during day cycle. young adult and adult individuals who are allocated into the hub if they are active*. maximum group size is . workplace number and size of determined for local government business survey data. weekdays during day cycle. adult individuals who are allocated into the hub if they are active * . maximum group size is . community represents all contact between individuals in the community that is not repeated on a daily basis. everyday during day cycle. all individuals make contacts if they are active*, contact is random but weighted towards pairs with nearby household locations. * all individuals are active during day cycles unless: he/she is symptomatically infected and chooses to withdraw to household ( % chance for adults, % for children); or if his/her school or workplace is affected by social distancing interventions; or if he/she is a parent of a child who is inactive (only one parent per family is affected this way). the baseline transmission coefficient β was initially chosen to give an epidemic with a final attack rate of . %, which is consistent with seasonal influenza as estimated in [ ] (in table three of that paper). to achieve simulations under a range of basic reproduction numbers (r ), β was increased from this baseline value to achieve epidemics of various r magnitudes; details of the procedure for estimating β and r are given in [ ] . a reproduction number of . was used as a baseline assumption, and the sensitivity of results to this assumption was gauged by repeating all simulations and analyses for alternative reproduction numbers of . and . . a pandemic with a reproduction number of . corresponds to some estimations of the basic reproduction number of the pandemic [ ] [ ] [ ] [ ] , while a reproduction number of . corresponds to an upper bound on estimates of what may have occurred in the pandemic, with most estimates being in the range . - . [ , ] . the disease infectivity parameter inf(i i ) was set to for symptomatic individuals at the peak period of infection and then to . for the rest of the infectivity period. the infectiousness of asymptomatic individuals was also assumed to be . and this applies to all infected individuals after the latent period but before onset of symptoms. the infection profile of a symptomatic individual was assumed to last for days as follows: a . day latent period (with inf(i i ) set to ) was followed by day asymptomatic and infectious, where inf(i i ) is set to . ; then days at peak infectiousness (with inf(i i ) set to . ); followed by . days reduced infectiousness (with inf(i i )set to . ). for an infected but asymptomatic individual the whole infectious period (of . days) was at the reduced level of infectiousness with inf(i i ) set to . . this infectivity profile is a simplification of the infectivity distribution found in a study of viral shedding [ ] . as reported below in the results section for the unmitigated no intervention scenario, these assumptions regarding the duration of latent and infectious periods lead to a mean generation time (serial interval) of . days which is consistent with that estimated for h n influenza [ , , ] . following infection an individual was assumed to be immune to re-infection for the duration of the simulation. we further assume that influenza symptoms developed one day into the infectious period [ ] , with % of infections being asymptomatic among children and % being asymptomatic among adults. these percentages were derived by summing the age-specific antibody titres determined in [ ] . symptomatic individuals withdrew into the home with the following probabilities; adults % and children %, which is in keeping with the work of [ , ] . the susceptibility parameter susc(i s ) is a function directly dependent on the age of the susceptible individual. it captures age-varying susceptibility to transmission due to either partial prior immunity or age-related differences in contact behaviour. to achieve a realistic age specific infection rate, the age-specific susceptibility parameters were calibrated against the serologic infection rates for seasonal h n in - in tecumseh, michigan [ ] . the resulting age-specific attack rates are consistent with typical seasonal influenz, with a higher attack rate in children and young adults (details of the calibration procedure may be found in [ ] ). the antiviral efficacy factor avf(i i ,i s ) = ( -ave i )*( -ave s ) represents the potential reduction in infectiousness of an infected individual (denoted by ave i ) induced by antiviral treatment, and the reduction in susceptibility of a susceptible individual (denoted by ave s ) induced by antiviral prophylaxis. when no antiviral intervention was administrated the values of both ave i and ave s were assumed to be , indicating no reduction in infectiousness or susceptibility. however, when antiviral treatment was being applied to the infectious individual the value of ave i was set at . , capturing a reduction in infectiousness by a factor of % [ ] . similarly, when the susceptible individual was undergoing antiviral prophylaxis the value of ave s was set to . indicating a reduction in susceptibility by a factor of % [ ] . this estimate is higher than most previous modelling studies [ , , ] , which assume an ave s of %. this common assumption appears to stem from an estimate made in [ ] based on - trial data. our higher value is based on a more comprehensive estimation process reported in [ ] , which also incorporated data from an additional study performed in - [ ] . it is also in line with estimates of %- % reported in [ ] . we examined a comprehensive range of intervention strategies including school closure, antiviral drugs for treatment and prophylaxis, workplace non-attendance (workforce reduction) and community contact reduction. these interventions were considered individually and in combination and social distancing interventions were considered for either continuous periods (that is, until the local epidemic effectively ceased) or periods of fixed duration ( weeks or weeks). antiviral drug interventions and social distancing interventions were initiated when specific threshold numbers of symptomatic individuals were diagnosed in the community, and this triggered health authorities to mandate the intervention response. this threshold was taken to be . % of the population. this threshold was chosen based on a previous study with this simulation model, which found that it represents a robust compromise between early, effective intervention and "premature" intervention, which can result in sub-optimal outcomes when limited duration interventions are used [ ] . it was assumed that % of all symptomatic individuals were diagnosed, and that this diagnosis occurred at the time symptoms appeared. for continuous school closure, all schools were closed simultaneously once the intervention trigger threshold was reached. for fixed duration (e.g. weeks or weeks) school closure, schools were closed individually as follows: for a primary school the whole school was closed if or more cases were detected in the school; in a high school only the class members of the affected class were isolated (sent home and isolated at home) if no more than cases were diagnosed in a single class; however if there were more than cases diagnosed in the entire high school the school was closed. note that these school closure policies were only activated after the community-wide diagnosed case threshold was reached; cases occurring in schools before this time did not result in school closure. this policy of triggering school closure based on epidemic progression avoids premature school closure which can reduce the effectiveness of limited duration school closure [ , , ] ; see [ ] for a detailed description of school closure initiation triggering strategies. two primary antiviral drug strategies have been examined; antiviral drugs used solely for treatment of symptomatic cases (strategy t), and treatment plus prophylaxis of all household members of a symptomatic case (strategy av). a further strategy was also examined, in which prophylaxis was also extended to the contact group (school or workplace contacts) of a symptomatic case (strategy t + h + e). due to the logistical resources required, it is unlikely that this extended strategy could be implemented throughout a pandemic, and we do not report the results of this strategy in the main paper; full results are however given in (additional file ). antiviral treatment (and prophylaxis for household or work / school group contacts) was assumed to begin hours after the individual became symptomatic. it was assumed that an individual would receive at most one prophylactic course of antiviral drugs. further details of antiviral interventions are given in [ , ] . workforce reduction (wr) was modelled by assuming that for each day the intervention was in effect, each worker had a % probability of staying at home and thus did not make contact with co-workers. community contact reduction (ccr) was modelled by assuming that on days when the intervention was in effect, all individuals made % fewer random community contacts. the most rigorous social distancing interventions considered in this study, which we denote as strict social distancing, involve the combined activation of school closure with workforce reduction and/or community contact reduction, and for this to occur for significant time periods; continuous and weeks duration were considered. in the present study we simulated a total of intervention scenarios (for each of three reproduction numbers . , . and . ). to simplify the results, we only present those interventions that reduce the unmitigated illness attack rate by at least %. we defined five severity categories based on those proposed by the cdc [ ] . the cdc pandemic index was designed to better forecast the health impact of a pandemic, based on categories having cfrs ranging from < . % to > = . %, and allow intervention recommendations to match pandemic severity. the discrete cfrs used are listed in table . we extend the cdc categories to further include rates of hospitalisation and icu treatment, as described below using data collected during the pandemic in western australia, by the state department of health. these data permit case hospitalisation (icu and non-icu) and case fatality ratios (cfr) to be related, as described below. the least severe pandemic considered (category ) has cfr of . % which is at the upper end of estimates for the pandemic. initially, the pandemic cfr was estimated to be in the range . % - . % [ ] ; however recent reanalysis of global data from suggest a cfr (for the - age group) in the range . % - . % [ ] . cost analysis results for a pandemic with h n characteristics using a similar simulation model to the one described here can be found in [ ] . calculation of costs arising from lost productivity due to death and from hospitalisation of ill individuals requires that individual health outcomes (symptomatic illness, hospitalisation, icu admission, and death) be estimated for each severity level. the pandemic data from western australia was used to provide this relationship between the mortality rate and numbers requiring hospitalisation and icu care. these data indicated a non-icu hospitalisation to fatality ratio of : and an icu admission to fatality ratio of : . these values align with those in a previous study by presanis et al. in [ ] , which estimated the ratios in the ranges - to and . - . to , respectively. the economic analysis model translates the age-specific infection profile of each individual in the modelled symptomatic infectiousness timeline . day latent (non infectious), day asymptomatic; days peak symptomatic; . days post-peak symptomatic [ ] asymptomatic infectiousness timeline . day latent; . days asymptomatic [ ] asymptomatic infectiousness . [ ] peak symptomatic infectiousness . post-peak symptomatic infectiousness . [ ] probability of asymptomatic infection . [ ] probability average school closure cost (per student per day) $ . [ ] average gp visit cost $ . [ ] average hospitalization cost (per day) $ [ ] average icu cost (per day) $ [ , ] population, as derived by the albany simulation model, into the overall pandemic cost burden. total costs involve both direct healthcare costs (e.g. the cost of medical attention due to a gp visit, or for hospitalisation) and costs due to productivity loss [ , ] . pharmaceutical costs (i.e. costs related to antiviral drugs) are also estimated. all costs are reported in us dollars using consumer price index adjustments [ ] . us dollar values are used to make the results readily convertible to a wide range of countries. age-specific hospitalisation costs are achieved by multiplying the average cost per day by average length of stay for each age group [ , ] . hospitalisation costs, including icu costs, those involving medical practitioner visits, and antiviral drug (and their administration) costs are taken from the literature and are presented in table [ , , ] . the antiviral costs include the costs of maintaining an antiviral stockpile. this was calculated by multiplying the antiviral cost per course (but not the dispensing cost per course, which was included separately) by the expected number of times each antiviral course would expire and be replaced between pandemics, assuming a mean inter-pandemic period of . years (based on the occurrence of pandemics in , , and ) and an antiviral shelf life of years [ ] . treatment costs, lengths of stay in hospital (both icu and non-icu), and other cost data used in establishing the overall cost of mitigated and unmitigated epidemics in the modelled community are given in table . productivity losses due to illness and interventions (e.g. necessary child-care due to school closure and workforce reduction) were calculated according to the human capital approach, using average wages and average work-days lost; the latter being determined from day-to-day outbreak data generated by the simulation model. assumed average wages are given in table . school closure is assumed to give rise to two costs. the first, following the work of perlroth et al. [ ] , is a $ per student school day lost. this is intended to approximate the cost of additional education expense incurred in the futurewhich might occur for example in the form of additional holiday classes. the second component is lost productivity of parents staying at home to supervise children. the simulation model calculates whether this occurs for every day for every household, based on what interventions are in force (school closure and/or workforce reductions), whether children or adults are ill, the number of adults in the household, whether it is a school day, etc., and accumulates the cost accordingly. indirect production losses due to death were also derived using a human capital approach, based on the net present value of future earnings for an average age person in each age group. this was calculated by multiplying the age-specific number of deaths due to illness by the average expectancy in years of future earnings of an individual by an average annual income [ ] . we assumed a maximum earning period up to age . productivity losses due to death were discounted at % annually, which is a standard discounting rate used to express future income in present value [ ] . to provide an alternative analysis, total costs were also calculated without this long-term productivity loss due to death component. overview figure presents the final attack rate (ar) and the total cost of the epidemic for each intervention strategy applied, for a pandemic with a basic reproduction number of r = . . although costs are calculated from the whole-of-society perspective, total costs are presented as a cost per person in the community, calculated by dividing the simulated cost of the pandemic by the population of~ , , in order to make the results more easily transferable to communities of various sizes. strategies are ordered from left to right by increasing effectiveness (i.e. their ability to decrease the attack rate), and only intervention strategies that reduce the attack rate by at least % are included. figure shows three distinctive features. firstly, for an epidemic with basic reproduction number r = . , no single intervention is effective in reducing the attack rate by more than %, and thus do not appear in figure . this finding is consistent with previous modelling studies which found that layering of multiple interventions is necessary to achieve substantial attack rate reductions [ ] [ ] [ ] [ ] [ ] [ ] , , ] . secondly, higher severity pandemics have higher total costs. total costs of unmitigated pandemics range from $ to $ per person for pandemics from category to category (see table ). thirdly, for high severity pandemics total costs are lower for the more effective intervention strategies. figure presents the constituent components that make up the total cost of each intervention and severity category, measured in terms of cost per person in the modelled community. three distinctive features can be seen in figure . firstly, for high severity pandemics costs are dominated by productivity losses due to death and health care costs. secondly, for low severity pandemics costs are dominated by social distancing and illness costs. thirdly, for all severity categories antiviral costs are comparatively low when compared with all other cost components of antiviral based intervention strategies. antiviral costs never constitute more than % of the total cost, and for all severity categories greater than (cfr > . %) antiviral costs are always the smallest cost component. below we report on effectiveness, total costs and cost components of interventions for pandemics with high and low severity. these cost data are presented in table . figure summarises the characteristics of key intervention strategies. for high severity pandemics (categories and , with case fatality rates above . %) the least costly strategy combines continuous school closure, community contact reduction, antiviral treatment and antiviral prophylaxis. at category this strategy has a total cost of $ , per person, a net benefit of $ per person compared to no intervention. this strategy is also the most effective intervention strategy, reducing the attack rate from % to . %. the results indicate that strategies with the lowest total costs are also the most effective. for a category pandemic the most effective strategies, all of which reduce the attack rate to less than %, have total costs ranging from $ , to $ , per person, which is less than one-third the cost of the unmitigated pandemic ($ , ), showing the substantial net benefit of effective interventions for high severity pandemics. these strategies all feature continuous school closure, with either continuous community contact reduction or antiviral treatment and prophylaxis. the ability of highly effective interventions to reduce the total cost of a high severity pandemic is due to the largest component of the overall cost being productivity losses arising from deaths. this is illustrated in figure which shows the cost components for each intervention. it can be seen that the majority of the cost for an unmitigated pandemic of severity category and is due to death-related productivity losses (shown in purple). although highly effective interventions incur large intervention-related productivity losses (shown in green), for high severity pandemics these intervention costs are more than outweighed by the reduction in medical costs and death-related productivity losses. the most costly intervention considered (i.e. which still reduced the attack rate by at least %) is continuous school closure combined with continuous workforce reduction, which costs $ , per person. for low severity pandemics (in category , having cfr < = . %) the intervention strategy with the lowest total cost considered is weeks school closure combined with antiviral treatment and prophylaxis, costing $ per person which represents a net saving of $ per person compared to no intervention. however, this strategy is not as effective as other intervention strategies, reducing the attack rate to only %. the most effective intervention (combined continuous school closure, community contact reduction, and antiviral treatment and household prophylaxis), which reduces the attack rate to . %, costs $ per person, a net benefit of $ per person compared to no intervention. figure shows that for category and pandemics, although highly effective intervention measures reduce medical costs and death-related productivity losses, they incur larger costs due to intervention-related lost productivity. the most costly intervention considered is continuous school closure combined with continuous workforce reduction, which costs $ , per person, a net cost of $ per person compared to no intervention. this is due to the large cost associated with % workforce absenteeism. an important subset of intervention strategies are those consisting of purely social distancing interventions. in the case that antiviral drugs are unavailable or ineffective, only these non-pharmaceutical interventions strategies will be available. the most effective non-pharmaceutical strategy is the continuous application of the three social distancing interventions, school closure, workforce reductions, and community contact reduction, which reduces the attack rate to %. this intervention has a total cost ranging from $ , to $ , per person for severity categories ranging from to respectively. the least costly non-pharmaceutical strategy omits workforce reduction, resulting in a slightly higher attack rate of %. this intervention has a total cost ranging from $ to $ , per person for severity categories ranging from to respectively. the costing model used for this analysis includes future productivity losses from deaths caused by the pandemic. this long-term cost is often not included in cost-utility analyses. the inclusion of death-related productivity losses greatly increases the total costs of severe pandemics. however, even if these costs are not included, medical costs (due to hospitalisation and icu usage) play a similar, although less extreme, role. if long-term productivity losses due to death are not included in the costing model, the total cost of the pandemic is not surprisingly lower. however the effectiveness and relative total costs of intervention strategiesthat is, the ranking of intervention strategies by total cost -remains the same whether or not death-related productivity losses are included (spearman's rank correlation coefficient r = . , p = . for a null hypothesis that rankings are uncorrelated). full cost results of an alternate analysis that omits death-related productivity losses is contained in an additional file accompanying this paper (additional file ), and is summarised below. for category , when death-related productivity losses are not included the total cost of intervention strategies ranges from $ to $ , . this range is much smaller than if death-related productivity losses are included, in which case total cost ranges from $ , to $ , . for lower severity pandemics with lower case fatality ratios, the contribution of death-related productivity losses is naturally smaller. for category , when death-related productivity losses are not included total cost ranges from $ to $ , ; with death-related productivity losses the range is $ to $ , . if death-related productivity losses are not included, social distancing and illness costs dominate the total cost of each intervention strategy for low severity pandemics, while health care costs dominate the cost profile for high severity pandemics. sensitivity analyses were conducted to examine the extent to which these results depend upon uncertain model parameters that may impact on the cost or effectiveness of interventions. the methodology adopted was to identify assumptions and model parameters known to have an effect on intervention outcomes, taken from previous studies with this simulation model [ , , , , , ] , and to perform univariate analyses on each, examining parameter values both significantly higher and lower than figure breakdown of pandemic cost components. breakdown of pandemic costs shown as horizontal bar, for each intervention strategy and each severity category. coloured segments of each bar represent cost components as follows: (blue) health care; (red) antiviral drugs, including dispensing costs; (green) productivity losses due to illness and social distancing interventions; (purple) productivity losses due to deaths. note that horizontal scale is different for each severity category. values are for a pandemic with unmitigated transmissibility of r = . . interventions abbreviated as: scschool closure; ccr - % community contact reduction; wr - % workforce reduction; , intervention duration in weeks; contcontinuous duration; avantiviral treatment of diagnosed symptomatic cases and antiviral prophylaxis of household members of diagnosed symptomatic cases. the baseline values. alternative parameter settings were analysed for transmissibility (as characterised by the basic reproduction number r ), voluntary household isolation of symptomatic individuals, antiviral efficacy, compliance to home isolation during school closure, degree of workforce reduction, and degree of community contact reduction. a common finding across all sensitivity analyses was that alternative parameter settings that rendered interventions less effective resulted in strategies that not only had higher attack rates, but also had higher total pandemic costs, with this effect being most pronounced for pandemics of high severity. further details and results of the sensitivity analysis can be found in an additional file accompanying this paper (additional file ). the need for an unambiguous, extended definition of severity has been noted in the world health organization report on the handling of the pandemic [ ] , which highlights the impact pandemic severity has on health care provision and associated costs. in the absence of such definitions, an extended severity metric is presented. this extends the case fatality ratio (cfr) severity scale devised by the cdc [ ] , with hospitalisation and intensive care unit (icu) data collected in australia during the pandemic. these data have been used to generate a more extensive notion of pandemic severity, relating actual age-specific attack rates with agespecific hospitalisation and mortality rates, thereby contributing to the realism of both the simulation model and the economic analysis. this pandemic severity scale together with a pandemic spread simulation model allows the calculation of the total cost of a pandemic, and to estimate the relative magnitude of all the factors that contribute to the pandemic cost, including not only pharmaceutical and medical costs, but also productivity losses due to absenteeism and death. the severity of a future pandemic is shown to have a major impact on the overall cost to a nation. unsurprisingly, high severity pandemics are shown to be significantly more costly than those of low severity, using a costing methodology which includes costs arising from losses to the economy due to death, in addition to intervention and healthcare costs. a key finding of this study is that at high severity categories, total pandemic costs are dominated by hospitalization costs and productivity losses due to death, while at low severities costs are dominated by productivity losses due to social distancing interventions resulting from closed schools and workplaces. consequently, findings indicate that at high severity, the interventions that are the most effective also have the lowest total cost. highly effective interventions greatly reduce the attack rate and consequently the number of deaths, which in turn reduces productivity losses due to death. although highly effective interventions incur significant intervention-related productivity losses, for severe pandemics having high cfr, these intervention costs are more than compensated for by the reduction in death-related productivity losses, resulting in lower overall costs. conversely, for low severity pandemics, although highly effective intervention measures do reduce medical costs and death-related productivity losses, these savings can be smaller than costs incurred due to intervention-related lost productivity, resulting in total costs that are higher than the unmitigated baseline. antiviral strategies alone are shown to be ineffective in reducing the attack rate by at least %. however, the addition of antiviral case treatment and household prophylaxis to any social distancing strategy always resulted in lower attack rates and lower total costs when compared to purely social distancing interventions. the cost of all antiviral interventions constitutes a small fraction of total pandemic costs, and these costs are outweighed by both the healthcare costs prevented, and productivity gained, by their use in preventing illness and death. it should be noted that the lowest severity category considered, pandemic category , has a cfr of . % which is at the upper end of cfr estimates for the pandemic, which has been estimated to have a cfr of between . % and . % [ ] . thus, the cost results are not directly applicable to the pandemic. vaccination has been deliberately omitted from this study. the effectiveness and cost effectiveness of vaccination will depend crucially on the timing of the availability of the vaccine relative to the arrival of the pandemic in the communityvaccination cannot be plausibly modelled without considering this delay, and how it interacts with the timing of introduction and relaxation of other, rapidly activated interventions. the examination these timing issues for realistic pandemic scenarios that include both vaccination and social distancing / antiviral interventions is an important avenue for future work. as they stand, the results of this study, specifically the "continuous" duration social distancing strategies, can be considered to be models of interim interventions to be used prior to a vaccination campaign. the results are based on the community structure, demographics and healthcare system of a combined rural and urban australian community, and as such may not be applicable to developing world communities with different population or healthcare characteristics. although the cost and effectiveness results are directly applicable to pandemic interventions in a small community of , individuals, we expect that the per-capita costs and final attack rate percentages derived in this study can be extended to larger populations with similar demographics, provided a number of conditions are met. for the results to be generalisable, it needs to be assumed that communities making up the larger population implement the same intervention strategies, and instigate interventions upon the arrival of the pandemic in the local community (according to the criteria described in the methods section). the assumption is also made that there are no travel restrictions between communities. it should be noted that the single-community epidemic results do not predict the overall timing of the pandemic in the larger population. the simulation model used in this study has been used in previous studies to examine various aspects of social distancing and pharmaceutical (antiviral and vaccine) pandemic influenza interventions [ , , , , , ]. this simulation model shares characteristics with other individual-based pandemic influenza simulation models that have been employed at a variety of scales, including small communities [ , , , , , ] , cities [ , ] , countries [ , , , ] and whole continents [ ] . several related studies which also used individualbased simulation models of influenza spread coupled with costing models are those of those of sander et al., perlroth et al., brown et al., and andradottir et al. [ , , , ] . the current study extends upon the scope of these studies in several ways: five gradations of pandemic severity are considered, more combinations of interventions are considered, social distancing interventions of varying durations are considered, and probabilities of severe health outcomes for each severity category are based on fatality, hospitalization and icu usage data as observed from the pandemic. also in contrast with those models, we have chosen to include a cost component arising from productivity loss due to death, though a similar costing without death-related productivity losses has been included in (additional file ). for a pandemic with very low severity, with a cfr consistent with mild seasonal influenza, and that of the pandemic, previous results with the simulation and costing model used for this paper coincide with the studies mentioned above [ ] . specifically, they showed that antiviral treatment and prophylaxis were effective in reducing the attack rate and had a low or negative incremental cost, and that adding continual school closure further decreased attack rates, but significantly increased total cost. for high severity pandemics the inclusion of productivity loss following death, as presented in this study, leads to a markedly different assessment of total costs when compared to the two studies quoted above that considered severe pandemics [ , ] . for example, perlroth et al. found that the incremental cost of adding continuous school closure to an antiviral strategy was always positive, even for pandemics with high transmissibility (r = . ) and a cfr of up to %, meaning that adding school closure always increased total costs. similarly sander et al. found that the addition of continuous school closure to an extended antiviral strategy also increased total costs, including pandemics with a % cfr. in contrast, we found that adding continuous school closure to an extended prophylaxis strategy reduced total costs where the cfr was . % or greater (i.e. category and above), for a pandemic with r = . . the study of smith et al. estimated the economic impact of pandemic influenza on gross domestic product for a range of transmissibility and severity values [ ] . consistent with our study was the finding that at low severity the largest economic impacts of a pandemic would be due to school closure (effective but costly) and workplace absenteeism (largely ineffective and costly). like the other two studies mentioned above, the study of smith et al. did not include future productivity losses due to death. as a result, in contrast to our findings, they did not find that, for severe pandemics, the high short-term costs of rigorous social distancing interventions were outweighed by future productivity of people whose lives were saved by the intervention. in this study we considered the case of a pandemic that infects a significant proportion of the population, and thus incurs significant direct costs stemming from medical costs and productivity losses. however, in the case of a pandemic perceived by the public to be severe, there are likely to be additional indirect macroeconomic impacts caused by disruption of trade and tourism, consumer demand and supply, and investor confidence [ , ] . in the case of a pandemic of high severity (i.e. high case fatality ratio) but low transmissibility, these indirect effects and their resulting societal costs may constitute the main economic impact of the pandemic, an effect seen with the sars outbreak in [ ] . the results of this study are relevant to public health authorities, both in the revision of pandemic preparedness plans, and for decision-making during an emerging influenza pandemic. recent modelling research has shown that combinations of social distancing and pharmaceutical interventions may be highly effective in reducing the attack rate of a future pandemic [ , , , , , , , , ] . public health authorities are aware that rigorous social distancing measures, which were used successfully in some cities during the pandemic [ , ] , when pharmaceutical measures were unavailable, would be highly unpopular due to resulting societal disruption, and costly due to associated productivity losses [ ] . the results of this study give guidance as to the pandemic characteristics which warrant the use of such interventions. the results highlight the importance of understanding the severity of an emergent pandemic as soon as possible, as this gives guidance as to which intervention strategy to adopt. in the likely situation where the severity of an emerging pandemic is initially unknown (but is suspected to be greater than that of seasonal influenza), the results indicate that the most appropriate intervention strategy is to instigate school closure and community contact reduction, combined with antiviral drug treatment and household prophylaxis, as soon as transmission has been confirmed in the community. if severity is determined to be low, public health authorities may consider relaxing social distancing measures. in the case of a category pandemic (cfr approximately . %), little is lost by the early imposition and subsequent relaxation of social distancing interventions: results indicate that even if schools are closed for weeks while severity is being determined, the total cost of the pandemic is lower than if no interventions had been enacted. if severity is determined to be high, extending the duration of social distancing interventions results in both net savings to society and reduction in mortality. anzic influenza investigators: critical care services and h n influenza in australia and new zealand europe's initial experience with pandemic (h n ) -mitigation and delaying policies and practices mortality from pandemic a/h n influenza in england: public health surveillance study analysis of the effectiveness of interventions used during the h n influenza pandemic developing guidelines for school closure interventions to be used during a future influenza pandemic mitigation strategies for pandemic influenza in the united states targeted social distancing design for pandemic influenza reducing the impact of the next influenza pandemic using household-based public health interventions effective, robust design of community mitigation for pandemic influenza: a systematic examination of proposed us guidance a small community model for the transmission of infectious diseases: comparison of school closure as an intervention in individual-based models of an influenza pandemic simulation suggests that rapid activation of social distancing can arrest epidemic development due to a novel strain of influenza school closure is currently the main strategy to mitigate influenza a(h n )v: a modelling study modelling mitigation strategies for pandemic (h n ) nature outlook: influenza airborne transmission of influenza a/h n virus between ferrets experimental adaptation of an influenza h ha confers respiratory droplet transmission to a reassortant h ha/h n virus in ferrets the potential for respiratory droplet-transmissible a/h n influenza virus to evolve in a mammalian host statistics of influenza morbidity with special reference to certain factors in case incidence and case fatality emerging infections: pandemic influenza australian census a bayesian mcmc approach to study transmission of influenza: application to household longitudinal data estimating the impact of school closure on influenza transmission from sentinel data strategies for mitigating an influenza pandemic papoulis a: probability, random variables and stochastic processes tecumseh study of illness xiii. influenza infection and disease, - pandemic potential of a strain of influenza a (h n ): early findings pandemic (h n ) influenza community transmission was established in one australian state when the virus was first identified in north america estimating the reproduction number of the novel influenza a virus (h n ) in a southern hemisphere setting: preliminary estimate in new zealand epidemiological and transmissibility analysis of influenza a (h n ) v in a southern hemisphere setting: peru time lines of infection and disease in human influenza: a review of volunteer challenge studies early transmission characteristics of influenza a (h n ) v in australia: victorian state serial intervals and the temporal distribution of secondary infections within households of pandemic influenza a (h n ): implications for influenza control recommendations influenzavirus infections in seattle families, - containing pandemic influenza at the source design and evaluation of prophylactic interventions using infectious disease incidence data from close contact groups temporal factors in school closure policy for mitigating the spread of influenza the impact of case diagnosis coverage and diagnosis delays on the effectiveness of antiviral strategies in mitigating pandemic influenza a/h n containing pandemic influenza with antiviral agents management of influenza in households: a prospective, randomized comparison of oseltamivir treatment with or without postexposure prophylaxis neuraminidase inhibitors for influenza simulating school closure strategies to mitigate an influenza epidemic interim pre-pandemic planning guidance: community strategy for pandemic influenza mitigation in the united states cost-effectiveness of pharmaceutical-based pandemic influenza mitigation strategies health outcomes and costs of community mitigation strategies for an influenza pandemic in the united states economic evaluation of influenza pandemic mitigation strategies in the united states using a stochastic microsimulation transmission model direct medical cost of influenza-related hospitalizations in children responding to pandemic (h n ) influenza: the role of oseltamivir world health organization: making choices in health: who guide to cost-effectiveness analysis. geneva: world health organization the severity of pandemic h n influenza in the united states estimated global mortality associated with the first months of pandemic influenza a h n virus circulation: a modelling study cost-effective strategies for mitigating a future influenza pandemic with h n characteristics vaccination against pandemic influenza a/h n v in england: a real-time economic evaluation usa historical consumer price index economics of neuraminidase inhibitor stockpiling for pandemic influenza economic analysis of pandemic influenza vaccination strategies in singapore reactive strategies for containing developing outbreaks of pandemic influenza measures against transmission of pandemic h n influenza in japan in : simulation model who: report of the review committee on the functioning of the international health regulations ( ) in relation to pancemic (h n ) . geneva: world health organization an influenza simulation model for immunization studies individual--based computational modeling of smallpox epidemic control strategies modeling targeted layered containment of an influenza pandemic in the united states mitigation measures for pandemic influenza in italy: an individual based model considering different scenarios the role of population heterogeneity and human mobility in the spread of pandemic influenza would school closure for the h n influenza epidemic have been worth the cost?: a computational simulation of pennsylvania the economy-wide impact of pandemic influenza on the uk: a computable general equilibrium modelling experiment globalization and disease: the case of sars. asian economic papers global macroeconomic consequences of pandemic influenza. sydney australia: lowy institute for international policy the effect of public health measures on the influenza pandemic in u.s. cities quantifying social distancing arising from pandemic influenza economic analysis of pandemic influenza mitigation strategies for five pandemic severity categories additional file : additional results and sensitivity analyses. "milne pandemiccostadditionalfile .doc". competing interests gjm has received a travel grant from glaxosmithkline to attend an expert meeting in boston, usa; mjp has received travel grants from glaxosmithkline and wyeth to attend expert meetings in reykjavik, iceland, boston, usa and istanbul, turkey. jkk and nh have no potential competing interests. key: cord- -ih ci cl authors: overby, madison; pu, qinqin; wei, xiawei; wu, min title: calling for a united action to defeat covid- date: - - journal: precis clin med doi: . /pcmedi/pbaa sha: doc_id: cord_uid: ih ci cl the widespread and lingering pandemic of covid- is partly due to disjointed international countermeasures and policies enforced by different countries. and we have been witnessing disparity in policies and measures in different countries or regions, some in much better control. to effectively deal with this and future devastating pandemics, we as human beings must work together to coordinate a concerted, cooperative international policy to reduce or possibly avoid unnecessary health crisis, life and economic losses. portion of the international communities with irrational approaches to make the job much more difficult in curbing this disease and future pandemics. here, we attempt to discuss the lack of collaborations and how we can work in parallel internationally to avoid further devastating damages and contain the pandemic as soon as possible. policy changes implemented by central governments have been the single most effective way of controlling the spread thus far. "flattening the curve" has become a household term, which emphasizes the effect of staying home and preventing mass spread of covid- to decrease both infection rates and mortality rates. china was one example especially in asian countries that was able to lower transmission rates to near zero in the early months. they did this by enforcing the strictest isolation strategy: the suppression strategy . "traffic control, limitation of travel, extension of the chinese new year vacations, delay of returning to work, rigorous management of communities and even the wartime management have ensured that the susceptible population stay home" , . more countries are going to need to look towards the strict governmental action of china in order to get the virus under control sooner rather than later and prevent the potential "second wave and even multiple waves". the suppression strategy adopted by china and other asian countries such as south korea, japan, singapore, etc. is in contrast to the mitigation strategy which is most commonly executed in the western nations. the goal of the mitigation strategy is to slow the spread of the disease and mitigate the effects of the virus on the healthcare system as well as the social perception of the epidemic whereas the suppression strategy aims to reduce the transmission rate (r ) to less than one which essentially reverses the epidemic . policy implementations thus far are the only way all people will stay home and commit to social distancing. this was also seen more recently in spain, which was originally projected to have a similar outcome to the high mortalities of italy . spain hit its peak in late-march to early-april (ecdc, november, particularly frequently seen in old populations, like covid- " . this information has not been confirmed with other reports. however, had the italian authority taken strong action earlier after seeing the first case at the end of january , the situation would have not been such devastating. this suggests that the italian nation may have suffered the problem without sufficient awareness before the disease progressed to almost uncontrollable. policy changes are required to combat this type of pandemic. policy changes and an increase in social distancing will also ensure that medical personnel and supplies are not exhausted. the key to a successful pandemic response is control of medical supplies. there needs to be an abundance of supply in reserves in the case of disease outbreak as well as sufficient allocation of emergency medical supplies . the challenge for policy change is to make a unified and internationally coordinated effort to counteract an emerging pandemic, which is urgently lacking at the moment. due to the currently disorganized actions, people have witnessed covid- waves in multiple areas, countries and continents, which seems impossible to control in a timely manner and may result in continued and lingering recurrence. this is compounded by the mutations of the sars-cov- virus, which seems to be gaining strength during the spreading. as a typical example, the small spike in beijing from june - , was possibly a reentry from europe, appearing more lethal than the original wuhan strains infected with covid- while working with these patients. in the lombardy region of italy, which was faced with extreme shortages of both medical supplies and workers, % of healthcare workers contracted covid- during their attempt to diagnose and treat patients . the situation in lombardy got much worse before it got better, where medical personnel were being forced to distribute supplies based on personal discretion: deciding which patients were more likely to live or die with the assistance of medical support . in contrast to the situation in lombardy, a hospital in belgium had a high availability of ppe, high standards of infection prevention, pcr screening for symptomatic staff, and focused intensely on contact tracing and quarantine .the hospital in belgium tested hospital employees and people tested positive for igg antibodies for sars-cov- , which is approximately . % . finally, testing needs to be rapid and accurate to slow the spread of the virus both now and in the future. the high amount of asymptomatic cases makes this absolutely necessary. in order to return to normal life, people will have to be tested regardless of whether they are experiencing symptoms or not, which at this moment in time is not possible . early diagnosis, isolation, and treatment would ensue. this strategy of testing a majority of the population has seen success in south korea. as of february , , the average reproductive rate in korea was determined to be . . as a result of early widespread testing and an extremely fast social distancing response put in place by the government in korea, the basic reproductive rate was able to be kept to less than half of the international average. this very clearly shows the importance of a fast and thorough response in the eye of a pandemic storm. we know that during the current time international collaboration is a great trend and may be the only path to develop effective drugs and vaccines to conquer the pandemic. it is a positive response from some of pharmaceutic and philanthropic entities to bring together the dollars and workforces to more quickly discover and validate effective therapeutics or prevention measures. sources and has shown promise in its short three-year history. humanity will continue to foster this type of organization with more government involvement to expand efforts and funding levels. we believe that there will be bright future in front of us for vaccines and drug research. in summary, we have discussed the strategies and countermeasures from global levels to combat the insurmountable, devastating, lingering covid- pandemic. the single most important factor is the policy changes, which may be evolved with time, but should be based on solid and up to date scientific evidence, other nations' successful examples, and experts' opinions from international communities rather than individual leadership preference, cultural variation and political opinion. second, social distancing is widely applied internationally as a moderate means to curb the disease spread but requires high levels of individual cooperation. as the complete lockdown is highly effective to rapidly stop spreading it may be taken into modeling the control of covid- : impact of policy interventions and meteorological factors effectiveness of the measures to flatten the epidemic curve of covid- . the case of spain impact of climate and public health interventions on the covid- pandemic: a prospective cohort study international public health responses to covid- outbreak: a rapid review covid- and italy: what next? challenges to the system of reserve medical supplies for public health emergencies: reflections on the outbreak of the severe acute respiratory syndrome coronavirus (sars-cov- ) epidemic in china inter-hospital communication and transfer practices during covid- pandemic in karachi, pakistan. a brief overview should the world be worried about the 'explosive' new outbreak of coronavirus in beijing? time hospital-wide sars-cov- antibody screening in staff in a transmission potential and severity of covid- in south korea covid- : oxford team begins vaccine trials in brazil and south africa to determine efficacy safety, tolerability, and immunogenicity of a recombinant adenovirus type- vectored covid- vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial an mrna vaccine against sars-cov- -preliminary report remdesivir for or days in patients with severe covid- the authors acknowledge the national institutes of health for grants r ai , r ai - a , and p gm . the authors declare no conflicts of interest. mo and mw wrote the manuscript, qp, xw made comments. qp, mo, xw and mw revised the manuscript. key: cord- -fdn c hx authors: leanza, matthias title: the darkened horizon: two modes of organizing pandemics date: - - journal: how organizations manage the future doi: . / - - - - _ sha: doc_id: cord_uid: fdn c hx this chapter deals with the recent darkening of the future horizon in the global fight against pandemics. since roughly the year , the world health organization has collaborated with a large number of local actors and made a concentrated effort to protect the world’s population against emerging infectious diseases, such as severe acute respiratory syndrome (sars), swine flu, ebola and zika. although efforts have been made so that the spread of future infectious diseases will be contained through early intervention, the actors in charge anticipate that the extant measures will fail to some degree. they believe it is simply impossible to prevent all pandemics from happening. but steps can and should be taken to lessen the impact of an unavoidable pandemic through emergency preparation. this chapter deals with organizations and organizational networks as key actors in these processes of emergency planning. without the capacity of organizations to produce binding decisions for their members, which makes planning for an uncertain future possible, pandemic preparedness would not be feasible—especially not on a global scale. the horizon has darkened. the future no longer seems like an open space full of opportunities and risks. rather, what is in store appears to be deeply threatening. whether one thinks of global warming, terrorism or the continuing instability of the banking and finance sector, our expectations for the future in many areas of public life exemplify what craig calhoun ( , p. ) calls an 'emergency imaginary': 'a discourse of emergencies is now', as he wrote more than years ago in a diagnosis that is even more applicable today, 'central to international affairs. it shapes not only humanitarian assistance, but also military intervention and the pursuit of public health.' due to this emergency imaginary, we feel that our social institutions, our health and well-being, and even, as in the case of global warming, the future of mankind as such are deeply endangered. m. leanza (*) sociology department, university of basel, basel, switzerland this chapter deals with the recent darkening of the future horizon in the global fight against pandemics. around the year , the world health organization (who) started collaborating with a large number of local actors and made a concentrated effort to protect the world's population against emerging infectious diseases such as severe acute respiratory syndrome (sars), swine flu, ebola and zika. although efforts have been made so that the spread of future infectious diseases will be contained through early intervention, the actors in charge expect the extant measures to fail to some degree. they believe it is simply impossible to prevent all pandemics from happening. but steps can and should be taken through emergency preparation to lessen an unavoidable pandemic's impact. as andrew lakoff ( , pp. - ) summarizes: preparedness assumes the disruptive, potentially catastrophic nature of certain events. since the probability and severity of such events cannot be calculated, the only way to avert catastrophes is to have plans to address them already in place and to have exercised for their eventuality-in other words, to maintain an ongoing capability to respond appropriately. in recent years, scholars of security studies, cultural studies and other research areas have paid much attention to these developments in emergency preparedness, which, it is worth noting, are not limited to the domain of public health. this issue has primarily been addressed at two levels: first, by changing global security policies after the / attacks, and, second, by scrutinizing the narratives and rhetorical strategies through which the emergency imaginary is constructed and gains plausibility (e.g. massumi ; aradau and van munster ; horn ) . in this chapter, i will focus on organizations as key actors in these processes of emergency planning. without the capacity of organizations to produce binding decisions for their members, which allows them to plan for an uncertain future, pandemic preparedness would not be feasibleespecially not on a global scale. i will unfold my argument in four steps. with regard to the who, which was established in , i will discuss the question of how supranational coordination and planning for the future is rendered possible by building formal organizations and organizational networks at a global level. i will then highlight some aspects of the attempts undertaken by the who and its partners after the year to fight pandemics on a global scale. my analysis of relevant policy papers, legal norms and manuals shows that two different though complementary strategies are applied: early intervention and emergency planning. these are, as i will discuss more explicitly in the final section, two different kinds of organizing (for) the future or, to put it differently, two modes of how organizations manage pandemics. the overall aim of the empirical analysis offered in this chapter is to reconstruct organizational programmes and rationales rather than to give an account of the actual operations of these systems. the focus lies on public discourses and normative texts and not so much on the 'inside' of these organizations, meaning their day-to-day routines and practices. contagious diseases do not stop at state borders. pathogens circulate without regard for political and administrative spheres of influence. what gilles deleuze and félix guattari ( , introduction) establish for rhizomes in general also applies to infection chains in particular: by growing rampantly, they produce a 'deterritorializing effect'. pathogens connect distant regions and different kinds of people; zoonoses even trespass the boundary between animals and humans. by doing so, communicable diseases create spaces and communalities that did not exist before. this is also the reason why every epidemic requires new maps (e.g. koch ) . even though pathogens do not stop at state borders, sovereignty ends there, and the difficult terrain of diplomacy begins. the international sanitary conferences, which took place between and , made a first step towards creating a global field of public health (howard-jones ; bynum ) . while the first couple of these conferences-there were in all-dealt primarily, though not exclusively, with cholera, further diseases and topics were discussed and negotiated beginning in the s. laborious agreements regarding quarantine, inspection and surveillance measures were worked out and in some cases ratified. but the field of global health diplomacy did not receive a coordination and control unit until with the establishment of the who as a specialized agency of the united nations (zimmer ) . in passing the international health regulations (ihr) of , which superseded the international sanitation regulations of , the who established standards and norms with a legally binding character for its signatory states. the primary goal of these regulations was to provide 'maximum security against the international spread of disease with the minimum interference with world traffic' (who , p. ) . to this end, epidemiological surveillance and alarm systems were installed in signatory states, or already existing structures were expanded. in addition, the who made more specific efforts to combat infectious diseases. one of the first large projects was the global malaria eradication program ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . in order to defeat the dangerous tropical disease, the insecticide ddt (dichloro-diphenyl-trichloroethane) was used liberally and repeatedly in over countries. even though certain regions profited from this measure, the actors in charge had to accept in the end that this goal was, on the whole, too ambitious (zimmer , pp. - ) . more successful, however, was the vaccination programme against smallpox, which was enacted in and intensified in (fenner et al. (fenner et al. , pp. - , . after roughly years, it finally reached its goal. in , the who announced: 'smallpox is dead!' (ibid., p. ). sovereign nation states use the mechanism of formal organization to cooperate in this and further policy areas of international concern. while 'leagues of subjects' within a state 'savour of unlawful design', as thomas hobbes ( , p. ) famously wrote in leviathan, 'leagues between commonwealths, over whom there is no human power established to keep them all in awe, are not only lawful, but also profitable for the time they last'. as well as mutual agreements and legally binding contracts, inter-or supranational organizations are a specific form taken by such leagues today. drawing on niklas luhmann ( ) , organizations can be perceived as a type of social system that is defined by formal membership roles and processes of decision-making. as inter-or supranational organizations demonstrate, not only natural but also legal persons, such as states, can become members of organizations. by entering an organization, sovereign nation states are, in principle, capable of producing collectively binding decisions on a global level, without losing their autonomy to a sovereign world state. today, a wide range of organizations constitute the global field of public health and disease control (youde , part ) . besides the who, they include the world bank, unaids (which was established in ) and governmental and nongovernmental organizations. these organizations are the main action centres within the field of global public health. they deliver expertise, develop policies, launch programmes and mobilize the global community. to achieve their goals, they regularly ally with other organizations and build networks that can be activated when necessary. this especially holds true for the global fight against pandemics. in certain respects, in order to deal with an unfolding threat, organizational networks have to spread as rampantly as the pathogens themselves. otherwise they will be unable to prevent further harm. in , and thus very much in the shadow of the global aids crisis, the who laid the foundation for a new regime in the global fight against pandemics by setting up the global outbreak alert and response network (goarn). since then it has acted in more than cases (mackenzie et al. ). through 'rapid identification, verification and communication of threats' (who , p. ), goarn seeks to contain the spread of infectious diseases, especially highly infectious ones. 'no single institution or country', so the main argument for this international cooperation goes, 'has all of the capacities to respond to international public health emergencies caused by epidemics and by new and emerging infectious diseases' (who n.d.) . in - , the sars pandemic, which resulted in nearly registered deaths, triggered a global health alarm due to goarn, though the communication of this risk kindled by the predicted future potential of the pandemic outstripped, in certain respects, its actual impact (smith ; ong ). the thoroughly redesigned ihr from , which came into force in , further developed and shaped this process. in contrast to the regulations it replaced-the international sanitation and health regulations of and , which, in comparison, were quite static since they only applied to a specific catalogue of communicable diseasethe ihr now includes an early warning system that seeks to detect every potential 'public health emergency of international concern' (pheic) (fidler ) . the focus is on so-called points of entry, especially sea-and airports (who a, pp. - , - ) . the member states of the who are responsible for implementing this global safety net at the local level; they must establish surveillance, contact and coordination units. in germany, for instance, the federal office of civil protection and disaster assistance coordinates and oversees this implementation process in cooperation with the robert koch institute. the robert koch institute, in turn, works with the european centre for disease prevention and control, which is an important partner of goarn. because many different kinds of organizations across a wide range of countries are connected in this network, it is necessary to standardize decision-making. without the 'structural coupling' (maturana and varela , pp. - ) of a shared decision process, cooperation and coordination between the participating organizations would not be feasible. decisions would simply not be able to circulate within the network. instead, they would have to be re-evaluated at every nodal point. for this reason, the ihr (who a, pp. - ; see also who ) stipulates a risk-assessment matrix for signatory countries: after a local surveillance unit has detected an event 'that may constitute a public health emergency of international concern' (who a, p. ) , three yes/no questions regarding its actual and potential impact must be answered. then, it is determined whether the event should be rated as unusual or unexpected. if the answers are all positive, the who must be notified within hours. if they are not all positive, there are two further levels of such yes/no questions, which address the risk of international spread and, in a final step, the possibility that countries or other entities would impose international travel or trade restrictions in response to the outbreak. the answers to these questions then determine whether notifying the who is required or not. this decision-making tool can be understood as an 'attention filter'. since there are now many globally connected surveillance units, mechanisms have to be installed that not only allow and trigger but also suppress communication between them. otherwise, the network would be flooded with more information than it can process. in other words, the elements within this structure would be too closely connected. nonetheless, the goal is to set the attention thresholds as low as possible. even if notifying the who is not required at one point, the event in question has to be kept under surveillance. this, of course, does not prevent the situation from being evaluated incorrectly. the - ebola outbreak, for instance, was declared a pheic relatively late because the actors in charge initially viewed it as only a local problem of a poor region in west africa (lakoff et al. ) . together with the attention thresholds, the reaction times of the relevant public health organizations are also to be lowered. while the decentralized structure of networks improves the alarm function, since attention is widely distributed, a missing or weakly developed action centre has an adverse effect on the intervention function. in defiance of all network rhetoric, the global fight against pandemics cannot proceed without the structural principles of hierarchy and the distribution of tasks. according to the ihr, after being informed of a positive risk assessment by local organizations, the who has to provide them with further information and instructions and send experts to the affected regions (who a, pp. - , - , - ) . the who is the 'obligatory passage point' (callon ) for this process. a combination of the network, hierarchy and the distribution of tasks aims to make rapid intervention possible. even though the who wants, in principle, global traffic to flow without any hindrance, in some cases a temporary interruption of the circulation of goods and people may be considered necessary to protect global public health (stephenson ; opitz ) . the ihr and national regulations therefore stipulate travel restrictions on certain people and allow measures like quarantine and isolation to be imposed. in an age of global flows and a greater awareness of fundamental rights, this specific kind of intervention has to some extent become problematic. as the first principle of the ihr states 'the implementation of these regulations shall be with full respect for the dignity, human rights and fundamental freedoms of persons' (who a, p. ) . similarly, the who ( , p. ) explained in : 'in emergency situations, the enjoyment of individual human rights and civil liberties may have to be limited in the public interest. however, efforts to protect individual rights should be part of any policy. measures that limit individual rights and civil liberties must be necessary, reasonable, proportional, equitable, non-discriminatory and in full compliance with national and international laws.' besides these reservations, the global fight against pandemics cannot proceed without restrictive measures, as the sars pandemic and ebola outbreak have shown. although a concentrated global effort has been made to prevent pandemics via early detection and rapid response, the actors in charge expect them to happen. it is only a matter of time, they believe, until the next health emergency occurs. 'influenza experts agree', the who ( b, pp. vi-vii) warned in , 'that another pandemic is likely to happen but are unable to say when. the specific characteristics of a future pandemic virus cannot be predicted. nobody knows how pathogenic a new virus would be, and which age groups it would affect.' although its exact time of emergence, etiological nature and epidemiological distribution pattern may be unpredictable, it is considered a fact that the next pandemic will occur in the near or not so distant future (see also macphil ). a glossy brochure on pandemic planning by the us department of homeland security ( , p. ) presented a similar way of looking at things. in a quotation in the brochure, the us secretary of health and human services, mike leavitt, states: 'some will say this discussion of the avian flu is an overreaction. some may say, "did we cry the wolf?" the reality is that if the h n virus does not trigger pandemic flu, there will be another virus that will. ' this statement demonstrates that the general trend of thinking about emergencies and accidents as 'normal' has permeated the field of global public health (calhoun ; lakoff ) . in the s, in many areas of public life, the future was already perceived as unsafe and potentially catastrophic, and this view was intensified after the year (aradau and van munster ; horn ) . although the future horizon has darkened with the looming prospect of ecological, political and economic crises, not all hope is lost. the occurrence of (massive) harm might be inevitable, but what can yet be prevented is the worst-case scenario. it is assumed that through emergency planning, the severity of the potential damage can be lessened. this is what 'preparedness' means: acting, deciding and governing under conditions of insecurity (lentzos and rose ; anderson ) . as the who explained in : 'although it is not considered feasible to halt the spread of a pandemic virus, it should be possible to minimize its consequences through advance preparation to meet the challenge' (who c, p. ) . in his address to the nd world health assembly in , the un secretary-general, ban ki-moon, posed the same question: 'how do we build resilience in an age of unpredictability and interconnection?' through emergency planning is his answer. 'this is how we will make the global community more resilient. this is how we ensure that wherever the next threat to health, peace or economic stability may emerge, we will be ready.' of special interest in this regard are critical infrastructures, such as water supply, that might be affected by a severe disease outbreak. local public health emergency centres, which the who ( ) assembled as a global network (eoc-net) in , are responsible for the planning process. as well as taking stock of the available resources and contingents in a country or region, scenario planning and agent-based computer simulations are of fundamental importance ; they enable us to imagine possible scenarios via enactment and visualization without the necessity of making any probability assumptions. it is believed that in order to be prepared for future emergencies, the organizational imagination must to some extent be liberated from restrictions imposed by past experiences. organizations are of crucial importance for the planning process. for instance, the who guidelines, whole-of-society pandemic readiness, aim 'to support integrated planning and preparations for pandemic influenza across all sectors of society, including public and private sector organizations and essential services' (who , p. ) . to strengthen organizational resiliency against the stresses and strains that may result from a pandemic, thorough preparation is required. 'in the absence of early and effective planning, countries may face wider social and economic disruption, significant threats to the continuity of essential services, lower production levels, distribution difficulties, and shortages of supplies' (p. ). emergency planning is furthermore imperative since '[t]he failure of businesses to sustain operations would add to the economic consequences of a pandemic. some business sectors will be especially vulnerable (e.g. those dependent on tourism and travel), and certain groups in society are likely to suffer more than others' (p. ). the 'readiness framework' therefore asks all organizations that provide basic services such as food, water, health, defence, law and order, finance, transportation, telecommunications and energy to prepare for pandemics via simulation exercises and drills based on different scenarios. furthermore, business continuity plans have to be developed. for this purpose, a pandemic coordinator should be assigned to oversee the planning process. all organizations that are crucial for public life are strongly advised to prepare themselves for the next pandemic. given the interdependencies between these organizations, general preparedness is the only way to prevent a complete breakdown. or, as the guidelines put it: 'it is prudent to plan for the worst, while hoping for the best' (p. ). according to lakoff ( ) , today's highly differentiated field of global health is characterized by, among other things, the juxtaposition of two regimes: global health security and humanitarian biomedicine. 'each of these regimes', he elaborates, 'combines normative and technical elements to provide a rationale for managing infectious disease on a global scale. they each envision a form of social life that requires the fulfillment of an innovative technological project. however, the two regimes rest on very different visions of both the social order that is at stake in global health and the most appropriate technical means of achieving it' (p. ). while global health security turns its attention to emerging infectious diseases, 'which are seen to threaten wealthy countries, and which typically (though not always) emanate from asia, sub-saharan africa, latin america', humanitarian biomedicine deals with 'diseases that currently afflict the poorer nations of the world, such as malaria, tuberculosis, and hiv/aids' (p. ). in addition to lakoff's ( lakoff's ( , see also distinction between the two regimes of global health, my analysis highlights two layers that are encompassed by one of these regimes, the global fight against emerging infectious diseases. the two modes of organizing of such pandemics are not organizations themselves. they are programmes that structure the organizational decision-making and the corresponding membership roles. in analysing these programmes, the focus lies not so much on the actual operation of the system-since it is always a creative translation of cognitive and normative schemes into concrete practice-but rather on the intended actions of the system. a first line of defence is defined through early intervention. for this purpose, a wide and ramified organizational network is put in place. it allows pandemics to be detected while they are still emerging, and this makes it possible to limit the potential scope of their spread. because the goal is to prevent a further unfolding of potential threats into actual damages, time is of the essence in detection. the organizations must react quickly while ensuring, at same time, that the information they generate, process and communicate to others is reliable. the strategies they decide to follow also have to be effective. otherwise the primary goal is not achieved: preventing pandemics from happening. in reality, this highly ambitious goal cannot always be met. but the organizations in charge know their limitations and are therefore requested to install a second line of defence: emergency planning. all organizations that are critical for society are asked to have emergency plans in place so that, in the case of a pandemic, they would still be able to react. the goal here shifts from preventing the spread of disease towards securing the 'autopoiesis' (maturana and varela , pp. - ) of the system, meaning its ability to reproduce itself even under enormous environmental pressures. while early intervention requires organizations to be capable of acting quickly, pandemic preparedness aims to produce robust systems that are immune to breakdown. despite operating from different angles, these two modes of organizing pandemics are complementary. early intervention relates to preventable damages. the underlying assumption is that pandemics can be avoided through early detection and rapid response. the future scenario of early intervention is therefore an altogether positive one, in which organizations are capable of doing their job in the face of danger, namely containing infectious diseases. pandemic preparedness, in contrast, works not with one but with two kinds of damages: primary damages, which cannot be prevented, and preventable consequential damages, which pose an existential threat. the aim is still to prevent harm, but preparedness does not focus on the pandemics per se but on the fatal repercussions that they might have for societies. this is a minimal form of prevention, and it is no longer believed that it is possible to escape such a pandemic unscathed. both modes of relating to the future do not exclude but rather complement each other. if early intervention does not work in a specific scenario, there is still a second prevention strategy, which, of course, can only partially contain the effects of the pandemic since (massive) harm will have already occurred. but by strengthening the resilience of organizations and societies, pandemic preparedness aims to preserve existential functions and operations. in his by now classic essay from , charles perrow describes organizations, especially large ones, as a key element of modern societies. according to perrow, fundamental social functions are maintained by private and public organizations. this also holds true for responding to pandemics. in a 'society of organizations' (perrow ) , it is organizations and their professionals who manage pandemics. but two kinds of organizations have to be distinguished which correspond to the two modes or programmes for managing emerging infectious diseases: first, organizations and professionals in the public health sector try to prevent pandemics through early intervention (and further preventative measures, such as vaccination programmes). it is their job to protect the general public from health risks; this is the purpose of these specialized organizations and the goal of their corresponding professional activities. second, and in contrast, all organizations that provide basic services for society are asked to make emergency plans and prepare themselves for the next pandemic. this includes public health organizations but is also addressed to, first and foremost, private and public organizations that provide food, water, defence, law and order, finance, transportation, telecommunications and energy. the second programme is no less ambitious than the first. organizations and professionals in the public health sector may not always succeed in preventing pandemics: as we have seen, they are well aware of this fact, and that is why emergency plans are developed in the first place. but this implies that, in principle, all organizations that provide basic services for society have to professionalize themselves in this specific area. one could describe this as a 'colonization' of non-health organizations through public health imperatives. this is, of course, not a completely new development if one considers, for instance, company doctors or health and safety officers. furthermore, many large organizations have undergone a professionalization in areas that do not traditionally belong to their core activities, such as when they maintain legal, public relations or research departments, or when they offer childcare or psychological counselling to their employees. to some extent, this is a likely consequence of the 'functional differentiation of modern societies' (luhmann ) : even if organizations are typically specialized in providing only one or two services, they have to take further social functions into account. what is new here is the kind of task, that is, preparing for pandemics in order to prevent the worst-case scenario-a complete breakdown of the system that would result from the absence of employees due to illness. in a society of organizations, the autopoiesis of society as whole cannot be separated from the autopoiesis of its organizations. preserving society in a public health emergency depends on keeping organizations functional. for measures of disease assessment and control in germany, see the 'gesetz zur neuordnung seuchenrechtlicher vorschriften for a discussion of how biosecurity intertwines the field of public health with the security sector, see also fidler and gostin preemption, precaution, preparedness: anticipatory action and future geographies politics of catastrophe: genealogies of the unknown policing hearts of darkness: aspects of the international sanitary conferences a world of emergencies: fear, intervention, and the limits of cosmopolitan order some elements of a sociology of translation: domestication of the scallops and the fishermen of st brieuc bay pandemic influenza: preparedness, response, and recovery; guide for critical infrastructure and key resources european centre for disease prevention and control smallpox and its eradication from international sanitary conventions to global health security: the new international health regulations biosecurity in the global age: biological weapons, public health, and the rule of law leviathan or the matter, forme & power of a common-wealth ecclesiasticall and civil the scientific background of the international sanitary conferences - resilience and solidarity: our best response to crisis. address to the nd world health assembly mapping medical disasters: ebola makes old lessons preparing for the next emergency two regimes of global health governing insecurity: contingency planning, protection, resilience funktionen und folgen formaler organisation the global outbreak alert and response network a predictable unpredictability: the h n pandemic and the concept of 'strategic uncertainty' within global public health fear (the spectrum said) the tree of knowledge: the biological roots of human understanding assembling around sars: technology, body heat, and political fever in risk society regulating epidemic space: the nomos of global circulation defining epidemics in computer simulation models: how do definitions influence conclusions? a society of organizations responding to global infectious disease outbreaks: lessons from sars on the role of risk perception, communication and management emerging infectious diseases/emerging forms of biological sovereignty who checklist for influenza pandemic preparedness planning. geneva: who. ---. c. who global influenza preparedness plan: the role of who and recommendations for national measures before and during pandemics welt ohne krankheit: geschichte der internationalen gesundheitspolitik - key: cord- -ay ybcm authors: davies, stephen title: pandemics and the consequences of covid‐ date: - - journal: nan doi: . /ecaf. sha: doc_id: cord_uid: ay ybcm nan pandemics are a regular feature of human history from ancient times onwards (mcneill, ) . as major eruptions of the harsh realities of nature into the settled life of civilisations (for it is civilisations that suffer from them, for various reasons), they loom large in historical accounts and the memoirs of those who lived through them. historically, pandemics have brought about sweeping social, political, and cultural changeor at least they seem to have done so, for the reality is that they give a massive push to movements and trends that were already under way. in the extreme cases, pandemics have figured largely in the collapse of empires and civilisations, as for example in the havoc the bubonic plague wrought on both the eastern roman and sasanian empires in the sixth century (little, ) . in the modern world (since around ) their impact has been less dramatic but it is still considerable. there have been almost pandemics in the modern era and they have played a central part in the development and growth of the modern state. there is also an inescapable economic aspect to pandemics, in terms of both their dynamics (the way they spread and the reasons why they appear when and where they do), and their consequences, among which economic impacts loom large. it is important to understand what a pandemic is and how it is distinct from an ordinary and localised epidemic outbreak. the latter is a constant feature of human life. an infectious disease will break out in a particular location and initially spread rapidly among the local population (which may be large). after a while the rate of growth slows down and eventually stops, with the number of cases peaking. there is then an almost equally rapid decline, so the path of an epidemic resembles an inverted v. sometimes, however, the epidemic spreads widely beyond its original point of origin and becomes extensively dispersed geographically. such an epidemic is commonly called a pandemic, although strictly speaking that term should be used only for the ultimate case of an epidemic that has diffused so widely that outbreaks are found at roughly the same time all over the populated planet. a pandemic has a different pattern from that of a local epidemic. the disease, which is typically novel and caused by a new or mutated pathogen, appears at one point on the planet. it then spreads along trade routes and travel routes to other parts of the world (tatem, rogers, & hay, ) . travellers (tourists today but also pilgrims and business travellers), merchants, and soldiers are historically the major carriers (mcneill, ) . the transmission at this point is not geographically continuous; instead, the disease spreads along trade routes from one trade hub to another, leaping over intervening territory. this leads to widespread and scattered nearsimultaneous outbreaks across the world, which can then in turn lead to further transmission. this is the first phase of the pandemic. eventually these localised outbreaks subside, in the same way as a truly local epidemic does. however, in a pandemic that is not the end of the story. the epidemic now enters a second phase, usually called the 'smouldering' phase (viboud, grais, lafont, miller, & simonsen, ) . in this phase the disease spreads out from the original foci and becomes much more widely and uniformly dispersed. this phase is marked by scattered outbreaks on a small scale, so the overall number of cases does not rise or does so slowly. gradually, however, the local outbreaks start to coalesce, and after some time (which, depending on the pathogen, can be anything from a few months to several years) the third phase is entered. this is a second wave of accelerating infection, but much more widely dispersed and uniform than the first one (although some of the areas most hard hit in the first phase get off lightly, because of higher levels of acquired immunity) (cockburn, delon, & fereira, ; kindrachuk & nickol, ) . this third phase, or second wave, is typically much larger than the first wave in terms of both the number of cases and the geographical spread, and often does far more damage. with viral pathogens the second wave is often more virulent than the first (this happened for example in the spanish flu pandemic of - ) but it can be milder (kilbourne, ; potter, ; spinney, ) . after the third phase the epidemic becomes quiescent again but it often returns in a third and even a fourth wave. these, however, are almost always milder than the earlier waves in terms of their medical effects. how then does the covid- pandemic of fit into that kind of story? clearly it is not on the same scale as the truly massive ones of the past, such as the antonine plague of the second century (probably smallpox) or the plague of justinian in the sixth century and the black death in the fourteenth (both of these being bubonic plague). these all killed upwards of per cent of the affected populations, a truly devastating mortality rate (benedictow, ; horrox, ; little, ; mcneill, ) . by contrast, covid- appears so far to have an infection fatality rate of around . - . per cent (so much milder than those cases but also several times worse than regular seasonal influenza). the medical effect is so far much less than that of the spanish flu pandemic of - , although it may end up being slightly worse than in the asian flu and hong kong flu pandemics ( - and - respectively) . the covid- virus is seemingly less infectious than influenza but has a longer incubation period and a very high proportion of asymptomatic cases, which means it still spreads widely. the major differences from the past are the greater medical capacity available, in terms of both knowledge and actual resources, and the greater administrative capacity of modern states. in - local controls, often sweeping, were imposed, but there were nothing like the national responses seen in (spinney, ) . policies of lockdown initially and testing, tracing and isolating (tti) subsequently may smother the smouldering phase and prevent a second wave or third phase this time, holding the line until a vaccine is developed. (countries that were able to put a programme of tti in place early on, such as south korea, have avoided the need for a strict lockdown.) at the time of writing (may ), we still do not know whether we will escape a third phase. one problem is that the development and spread of the virus is at every stage a complex system in the technical sense of that term. that is, we cannot simply extrapolate existing trends, or predict from initial conditions and parameters how things will work out subsequently. in addition, too much is still not known, most notably the proportions of populations that have already been infected and are consequently now immune. what evidence we have suggests an infection rate in most places of between per cent and per cent (ahlander & pollard, ; urra, ) . the problem is that this means populations are a long way from so-called 'herd immunity' where the number of susceptible people in a given population is at a level where one case will give rise to fewer than one new case, because of the physical difficulty of finding a vulnerable person (this level is at least per cent for a virus with the known features of . all this means that policymakers are operating in a situation analogous to the 'fog of war', with incomplete or absent information and constantly and unpredictably changing circumstances. they face an acute knowledge problem, in other words. given this, it will be a major achievement if controls and other measures do succeed in dousing the smouldering stage of the pandemic. the experience of the past, and the way pandemics have happened, tell us a number of things. because the initial spread beyond a locality is a function of transmission along channels such as trade and travel routes (including pilgrimage ones), very widespread epidemics are almost by definition cases where an epidemic has reached every part of an ecumene, that is, a part of the planet that is economically integrated through trade and exchange. today that means the entire planet. in the past for the entire planet to be reached the pathogen would take several steps geographically, going through the cycle described above in each step (we can see this in the black death, for example). today, because of air travel and things such as austrian ski holidays, the coronavirus was able to spread from wuhan in china to the whole planet in a matter of just weeks. (in - the time it took spanish flu to travel from one part of the world to another was measured in months.) all this leads to the conclusion that several features of the world we live in, such as high levels of economic integration and trade, widespread mass travel, and rapid modes of transport, make it much more vulnerable to a true pandemic. to that list we should add such things as the nature of modern livestock farming and acute pressure on wildlife habitats, both of which contribute significantly to the appearance of novel pathogens and transmission from animals to humans. these and other features of the modern world also mean that the economic impact of an extensive epidemic is going to be much greater than was the case in, for example, - . international travel is now a much more significant and valuable activity, so its curtailment will have much bigger effects. much manufacturing and other economic activity now depends on long and complex supply chains that, again, will be disrupted by both the epidemic itself and the measures taken to contain it. changes in consumption patterns also make contemporary economies more vulnerable. for example, in the last three decades americans have taken to eating out more and more, to the point where just over half of the food consumed is eaten in bars and restaurants. these have been closed down but even before then their trade had collapsed. this has had a much bigger effect than would have been the case in , not least because the entire food supply system is now geared up to sending half its output to restaurants rather than grocery stores, and it is extremely difficult to adjust quickly to restaurant closure (bedford, ) there are similar examples in other areas, such as clothing purchasing. another change is the much greater significance of credit, with far more businesses highly leveraged and operating on very tight margins. this means that a prolonged interruption to normal business conditions will have its effect amplified by finance, in a way that was not true years ago. one social change that also has this effect is the movement of women with children into the labour force in large numbersthis magnifies the economic impact of school closures (keogh-brown, wren-lewis, edmunds, beutels, & smith, ) . all this means that a pandemic such as the hong kong flu is going to have bigger effects if it were to happen today than the original did back in - . the covid- virus is, on the evidence, more medically severe, so we should expect it to have if anything a still larger impact. at first sight it would seem obvious that the measures taken by governments to try to suppress the spread of the virus and head off a second wave (by stamping out the 'smouldering' phase) have in turn increased that impact even further, massively so. certainly, the impact has been dramatic, with a record rise in us unemployment claims and a dramatic rise in claims for universal credit in the uk. most businesses are presently shut down in the uk and elsewhere, and only measures such as the furlough scheme introduced into the uk have prevented a rise in unemployment not seen since the dark days of , given a collapse in gdp that some commentators estimate to be the worst since the s or s (bruce, ; faulconbridge & bruce, ) . however, initial forecasts indicate that the additional impact of lockdowns is far less than most imagine. there is no clear correlation between the severity of lockdown and the size of the hit to gdp, with countries such as sweden that have avoided lockdowns and gone instead for social distancing predicted to see a decline in gdp similar to the ones expected in countries that did impose one (milne, ) . moreover, the early signs are that lockdowns may not have had such a dramatic effect on rates of infection and rapidity of spread during the first phase of this pandemic. it seems that it is measures such as effective tti policy, closing of borders, and successfully protecting vulnerable groups such as the elderly that have had the biggest effect. the tentative but increasingly strong conclusion is that it was the spontaneous responses and reactions of the public that brought about both the medical effect of slower spread and the bulk of the economic impact (this also highlights the fragility of much of the contemporary economy). what kinds of administrative and political effects have pandemics had historically and how might that play out this time? one important point is that pandemics seldom lead to something truly novel: they typically provide a big boost to processes that were already under way. they do not bring down institutions and systems that are in good shape, but they do precipitate the collapse and end of ones that were already in a poor state. so most of the firms or sectors that go under will be ones that were already having serious difficulty or were already vulnerable, such as retail. we will see the same pattern in politics. the pandemic will lead to a resurgence of nationalism and the nation state, while undermining a rules-based international order and supranational forms of governance. unfortunately, it will boost the trend towards protectionism and economic nationalism that is already under way. it will also lead to a decline in international integration as supply chains are shortened and production 'reshored' in response to revealed vulnerabilities (again, this is already under way). it will almost certainly trigger a financial crisis centred on the unsustainable accumulation of private debt, this again being a case of it providing the push that brings down something that is already on the verge of falling over. historically, pandemics have played a central part in the emergence of the modern administrative state, through the creation of modern systems of public health in response to major epidemics. it was the six great cholera pandemics of the nineteenth century that were particularly important for this, leading as they did to governments acquiring extensive powers to inspect, regulate, and register their populations and to the state taking on responsibility for sanitation and providing potable water (wilford, ) . they also led to a profound change in the way large towns and cities were administered and subsequently to the development of an extensive and often coercive set of public health programmes, such as compulsory vaccination, as well as health visitors and district nurses to support but also chivvy and push the general public. it seems likely that the coronavirus pandemic will therefore lead to a reassessment of the extent, power, and functions of government. in some areas this will result in a growth or extension of powers but in others there will likely be a pulling back or withdrawal as public administration is found to be lacking or self-defeating. a lot of regulations, particularly ones to do with medicines and drugs but also things such as occupational licensure (in the united states in particular) are likely to be cut back or abolished. in contrast, surveillance powers are probably going to become more extensive. one likely change is in the area of health services: in most countries (east asian ones and germany are the big exceptions) these have come to be dominated by hospitals and therapeutic medicine at the expense of health maintenance and public health (hawe, yuen, & baillie, ) . this has been revealed as brittle and highly vulnerable to shocks such as a major epidemic (in it was panic about the pressure on hospital systems that led to the decision to impose a lockdown, in most cases). one area where there will be much debate is over the relative performance and effectiveness of decentralised and localised systems as compared to centralised or national ones: this is actually an area where the evidence can support both sides, with the correct answer differing according to local circumstances. the pandemic will also have other, less predictable, effects, but some of these can already be discerned and others can be guessed at from historical experience. one rather grim result will be a heightening of international tensions, particularly between china and both the us and europe. there may be significant consequences for education and higher education in particular. despite what some hope or fear, there are unlikely to be lasting consequences for pedagogy but the financial and organisational structure of the higher education industry is likely to face dramatic disruption and reorganisation, on a worldwide basis. another area that will probably see a major impact in some countries is welfare policy, where the idea of a universal basic income, already gaining support of late, is going to move to the centre of debate. on the historical evidence there will also be unpredictable but extensive cultural effects (cantor, ) . usually there is a simultaneous movement towards both greater seriousness and impatience with intellectual frivolity on the one hand and a desire to live for the moment and take pleasure where it may be found on the other. other things are simply a matter of guesswork (or, too often, projection of hopes and fears). perhaps there will be a revulsion against the way everyday work is organised and away from a system where almost all adults are employed. perhaps working from home will become a new normal, or alternatively people will be desperate for the company of a workplace. there may well be an uptick in the birth rate: as one person observed to me, if lockdown does not get the uk birth rate back above replacement level, nothing will. note for up-to-date information, see worldometer data at https://www.worldometers.info/coronavirus/ swedish antibody study shows long road to immunity as covid- toll mounts. reuters how and why america's food system is cracking. the federalist the black death - : the complete history worst uk slump in 'centuries' looms as lockdown slams business. reuters in the wake of the plague: the black death and the world it made origin and progress of the - hong kong influenza epidemic never had it so bad? plague, weather, and war did worse to the uk economy. reuters ohe guide to uk health and healthcare statistics. london: office of health economics the black death the possible macroeconomic impact on the uk of an influenza pandemic influenza pandemics of the twentieth century plague and the end of antiquity: the pandemic of - plagues and peoples sweden unlikely to feel economic benefit of no-lockdown approach a year of terror and a century of reflection: perspectives on the great influenza pandemic of - pale rider: the spanish flu of and how it changed the world global transport networks and infectious disease spread antibody study shows that just % of spaniards have contracted the coronavirus. el pais multinational impact of the hong kong influenza how epidemics helped shape the modern metropolis how to cite this article: davies s. pandemics and the consequences of covid- key: cord- -k l unc authors: lu, li; lankala, srinivas; gong, yuan; feng, xuefeng; chang, briankle g. title: forum: covid- dispatches date: - - journal: cult stud crit methodol doi: . / sha: doc_id: cord_uid: k l unc covid- pandemic is the first truly global crisis in the digital age. with death count worldwide reaching , merely months after its first outbreak in china in late december and . million cases reported in countries and territories as of july , this ongoing pandemic has spread far beyond domain of world health problem to become an unprecedented challenge facing humanity at every level. in addition to causing social and economic disruptions on a scale unseen before, it has turned the world into a site of biopolitical agon where science and reason are forced to betray their impotence against cultish thinking in the planetary endgame depicted in so many dystopian science fictions. it is in this context that this forum offers a set of modest reflections on the current impacts incurred by the covid- virus. blending ethnographic observations with theory-driven reflections, the five authors address issues made manifest by the crisis across different regions, while keeping their sight on the sociopolitical problems plaguing our life both individually and collectively. taken together, they provide a grounded documentary for the archive that the covid- virus is making us to construct. the apparition of these faces in the crowd. -ezra pound, "in a station of the metro" the french word envoi is polysemic, defined as dispatch, the action of sending, something that is sent, a poetic dedication or dedication of a literary work, and the marking of the beginning of a process. this article is a dispatch from hubei, china, based on the author's -month stay in his hometown qianjiang, a small city in the middle of hubei, during the coronavirus pandemic. firsthand observations sent from the epicenter give us a clear picture of what the coronavirus has done. moreover, this article argues that the coronavirus marks a spectral moment in which a repressed trauma returns. there have been fierce debates on the origins of the coronavirus and the political, economic, and social significances of the pandemic. popular representations of the coronavirus which isolate, stigmatize, and terrify the other are symptoms of a returning trauma, which is caused by bodily memories of being victims in past disasters. a derridean reading of the envoi highlights the inherent failure of sending: what is sent can always be held up by a malfunctioning in the process of the sending or postal system, and the meaning of the trauma is lost. this traumatic failure results in a repetition in representation and the return of what is sent to the writer/sender. proposing a supplement, this article foregrounds bodily knowledge acquired through social and political trauma by virtue of fear of the coronavirus. this fear of what is familiar reminds us of the feeling of the uncanny. according to freud and derrida, the uncanny is related to the spectral working of a hidden desire that repeatedly returns as a haunting body, representation, and history. this line of thinking helps us to better understand conflicting representations of the coronavirus. the coronavirus is a ghost. this is not merely a metaphorical proposition; this is accurate in the sense that the coronavirus instantiates our phantasms, fears, and desires toward ghosts. in this regard, derrida's specters of marx provides us with a basic framework for understanding the coronavirus as a ghost. the first teaching of derrida is that ghosts do not come at just any time but in spectral moments that do not belong to time. by pointing precisely to the c scxxx . / cultural studies <span class="symbol" cstyle="symbol">↔</span> critical methodologiesli et al. present or now-time, derrida ( ) regards spectral time as "a disjointed now that always risks maintaining nothing together in the assured conjunction of some context whose border would still be determinable" (p. ). second, a ghost is a phenomenon in the game of repetition and difference. neither exclusively situated in life nor in death, neither visible nor invisible, a ghost is "the frequency of a certain visibility. but the visibility of the invisible. and visibility, by its essence, is not seen, which is why it remains epekeina tes ousias, beyond the phenomenon or beyond being" (derrida, , p. ) . third, to "make oneself fear" is essentially ineluctable in the experience of a ghost. one becomes frightened of a ghost "on the condition that one can never distinguish between the future-to-come and the comingback of a specter" (derrida, , p. ) . in other words, what one fears is not the ghost, but the fear, imagination, and one's subject inspired by the ghost. finally, "a ghost never dies, it remains always to come and to come-back" (derrida, , p. ) . whatever repression the dead may suffer, the return of the dead is anticipated, and "this being-with specters would also be, not only but also, a politics of memory, of inheritance, and of generations" (derrida, , p. xviii) . in light of derrida's framework on specters, once the coronavirus finds a host, it starts to live a ghostly life. the coronavirus pandemic irrupted during a time of turmoil. as the chinese president xi jinping has expressed, the world is experiencing profound shifts unseen in a century. while the trend of globalization is markedly receding, nationalism, popularism, and isolationism are on the rise. the eulogic discussions of "chimerica," a popular term coined by the british epidemiologist neil ferguson in , are being replaced by the theories and practices of the china-u.s. decoupling. the trade dispute between china and the united states puts an end to the chinese ideal of great harmony in the world. in addition, as his campaign slogan "america first" shows, donald trump epitomizes the idea of american exceptionalism. in traditional chinese thinking, famine, natural disasters, and plague happen when the political order or legitimacy are out of joint. during this disjointed moment, a plague was anticipated, even fabricated before it came. according to a widely circulated story in the we-media during the height of the coronavirus, wang yongyan, an academician specializing in chinese medicine at the chinese academy of engineering, predicted half a year ago that a plague would come after the dongzhi (winter solstice), one of the chinese solar periods. in addition, he predicted that the plague would last until next spring. in hindsight, rumors about a new virus were spreading right after the dongzhi. or, simply put, divination went hand in hand with the plague during a time of disjointing, disjunction, or disproportion. while scientists are still trying to track down patient zero, conspiracy theories about the origins of coronavirus have been spreading. bat soup and biological warfare are on the top of the list of suspected criminals. like ghosts, the coronavirus takes shape in the game of visibility and invisibility. in this game, ways of seeing determine how a virus can be understood. approximately made up of . microns, the coronavirus can only be seen under an electron microscope, made visible with the help of scientific equipment and representations. in contrast, a poet like ezra pound sees the invisible through his gifted imagination. his imaginative inspiration and aesthetic reflection allow his keen observation to become a line of poetic beauty and philosophical complexity. through this form of observation, an invisible apparition becomes visible in the faces of the crowd. similarly, the depiction of a fictional killer-virus called wuhan- in dean koontz's novel the eyes of darkness, re-gained popularity among those who regard it as an imaginative depiction of the coronavirus. in line with this imaginative depiction, mr. wang, well-trained in traditional chinese medicine, claimed that his prediction was based on his reading of the xiang (image) of the sky, earth, plants, animals, and human beings. visible to the naked eye, xiang functions as the visible traces from which an invisible plague becomes visible to an expert in traditional chinese medicine. in other words, with scientific support, talent, and training, people are able "to see this invisibility, to see without seeing, thus to think the body without body of this invisible visibility" (derrida, , p. ) . in this way, the ghostly nature of the coronavirus lies in the different frequencies of its visibility. however, despite our faith in being able to depict, and make distinctions between, the invisible and the visible, the way of seeing the coronavirus, especially in this time of turmoil, is politically conditioned and manipulated. when i took a night bullet train to wuhan with my family for vacation, it felt like an ordinary chinese family reunion trip during the spring festival: carriages packed with passengers, luggage, excitement, anxiety, and weariness in the air. one of the reasons for the peaceful atmosphere was that china and the united states had signed a trade agreement a few days before, sending a false message to the world that rationality and peace would return. one thing was markedly noticeable on the train: most passengers wore a facial mask for fear of an officially unidentified but unofficially sarslike virus. to my surprise, a line of masked faces was greeted at the exit by the smiling faces of relatives or friends, the indifferent faces of railroad workers, and the shrewd faces of barkers at the hankou railway station. this lack of consistency indicates that aspects of the coronavirus were kept secret. furthermore, this scenario at the station reminded me of a horrifying scene in the film the cassandra crossing, an eye-opening disaster thriller for my generation directed by george p. cosmatos. in this harrowing film, an international express carrying a virus-infected terrorist approaches a station at night. when the train reached the station, the passengers, who were kept from the truth, were confronted with members of the u.s. army in white biological hazard protective suits lined up on both sides of the platform. in both cases, the dynamic of the visibility and the invisibility of a virus was of political significance. the facial masks and the protective suits were used not only to protect people from a virus but also to make the secret of the virus both visible and invisible. in other words, political manipulation complicates the ways that a virus is seen and how the coronavirus, in particular, is seen as a political ghost. the coronavirus pandemic frightened people because it looked like the return of a specter, namely sars. because of its fatality and residua, sars remains an unresolved trauma for many chinese. at the early stages of the coronavirus pandemic, what was most frightening was its assumed high fatality rate. similarly, the short notice given for the lockdown of wuhan, a huge city of more than million residents, sent a clear message to everyone that the novel coronavirus was the grim reaper. corona, the brand of the first car i owned and of the beer i had on my first visit to a mexican restaurant, was colored by images of a fearful virus, deserted streets, calm officials on tv news channels, and panicking crowds in wuhan hospitals caught on video by the we-media. unlike the countries who proposed or actually enacted herd immunity, the chinese authorities imposed very tough immunity measures, a lesson learned from the sars pandemic, when highways, the railway station, and docks in my hometown were closed overnight. nursing homes were under quarantine; no visitors were allowed in. local authorities advised avoiding public gatherings, including public square dancing and playing majiang. the most popular forms of social activity, especially for retired people, were no longer available. after the initial panic, it was discovered that the fatality rate of the coronavirus was much lower than sars. according to the world health organization, the sars mortality rate worldwide was about %. in early february, the chinese authorities claimed that the coronavirus mortality rate in wuhan was about %. subsequently, what elicited fear in the population was the future-to-come, particularly in the form of social unrest. on one hand, stricter quarantine measures were implemented: all roads were quickly blocked with cranes or tankers or stones; vehicles' use was not allowed, unless a special permit was issued; all grocery shops, markets, restaurants, and hotels were shut down; residents were not allowed to exit their residential areas except for grocery shopping at an arranged supermarket. in addition, central and local authorities watched closely for other concerns, such as food shortages and the inflation of prices. thanks partly to its rich agricultural products in a land of fish and rice, the impact of the coronavirus on food supply and prices did not affect my hometown. however, under the restrictions put in place, my hometown looked like a ghost town, and the uncertainty of the future frightened people of all social strata. in fact, what people fear most is that the coronavirus will never die and will come back again and again, either in the form of a future-to-come or a return of the dead. regardless, despite the medical or political ambition to eradicate the coronavirus, we might have to accept the fact that the virus will co-exist with us forever. for instance, the coronavirus has been mutating, and the way the coronavirus replicates itself in the cells of other organisms is ubiquitous. this mechanism of repetition and difference functions both literally and metaphorically. on one hand, the coronavirus reproduces itself through difference. merely a collection of genetic materials that seems to think with/like a human once it infects its host, the virus induces a feeling of the uncanny, a topic to which i will return later. in addition, news sources reported that infected patients tested positive again after they had been released from the hospital. robert redfield, director of the u.s. centers for disease control and prevention, admitted that some deaths from coronavirus have been discovered posthumously (cnn, ) . in other cases, the coronavirus acted like a whimsical tyrant who inadvertently signed a death sentence. for example, the only cases of death in my residential area was an old couple who lived in an apartment very close to that of my parents. they got infected by their son and daughter who came back from wuhan. what remained a mystery was that the son and the daughter had stayed with their parents for more than days, much longer than the latent period of coronavirus. days after they were hospitalized, they died one after another. on the other hand, the coronavirus reproduces difference in its host organisms. the neighborhood my mother lives in is an acquittance community and an aging society. cadres and volunteers from the neighborhood committee have diligently attended to the needs of the old. aware of the higher fatality rate of the old, an ageist exhortation to quarantine was broadcast repeatedly through a portable loudspeaker placed at the gate of the neighborhood committee building. as stigmatized targets, senior residents were susceptible to the emotion of shame and, for this reason, chose to stay at home. the use of broadcasts and the instigation of shame illustrates how the coronavirus (re)produces, moderates, and polices the line between the public and private spheres. the coronavirus also changed the affective, moral, and power economy of the family. the spring festival is supposed to be the perfect time for a temporary family reunion of joy and harmony. when the lockdown continued longer than everyone expected, generational conflicts broke out. in extreme cases, the political infected families while they were trying to contend with the coronavirus during quarantine. for example, fang fang, a veteran chinese writer who lived in wuhan, posted her thoughts on life in quarantine on her or her friend's weibo account. those posts were later collected and published under the title wuhan diaries. public opinion on those posts varied and eventually led to a political debate between left-wing and right-wing netizens, eventually affecting family members who conflicted in their attitudes toward the wuhan diaries. along with the coronavirus, the memory of personal, generational, and political traumas returned. sars, the cultural revolution, natural disasters, and national humilities were recurring themes in representations of the coronavirus. the suffering and trauma in the epicenter deserve an envoi/dedication, and efforts have been made to achieve this goal, such as daily national and international coverage, fang fang's wuhan diaries, and we-media postings. in these kinds of representation, a rhetoric of "suffering as sublime" is usually at play. in addition, stigmatizing the suffering of others, or blaming the other for one's suffering, is another kind of dedication. both kinds of representations of the coronavirus attempt to take the moral higher ground by attempting to fix the coronavirus as a mere object awaiting to be represented. no matter what position the representation takes toward the coronavirus and its significances, the will to truth turns a dedication quickly into a testimony and even a perjury. a virus is an infectious agent that replicates only within a host organism. for the host, a coronavirus is a deadly stranger and an intimate family member at the same time. familiar, frightening, and secretive, the coronavirus reminds us of the uncanny, as discussed by freud. in his pioneering study, freud focused on the unsettling psychological state of the uncanny. distinct from the feeling of fear, the uncanny is a kind of terrifying feeling that is associated with something known and familiar. after an etymological investigation of the german words heimliche/unheimliche, and a close reading of hoffmann's story "the sand-man," freud ( ) unearthed the origins of the uncanny: "it may be true that the uncanny [unheimlich] is something which is secretly familiar [heimlich-heimisch], which has undergone repression and then returned from it, and that everything that is uncanny fulfills this condition" (p. ). he also associates the feeling of the uncanny "with the omnipotence of thoughts, with the prompt fulfillment of wishes, with secret injurious powers and with the return of the dead" (freud, , p. ) . following the lead of freud, derrida worked on the concept of the uncanny to engage with marx's concepts of repetition, specter, and fear. refuting the claims that the tenants of marxism have died, derrida emphasizes the strange familiarity of the specter of marxism in the age of advanced capitalism. as derrida insists, the specter of marxism will continue to return from the future to visit us, to live with us, and to alert us. similarly, derrida ( ) interprets the uncanny through the concept of absolute hospitality, in which "one may deem strange, strangely familiar and inhospitable at the same time (unheimlich, uncanny)" (p. ). remaining structurally open to future interpretation, the uncanny in derrida's account presupposes a materialism without substance, a messianic without messianism. derrida's understanding of the uncanny is critical to my reading of the coronavirus as a ghostwriter of envoi. as a ghostwriter, the coronavirus is a ghost who writes from the future. as a stranger and a family member, it writes with and in the place of the host. by writing an envoi, a kind of writing haunted by failure and repetition, the coronavirus makes itself visible and frightening in a spectral moment. however, the envoi is not exclusively governed by a ghostly logic that is followed by and instantiated through the coronavirus. in critiquing the tendency to unearth an ultimate truth, eve kosofsky sedgwick & frank ( ) regard affects as a possible way out of the binary opposition of truth and falsehood in representation. by invoking the power of the performativity of shame, they highlight the negative affects neglected by identity politics, dismissed and stigmatized: without positive affect, there can be no shame: only a scene that offers you enjoyment or engages your interest can make you blush. similarly, only something you thought might delight or satisfy can disgust. both these affects produce bodily knowledges. (sedgwick & frank, , p. ) in their view, shame is neither subversive nor mandatory; it works with other affects, drives, and representations to adapt the body to its situation. foregrounding bodily knowledge acquired through trauma commits us to thinking differently about representation and the envoi in question. fear of the coronavirus is not only the fear of a returning trauma as a ghostly logic in representation. more importantly, the coronavirus writes itself and writes about bodily memories of trauma in a constant play of materialization: inscribing fear in itself and on the body of the host permanently. with the end of the lockdown in hubei, the coronavirus pandemic is almost over in china. however, the coronavirus has been sending, and will keep sending, its fearful envoi. the enduring sign of the coronavirus pandemic for indians was not related to medicine or public health. it was the unprecedented exodus of migrant workers from metropolitan centers to their native rural districts, sometimes hundreds of miles away (mukhopadhyay & naik, ; petersen & chaurasia, ) . the scale of this migration was vast and is still being understood. it certainly provokes disturbing questions about urbanity and the fragility of a political compact that kept people in their place through calibrated deprivation (dahdah et al., ) . but for our purposes here, i will explore the ways in which it underscores the varying effects of the pandemic on different classes of people and the diversity of its signification. the virus in india is both a medical event to be dealt with through appropriate public health measures and a mediated discourse that has developed its own ramifications and responses. i argue that both forms of the virus have had tragic and miserable consequences, but on different classes and groups of people. like the televised persian gulf war of that jean baudrillard found to be a distinct and distorted signifier of the actual fighting on the ground, the virus itself is not the same phenomenon once it is transformed into a signifier for other meanings and purposes. the novel coronavirus later named covid- emerged in the public consciousness as a distinct problem with the rapid rise in infections in several indian states by february . in march, the government of india mandated an immediate "lockdown" of the entire country. this new term burned itself into the national consciousness and its many vernaculars almost instantly, as its meaning became physically apparent. it involved the physical arrest of people wherever they happened to be at the moment, and the prohibition of all commerce, traffic, and circulation. it was announced with a -day notice period by the prime minister, in an eerie echo of a similar announcement in of the withdrawal of paper currency. that tragic farce had laid a historical precedent for this second tragedy to come. as a deeply iniquitous society and economy were forced to a halt, the effect was expectedly unequal. metropolitan indian citizens soon learned to cope with the new hardships of "work-from-home," homeschooling, online classes and meetings, and such social-media-driven innovations as cooking and cleaning without domestic servants and entertaining themselves in their houses and apartments. the government also encouraged the adoption of derivative coping mechanisms as soon as they were observed in other countries: applauding medical workers from the safe confines of apartment balconies and terraces; singing, chanting and clanging metal plates and dishes with utensils in cacophonous, solidarity of the gated classes; lighting lamps and candles; and waving mobile phone flashlights at appointed times (krishnan, ) . however, the actual effect of the virus became inseparable from the effect of the "lockdown." the sudden impoverishment of the majority of the country's population led to starvation, medical neglect, and a national panic. while invisible to the citizens in its first few weeks, it became impossible to ignore, when workers across indian cities started to simply walk back to their native villages. their exit from cities also emphasized the fragility of urban belonging: that in a crisis, indian cities were fundamentally empty shells, drawing people not through cosmopolitan attractions or civic rewards but by rural misery. at this point, the virus was still largely a media phenomenon, while the "lockdown" was what had directly affected most indians: the sudden disappearance of work, wages, commerce, and circulation magnified the precarity of urban existence. the largely informal national economy quickly unraveled in a crisis. this crisis was exacerbated by the role of the virus in continuing the ideological and political discourses of the chaotic period immediately preceding the lockdown. the use of the virus to carry out "politics by other means" can be seen in other polities as well, but its entanglement with indian politics is particularly useful as a means to understand the virus as a set of signifying practices. the context of this political use of the virus as a signifier is also inseparable from the highly mediatized nature of indian politics and society. the virus emerged as a discursive phenomenon in india at a crucial juncture in a national conflict over changes to the country's citizenship laws. with the rise to national power of the ruling rashtriya swayamsevak sangh (rss, or the national volunteers organization-a fascist group founded in ), india's national government had been attempting since to achieve its political goal of abolishing its secular and liberal constitution through a steady dismantling of public institutions (roy, ) . this conflict worsened in with the re-election of the rss-controlled government headed by the current prime minister, and the consequent repeal of laws that had hitherto guaranteed the autonomy of the occupied territory of kashmir. this was followed by a critical change to citizenship laws to specifically exclude muslims from gaining indian citizenship and institute a new "citizens' register" to determine afresh the legal status of all residents. with reports of the parallel construction of detention camps outside major cities, the fascist inspiration and ominous intent of the new laws became clearer and more immediate. protests and political resistance to the new measures emerged across the country, and were met with violent responses from the police and rss groups. matters had reached a head when the nationwide lockdown was suddenly imposed. except in a few indian states such as kerala, with still functioning local health systems, the lockdown did not involve any public initiative to test or prevent the spread of the virus. instead, in keeping with the ruling ideology of our time, citizens were mandated to protect themselves, on pain of being brutalized by the police if they failed. in this chaotic sauve qui peut scenario, the rhetoric of basic preventive measures took on ominous ideological connotations depending on who you were and where you lived. as it became clear that only access to clean running water, adequate space, and a home to live in would guarantee the efficacy of the public health guidelines, medical advice became meaningless for much of the country's population, especially the inhabitants of vast informal urban settlements in the metropolitan cities. in effect, a dual situation emerged: a parallel virus had infected the classes who lived in gated urban communities and formal neighborhoods and who followed its progress in daily primetime news trackers. positive cases, testing ratios, death rates, and other numbers soon flew across television and website screens in macabre charts, graphs, and complex animations, as breathless studio anchors enthusiastically tracked the competitive fatalities across states, regions, cities, and countries. as the formal state and civil society response to the virus grew more and more into a media discourse, its actual effect on the population was determined by existing social conditions and ideological practices than by the ideals of public health. in the early period of its spread, the illusion of its control was maintained through the interpellation of the mass television audience as ideal national subjects. in a series of televised speeches, the prime minister exhorted citizens to planned acts of mass discipline, such as the applause, noise-making, and lamp-lighting exercises mentioned earlier. it took several costly weeks for the citizens to realize that this national son-et-lumière had only served to deafen and obscure a different and more real virus that had silently spread illness and death among urban populations who did not have houses or apartments with balconies. a starved public health system soon proved inadequate and unprepared. because this real crisis was not mediated or televised, there was no appropriate or meaningful response to it. the easy congruity of the eagerly adopted virus prevention measures with the practice of caste-based rituals of discrimination was not lost on most indians (george, ) . this fortunate coincidence enabled the easy normalization of virus prevention as a legitimization of existing hierarchical practices. the convenient prescription of social distancing appeared to keep the privileged class of wealthy and respectably middle-class white-collar workers as far away as possible from the physical contact or proximity of their social inferiors. the pandemic thus seemed tailor-made for defenders of hindu caste hierarchies, a righteous and suitably scientific legitimation of social discrimination. the fantasy of caste purity would have remained an abhorrent social remnant if it had not become part of state policy in the last few years. but in the context of the stateled legitimation of religious hierarchies and the consequent onslaught on emancipatory laws, this entanglement of the virus with caste and with the violent hate crimes against muslims acquired a dangerous dimension. it is this distrust of and disgust with a compromised public health system that drove so many indians streaming out of cities and into the relative safety of their impoverished rural communities. the alienation of muslims as a national other has been a part of the basic doctrine of india's current ruling group ever since its founders, awed by the nazi policy of extermination, adopted a similar goal for the erasure of non-hindu communities in india. the mass protests and popular uprising against the rss's attempts to irrevocably alter the basic structure of the country's republican constitution had reached a tipping point when the covid- epidemic was suddenly deemed emergent enough to impose an unprecedented "lockdown," in effect a de facto police state across the country. the imposition of the lockdown allowed police to destroy protest sites, detain protestors, and unleash a reign of terror across indian cities. caught in the initial crossfire were members of an apolitical muslim religious group, the tablighi jamaat, whose convention in delhi had been interrupted by the lockdown. jamaat members trapped in the organization's premises by the curfew were found to be infected with the virus. the consequent media narrative of the discovery of the infection among the jamaatis veered into the fantastical, with nightly news anchors debating the strategies of a "corona jihad" that was to be waged by militant muslims using the virus as a weapon (perrigo, ) . this dog-whistle narrative of muslim bodies as unclean spreaders of a foreign disease dovetails with similar narrative frames used to portray hindus from laboring and working castes as well. the manufacture of conspiracies surrounding the coronavirus can be seen across the world and is not unique to india. a disturbingly large proportion of americans, for example, appear to believe that the virus has been manufactured to enable mind-control through vaccination and g cellular signals by a ruling elite (fisher, ) . on rare occasions, these conspiracies do spiral out into real effects such as the bombing of cellular towers in britain and the anti-vaccination movement in the united states. in india, however, the covert encouragement of such theories by the state itself, to legitimize the hatred toward muslims, exacerbates and normalizes the rumors as mainstream prime time news which is then amplified and shared through an organized social media campaign (ellis- petersen & rahman, ) . the vilification of the muslim other serves two purposes, one of furthering the state's broader agenda of religious and caste purity, and the other more immediate goal of providing a scapegoat for the inescapable rise in infections and deaths due to the virus and the inability of the state and society to understand the crisis. the brutal police crackdown that accompanied the lockdown and the violence of its imposition across the country were a small reminder of the routinization of the "lockdown" as a way of life in the occupied valley of kashmir, part of the only muslim-majority state in the indian union. the effects of the police state as a normalized entity have been multiplied since the abrogation in of constitutional laws guaranteeing the region's autonomy, even if such laws were honored more in the breach in preceding decades (zia, ) . the uncanny resemblance of a public health curfew to a military occupation is not coincidental, but the result of the colonial origins of both, and of the state institutions they represent. the symbiotic existence of caste-based discrimination, the extermination of a religious minority, and the colonial occupation of an entire province within the same body politic is made possible by the continuous interpellation of the mass of people to become national citizen-subjects. this call to obedience, broadcast daily through primetime television and magnified through the near-mandatory use of mobile phones, is the only sign of a nation-state that is otherwise absent in the real world. the failure to stop the spread of the real virus is obscured as the interpellated citizen is urged, cajoled, and threatened to participate in the simulacral fight against a mediated virus in a purely semiotic realm. the washing of hands without the precious reality of running water, the maintenance of "social distance" in the absence of space, the exhortation to "work from home" for a population that is not housed, and the discourses of online socialization and commerce are all much more than signs of mere denial: they are the components of this new semiotic space, enabling the call to national belonging in a new domain, bereft of its mooring in the world. from a broader historical perspective, the coronavirus epidemic does not appear to have affected indians as much as the far greater fatalities caused by more prosaic diseases, hunger, and the increasingly toxic air and water (rukmini, ) . what has caused the greatest pain and panic is the response to the epidemic. this response has been not to the virus itself, but to a simulacral virus that appears to occupy the same space and shares the same name as covid- , but which is a mere signifier, pointing to other, older evils. like baudrillard's hyperreal war, it has surpassed the real virus itself and has come to occupy its place. it cannot be wished away or prevented with a vaccine, it needs a response in kind: of new counter-signs and counter-discourses. a catastrophic pandemic unseen in a century, the current raging of covid- around the globe has undoubtedly produced a unique symbolic site for global, regional, and national imaginations. as the earliest epicenter of this infectious illness, china has witnessed the proliferation of discourses about the evolution of the pandemic on various media platforms, through which the chinese public has the rare chance to reflect on important issues regarding identity construction, social reformation, and nation building. while much attention has been paid to the stigmatization of china in euro-american politics, media, and everyday whisper that label the natural coronavirus as a cultural and ethnic fault (fu, ) , what has been overlooked is how china has portrayed other countries in this global health crisis, especially those surrounding nation-states in the same geopolitical area. east asia, or the sinosphere in the broader sense, with the collective memory of fighting sars in , is thought to have responded to covid- more efficiently than many western countries (salmon, ) . how, then, is the east asian encounter with covid- depicted in the chinese public discourse? how does such depiction envisage china's relations with neighboring countries and its position in the area? in this essay, i discuss the ways in which the coronavirus pandemic has been appropriated by the chinese public for a (re)imagination of east asia. by exploring the evolving representations of its neighboring countries throughout the epidemic on chinese media platforms including weibo, wechat, and zhihu, i argue that the talk of the regional responses to covid- envisions a china-centered union of selected east asian countries in parallel with the historical tributary system of the sinosphere. through the expression of the nostalgia for imperial china, the discursive reconstruction of the east asian identity is a ratification of china's contemporary ambition to reclaim its geopolitical dominance. synchronized with the rapid transmission of the coronavirus in china and east asia between january and march , the chinese public in this early phase drew close attention to the unfolding of the epidemic in its nearby countries, and japan and south korea in particular. with the disease breakout involving diamond princess (japan) and shincheonji church of jesus (south korea) frequently making news headlines, the discussions of how those countries responded to covid- flourished online, which, in combination with the continuous debates over china's own pandemic threat management, contributed to the imagination of the covid- rampancy as a regional challenge that china and its neighbors faced together. central to the discursive formation of this imagined community was the celebration of the incessant interaction and cooperation between china and some east asian countries to combat the virus collectively. in the wake of the outbreak when china was threatened by the crumbling of its health care system, the countries under the spotlight-japan and south korea-were widely appraised for the sympathetic and supportive approaches they took to help china overcome the severe shortage of medical resources. the media reports of japanese and south korean governments leading the international aids to china (gong, ) were echoed by numerous warm anecdotes on social media championing the heartfelt support from their people. perhaps the most well-known story of this kind, a japanese institution wrote a chinese-language verse on the boxes of masks it donated to the province of hubei: "rivers low, mountains high; the same moon in the sky" (trans. zhao, ) ("山川异域，风 月同天"), which immediately went viral online because of its signification of the long-lasting friendship between china and japan. according to account of the expedition to the east by the great master (唐大和上东征传) written by omi no mifune (淡海三船) (see wong, ) , this sentence was from an ancient poem written on the edges of the buddhist robes japanese missions (遣唐使) brought to tang china as the tribute from prince nagaya (長屋王). given its profound roots in the history of japanese envoys to imperial china learning from the chinese culture and civilization, this verse went beyond re-fostering the traditional sino-japanese solidarity. analogizing japan's mask donation with ancient japanese envoys' gifts, it also evoked the retrospective commemoration of the hierarchy between china and japan in history which almost vanishes in the modern era. therefore, the popularity of this verse may indicate the aspiration for the reoccurrence of such bi-lateral relations. indeed, this was only one example of the ubiquitous imaginary of the pan-east asian cooperation and exchange of goods and information as a modern emulation of the tributary system through which imperial china maintained its diplomatic and trade relations to neighboring countries and consolidated its dominance in the region for over a millennium. after china started to keep the pandemic under control and resume the production of medical supplies, this metaphor was further perpetuated in an attempt to accentuate that china's supplies of medical goods and anti-epidemic lessons to nearby countries drastically outnumbered what it was initially given. on weibo, china's return of masks and respirators to its neighbors was often explicitly compared with the "vassals' gifts" chinese emperors assigned to tributary states in posts like this: tribute is both the highest form of alliance and an advanced way of investment, but (this time) it is based on masks! recently, xinwu district in wuxi, jiangsu province donated , to toyokawa, aichi prefecture in japan in return for the , masks, protective clothing and other anti-epidemic materials toyokawa donated to xinwu district in february. (weibo source, march , ) this nostalgic use of metaphor implies a crucial undertone of sinocentrism of the public imagination of the community comprising china and bordering countries fighting against the coronavirus. the tracing of the origin of east asian solidarity to the past is suggestive of the ambition of the present. the chinese public not only fantasizes about a reunion of china, japan, and south korea for covid- but more importantly yearns for the recovery of their nation's leadership and centrality in this battle. as the coronavirus expands rampantly to the rest of the world from march onward, chinese media coverage quickly catches up with the shift of the epicenters from east asia to europe and north america and reformulates the pandemic as a global health crisis. against the depiction of how covid- created chaos, helplessness, and dysfunction in western societies stands the stark contrast of east asia as a safer zone where the outbreaks have been largely contained with success. with the similar control of cases less than , , japan and south korea remain at the heart of this imagined safe zone in company with china even though the reality has seen even fewer confirmed cases in other parts of asia as well as the recent resurgence of virus spreading in all these three countries. this rhetoric is in concert with the prevalence of online deliberations about why east asia as an area has performed better than other parts of the globe in the containment of the virus. at the core of these discourses lies the construction of an east/west binary which frames the global responses to the pandemic into a competition in which "we" (the east/ east asia) have triumphed "them" (the west/euro-america). although china and neighboring countries diverge in the official approaches to handle the pandemic, their relative efficiency in virus containment in comparison with the west is considered to be guided uniformly by the cultural values they share as part of the "confucius east." in particular, collectivism-the principles of prioritizing community interests to personal interests, pursuing social harmony, compliance to authority, avoid causing inconvenience to others-has been glorified as the main drive for the people in east asia to more effectively cope with the governmental strategies in contact tracing, testing, social distancing, and mask wearing. similarly, the regional cooperation in the pandemic management is regarded as a manifestation of these values. for example, the reflections on how south korea has set a model of disease control using mass tracing and testing tend to recognize the smooth uptake of this procedure facilitated by koreans' collectivist mind-set that downplays individual privacy and complies with the data-mining measures to track and publicize their locations, activities, and close contacts. meanwhile, other popular discussions blame the religiosity of the shincheonji church members whose gatherings caused the initial covid outbreak in south korea, which is reflected from the titles of zhihu posts that describe the diffusion of the virus through "hallelujah" such as "the occupation of south korea by covid- , everything has to start from 'hallealia'" and "south korean cult hallelujah devastated the country." apparently, these titles have no intention to mask the underlying tone mocking at the role of christianity in the acceleration, not mitigation, of disease spreading, which further serves as a foil to the power of confucianism to help south korea navigate away from the disaster. in fact, satire targeting at christianity represents the broader criticism of western cultural values in hindering the efficacious enforcement of restrictive and surveilling measures against the coronavirus. the east asian identity is thus reaffirmed through the clashes between the eastern and western civilizations. however, it is worth noting that the narratives about the east asian conquest of covid- are again permeated with the metaphor of the tributary system delineating china as the leader and role model in this imagined "safe zone." not only does the attribution of the regional success to confucianism call up the historical chinese centrality in the sinosphere but the emphasis on china's ability to offer lessons and instructions from its early experience for its neighbors to benefit from also ratifies the restoration of the "teacher/student" relation between imperial china and pre-modern japan and korea. far from a total reenactment of the historical sinosphere, this chinese imaginary of east asia engages with a purposeful selective process that amplifies china's solidarity with some east asian countries but simultaneously mutes others in the same region. as remarked earlier, a majority of the online narratives about the cooperative responses to covid- in east asia revolves around china, japan, and south korea, with less frequent inclusion of singapore as well as occasional reference to such countries as mongolia and myanmar. this emphasis on forming a coalition with japan and south korea is compatible with china's longterm agenda of promoting and dominating the china-japan-south korea union (中日韩一体化), which was recently reiterated by the three governments' consensus to speed up the negotiation of the free trade zone (中日韩自贸 区) (wang, ) . in this sense, the covid- crisis has offered a discursive site for the chinese state to rebuild this trilateral bond and remodel its significant neighbors whose national images, due to the respective disputes around diaoyu islands and thaad (terminal high altitude area defense), have been negative in china for almost a decade. while the china-japan-south korea triangle is romanticized in connection with other small countries, the alienation of some confucius societies from this imagined "cooperative" east asia is quite striking, especially given the outstanding results some of them have produced in the prevention of disease transmission. the first excluded category includes taiwan, hong kong, and macau-the territories outside the mainland in the great china area. whereas macau is often forgotten by the media as it has always been, both taiwan and hong kong are widely criticized and mocked for their attempt to politicize the pandemic as a weapon to confront beijing and increase international recognition. the second group pertains to north korea and vietnam-the authoritarian states that have close political and ideological bonds with china. for instance, north korea has been constantly questioned and satirized because of the lack of transparency in the disclosure of its epidemic circumstances. vietnam's outstanding handling of the virus which led to only confirmed cases and death was nearly silenced in the mainstream media coverage. in the unusual reference to vietnam in some zhihu conversations, vietnam's success was rarely celebrated but considered as a "threat" to china's leadership in containing the pandemic in the area. the trivialization and exclusion of these countries/ regions from the chinese imagination of east asia as a collective force fighting against covid- is not unexpected. in the first place, the negative attitudes toward them (except macau) reflects a backlash against the restrictive, noncooperative methods those governments have enforced to block the virus from mainland china (e.g., full border closure; ban on exports of medical supplies), which signifies their resistance to be incorporated into the modern tributary system chinese people have aspired. yet for taiwan and hong kong, this exclusion repeats the endeavor of chinese official propaganda to erase the distinction between them and the mainland and disavow their political autonomy. instead of being completely out of the picture, their responses to the coronavirus are mainly discussed as part of the chinese experience to consolidate the national identity. for north korea and vietnam, the negative impression may partly result from china's ongoing diplomatic conflicts with them in recent years regarding the south china sea and denuclearization, respectively. nevertheless, the shaking of the "socialist brotherhood" on the matter of covid- also implies the reluctance of the chinese public to articulate a regional identity around the axis of a shared political regime. in fact, assimilating itself with ideological and political allies is likely to obscure the focus of this imaginary on china's historical and cultural alignment with japan and south korea. as covid- begins to shift both the scholarly and media focus on an international scale to reconsidering the dark sides of globalization (chan & haines, ) and mourning for the disruption of european union (trofimov & pancevski, ) , china's reversed agenda of imagining a regional union is stunningly intriguing. on one hand, the eagerness to build solidarity with east asian countries represented by japan and south korea might be a strategy to react to the racialization of covid- as a "chinese virus" and the demonization of china as a "public enemy" and "trouble maker" in the euro-american political and media agenda (viala-gaudefroy & lindaman, ). by articulating china's resemblance (and collaboration) with the bordering democratic capitalist states (rather than the "socialist brothers") in the "confucius-inspired" success of halting the virus, the public discourse strives to construct a collective identity of the east so as to brush off china's label of the other imposed by the western imagination. ironically, this consolidation of the eastern identity also serves as a repercussion to otherize the west as the loser to the coronavirus. on the other hand, the rise of this east asian imaginary centering around china's historical and cultural bonds with japan and south korea has far-reaching implications for china's geopolitical strategies beyond the covid- pandemic and the realm of public health. rested upon the trope of the imperial tributary system, this imagination reflects how the chinese public discourse echoes the state ambition to recuperate the historical dominance of china in the sinosphere, which is part of chinese communist party's long-term project of "the great revival of the chinese nation" (中华民族伟大复兴), or in xi jinping's term, the "chinese dream" (中国梦). incorporating japan and south koreathe most important american allies in east asia-into the imagined tributary network might serve the specific purpose of weakening the u.s. hegemony in the region (see ikenberry, ) , whereas the tactic exclusion of north korea and vietnam indicates the indifference of many chinese to the state's political and ideological "comrades" (whose traditional alliance with china has often proven itself unstable and delusionary in the changeable economic and political dynamics in east asia). more importantly, this selective reimagination of the eastern union expresses the chinese public's nostalgic ideal of the nation's revival, which dreams of a return to the middle kingdom, the empire that reunites and leads east asia through culture and history. during the year , which is anticipated to be the warmest year in human history, we failed to stop the rampant spread of a coronavirus called covid- and its disastrous impact on societies and individual lives. unlike its "cousin" sars, which broke out in early and vanished into thin air largely because of rising temperatures, the current respiratory epidemic has yet to show any sign of amelioration with the arrival of summer. news photos have shown audiences an incredibly bleak, bizarre, and somewhat surreal picture of life during the pandemic. streets are evacuated. stores are closed. public services are paralyzed. modernized cities have become empty and ghostly quiet. only scattered people equipped with medical face masks walk anxiously in this futurist, apocalyptic scene. to use timothy morton's concept, the covid- pandemic has become a "hyperobject," a phenomenon that possesses an ahuman time scale and an extremely diffused quality in occupying space. in such a space-time reconfiguration, or, in plain language, during this type of disaster, humankind becomes an obsolete idea, as humans no longer play a meaningful role in the space-times created by and for "hyperobjects." unfortunately, such a concept bares relevance in light of the uncontrollable proliferation of the coronavirus across the globe at this juncture. worse still, some epidemiologists warn that a new round of outbreak will likely occur soon in the coming fall. a possible scenario could repeat the conditions after the / fukushima daiichi nuclear disaster, when breathing with face masks, people eventually became accustomed to a state of emergency as the conditions for living and dying in the anthropocene. "[p]oison has become a normal feature of daily life, the second nature we have to inhabit" (berardi, , p. ) . while one can attribute the deterioration of nature to neoliberalism and its disastrous governance, this essay, rather, speculates on what foregrounds the involutional relationship between humans and the earth beyond the "nature-culture" divide. whether one is willing to admit or not, viruses are neither creation ex nihilo nor culturally and politically constructed representation. instead, they are beings that have always been part of earth's composition. in a prophetic book, the natural contract, the late philosopher michel serres ( ) describes the evolution of the earth's composition. in ancient law and modern science, nature was treated as an objective reference point, because it had no subject. existing objectively "out there," the earth was a space that did not depend on humans but only acted passively in relation to causality. yet, witnessing the ecological crisis arising in the th century, humans realized that the earth has been affected by our behavior and is now behaving like an aberrant subject! in recent scholarship, this subject has been referred to as gaia, the capricious goddess of the earth (see latour, , p. ) . the earth is full of action and so is covid- . as described in news reports, the coronavirus looks for and hijacks its hosts; it finds easy purchase on, and takes control of, human bodies; it kills many, but not all, of its hosts so as to keep moving, spreading, replicating, and surviving. it would be impossible to talk about the virus without referring to those actions. cited by the washington post, a virologist came up with a vivid analogy for viruses by comparing them with destructive burglars. "they break into your home, eat your food, use your furniture and have , babies" (kaplan et al., ) . as the word "object" refers to entities that are inanimate and subject to chains of causality, viruses, in this sense, hardly fit into this definition. for instance, covid- remains mostly enigmatic, not least because it is considered strikingly sneaky-"the virus doesn't really want to kill us. it's good for them, good for their population, if you're walking around being perfectly healthy," said another virologist in the same washington post article (kaplan et al., ) . besides doing things such as breaking-into, eating, and having-babies, the virus is further endowed with intentions-it does not want to kill us! however, the coronavirus should not be mistaken for a subject, especially a subject-agent, which is historically associated with liberal humanism since the enlightenment and which is deeply rooted in the "nature-culture" divide, an ontological regime referred to by latour as "the modern constitution" (see latour, b) . the idea of the subject as a product of euro-american modernity is indivisible from its aim to achieve individual sovereignty and autonomy. in a politico-legal sense, bounded individualism is the most evolved form of this idea in the wake of the global expansion of capitalism. faced with an unprecedentedly active earth in the late th century, nonetheless, this anthropocentric conception of the subject-agent has been confronting exponential challenges, among which the current coronavirus pandemic constitutes the latest one. to be clear, the term "subject" is a mismatch for covid- , not because it is agentless and incapable of doing the same things that humankind does. the contrary is true: the state of being of the virus-what it is-can unfold only through its actions and long after its performances. at stake for the virus and humans is that there are "no pre-constituted subjects and objects, and no single sources, unitary actors, or final ends" (haraway, , p. ) far from being a de-animated object, or an anthropomorphized subject, gaia, the increasingly "rioting" earth, is a collective of actions that distributes agency in heterogeneous and surprising ways. as a result, "we must not believe in advance that we know whether we are talking about subjects or objects, men or gods, animals, atoms, or texts" (latour, a, p. ) , and also viruses until their actions are captured, and rendered into shapeswhether the shape of a human or of a virus. the story of the human-centered history is being replaced by an explosion of narratives about the increasingly animated and animating earth. however, the dualism of the subject versus the object, unfortunately, is still perniciously conserved in the mainstream reaction to the covid- pandemic. when societies are forced to act on the pandemic, the virus is almost exclusively treated as an object subject to the chain of causality. this tendency is clearly reflected in the mobilization of wartime rhetoric and discourses in conjunction with governments' anti-epidemic measures. for instance, when visiting wuhan right after its lockdown, sun chunlan, china's vice premier, warned that the country was facing "wartime conditions." likewise, only month later, president donald trump declared a national state of emergency over the coronavirus outbreak in the united states. in this antagonistic discourse, contending with the virus, a not-yet-tamed and potentially threatening other, is framed as a relationship between humans and their enemies. for those who believe humans and only humans make history, a self-proclaimed war on the virus is unavoidable! peace, accordingly, is only imaginable to be reached, or more precisely restored, to an already existing order, established primarily for humans. mobilized to describe the relationship between covid- and humans, "war" is a terrible and even dangerous choice in terminology, due to its undertone of human exceptionalism. in fact, nearly % of the cells in a human body is "part of a vast community of companion species, particularly bacteria and viruses" (smart & smart, , kindle ) . unfortunately, most humans have yet to learn the meaning of living and becoming-with these beings who are made by and making humans at the same time. in her book staying with the trouble: making kin in the chthulucene, donna haraway ( ) invites readers to contemplate our troubling present, the chthulucene, an emerging regime of naturecultures, as opposed to the "nature-culture" divide. contrasting to the discourse of the anthropocene and the capitalocene, both of which are conceived as human-induced condition, the "chthulucene" is, first and foremost, concerned with earth beings who live in "manifold forms and manifold names in all the airs, waters, and places of earth"-they are monsters which "demonstrate and perform the material meaningfulness of earth processes" (haraway, , p. ) . the vicious coronavirus is evidently one of these monsters. despite the havoc it is creating in the present, the epidemic is a manifestation of the biotic and abiotic powers inherent in earthly actors and is part of "ongoing multispecies stories . . . in times that remain at stake" (haraway, , p. ) . as implied by the title, one of the valuable lessons of haraway's book is that, for humans in particular, there might be no better option other than to stay with troubles, of which humans are never innocent. staying with the troubles demands caring for all the threads that bind us together and make our existence possible in the first place-humans are made by countless earth beings and vice versa. it also means that we are required to weave unexpected and even dangerous connections with others, in haraway's ( ) words, making kin as oddkin "in unexpected collaborations and combinations . . . we become-with each other or not at all" (p. ). this insight is particularly useful for thinking about viruses. because viruses have "no cellular machinery of their own, they become intertwined with ours. their proteins are our proteins" (kaplan et al., ) . in this sense, the evolution of humans and viruses is inseparable from the process of involution of the two into one. in other words, becomingwith means that, by definition, a "we" always precedes an "i," a "you," or a "they." the so-called "asymptomatics" provide an excellent example of this point. asymptomatics refer to those who test positive for covid- but, confusingly, do not suffer from illness or show any symptom of the disease. asymptomatic infections or carriers are possibly greater in number than those with symptoms. at this point, it is impossible to decide which of the two types is more typical of covid- infections, because, as a researcher at the university of oxford says, "there is not a single reliable study to determine the number of asymptomatics" (shukman, ) . in the same news report, neil hall, a biomedical expert, suggests considering asymptomatic cases of the coronavirus as the "dark matter" of the epidemic, as invisible and not-yet identified dark matter is believed to make up most of the matter in the universe. despite the fact that no conclusion has been reached about the enigmatic phenomenon of asymptomatics, the differences that manifest among patients reveal that the virus, and the particular cases of infection, should be examined as specific units. in other words, between the virus and humans, the specificity of an encounter matters. unlikely to be autopoietic systems that reproduce autonomous units, the virus and an infected body constitute a collectively produced, sympoietic system that does not have self-defined spatial or temporal boundaries. in these cases, and from a non-anthropocentric, philosophical point of view, the idea of bounded individualism has to be discarded for good. beyond the divide between the subject and the object, what emerges are ontologically heterogeneous practitioners who are involved in each other's lives. besides evolution, living also relies on involution. without any intention of "romanticizing" covid- and the current pandemic, staying with the trouble, as articulated by haraway ( ) , is "to make kin in lines of inventive connection as a practice of learning to live and die well with each other in a thick present" (p. ). the coronavirus does not happen as a matter of fact, which "passively" waits to be discovered, investigated, tamed, or neutralized by "active" humans. what we call the covid- pandemic manifests itself as a differentiating and relational effect because it matters by bringing into being various relations between humans, and between humans and their oddkin. in this view, science is only one practice among many others to capture the efficacy of its mattering. in addition to biomedical measures, a more critical question for the coronavirus crisis is "what method does the matter demand" (thompson, , p. ) ? proposed by haraway for living in the chthulucene, the string figure might also serve as an appropriate method and image for the pandemic, characterized by its exceptional contagiousness and interactivity. consisting of "passing on and receiving, making and unmaking, picking up threads and dropping them," the string figure is all about "becoming-with each other in surprising relays" (haraway, , p. ) . crucial to this method is that it does not guarantee what is obtained turns out to be good in the end, because living itself has become so dangerous in this very thick present-agencies are distributed, conflicting, and entangled in a myriad of practitioners, human and non-human alike. in this pandemic, we are all playing the game of string figures with our oddkin. it is not beneficial to judge in advance who is a subject and who is an object, or which one is active and which one passive, as all participants might be capable of something that matters in one way or another. for example, one thing that the respiratory disease teaches us is that not only breathing matters but also the manner how one breathes matters to others. life and death happen inside specific connections and their mattering in mundane, and even fleeting, encounters. making covid- matter requires us to reanimate "what is coming into states of matter and mattering in bodies, stories, acts, and events" (stewart, , p. ) , in other words, in the vicissitudes of our ordinary lives. for the future of this thick present, one key is to stop imagining the crisis of the coronavirus as something wholly predicated on effective vaccines and scientific solutions. instead, humans must learn to connect and also care for threads, some of which are obvious, some elusive, some vicious and dangerous, and some fictional. we may need to discard terms such as "overcoming" or "solution," and turn to terms like "participation" concerning all that we are uncertain of but have to live and become with, together, in the "metamorphic zone" called the earth (latour, , p. ). what does it mean, the plague? it is life, that is all. the most abundant biological entities on earth, viruses are forever and everywhere. suspended between living and being dead, they are simply there, a slimy strip of ribonucleic acid (rna), as biologists tell us. poorer in life than tardigrades, incapable of movement, and having no logistic of their own, they ride on and feed off others to replicate themselves, to become the viruses that they are. as smart schoolchildren know, they are transmissible and must be so transmitted as to go viral, to become the viruses as we know them. dependent entirely on carriers, that is, exploiting others' hospitality, without which they have no life (but also no death either), viruses exemplify transmissibility. they live and thrive, as it were, only if their hosts are susceptible, in motion, and in contact and they die or die down when susceptible hosts are either unavailable or no longer hospitable. defined, that is, made finite, by transmissibility, and yet transcending its barren finitude through parasitism, viruses exist and operate like pure media, self-generating and selfgenerated by being entirely coterminous with the channel through which they flow and multiply. interpolating and encoding themselves in the metabolic cycle of others, thereby reproducing themselves passive-actively, they mediate by colonizing others and, in so doing, mediate themselves by proxy, going about so energetically and indiscriminately as to cause the demise and thus thwarting unwittingly their own propagation. if viruses communicate anything, if their shadowy occupation of host bodies sends any message, it is their very own communicability, their ability to disseminate themselves over a large population with effort less than minimal. although all over creation and in abundance, most of the viruses cause us no harm and we pay them little attention, even though they populate our body and capitalize on its resources. they become a matter of grave concern when they infect us, when they not only put themselves inside (in-ficere) our body and stain its normal functioning, but also threaten to afflict as many people as their "infectivity" attacks. more dangerous and less tamable than most microbes, viruses invade our body and compromise it at the cellular level. they do not just make us sick; they bring about plague. once seen as a cause of infection, viruses accrue significance and take on the label "pathogens." to refer to viruses as pathogens implies that they are "medicalized," that they not only enter into a relation with humans who regard them as toxic and virulent, but are also seen as a problem to be addressed in a methodical, systematic, that is, "scientific," manner. it is through this medicalization that viruses are individuated and identified as a distinct biological entity and, having been so captured and given a name-for example, h n , mers-cov, sars-cov- , covid- , and the like-by what might be called the "clinical gaze" and its taxonomic procedures, they enter into sciences and become a focus of medical research, made all the more pressing if and when they create public health crisis. more than one hundred years after martinus beijerinck gave the name contagium virum fluidum (contagious living fluid) to the incitant of tobacco mosaic first discovered by adolf mayer and dimitri ivanovsky, viruses are now actively collected, classified, and manipulated by scientists in highly restricted spaces called laboratories, most of which, like the viruses housed carefully therein, are hidden from public eyes. while slimy poisons were once thought to be sent down by god to punish us for our sins, we now see viruses not only as an object of scientific investigation but also as a medical challenge that nature poses to us as biological creatures on earth. like birds, bats, and rats, we are all equal opportunity hosts to killer germs. not all viruses are fully pathogenic, but pathogenic viruses are ever ready to go viral when the conditions are ripe. however, although viral infection may break out and spill over, it does not mean that there is a pandemic. "pandemics," as virologists tell us, "begin when a brandnew virus infects a human who also at that point is able to transmit the virus to other humans" (buettner, ) . two points should be noted without delay. first, pandemics are not created by transmission of viruses from some source to humans, but from humans to humans. breakouts of viral infections among members of a primate community deep in the amazon rainforests, for example, may be large scale and may disturb ecological balance alarming to conservationists, but they do not for all that count as pandemics in the sense that the term is properly used. viruses might infect one or more individuals, but humans are responsible for creating the conditions that transform infections to outbreaks and outbreaks into pandemics. pandemics, in other words, are not natural or biological phenomena; they name a human crisis, a contagious malady plaguing humans who are both agents and patients at the same time. contagious diseases are disastrous to all, locked, as we are, in the same bubble in which microbes live and grow, but pandemics are decidedly more pernicious in that we become, often unknowingly, the source and the cause of our own infestation. second, pandemics are "declared." as is the case with catastrophic events in history, like wars, famines, or mass cultural anomaly as bizarre as the chinese sorcery scare of , whose duration and identity result from an act of punctuation and sense-making entirely sociopolitical in nature, pandemics too begins with a performative act that announces their beginning and, having made them to begin in this way, determines when they reach their end, even though the viruses and their carriers may still be with(in) us (see kuhn, ) . naming not microbial activities in nature but a crisis for humans, pandemics are events made real, public, and urgent, as just said, by a performative-a speech act, to be exact-whose authority in pronouncing their beginning and end depends on the very force that makes the declaration authoritative and forceful in the first place. brought into being by discourse and public communications, pandemics are social constructions; they signal a state of emergency-appearing, first, as physical ailments on the part of individuals, subsequently identified and ratified by medical and scientific community as a real health problem, and finally materialized by authoritative broadcast and public acknowledgment, thereupon becoming a public policy issue to be addressed by political leadership, all these over a determinate territory. once established as such, a pandemic individualizes a collective paroxysm, making it a public enemy by giving it a face, a name, a certain life span in the social calendar, without which the havocs wreaked by the virus would not be the crisis its name designates and invokes. it is in this declarative nature of pandemics that we can see how viruses, once medicalized and publicly acknowledged, are inevitably entangled with science, history, culture, and politics. socially constructed by a decision, by a cut or break into regular time, they mark a "zone of exception," a temporal heterotopic, as it were, where we, individually and collectively, stand to one another as equal subjects to illness, unfreedom, and death in the unending drama of man against nature and its hostile elements. viruses are viruses are viruses. they have no political content; operating according to the laws of physics, chemistry, and biology, they come and go on their own rules and on their own times, as nature dictates. in sharp contrast, pandemics are biopolitical phenomena; they are moments of discontinuity or rupture in social order, shot through from start to finish with forces and factors that shape culture, history, and economy, which in turn determine what they mean and how they come about and come to pass. moreover, and importantly, a pandemic is not a single, monolithic event; it is a series of localized epidemics, each with its own point of origin, its own history, its own epidemiological pattern and impacts. further still, all these factors crisscross one another in a complex, nonlinear fashion, amassing multiple agents and stakeholders in such a critical fashion that the language of war is often used by the authority in charge to quell the infectious assault. pandemics force social changes precisely because the changes they incur invite resistance. it is for this reason, perhaps for this reason alone, that pandemics inevitably appear as a site of social contestations, politicizing and politicized by the heterogeneous constructions barely betrayed by the name of a single virus. it is for this reason too that pandemics assert themselves as a sign of generalized cultural and economic strife, a symptom of social struggle underlying the health terror that a viral breakout unfailingly induces. covid- is a novel virus, novel in that scientists do not fully understand how it afflicts the body and therefore cannot predict its epidemiological paths. to control its spread, we have no choice but to employ methods developed from past experiences, such as quarantine/isolation, social distancing, face coverings, and contact tracing, to name a few now well-known. because viruses are infectious, to control its spread is, understandably, to separate and to isolate. this means that people be kept away from one another. instead of gathering or being together, we make ourselves scare; better yet, we isolate ourselves, even if begrudgingly. more than that, the injunction of isolation leads straightaway to insulation in that the ultimate, foolproof means of isolation is to literally atomize ourselves, to turn ourselves into windowless monads. indeed, all the mitigation measures we hear about of late-quarantine, mask wearing, hand washing, and social distancing-are in reality anti-social measures. don't reach out and don't touch anyone! cover up your face! just as social distancing-a contradiction in terms of sorts-means keeping physical distance, and just as mask wearing reduces mutual recognition based on simple vision to its unnatural minimum, (self-)isolation and quarantine all but eliminate human contact of all kinds. when the plagues struck, we were all lepers; when covid- strikes, we are all windowless monads. pandemics are born of communicable diseases, yet for this reason, they force us to be incommunicable. flattening individuals and bringing to a halt exchange and commerce of every kind, they turn a society into one that is against society. if there is a history of pandemics, it is a history of anti-social history. neither alive nor dead, neither this nor that, viruses are by nature improper. never proper, that is, never being (of) themselves, they appropriate-always ready to make others their own. they are pure media, as suggested earlier. viruses are pure because they mediate unconditionally. however, inasmuch as unconditional mediation performed by viruses leads to the demise of their host, upon whom they depend for their parasitic reproduction, viruses end up annihilating themselves by their very nature; they are always already their own collateral casualties. rendering themselves nil by simply being and subsisting as themselves, pure media are no (longer) media. unconditional mediation ends all mediations. by bringing society to go against itself, viruses commit suicide, so to speak, by killing their host, by the unconditional abuse of others' hospitality. and, alas, weat least some of us-are spared. covid- is a new virus. but, unlike the known flu viruses, or h n , sars, and the like, covid- is considered "novel," not the least because, as indicated earlier, it frustrates scientists' understanding. "it has been like nothing else on earth," says an infectious-disease expert, who falls victim to the virus; "i knew i had the disease; it couldn't have been anything else," but "i don't understand what's happening in my body" (yong, ) . there are many things, inanimate or living, on earth that are like nothing we know so far, and there are many things happing in our body that we do not understand at all. covid- can justifiably be called "novel," but isn't every virus novel in its own way and at some moment in time? isn't being novel the normal course of event in life and in life sciences as well? "there is novelty here," remarks a prominent epidemiologist karl friston upon leaving a lab meeting about covid- , but he quickly adds, "so this, from my point of view, is just an average day" (kosner, ) . being novel is the very characteristic of all viruses and many other things in nature as well. the novelty of covid- may not be as novel as we think. what is possibly novel about covid- is the fact that it gives us the first pandemic in our truly globalized age. the global village, in which we now live, is so hyper-connected-not only by technology but also through affluence, commerce, and global travel-that an infectant can travel from one city to another as fast as jet streams flow. connectivity translates qualitative diversity into measurable multiplicity, reducing distance and difference for the formation of the common, which in turn strengthens connectivity. to be alive, as few would disagree, is to be connected, literally and in every other sense. but this means that we must live in and with the risks that global connectivity brings to us. to be connected brings with it the possibility of being stranded in harm's way. as covid- makes clear, "connectivity is the killer" (kosner, ) . after all, life depends on maintaining boundaries and keeping differences. deadly viruses are deadly because they breach them. as infection rate rises, so does anxiety. and bleak scenes spread as wide as the virus goes. deserted streets, boardedup stores, closed factories, shot-down public transportations; remote learning, work-from-home; stock markets crashed . . . and, worse yet, "i just lost my job." individual solation leads quickly to desolation across the board. and economy bears the brunt of a colossal coronal attack. shortly after covid- spread out of wuhan, china, to europe in january , stories about the economic plight began to top the list of topics in public forums and news media. the future we face seems to lie in one of the two choices: to die from hunger or to die from the disease (餓死 或病死), as the expressions go in chinese media. it is not for no reason that a policy brief released in june by the united nations on the impact of the pandemic is given the title "the world of work cannot and should not look the same after this crisis" (guterres, ) . the address on the launch of this brief, given by the secretary-general antónio guterres ( ) , begins as follows: the covid- pandemic has turned the world of work upside down. every worker, every business and every corner of the globe has been affected. hundreds of millions of jobs have been lost . . . many small and medium-sized enterprises-the engine of the global economy-may not survive. after painting a depressing picture of the future and explaining how difficult it will be for the world economy to return to "normal," guterres's ( ) address makes a hardly perceptible turn when he says "let's not forgot the pre-covid- world was far from normal." it seems then that, rather than shattering the world of work as we know it, the covid- pandemic simply exposes in higher resolution the "tremendous shortcomings, fragilities and fault lines" that have been eroding society and economy from the bottom-up for decades. the pre-covid- world, in which we thought we lived a normal life, is not as normal as we think (see guterres, ) . to save the economy under siege is to "return to normal" as soon as possible, so cry the bureaucrats and journalists alike. but what is "normal" in this case? what does "being normal" mean exactly? is the world, old or new, ever normal? there are norms regulating life, but has there ever been a "normal life" as such? the so-called normal life, a life before covid- , to which we pray to return, is in truth one of recollection, a romantic one at that, as the un policy brief readily admits. just as a viral infection may display more than one symptom on the part of its victims, embody more than one single illness, and create more than one single public health challenge, life, as it is actually lived, is hardly reducible to one normal life. in fact, the socalled normal life is the one that brought us the pandemic in the first place. to live is to live normally; to return to normal is what living is all about. the so-called new normal is both new and not so new, which is to say, it is neither really new nor really normal. perhaps the world has never been and will never be normal, whatever our idea of "being normal" means. if a pandemic can turn the world upside down, it is because life has been turning and turning again. and anything that returns cannot be entirely new. humans have been haunted by viruses since time immemorial. from the prehistoric pandemics in northeastern china , years ago, uncovered at sites now called hamin mangha and miaozigou, to the justinian plague ( - ad) that may have helped to bring down feudalism, or the small pox outbreak that finally toppled the aztec empire before hernán cortés returned to the region in the spring of , viral infections have tormented the lands and their people over millennia. traveling with host animals and humans, viruses had gone global long before globalization became a fact. there are known pandemics in the last years, all displaying the same pattern of spiking in seasonal waves after the initial attacks. covid- , and some of its coronal cousins, will undoubtedly expand the list. to those who are living through its assault, the impacts brought about by covid- are more or less clear and more or less measurable. but what is the meaning of covid- when the current pandemic is over? will it be remembered? if so, in what way and to what extent? if the history of pandemics has taught us anything, it is that history tends to repeat itself, that viral outbreaks are an ineliminable part of the natural history, in which humans are a part and in which no "zone of being" is free from viral infection. recall the spanish flu of , the worst pandemic during the last two centuries. it is estimated to have wiped out million people worldwide, meanwhile infecting million, a third of the world's population at the time. however, despite its short distance of mere one hundred years from us, few people today know much about it, and still fewer are able to understand or feel the impact it had at that time. its centenary a short time ago passed noiselessly, certainly not for lack of stories or records. like the many plagues before it, the spanish flu, it seems, never quite made itself into what reinhart koselleck ( ) calls the "the space of experience" (p. ). failing to make its way into collective memory, it is also helpless in figuring into our "horizon of expectation" (koselleck, , p. ) . if the spanish flu faded largely from memory, all the woes caused by covid- are, likewise, likely to dissipate in time, regardless of how we feel and say about it now. there was a pre-coronavirus world, and there will be a post-coronavirus world, but viruses, known or novel, will outlast our worlds. viruses are everywhere and forever. so, plagues will never disappear for good (camus, , p. ) . but what then does it mean, the pandemic? it is life, that is all. a troubled memory, fading, under the vast indifference of the sky. until the gate of oran closes again. assembled in this forum, the five short essays provide some modest reflections on the coronavirus pandemic and its still unfolding consequences. committed to a variety of disciplinary perspectives and interests, the authors did not set out by pursuing any preset direction or common agenda supposedly carried out collectively in our intellectual labor. rather, what unifies the diverse inquiries in these essays is the shared awareness about the confusion in the public discourse that constantly fails to distinguish a coronavirus called covid- from the covid- pandemic, or as briankle reminds us in his essay, from "a series of localized epidemics." this alertness constitutes a common ground in addressing specific issues or phenomena in these essays. this forum is anything but comprehensive. if it can contribute to the discussion of the crisis, it is most likely because all the essays refuse to bind the pandemic exclusively with the coronavirus and to position the virus and humanity in rigid opposition to each other. in her multispecies ethnography, anna tsing tells a marvelous story about matsutake mushrooms. "when hiroshima was destroyed by an atomic bomb in ," says she, "it is said, the first living thing to emerge from the blasted landscape was a matsutake mushroom" (tsing, , p. ) . when human history temporarily comes to a halt in disasters, matsutake, and also viruses in our case, may well survive and continue to thrive with their own stories. histories are being made every day by humans and non-humans alike; however, the future for those histories to converge has still yet to come. as demonstrated in the essays gathered here, while governments and the public are desperate to frame the virus in their own social and political narratives, the virus also works hard to inscribe its historicity on the earth and humans too. if a message must be dispatched out to all at this juncture, it is that for a future of collaborative survival, the stake of living together has nothing to do with harmony and conquest, but is derived from "disturbance-based ecologies" (tsing, , p. ) , that is, plagues. plagues are life, that is all. the author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. the author(s) received no financial support for the research, authorship, and/or publication of this article. gong yuan https://orcid.org/ - - - xuefeng feng https://orcid.org/ - - - x notes . in a trilogy of contemporary essays, baudrillard ( ) argued that the war in the desert was a new phenomenon, because it was defined and shaped by its discursive aspect as a form of television programming, regardless of what happened on the ground. . that earlier announcement called "demonetisation" led to a vast contraction of commerce and an immiseration of a majority of the population which has still not recovered, and is now widely considered an unnecessary exercise of personal whimsy. for an analysis of the economic consequences, see ghosh et al. ( ) . . the decline of indian agriculture is not adequately discussed in the celebration of urban growth. its effects are however inescapable and directly lead to the growth of informal settlements in cities (balakrishnan, ; jaffrelot & thakker, ) . . mediatization, or the analysis of events with their mediated construction as the starting point, is a phenomenon that has grown in importance across cultural contexts, as media theorists attempt to understand the increasing influence of media forms on culture, especially with the virtualization of human interaction and the redefinition of community through the use of social media and mobile communication. for a fuller discussion, see couldry and hepp ( ) . discontents: an indian history ( ), jayal ( ) traces the current shift in the discourse of indian citizenship from an egalitarian rights-based model to a new regime predicated on religious and cultural identity, given shape through the concomitant technocratic frames of transactional welfare and biometric identity. . four short essays provide further context and narrate the response: shankar et al. ( ) . . partha chatterjee's ( chatterjee's ( , insightful categorization of indian society separates the distinct ontological domain of a small formal "civil society" that includes rights-bearing citizens, from the vast undifferentiated mass of the population that constitutes "political society" and which forms the actual locus of democratic practice. . the current indian government has dramatically increased the acquisition and use of big data in governance, including a reliance on biometric identification for access to welfare programs and the use of mobile phones for access to services: part of the government's covid- response was in the form of a mandatory mobile application that purported to use location tracking to show active virus infections in the user's vicinity. an analysis of its invasive nature can be found in a working paper by deb ( ). . societies always declared war on problems they cannot solve: war on drugs, war on poverty, and the like. it is no surprise to see donald trump refers to covid- as an "invisible enemy" and calls himself a war-time president in his speeches on the covid- pandemic. similar examples abound across the board throughout history. it is widely recognized by epidemiologists today that the model developed by john snow based on the cholera outbreaks between and in england is too linear to be of any use in contemporary pandemics. like the global climate instability or financial market volatility, pandemics are nonlinear phenomena, displaying a high degree of uncertainty that defies simple causal explanation. on this, see kosner ( ) . . it is therefore not surprising that we observe donald trump repeatedly refers to covid- as wuhan virus or kung flu in reaction to his rise and fall in poll and public opinion as he tries to find scapegoat, in this case, china, for his sorry failure in handling the crisis. a virus is always more than a virus when it enters the body politic. india's brutally uneven development patterns are mapped in routes migrant workers are taking home. scroll the gulf war did not take place bifo covid- : straight answers from top epidemiologist who predicted the pandemic the plague. vintage diseasescape: coping with coronavirus, mobility, and politics. global-e the politics of the governed: reflections on popular politics in most of the world lineages of political society: studies in postcolonial democracy cdc director says some coronavirus-related deaths have been found posthumously conceptualizing mediatization: contexts, traditions, arguments the covid- crisis in india: a nascent humanitarian tragedy. books & ideas public policy imperatives for contact tracing in india specters of marx: the state of the debt, the work of mourning and the new international coronavirus conspiracy theories targeting muslims spread in india. the guardian why coronavirus conspiracy theories flourish, and why it matters. the new york times the standard edition of the complete psychological works of sigmund freud as coronavirus spreads, so does racism and xenophobia covid- lockdown and the pandemic of caste demonetisation decoded: a critique of india's currency experiment chinese-japanese-s. korean relations evolve to meet the challenge of covid- . global times the world of work cannot and should not look the same after this crisis the companion species manifesto staying with the trouble: making kin in the chthulucene american hegemony and east asian order by revealing magnitude of migrant worker phenomenon, covid- points to rural distress. the indian express reconfiguring citizenship in contemporary india the coronavirus isn't alive. that's why it's so hard to kill sediments of time: on possible histories karl friston takes on the pandemic with the brain's arsenal high on talk, low on substance: modi's speech showed india is ill-prepared for covid. the caravan soulstealers: the chinese sorcery scare of the pasteurization of france we have never been modern agency at the time of the anthropocene migrant workers distrust a state that does not take them into account it was already dangerous to be muslim in india. then came the coronavirus india racked by greatest exodus since partition due to coronavirus. the guardian india: portents of an ending: modi, the rss and the rise of the hindu far right. the nation how covid- compares against other killer diseases in india why east beat west on covid- : east asia has handled and contained the pandemic far better than the west on nearly all metrics shame in the cybernetic fold: reading silvan tomkins the natural contract the demagogue and his labyrinth. the baffler coronavirus: the mystery of asymptomatic "silent spreaders posthumanism: anthropological insights mattering compositions labyrinth of linkages: cinema, anthropology, and the essayistic impulse coronavirus crisis threatens to split an already fractured eu the mushroom at the end of the world: on the possibility of life in capitalist ruins donald trump's "chinese virus south korea agree to continue push for free-trade deal despite ongoing tensions across region. south china morning post buddhist pilgrim-monks as agents of cultural and artistic transmission: the international buddhist art style in east asia, ca covid- can last several months the popularity of "rivers low, mountains high; the same moon in the sky" and its english translation the hindu rashtra comes of age. contending modernities li lu is an associate professor of literary theory at the school of chinese language and literature and a research associate at the center for literary theory at beijing normal university. he teaches courses on marxian aesthetics, critical theory, and translation theories.srinivas lankala teaches in the department of communication at the english and foreign languages university, hyderabad. he works in the areas of semiotics and critical theory, and engages with questions of politics, history, and nationalism. key: cord- -no mojz authors: gaddy, sarah; gallardo, ressa; mccluskey, shelley; moore, leanna; peuser, alex; rotert, rachel; stypulkoski, corinne; lagasse, a blythe title: covid- and music therapists’ employment, service delivery, perceived stress, and hope: a descriptive study date: - - journal: music ther perspect doi: . /mtp/miaa sha: doc_id: cord_uid: no mojz in early , the covid- pandemic was declared, which impacted music therapists in terms of employment, service delivery, and mental health. however, the extent of changes within the profession was unknown. the purpose of this study was to determine the impact of the pandemic on the employment, service delivery, stress, and hope of music therapy professionals in the united states. music therapists (n = , ) responded to a -item survey including questions related to employment and service delivery. the study also included the adult hope scale and the perceived stress scale- (pss- ). results indicated that many music therapists experienced changes in their positions, including a decrease in client contact hours and an increase in using alternative services, such as telehealth. changes in service hours and delivery were higher for individuals who worked in private practice than for other settings. primary respondent concerns included being a carrier of covid- , being isolated from loved ones, and income loss. compared with prior general population samples from the united states, respondents reported higher levels of hope, with a majority of respondents also reporting a high level of hope for the profession. respondents also indicated a moderate level of perceived stress on the pss- . open response comments provided additional insights into the situational stressors and feelings of hope at this time in the pandemic. the results of this study indicate that music therapists adapted to service delivery changes and continued to provide services to clients, despite the many difficulties faced during the pandemic. abstract: in early , the covid- pandemic was declared, which impacted music therapists in terms of employment, service delivery, and mental health. however, the extent of changes within the profession was unknown. the purpose of this study was to determine the impact of the pandemic on the employment, service delivery, stress, and hope of music therapy professionals in the united states. music therapists (n = , ) responded to a -item survey including questions related to employment and service delivery. the study also included the adult hope scale and the perceived stress scale- (pss- ). results indicated that many music therapists experienced changes in their positions, including a decrease in client contact hours and an increase in using alternative services, such as telehealth. changes in service hours and delivery were higher for individuals who worked in private practice than for other settings. primary respondent concerns included being a carrier of covid- , being isolated from loved ones, and income loss. compared with prior general population samples from the united states, respondents reported higher levels of hope, with a majority of respondents also reporting a high level of hope for the profession. respondents also indicated a moderate level of perceived stress on the pss- . open response comments provided additional insights into the situational stressors and feelings of hope at this time in the pandemic. the results of this study indicate that music therapists adapted to service delivery changes and continued to provide services to clients, despite the many difficulties faced during the pandemic. keywords: covid- pandemic, employment, hope, music therapy service delivery on march , , the covid- pandemic (henceforth referred to as the pandemic) was declared by the world health organization (who, ) . the covid- virus was originally detected in november and began to spread throughout the united states in early march . the spread of a novel virus leads to uncertainty due to the unpredictable nature of the virus and continual changing information about risk, mortality, and severity (harwood, ; morens & taubenberger, ) . researchers and mental health professionals recognized the potential for the pandemic to affect stress and mental health (mucci et al., ) , with researchers highlighting the negative impact of the pandemic on the mental health of healthcare professionals (moazzami et al., ) . as healthcare professionals, music therapists (mts) experienced personal and professional changes due to the pandemic; however, the extent of change within the united states was not yet established. one of the first responses to the pandemic in the united states was for state governments to implement social distancing, "stay at home," and/or quarantine protocols (mervosh et al., ) , in an effort to slow the spread of the pandemic and decrease the impact on healthcare facilities (centers for disease control and prevention [cdc] , ). these protocols had a drastic impact on the economy and employment, as the united states reached an unemployment rate of . % in april (long, ) . changes in employment were seen across many nonessential healthcare workers, as social distancing and quarantine protocols restricted the ability for these professionals to provide in-person services (e.g., department of health and human services, ). balanzá-martínez et al. ( ) highlighted how the combined impact of financial difficulties and social isolation could further impact mental health and the overall feelings of stress. social distancing and quarantine protocols created an immediate need for many professionals to shift away from in-person services to telehealth and other alternative services (cdc, ). on march , , the american music therapy association (amta, ) posted a statement indicating that mts were needing to make difficult decisions about in-person services, given the risk of viral spread during face-to-face contact. the shift to telehealth within the profession was documented on april , , with a statement from amta supporting telehealth as a beneficial means for providing services to clients. resources were added to the amta website, including a guide for virtual service delivery that provided suggestions for curating/creating virtual content and providing telehealth services (block & knott, ) . although these alternative services provided an opportunity for clients to continue receiving music therapy, professionals were required to quickly learn about online service delivery, including securing permissions and ensuring compliance with the health insurance portability and accountability act (hipaa). furthermore, the extent to which these services were employed by mts was still unknown. the rapid changes required in response to the pandemic, combined with uncertainty about the future of employment and/or service delivery, may have impacted the perception of stress and feelings of hope in music therapy professionals. according to folkman ( ) , decreased control over one's own circumstances can impact a person's feelings of hope, particularly in times of high psychological stress. furthermore, uncertainty can exist within stressful situations, and hope is one way to cope with uncertainty. according to snyder ( ) , hope is comprised of two concepts (ways of thinking): pathways and agency. pathways relate to an individual's ability to produce a plan to meet a goal, whereas the agency describes an individual's motivation to meet those goals by the determined pathways. individuals with high hope are more likely to generate alternative routes to goal attainment and be more adaptable when encountering obstacles (snyder, ) . measuring perceptions of hope and stress could provide the music therapy community with information on how music therapy professionals responded to circumstances surrounding their careers during the pandemic. the purpose of this project was to determine the impact of the pandemic on the employment, service delivery, hope, and stress of music therapy professionals. to this effect, the researchers asked the following research questions: ( ) what changes are music therapy professionals experiencing in terms of contracts/job hours? ( ) what changes are music therapy professionals experiencing in terms of income? ( ) what changes are music therapy professionals experiencing in types of services provided? ( ) what are the feelings of hope reported by music therapy professionals? and ( ) what is the level of stress reported by music therapy professionals? this study received ethical approval from the university institutional review board (irb - h). the survey was sent via email from the certification board for music therapists (cbmt) roster, which included , mts in the united states. the survey link was also posted on social media platforms such as facebook and linkedin. consent was obtained from , individuals, yielding a % response rate. five individuals working outside the united states and individuals who did not complete the demographics section were excluded from the results. the remaining , ( . %) survey respondents were included in the data analysis, of which , completed the entire survey. at the end of the survey, respondents had an option to enter their email for a chance to win a $ gift card and could elect to receive notification of follow-up surveys. individuals were provided with a list of resources in case they experienced stress. the full survey is available in appendix a of online supplementary material. the survey demographic and employment questions were created by the researchers, using kern and tague ( ) as a model. the survey was sent to two researchers with experience in descriptive research and piloted with mts prior to release. the survey was administered using qualtrics beginning on april , , and remained open for two weeks. the survey consisted of items within four sections: ( ) demographics, ( ) employment/services provided, ( ) levels of hope, and ( ) levels of stress. respondents were allowed to select all options that applied in sections pertaining to current situation, job position, and client populations, due to the multiple roles held by mts. participants were permitted to advance without answering all questions, and items that were not relevant to them were skipped. the survey included two standard scales: the adult hope scale and the perceived stress scale- (pss- ). adult hope scale. the adult hope scale is a standardized questionnaire that asks respondents to self-report degrees of agreement to statements on an -point likert scale (snyder, ) , with a range from (low hope) to (high hope). eight of the statements are broken down to two subscales representing participants' agency (items , , , and ) and pathways (items , , , and ), with each subscale ranging from (low hope) to (high hope). the additional four questions are filler items. agency and pathways scores are added to determine a total hope score, with higher scores reflecting higher levels of hope. snyder ( ) noted the mean total hope score for the general population was (sd = ). the instrument has shown high internal consistency, with alphas from . to . , across samples (snyder, ; snyder et al., ) . the researchers added an additional question to capture respondents' feelings of hope for the state of the profession. perceived stress scale. the pss- (cohen et al., ; cohen, ) was used to measure mts' perceptions of stress during the pandemic. the pss- asks the respondent about the stress in the previous month using questions about perceived feelings. individuals rate their frequency of each feeling on a -point likert scale from (never) to (very often). there are four positively worded questions that are reverse scored. scores on the pss- are compiled into a single score that ranges from (lowest perceived stress) to (highest perceived stress). the instrument has been shown as reliable, with relatively high internal consistency (ɑ > . ) across studies of different populations (lee, ) . in , the pss- was administered to , individuals in the united states, with an overall mean score of . (sd = . ) (cohen and williamson, ) . the pss- has been used in previous music therapy research with student participants (moore & wilhelm, ) . the online survey included quantitative and qualitative data in order to more comprehensively capture mts' experiences during the pandemic. the research team completed a descriptive analysis for multiple choice, ranked, and percentage answer questions. this included a tally (number of responses and percentage) for questions regarding changes in workload/assignments and providing different services. it should be noted that response counts for each individual question varied, as respondents could advance through the survey without answering all questions. there were two standard scales included in the study. for the adult hope scale, the researchers calculated the mean and standard deviations of the agency subscale, pathways subscale, and total score (summation of agency and pathways scores). the researcher-added question about hope in the music therapy profession was not included in the subscales or total score calculations. for the pss- , the researchers calculated the total score by reverse scoring the positively worded items and then adding the items for each participant. the researchers computed a cronbach's alpha value to determine internal consistency. levels between . and . are considered within an acceptable range (tavakol & dennick, ) . the researchers conducted pearson's correlations to examine the strength of the relationship between pss- scores and three scores related to the adult hope scale (agency subscale, pathways subscale, and the overall hope scores). the researchers also conducted a correlation to examine the relationship between the total adult hope scale score and the hope for the music therapy profession score. in this survey, there were two open-ended questions, one focused on feelings of hope for the profession and the other allowing respondents to comment regarding their experiences during the pandemic. similar to the procedures used in rushing et al. ( ) , two members of the research team independently read comments, developing a list of possible codes. the researchers then clustered these codes into themes and subthemes. the researchers completed these steps separately, and then discussed discrepancies to agree upon themes. each pair of researchers used excel to individually count the frequency of the themes and subthemes and reported these counts within the results. a total of , responses were received from mts working in the united states. respondent ages ranged from to , with nearly half the respondents representing the to age group ( . %). the majority ( . %) reported having a bachelor's degree as their highest level of education while . % reported having a master's degree. all regions of amta were represented. over half ( . %) of respondents reported working in the profession between and years (table i) . the first research question involved changes in contracts/ job hours during the pandemic. out of , respondents, ( . %) reported working full time, ( . %) reported working part-time, and ( . %) reported contracting for an agency or private practice prior to the pandemic (table i) . only . % of respondents reported being either unemployed or not currently working in the profession prior to the pandemic. when providing information about changes in employment (n = , ), ( . %) respondents reported no changes to their work duties. respondents reporting changes in employment (n = ) were most often providing remote clinical services from home ( . %). fewer respondents reported being assigned different duties to complete on-site ( . %) or from home ( . %). one hundred and forty ( . %) reported having their positions furloughed, and ( . %) reported having their positions eliminated. of the respondents who reported working at the time of this survey, provided information about their hours at this time in the pandemic (compared with , before the pandemic). sixty-one respondents ( . %) reported having ≥ client contact hours per week, compared with ( . %) prior to the pandemic. eighty-six ( . %) reported to client contact hours per week, in comparison to ( . %) prior to the pandemic. the greatest increase was seen in the category of to hours per week, with ( . %) compared with ( . %) before the pandemic. figure shows the change in contact hours by selected settings. the second research question explored income changes that mts have experienced as a result of the pandemic. when asked about their pay situation at the time of the survey, half of the , respondents indicated no changes in at least one source of income since the onset of the pandemic ( . %). some respondents indicated reduced compensation ( . %) or no compensation ( . %) as mts. one hundred and forty-six mts ( . %) reported using paid time off, public assistance/unemployment, or sick leave. of the respondents ( . %) who indicated "other (please describe)," nearly half of the write-in comments indicated reduced income. the most commonly mentioned reasons for this reduction included drastically reduced clinical hours, lack of virtual service availability, and lack of client/facility willingness to accept virtual services. various subgroups reported negative income changes more frequently than others. when analyzing reported income changes across clinical settings, private practice mts reported the lowest rates of stable income ( . %) and the highest rates of decreased ( . %) or eliminated ( . %) income. private practice owners seemed to be the most affected subgroup, with just under a third of this subgroup ( . %) reporting no mt-related income at the time of the survey. approximately, a third of mts in schools ( . %) and skilled nursing facilities ( . %) reported maintenance of full income, compared with over half of respondents working in universities ( . %), medical settings ( . %), and mental table i) . the third research question was focused on changes in types of services provided, with , respondents providing information about their pre-pandemic service provision and providing information during the pandemic. respondents who indicated no current clinical hours due to a furloughed or eliminated position were not asked about current service delivery. individual services accounted for a mean of . % of services provided (sd = . ) prior to the pandemic, compared with . % (sd = . ) at the time of survey. this corresponded with a decrease in group services from a mean of . % (sd = . ) of services provided to . % (sd = . ) at the time of survey. other services provided during the pandemic were offered . % (sd = . ) of the time, and open responses indicated that these services primarily included alternative services (such as prerecorded videos/material creation, staff support, and administrative tasks; online supplementary figure ) . of the respondents indicating current contact hours, a majority ( . %) reported that they were providing alternative services due to the pandemic. alternative services used often or very often included telehealth services ( . %), virtual music lessons ( . %), prerecorded songs/playlists ( . %), and prerecorded video sessions ( . %). figure shows the number of mts using alternative services often or very often within different settings. the shift of resources was also prevalent for alternative profession-related activities, with mts ( . %) reporting learning to use/researching telehealth often or very often during this time of the pandemic (see supplementary table ii for all professional activities). the adult hope scale had good internal consistency for the pathways subscale (ɑ = . ), the agency subscale (ɑ = . ), and the total scale (ɑ = . ). internal consistency remained high with the researcher-added question about hope for the music therapy profession (ɑ = . ). respondents' (n = , ) mean total hope score was . (sd = . ) during this time in the pandemic. this score is greater than the score published by snyder ( ) as a typical mean score (m = , sd = ). subscale scores for agency (m = . , sd = . ) were higher than pathways (m = . , sd = . ). when asked how they agreed with the statement "i feel hopeful about the music therapy profession," respondents most often indicated mostly true ( . %), definitely true ( . %), somewhat true ( . %), and slightly true ( . %). collectively, . % of respondents indicated agreement of feeling hopeful about the profession during the pandemic. mean hope scores and response to the question on hope about the music therapy profession were broken down according to respondents' reported employment status (supplementary figure ) . subgroups with lowest scores of hope for the profession included those experiencing furlough (m = . , sd = . ) or eliminated positions (m = . , sd = . ). there was a weak positive correlation (r = . , p < . ) between hope for the profession and total hope score. of the , respondents, ( . %) provided responses to the prompt "please comment on your feelings of hopefulness in the music therapy profession." a total of statements were included in the final analysis. ten major themes and representative statements identified from the analysis of the responses are displayed in table ii (and expanded supplementary table iii) . the most common theme was ongoing professional issues ( . %) that were unrelated to the pandemic. the next most common themes were: covid- as a source of growth for the profession ( . %), the adaptability and resilience of mts ( . %), and telehealth ( . %). of those who commented on telehealth, most respondents viewed telehealth as beneficial. a descriptive analysis of the -item pss- was completed for the respondents who answered all questions (n = , ). a cronbach's alpha showed that the pss- had good internal consistency (ɑ = . ). the mean scores for the respondents indicated that the mts perceived a moderate level of stress (m = . , sd = . ). individuals who had their position eliminated reported a slightly higher stress level (m = . , sd = . ) compared with the overall mean score. respondents who provided telehealth services (n = ; m = . , sd = . ) and who worked in different settings had perceived stress scores similar to the mean overall score (table iii) . results of correlational analyses between the pss- total scores and adult hope scale total scores indicated a significant negative correlation, with a weak relationship between higher hope scores and lower stress scores (n = , , r = −. , p < . ). a correlation between the two subscales and the pss- total score indicated a significant weak negative correlation for both pathways (r = −. , p < . ) and agency subscales (r = −. , p < . ). across all clinical settings and age groups, respondents (n = , ) reported that their top concerns at the time of this survey included: becoming a carrier of covid- (getting self or others sick; . %), being separated from loved ones ( . %), and loss of income ( . %). although nearly all age and setting subgroups reported getting self or others sick as their top-ranked concern, respondents working in private practice reported the loss of income as their most prominent concern at the time of this survey. fewer than % of respondents (n = ) reported that they had no concerns related to the pandemic at the time of this survey. open responses regarding "other concerns" (n = , . %) most often related to health and safety of self and family ( . %), client wellness/access to services ( . %), financial security ( . %), and shifting work responsibilities ( . %). an open-response question at the end of this survey asked the following: "is there anything else that you would like to tell us about your experience since the covid- outbreak?" five hundred ten individuals ( . %) submitted responses to this question. ten central themes emerged within these comments, all of which are outlined in table iv (and expanded supplementary table iv benefits than the difficulties of such services, with many mentioning the lack of access to virtual service delivery options at the time of survey and some expressing mixed perspectives regarding this type of service delivery. this descriptive study explored how the pandemic had affected music therapy employment, contact hours, and service delivery in the united states as of early april . research questions also explored mts' perceived stress and hope during this time in the pandemic. open-ended comments were analyzed in order to gain a greater understanding of the most prominent experiences of mts during this time. the majority of mts ( . %) reported a shift toward alternative service delivery methods during the pandemic, with telehealth emerging as the most frequently utilized service in this category. it is possible that mts shifted to telehealth out of consideration for shelter-in-place orders and quarantine restrictions. mts also serve high-risk populations; therefore, the need for telehealth during the pandemic likely increased in order to keep clients and mts safe. one respondent stated, "telehealth has, by necessity, become a way we can access people who are either in remote locations or who are among the very sick or immunocompromised." therefore, when social distancing protocols began emerging, it appears that many mts recognized the potential of technology to allow continuity of care while also optimizing client and clinician safety. mts quickly adapted to telehealth and used this service more frequently than any other reported service. telehealth, while not an in-person service, still provides a live interaction between the client and therapist, making it useful for working in real-time. mts who continued to deliver on-site clinical services largely shifted from group to individual sessions, again highlighting the impact of the pandemic on the provision of services. despite the willingness of many mts to utilize virtual service delivery methods, many still experienced stark reductions in contact hours or lack of agency/client willingness to consent to alternate services. overall, the private practice/ contractual and education settings appeared to have the largest shift of weekly client contact hours, going from at least hours a week down to nine hours or fewer. respondents employed full-time by agencies and universities reported stable income levels during the pandemic more often than contract-based and private practice mts. private practice employees retained full pay slightly more than practice owners. several private practice owners shed light on this phenomenon by mentioning within comments that they were more willing to cut their own pay than staff pay. this points to the difficult decisions that many mts faced, including choosing the security of others before themselves. mts in medical, mental health, and university settings reported the highest rates of income stability, with fewer of these respondents reporting income elimination. conversely, mts in schools and skilled nursing facilities reported much lower rates of income stability, along with private practice mts. when analyzing income changes across pre-pandemic primary settings and professional roles, private practice mts were the most affected group across both factors. respondents primarily working in private practice were also the only subgroup table iv . to report "loss of income" as their number one current concern. all other respondent subcategories reported carrying or contracting covid- as their most prominent concern. these data indicate that private practitioners may have experienced unique barriers during the pandemic that prevented the continuity of income and services. overall, mts who responded to the survey reported levels of hope that were higher than snyder's ( ) published mean score on the adult hope scale. respondents had higher agency scores than pathways scores, which may suggest that they felt a strong sense of determination or motivation to attain their goals, even though the plausible route may have been less clear. comments from mts indicated that many were ready resume services and "normal" activities. furthermore, comments indicated that mts were faced with many barriers, such as difficulties with telehealth or billing issues. these comments may indicate that, despite a motivation to get back to "normal," mts were dealing with uncertainties as to how they would return to services/daily activities at this point in the pandemic. furthermore, the higher agency scores may be a reflection of motivation that some mts felt in learning new skills to utilize within service delivery. overall, the scores of the adult hope scale were reflected in many of the open-ended hope question responses. comments indicated that mts frequently identified the challenges presented by the pandemic as a positive source of growth for the profession. furthermore, mts made frequent statements on the adaptability and resilience of mts. many respondent comments noted that mts would likely be needed more following the pandemic, specifically to assist in grief work and trauma processing. some mts felt that the public use of the arts for coping and expression during the pandemic may lead to an increased need for creative arts therapies in the future. others identified ways in which the pandemic would provide the means necessary to reach new clients through remote services and new skills acquired during the pandemic. though some mts were frustrated with the transition to telehealth, most who commented on telehealth viewed it as beneficial at the time of the survey. several mts noted the temporality of the situation and shared hope that services would return to "normal" in time. financial instability appeared to cause the most concern for respondents. this included concerns for themselves, for other mts (particularly those in private practice), and for clients and facilities who may no longer have room for services in their budgets. some respondents noted that they were considering leaving the profession, but most cited reasons that were unrelated to the pandemic. although these concerns were prominent, respondents also shared that they felt an increased sense of connection to the music therapy community through resource sharing and emotional support provided online. in regard to the music therapy profession, the majority of respondents ( . %) reported having hope. subgroups with lowest scores on hope for the profession included mts experiencing furlough or eliminated positions. however, a correlation indicated that there was not a strong relationship between hope for the profession and the overall hope score. comments indicated that feelings of hope (and concern) about the profession extended beyond the current pandemic, as ongoing professional issues were at the forefront of responses. many respondents stated that their current levels of hope pertained to advocacy needs, education standards, equity in music therapy practice, state licensure, and ongoing research practices. although not the focus of this study, these topics were clearly of importance to the respondents. the mts in this study had a mean pss- score of . , which is higher than the published normative score of . (cohen and williamson, ) . according to cohen and williamson ( ) , this score reflects the degree to which participants felt unpredictability, uncertainty, and overload in their lives. this seems to confirm literature indicating that novel pandemics create uncertainty (harwood, ) , which may result in heightened stress for healthcare professionals (moazzami et al., ) . this may be further confirmed by the similarity of the mean pss- scores across subgroups for employment changes, essential status, and job settings. although these findings may be an indication of the current situation, more research is needed to determine the perceived stress levels of mts outside of a global pandemic. there was a weak negative correlation between the pss- and total adult hope scale scores, which may indicate that mts maintain a higher perception of hope regardless of situational stressors. since the adult hope scale is meant to capture a person's overall feelings of hope, it may be less sensitive to situational stress, whereas the pss- is designed to capture situational stress. snyder et al. ( ) explored the interaction between stress and hope, finding that people with higher hope scores were able to maintain hope when confronted with stressors. conversely, people with lower overall hope scores demonstrated decreased hope when confronted with stressors (snyder et al., ) . therefore, the observations in this study may indicate that mts were able to maintain hope, despite varying levels of stress at this time in the pandemic. open response analysis revealed an assortment of information that sheds light on the professional, personal, financial, and emotional experiences of mts related to the pandemic. regarding virtual services (the most frequent topic), some mts expressed gratitude for the opportunity to continue earning money and providing services during this time of social distancing. others expressed frustration that virtual service technology is difficult to learn, not appropriate for all clients, and cost prohibitive for many clients and clinicians. additionally, mts mentioned barriers and inequities, which kept clients from accessing these services. personal mental health was the second-most frequent concern within these comments, and respondents in this group often described multiple sources of stress, anxiety, and negative affect change related to the pandemic. many who reported personal mental health concerns also mentioned health/safety concerns, symptoms of burnout, and family balance difficulties. concerns categorized within the personal mental health theme often intersected with expressions of loss and uncertainty related to the pandemic. within the finance, gratitude, and systemic privilege themes, respondents often recognized the hardships and inequities faced by others. even those reporting partial income loss due to the pandemic often expressed personal resilience and empathy for those experiencing increased barriers to economic stability. within the health and safety theme, less than half ( . %) of respondents mentioned concern for their own health risks related to the pandemic, while others focused primarily on protecting individuals at higher risk for severe outcomes. many comments within this theme mentioned the limited availability of personal protective equipment in the workplace, creating barriers related to safe and ethical service delivery. some mentioned that new safety regulations created barriers to effective service access for many clients. despite reports of increased adversity during the pandemic, many respondents used the open comments field as an opportunity to express gratitude for their jobs, for research on the pandemic, for employer support, for their own financial stability, and for the supportive nature of the mt community. in the face of increased collective stress and uncertainty due to the pandemic, the research team found it encouraging to witness evidence of support and resilience within the mt community. as with most survey studies, there is great potential for nonconsent bias within the responses of participants. several respondents mentioned that it can be stressful and unpleasant to reflect on the nature of this pandemic as effects are ongoing, which may have been a key reason for the low response rate. the research team elected to not send follow-up reminders via email due to the sensitivity of the topic; therefore, the survey was promoted via email once. the team wanted to be sensitive to additional stress at this time, thus completion reminders were not sent to non-completers. another limitation was the lack of recent normative data for interpretation of the pss- scores, as well as research regarding mts' pss- scores prior to the pandemic. responses recorded in the open comment section were taken at the end of the survey. given the length of the survey, participants may not have provided additional comments and therefore a broader description may have been missed. this is the first known study on the impact of the covid- pandemic on music therapy professionals' employment, service delivery, stress, and hope. future research should consider the impact of the pandemic over time, as the lasting effects of the pandemic may change aspects of employment, service delivery, stress, and hope. further research on stress and hope would also help indicate if the scores found in this study are outside common ranges for music therapy professionals. additional information on telehealth delivery would be beneficial to inform the profession on how technology was used in service delivery, including platforms, difficulties, and changes to services. the results of this survey provide an overview of changes in employment, service delivery, perceived stress, and level of hope in mt professionals as of april , during the covid- pandemic. the results of the study indicated that mts adapted service delivery in order to continue providing services, despite various difficulties. music therapists also experienced changes in income and client contact hours, with mts in private practice impacted more than mts in other settings. this survey indicated that mts had a moderate perceived stress level while maintaining hope during the challenges of the pandemic. overall, this survey indicated that the pandemic has impacted many mts. as such, it is the central hope from this research team that all mts will gain the resources needed to endure this unparalleled season. supplementary material is available online at music therapy perspectives. funding: none declared. conflicts of interest: none declared. covid- and seeing clients lifestyle behaviours during the covid- -time to connect virtual music therapy service delivery: developing new approaches & models perceived stress scale perceived stress in a probability sample of the united states a global measure of perceived stress guidance for infection control and prevention of coronavirus disease (covid- ) in nursing homes (revised) stress, coping, and hope pandemic uncertainty: considerations for nephrology nurses music therapy practice status and trends worldwide: an international survey study may ). u.s. unemployment rate soars to . percent, the worst since the depression era. the washington post review of the psychometric evidence of the perceived stress scale see which states and cities told residents to stay at home. the new york times covid- and telemedicine: immediate action required for maintaining healthcare providers well-being a survey of music therapy students' perceived stress and self-care practices pandemic influenza: certain uncertainties lockdown and isolation: psychological aspects of covid- pandemic in the general population what guides internship supervision? a survey of music therapy internship supervisors. music therapy perspectives hope theory: rainbows in the mind the will and the ways: development and validation of an individual-differences measure of hope making sense of cronbach's alpha who director-general's opening remarks at the media briefing on covid- - key: cord- -ub ynjai authors: hoyer, carolin; ebert, anne; szabo, kristina; platten, michael; meyer-lindenberg, andreas; kranaster, laura title: decreased utilization of mental health emergency service during the covid- pandemic date: - - journal: eur arch psychiatry clin neurosci doi: . /s - - -w sha: doc_id: cord_uid: ub ynjai during the rapid rise of the covid- pandemic, a reduction of the numbers of patients presenting to emergency departments has been observed. we present an early study from a german psychiatric hospital to assess the dynamics of mental health emergency service utilization rates during the covid- pandemic. our results show that the numbers of emergency presentations decreased, and a positive correlation between these numbers and mobility of the general public suggests an impact of extended measures of social distancing. this finding underscores the necessity of raising and sustaining awareness regarding the threat to mental health in the context of the pandemic. the ongoing covid- pandemic affects most aspects of society and represents a major psychosocial stressor whose impact on the incidence of mental disorders has already been noted [ ] . it is therefore potentially worrisome that a reduction of numbers of patients seeking medical emergency care has been observed by clinicians worldwide [ , ] . reasons for this phenomenon are not properly understood even though some suggest that patients' fear of in-hospital infection causes avoidance behavior. this retrospective study aimed to quantify the dynamics of mental health emergency service utilization during the covid- pandemic and to assess a potential impact of the partial lockdown in germany. it was performed at the central institute of mental health, mannheim, germany, a large psychiatric hospital serving a catchment area of ~ , people caring for nearly all psychiatric emergencies in the city of mannheim (~ presentations/year). patient allocation to the hospital's emergency service is carried out by practice-based physicians, physicians from other hospitals in the city, emergency medical service providers and/or police departments. the service is also open for selfreferring patients. all patients requiring evaluation and/or treatment for a mental health condition are seen by the emergency service staff. during the pandemic, the service has been operating unrestrictedly, however, precautionary measures have been taken to minimize risk of infection transmission. all presenting patients were asked to disinfect their hands and don a face mask upon arrival in the hospital. as part of a screening assessment to identify potentially infected patients, a targeted history regarding symptoms of illness and recent contact with patients with proven sars-cov- infection was obtained and patients' temperature was taken. if patients were unable to provide necessary information, every effort was made to obtain this from family or acquaintances. data of patients seeking help from hospital emergency service between / / and / / and between / / and / / were collected from clinical service records and included demographic data and final diagnosis after psychiatric evaluation. anonymized mobility data of the general public were obtained from teralytics, zurich, switzerland. week when the pandemic risk was raised to "high" by the german regulator was defined as the week when the covid- pandemic impacted public life and extended measures for social distancing, e.g., through the closure of schools and daycare institutions, were beginning to be implemented. weeks - (early) and - (late) were categorized into a variable "epoch" for years and . poisson regression was used to test if the rate of admissions changed as a function of year, epoch and year-by-epoch interaction (reflecting impact of the pandemic), expressed as rate ratio (rr) along with its % confidence interval. with spearman's rho, correlations between mobility and emergency service presentations were analyzed. statistical analysis was performed using ibm spss statistics version . emergency service presentation rates decreased significantly by . % [rr = . , p = . , % confidence interval (ci) . - . ] between early (weeks - ) and late (weeks - ) epochs in and , reflecting the impact of the covid- pandemic. significant yearby-epoch-interactions were found for presentations due to organic mental disorders including dementia (− . %, rr . , p = . , % ci . - . ) and affective disorders (− . %; rr = . , p = . , % ci . - . ) but only in the latter did we find an interaction driven by a difference between the epochs before and after the pandemic's onset. beginning week , a pronounced decrease in mobility of the general public in mannheim was observed, which predicted reduced emergency service utilization (number of trips r s . , p = . , kilometers traveled r s = . , p = . ) and a reduced number of presentations due to affective disorders (number of trips r s = . , p = . , kilometers traveled r s = . , p = . ; fig. ). this study identified a decrease of mental health emergency service utilization during the covid- pandemic and for the first time extends observations made in other specialties [ , ] to psychiatry. in the context of quarantine and social distancing, themselves risk factors for mental disorders [ ] , as well as their repercussions on financial and job security, mental health issues are expected to increase during the pandemic, as they did during previous societal crises. we identified a particular impact of the pandemic on the number of presentations due to affective disorders, which is concerning since bi-directional influences between depressive symptoms and social disconnectedness and isolation exist [ ] . the correlation of lower service utilization rates and decreased population mobility moreover suggests an impact of extended measures of social distancing on patients' willingness to seek help for mental health problems through in-hospital consultations. on a related note, medical workers from all around the world have been joining campaigns urging people to stay home, which may inadvertently contribute to this development. our observation warrants serious attention even more so because this development occurred against a backdrop of sufficient capacities for patient evaluation, admission and care with the hospital's emergency mental health service operating in an uninterrupted and unrestricted manner during the pandemic. disasters such as the current pandemic in particular impact on society's most vulnerable populations, among them patients with mental illness. our findings underscore the need for raising and sustaining awareness regarding the threat posed by the covid- pandemic for mental health-for those with mental illness but potentially also for previously healthy people [ ] . it is paramount for psychiatry to ensure that state-of-the-art service be delivered in these challenging times through the development and refinement of adaptive strategies in patient care within the broader context of the healthcare system through engaging with patients, clinicians and health policies [ ] . these include, for example, the implementation and extended use of alternative strategies of mental healthcare delivery like telehealth [ , ] to ensure accessibility to psychiatric care, the development of online tools to support individuals with risk factors and mitigate the effects of social isolation [ ] , and the creation of encouraging, safe and trusting environments for walk-ins. efforts like these will be essential to avoid serious healthcare and economic consequences resulting from undiagnosed or untreated mental disorders. generalized anxiety disorder, depressive symptoms and sleep quality during covid- outbreak in china: a web-based cross-sectional survey on being a neurologist in italy at the time of the covid- outbreak reduction in st-segment elevation cardiac catheterization laboratory activations in the united states during covid- pandemic the psychological impact of quarantine and how to reduce it: rapid review of the evidence social disconnectedness, perceived isolation, and symptoms of depression and anxiety among older americans (nshap): a longitudinal mediation analysis a global needs assessment in times of a global crisis: world psychiatry response to the covid- pandemic addressing the covid- pandemic in populations with serious mental illness mental health treatment online during the covid- outbreak digital technology in psychiatry: towards the implementation of a true person-centered care in psychiatry agile requirements engineering and software planning for a digital health platform to engage the effects of isolation caused by social distancing: case study we would like to thank matthias gondan, associate professor, department of psychology, university of copenhagen, denmark, for statistical advice.funding ch receives a grant for postdoctoral lecture qualification within the olympia morata program of heidelberg university. conflict of interest on behalf of all authors, the corresponding author states that there is no conflict of interest. key: cord- - mma rva authors: harper, d. r.; davies, l. m.; gadd, e. m.; costigan, s. c. title: science into policy: preparing for pandemic influenza date: - - journal: j public health (oxf) doi: . /pubmed/fdn sha: doc_id: cord_uid: mma rva authoratative government pandemic preparedness requires an evidence-based approach. the scientific advisory process that has informed the current uk pandemic preparedness plans is described. the final endorsed scientific papers are now publicly available. public expectations of effective government interventions in health crises are high in developed countries. authoritative action and provision of information to the public can help in avoiding public disquiet or panic and in mitigating the societal risks of a pandemic, complementing the direct health effects of any interventions. conversely, disagreement over the scientific evidence base, particularly where considerable uncertainties and gaps in information exist, can open the way to debate based primarily on established beliefs and prejudices. in the face of a future event such as an influenza pandemic, the timing and precise nature of which is unknown, robust preparation will be strengthened by an agreed scientific understanding of the risks and the options for response. the uk government has followed an extensive process to review and confirm an agreed summary of the international evidence base. this underpins policy development on countermeasures within its pandemic influenza preparedness programme and can be of use to other countries developing pandemic preparedness plans as well. under the auspices of the uk scientific advisory group on pandemic influenza, five scientific papers dealing with the main clinical countermeasures (antivirals, pre-pandemic and pandemic specific vaccines, antibiotics and facemasks) and the risk of a pandemic originating from an h n virus were developed. these papers were reviewed and revised by additional national and international expert scientific reviewers and subsequently at a colloquium, convened by the secretary of state for health, of scientific experts. revised papers were then submitted to the scientific advisory group for final endorsement as reflecting an accurate and comprehensive summary of the state of knowledge in june . the final endorsed papers have now been made publicly available as a resource to all. papers reviewing the scientific evidence base in the following areas are available at: http://www.advisorybodies.doh.gov.uk/ spi/evidence.htm (i) the use of antiviral drugs in a pandemic; (ii) pre-pandemic and pandemic specific influenza vaccines; (iii) the use of antibiotics for pandemic influenza; (iv) the use of face masks during a pandemic; and (v) the risk of a pandemic originating from h n . this widely agreed scientific state of the art offers a firm foundation for complex and potentially expensive policy and procurement decisions on pandemic countermeasures. within the uk, the papers have already informed the recently published framework and policy statement. they will continue to inform policy decisions across government. the scientific knowledge in this field is continually evolving and improving, and the uk will therefore continue to review and refine its assessment of the evidence base. scientific advisory group on pandemic influenza, review of the evidence base underpinning clinical countermeasures and risk from h n pandemic flu: a national framework for responding to an influenza pandemic parliamentary debates (hansard) key: cord- -gm b u authors: fazeli, shayan; moatamed, babak; sarrafzadeh, majid title: statistical analytics and regional representation learning for covid- pandemic understanding date: - - journal: nan doi: nan sha: doc_id: cord_uid: gm b u the rapid spread of the novel coronavirus (covid- ) has severely impacted almost all countries around the world. it not only has caused a tremendous burden on health-care providers to bear, but it has also brought severe impacts on the economy and social life. the presence of reliable data and the results of in-depth statistical analyses provide researchers and policymakers with invaluable information to understand this pandemic and its growth pattern more clearly. this paper combines and processes an extensive collection of publicly available datasets to provide a unified information source for representing geographical regions with regards to their pandemic-related behavior. the features are grouped into various categories to account for their impact based on the higher-level concepts associated with them. this work uses several correlation analysis techniques to observe value and order relationships between features, feature groups, and covid- occurrences. dimensionality reduction techniques and projection methodologies are used to elaborate on individual and group importance of these representative features. a specific rnn-based inference pipeline called doublewindowlstm-cp is proposed in this work for predictive event modeling. it utilizes sequential patterns and enables concise record representation while using but a minimal amount of historical data. the quantitative results of our statistical analytics indicated critical patterns reflecting on many of the expected collective behavior and their associated outcomes. predictive modeling with doublewindowlstm-cp instance exhibits efficient performance in quantitative and qualitative assessments while reducing the need for extended and reliable historical information on the pandemic. i n the early days of the year , the world faced another widespread pandemic, this time of the covid- strand, otherwise known as the novel coronavirus. the family of coronaviruses to which this rna virus belongs can cause respiratory tract infections of various severities. these infections range from cases of the common cold to the more lethal degrees. many of the confirmed cases and deaths reported due to covid- showed evidence of severe forms of the aforementioned infections [ ] , [ ] , [ ] . the origin of this new virus is still not clearly understood; however, it is believed to be mainly connected to the interactions between humans and particular animal species [ ] . the rapid spread of this virus has led to many lives being lost and extremely overwhelmed the health-care providers. it also led to worldwide difficulties and had considerable negative economic impacts. it is also expected to have adverse effects on mental health as well due to prolonged shutdowns and quarantines, and there are guidelines published to help minimize this negative impact [ ] . in this work, we have gathered, processed, and combined several well-known publicly available datasets on the covid- outbreak in the united states. the idea is to provide a reliable source of information derived from a wide range of sources on important features describing a region and its population from various perspectives. these features primarily have to do with demographics, socio-economic, and public health aspects of the us regions. they are chosen in this manner because it is plausible to assume that they can be potential indicators of commonalities between the affected areas. even though finding causality is not the objective of this work, our analyses attempt to shed light on these possible commonalities that allow public health researchers to obtain a better perspective on the nature of this pandemic and the potential factors contributing to a slower outbreak. this is vitally important as the critical role of proper policies enforced at the proper time is evident now more than ever. there has been widespread attention in the design and utilization of artificial intelligence-based tools to obtain a better understanding this pandemic. accordingly, we present a neural architecture with recurrent neural networks in its core to allow the machine to learn to predict pandemic events in the near future, given a short window of historical information on static and dynamic regional features. the main assumption that this work attempts to empirically validate is that the concise arxiv: . v [cs.cy] aug pandemic-related region-based representations can be learned and leveraged to obtain accurate outbreak event prediction with only minimal use of the historical information related to the outbreak. aside from the theoretical importance, an essential application of this framework is when the reported historical pandemic information, e.g., number of cases, is not reliable. an example of this is when a region discovers a problem in its reporting scheme that makes the historical information on the pandemic inaccurate due to overestimation or underestimation. such unreliability will severely affect the models which use this historical information as the core of their analysis. in summary, the contributions of this work are as follows: • gathering and providing a thorough collection of datasets for the fine-grained representation of us counties as subregions. this collection includes data from various us bureaus, health organizations, the center for disease control and prevention, and covid- epidemic information. • evaluation of the informativeness of individual features in distinguishing between regions • correlation analyses and investigating monotonic and non-monotonic relationships between several key features and the pandemic outcomes • proposing a neural architecture for accurate short-term predictive modeling of the covid- pandemic with minimal use of historical data by leveraging the automatically learned region representations given the importance of open-research in dealing with the covid- pandemic, we have also designed olivia [ ] . olivia is our online interactive platform with various utilities for covid- event monitoring and analytics, which allows both expert researchers and users with little or no scientific background to study outbreak events and regional characteristics. the codes for this work and the collection of datasets are also available as well. since the beginning of the covid- pandemic, there have been efforts in utilizing computerized advancements in controlling and understanding this disease. an example is the applications developed to monitor the patients' locations and routes of movement. a notable work in this area is mit's safepaths application [ ] that contains interview and profiling capability for places and paths. it is worthwhile to mention that these platforms have also caused worries regarding maintaining patients' privacy [ ] . to provide researchers and government agencies with frequently updated monitoring information regarding the coronavirus, point acres team has provided an api that allows access to the daily updated numbers of coronavirus cases [ ] , [ ] . several datasets such as [ ] are also released to the public. a large corpus of scientific articles on coronaviruses is released as well as a result of a collaboration between allenai institute, microsoft research, chan-zuckerberg initiative, nih, and the white house [ ] . there have been projects such as a work at john hopkins university that are focused on providing us county-level summaries of covid- pandemic information and important attributes [ ] , [ ] . the information in social networks has also been used in predicting the number or covid- cases in mainland china [ ] . the work in [ ] is also focused on an ai-based approach for predicting mortality risk in covid- patients. there have been numerous approaches to model the pandemic using ai that have the historical outbreak information at the core of their analyses, such as the modified versions of seir model and arima-based analysis [ ] , [ ] , [ ] , [ ] , [ ] , [ ] . this work is distinguished from the mentioned projects and the majority of statistical works in this area in the sense that it is targeting the role of region-based features in the spatio-temporal analysis of the pandemic with minimal use of historical data on the outbreak events. the area unit of this work is us county which enables a more fine-grained prediction scheme compared to the other works that have mostly targeted the state-level analytics. to our best knowledge, the works in [ ] and [ ] are the only attempts in county-level modeling of the disease dynamics. in [ ] , authors have proposed a non-parametric model for epidemic data that incorporates area-level characteristics in the sir model. the work in [ ] uses a combination of iterated filtering and the ensemble adjustment kalman filter for tuning their model, and their approach is based on a county-level seir model. the empirical results show that our approach outperforms these models on the evaluation benchmarks while providing a framework for utilizing deep learning in analysis and modeling the short-term pandemic events. we have made our codes and data publicly available and regularly maintained to help to expedite the research in this area. this study focuses on analyzing the regions of the united states with statistical and ai-based approaches to obtain results and representations associated with their pandemic-related behavior. a primary and essential step in doing so is to prepare a dataset covering a wide range of information topics, from socio-economic to regional mobility reports. more details regarding the primary data sources from which we have obtained information for this work's dataset are elaborated upon hereunder. ) covid- daily information per county: our first step towards the mentioned objective is to gather the daily covid- outbreak data. this data should include the number of cases that are confirmed to be caused by the novel coronavirus and its associated death toll. we are using the publicly accessible dataset api in [ ] , [ ] to fetch the relevant data records. the table of data obtained using this api contains the numerical information along with dates corresponding to each record, and each document includes the number of confirmed cases and the number of deaths that occurred due to covid- on that date. it also includes the number of recoveries from covid- in the same format. this dataset's significance is that it provides us with a detailed and high-resolution temporal trajectory of the covid- outbreak in different urban regions across the united states. using the dates, one can constitute a set of time-series for every county and monitor the outbreak along with the other metadata to make relevant inferences. ) us census demographic data: the us census demographic data gathered by the us census bureau [ ] plays a critical role in our analysis by providing us with necessary information on each region's population. additionally, this information includes specific features such as the types of work people in that region mainly take part in, their income levels, and other invaluable demographical and social information. ) us county-level mortality: the fluctuations in the mortality rate of a region is also a potential critical feature in pandemic analytics. the us county-level mortality dataset was incorporated into our collection to add the high-resolution mortality rate time-series throughout the years [ ] , [ ] . the age-standardized mortality rates provide us with information on variables, the values of which can be considered as the effects of specific causes. it is crucial since some of these causes might have contributed to the faster spread of covid- in different regions [ ] . ) us county-level diversity index: another dataset that offers a race-based breakdown of the county populations is available at [ ] with the diversity index values corresponding to the notion of ecological entropy. for a particular region, if k races comprise its population, the value of diversity index can be computed using the following formula: in the above formula, n is the total population and n i is the number of people from race i. this formula represents the probability p, which means that if we randomly pick two persons from this cohort, they are of different races with probability p. in addition to that, we have the percentages of different races in the regional population as well. ) us droughts by county: another source of valuable information regarding the land area and water resources per county is the data gathered by the us drought monitor [ ] , [ ] . this data is incorporated into our collection as well. ) election: based on the us presidential election, a breakdown of county populations' tendencies to vote for the main political parties is available [ ] . these records are added to our collection as the democratic-republican breakdown of regional voters can reflect socio-economic and demographical features that form the underlying reasons for the regional voting tendencies. ) icu beds: since covid- imposes significant problems in terms of the extensive use of icu beds and medical resources such as mechanical ventilators, having access to the number of icu beds in each county is helpful. this information offers a glance at the medical care capacity of each region and its potential to provide care for the patients in icus [ ] . it could be argued that having knowledge of the icu-related capacity of regional healthcare providers can, to some extent, represent the amount of their covid- related resources, such as ventilators and other needed resources. the aggregate dataset on central statistical values on the us household income per county (including average, median, and standard deviation) is used to provide information on the financial well-being of the affected regions' occupants [ ] . ) covid- hospitalizations and influenza activity level: aside from the socio-economical and demographical features of a region, the number of active and potential covid- cases is a critical factor. this information can be leveraged to provide a possible threat level for the region. these records are made available by cdc for specific areas and are incorporated into our collection as well [ ] , [ ] . ) google mobility reports: the covid- virus is highly contagious. therefore, the self-quarantine and social distancing measures are principal effective methodologies in bolstering the prevention efforts. our collection includes google's mobility reports obtained from [ ] . these records elaborate on the mobility levels across us regions, which are broken down into the following categories of mobility: ) retail and recreation ) grocery and pharmacy ) parks ) transit stations ) workplaces ) residential in addition, we have computed a compliance measure that has to do with the overall compliance with the shelter at home criteria: . in the above formula, m i is the mobility report for the ith mobility category. this value is computed through time to provide an overall measure of mobility through time. the compliance measures of + and − mean + % and − % changes from the baseline mobility behavior, respectively. ) food businesses: restaurants and food businesses are affected severely by the economic impacts of this outbreak. at the same time, they have not ceased to provide services that are essential and required by many. to reach a proper perspective of the food business in each region, we have prepared another dataset based on records in [ ] to provide statistics on regional restaurant revenue and employment. analysis of restaurants status is important in the sense that they are mostly public places that host large gatherings, and in the time of a pandemic, their role is critical. ) physical activity and life expectancy: various features have been selected from the dataset in [ ] to reflect on the obesity and physical activity representation for different us regions. these features include the last prevalence survey and the changes in patterns. also, life expectancy related features are valuable information for representing each region. they are included as well in our analyses. ) diabetes: different features to represent a region according to the diabetes-related characteristics were selected from the data in [ ] . these include age-standardized features and clusters that have to do with diabetes-related diagnoses. ) drinking habits: information on regional drinking habits from - has also been used in this work [ ] . this information includes the proportions of different categories of drinkers clustered by sex and age. the categories are as follows: • any: a minimum of one drink of any alcoholic beverage per days • heavy: a minimum average of one drink per day for women and two drinks for men per days • "binge: a minimum of four drinks for women and five drinks for men on a single occasion at least once per days ) analytics: in what follows, the analytical techniques that we have designed and used in this work are explained. to draw meaning from the data that we have at hand, we have designed and utilized a variety of techniques. these methodologies range from traditional statistical methodologies to the design and testing of deep learning inference pipelines for event prediction. we select a set of representative features to use in our analytics from the gathered collection of datasets. more details on the nature of these features are shown in table i. ) feature informativeness for sub-region representation: an important question that is raised in analyzing a dataset with well-defined categories of features is how important these features are in describing the entities associated with them. from the particular perspective of enabling the differentiation between two regions, it can be said that a measure of importance is the contribution of each one of these selected features to the overall variation in datapoints. the boundary case is that if a feature always has the same value, it is not informative as there is no entropy value associated with its distribution. to begin with, we associate a mathematical vector with each data point, which contains the values of all its dynamic and static features associated with a specific date and location. since we are mainly targeting us counties in this study, each record would be associated with a us county at a specific date. we then use linear principal component analysis [ ] to reduce the dimensionality of these data points and to evaluate the importance of the selected features in terms of their contribution to the overall variation. results show that in order to retain over % of the original variance, a minimum of principal components should be considered. each one of these components is found as a linear combination of the original set of features, and that along with ii the equations for the three main correlation analysis techniques used in this work, namely pearson the percentage of variance along the axis of that component can be used as a measure of performance. to be more specific, considering n features and m data points that result in p pca components to retain % of the variation, we will have: and u i is the total variance along the axis of ith pca component. this can be thought of as a measure of importance for the pca components, and the absolute value of v i s magnitudes can be considered as the importance of original feature i's contribution to its making. therefore, we will have the following measure of informativeness defined for our features: the features can be sorted according to these values, and the categories can also be considered in their relevant importance. note that this is just one definition of informativeness; for example, certain features might not vary a lot, but when they do, they are potentially associated with severe changes in the covid- events. therefore, the importance score that has been captured here merely has to do with how better we are able to distinguish between locations based on a feature. in order to better understand the co-occurrences of the features in our input dataset and their corresponding covid- related events, we have performed an in-depth correlation analysis on them. we have considered four principal measures of correlation, namely: pearson, kendall, histogram intersection, and spearman, as described in table ii . we have used the pearson correlation coefficient along with the p-values to shed light on the presence or absence of a significant relationship between the values of each specific feature and each category of pandemic outcome. we have also computed nonparametric spearman rank correlation coefficients between any two of our random variables. this value would be computed as the pearson measure of the raw values converted to their ranks. the formulation is shown in table ii in which d i is the difference in paired ranks. mutual information has also been used to provide additional information on such relationships. this coefficient measures the strength of the association between the values of these random variables in terms of their ranks. since many of the relationships in our dataset can be intuitively thought of as monotonic, these values are particularly important. to better understand the concordance and discordance, kendall correlation is computed as well. in the formulation shown in table ii , m and m are the numbers of concordant and discordant pairs of values, respectively. normalized histogram intersection is another methodology directly targeting the distributions of these variables. the degree of their overlap represents how closely xs distribution follows the distribution of y. it has also been utilized in finding the results of this section. in continuation of our statistical analyses on covid- event distributions, we have designed a neural inference pipeline to help with the effective utilization of both learned deep representations and the embedded sequential information in the dataset. in this work, we introduce a neural architecture, which is trained and used for covid- event prediction across the us regions. the double window long short term memory covid- predictor (dwlstm-cp) is comprised of multiple components for domain mapping and deep processing. first, using its dynamic projection which is a fully connected layer, the dynamic feature vectors which reflect on temporal dynamics will be mapped to a new space and represented with a further concise mathematical vector. this step is essential due to the fact that an optimal deep inference pipeline is the one that retains only the information required by each level and minimizes redundancies [ ] . the projections are designed to help the network achieve this objective. these are then fed to the lstm core for processing. each one of these outputs is concatenated with the projected version of static features, f static projection (x static ), and fed to the output regression unit. the outputs are compared with the ground truth time-series, and a weighted mean squared error loss along with norm-based regularization is used to guide the training process while encouraging more focus on the points with large values. the overall pipeline is shown in figure . it is worth mentioning that this approach leverages and utilizes all of the features discussed in the previous sections. it learns representations that take various factors, from different categories of mobility and activities to socio-economic information, to make accurate short-term predictions while reducing the need for lengthy historical data on the pandemic outcomes. there are many occasions in which accurate and reliable historical data on the pandemic is not available due to a variety of reasons (e.g., a problem in reporting scheme), which motivates approaches with less dependency on it. the results on our regional dataset in terms of feature importance from the principal component analysis indicate the following features contribute to the overall representation significantly: • restaurant businesses, namely the contribution to the state economy and the count of food and beverage locations. even though we only have access to state-level data, its importance can be intuitively argued as it reflects on the counties that the state includes. this is due to the fact that the status of restaurants plays an essential role in such pandemics. • the influenza activity level is another critical feature in the analysis. given the similarity of symptoms between influenza and covid- infection, monitoring influenza activity is very helpful for covid- pandemic understanding. • diversity index, which signifies the probability of two randomly selected persons belonging to different races from a population, also plays a crucial role in representing the regions. • the changes in the mortality rate that is not associated with covid- are beneficial as well. this is also intuitively arguable as it can be thought of as a measure of mortality related sensitivity for the regions. figure shows how the projected points scatter after the pca as well. the results indicate that pca components are required to retain over % of the variance of the dataset, and figure shows the progress of covering the variance by adding the results of correlation analyses help empirically and quantitatively validate many of the relationships mentioned in the known hypotheses regarding the covid- outbreak. the pearson correlation of − . % with the p-value of . indicates a significant relationship between the percentage of food businesses in the state economy, and the average cumulative death count in its counties. another example is the value of the spearman correlation coefficients between the different types of commute to work associated with each county and the values of the pandemic-related events. from table iv , it is apparent that there is a positive relationship between the proportion of public transit as a method of commute to work and the spread of covid- in the region. another example is the pearson correlation between the ratio of different races in regions and the pandemic outcomes. it is known that covid- is affecting the african american community disproportionately [ ] . accordingly, the values in table v show a higher correlation between the ratio of african americans and the severity of covid- outcomes. cumulative covered variance by using pca components sorted by their informativeness fig. . the cumulative amount of variance covered by using up to a certain number of pca components. this is assuming that they are sorted by their corresponding eigenvalue, meaning that the first component contributes more to variance coverage than the ones selected after it. the collected set of datasets in this work provide a sufficient number of records for enabling the efficient use of artificial intelligence for spatio-temporal representation learning. we show this by training instances of our proposed doublewindowl-stm architecture on the two main short-term tasks regarding epidemic modeling; namely, new daily death and case count. in our dataset, we considered the us covid- information from march st, to july nd, , in which the july data is used for our evaluations, and the rest are leveraged for training and cross-validation. the objective using which the proposed architecture was trained is a multi-step weighted mean squared error (mse) loss, which helps to minimize a notion of distance between the predictions and the target ground-truth while encouraging (by assigning larger weights) to the windows that exhibit larger values. these thresholds are empirically tuned and set prior to the training procedure. the learning curves for both experiments indicate clear convergence in figure . to quantitatively evaluate the performance, we have reported the root mean square error (rmse) for the prediction of new daily deaths and cases due to covid- in table vi . for comparison, we have used the arima model as well with the parameters set according to the work in [ ] that have fine-tuned this scheme for forecasting the dynamics of covid- cases in europe. we have also found the best arima model in each scenario according to augmented dickey-fuller (adf) tests and based on akaike information criterion (aic) and reported the results denoted by arima*. to compare with other works in this area, we had to aggregate our county-level findings to form estimators for state-level prediction. from the results reported in table vii , it is interesting to observe that the aggregated estimator based on our model achieves strong evaluation result comparable to the models that achieve highest scores, while clearly outperforming the other two models that are inherently county-level, namely, the works in [ ] and [ ] . the predictions for severak regions exhibiting different severities are shown in figure . these results can help the reader in a qualitative assessment of the model performances, in which the outputs of our approach demonstrate high stability and follow the trajectory of the ground-truth with precision. the primary objective of this work is focused on leveraging regional representations for accurate short-term predictive modeling of the epidemic with minimal use of historical data. it is plausible to assume that the features chosen in this work, which reflect on different characteristics of a region, include valuable information for efficient prediction of pandemic events. the static features include various socio-economic and demographical properties associated with a region and its population. combined with the dynamic set of features such as influenza activity level and mobility patterns, this information was leveraged along with a short track of pandemic time-series for predictive modeling. we do not claim that the data points coming from this domain are statistically sufficient for the pandemic event prediction tasks; however, empirical results indicate that they can be effectively utilized for these objectives. there are occurrences outside of this domain that can impact the outcomes (e.g., the initial impact of a large number of infected people arriving in a specific location is not initially captured by our scheme). nevertheless, the results indicate that the data points coming solely from this work's domain can help in the effective knowledge extraction regarding the current and future values of pandemic-related time-series. the result section elaborated on the statistical findings and introduced a measure of feature importance. in addition, a neural network architecture that has a long short-term memory configured recurrent neural network in its core was introduced to serve as a new baseline for covid- event prediction. since the beginning of the covid- outbreak, there have been works focusing on gathering information or performing statistical analysis related to this epidemic. this work is focused on learning and analysis of the high-resolution spatiotemporal representation of urban areas. we provide a collection of datasets and select a large number of features to reflect on various demographics, socio-economics, mobility, and pandemic information. we have used statistical analysis techniques to investigate the relationships between individual features and the epidemic, while also considering the contribution of such features to the overall representation power. we have also proposed a deep learning framework to validate this idea that such region-based representations can be leveraged to obtain accurate predictions of the epidemic trajectories while using but a minimal amount of historical data on the outbreak events (e.g., number of cases). even though are model is trained with the objective of providing county-level predictions, we have aggregated these county-level predictions and used these now state-level estimators to evaluate the loss on the most recent data. in table , we have compared these results with the information on the similar performance measure of the eight covid- prediction works that perform state-level inference making. it can be seen that our framework provides a simple solution which outperforms the other county-level methodologies (namely, [ ] and [ ] ) on this task. the importance of clearly defined policies enforced at the proper time on alleviating the adverse impacts of a pandemic in different areas is crystal clear. one of the important applications of this work is in providing researchers and agencies with a more in-depth understanding of the co-occurrence of idiosyncratic patterns associated with regions and the predicted pattern of the outbreak. this information can be used to assist policymakers, for example, to render the details of their decisions such as lockdowns, more fine-grained and attuned to the regional needs. these include the intensity and length of enforcing such measures. the ability to predict pandemic-related occurrences (e.g., number of deaths, cases, and recoveries) is another valuable application of this work. this knowledge will provide hospitals and healthcare facilities with targeted information to help with the efficient allocation of their resources. another important application of this work is when there is a lack of availability for accurate and reliable historical data on the epidemic events. for example, when it is realized that the previous reports on the number of cases and deaths due to the pandemic were not reliable, such finding will not affect our solution due to its less degree of dependence on the historical data on the epidemic than other models which base their analysis on them at the core of their analyses. this study has several limitations that should be discussed. the initial notion of feature informativeness which was discussed in the earlier sections of this article mainly has to do with the contribution of features to the variance in representing regions and areas. given the nature of this study, combining this and the relationship between them and the pandemic and providing more in-depth prior domain knowledge can help with a better definition of feature importance. our methodology provides a means to use region-based representations to obtain predictions with less reliance on the historical epidemic data. nevertheless, generalizing the network architecture in this work and providing access to more extended and reliable historical data, if possible, can be an improvement and is worthwhile as a potential future direction. utilizing attention-based methodologies and other interpretation techniques with the pre-trained weights is also a well-suited future direction to better understand what the models learn. in this study, we gathered a collection of datasets on a wide range of features associated with us regions. our approach then used various statistical techniques and machine learning to measure the relationship between these regional representations and the pandemic time-series events and perform predictive modeling with minimal use of historical data on the epidemic. both quantitative and qualitative evaluations were used in assessing the efficacy of our design, which renders it suitable for applications in various areas related to pandemic understanding and control. this is crucial since the information on the patterns and predictions related to an outbreak play a critical role in elaborate preparations for the pandemic, such as improving the allocation of resources in healthcare systems that will otherwise be overwhelmed by an unexpected number of cases. it is important for a predictive modeling approach on the pandemics to be able to help when the epidemic is in its early stages. to evaluate the performance of our approach, we have performed experiments on the early stages of the covid- pandemic as well. in this particular dataset, the march st, to may th, date range is covered. using a k-fold validation approach, the performance of the model is evaluated and reported in table ? ?. it is shown that the network operates significantly better than arima*, the details of which were discussed in the article. please note that arima based models have shown success in predicting covid- events in the literature. in the first appendix, the performance of the model on the two main tasks regarding covid- predictions and simulations was demonstrated. to add on that, table x shows the performance of the model on the task of predicting normalized cumulative table ix this table shows the average daily root mean square error for the dwlstm model compared to the arima* predictions. the evaluations are done using a dataset that contains only the early stages of the covid- outbreak in the us. the objective in the following experiments was to predict the new daily confirmed covid- death counts for each county which is attributed to the pandemic. the other factor that is shown in table x is the variations of the performance level by changing the length of the prediction window. this suggests that in the early stages, since the available data is limited, choosing smaller windows would help with the performance. however, based on the results in the article we came to know that as more data becomes available, the performance on the longer windows can be significantly improved. as an experiment to show the impact of the highly affected areas in teaching the machine learning model in our approach, we have tried removing the counties of new york state from the dataset and showed the results in table ? ?. the results indicate that in terms of quantitative assessment, the lack of presence for the highly affected areas causes a significant drop in the loss values. however, the qualitative analysis showed that the models do not perform well in the case of rising values, as the amount of information available on such cases to train the network on is fairly limited. this causes both family of models to be biased in making predictions that tend to underestimate the target values. virus taxonomy bat coronaviruses in china viral metagenomics revealed sendai virus and coronavirus infection of malayan pangolins (manis javanica) mental health and coping with stress during covid- pandemic olivia health analytics platform private kits: safepaths; privacy-by-design covid solutions using gps+bluetooth for citizens and public health officials apps gone rogue: maintaining personal privacy in an epidemic covid- /coronavirus real time updates with credible sources in us and canada covidnet: to bring the data transparency in era of covid- novel coronavirus dataset covid- open research dataset challenge (cord- ) a county-level dataset for informing the united states' response to covid- comparing and integrating us covid- daily data from multiple sources: a county-level dataset with local characteristics using reports of symptoms and diagnoses on social media to predict covid- case counts in mainland china: observational infoveillance study predicting mortality risk in patients with covid- using artificial intelligence to help medical decision-making spatiotemporal dynamics, nowcasting and forecasting of covid- in the united states covid- simulator learning to forecast and forecasting to learn from the covid- pandemic fast and accurate forecasting of covid- deaths using the sikja model arima-based forecasting of the dynamics of confirmed covid- cases for selected european countries initial simulation of sars-cov spread and intervention effects in the continental us us census demographical data us mortality rates by county us county-level mortality us county-level trends in mortality rates for major causes of death diversity index of us counties us drought monitor united states droughts by county county presidential election icu beds by county in the us us household income statistics a weekly summary of us covid- hospitalization data laboraty-confirmed covid- associated hospitalizations state statistics us data for download principal component analysis deep learning and the information bottleneck principle reasons coronavirus is hitting black communities so hard covid- data in the united states us facts dataset key: cord- - yq kf d authors: mcdonnell, sarah; mcnamee, emma; lindow, stephen w.; o’connell, michael p title: the impact of the covid- pandemic on maternity services: a review of maternal and neonatal outcomes before, during and after the pandemic date: - - journal: eur j obstet gynecol reprod biol doi: . /j.ejogrb. . . sha: doc_id: cord_uid: yq kf d objective: to explore any apparent trends in maternal or neonatal outcomes during the covid- pandemic by comparing the maternity outcomes before, during and after the pandemic. study design: a retrospective review was performed of maternity statistics recorded on the hospital database of a large tertiary referral centre in dublin with over , deliveries per annum from st january to st july . this time period represented the months prior to, during the peak and following the pandemic in ireland. results: there was no correlation between the monthly number of covid deaths and the monthly number of perinatal deaths (r = . , ns), preterm births (r = . , ns) or hypertensive pregnancies (r = . , ns). compared to the combined numbers for the same month in and , there were no significant changes in perinatal deaths or preterm births in the months when covid deaths were at their height. the rate of preterm birth was significantly less common in january-july compared to january-july in / ( . % v , %, chi-sq . , p = . ) conclusion: the was no evidence of a negative impact of the covid- pandemic on maternity services, as demonstrated by maternal and neonatal outcomes. the impact of the covid- pandemic on maternity services: a review of maternal and neonatal outcomes before, during and after the pandemic body of text the impact of the covid- pandemic on maternity services: a review of maternal and neonatal outcomes before, during and after the pandemic covid- has been described as the pandemic of the century implemented. the country is now in the delay phase, with successful suppression of the virus in the community, although concern mounts for a possible 'second wave' , . table represents the incidence of and deaths with sars-cov in the republic of ireland from january to july . there was widespread transmission and diagnosis of the virus, and virus-related deaths from march, peaking in april and declining sharply thereafter. j o u r n a l p r e -p r o o f the initial response to the virus saw a radical overhaul of the irish healthcare system in order to mitigate the impact of the pandemic on healthcare resources. restrictions were placed on elective and outpatient services with a focus on maintaining emergent and essential clinical services . as pregnancy is a time-limited condition, provision of maternity care is an essential service which continued to function throughout the pandemic, albeit with adjustment to care pathways , , . now in the delay phase, a retrospective analysis of the impact of the pandemic on maternity services is appropriate. it is possible that there are direct effects of the virus in pregnant women, but it is also plausible that there are subtle effects resulting from the change in service delivery, or possibly to due to maternal stress and anxiety arising during this period. the time is right to explore any apparent trends in maternal or neonatal outcomes during this time period by comparing the maternity outcomes before, during and after the pandemic. this was a retrospective review of maternity outcomes over a -month period in the largest provider of women and infants healthcare in the republic of ireland. deliveries per annum. all maternities are recorded on the hospital database that is used to generate a published annual report. maternal and neonatal outcomes from st january to st july were reviewed. this time period encompasses the time from the pre-pandemic phase, through the peak incidence of covid- cases in ireland, to the period where national lockdown measures were eased following successful containment of the virus. the monthly number of covid deaths was correlated with monthly birth statistics (pearsons correlation co-efficient) to reveal any significant associations with the progress and resolution of the pandemic. in addition, the monthly perinatal mortality and preterm birth statistics from and were combined and then analysed against the statistics from using chisquared analysis or fishers exact test as appropriate. the aim was to identify any statistically significant trends in maternal or neonatal outcomes during this period and examine the impact of the pandemic on healthcare delivery. hospital senior management authorised the collection and analysis of data from the hospital database. monthly maternity statistics for the coombe women & infants university hospital are shown in table . the mode of delivery did not show any significant correlations but april (the month of highest covid-related mortality) had the lowest normal delivery rate. the number of inductions of labour was negatively correlated with the number of covid deaths (r=- . , p< . ) and the lowest labour induction rate was also seen in april. (table and figure ). j o u r n a l p r e -p r o o f the diagnosis of antenatal complications such as hypertensive diseases of pregnancy occurred at the same rate pre-pandemic as in the months during the pandemic ( table ) . no difference was seen in the rate of intrapartum or postpartum complications, and low birthweight infants were seen at the same frequency throughout the study period ( table ) . table : intrapartum and postnatal complications, cwiuh, jan -july . there was no correlation in the rate of unbooked pregnancies, or infants born before arrival to hospital and the number of covid deaths in the review period ( table ) . disclosures of domestic violence at booking visit appear to be less during the peak pandemic period, although this was not found to be statistically significant. j o u r n a l p r e -p r o o f j o u r n a l p r e -p r o o f in summary, there is no correlation between covid deaths (representing the pandemic peak) and preterm births, perinatal mortality, mode of delivery or maternity complications across the months of january to july . when monthly statistics are compared to and combined, there is an overall reduction in preterm births and more specifically, a difference observed in february . there is a significant reduction in perinatal deaths in july compared to july and combined but no difference in the overall perinatal mortality rate during the pandemic period reviewed compared with previous years. there has been a wealth of data published on covid- infection in pregnancy and our knowledge of the effects of sars-cov on maternal and neonatal outcomes has rapidly evolved, with reports of perinatal transmission increasing , . in contrast, although much has been written regarding potential unintended adverse effects of the pandemic on provision of maternity services and the resulting impact on maternal and neonatal outcomes, there has been little actual data to support or refute these concerns, particularly since many countries continue to experience widespread infection and so are not yet in a position to perform reflective analysis , , . this study of overall hospital statistics compares monthly outcomes and relates them to the severity of the pandemic and also to the combined hospital statistics of the same month in and . the severity of the pandemic was assessed by the number of covid related deaths in the roi. the number of covid deaths rather than covid- infection rate was used as a disease marker as it is a more reliable measure, being unaffected by testing availability, inaccuracies, delayed reporting and missing asymptomatic individuals. published data suggests an increase in preterm births in covid- affected pregnancies, the majority of which is iatrogenic due to maternal illness or fetal compromise , . . a large j o u r n a l p r e -p r o o f population-based study in the uk by knight et al ( ) showed a % preterm birth rate amongst covid- affected pregnancies and % of these were iatrogenic . however, a regional maternity unit in ireland has described a reduction in preterm deliveries of very low birth weight infants during the covid- pandemic in their population. the authors postulated this resulted from a socio-environmental impact of mandated lockdown on pregnant women unaffected by covid- . the study is, however, based on a four month period from january to april , which includes a month period from when sars-cov was first diagnosed in ireland (march and april), and a week period of lockdown (from th march onwards) . yet data from our unit, with almost double the delivery rate and evaluating the complete course of the pandemic, does reveal a reduction in preterm deliveries in comparison to the same time period in the preceding two years. it could be reasoned that this may be secondary to social and health behaviours amongst the obstetric population in the midst of a pandemic with enforced lockdown. however, february was the only month individually to demonstrate a statistically significant difference from the same month in the preceding two years, which was prior to the first diagnosis of sars-cov in ireland. the preterm delivery rate for march and april was not significantly different from the same months in and and overall there was no correlation between the preterm delivery rate in and the peak pandemic period, represented by incidence of covid-related deaths. one factor which warrants consideration is the impact of the newly enacted legislation on st january allowing for termination of pregnancy in limited circumstances in ireland. termination of pregnancies with chromosomal or congenital anomalies which may have been predisposed to either spontaneous or iatrogenic preterm delivery may in part contribute to the noted reduction in preterm birth rate in . the perinatal mortality rate in cwiuh remained stable throughout the peak of the pandemic, however there was a significant reduction noted in july in comparison with previous years. in contrast, khalil et al ( ) compared birth trends in their london unit in a pre-pandemic and pandemic time period and found a significantly increased incidence of stillbirth, none of which occurred in women diagnosed with covid- . however, the testing strategy in the uk at that time was limited to symptomatic individuals requiring hospitalisation and it is noted that surveillance data suggests up to % asymptomatic infection rate among pregnant populations [ ] [ ] [ ] [ ] . there is also no evidence of sars-cov testing of these women following the diagnosis of intrauterine fetal demise, nor postmortem testing of fetal or placental tissue. there was a negative correlation between the induction rate and the number of covid deaths (p< . ), with the lowest rate of inductions occurring in april ( %), during the peak of covid- case diagnoses and deaths. this may demonstrate less obstetric intervention, however this is negated by the mode of delivery statistics which show april had the lowest rate of normal deliveries ( %) and the highest rate of caesarean sections ( %) in the seven month period. a statistically significant decrease in hypertensive disorders of pregnancy during the pandemic period was described in the study by khalil et al ( ) . the authors hypothesised that this, together with the increased stillbirth incidence, may be secondary to reduced antenatal surveillance or women less likely to attend hospital during the pandemic if unwell or concerns with fetal movements . worries regarding the possibility of missed antenatal complications were also raised by other publications, secondary to the rapid reconfiguration of maternity services during the pandemic . however, as shown in table , there was no difference in pregnancy or delivery complications in the cwiuh during this time period. antenatal visits continued with regular frequency and although anecdotally women may have been deterred from attending the hospital on an emergent basis, there was no demonstrable impact on pregnancy outcomes. j o u r n a l p r e -p r o o f corbett et al ( ) , in a study performed in an obstetric population during the first two weeks of the pandemic delay phase in ireland, found that over half of women surveyed worried about their health often or all of the time, with % reporting concern about their unborn baby. they reported an overall increased level of health anxiety in this population, which may explain why initial fears that women would be deterred from attending hospital or seeking emergent care in pregnancy have not been evidenced in our study . there was no difference in unbooked pregnancies or infants born before arrival to hospital during the months pre-and post-pandemic peak or in the midst of it. concern regarding an increase in domestic violence due to the effects of social isolation and enforced lockdown measures during the pandemic has been well-documented . the irish government ran a campaign across television, radio and social media to reassure victims of domestic violence that supports remained available in spite of the covid- pandemic . pregnancy is an acknowledged risk factor for domestic violence which compounds the risk in the obstetric population during this period of mandated lockdown , . at the booking visit in our unit, all women are asked if they have or are experiencing domestic violence to identify those at risk. interestingly, less women disclosed domestic violence at booking during the peak pandemic period when lockdown was enforced in the months of march and april, women in each month, in comparison with the pre-pandemic months of january and february where and women respectively, made disclosures ( j o u r n a l p r e -p r o o f we continue to live through the covid- era, with uncontrolled spread and resurgence of the virus in many countries across the world. the rapid control and ongoing successful suppression of the covid- pandemic in the republic of ireland over a short timeframe affords us the ability to provide a unique insight into the effects of the pandemic on maternity services in a high-income country with universal access to healthcare. there was a statistically significant difference in the number of preterm births over the study period in comparison to previous years, however further research is required before attributing this finding to behavioural and environmental changes secondary to the effects of the pandemic. there were no differences in all other maternal and neonatal outcomes reviewed. it is important to realise the impact of the pandemic on pregnant women, and information sharing with studies like ours will assist in reassuring the obstetric population that the overall results approximate to those expected. ongoing review of maternity statistics also allows us to remain vigilant for developing trends or problems to enable us to adapt our services as needed. it is also important to validate the efforts of healthcare providers who continually strive to provide high quality healthcare in ever-challenging circumstances. j o u r n a l p r e -p r o o f authors have no conflict of interest to declare. the project was conceived by sl, who performed the statistical analysis and contributed to the final draft. smd wrote the manuscript with support from sl and moc. emn performed the data collection. all authors approved the final version submitted for publication. ethical approval was not required for this study. hospital maternity statistics including those used for this study are published annually in a report which is publicly available. permission was sought to utilise this data in advance of report publication from the hospital ceo. no funding was received for this study. ☒ the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. j o u r n a l p r e -p r o o f considerations for obstetric care during the covid- pandemic. american journal of perinatology public health measures for covid- ireland's response to covid- (coronavirus) ireland's covid data hub ireland's national action plan in response to covid- (coronavirus) mfm guidance for covid- the impact of the coronavirus (covid- ) pandemic on maternity care in europe. midwifery a snapshot of the covid- pandemic among pregnant women in france characteristics and outcomes of pregnant women admitted to hospital with confirmed sars-cov- infection in uk: national population based cohort study. bmj early estimates of the indirect effects of the covid- pandemic on maternal and child mortality in low-income and middle-income countries: a modelling study. the lancet global health sustaining quality midwifery care in a pandemic and beyond. midwifery reduction in preterm births during the covid- lockdown in ireland: a natural experiment allowing analysis of data from the prior two decades. medrxiv change in the incidence of stillbirth and preterm delivery during the covid- pandemic pregnancy and postpartum outcomes in a universally tested population for sars-cov- in new york city: a prospective cohort study prevalence of sars-cov- among patients admitted for childbirth in southern connecticut universal screening for sars-cov- in women admitted for delivery health anxiety and behavioural changes of pregnant women during the covid- pandemic the pandemic paradox: the consequences of covid- on domestic violence about the awareness campaign -still here campaign effects of isolation on mood and relationships in pregnant women during the covid- pandemic key: cord- -fqy sm authors: huremović, damir title: brief history of pandemics (pandemics throughout history) date: - - journal: psychiatry of pandemics doi: . / - - - - _ sha: doc_id: cord_uid: fqy sm intermittent outbreaks of infectious diseases have had profound and lasting effects on societies throughout history. those events have powerfully shaped the economic, political, and social aspects of human civilization, with their effects often lasting for centuries. epidemic outbreaks have defined some of the basic tenets of modern medicine, pushing the scientific community to develop principles of epidemiology, prevention, immunization, and antimicrobial treatments. this chapter outlines some of the most notable outbreaks that took place in human history and are relevant for a better understanding of the rest of the material. starting with religious texts, which heavily reference plagues, this chapter establishes the fundamentals for our understanding of the scope, social, medical, and psychological impact that some pandemics effected on civilization, including the black death (a plague outbreak from the fourteenth century), the spanish flu of , and the more recent outbreaks in the twenty-first century, including sars, ebola, and zika. given to ways plagues affected the individual and group psychology of afflicted societies. this includes the unexamined ways pandemic outbreaks might have shaped the specialty of psychiatry; psychoanalysis was gaining recognition as an established treatment within medical community at the time the last great pandemic was making global rounds a century ago. there is a single word that can serve as a fitting point of departure for our brief journey through the history of pandemics -that word is the plague. stemming from doric greek word plaga (strike, blow), the word plague is a polyseme, used interchangeably to describe a particular, virulent contagious febrile disease caused by yersinia pestis, as a general term for any epidemic disease causing a high rate of mortality, or more widely, as a metaphor for any sudden outbreak of a disastrous evil or affliction [ ] . this term in greek can refer to any kind of sickness; in latin, the terms are plaga and pestis (fig. . ). perhaps the best-known examples of plagues ever recorded are those referred to in the religious scriptures that serve as foundations to abrahamic religions, starting with the old testament. book of exodus, chapters through , mentions a series of ten plagues to strike the egyptians before the israelites, held in captivity by the pharaoh, the ruler of egypt, are finally released. some of those loosely defined plagues are likely occurrences of elements, but at least a few of them are clearly of infectious nature. lice, diseased livestock, boils, and possible deaths of firstborn likely describe a variety of infectious diseases, zoonoses, and parasitoses [ ] . similar plagues were described and referred to in islamic tradition in chapter of the qur'an (surat al-a'raf, v. ) [ ] . throughout the biblical context, pandemic outbreaks are the bookends of human existence, considered both a part of nascent human societies, and a part of the very ending of humanity. in the apocalypse or the book of revelation, chapter , seven bowls of god's wrath will be poured on the earth by angels, again some of the bowls containing plagues likely infectious in nature: "so the first angel went and poured out his bowl on the earth, and harmful and painful sores came upon the people who bore the mark of the beast" (revelation : ). those events, regardless of factual evidence, deeply shaped human history, and continue to be commemorated in religious practices throughout the world. as we will see, the beliefs associated with those fundamental accounts have been rooted in societal responses to pandemics in western societies and continue to shape public sentiment and perception of current and future outbreaks. examined through the lens of abrahamic spiritual context, serious infectious outbreaks can often be interpreted as a "divine punishment for sins" (of the entire society or its outcast segments) or, in its eschatological iteration, as events heralding the "end of days" (i.e., the end of the world). throughout known, predominantly western history, there have been recorded processions of pandemics that each shaped our history and our society, inclusive of shaping the very basic principles of modern health sciences. what follows is an outline of major pandemic outbreaks throughout recorded history extending into the twenty-first century. the athenian plague of b.c. the athenian plague is a historically documented event that occurred in - b.c. during the peloponnesian war, fought between city-states of athens and sparta. the historic account of the athenian plague is provided by thucydides, who survived the plague himself and described it in his history of the peloponnesian war [ ] . the athenian plague originated in ethiopia, and from there, it spread throughout egypt and greece. initial symptoms of the plague included headaches, conjunctivitis, a rash covering the body, and fever. the victims would then cough up blood, and suffer from extremely painful stomach cramping, followed by vomiting and attacks of "ineffectual retching" [ ] . infected individuals would generally die by the seventh or eighth day. those who survived this stage might suffer from partial paralysis, amnesia, or blindness for the rest of their lives. doctors and other caregivers frequently caught the disease, and died with those whom they had been attempting to heal. the despair caused by the plague within the city led the people to be indifferent to the laws of men and gods, and many cast themselves into self-indulgence [ ] . because of wartime overcrowding in the city of athens, the plague spread quickly, killing tens of thousands, including pericles, athens' beloved leader. with the fall of civic duty and religion, superstition reigned, especially in the recollection of old oracles [ ] . the plague of athens affected a majority of the inhabitants of the overcrowded city-state and claimed lives of more than % of the population [ ] . the cause of the athenian plague of b.c. has not been clearly determined, but many diseases, including bubonic plague, have been ruled out as possibilities [ ] . while typhoid fever figures prominently as a probable culprit, a recent theory, postulated by olson and some other epidemiologists and classicists, considers the cause of the athenian plague to be ebola virus hemorrhagic fever [ ] . while hippocrates is thought to have been a contemporary of the plague of athens, even possibly treating the afflicted as a young physician, he had not left known accounts of the outbreak [ ] . it was another outbreak that occurred a couple of centuries later that was documented and recorded by contemporary physicians of the time. the outbreak was known as the antonine plague of - ad and the physician documenting it was galen; this outbreak is also known as the plague of galen [ ] . the antonine plague occurred in the roman empire during the reign of marcus aurelius ( - a.d.) and its cause is thought to be smallpox [ ] . it was brought into the empire by soldiers returning from seleucia, and before it abated, it had affected asia minor, egypt, greece, and italy. unlike the plague of athens, which affected a geographically limited region, the antonine plague spread across the vast territory of the entire roman empire, because the empire was an economically and politically integrated, cohesive society occupying wide swaths of the territory [ ] . the plague destroyed as much as one-third of the population in some areas, and decimated the roman army, claiming the life of marcus aurelius himself [ ] . the impact of the plague on the roman empire was severe, weakening its military and economic supremacy. the antonine plague affected ancient roman traditions, leading to a renewal of spirituality and religiousness, creating the conditions for spreading of new religions, including christianity. the antonine plague may well have created the conditions for the decline of the roman empire and, afterwards, for its fall in the west in the fifth century ad [ ] . the justinian plague was a "real plague" pandemic (i.e., caused by yersinia pestis) that originated in mid-sixth century ad either in ethiopia, moving through egypt, or in the central asian steppes, where it then traveled along the caravan trading routes. from one of these two locations, the pestilence quickly spread throughout the roman world and beyond. like most pandemics, the justinian plague generally followed trading routes providing an "exchange of infections as well as of goods," and therefore, was especially brutal to coastal cities. military movement at the time also contributed to spreading the disease from asia minor to africa and italy, and further to western europe. described in detail by procopius, john of ephesus, and evagrius, the justinian epidemic is the earliest clearly documented example of the actual (bubonic) plague outbreak [ ] . during the plague, many victims experienced hallucinations prior to the outbreak of illness. the first symptoms of the plague followed closely behind; they included fever and fatigue. soon afterwards, buboes appeared in the groin area or armpits, or occasionally beside the ears. from this point, the disease progressed rapidly; infected individuals usually died within days. infected individuals would enter a delirious, lethargic state, and would not wish to eat or drink. following this stage, the victims would be "seized by madness," causing great difficulties to those who attempted to care for them [ ] . many people died painfully when their buboes gangrened; others died vomiting blood. there were also cases, however, in which the buboes grew to great size, and then ruptured and suppurated. in such cases, the patient would usually recover, having to live with withered thighs and tongues, classic aftereffects of the plague. doctors, noticing this trend and not knowing how else to fight the disease, sometimes lanced the buboes of those infected to discover that carbuncles had formed. those individuals who did survive infection usually had to live with ''withered thighs and tongues'', the stigmata of survivors. emperor justinian contracted the plague himself, but did not succumb [ ] . within a short time, all gravesites were beyond capacity, and the living resorted to throwing the bodies of victims out into the streets or piling them along the seashore to rot. the empire addressed this problem by digging huge pits and collecting the corpses there. although those pits reportedly held , corpses each, they soon overflowed [ ] . bodies were then placed inside the towers in the walls, causing a stench pervading the entire city. streets were deserted, and all trade was abandoned. staple foods became scarce and people died of starvation as well as of the disease itself [ ] . the byzantine empire was a sophisticated society in its time and many of the advanced public policies and institutions that existed at that time were also greatly affected. as the tax base shrank and the economic output decreased, the empire forced the survivors to shoulder the tax burden [ ] . byzantine army suffered in particular, being unable to fill its ranks and carry out military campaigns, and ultimately failing to retake rome for the empire. after the initial outbreak in , repetitions of the plague established permanent cycles of infection. by , it is possible that the population of the empire had been reduced by %. in the city of constantinople itself, it is possible that this figure exceeded % [ ] . at this point in history, christian tradition enters the realm of interpreting and understanding the events of this nature [ ] . drawing on the eschatological narrative of the book of revelations, plague and other misfortunes are seen and explained as a "punishment for sins," or retribution for the induction of "god's wrath" [ ] . this interpretation of the plague will reappear during the black death and play a much more central role throughout affected societies in europe. meanwhile, as the well-established byzantine empire experienced major challenges and weakening of its physical, economic, and cultural infrastructure during this outbreak, the nomadic arab tribes, moving through sparsely populated areas and practicing a form of protective isolation, were setting a stage for the rapid expansion of islam [ , ] . the black death "the plague" was a global outbreak of bubonic plague that originated in china in , arrived in europe in , following the silk road. within years of its reign, by , [ ] it reduced the global population from million to below million, possibly below million, with the pandemic killing as many as million. some estimates claim that the black death claimed up to % of lives in europe at that time [ ] . starting in china, it spread through central asia and northern india following the established trading route known as the silk road. the plague reached europe in sicily in . within years, it had spread to the virtually entire continent, moving onto russia and the middle east. in its first wave, it claimed million lives [ ] . the course and symptoms of the bubonic plague were dramatic and terrifying. boccaccio, one of the many artistic contemporaries of the plague, described it as follows: in men and women alike it first betrayed itself by the emergence of certain tumours in the groin or armpits, some of which grew as large as a common apple, others as an egg...from the two said parts of the body this deadly gavocciolo soon began to propagate and spread itself in all directions indifferently; after which the form of the malady began to change, black spots or livid making their appearance in many cases on the arm or the thigh or elsewhere, now few and large, now minute and numerous. as the gavocciolo had been and still was an infallible token of approaching death, such also were these spots on whomsoever they showed themselves [ ] . indeed, the mortality of untreated bubonic plague is close to %, usually within days, while the mortality of untreated pneumonic plague approaches %. treated with antibiotics, mortality drops to around % [ ] . at the time, scientific authorities were at a loss regarding the cause of the affliction. the first official report blamed an alignment of three planets from for causing a "great pestilence in the air" [ ] . it was followed by a more generally accepted miasma theory, an interpretation that blamed bad air. it was not until the late xix century that the black death was understood for what it was -a massive yersinia pestis pandemic [ ] . this strain of yersinia tends to infect and overflow the guts of oriental rat fleas (xenopsylla cheopis) forcing them to regurgitate concentrated bacteria into the host while feeding. such infected hosts then transmit the disease further and can infect humans -bubonic plague [ ] . humans can transmit the disease by droplets, leading to pneumonic plague. the mortality of the black death varied between regions, sometimes skipping sparsely populated rural areas, but then exacting its toll from the densely populated urban areas, where population perished in excess of , sometimes % [ ] . in the vacuum of a reasonable explanation for a catastrophe of such proportions, people turned to religion, invoking patron saints, the virgin mary, or joining the processions of flagellants whipping themselves with nail embedded scourges and incanting hymns and prayers as they passed from town to town [ ] . the general interpretation in predominantly catholic europe, as in the case of justinian plague, centered on the divine "punishment for sins." it then sought to identify those individuals and groups who were the "gravest sinners against god," frequently singling out minorities or women. jews in europe were commonly targeted, accused of "poisoning the wells" and entire communities persecuted and killed. non-catholic christians (e.g., cathars) were also blamed as "heretics" and experienced a similar fate [ ] . in other, non-christian parts of the world affected by the plague, a similar sentiment prevailed. in cairo, the sultan put in place a law prohibiting women from making public appearances as they may tempt men into sin [ ] . for bewildered and terrified societies, the only remedies were inhalation of aromatic vapors from flowers or camphor. soon, there was a shortage of doctors which led to a proliferation of quacks selling useless cures and amulets and other adornments that claimed to offer magical protection [ ] . entire neighborhoods, sometimes entire towns, were wiped out or settlements abandoned. crops could not be harvested, traveling and trade became curtailed, and food and manufactured goods became short. the plague broke down the normal divisions between the upper and lower classes and led to the emergence of a new middle class. the shortage of labor in the long run encouraged innovation of labor-saving technologies, leading to higher productivity [ ] . the effects of such a large-scale shared experience on the population of europe influenced all forms of art throughout the period, as evidenced by works by renowned artists, such as chaucer, boccaccio, or petrarch. the deep, lingering wake of the plague is evidenced in the rise of danse macabre (dance of the death) in visual arts and religious scripts [ ] , its horrors perhaps most chillingly depicted by paintings titled the triumph of death (fig. . ) [ ] . the plague made several encore rounds through europe in the following centuries, occasionally decimating towns and entire societies, but never with the same intensity as the black death [ ] . with the breakdown of societal structure and its infrastructures, many professions, notably that of medical doctors, were severely affected. many towns throughout europe lost their providers to plague or to fear thereof. in order to address this shortage in times of austere need, many municipalities contracted young doctors from whatever ranks were available to perform the duty of the plague doctor (medico della peste) [ ] . venice was among the first citystates to establish dedicated practitioners to deal with the issue of plague in . their principal task, besides taking care of people with the plague, was to record in public records the deaths due to the plague [ ] . in certain european cities like florence and perugia, plague doctors were the only ones allowed to perform autopsies to help determine the cause of death and managed to learn a lot about human anatomy. among the most notable plague doctors of their time were nostradamus, paracelsus, and ambrois pare [ ] . the character of the plague doctor was drawing from experiences from ancient cultures that had dealt with contagious diseases, medieval societies observed the connection between the passage of time and the eruption of symptoms, noting that, after a period of observation, individuals who had not developed symptoms of the illness would likely not be affected and, more importantly, would not spread the disease upon entering the city. to that end, they started instituting mandatory isolation. the first known quarantine was enacted in ragusa (city-state of dubrovnik) in , where all arrivals had to spend days on a nearby island of lokrum before entering the city. this period of days (trentine) was later extended to days (quarenta giorni or quarantine) [ ] . the institution of quarantine was one of the rarely effective measures that took place during the black death and its use quickly spread throughout europe. quarantine remains in effect in the present time as a highly regulated, nationally and internationally governed public health measure available to combat contagions [ ] . the spanish flu pandemic in the first decades of the twentieth century was the first true global pandemic and the first one that occurred in the setting of modern medicine, with specialties such as infectious diseases and epidemiology studying the nature of the illness and the course of the pandemic as it unfolded. it is also, as of this time, the last true global pandemic with devastating consequences for societies across the globe [ ] . it was caused by the h n strain of the influenza virus, [ ] a strain that had an encore outbreak in the early years of the twenty-first century. despite advances in epidemiology and public health, both at the time and in subsequent decades, the true origin of spanish flu remains unknown, despite its name. as possible sources of origin, cited are the usa, china, spain, france, or austria. these uncertainties are perpetuated by the circumstances of the spanish flu -it took place in the middle of world war i, with significant censorships in place, and with fairly advanced modes of transportation, including intercontinental travel [ ] . within months, the deadly h n strain of influenza virus had spread to every corner of the world. in addition to europe, where massive military movements and overcrowding contributed to massive spread, this virus devastated the usa, asia, africa, and the pacific islands. the mortality rate of spanish flu ranged between % and %. with over a quarter of the global population contracting that flu at some point, the death toll was immense -well over million, possibly million dead. it killed more individuals in a year than the black death had killed in a century [ ] . this pandemic, unusually, tended to mortally affect mostly young and previously healthy individuals. this is likely due to its triggering a cytokine storm, which overwhelms and demolishes the immune system. by august of , the virus had mutated to a much more virulent and deadlier form, returning to kill many of those who avoided it during the first wave [ ] . spanish flu had an immense influence on our civilization. some authors (price) even point out that it may have tipped the outcome of world war i, as it affected armies of germany and the austrian-hungarian empire earlier and more virulently than their allied opponents (fig. . ) [ ] . many notable politicians, artists, and scientists were either affected by the flu or succumbed to it. many survived and went on to have distinguished careers in arts and politics (e.g., walt disney, greta garbo, raymond chandler, franz kafka, edward munch, franklin delano roosevelt, and woodrow wilson). many did not; this pandemic counted as its victims, among others, outstanding painters like gustav klimt and egon schiele [ ] , and acclaimed poets like guillaume apollinaire. it also claimed the life of sigmund freud's fifth child -sophie halberstadt-freud. this pandemic was also the first one where the longlingering effects could be observed and quantified. a study of us census data from to found that the children born to women exposed to the pandemic had more physical ailments and a lower lifetime income than those born a few months earlier or later. a study in the journal of political economy found that "cohorts in utero during the pandemic displayed reduced educational attainment, increased rates of physical disability, lower income, lower socioeconomic status, and higher transfer payments compared with other birth cohorts" [ ] . despite its immense effect on the global civilization, spanish flu started to fade quickly from the public and scientific attention, establishing a precedent for the future pandemics, and leading some historians (crosby) to call it the "forgotten pandemic" [ ] . one of the explanations for this treatment of the pandemic may lie in the fact that it peaked and waned rapidly, over a period of months before it even could get adequate media coverage. another reason may be in the fact that the pandemic was overshadowed by more significant historical events, such as the culmination and the ending of world war i. a third explanation may be that this is how societies deal with such rapidly spreading pandemicsat first with great interest, horror, and panic, and then, as soon as they start to subside, with dispassionate disinterest. hiv/aids is a slowly progressing global pandemic cascading through decades of time, different continents, and different populations, bringing new challenges with every new iteration and for every new group it affected. it started in the early s in the usa, causing significant public concern as hiv at the time inevitably progressed to aids and ultimately, to death. the initial expansion of hiv was marked by its spread predominantly among the gay population and by high mortality, leading to marked social isolation and stigma. hiv affects about million people globally (prevalence rate: . %) and has killed almost the same number of people since [ ] . it causes about one million deaths a year worldwide (down from nearly two million in ) [ ] . while it represents a global public health phenomenon, the hiv epidemic is particularly alarming in some sub-saharan african countries (botswana, lesotho, and swaziland), where the prevalence tops % [ ] . in the usa, about . million people live with hiv and about , die every year (down from over , per year in the late s). hiv in the usa disproportionately affects gay population, transgendered women, and african-americans [ ] . being a fairly slowly spreading pandemic, hiv has received formidable public health attention, both by national and by international administrations and pharmaceuticals. advances in treatment (protease inhibitors and anti-retrovirals) have turned hiv into a chronic condition that can be managed by medications. it is a rare infectious disease that has managed to attract the focus of mental health which, in turn, resulted in a solid volume of works on mental health and hiv [ ] . by studying the mental health of hiv, we can begin to understand some of the challenges generally associated with infectious diseases. we know, for example, that the lifetime prevalence rate for depression in hiv individuals is, at %, more than twice the prevalence rate in general population [ ] . we understand how depression in hiv individuals shows association with substance abuse and that issues of stigma, guilt, and shame affect the outlook for hiv patients, including their own adherence to life-saving treatments [ ] . we know about medical treatments of depression in hiv and we have studies in psychotherapy for patients with hiv. some of those approaches can be very useful in treating patients in the context of a pandemic. given the contrast between the chronicity of the hiv and the acuity of a potential pandemic, most of those approaches cannot be simply translated from mental health approach to hiv and used for patients in a rapidly advancing outbreak or a pandemic. smallpox was a highly contagious disease for which edward jenner developed the world's first vaccine in . caused by the variola virus, it was a highly contagious disease with prominent skin eruptions (pustules) and mortality of about %. it may have been responsible for hundreds of millions of fatalities in the twentieth century alone. due to the wellcoordinated global effort starting in under the leadership of donald henderson, smallpox was eradicated within a decade of undertaking the eradication on a global scale [ ] . the smallpox outbreak in the former yugoslavia in was a far cry from even an epidemic, let alone a pandemic, but it illustrated the challenges associated with a rapidly spreading, highly contagious illness in a modern world. it started with a pilgrim returning from the middle east, who developed fever and skin eruptions. since a case of smallpox had not been seen in the region for over years, physicians failed to correctly diagnose the illness and nine healthcare providers ended among cases infected by the index case and first fatality [ ] . socialist yugoslavia at the time declared martial law and introduced mandatory revaccination. entire villages and neighborhoods were cordoned off (cordon sanitaire is a measure of putting entire geographic regions in quarantine). about , individuals who may have come into contact with the infected were placed in an actual quarantine. borders were closed, and all non-essential travel was suspended. within weeks, the entire population of yugoslavia was revaccinated (about million people at the time). during the outbreak, cases were identified, with fatalities. due to prompt and massive response, however, the disease was eradicated and the society returned to normal within months [ ] . this event has proven to be a useful model for working out scenarios ("dark winter") [ ] for responses to an outbreak of a highly contagious disease, both as a natural occurrence [ ] and as an act of bioterrorism [ ] . severe acute respiratory syndrome (sars) was the first outbreak in the twenty-first century that managed to get public attention. caused by the sars corona virus (sars-cov), it started in china and affected fewer than , individuals, mainly in china and hong kong, but also in other countries, including cases in canada (toronto) [ ] . the severity of respiratory symptoms and mortality rate of about % caused a global public health concern. due to the vigilance of public health systems worldwide, the outbreak was contained by mid- [ ] . this outbreak was among the first acute outbreaks that had mental health aspects studied in the process and in the aftermath, in various part of the world and in different societies, yielding valuable data on effects of an acute infectious outbreak on affected individuals, families, and the entire communities, including the mental health issues facing healthcare providers [ ] . some of the valuable insights into the mental health of patients in isolation, survivors of the severe illness, or psychological sequelae of working with such patients were researched during the sars outbreak. "swine flu" or h n / pandemic the h n pandemic was a reprise of the "spanish flu" pandemic from , but with far less devastating consequences. suspected as a re-assortment of bird, swine, and human flu viruses, it was colloquially known as the "swine flu" [ ] . it started in mexico in april of and reached pandemic proportions within weeks [ ] . it began to taper off toward the end of the year and by may of , it was declared over. it infected over % of the global population (lower than expected), with a death toll estimated varying from , to over , [ ] . although its death rate was ultimately lower than the regular influenza death rates, at the time it was perceived as very threatening because it disproportionately affected previously healthy young adults, often quickly leading to severe respiratory compromise. a possible explanation for this phenomenon (in addition to the "cytokine storm" applicable to the h n outbreak) is attributed to older adults having immunity due to a similar h n outbreak in the s [ ] . this pandemic also resulted in some valuable data studying and analyzing the mental health aspects of the outbreak. it was among the first outbreaks where policy reports included mental health as an aspect of preparedness and mitigation policy efforts. this outbreak of h n was notable for dissonance between the public sentiment about the outbreak and the public health steps recommended and undertaken by who and national health institutions. general public sentiment was that of alarm caused by who releases and warnings, but it quickly turned to discontent and mistrust when the initial grim outlook of the outbreak failed to materialize [ ] . health agencies were accused of creating panic ("panicdemic") and peddling unproven vaccines to boost the pharmaceutical companies (in , some extra $ , billion worth of h n vaccines were purchased and administered in the usa) [ ] . this outbreak illustrated how difficult it may be to gauge and manage public expectations and public sentiments in the effort to mobilize a response. it also demonstrated how distilling descriptions of the impact of a complex public health threat like a pandemic into a single term like "mild," "moderate," or "severe" can potentially be misleading and, ultimately, of little use in public health approach [ ] . ebola virus, endemic to central and west africa, with fruit bats serving as a likely reservoir, appeared in an outbreak in a remote village in guinea in december . spreading mostly within families, it reached sierra leone and liberia, where it managed to generate considerable outbreaks over the following months, with over , cases and over , fatalities. a very small number of cases were registered in nigeria and mali, but those outbreaks were quickly contained [ ] . ebola outbreak, which happened to be the largest outbreak of ebola infection to date, gained global notoriety after a passenger from liberia fell ill and died in texas in september of , infecting two nurses caring for him, and leading to a significant public concern over a possible ebola outbreak in the usa [ ] . this led to a significant public health and military effort to address the outbreak and help contain it on site (operation united assistance) [ , ] . zika virus was a little known, dormant virus found in rhesus monkeys in uganda. prior to , the only known outbreak among humans was recorded in micronesia in . the virus was then identified in brazil in , after an outbreak of a mild illness causing a flat pinkish rash, bloodshot eyes, fever, joint pain and headaches, resembling dengue. it is a mosquitoborne disease (aedes aegypti), but it can be sexually transmitted. despite its mild course, which initially made it unremarkable form the public health perspective, infection with zika can cause guillain-barre syndrome in its wake in adults and, more tragically, cause severe microcephalia in unborn children of infected mothers (a risk of about %) [ ] . in brazil, in , for example, there were birth defects and infant deaths due to suspected zika infection [ ] . zika outbreak is an illustrative case of the context of global transmission; it was transferred from micronesia, across the pacific, to brazil, whence it continued to spread [ ] . it is also a case of a modern media pandemic; it featured prominently in the social media. in early , zika was being mentioned times a minute in twitter posts. social media were used to disseminate information, to educate, or to communicate concerns [ ] . its presence in social media, perhaps for the first time in history, allowed social researchers to study the public sentiment, also known as the emotional epidemiology (ofri), in real time [ ] . while both public health institutions and the general public voiced their concern with the outbreak, scientists and officials sought to provide educational aspect, while concerned public was trying to have their emotional concerns addressed. it is indicative that out of posts on zika on social media were accurate; yet, those that were "trending" and gaining popularity were posts with inaccurate content (now colloquially referred to as the "fake news") [ ] . this is a phenomenon that requires significant attention in preparing for future outbreaks because it may hold a key not only to preparedness, but also to execution of public health plans that may involve quarantine and immunization. since , zika has continued to spread throughout south america, central america, the caribbean, and several states within the usa. it remains a significant public health concern, as there is no vaccine and the only reliable way to avoid the risk for the offspring is to avoid areas where zika was identified or to postpone pregnancy should travel to or living in affected areas be unavoidable [ ] . disease x disease x is not, as of yet, an actual disease caused by a known agent, but a speculated source of the next pandemic that could have devastating effects on humanity. knowing the scope of deleterious effects a pandemic outbreak can have on humankind, in the wake of the ebola outbreak, the world health organization (who) decided to dedicate formidable resources to identifying, studying, and combating possible future outbreaks. it does so in the form of an r&d blueprint, though devising its global strategy and preparedness plan that allows the rapid activation of r&d activities during epidemics [ ] . r&d blueprint maintains and updates a list of so-called identified priority diseases. this list is updated at regular intervals and, as of , it includes diseases such as ebola and marburg virus diseases, lassa fever, middle east respiratory syndrome coronavirus (mers-cov) and severe acute respiratory syndrome (sars), nipah and henipa virus diseases, zika, and others [ ] . for each disease identified, an r&d roadmap is created, followed by target product profiles (i.e., immunizations, treatment, and regulatory framework). those efforts are important to help us combat a dangerous outbreak of any of the abovementioned diseases, but also to fend off disease x. since disease x is a hypothetical entity, brought by a yet unknown pathogen that could cause a serious international pandemic, the r&d blueprint explicitly seeks to enable cross-cutting r&d preparedness that is also relevant for both existing culprits and the unknown future "disease x" as much as possible. who utilizes this r&d blueprint vehicle to assemble and deploy a broad global coalition of experts who regularly contribute to the blueprint and who come from several medical, scientific, and regulatory backgrounds. its advisory group, at the time, does not include mental health specialists [ ] . the black death: the greatest catastrophe ever the great leveler: violence and the history of inequality from the stone age to the twenty-first century. chapter : the black death mortality risk and survival in the aftermath of the medieval black death an epidemiologic analysis of the ten plagues of egypt the noble qur'an surah thucydides' description of the great plague the plague of athens: epidemiology and paleopathology the thucydides syndrome: a new hypothesis for the cause of the plague of athens the thucydides syndrome: ebola déjà vu? (or ebola reemergent?). emerg infect dis hippocrates of kos, the father of clinical medicine, and asclepiades of bithynia, the father of molecular medicine the antonine plague and the decline of the roman empire the plague under marcus aurelius and the decline and fall of the roman empire the antonine plague: a global pestilence in the ii century d justinian's plague ( - ce) loeb library of the greek and roman classics justinian's flea: plague, empire, and the birth of europe plague in the ancient world: a study from thucydides to justinian ecclesiastical history (ad - ), trans the attitude of the secular historians of the age of justinian towards the classical past the justinian plague (part one) influence of the epidemic on the rise of the islamic empire mortality risk and survival in the aftermath of the medieval black death death and miasma in victorian london: an obstinate belief adaptive strategies of yersinia pestis to persist during inter-epizootic and epizootic periods the black death - : the complete history medieval europe: a short history black death. simon and schuster the black death the air of history (part ii) medicine in the middle ages mixed metaphors. the danse macabre in medieval and early modern europe the theme of death in italian art: the triumph of death daily life during the black death communities and crisis: bologna during the black death nostradamus: the new revelations. barnes & noble books images of plague and pestilence: iconography and iconology the origin of quarantine lessons from the history of quarantine, from plague to influenza a. emerging infectious diseases cdc: remembering the influenza pandemic molecular virology: was the flu avian in origin? plagues & wars: the 'spanish flu' pandemic as a lesson from history pandemic versus epidemic influenza mortality: a pattern of changing age distribution contagion and chaos expressionist portraits is the influenza pandemic over? long-term effects of in utero influenza exposure in the post- u.s. population america's forgotten pandemic: the influenza of the spread, treatment, and prevention of hiv- : evolution of a global pandemic estimates of global, regional, and national incidence, prevalence, and mortality of hiv, - : the global burden of disease study academy of consultation-liaison psychiatry, hiv psychiatry bibliography meta-analysis of the relationship between hiv infection and risk for depressive disorders cognitive behavioural therapy for adherence and depression in patients with hiv: a three-arm randomised controlled trial the last major outbreak of smallpox (yugoslavia, ): the importance of historical reminders shining light on "dark winter evaluating public health responses to reintroduced smallpox via dynamic, socially structured, and spatially distributed metapopulation models extracting key information from historical data to quantify the transmission dynamics of smallpox responding to global infectious disease outbreaks: lessons from sars on the role of risk perception, communication and management summary of probable sars cases with onset of illness from was sars a mental health catastrophe? gen hosp psychiatry geographic dependence, surveillance, and origins of the influenza a (h n ) virus in new theory, swine flu started in asia, not mexico. the new york times estimated global mortality associated with the first months of pandemic influenza a h n virus circulation: a modelling study risk factors for hospitalisation and poor outcome with pandemic a/ h n influenza: united kingdom first wave assessing the severity of the novel influenza a/ h n pandemic doctors rake in billions battling h n flu by dalia fahmy. abc news reflections on pandemic (h n ) and the international response the emergence of ebola as a global health security threat: from 'lessons learned' to coordinated multilateral containment efforts overview, control strategies, and lessons learned in the cdc response to the - ebola epidemic ebola outbreak in west africa military ebola mission in liberia coming to an end zika: the origin and spread of a mosquito-borne virus the microcephaly epidemic and zika virus: building knowledge in epidemiology propagating and debunking conspiracy theories on twitter during the - zika virus outbreak the emotional epidemiology of h n influenza vaccination spreading the (fake) news: exploring health messages on social media and the implications for health professionals using a case study who: r&d blueprint, about the r&d blueprint who: r&d blueprint, scientific advisory group members key: cord- -vhghhvnu authors: schwartz, benjamin; orenstein, walter a. title: prioritization of pandemic influenza vaccine: rationale and strategy for decision making date: - - journal: vaccines for pandemic influenza doi: . / - - - - _ sha: doc_id: cord_uid: vhghhvnu few catastrophes can compare with the global impact of a severe influenza pandemic. the – pandemic was associated with more than , deaths in the usa and an estimated – million deaths worldwide, though some place the global total much higher. in an era when infectious disease mortality had been steadily decreasing, the – pandemic caused a large spike in overall population mortality, temporarily reversing decades of progress. the us department of health and human services, extrapolating from the – pandemic to the current us population size and demographics, has estimated that a comparable pandemic today would result in almost two million deaths. vaccination is an important component of a pandemic response. public health measures such as reduction of close contacts with others, improved hygiene, and respiratory protection with facemasks or respirators can reduce the risk of exposure and illness (germann et al. ; ferguson et al. ), but would not reduce susceptibility among the population. prophylaxis with antiviral medications also may prevent illness but depends on the availability of large antiviral drug stockpiles and also does not provide long-term immunity. by contrast, immunization with a well-matched pandemic vaccine would provide active immunity and represent the most durable pandemic response. however, given current timelines for the development of a pandemic influenza vaccine and its production capacity, vaccine is likely not to be available in sufficient quantities to protect the entire population before pandemic outbreaks occur, and thus potentially limited stocks may need to be prioritized. this chapter reviews information on influenza vaccine production capacity, describes approaches used in the usa to set priorities for vaccination in the setting of limited supply, and presents a proposed strategy for prioritization. few catastrophes can compare with the global impact of a severe influenza pandemic. the - pandemic was associated with more than , deaths in the usa and an estimated - million deaths worldwide, though some place the global total much higher. in an era when infectious disease mortality had been steadily decreasing, the - pandemic caused a large spike in overall population mortality, temporarily reversing decades of progress. the us department of health and human services, extrapolating from the - pandemic to the current us population size and demographics, has estimated that a comparable pandemic today would result in almost two million deaths. vaccination is an important component of a pandemic response. public health measures such as reduction of close contacts with others, improved hygiene, and respiratory protection with facemasks or respirators can reduce the risk of exposure and illness (germann et al. ; ferguson et al. ), but would not reduce susceptibility among the population. prophylaxis with antiviral medications also may prevent illness but depends on the availability of large antiviral drug stockpiles and also does not provide long-term immunity. by contrast, immunization with a well-matched pandemic vaccine would provide active immunity and represent the most durable pandemic response. however, given current timelines for the development of a pandemic influenza vaccine and its production capacity, vaccine is likely not to be available in sufficient quantities to protect the entire population before pandemic outbreaks occur, and thus potentially limited stocks may need to be prioritized. this chapter reviews information on influenza vaccine production capacity, describes approaches used in the usa to set priorities for vaccination in the setting of limited supply, and presents a proposed strategy for prioritization. an influenza pandemic occurs with the introduction and spread of a new influenza a virus subtype among people. although some cross-protection against antigenically different influenza viruses within a subtype occurs following prior infection or vaccination, the entire population is likely to be susceptible to an influenza a virus subtype that has not circulated (or has not circulated recently) among people. consequently, in an influenza pandemic, rates of illness are higher, severity is greater, and the distribution of mortality is more widespread compared with seasonal influenza (simonsen et al. ) . given the susceptibility of the entire population, the goal of the united states' pandemic vaccination program is to offer vaccination to everyone living in the usa. there are several potential approaches to implementing pandemic influenza vaccination when vaccine supplies are inadequate to rapidly vaccinate the entire population: vaccine could be administered on a "first come, first served" basis or could be targeted first to individuals and groups based on specified criteria. criteria for targeting in other mass vaccination campaigns have included geographic area (e.g., group a meningococcus in the african meningitis belt), exposure or proximity to a case (e.g., smallpox), age (e.g., polio), risk of infection (e.g., h. influenzae type b), risk of complications from infection (e.g., seasonal influenza), risk for transmitting infection (e.g., rubella), or (most often) a combination of these factors. targeting has been justified as providing earliest protection to those who are most vulnerable to infection, most at risk of severe or fatal disease, or whose protection may prevent or reduce further transmission (heymann and aylward ) . when vaccine supply, the capacity to administer it, or funding is limited, so that the optimal strategyrapid universal vaccination-is impossible to implement, targeting mass vaccination becomes more important to achieve the best possible outcomes. in the national strategy for pandemic influenza, the president defined a goal of establishing domestic manufacturing capacity that produces sufficient vaccine to vaccinate the entire us population within six months of the emergence of a virus with pandemic potential (the white house ). to achieve this, over $ billion has been allocated ( ) to expand domestic egg-based influenza vaccine production, ( ) to support advanced development of new vaccine production technologies, such as growth of influenza virus in cultured cells or development of recombinant vaccines, and ( ) to support the advanced development of "antigen-sparing" approaches, such as new adjuvants, that can stimulate a more robust immune response, allowing manufacturers to reduce the amount of antigen in each dose and formulating the antigen produced into more vaccine doses. until the promise of these approaches is realized, however, pandemic influenza vaccine supply is likely to be far less than pandemic response needs. for the - influenza season, most of the influenza vaccine administered in the usa was produced in other countries, and these sources of supply may not be available during a pandemic. moreover, the amount of antigen needed to achieve a protective immune response could be substantially greater for a pandemic virus compared with seasonal influenza viruses. a clinical trial of an unadjuvanted candidate h n vaccine showed that two doses containing mg of hemagglutinin antigen were needed to achieve an immune response that may correlate with protection in more than half of healthy adult recipients (treanor et al. ) . this per dose concentration is sixfold higher than the quantities of hemagglutinin antigen included for each strain in the seasonal trivalent inactivated vaccines (tiv), and twofold higher than the total hemagglutinin in a standard dose of tiv. since two doses of the h n vaccine were needed to achieve adequate immunogenicity, the quantity of antigen needed to immunize an adult would be -fold higher than the amount of antigen to vaccinate against a seasonal strain. initial trials with other candidate h n vaccines that contain alum, novel lipid-based adjuvants, or that use the inactivated whole virus documented immunogenicity with two doses of mg, . , and mg, respectively (bresson et al. ; leroux-roels et al. ; lin et al. ). while additional studies are needed, these results suggest a potentially wide range of antigen quantities needed in different vaccine formulations, which will directly impact how quickly the population can be effectively vaccinated in the event of a pandemic. vaccine supply, therefore, would depend on the production capacity for different vaccine formulations at the time a pandemic occurs. under some scenarios, vaccine supply would be very limited, whereas under others, assuming success in evaluating and licensing new formulations and producing them in the usa, supply may be robust. the time required to develop, license, and manufacture pandemic influenza vaccine is also an important variable. using current technologies, at least weeks would be required from the time the pandemic virus was identified until the first vaccine doses become available. depending on a combination of factors, including where the pandemic begins, how quickly it is detected, the effectiveness of containment measures and the season, the first us pandemic wave may occur before any pandemic vaccine becomes available or after sufficient lead time such that vaccination is already widespread (ferguson et al. ; longini et al. ). in the pandemic, the first us cases occurred in june but no community outbreak occurred until august and the first pandemic wave did not peak until the end of october; by this time almost half of the approximately million vaccine doses eventually produced had been delivered. by contrast, in , the pandemic was not recognized until later in the year, and at the time initial us outbreaks began few persons had been vaccinated (schwartz and wortley ) . because influenza vaccine production capacity, vaccine formulation, and the time from pandemic recognition to onset of us outbreaks all are uncertain for the next pandemic, we are unable to predict how many people will be vaccinated before pandemic disease is widespread. thus, prioritizing who is vaccinated earlier and who later will best target available supply to achieve national pandemic response goals. us pandemic response goals include slowing the spread of pandemic disease and reducing the health, societal, and economic impacts of the pandemic (the white house ). the approach to using a limited supply of pandemic vaccine may differ depending on which goals are considered most important. results of mathematical models suggest that vaccinating school-aged children can best reduce transmission of influenza, slowing disease spread and reducing overall community attack rates (germann et al. ) . while studies of vaccination for seasonal influenza support a strategy of vaccinating children to protect others in the community through herd immunity (monto et al. ; piedra et al. ; reichert et al. ) , uncertainty in the amount of vaccine that will be available or its timeliness make reliance on trying to induce indirect protection a risky strategy. hospitalizations and deaths from pandemic illness can be reduced by directly vaccinating those at highest risk for these severe outcomes. based on age-specific mortality rates in the and pandemics, vaccinating persons ³ years old would have prevented substantially more deaths compared with vaccinating other age groups, despite the lower vaccine efficacy among the elderly (in this would not have been the case because of the high mortality rate among young adults). another approach to reduce the health impacts of a pandemic would be to vaccinate healthcare workers so that they can continue to provide care to others. in an unmitigated pandemic, the demand for healthcare services will be overwhelming at a time when healthcare workers may be out of work due to illness, the need to care for sick family members, or because they are afraid of becoming infected at the workplace. a survey of county health department workers in maryland found that % of respondents indicated they would not report to work in a pandemic. in a multivariable analysis, confidence in one's personal safety was significantly associated with a willingness to work (balicer et al. ) . whether response to a survey is predictive of actual behavior is unclear; anecdotally, virtually all healthcare workers in toronto reported to work during the sars outbreak, despite the fear associated with a new disease and the spread that occurred within hospitals. whether vaccinating healthcare providers to maintain effective care or vaccinating those at highest risk of illness would better reduce the health impacts of a pandemic is unknown. the potential societal and economic impacts of a pandemic are associated with pandemic severity, although even in a severe pandemic these impacts cannot accurately be predicted. historical experience does not provide a guide, as a severe pandemic has not occurred for almost a century. a report by the us department of homeland security's national infrastructure advisory committee (niac) analyzed the components of critical infrastructure sectors that would be essential to society in a pandemic and the workforce needed to maintain those products and services (national infrastructure advisory council ). the report identifies significant interdependency between sectors, expresses concern about the maintenance of supply chains, many of which stretch overseas, and emphasizes the importance and challenges of implementing a targeted vaccination program. of the approximately million workers in these sectors, . million were defined by niac as essential in a pandemic. about nine million of these workers are in the healthcare and emergency services (emergency medical services, law enforcement, and fire protection) sectors. in other sectors, the proportion of the workforce defined as critical ranges from almost % in the nuclear sector to less than % of the food and agriculture sector. because the availability of pandemic vaccine before disease outbreaks is not assured, business planning includes other measures such as "social distancing," improved hygiene, use of facemasks or respirators, and possibly antiviral drug prophylaxis to protect workers in essential operations. because of the uncertainties about the severity and epidemiology of the next pandemic, vaccine supply, and the best approach to using vaccine to reduce health, societal and economic impacts, there is no scientific method to define the optimal use of pandemic influenza vaccine. in , a working group from two us advisory committees, the advisory committee on immunization practices (acip) and the national vaccine advisory committee (nvac) met to develop a pandemic vaccine prioritization strategy. the working group considered the epidemiology and impacts of pandemics, the groups at highest risk for complications and death from influenza, vaccine efficacy, critical societal functions, and ethical issues. the prioritization strategy proposed by the committees included vaccinating groups defined in tiers and subtiers, depending on vaccine supply. groups that were prioritized for earliest vaccination included healthcare workers, manufacturers of pandemic vaccine and antiviral drugs, and persons at high risk of severe illness and death. personnel in critical infrastructure sectors other than healthcare were prioritized after these groups, which include over million persons. this strategy was published in the department of health and human services' pandemic plan to provide guidance to state planners and stimulate further discussions (us department of health and human services ). shortly after publication of the plan, a federal working group was created to reassess and potentially revise pandemic vaccine prioritization guidance. factors contributing to the decision to reassess the recommendations included a shift in national pandemic planning assumptions to a more severe pandemic scenario extrapolated from the pandemic (table ); recognition that the hhs guidance did not include groups that could be considered for prioritization such as border protection personnel or the military; a broader understanding of the risk to essential services stimulated by the niac report; and a series of public engagement meetings convened by the cdc, where participants identified protecting essential community services as the most important goal for pandemic vaccination rather than protecting those who are at highest risk (public engagement pilot project on pandemic influenza ). the federal working group process included consideration of the scientific issues reviewed in the earlier prioritization process, assessment of mathematical modeling results, and discussion with public health officials, critical infrastructure providers and homeland and national security experts. recognizing that science alone cannot define the best approach to pandemic vaccine prioritization, key elements of the process were consideration of ethical issues, input from the public and stakeholders, and a formal decision analysis. ethical input into the working group process was achieved through the participation of public and private sector ethicists and an analysis conducted by the ethics subcommittee of cdc's advisory committee to the director (ethics subcommittee of the advisory committee to the director, cdc ). a strategy of targeting pandemic influenza vaccination to reduce health, societal and economic impacts was considered ethically appropriate. although a strict utilitarian principle could not be applied because of uncertainty about what strategy would provide the most benefit, targeting protection of society in a broad sense was given higher priority than protecting individuals at high risk of complications from influenza. fairness and equity are important principles where everyone is recognized to have equal value, and all table national pandemic planning assumptions. note that planning for some responses such as nonpharmaceutical community mitigation strategies is done across a range of pandemic severities, as defined by the pandemic severity index (cdc, community mitigation guidance) clinical illness attack rate of % (rates highest among school-aged children, about %, and declining with age); us national estimate: , , cases° care seeking by about half of those who are clinically ill° hospitalization of % of clinical cases; us national estimate: , , ° case fatality rate of . %; us national estimate: , , • risk groups for severe illness and death will depend on the pandemic virus and are likely to include infants, pregnant women, persons with chronic and immunosuppressive medical conditions, and the elderly • outbreaks will last - weeks in affected communities; effective use of nonpharmaceutical community mitigation strategies (e.g., social distancing) will prolong community outbreaks but reduce their overall magnitude • multiple waves of illness will occur, with each wave lasting - months persons within a targeted group should have similar access to vaccination. reciprocity, which posits that protection should be afforded to those who assume increased risk in an occupation that benefits society, also was considered important, and a reasonable corollary to healthcare providers' "duty of care" where one is committed to provide care even in settings that increase personal risk. procedural ethical principles of inclusiveness and transparency were met through a process of engaging with the public and stakeholders in meetings, and through a request for comments posted in the federal register and on the government's pandemic influenza website. the goal of the public and stakeholder meetings was to identify the objectives of a pandemic vaccination program that participants felt were most important to pursue. public meetings were held in two demographically different communities with participants recruited by community groups. stakeholder representatives from government, healthcare, business, and community organizations participated in a third meeting. each meeting included initial presentations to educate participants on influenza and influenza vaccine, pandemics, and the rationale for vaccine prioritization. participants discussed potential objectives of pandemic vaccination in small groups and then met in a plenary session where the objectives were discussed further. finally, participants rated the importance of each of ten proposed objectives using a seven-point likert scale ranging from "extremely important" (a score of ) to "not important" (a score of ). despite the differences between groups in terms of geographic location, demographic characteristics, and occupational background, the values expressed at each meeting were similar (table ) . table importance of pandemic vaccination program objectives based on scores assigned by participants at public engagement meetings in las cruces, new mexico, and nassau county, new york, and a stakeholders meeting in washington, dc. scores were assigned from a seven-point likert scale ranging from = extremely important to = not at all important key outcomes of this process included the importance of achieving multiple objectives with the pandemic vaccination program, the value given to protecting critical services and exposed workers, and the preference for vaccinating children before those who are most likely to become sick or to die-older adults and those who have underlying medical conditions. results from the public and stakeholder engagement process provide insight into the values and preferences of the population but do not translate directly into a prioritization strategy for pandemic vaccine. we therefore conducted a formal decision analysis to assess the priority of different population groups. we identified potential target groups for pandemic vaccination defined by their occupation or by their age and health status. the degree to which each group met each of the ten vaccination program objectives was then assessed and scored: how well each group met objectives related to occupational role or exposure was scored by representatives on the federal working group; for objectives where clinical trial or epidemiological data can be used to assess how well a group met an objective, scoring was done by influenza experts from cdc and academic medical centers. the score assigned to each group for each objective was then weighted by the average rating of the objective's importance from the public engagement and stakeholders meetings ( table ) . a total score was calculated for each group as the sum of the objective scores multiplied by their weights for the ten vaccination program objectives, as described by s x = o w + o w + ... + o w , where s x is the total score for group x; o - are the scores the group received for each of the ten objectives; and w - are the weights for each of the objectives. as an example, medical care practitioners received high scores from the working group for objectives of fighting the pandemic and providing care, providing an essential community service, being vulnerable due to their jobs, and being at risk of spreading infection to those who are unprotected (their patient population). because most healthcare workers are healthy adults who would respond well to vaccination, they also received high scores for the objective of being most likely to be protected by the vaccine. medical care practitioners score lower for providing essential economic services, protecting homeland and national security, and being most likely to get sick or die (as some may have underlying medical conditions or be years old or older). this group would receive no points for keeping the pandemic out of the usa or being children. based on this analysis, groups scoring highest for vaccination were front-line public health workers involved in the pandemic response (for example, providing vaccinations), medical care practitioners, emergency medical service personnel, law enforcement personnel, and emergency relief workers. occupational groups invariably scored higher than general population groups defined by their age and health status because more of the ten program objectives were relevant (i.e., they would receive some score for objectives related to one's occupational role and exposure risk as well as one's age-and health-related risk of influenza, ability to be protected by vaccination, and potential role in disease spread). by contrast, general population groups received no score for the occupationally-related objectives. to control for this difference, we stratified potential vaccination target groups into four categories: those that provide healthcare and community support services; those that provide critical infrastructure services; those that protect homeland and national security; and the general population. within these categories, target groups were clustered based on their scores, with breakpoints between clusters defined by difference between scores. groups scoring highest among each of these categories are shown in table . the us pandemic vaccine prioritization guidance incorporates both the tier structure from the guidance included in the hhs pandemic plan and the target group categorization used in the decision analysis. reflecting the similar value placed by the public on protecting persons who provide pandemic healthcare, who maintain essential community services or are at high occupational risk, and protecting children, each of the highest vaccination tiers for a severe pandemic includes groups from each category (table ) . generally, the specific groups included in each tier track closely with the results of the decision analysis. some groups, such as deployed military forces and those who provide support for their mission, are placed in a higher tier in recognition that they may be affected in a pandemic earlier than persons in the usa due to their geographical locations, their increased risk because of crowded living conditions, and the impact of illness on their ability to function effectively. in some critical infrastructure sectors, target groups are prioritized in a lower tier because their expected occupational burden would likely decrease in a pandemic (e.g., passenger transportation), they can largely be protected by changes in work practices such as teleworking, and/or the workforce or work is "fungible;" essential support and sustainment pers. , intelligence services , border protection personnel , national guard personnel , other domestic national security pers. , other active duty and essential suppt. that is, the impact of absenteeism or reduced function can be mitigated by the redundancy within the sector (e.g., trucking, food processing). workers in infrastructure sectors are targeted for early pandemic vaccination to maintain the essential services they provide in recognition of the interdependencies between sectors. healthcare, for example, relies on the sectors that provide electricity, clean water, communications, information technology, transportation, pharmaceuticals, food, and chemicals. in a less severe pandemic, however, historical experience suggests that these services are unlikely to be substantially affected. in both the and pandemics, essential services were maintained without targeting pandemic vaccination. therefore, the us strategy differs for severe, moderate, and less severe pandemics, with some of the occupational groups not targeted in moderate and less severe pandemics, and those workers being vaccinated with their age and health status group in the general population category. pandemic severity is classified using the pandemic severity index, which defines five categories based on the case fatality rate of pandemic illness (cdc ) . a category pandemic, defined by a case fatality rate of < . %, would result in a mortality only slightly greater than a severe seasonal influenza epidemic, and the proposed us vaccine prioritization guidance for less severe pandemics (categories and ) is formulated to be more similar to recommendations for annual influenza vaccination. pandemic vaccine prioritization strategies developed in other industrialized countries are generally based on similar ethical principles and target similar groups to those in the us plan. while healthcare providers and those critical to a pandemic response are the groups targeted first in many plans, workers in other infrastructure sectors may not be targeted. this may reflect national planning assumptions for a less severe pandemic, lower predicted rates of worker absenteeism, and a belief that infrastructures can be protected by planning to protect workers using nonpharmaceutical interventions and antiviral medications to treat or prevent illness. some countries, such as canada or australia, which have substantial domestic influenza vaccine manufacturing capacity and small populations, may choose not to prioritize vaccination because of the ability to vaccinate everyone over several months. to our knowledge, only the us strategy explicitly presents different vaccine targeting based on pandemic severity, although every country is likely to reassess and potentially modify their national plan based on the epidemiology of the pandemic. prioritizing pandemic vaccination addresses only a single component of planning an effective pandemic influenza vaccination program. plans are also needed on how the vaccine supply will be allocated among the states or other jurisdictions, how it will be distributed, and how the program will be implemented. key implementation issues include the method of identifying persons who are in target groups, validation at the vaccination site, vaccine administration and tracking, and monitoring for the occurrence of adverse events. a major problem could be having to turn away persons who are panicked about the severity of a pandemic yet do not meet the criteria for vaccination at that time under the prioritization strategy. currently, no comparable program exists and each step will need to be planned and tested in preparedness exercises. effective communications also will be important. while substantial public involvement in the development of the vaccine prioritization strategy increases the chance that the approach will be acceptable to the public, communications goals will be to assure the public that the entire population will have the opportunity to be vaccinated, to communicate the rationale for prioritization and the prioritization strategy, and to inform people when it is their turn to be vaccinated. rationing of healthcare is not an issue that most americans have had to face in the past. outside of military settings, healthcare services generally have not been limited by availability as much as by economic or geographic factors. prioritizing pandemic influenza vaccine introduces a new paradigm. the approach taken by us planners considering science, ethics, and public values and preferences creates a model for how such rationing can take place. nevertheless, the optimal solution is to pursue preparedness activities that will obviate the need to prioritize. ongoing programs to increase influenza vaccine production capacity, to stretch vaccine supply through the use of new adjuvants, and to develop influenza vaccines targeted at antigens that are conserved across the different influenza a subtypes may all lead to a time when pandemic influenza vaccine prioritization will be unnecessary. local public health workers' perceptions toward responding to an influenza pandemic safety and immunogenicity of an inactivated split-virion influenza a/vietnam/ / (h n ) vaccine: phase randomised trial community strategy for pandemic influenza mitigation ethics subcommittee of the advisory committee to the director, cdc ( ) ethical guidelines in pandemic influenza strategies for containing an emerging influenza pandemic in southeast asia strategies for mitigating an influenza pandemic mitigation strategies for pandemic influenza in the united states mass vaccination: when and why antigen sparing and cross-reactive immunity with an adjuvanted rh n prototype pandemic influenza vaccine: a randomised controlled trial safety and immunogenicity of an inactivated adjuvanted whole-virion influenza a (h n ) vaccine: a phase randomised controlled trial containing pandemic influenza at the source effect of vaccination of a school-aged population upon the course of an a /hong kong influenza epidemic the prioritization of critical infrastructure in a pandemic influenza outbreak in the united states: final report and recommendations by the council herd immunity in adults against influenza-related illnesses with use of the trivalent-live attenuated influenza vaccine (caiv-t) in children public engagement pilot project on pandemic influenza ( ) citizen voices on pandemic flu choices the japanese experience with vaccinating schoolchildren against influenza mass vaccination for annual and pandemic influenza pandemic versus epidemic influenza mortality: a pattern of changing age distribution national strategy for pandemic influenza safety and immunogenicity of an inactivated subvirion influenza a. (h n ) vaccine pandemic influenza plan: appendix d key: cord- -mi gcfcw authors: davis, mark d m; stephenson, niamh; lohm, davina; waller, emily; flowers, paul title: beyond resistance: social factors in the general public response to pandemic influenza date: - - journal: bmc public health doi: . /s - - - sha: doc_id: cord_uid: mi gcfcw background: influencing the general public response to pandemics is a public health priority. there is a prevailing view, however, that the general public is resistant to communications on pandemic influenza and that behavioural responses to the / h n pandemic were not sufficient. using qualitative methods, this paper investigates how members of the general public respond to pandemic influenza and the hygiene, social isolation and other measures proposed by public health. going beyond the commonly deployed notion that the general public is resistant to public health communications, this paper examines how health individualism, gender and real world constraints enable and limit individual action. methods: in-depth interviews (n = ) and focus groups (ten focus groups; individuals) were conducted with community samples in melbourne, sydney and glasgow. participants were selected according to maximum variation sampling using purposive criteria, including: ) pregnancy in / ; ) chronic illness; ) aged years and over; ) no disclosed health problems. verbatim transcripts were subjected to inductive, thematic analysis. results: respondents did not express resistance to public health communications, but gave insight into how they interpreted and implemented guidance. an individualistic approach to pandemic risk predominated. the uptake of hygiene, social isolation and vaccine strategies was constrained by seeing oneself ‘at risk’ but not ‘a risk’ to others. gender norms shape how members of the general public enact hygiene and social isolation. other challenges pertained to over-reliance on perceived remoteness from risk, expectation of recovery from infection and practical constraints on the uptake of vaccination. conclusions: overall, respondents were engaged with public health advice regarding pandemic influenza, indicating that the idea of public resistance has limited explanatory power. public communications are endorsed, but challenges persist. individualistic approaches to pandemic risk inhibit acting for the benefit of others and may deepen divisions in the community according to health status. public communications on pandemics are mediated by gender norms that may overburden women and limit the action of men. social research on the public response to pandemics needs to focus on the social structures and real world settings and relationships that shape the action of individuals. conclusions: overall, respondents were engaged with public health advice regarding pandemic influenza, indicating that the idea of public resistance has limited explanatory power. public communications are endorsed, but challenges persist. individualistic approaches to pandemic risk inhibit acting for the benefit of others and may deepen divisions in the community according to health status. public communications on pandemics are mediated by gender norms that may overburden women and limit the action of men. social research on the public response to pandemics needs to focus on the social structures and real world settings and relationships that shape the action of individuals. the re-emergence of infectious diseases is a leading public health problem. pandemics and epidemics [ ] including avian influenza, sars, ebola, and pandemic influenzaand the rise of anti-microbial organisms [ ] now threaten the health of populations around the globe. it has been argued that the re-emergence of these diseases marks the end of the golden age of medicine and the dawning of a period where health and security will be undermined by resurgent infectious diseases [ ] . pandemic influenza stands out in this situation because: it spreads quickly around the globe affecting many millions of people; it is associated with, potentially, high mortality, and; the world experienced a highly publicised, though ultimately mild for most, pandemic influenza in / . it is believed that another, more serious influenza pandemic is inevitable, though no-one, as yet, can predict when it will occur. for these reasons, explaining infectious diseases threats to the general public and encouraging them to adapt their health behaviours is high on the public health agenda. in relation to pandemic influenza, public communications feature in preparedness and response planning which requires that members of the general public adopt measures during a public health emergency, including: hygiene (e.g., covering the mouth and nose when sneezing or coughing, washing hands, keeping surfaces clean, avoiding sharing personal items) and the avoidance of close contact with others [ ] . understanding how populations respond is also crucial for the science that supports response planning. for example, mathematical models, which underpin pandemic response planning, factor in biological, psychological and sociological assumptions of how populations respond to infectious diseases [ , ] . effective communications with the general public and understanding how they respond, therefore, have a pivotal role to play in the management of pandemic influenza, in particular, and in the area of emerging infectious diseases, in general. however, knowledge of how to best communicate on pandemics with the general public and how they take up these messages is an emerging field with some inconsistencies [ ] . evaluations of the public health response to the / pandemic influenza claim that public communications were largely successful in preparing and reassuring publics during the emergency [ , ] . these findings need to be read against the fact that the pandemic was a short-lived and ultimately mild public health emergency for most people. there is a view, also, that members of the general public are resistant to pandemic risk messages. some commentary has suggested that the general population is increasingly resistant to public policy on global threats, including climate change and emerging infectious diseases [ ] . surveyswhich dominate the social scientific view on public responsesconducted during the pandemic indicate that populations in the uk and australia were complacent with regard to h n and reported insufficient behavioural responses [ ] [ ] [ ] [ ] [ ] . broad brush, risk communication research has identified that material circumstances and symbolic framing of risk [ ] , inequalities in education and access to media [ ] , (mis)trust in media and governmental advice [ , ] , all shape how members of the general public respond to communications on pandemics. close-focus, qualitative research offers the view that while the general public endorses governmental advice, in the circumstances of the / pandemic they were also unlikely to act in the ways advised by governments [ , ] . there are additional explanations for the apparent resistance on the part of the general public. for example, because they are bombarded with so many messages, including those pertaining to pandemics, members of the general public may by subject to 'health threat fatigue' [ ] . this is not the same as resistance. it is, instead, a dulling of alertness seated in screening out of overwhelming and competing risk messages. members of the general public appear to digest and critically reflect on risk communications messages [ ] , and tailor risk reduction strategies to their personal circumstances [ ] . it is also argued that the general public is only too aware of the 'boy who cried wolf ' syndrome [ ] , where too frequent assertion of danger leads publics to dismiss public health warnings. in addition, audience reception of communications on health is framed by the historic rise of individualism in society [ ] and health systems [ ] . individualism implies that members of the general public take on the view that responsibility for their health is a matter of personal volition and effort. this view is often utilised in health communications that call on people to take care of themselves, but it is a perspective that can obscure factors that are not within the control of the individual. it is also an approach to risk that has a moral loading and therefore a negative effect for those who are unablethrough choice or otherwiseto avoid health harms. exactly how individualism plays out in relation to pandemic influenza warrants further inquiry. because it is so vital that public health authorities communicate with members of the general public as effectively as possible and as there are competing explanations and routes of inquiry available in the literature, it is necessary to re-examine the apparent resistance to communications and advice on the part of the general public. a central challenge is to get beyond prevailing assumptions and build up a theory of public engagement informed by the life worlds of the general public [ ] . understanding why populations fail to sufficiently enact precautions must involve taking account of how lives are lived and the meanings ascribed to the threat of infectious diseases. indeed, what might look like lack of precaution may turn out to be reasonable given the material and symbolic circumstances of affected individuals and populations. a related challenge, then, is re-examining how public health characterises the general public in research on pandemics and in the more general area of emerging infectious diseases. taking these steps is vital to ensure that the public health response and its communications with the general public are as resonant, meaningful and effective as possible. this paper, therefore, uses inductive, qualitative research methods to develop new knowledge on how members of the general population respond to pandemic influenza, set against the backdrop of the assumed resistance on the part of the general public and related critiques, including, health risk fatigue, the risk communication dilemma and individualism. the analysis poses the question: how do members of the general public respond to the threat of pandemic influenza and to the hygiene, social isolation and other measures proposed by public health? by addressing this question in the manner indicated, the paper offers an alternative framing of pandemic influenza perceptions and behaviours in an effort to contribute to the better health of individuals and populations facing risk of infectious diseases. the following analysis was generated in international research (australian research council discovery project dp ) focusing on the responses of members of the general public to the events of alongside interviews with researchers, clinicians and policy-makers [ , ] and analyses of the public policy texts on pandemic influenza control [ ] . this research has examined general public data in light of sociological and psychological perspectives on responses to pandemic influenza [ , [ ] [ ] [ ] [ ] . the present paper synthesises and builds on the research undertaken on the general public, in particular, and introduces new data analysis to address the public health challenge of effective communication and engagement with members of the general public. interview and focus group participants were recruited through community sampling in melbourne, sydney and glasgow. generating data in australia and scotland addressed the international dimension of pandemic influenza and the events of . australia was closely observed by other nations as early stages of the global pandemic in coincided with the southern hemisphere influenza season. the pandemic quickly affected melbourne, which reported a high and early peak of known infections [ , ] . the city, for a time was known as the 'flu capital of the world.' the first confirmed cases in the uk were in scotland among passengers on a flight from mexico to glasgow [ ] . the uk and australia reported [ ] and [ ] deaths, respectively, associated with the h n pandemic. our analysis of interview and focus group texts reveals more convergence than difference between melbourne, sydney and glasgow, perhaps because the pandemic was managed in those cities by public health professionals who were members of a global pandemic response network. the research aimed to identify how members of the general public respond to pandemic influenza so that public health communications can be designed to engage with how its audiences respond to risk messages and how they enact hygiene, social isolation and related measures. four purposive criteria were used to select respondents in each city: women who were pregnant during (or with a new baby); older members of the community ( years of age and older); people with compromised immune systems and or respiratory illness such as asthma; and people who self-identified as being 'healthy' (e.g., no disclosed health problems) and who did not belong to one of the former categories. in addition, selection of participants was conducted to ensure: a balance of male and female participants and a range of ages from years upwards. drawing on interviews and focus groups ensured depth and breadth. interviews explored in-depth discussion of personal experiences of living through the h n pandemic, seasonal influenza and related concerns. focus groups examined social norms concerning precautionary behaviours regarding pandemic influenza. between april and may , people participated in the research (see table ) in interviews and ten focus groups (with participants). interviews included people from the purposive criteria (pregnant = ; + = ; hiv/respiratory illness = ; healthy = ); a gender mix (women = ; men = ), and; an age range of to + years. focus groups included people from the + group ( ); hiv/respiratory illness ( ) and the healthy group ( ); a gender mix (women = ; men = ), and; an age range of to + years. this pattern of participation reflects the challenges of recruiting women who were pregnant in , the very elderly and men. seven respondents reported having been diagnosed with h n ; none through a laboratory-confirmed test (a reflection of our community sampling). a further eleven interviewees reported that a relative, friend or other social contact had been diagnosed, clinically. it needs to be acknowledged, however, that, as influenza is not ordinarily diagnosed with a laboratory confirmed test [ ] , public health professionals and members of the general public identify and manage the infection on the basis of symptoms. indeed, respondents noted difficulty determining whether they had had influenza participants were asked to speak about their experiences with influenza and the public health response to the pandemic. topics for discussion included: health background (including pre-existing medical conditions, other infectious diseases, influenza vaccination); influenza experiences (including knowledge of pandemic influenza, sources of knowledge, experiences with the pandemic and seasonal influenza, prevention of infection, caring for self and/or someone else with infection); public communications (including broadcast and electronic media, public health advice, advice from gps, workplace and schools). verbatim transcripts of interviews and focus groups were analysed using an inductive, theory-building method. all transcripts were open coded to generate themes for analysis. interpretive memoranda were generated which explained each theme and how it connected with existing perspectives on the general public response to pandemic influenza. the research team reviewed these themes and memoranda to ensure that the themes were understood and that they could withstand refutation. this discussion also provided the basis for an agreed coding scheme that was used to re-code all data. key themes were identified for subsequent, in-depth written analysis in the form of technical reports and draft manuscripts. our approach to coding, memo writing and in-depth analysis sustains a dialogue between theory (pre-existing categories derived from social science theory and the relevant literature) and data (inductively-derived themes). this approach avoids the traps of overly dataor theory-driven analysis and ensures that the research has relevance to the field. this paper, therefore, is based on in-depth, nuanced analysis of interview and focus group texts that offers new perspectives and propositions, which provide the basis for interrogating prevailing assumptions regarding the general public response to pandemic influenza. this approach is consistent with social inquiry of the highest standard [ ] . the assumed complacency and resistance on the part of members of the general public was not in evidence in the narratives provided by our research participants. other factors, centred around health individualism and contextual factors such as gender and biomedical situation do appear to influence how people respond to the threat of pandemic influenza. in what follows, we focus on themes that establish and complicate the role of health individualism and its effects in the responses of members of the general public to pandemic influenza. the interviews and focus groups revealed a tension to do with self and other in relation to the threat of pandemic influenza. as we have discussed elsewhere, respondents endorsed the pandemic control measures advocated by public health authorities [ ] . they agreed that hygiene control measures (coughing and sneezing etiquette) and social distancing were valuable. this endorsement held in australia and scotland. characteristically, however, respondents did not believe that pandemic influenza could be prevented in the long run. they believed that the influenza virus was easy to catch and that hygiene measures and social isolation were difficult given that social interaction was needed to sustain work, schooling, the family and daily life. for this reason, respondents focused on strengthening their immunity through, for example, taking vitamins and eating healthy food: i think if you're healthy, keep up your vitamins and eat the right foods, drink healthily, eat healthily and live healthily. exercise. you've got to do all those things. (heather, +, melbourne) this immunity boosting was seen as a prudent defence against the seemingly inevitable moment of exposure and a means of coping with infection when and if it occurred. importantly, this focus on one's body and immunity in the face of seemingly inevitable infection accentuated health individualism, encouraging members of the general public to focus on their body's abilities to resist and cope with infection. there was evidence that immune boosting has the status of a social norm as those who were seen to succumb to infection were sometimes judged as failing to adequately care for themselves, even though it was admitted that the virus was easy to catch. to some extent individualism is an asset for public health interventions that seek behaviour change at the individual level. however, an individualistic approach to pandemic risk may obscure factors that the individual cannot control and, as indicated by the judgement of those who acquired infection, health individualism may be moralising. health individualism was not the only factor influencing how members of the general public perceived risk for pandemic influenza and took action. respondents who had responsibilities for others (e.g., pregnant women, people in couples or caring for people with health problems, families with children) or who saw themselves as vulnerable to influenza (e.g., respiratory illness, immune disorders) focused on social units such as the couple, family and colleagues at work: well given that the flu broke out at xxxx street primary school and my son was three and he was at xxxx street childcare, i pulled him out. so when my husband picked him up that day i was at work. i said, 'take him home. give him a bath. wash his clothes.' yeah. i stopped sending him and i was one week off my maternity leave so i stopped work a week early … i didn't go to the supermarket, didn't really mix. (gill, pregnant, melbourne, - years) it appears, then, that both health individualism and relationships with important others influence what people do. in this regard, social proximity appears to be important, that is, those others who are close to oneself in terms of social and emotional ties and living situation are factored into health precautions. this social proximity also showed up in the ways in which respondents saw geographical distance and low population density as protective. those respondents living further away from the populous 'epicentres' of infectioncentral melbourne, for examplebelieved that they were less likely to encounter someone with the virus. ' we're familiar with chest infections' one important way in which this tension between responsibility to oneself and to others came to light in interviews and focus groups related to differences between the responses of those with pre-existing conditions and those who identified as 'healthy.' those who faced increased risk of serious disease focused on their relationships with othersincluding strangers they might encounter in public spaceslargely in an effort to protect themselves. those with no vulnerabilities showed themselves to be archetypally focused on their individual health. for example, people with severe respiratory illness reported that engagement with the risks of influenza was a 'well trodden path' for them: as lung patients, we're, we're familiar with chest infections and, as joy says, we could, we could have a flu and not know it. and the gp checks us over. and the only way that i know that they'll know whether it's a chest infection or flu, or pneumonia, is for an x-ray. (arthur, lung disease, melbourne, + years) people with pre-existing lung conditions, then, were commonly hyper-vigilant during the pandemic and their accounts were peppered with examples of how social interaction was imbued with risk for them and also some resentment that the healthy majority seemed to not understand the significant threat that influenza infection might pose to their health [ ] . people with immune disorders in our sampleprimarily hivunderstood they needed to be vigilant but saw influenza as a lower priority than their hiv infection and its effective management. older respondents ( +) conveyed judicious vigilance tempered with an unwillingness to be seen to overreact. important in these accounts was awareness of the vectors of transmission and that one's health was to some extent dependent on those with whom one interacted. in contrast, the healthy majority of our respondents saw pandemic influenza as a personal, though distant, health threat. they saw themselves 'at risk' and possibly as 'a risk' to close family, but not as 'a risk' to unknown others (e.g. a person sitting beside them on public transport). this focus on the 'at risk' self to the exclusion of the self as 'a risk' to others underlines how health individualism manifests in the responses of the 'healthy' majority of the general public. this focus of the healthy on their own health risks (at the expense of others) surfaced in narrative on expectations of recovery from influenza: like you sort of just, you think, maybe you just think influenza as a common cold sort of thing. and it's like, 'it'll pass. i might go to the doctor's and get some, something to help me get through it, ' or something. but yeah, i don't know … it's just like, 'just ignore it and push through.' (chris, healthy, melbourne, - years) this interview participant shows how a healthy individual engages with pandemic influenza as a commonplace and personal risk, in contrast to those with pre-existing conditions who have to take pandemic, and even seasonal, influenza seriously. this expectation that one can 'push through' reinforces the previous theme noted with regard to the focus on the capacity of one's body to deal with infection. it is also an orientation to influenza risk that sets the scene for individuals to determine that infection is a risk worth taking since recovery is likely. also, recovery expectations synergise with the belief that infection is difficult to avoid in the long run. this means that people may assume that, while non-pharmaceutical strategies of pandemic control are sensible, their limited utility is set against the likelihood of recovery. this nexus of risk calculation helps explain why segments of populations appear to be complacent in surveys, as noted above. they may in fact be making multi-layered risk assessments of the likelihood of infection, their health status and expectations of recovery. another important provision on health individualism was the gendered meanings of one's response to infection. particularly in domestic settings, the management of respiratory illness was largely feminised. women provided elaborate accounts of managing the respiratory infections of family members while men did not. importantly, the pejorative term 'man flu' was used to denote the over-inflation of mild symptoms to gain sympathy and respite from normal activities, with connotations of questionable masculinity: it's always a little difficult to tell when you're moving from, sort of, a cold through the man flu to proper influenza. (vincent, healthy, sydney, - years) these findings imply that responses to pandemic influenza in real world settings areas with other health problemsassociated with gender roles which shape behaviour, for example, women may be expected to perform infection control and symptom management, while men are expected to not show their symptoms and 'soldier on' or face accusations of 'man flu.' the uniform implementation of social distancing and other protective measures may therefore be compromised. accentuating the role of gender in response to messages concerning pandemic influenza, pregnant women found themselves thrust into a position of particular risk during the / pandemic, at a time when they were already taking responsibility for the well-being of their unborn child. in particular, the prospect of vaccination elicited varied, often emotion-laden, responses: well, (sigh) when you're pregnant everything is about the baby … you just want to try and make your baby as healthy as possible and you want to try and keep your baby safe. (rebecca, pregnant in , glasgow, - years) the imperatives of good motherhood and responsibility for their unborn children placed these women into the emotionally-charged position of having to make decisions regarding virus protection in circumstances of intense uncertainty [ ] . some distress was apparent among the pregnant women respondents, but also great resilience and active use of public policy information to protect themselves and their babies. as rebecca's account, above, indicates, health individualism in tension with responsibilities to others, gender and one's life situation played out in engagements with vaccination. though recollection was variable, respondents in the present research ( %) reported that they had had an influenza vaccination at some point in their lifetime and there was no evidence of 'in principle' resistance to vaccination. this is a notable finding given that participants were sought in community settingswhere those with anti-vaccine views are thought to be locatedand in light of commentary that members of the general public are resistant to the science and technology used to manage global threats. indeed, endorsement of public health measures and attempted compliance characterised the respondents' accounts, with the provisos on the practical value of non-pharmaceutical strategies of infection control and management, as already discussed. but, taking on vaccination was not always straightforward: i saw in the press releases about the vaccine and i remember ringing the clinic and they said,'well if we were to give it to you, you'd have to come to the hospital and that's gonna put you at risk of getting exposed to it so we'd rather you not come in for the, for the vaccine.' and i was thinking,'well that's a bit of a catch importantly, though, vaccination, like non-pharmaceutical infection control, was mostly discussed as a personal strategy of health protection. apart from those with pre-existing vulnerabilities, vaccination was not readily understood as a method for protecting others and therefore society. this individualistic focus on one's own health implies that efforts to promote 'herd immunity' may not accord with perceptions and behaviours of the healthy majority. the findings question the prevailing view that the general public resists risk communication with regard to pandemic influenza. nor do the related ideas of complacency and fatigue seem relevant. more salient was multi-layered risk management informed by health individualism and to some extent tempered by interpersonal responsibilities, one's personal circumstances, gender, expectations of recovery, and prior experiences with influenza. as others using qualitative methods have also suggested [ ] , respondents did not reject what was done by governments in . they show interest in pandemic influenza, though their mode of engagement with it varied. they indicated that they wished to be informed but reserved the right to interpret and apply advice according to their own situation. public health guidance on hygiene and social isolation was endorsed, though its utility was largely found to have practical, long-term limitations given that social interaction was fundamental to daily life and the transmission of the virus. resistance and the related notions of complacency and fatigue, then, appear to have limited value for explaining how members of the general public respond to pandemics. part of the reason for this inapt attribution of research results to public resistance concerns research approach. forced choice surveys produce measures of hypothesised variables thought to influence behaviour. in-depth interviews and focus groups yield a different picture, where general public perceptions of the dangers of pandemics are placed in the context of what appears to be endorsement of the efforts of public health, tempered with awareness of the practical difficulties of managing influenza on a local basis. personal experience narratives reveal members of the general public to be engaged and willing to apply guidance in real world settings, though also aware of limits on what might be possible in time of pandemic. going beyond the idea of resistance, our analysis offers an alternative framing of how members of the general public respond to pandemic influenza. health individualism complicated by life circumstances (family life, health status) and the gendering of the meanings and practices surrounding the experience of influenza and how to deal with it in real world settings, appear to be important. risk communications are likely to benefit by addressing these influences on risk management behaviours. in particular, emphasising individual responsibility in risk communication may amplify divisions between people with different biomedical vulnerabilities and encourage those who consider themselves healthy to think of themselves as 'at risk' but not 'a risk' to others. this is a major hurdle for public health, particularly when hygiene, social isolation and vaccination are likely to become more important methods for controlling the spread of re-emerging infectious diseases. the pejorative, gendered meanings of influenza, of which 'man flu' stands as exemplary, point towards the deeply inscribed gendering of responses to infectious diseases. the role of gender in social aspects of health care is no surprise, but fully-fledged gender analysis is yet to be acknowledged in the public health address to the general population with regard to pandemics. in particular, messages to enact hygiene and social isolation are likely to accentuate already feminised health care in the domestic sphere. further, it is not simply that women are burdened with the labour of influenza care and men not. if men do find themselves unwell they risk accusations of 'man flu' and may therefore avoid making themselves available for health care interventions, a dynamic which keeps men out of the gp clinic in general [ ] . as recent reviews have indicated [ , ] , the influences of social factors on responses to pandemics need to be foregrounded in the social research agenda for better public health. our research indicates that health individualism and gender need to be part of this new research agenda. our findings also point to several further, specific, challenges for risk communication: ideas of proximity to risk; expectations of recovery, and; vaccination. proximity appears to be a blind spot in risk communications. public health messages of emergency are filtered by perceptions of proximity to threat, consistent with psychological theory [ ] and cultural constructs where the source of contagion is placed at a distance from self [ ] . we found that these ideas of proximity did surface in the narratives of members of the general public. yet, we know that, for example, within six weeks of the infection being detected in australia, people in remote communities in australia were found to be infected [ ] . risk communication needs to attend to these ideas of distance from risk and the related underestimation of the speed with which the influenza virus can travel in a hyper-connected world. expectations of recovery from influenza also appear to dominate narratives. as others have argued [ ] , healthy respondents recognised influenza infection as severerequiring bed and restbut thought that they would eventually recover. this finding implies that members of the general public may interpret infection as a risk worth taking, that is, that they can cope with infection if prevention fails them, due to their own choices or otherwise. members of the general public appear to be actively engaged with manifold risks that they juggle and prioritise in real world settings. our findings also suggest that taking up vaccination is not a simple matter, even among those who endorse the use of the biotechnology. survey findings have found that approximately % of australians are concerned about general vaccine safety [ ] and that australian [ ] and worldwide [ ] rates of h n vaccination have been found to be insufficient, prompting concerns that the 'anti-vaccine lobby' and other detractors are influencing use of this biotechnology. as noted, a slight majority of our respondents reported that they had been vaccinated in their lifetime and none spoke of vaccination as dangerous, though, of course, some may have held these views and not revealed them or opted out of our community-based recruitment strategies. our research, however, points to more immediate and practical considerations that shape how and when people vaccinate, including considerations of relative risk and whether or not a new vaccine should be used in pregnancy. attending to these more immediate concerns may be beneficial for public health, though we acknowledge that public perception of vaccine technologies is also an important public health agenda. the analysis presented is retrospective as the interviews and focus groups were conducted after the end of the pandemic on august [ ] , and therefore when it was known that the mortality rate had at first been overestimated [ ] . importantly, too, the respondents were volunteers selected according to purposive criteria, implying that the sample is not representative and that generalisations to populations are not strictly tenable. what the analysis offers, however, is the opportunity to drill down into how people make sense of pandemic influenza, therefore providing the basis for building theory on how members of the general public, think, feel and act in the contemporary era of efforts to manage global health threats. the perspectives identified here help situate what we know in social context and alert public policy to some dilemmas and alternative explanations of why members of the general public do what they do. for public health to shape the actions people take prior to and during a pandemic, we need to understand and engage with the perspectives of those acting. viewed from the outside, the behaviour of the general public has been cast as resistant. however, viewed from the perspective of ordinary people involved in anticipating and responding to infection, it is clear that public health has engaged its publics. this engagement is frequently informed by individualistic ways of assessing and responding to risk, social norms (e.g. gender roles), knowledge of the clinical uncertainties of influenza infection, and reasoned thinking about the limits of preventing influenza transmission. the current challenge for pandemic influenza preparedness and response is not so much to address public disinterest, but to acknowledge and engage with members of the general publics' experiences of influenza and how they make sense of, and act on, pandemics in real world settings. factors in the emergence of infectious diseases antibiotic resistance: long-term solutions require action now world health organization. the world health report : a safer future: global public health security in the st century the effect of public health measures on the influenza pandemic in u.s. cities strategies for containing an emerging influenza pandemic in southeast asia unresolved issues in risk communication research: the case of the h n pandemic influenza pandemic: an independent review of the uk response to the influenza pandemic report of the review committee on the functioning of the international health regulations ( ) in relation to pandemic (h n ) . report by the director-general. geneva: world health organisation special report: living in denial public perceptions, anxiety, and behaviour change in relation to the swine flu outbreak: cross sectional telephone survey the impact of communications about swine flu (influenza a hiniv) on public responses to the outbreak: results from national telephone surveys in the uk the community's attitude towards swine flu and pandemic influenza why do i need it? i am not at risk! public perceptions towards the pandemic (h n ) vaccine university life and pandemic influenza: attitudes and intended behaviour of staff and students towards pandemic (h n ) what have we learned about communication inequalities during the h n pandemic: a systematic review of the literature lessons from the pandemic: the need for new tools for risk and outbreak communication the challenge of providing the public with actionable information during a pandemic public views of the uk media and government reaction to the swine flu pandemic public responses and reflexivity during the swine flu pandemic in australia public apprehension of emerging infectious diseases: are changes afoot? understanding responses to government health recommendations: public perceptions of government advice for managing the h n (swine flu) influenza pandemic immunity, biopolitics and pandemics: public and individual responses to the threat to life biocommunicability and the biopolitics of pandemic threats individualisation: institutionalised individualism and its social and political consequences healthy living and citizenship: an overview we had to do what we thought was right at the time': retrospective discourse on the h n pandemic in the uk. sociol health illn australia's pandemic influenza 'protect' phase: emerging out of the fog of pandemic compliant, complacent or panicked? investigating the problematisation of the australian general public in pandemic influenza control we became sceptics": fear and media hype in general public narrative on the advent of pandemic influenza understanding pandemic influenza behaviour: an exploratory biopsychosocial study biography, pandemic time and risk: pregnant women reflecting on their experiences of the influenza pandemic. health (london) mobilising "vulnerability" in the public health response to pandemic influenza pandemic (h n ) influenza community transmission was established in one australian state when the virus was first identified in north america pandemic (h n ) risk for frontline health care workers swine flu confirmed in the uk. in: the guardian australian government department of health and ageing. review of australia's health sector response to pandemic (h n ) : lessons identified. canberra: commonwealth of australia influenza symptoms and the role of laboratory diagnosis making social science matter: why social inquiry fails and how it can succeed again my wife ordered me to come!': a discursive analysis of doctors' and nurses' accounts of men's use of general practitioners a protection motivation theory of fear appeals and attitude change contagious: cultures, carriers, and the outbreak narrative remote community not in quarantine despite nation's first swine-flu death representations of influenza and influenza-like illness in the community-a qualitative study adult vaccination survey: summary results. cat. no. phe the - influenza pandemic: effects on pandemic and seasonal vaccine uptake and lessons learned for seasonal vaccination campaigns world health organization. h n in post-pandemic period: director general's opening statement a virtual press conference influenza a(h n ): lessons learned and preparedness submit your next manuscript to biomed central and take full advantage of: • convenient online submission • thorough peer review • no space constraints or color figure charges • immediate publication on acceptance • inclusion in pubmed, cas, scopus and google scholar • research which is freely available for redistribution submit your manuscript at www this research was funded by an australia research council discovery project grant (dp ) with additional funding from glasgow caledonian university. we are grateful to casimir macgregor for assisting with interviews and to everyone who agreed to participate in interviews and focus groups. the authors declare that they have no competing interests.authors' contributions md helped conceive of this research, drafted this manuscript, managed the data collection and analysis in melbourne and integration with all data, and is a grantholder. ns helped conceive of this research, contributed sociology of public health perspectives to the manuscript and edited it, managed data collection and analysis in sydney and integration with all data, and is a grantholder. dl collected and analysed data used in this paper, conducted a literature review used in this paper, and contributed to the draft manuscript. ew collected and analysed data used in this paper and contributed to the draft manuscript. pf helped conceive of this research, contributed health psychology perspectives to the manuscript and edited it, managed data collection and analysis in glasgow, and is a grantholder. all authors read and approved the final manuscript. key: cord- -lfdvl a authors: singer, b. j.; thompson, r. n.; bonsall, m. b. title: the effect of the definition of 'pandemic' on quantitative assessments of infectious disease outbreak risk date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: lfdvl a in the early stages of an outbreak, the term 'pandemic' can be used to communicate about infectious disease risk, particularly by those who wish to encourage a large-scale public health response. however, the term lacks a widely accepted quantitative definition. we show that, under alternative quantitative definitions of 'pandemic', an epidemiological metapopulation model produces different estimates of the probability of a pandemic. critically, we show that using different definitions alters the projected effects on the pandemic risk of key parameters such as inter-regional travel rates, degree of pre-existing immunity, and heterogeneity of transmission rates between regions. our analysis provides a foundation for understanding the scientific importance of precise language when discussing pandemic risk, illustrating how alternate definitions affect the conclusions of modelling studies. this serves to highlight that those working on pandemic preparedness must remain alert to the variability in the use of the term 'pandemic', and provide specific quantitative of analysis that we show to be sensitive to the pandemic definition. in the early stages of an infectious disease outbreak, it is important to determine whether the pathogen responsible may go on to cause an epidemic or a pandemic [ ] [ ] [ ] [ ] [ ] . there is extensive literature on determining the probability of a major epidemic given a small population of initial infected hosts [ ] [ ] [ ] [ ] . this research has produced a natural mathematical definition of an epidemic, based on the bimodal distribution of outbreak sizes given by simple epidemiological models when r is larger but not close to one [ ] . the term 'pandemic' has no corresponding theoretical definition, and there is no consensus mathematical approach to determining the probability of a pandemic. in this study, we examine how alternative definitions of 'pandemic' affect quantitative estimates of pandemic risk assessed early in an infectious disease outbreak. the term 'pandemic' is used extensively, appearing in phrases such as 'pandemic preparedness' [ ] [ ] [ ] , 'pandemic influenza' [ ] [ ] [ ] , and 'pandemic potential' [ ] [ ] [ ] . a google scholar search returns , results using the term 'pandemic' for alone. the international epidemiology association's dictionary of epidemiology defines a pandemic as "an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and usually affecting a large number of people" [ ] . notably this definition makes an explicit reference to national there is little in common between all disease outbreaks that have been referred to as pandemics, except that they have a wide geographical extension [ ] . these kinds of differences between pandemic definitions can often go unnoticed, but in certain circum- stances they can cause confusion between different stakeholders (e.g. between scientists and governments, or governments and the public), who may not have a shared background understanding of the term. in , the world health organisation (who) declared a pandemic of h n influenza, using criteria related to the incidence and spread of the virus in different who regions [ ] . the criteria did not include reference to of novel viruses [ ] . others treat the spread of a pathogen at a pandemic level as a context in which to study transmission dynamics, without paying special attention to how those dynamics lead to a pandemic as distinct from an epidemic or a more limited outbreak [ ] [ ] [ ] . in this paper, we examine the effects of alternate pandemic definitions on the analysis of key epidemiological questions. the results provide a foundation for deciding the appropriate quantitative definition of 'pandemic' in a given context. we make use of a metapopulation model to investigate the effects of pandemic definition on the results of a quantitative assessment of the probability of a pandemic. metapopulation models are commonly applied to pathogens that spread between regions of the world, and so are appropriate for modelling pandemics [ ] [ ] [ ] [ ] [ ] [ ] . we explore two different kinds of pandemic definition, following morens et al. [ ] , specifically: • the family of transregional definitions, where a pandemic is defined as an outbreak in which the number of regions experiencing epidemics meets or exceeds some threshold number n. we refer to specific transregional definitions as n-region transregional definitions, e.g. a -region transregional definition. • the interregional definition, where a pandemic is defined as an outbreak in which two or more non- adjacent regions experience epidemics. note that these definitions require a specific sense of 'region'. these regions could be countries, or they could be larger or smaller than individual countries-from counties to health zones to who regions. our metapopulation model (detailed in the methods section below) can be used to model regions of any size. we have chosen not to include definitions with criteria relating to the number of people infected or killed, instead of, or in addition to, geographical extension. extension is the only universal factor in pandemic definitions, and so is the focus of the current study [ ] . three questions that feed into public health policy at the beginning of an outbreak are: • would interventions restricting travel reduce the risk of a pandemic? • does a portion of the population have pre-existing immunity, and does this affect pandemic risk? whose connections and weighting can be set at fixed values representing the rates of travel between regions. we choose the simplest networks that can illustrate the effects of our different pandemic definitions-namely, the star network, in which one central region is connected to all others with equal weighting and the non- central regions lack any other connections, and the fully connected network, in which each region is connected to every other with equal weighting. figure illustrates that the connectivity of the full network is much higher than that of the star network. using the star network allows us to make the distinction between adjacent and non-adjacent regions, thus allowing us to distinguish between transregional and interregional pandemic definitions. unless otherwise stated, all figures in the current study are generated with a transmission rate of β = . per day, a recovery rate of µ = . per day, and an inter-regional travel rate of × − per day. this : pandemic probability for a range of between-region transmission rates and a range of pandemic definitions in terms of number of regions experiencing epidemics. the "pandemic threshold number" refers to the minimum number of regions that must experience epidemics before a pandemic is declared. pandemic probability is, in general, sensitive to the pandemic definition used, but the degree of sensitivity depends on network structure and travel rates. a) pandemic probability for a star network. pandemic probability is, in general, highly sensitive to the pandemic definition used. b) pandemic probability for a fully connected network. the sensitivity of pandemic probability to the pandemic definition used is significantly reduced at high travel rates. we can also look at the difference in pandemic probability between the transregional and interregional is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted october , . . per day. in the full network there is sudden transition from higher risk to lower risk, as cross-immunity approaches one. however, in the star network there is less circulation of the initial pathogen, so the effect of cross-immunity is less dramatic. increased cross-immunity can also increase the difference in risk for different pandemic definitions-for the fully connected network, once cross-immunity reaches around α = . , differences in probability between different thresholds become visible that are much smaller at lower values. this suggests that the declaration of a pandemic may be more sensitive to the exact pandemic definition for outbreaks of pathogens that encounter pre-existing immunity than for pathogens which encounter only fully susceptible populations. however, this effect is not seen for the star network, in which the low connectivity of the network results in larger differences in probability between different thresholds even at low cross- immunity. a topic of great concern during a pandemic is heterogeneity in risk between different countries or regions [ , ]. cross-immunity can create one kind of heterogeneity, since it is common for previous exposure to a pathogen to differ between regions. another kind of heterogeneity is that due to different public health is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted october , . . the second question was "does a portion of the population have pre-existing immunity, and does this affect pandemic risk?" the presence of immunity can significantly alter the results discussed in the paragraphs above. in figure b , the leftmost column is equivalent to the column from figure b in which λ = . × − per day. however, as cross-immunity increases, a marked difference in the pandemic pro- bability between different definitions becomes visible. this shows that the conclusion that precise pandem- ic definitions are of reduced importance in a highly connected network with high travel rates is context sensitive-if the population has high immunity, differences between definitions re-emerge. the third question was "how is the risk of a pandemic affected by differences between regions?" in figure is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted october , . is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted october , . to determine how the final probabilities of epidemics depend on the pairwise probabilities qjm, we use a markov chain. the states of this markov chain assign one of three states to each region-n (for neutral), where it is not yet determined whether the region will experience an epidemic, e (for epidemic), where it is determined that the region will experience an epidemic but it is not yet determined in which further regions it will cause epidemics, and t (for terminal), where it is determined that the region will experience an epidemic and in which further regions it will cause epidemics due to onward transmission. as our model the initial probability of each global state z z ...zn (where zi ∈ {n, e, t }) is given by: where qj = min(( /r ,j) i j ( ) , ) is the probability that the initial population of infective individuals does is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted october , . . https://doi.org/ . / . . . doi: medrxiv preprint initial global state is given by the product of the probabilities of each region being in the corresponding initial regional state. in this system, all states in which no region is epidemic are absorbing, and in each transition at least one epidemic state must become terminal. this means that the system must reach an absorbing state in at most n transitions, since at least one region becomes terminal in each transition, and a fully terminal state is absorbing. so the final probability vector p final is given by with t as the transition matrix and p initial as the vector whose elements defined by equation ( ) the model described above can incorporate certain epidemiological details, such as heterogeneity of popu- lation parameters, but is restricted to treating quite simple disease dynamics. in this section we expand the model to treat pathogens that give those who overcome infection cross-protection against future strains of that pathogen. this is necessary to be able to investigate how pre-existing immunity changes how pandemic definitions affect the results of our model. we first describe the spread of a pathogen strain x using the methods above, introducing a superscript x to the relevant parameters to mark the strain, e.g. r x , r x (∞), and p x final . we assume that infection with pathogen x confers cross-immunity α to a second strain of the pathogen, which we call y . in each population pj we can define an effective basic reproductive number for y in the case that pj has experienced an epidemic of x, which we call r y e,j . this expression simply multiplies the basic reproductive number by the effective number of susceptible individuals given the prevalence of cross-immunity in the population. it is through this expression that cross-immunity enters the model-the parameter α does not otherwise appear in what follows. we can write down an equation for the expected total number of individuals in pj infected in an epidemic of y in analogy to equation ( ). in the case where there has been no previous epidemic of x in pj, the expected epidemic size is the solution r y j,nox (∞) of in the case where there has been a previous epidemic of x in pj, the expected epidemic size is the solution we assume that individuals infected with y travel at the same rate as individuals infected with x. we then define the pairwise probabilities of transmission of y between populations in analogy to equation ( ). that is, is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted october , . . https://doi.org/ . / . . . doi: medrxiv preprint where r y c,m = r y ,m when pm has not experienced a previous epidemic of x, r y c,m = r y e,m when pm has experienced a previous epidemic of x, r y b,j (∞) = r y nox,j (∞) when pj has not experienced a previous epidemic of x, and r y b,j (∞) = r y x,j (∞) when pj has experienced a previous epidemic of x. these expressions for q y jm can be substituted for qjm in equation ( ) to yield a transition matrix for modelling the spread of y , which we will call t y (s s ...sn), where sj is the final state (either n or t ) of the x outbreak in pj. we find the initial probabilities of each state with regards to y , p y initial , in analogy to equation ( ), given an initial number of individuals infected with y in each population i y j (∞). to find the overall probability of each combination of epidemics of y in various populations given a prior probability of each combination of epidemics of x (given by p x final (s s ...sn) defined in equation ( ) is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted october , . . https://doi.org/ . / . . . doi: medrxiv preprint characteristics of microbes most likely to cause pandemics and global catastrophes novel coronavirus outbreak in wuhan, china, : intense surveillance is vital for preventing sustained transmission in new locations effects of population density on the spread of disease spread of infectious disease through clustered populations how big is an outbreak likely to be? methods for epidemic final- size calculation threshold behaviour and final outcome of an epidemic on a random network with household structure will an outbreak exceed available resources for control? estimating the risk from invading pathogens using practical definitions of a severe epidemic community-based pandemic preparedness: covid- procedures of a manitoba first nation community modeling the worldwide spread of pandemic influenza: baseline case and containment interventions increased frequency of travel in the presence of cross-immunity may act to decrease the chance of a global pandemic pandemic potential of -ncov. the lancet infectious diseases interhuman transmissibility of middle east respiratory syndrome coronavirus: estimation of pandemic risk world health organization aids in the last years the spread, treatment, and prevention of hiv- : evolution of a global pandemic what is a pandemic? coronavirus disease (covid- ) press conference forecast and control of epidemics in a globalized world resurgent epidemics in a hierarchical metapopulation model the role of the airline transportation network in the prediction and predictability of global epidemics seven challenges for metapopulation models of epidemics, including households models forecasting the spatial transmission of influenza in the united states empirical evidence for the effect of airline travel on inter-regional influenza spread in the united states effectiveness of travel restrictions in the rapid containment of human influenza: a systematic review health organization dynamics of annual influenza a epidemics with immuno-selection response to ebola in the us: misinformation, fear, and new opportunities assessing the international spreading risk associated with the asymptomatic transmission, the achilles' heel of current strategies to control covid- severe acute respiratory syndrome coronavirus (sars-cov- ) and coronavirus disease- (covid- ): the epidemic and the challenges infectious disease surveillance and modelling across geographic frontiers and scientific specialties human mobility and time spent at destination : impact on spatial epidemic spreading transmission dynamics and final epidemic size of ebola virus disease outbreaks with varying interventions key: cord- -j qperwz authors: lallie, harjinder singh; shepherd, lynsay a.; nurse, jason r. c.; erola, arnau; epiphaniou, gregory; maple, carsten; bellekens, xavier title: cyber security in the age of covid- : a timeline and analysis of cyber-crime and cyber-attacks during the pandemic date: - - journal: nan doi: nan sha: doc_id: cord_uid: j qperwz the covid- pandemic was a remarkable unprecedented event which altered the lives of billions of citizens globally resulting in what became commonly referred to as the new-normal in terms of societal norms and the way we live and work. aside from the extraordinary impact on society and business as a whole, the pandemic generated a set of unique cyber-crime related circumstances which also affected society and business. the increased anxiety caused by the pandemic heightened the likelihood of cyber-attacks succeeding corresponding with an increase in the number and range of cyber-attacks. this paper analyses the covid- pandemic from a cyber-crime perspective and highlights the range of cyber-attacks experienced globally during the pandemic. cyber-attacks are analysed and considered within the context of key global events to reveal the modus-operandi of cyber-attack campaigns. the analysis shows how following what appeared to be large gaps between the initial outbreak of the pandemic in china and the first covid- related cyber-attack, attacks steadily became much more prevalent to the point that on some days, or unique cyber-attacks were being reported. the analysis proceeds to utilise the uk as a case study to demonstrate how cyber-criminals leveraged key events and governmental announcements to carefully craft and design cyber-crime campaigns. the coronavirus pandemic which started in quickly became a global crisis event, resulting in the mass quarantine of s of millions of citizens across numerous countries around the world. at the time of writing, the world health organisation (who) coronavirus disease (covid- ) dashboard reported over . million confirmed cases and in excess of , deaths[ ] globally. as covid- spread across the globe, it also led to a secondary significant threat to a technology-driven society; i.e., a series of indiscriminate, and also a set of targeted, cyber-attacks and cyber-crime campaigns. since the outbreak, there have been reports of scams impersonating public authorities (e.g., who) and organisations (e.g., supermarkets, airlines)[ , ], targeting support platforms [ , ] , conducting personal protection equipment (ppe) fraud [ ] and offering covid- cures [ , ] . these scams target members of the public generally, as well as the millions of individuals working from home. working at home en-masse has realised a level of cyber security concerns and challenges never faced before by industry and citizenry. cybercriminals have used this opportunity to expand upon their attacks, using traditional trickery (e.g., [ ] ) which also prays on the heightened stress, anxiety and worry facing individuals. in addition, the experiences of working at home revealed the general level of unpreparedness by software vendors, particularly as far as the security of their products was concerned. cyber-attacks have also targeted critical infrastructure such as healthcare services [ ] . in response to this, on april th , the united kingdom's national cyber security centre (ncsc) and the united states department of homeland security (dhs) cybersecurity and infrastructure security agency (cisa) published a joint advisory on how cyber-criminal and advanced persistent threat (apt) groups were exploiting the current covid- pandemic [ ] . this advisory discussed issues such as phishing, malware and communications platform (e.g., zoom, microsoft teams) compromise. what is arguably lacking here and in research, however, is a broader assessment of the wide range of attacks related to the pandemic. the current state of the art is extremely dispersed, with attacks being reported from governments, the media, security organisations and incident teams. it is therefore extremely challenging for organisations to develop appropriate protection and response measures given the dynamic environment. in this paper we aim to support ongoing research by proposing a novel timeline of attacks related to the covid- pandemic. this timeline and the subsequent analysis can assist in understanding those attacks and how they are crafted, and as a result, to better prepare to confront them if ever seen again. our timeline maps key cyber-attacks across the world against the spread of the virus, and also measures such as when lockdowns were put in place. the timeline reveals a pattern which highlights cyber-attacks and campaigns which typically follow events such as announcements of policy. this allows us to track how quickly cyber-attacks and crimes were witnessed as compared to when the first pandemic cases were reported in the area; or, indeed, if attacks preempted any of these events. we expand the timeline to focus on how specific attacks unfolded, how they were crafted and their impact on the uk. to complement these analyses, we reflect more broadly on the range of attacks reported, how they have impacted the workforce and how the workforce may still be at risk. in many ways this timeline analysis also forms a key contribution of our work both in terms of the chronological sequencing of attacks and the representation of campaigns using an accepted attack taxonomy. this therefore provides a platform which aligns with current literature and also provides the foundation which other research can easily build on. this paper is structured as follows. section ii reflects on relevant cyber-attack and cyber-crime literature, and considers how opportunistic attacks have emerged in the past due to real-life crises/incidents. we then present our covid- -related cyber-attack timeline in section iii as well as a dedicated focus on the united kingdom as a case study of key-cyber-criminal activity. this is followed by a broader reflection on the attacks (those within and outside of the timeline). in section iv we discuss the impact of attacks on those working from home and wider technology risk. section v concludes the paper and outlines directions for future work. with the broad adoption of digital technologies many facets of society have moved online, from shopping and social interactions to business, industry, and unfortunately, also crime. the latest reports establish that cybercrime is growing in frequency and severity [ ] , with a prediction to reach $ trillion by (up from $ trillion in ) [ ] and even take on traditional crime in number and cost [ , ] . due to its lucrative nature [ ] and low risk level (as cyber-criminals can launch attacks from anywhere across the globe), it is clear that cybercrime is here to stay. cyber-crime, as traditional crime, is often described by the crime triangle [ ] , which specifies that for a cybercrime to occur, three factors have to exist: a victim, a motive and an opportunity. the victim is the target of the attack, the motive is the aspect driving the criminal to commit the attack, and the opportunity is a chance for the crime to be committed (e.g., it can be an innate vulnerability in the system or an unprotected device). other models in criminology, such as routine activity theory (rat) [ ] and the fraud triangle [ ] use similar factors to describe crimes, with some replacing the victim by the means of the attacker, which it can be considered otherwise as part of the opportunity. while attacks today have become more sophisticated and targeted to specific victims depending on attacker's motivation, for example for financial gain, espionage, coercion or revenge; opportunistic untargeted attacks are also very prevalent. we define "opportunistic attacks" as attacks that select the victims based on their susceptibility to be attacked [ ] . opportunistic attackers pick-up victims that have specific vulnerabilities or use hooks, usually in the form of social engineering, to create those vulnerabilities. thus, we define as hook any mechanism used to mislead a victim into falling prey of an attack. these hooks take advantage of distraction, time constraints, panic and other human factors to make them work [ , ] . when victims are distracted by what grabs their interest/attention or when they are panicked, they are more susceptible to be deceived. similarly, time constraints put victims under more pressure which can lead to mistakes and an increased likelihood to fall victim to scams and attacks. other examples include work pressure, personal change of situation, medical issues, or events that cause deep and traumatic impact in the whole society in general such as fatalities and catastrophes. opportunistic attackers always seek to maximise their gain, and therefore, will wait for the best time to launch an attack where conditions fit those mentioned above. a natural disaster, ongoing crisis or significant public event are perfect cases of these conditions [ ] . in the past, several opportunistic attacks have been observed that took advantage of specific incidents; below, we provide few examples: • natural disasters: in hurricane katrina caused massive destruction in the city of new orleans and surrounding areas in the usa [ ] . not long after, thousands of fraudulent websites appeared appealing for humanitarian donations, and local citizens received scam emails soliciting personal information to receive possible payouts or government relief efforts. similar scams and attacks have been witnessed in countless natural disasters since, such as the earthquakes in japan and ecuador in [ ] , hurricane harvey in [ ] , or the bush fires in australia in [ ] . • notable incidents or events: on th june , the tragic death of michael jackson dominated news around the world. only hours after his demise, spam emails claiming knowing the details of the incident were circulating online [ ] . waves of illegitimate emails echoing the fatality appeared soon after, containing links promising access to unpublished videos and pictures or jackson's merchandise, that in reality were linked to malicious websites, or emails with malware infected attachments [ ] . noteworthy public events also attract a range of cyber-crime activities. during the fifa world cup in for instance, there were various attempts to lure individuals with free tickets and giveaways [ ] . these were, in fact, scams leading to fraud. • security incidents: in , million of email addresses and passwords were exposed in a linkedin data breach [ ] . this data was not disclosed until years later, , when it appeared for sale in the dark market. soon after that, opportunistic attackers began to launch a series of attacks. many users experienced scams, such as blackmail and phishing, and some compromised accounts that had not changed their passwords since the breach, were used to send phishing links via private message and inmail [ ] . considering the variety of scams and cyber-attacks occurring around the events above, it is unsurprising that similar attacks have emerged during the ongoing covid- pandemic. the outbreak has caused mass disruption worldwide, with people having to adapt their daily routines to a new reality: working from home, lack of social interactions and physical activity, and fear of not being prepared [ , ] . these situations can overwhelm many, and cause stress and anxiety that can increase the chances to be victim of an attack. also, the sudden change of working contexts, has meant that companies have had to improvise new working structures, potentially leaving corporate assets less protected than before for the sake of interoperability. since the covid- started, the numbers of scams and malware attacks have significantly risen [ ] , with phishing being reported to have increased by % in march [ ] . during april , google reportedly blocked million malware and phishing emails related to the virus daily [ ] . to increase likelihood of success, these attacks target sale of goods in high demand (e.g., personal protection equipment (ppe) and coronavirus testing kits and drugs), potentially highly profitable in-vestments in stocks related to covid- , and impersonations of representatives of public authorities like who and aid scams [ , ] . brute force attacks on the microsoft remote desktop protocol (rdp) systems have increased as well [ ] , signaling attacks also on technology, not only on human aspects. it is clear then that attackers are trying the make the most of the disruption caused by pandemic, particularly given it continues to persist. as a consequence, several guidelines and recommendations have also been published to protect against attacks [ , , ] . these guidelines are imperative for mitigating the increasing threat, but to strengthen their basis, there first needs to be a core understanding of the cyber-attacks being launched. this paper seeks to address this gap in research and practice by defining a timeline of cyber-attacks and consideration of how they impact citizens and the workforce. the cyber-crime incidents erupting from the covid- pandemic pose serious threats to the safety and global economy of the world-wide population, hence understanding their mechanisms, as well as the propagation and reach of these threats is essential. numerous solutions have been proposed in the literature to analyse how such events unfold ranging from formal definitions to systemic approaches reviewing the nature of threats [ , , ] . while these approaches enable the categorisation of the attack, they often lack the ability to map larger, distributed events such as the ones presented in this manuscript, where numerous events stem from the pandemic are, however, unrelated. to this end, we opted for temporal visualisation, enabling us to map events without compromising the narrative [ ] . furthermore, this type of visualisation is used across the cyber-security domain to represent consequent cyberattacks [ , , ] . in this section, we outline the methodology used to create the timeline. we explain the search terms used to gather relevant covid- cyber-attack data, the data sources (search engines) utilised, the sources of information we chose to focus on, and types of attack. we also acknowledge the potential limitations of the work. ) nomenclature: we explore a range of cyberattacks which have occurred during the covid- pandemic. the novel coronavirus has been referred to by several different terms in the english-speaking world, including coronavirus, covid , covid- , -ncov, and sars-cov- . we use the term covid- to refer to the virus, which falls in line with terminology used by the world health organization [ ] . ) construction of the timeline: to aid in the construction of the timeline, we initially conducted a number of searches to identify cyber-attacks associated with the pandemic. these cyber-attacks were categorised by attack type, delivery method, and were ordered by date. the information gathered has been collated and is presented in figure which serves as a baseline for the construction of table i . information presented in the timeline includes the date china alerted the who about the virus, the date the pandemic was officially declared, and cyber-attacks which specifically relate to hospitals or medicine. additionally, key countries involved in the pandemic were identified, and for those, we present the first identified case, the date lockdown was implemented, and the first cyber-attack they suffered. the table seeks to examine a sub-set of the information from the timeline. furthermore, we have chosen to include a number of sources offering reports of attacks. the sources are a mixture of reputable news outlets (such as reuters, and the bbc), blog articles, security company reports, and social media posts. though blog articles and social media posts are not considered to be an academic source, in the context of this research where we are examining an emerging threat, they offer important insights into trends of cyber-attacks. it is also important to note that cyber-attacks may first be presented in these domains, before being highlighted by mainstream media outlets. with regards to the inclusion of news reports in the table of attacks and subsequent timeline, it should be acknowledged that these attacks are being presented through a journalistic lens, and as such may be written in an attempt to grab headlines. nevertheless, these reported cyber-attacks still pose a tangible threat to the general public during the covid- pandemic. the timeline seeks to provide an overview of attacks which have occurred. the state-of-the-art review of reports was performed from mid-march to mid-may . the timeline limits cyber-attacks to those experienced by st march. this is because we reached what we believed to be a saturation point comprising a sufficient number of cyber-attacks to be representative. following the conclusion of the search, the earliest reported attack was on th january [ ] , whilst the most recently listed attack in the timeline was st march [ ] . the most recently listed attack in the table was th may [ ] . the table progresses the time period a bit further as it intends to provide more detail in regards to cyber-attacks experienced during this time. sources were gathered from a number of locations. the criteria used to locate reports have been defined below and are presented in a similar way to existing reviews in cyber security literature [ , ] . the structure of the timeline is described in further detail in section iii-b. search engines: several search engines were used in the creation of the table and timeline. these were-google (us-based and dominates the search engine market share), baidu (chinese-based search provider), qwant (french-based search engine with a focus on privacy), and duckduckgo (us-based search engine with a focus on privacy). keywords used: a variety of keywords were used when collating reports of cyber-attacks. non-english terms were translated using the google translate service [ ] and additional independent sources were used as a means of validating the translation. when focussing on the virus itself, the following key words were used: sarscov- , covid, covid , coronavirus, 冠状病毒(chinese translation for coronavirus, confirmed by the world health organization [ ] ), コ ロ ナ ウ イ ル ス(japanese translation for coronavirus, confirmed by the japanese ministry of health, labour and welfare [ ] ). when searching for cyber-attacks, the following key phrases were used: 网络攻击(chinese translation means network attack [ ] or cyber attack [ ] ), サ イ バ 攻 (japanese translation for cyber attack or hacking attack [ ] ), attaque informatique (french translation for computer attack [ ] ), attacco informatico (italian translation for cyber attack [ ] ). time range: we attempted to find the earliest reported cyber-attack which was associated with the covid- pandemic. to allow for development of the timeline, and analysis of findings, mid-may was defined as a cutoff point, with the most recent news article being dated th may [ ] . exclusion criteria: although we have created a comprehensive table and timeline, a number of results were excluded from the research. these included results which a) were behind a paywall, b) required account creation before full article was displayed, c) were duplicates of existing news reports, and d) could not be translated. ) types of cyber-attacks : to guide our analysis and the creation of a timeline of covid- -related cyberattacks, we decided to define attacks based on their types. this allowed us to examine the prominence in certain types of attacks. although there exist numerous taxonomies relating to attacks and cyber-crimes (e.g., [ , , , ] ), there exists no universally accepted model [ ] . in this work therefore, we relied on the uk's crown prosecution service (cps) categorisation of fig. . cyber-dependent and cyber-enabled crimes [ ] cyber-crime. this definition includes cyber security by default and has inspired many international definitions of cyber-crime. the cps guidelines categorise cyber-crime into two broad categories: cyber-dependent and cyber-enabled crimes [ ] . a cyber-dependent crime is an offence, "that can only be committed using a computer, computer networks or other form of information communications technology (ict)" [ ] . cyber-enabled crimes are, "traditional crimes, which can be increased in their scale or reach by use of computers, computer networks or other forms of information communications technology (ict)" [ ] . these categories as well as examples of their subcategories can be seen in figure . some of the elements described by cps are often interlinked in a cyber-attack. for instance, a phishing email or text message (e.g., sms or whatsapp) might be used to lure a victim to a fraudulent website. the website then may gather personal data which is used to commit financial fraud, or it may install malware (more specifically, ransomware) which is then used to commit extortion. this notion of cyber-attack sequences is explained in further detail in section iii-b. similarly denial of service (dos) attacks are increasingly used by cyber-criminals to distract (or, act as 'smokescreens' for) businesses during hacking attempts [ , ] . in what follows, we consider the types of these attacks and reflect on how they have been launched, including any human factors or technical aspects (e.g., vulnerabilities) they attempt to exploit. phishing, or social engineering more broadly, includes attempts by illegitimate parties to convince individuals to perform an action (e.g., share information or visit a website) under the pretence that they are engaging with a legitimate party. quite often email messages are used, occasionally sms or whatsapp messages are used (referred to as smishing). pharming is similar to phishing but instead of deceiving users into visiting malicious sites, attackers rely on compromising systems (e.g., the user's device or dns servers) to redirect individuals to illegitimate sites. this type of attack is less common in general, as it requires more access or technical capabilities. financial fraud generally involves deceiving individuals or organisations using technology for some financial gain to the attacker or criminal. extortion refers to actions that force, threaten or coerce individuals to perform some actions, most commonly, releasing finances. hacking, malware and denial of service (dos) attacks are forms of crime that are often favoured by more technical attackers. hacking involves compromising the confidentiality or integrity of a system, and requires a reasonable about of skill; its techniques can involve exploiting system vulnerabilities to break into systems. malware refers to malicious software and can be used for disrupting services, extracting data and a range of other attacks. ransomware is one of the most common type of malware today [ , ] , and combines malware with extortion attempts. dos attacks target system availability and work by flooding key services with illegitimate requests. the goal here is to consume the bandwidth used for legitimate server requests, and eventually force the server offline. these types of attack provide the foundation for our analysis in the timeline and how we approach our discussion in later part of this research. ) limitations of the table: within table i , two columns referring to dates are provided. the first column "article date" refers to the date the reference was initially published. we acknowledge that in some cases, the web pages linked to the references continued to be updated with information following its inclusion with the paper. the table has been ordered by "article date" to provide a consistent chronological representation of events. we have also provided a second column,"attack date". when examining each reference, if a specific date was provided as to when the attack was executed, it was included. the rational behind including the attack date and report date is that an attack may not surface until several days after it has been carried out. ) limitations of the timeline: two types of cyberattack reports are considered within this manuscript, those which describe cyber-attacks without providing the date of the attack and those which describe cyberattacks and include the date of the perpetration. when the date of the attack is not included, the date provided in the timeline refers to the date of the publication. the rationale behind the inclusion of both types of reports is based on providing a chronological representation of events. furthermore, while the table provides an extensive overview of the threat landscape, it is by no means an exhaustive list of all the attacks carried out in relation to the pandemic, as gathering such information would not be possible in this context due to the lack and quality of reporting, the number of targeted incidents, the number of incidents targeted at the general public, the global coverage of the pandemic and the number of malicious actors carrying out these attacks. however, despite these limitations we have explored all resources available to depict the threat landscape as accurately as possible. in this section, we examine the cyber-attacks in further detail. figure provides a detailed temporal representation of the chain of key cyber-attacks induced by the covid- pandemic. the timeline includes the first reported cases in china, japan, germany, singapore, spain, uk, france, italy, and portugal and then the subsequent lockdown announcements. the timeline presents cyber-attacks categorised using the cps taxonomy described in section iii-a and abbreviated as: p:phishing (or smishing), m:malware. ph:pharming, e:extortion, h:hacking, d:denial of service and f:financial fraud. the events related to the crisis were validated against who timeline of events to ensure an accurate temporal reproduction. table i describes a number of cyber-attacks in further detail. within the table, cyber-attacks have been organised by attack date. if the attack date was not available within the reference, then the article date has been used. the target-country of each cyber-attack has been listed, alongside a brief description of the methods involved. finally, the attack type has also been classified in accordance with the cps taxonomy described earlier where it has been mentioned within the reference. both the figure and the table present specific cyberattacks and incidents and exclude: general advisories (e.g. from governmental departments), general discussions and summaries of attacks, and detailed explanations of techniques and approaches utilised by the attackers. the extent of the cyber-security related problems faced in the uk was quite exceptional, and in this section we use the uk as a case study to analyse covid- related cyber-crime. the discussion herein demonstrates that as expected and outlined above, there was a loose correlation between policy/news announcements and associated cyber-crime campaigns. the analysis presented herein focuses only on cyber-crime events specific to the uk. so for example, although many of the incidents identified in the previous section and particularly in [ ] are global cyber-attacks, the discussion herein ignores these. consequently, numerous announcements purportedly coming from reputed organisations such as who and a plethora of malware which reached uk citizens is ignored as these were not uk specific issues. indications of the extent of the uk cyber-crime incident problem experienced during the pandemic are provided by the reported level of suspect emails and fraud reported. by early may ( - - ), more than , 'suspect' emails had been reported to the national cyber security centre [ ] and by the end of may ( - - ), £ . m had been lost to covid- related scams with around , victims of phishing and / or smishing campaigns [ ] . in response, the national cyber security centre (ncsc) took down fake online shops [ ] and hmrc (her majesty's revenue and customs) took down fake websites [ ] . the timeline in figure shows a series of uk specific events and cyber-crime incidents. the timeline indicates a direct and inverse correlation between announcements and incidents. direct correlations are instances where perpetrators appear to follow announcements or events, they may have drawn on these events and carefully configured cyber-attacks around policy context. these are shown in the figure with a solid coloured connecting arrow. inverse correlations are instances where an incident has no clear correlation with an event or announcement. although inverse correlations do not appear to have a direct correlation, these may exist because a number of events were being actively highlighted in the media. for example, the issue of personal protective equipment (ppe) was in active discussion well before the uk government gave this priority consideration. similarly, the likelihood of a tax rebate scheme was in active consideration in early march before the budget announcement on - - . the first tax rebate phishing campaigns were in active circulation before the budget announcement. in both cases, we should emphasise that these are loose correlations and more work needs to be done in terms of whether a predictive model can be built using this data and data around the world as examples. on th march , the uk government made a number of important budgetary announcements [ ] which included: a £ bn emergency response fund to support the nhs and other public services in england; an entitlement to statutory sick pay for individuals advised to self-isolate; a contributory employment support allowance for self-employed workers; a £ m hardship fund for councils to help the most vulnerable in their areas; a covid- business interruption loan scheme for small firms; and the abolishment of business rates for certain companies. soon after, the government continued to make an-nouncements to support the citizenry and economy. these announcements included: a scheme to support children entitled to receive free school meals ( - - ) ; a hardship fund ( - - ) ; help for supermarkets to target vulnerable people ( - - ) ; the potential availability of home test kits ( - - ); a job retention scheme ( - - ) ; and the launch of the much awaited track and trace app ( - - ). events such as these increase the likelihood of a ) , and a charitable donation to the recipient. none of these events have associated governmental announcements or even general public speculation. examples supporting our notion of a correlation between events and cyber-security campaigns are provided in table ii and illustrated in figure . these examples indicate a loose correlation between events and cybercriminal campaigns. many of the cases outlined in table ii and figure , were very simple. potential victims were provided urls through email, sms, or whatsapp. an example of this is provided in figure . in this case, the url pointed to a fake institutional website which requests credit/debit card details. although there are elements of this process which are obviously suspicious to a more experienced computer user, for example, spelling errors (relieve instead of relief in the covid- relief scam), suspect reply email addresses and clearly incorrect urls, these are not immediately obvious to many users. the timeline shown in figure and the uk case study above creates an ideal platform through which to analyse the cyber-attacks that have occurred in light of the pandemic. from the point that the first case was announced in china ( - [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , the first reported covid- inspired cyber-attack took days. the next reported cyber-attack was days ( - - ) . from this point onwards, it is clear that the timeframe between events and cyber-attacks reduces dramatically. the cyber-attacks presented in the timeline can be further categorised as follows: • ( %) involved phishing and / or smishing • ( %) involved hacking • ( %) involved denial of service • ( %) involved malware fig. . the covid- -relieve scam [ ] • ( %) involved financial fraud • ( %) involved pharming • ( %) involved extortion whilst this analysis is useful, the sequence of events in the complete attack can also provide key attack insights. the timeline reveals these sequences and shows the complete campaign comprising of, for instance, the distribution of malware (m) through phishing (p) which steals payment credentials which are used for financial fraud (f ). we can describe this cyber-attack sequence as p,m,f. analysing cyber-attacks in this way is important because this indicates multiple points in a cyber-attack where protections could be applied. the timeline reveals the following cyber-attack sequences: this analysis does not include the sequence of events that took place in the two hacking and two denial of service incidents. it should be noted that although financial fraud is the most likely goal in most of the cyber-attacks described in the timeline, financial fraud was only recorded in the timeline where reports have clearly indicated that this was the outcome of a cyberattack. in reality, the p,m,f and p,ph,f cases are likely to be higher. figure provides a summary of the countries that were the target of early cyber-attacks during the pandemic, organised by attack date. as shown, china and the usa account for % of the attacks reported. it is also clear from table i that both of these countries were primary target from the start of the pandemic. the attacks then spread to the united kingdom and more other countries. by march however, a vast majority of the attacks are targeted at the whole world, with a reminder of attacks specifically focused at events in a single country, such as tax rebates due to covid- , or contact tracing phishing messages. it is useful to consider this in the context of uk specific cyber-attacks. this examination reveals that phishing was a component of all (n= ) the cyberattacks analysed. involved extortion as the final goal, the remaining involved financial fraud. cyberattacks comprised the sequence: p,ph,f, comprised the sequence p,f, the remaining comprised of p,e. it is notable that although an nhs malware distribution website was discovered and removed on - , none of the cyber-attacks we analysed appeared to involve malware in the same way that the global analysis reveals. there may be a number of reasons for this. launching a malware connected campaign requires more sophistication and time. there may be less opportunity to directly connect it to a specific event or announcement. the time delay between some of the announcements and the associated campaigns was remarkably short. for instance, the time delay between the lockdown announcement ( - - ) and the 'lockdown contravention fine' ( - - ) was days, and the time delay between the job retention scheme announcement ( - - ) and the job retention scam ( - - ) was also days. to reflect more generally on the cyber-attacks discovered, we can see that phishing (including smishing) were, by far, the most common based on our analysis. in total, it was involved in % of the global attacks. this is however, unsurprising, as phishing attempts are low in cost and have reasonable success rates. in the case of covid- , these included attempts at impersonating government organisations, the who, the uk's national health service (nhs), airlines, supermarkets and communication technology providers. the specific context of the attacks can be slightly different however the underlying techniques, and the end goal is identical. for instance, in one email impersonating the who, attackers attach a zip file which they claim contains an ebook that provides, "the complete research/origin of the corona-virus and the recommended guide to follow to protect yourselves and others" [ ] [ ]. moreover, they state: "you are now receiving this email because your life count as everyone lives count". here, attackers are using the branding of who, posing as helpful (the fig. . cyber-attack distribution across countries examined remainder of the email contains legitimate guidance), and appealing to people's emotions in crafting their attack email [ , ] . similar techniques can be seen in a fake nhs website created by criminals detected online, which possesses identical branding but is riddled with malware [ ] , and a malicious website containing malware which also presents the legitimate johns hopkins university covid- dashboard[ ]. it is notable that the fake who email contains spelling/grammatical errors. the discussion in section iii-c provides further specific examples of this. to further increase the likely success of phishing attacks cyber-criminals have been identified registering large numbers of website domains containing the words 'covid' and 'coronavirus' [ ] . such domains are likely to be believable, and therefore accessed, especially if paired with reputable wording such as who or centers for disease control and prevention (cdc) or key words (e.g., corona-virusapps.com, anticovid -pharmacy.com, which have been highlighted as in use [ ] ). communications platforms, such as zoom, microsoft and google, have also been impersonated, both through emails and domain names [ ] . this is noteworthy given the fact that these are the primary technologies used by millions across the world to communicate, both for work and pleasure. these facts, in combination with convincing social engineering emails, text messages and links, provide several notable avenues for criminals to attack. pharming attacks were much less common but did occur in % of cases. as can be seen table i, these often occur alongside other attacks. covid- -inspired fraud has leveraged governmental/scientific announcements to exploit the anxieties of users and seek financial benefit. from our analysis, fraud was typically committed through phishing and email attacks-we also can see this in our sequencing above. in one case, criminals posed as the cdc in an email and politely requested donations to develop a vaccine, and also that any payments be made in bitcoin [ ] . typical phishing techniques were used, but on this occasion these included requests for money: "funding of the above project is quite a huge cost and we plead for your good will donation, nothing is too small". a notable point about this particular attack is that it also ask recipients to share the message with as many people as possible. this is concerning given that people are more likely to trust emails they believe have been vetted by close ones [ ] . there were a range of other fraud attempts, largely based on threats or appeals. for instance, our analysis identified offers of investment in companies claiming to prevent, detect or cure covid- , and investment in schemes/trading options which enable users to take advantage of a possible covid- driven economic downturn [ ] . there were offers of cures, vaccines, and advice on effective treatments for the virus. the food and drugs administration (fda) issued warning letters between th march and st april to companies "for selling fraudulent products with claims to prevent, treat, mitigate, diagnose or cure" covid- [ , ] . the european anti-fraud office (olaf) has responded to the flood of fake products online by opening an enquiry concerning imports of fake products due to covid- pandemic [ ] , and in the uk, the medical and healthcare products regulatory agency (mhra) has began investigating bogus or unlicensed medical devices currently being traded through unauthorised and unregulated websites [ ] . extortion attacks were witnessed in our analysis but were less prevalent (appearing in only % of cases) compared to the others above. the most prominent case of this attack was an extortion email threatening to infect the recipient and their family members with covid- unless a bitcoin payment is made [ ] . to increase the believability of the message, it included the name of the individual and one of their passwords (likely gathered from a previous password breach). after demanding money, the message goes on to state: "if i do not get the payment, i will infect every member of your family with coronavirus". this attempts to use fear to motivate individuals to pay, and uses passwords (i.e., items that are personal) to build confidence in the criminal's message. malware related to covid- increased in prominence during the pandemic and impacted individuals and organisations across the world. as shown above, it was the second largest cyber-attack type, appearing in % of cases. vicious panda and mbr loader were the only new malware discovered in this period. the remaining malware attacks were variants of existing malware and included metaljack, rem-cos, emotet, lokibot, cxk-nmsl, dharma-crysis, netwalker, mespinoza/pysa, spymax (disguised as the corona live . app) guloader, hawkeye, formbook, trickbot and ginp. ransomware, in particular, was a notable threat and an example of such was covidlock, an android app disguised as a heat map which acted as ransomware; essentially locking the user's screen unless a ransom was paid [ ] . at the organisational level, ransomware has significantly impacted healthcare services-arguably the most fragile component of a country's critical national infrastructure at this time. attacks have been reported in the united states, france, spain and the czech republic [ , ] , and using ransomware such as netwalker. such attacks fit a criminal modus operandi if we assume that malicious actors will target areas where they believe they stand to capitalise on their attacks; i.e., health organisations may be more likely to pay ransoms to avoid loss of patient lives. interestingly there have since been promises from leading cyber-crime gangs that they will not (or stop) targeting healthcare services. in one report, operators behind clop ransomware, dop-pelpaymer ransomware, maze ransomware and nefilim ransomware stressed that they did not (normally) target hospitals, or that they would pause all activity against healthcare services until the virus stabilises [ ] . other notable malware examples during the pandemic include: trickbot, a trojan that is typically used as a platform to install other malware on victims' devicesaccording to microsoft, trickbot is the most prolific malware operation that makes use of covid- themed lures for its attacks [ ] ; a master boot record (mbr) rewriter malware that wipes a device's disks and overwrites the mbr to make them no longer usable [ ] ; and corona live . , an app that leveraged a legitimate covid- tracker released by john hopkins university and accessed device photos, videos, location data and the camera [ ] . as the pandemic continues, there are likely to be more strains of malware, targeting various types of harm, e.g., physical, financial, psychological, reputational (for businesses) and societal [ ] . during the covid- pandemic our analysis only identified a very small amount ( %) of dos attacks, but there were several reports of hacking. these reports suggested that hacking was not indiscriminate but instead, targeted towards institutions involved in research on coronavirus. in one report, fbi deputy assistant director stated, "we certainly have seen reconnaissance activity, and some intrusions, into some of those institutions, especially those that have publicly identified themselves as working on covid-related research" [ ] . this was further supported by a joint security advisory a month later from the uk's ncsc and usa's cisa [ ] . in this advisory, advanced persistent threat (apt) groupssome of which may align with nation states-were identified as targeting pharmaceutical companies, medical research organisations, and universities involved in covid- response. the goal was not necessarily to disrupt their activities (as with the ransomware case), but instead to steal sensitive research data or intellectual property (e.g., on vaccines, treatments). while a detailed analysis of these attacks has not yet surfaced, password spraying (a brute-force attack which applying commonly-used passwords in attempting to login to accounts) and exploiting vulnerabilities in virtual private network (vpn) have been flagged [ ] . attribution is another important consideration during such attacks. determining the true origin of cyber-attacks has always been difficult, however, in response to these covid- -related threats, the us openly named the people's republic of china (prc) as a perpetrator in a joint fbi/cisa announcement [ ] . the effects of the pandemic, the mass quarantine of staff and the measures put in place to facilitate remote working and resilience of existing cyber-infrastructures, against the attacks and timelines previously described, had a profound effect on the workforce -the people engaged in or available for work. the pandemic also had an effect on the resilience of technology, socio-economic structures and threatened, to a certain degree, the way people live and communicate. figure illustrates the covid- impact on the workforce across eight different categories. all categories seemingly integrate with cyber-enabled assets and tools and different categories may be impacted differently. the pandemic created risk conflicts, for example, strict compliance with security standards which discourage data sharing, could be more harmful than sharing the data. so, whilst there may be strict requirements for patient data not to be accessed at home by gps (general practitioners), this causes a greater harm during quarantine than enabling gps to access patient data. also, the way confidential patient information is processed requires a data protection impact assessment (dpia) to enable further nhs support where needed. this can have an impact in terms of the timely delivery of medical interventions in response to covid- . in traditional risk classification, elements like asset registration and valuation, threat frequency and vulnerability probability are at greater risk of cyber threat. we, therefore, anticipate changes on the way the workforce accesses those information assets and how strategic, tactical and operational tasks are executed to generate socio-economical outputs. these changes can be captured by the development and testing of risk statements capturing ) threat agents, ) vulnerabilities, ) policy/process violation and ) overall asset exposure on all emerging threat landscapes as illustrated in figure . these changes unavoidably cascade further changes to the threat landscapes associated with remote workforce activities and the increasing frequency of weaponised attack vectors related to the coronavirus spreading. given the current climate, it is difficult to predict whether these changes will have a long-lasting effect on the workforce, but their significance is already recorded [ ] . therefore, it is increasingly important that the control of information (storage, processing, transmission) has an elevated importance given the increase of cyber-attacks on important infrastructures. governments, private and public sectors throughout europe currently consider measures to contain and mitigate covid- impact on existing data structures and information governance frameworks (for example, fig. . covid- impact on workforce [ ] ). particular emphasis is placed upon the implications of the pandemic in the processing of personal data. the general data protection regulation (gdpr) legislation in the uk dictates that personal data must be processed only for the specific and explicit purposes for which it has been obtained [ ] . in addition, data subjects should always receive explicit and transparent information with regard to the processing activities undertaken, including that of features and nature of the activity, retention period and purpose of processing. there are challenges related to the governance legal and regulatory compliance landscape in terms of conformance versus rapid access and processing of data by different entities. this is quite apparent in cases where public authorities seek to obtain pii to reduce the spread of covid- . typical examples also include contact tracing applications and platforms in which the data is aggregated online for post-processing [ ] . specific legislative measures have to be re-deployed or introduced to safeguard public security while maintaining privacy at scale, while legal and regulatory principles continue to upheld [ ] . with the rapid increase of covid- symptoms, governments had to derive a plan that would enable them to understand epidemiological data further and identify positive interventions to contain and mitigate the impact of the pandemic. research shows a high correlation between the use of big data that includes private identifiable information in the effectiveness of these epidemiological investigations [ ] . that meant that in most cases, citizens had to provide this information voluntarily and that quickly resulted in discussions and debates on the tradeoffs between public safety versus personal privacy [ ] . the information has also been obtained through internet communication technology. medical testing equipment and coronavirus testing at a large-scale were used as instruments for data collection in the fight to reduce mortality rates. the legal and regulatory compliance frameworks differ between countries; thus, managing personal information was subject to different privacy protection measures. the de-identification of personal information was another component that governments had to exercise to satisfy personal privacy requirements and increase the trust of human participants during the epidemiological investigations. the process of collecting and process-ing personal information by applying de-identification technologies raised technical challenges with regards to accuracy and consent, safe and legally defensive data disposal and robustness of associated policies of data processing and management for epidemiological research. the urgency of the situation and the speed at which the data had to be acquired and processed, created a sense of distrust amongst citizens and challenged the efficacy of the existing processes in place [ ] . the extensive lockdown periods introduced in many countries (described in section iii) have also tested their ability to deploy strategies for business recovery after these periods. these strategies had to ensure smooth and phased out recovery within an ongoing pandemic, which has proved to be a challenging task. however, there is an unprecedented speed and scale on the r&d activities in response to the covid- outbreak forcing crossorganizational multilateral collaborations [ , ] . there is currently a challenge across europe to orchestrate information sharing in a timely and accurate manner as even mainstream media sources seem to have propagated false information [ ] . the increase on both frequency and impact of these attacks will test further our existing monitoring and auditing capabilities, logical and physical access controls, authentication and verification schemes currently deployed. also, as part of the current enterprise risk management approaches the way organisations sanitise incident reporting, media disposal and data destruction and sharing processes will also be tested alongside to traditional defence-in-depth principles currently established as de-facto. the finance sector is also affected as the predicted financial recession will leverage the sophistication and scale of targeted attacks as threat actors grow their capabilities [ ] . the covid- pandemic has generated remarkable and unique societal and economic circumstances leveraged by cyber-criminals. our analysis of events such as announcements and media stories has shown what appears to be a loose correlation between the announcement and a corresponding cyber-attack campaign which utilises the event as a hook thereby increasing the likelihood of success. the covid- pandemic, and the increased rate of cyber-attacks it has invoked have wider implications, which stretch beyond the targets of such attacks. changes to working practises and socialization, mean people are now spending increased periods of time online. in addition to this, rates of unemployment have also increased, meaning more people are sitting at home online-it is likely that some of these people will turn to cyber-crime to support themselves. the combination of increased levels of cyber-attacks and cyber-crime means there may be implications for policing around the worldlaw enforcement must ensure it has the capacity to deal with cyber-crime [ ] . the analysis presented in this paper has highlighted a common modus-operandi of many cyber-attacks during this period. many cyber-attacks begin with a phishing campaign which directs victims to download a file or access a url. the file or the url act as the carrier of malware which, when installed, acts as the vehicle for financial fraud. the analysis has also shown that to increase the likelihood of success, the phishing campaign leverages media and governmental announcements. although this analysis is not necessarily novel, we believe this is the first time that this has been supported with a context of actual live events. this analysis gives rise to the recommendation that governments, the media and other institutions should be aware that announcements and the publication of stories are likely to give rise to the perpetration of associated cyber-attack campaigns which leverage these events. the events should be accompanied by a note / disclaimer outlining how information relating to the announcement will be relayed. our research presents opportunity for further research. this research has shown what can best be described as a loose direct and inverse correlation between events and cyber-attacks. further research should investigate this phenomenon and outline whether a predictive model can be used to confirm this relationship. there is an abundant supply of cyber-attack case studies relating to countries around the world and a wider analysis of the problem can help in affirming this phenomenon. malware," , https://krebsonsecurity.com/ / /live-coronavirusmap-used-to-spread-malware/ (accessed june ). [ ] r. smithers, "fraudsters use bogus nhs contact-tracing app in phishing scam," , https://www.theguardian.com/world/ /may/ / fraudsters-use-bogus-nhs-contact-tracing-app-inphishing-scam (accessed may ). deals could have been avoided," , https://www.bloomberg.com/opinion/articles/ - - /coronavirus-trillions-in-aid-draws-scams-anddodgy-deals (accessed may ). [ ] d. galov, "remote spring: the rise of rdp bruteforce attacks," , https://securelist.com/remote-spring-therise-of-rdp-bruteforce-attacks/ (accessed may ). [ ] ncsc, "home working: preparing your organisation and staff," , https://www.ncsc.gov.uk/guidance/home-working (accessed may ). [ ] nist, "security for enterprise telework, remote access, and bring your own device (byod) solutions," , https://csrc.nist.gov/csrc/media/publications/shared/ documents/itl-bulletin/itlbul - .pdf (accessed may ). [ ] ftc, "online security tips for working from home," pandemic profiteering: how criminals exploit coronavirus phishing emails: how to protect against covid- scams us authorities battle surge in coronavirus scams, from phishing to fake treatments cybercrime and you: how criminals attack and the human factors that they seek to exploit hackers are targeting hospitals crippled by coronavirus uk's national cyber security centre (ncsc) and the us' department of homeland security (dhs) cybersecurity and infrastructure security agency (cisa) the hiscox cyber readiness report official annual cybercrime report less traditional crime, more cybercrime measuring the changing cost of cybercrime understanding the growth of cybercrime economy scene of the cybercrime the novelty of 'cybercrime' an assessment in light of routine activity theory other people's money; a study of the social psychology of embezzlement hacking: the next generation: the next generation understanding scam victims: seven principles for systems security how cybercriminals prey on victims of natural disasters hurricane katrina fraud how to help the earthquake victims in ecuador and japan watch out for hurricane harvey phishing scams hundreds of bushfire donation scams circulating michael jackson's death sparks off spam michael jackson's death spurs spam, malware campaigns you have not won! a look at fake fifa world cup-themed lotteries and giveaways blackmailing and passwords leaks compromised linkedin accounts used to send phishing links via private message and inmail tips to help if you are worried about coronavirus facing down the myriad threats tied to covid- threat spotlight: coronavirus-related phishing protecting businesses against cyber threats during covid- and beyond covid aid scams and dodgy a systematic approach toward description and classification of cybercrime incidents a cyber attack modeling and impact assessment framework a taxonomy and survey of intrusion detection system design techniques, network threats and datasets extracting narrative timelines as temporal dependency structures classification of cyber attacks in south africa sony's nightmare before christmas: the north korean cyber attack on sony and lessons for us government actions in cyberspace naming the coronavirus disease (covid- ) and the virus that causes it cybercrime -prosecution guidance vietnamese threat actors apt targeting wuhan government and chinese ministry of emergency management in latest example of covid- related espionage skype phishing attack targets remote workers' passwords fake coronavirus tracking apps are really malware that stalks you how to design browser security and privacy alerts bayesian network models in cyber security: a systematic review google translate coronavirus disease (covid- ) pandemic latest information on coronavirus disease (covid- ) research on computer network attack modeling based on attack graph who reports fivefold increase in cyber attacks, urges vigilance search (accessed municipal:"massive" computer attack at the town hall of marseille cyber attack on easyjet, compromised the data of nine million customers an extended model of cybercrime investigations a taxonomy of operational cyber security risks a taxonomy of technical attribution techniques for cyber attacks a taxonomy of network threats and the effect of current datasets on intrusion detection systems chapter : cyberdependent crimes cyber-enabled crimes -fraud and theft research reveals hacker tactics: cybercriminals use ddos as smokescreen for other attacks on business from cybersecurity deception to manipulation and gratification through gamification recent ransomware attacks define the malware's new age state of malware report social engineering attacks and covid- chinese hackers 'weaponize' coronavirus data for new cyber attack: here's what they did coronavirus email attacks evolving as outbreak spreads coronavirus phishing threat intel:cyber attacks leveraging the covid- /coronavirus pandemic hackers are using the "coronavirus" fear for phishing, please pay attention to prevention take advantage of the fire! "the epidemic is a bait" cyber attack global shipping industry attacked by coronavirus-themed malware fighting the spread of coronaviruses who faces severe cybersecurity threats indian hackers targeting chinese medical institutes amid coronavirus outbreak, says report analysis and suggestions on several types of network security threats during the epidemic prevention and control period coronavirus and ransomware infection -what's the connection? fresh virus misery for illinois: public health agency taken down by... web ransomware. great timing, scumbags coronavirus test results delayed by cyber-attack on czech hospital cyber-attack hits u.s. health agency amid covid- outbreak new threat discovery shows commercial surveillanceware operators latest to exploit covid- new android app offers coronavirus safety mask but delivers sms trojan scams, lies, and coronavirus cyber-attack threatens spanish hospital computer systems covid sms phishing attempt our @glospolice fcr have had calls asking if covid- texts like the below are genuine the school meals coronavirus text scam which could trick parents out of thousands android malware takes payment for 'coronavirus finder' map warning over coronavirus netflix scam cyber criminals create a spoof copy of the nhs website in the midst of the coronavirus pandemic to trick users into downloading dangerous malware that can steal their passwords and credit card data hackers exploit hmrc coronavirus job retention scheme with phishing email scam new coronavirus screenlocker malware is extremely annoying docusign phishing campaign uses covid- as bait new threat intelligence report: days of coronavirus ncsc shines light on scams being foiled via pioneering new reporting service coronavirus: fraud victims have lost more than £ . m to virus-related scams coronavirus: israel enables emergency spy powers hmrc shuts down almost covid phishing scam sites budget : what you need to know coronavirus scams pervasive ehealth services a security and privacy risk awareness survey baiting the hook: factors impacting susceptibility to phishing attacks cyber criminals create a spoof copy of the nhs website in the midst of the coronavirus pandemic to trick users into downloading dangerous malware that can steal their passwords and credit card data check point there are now more than , 'high-risk' covid- threats on the web covid- fraud a study on situational awareness security and privacy of wearable health monitoring devices food and drugs administration (fda) olaf launches enquiry into fake covid- related products uk medicines and medical devices regulator investigating cases of fake or unlicensed covid- medical products dirty little secret extortion email threatens to give your family coronavirus covidlock update: deeper analysis of coronavirus android ransomware spanish hospitals targeted with coronavirus-themed phishing lures in netwalker ransomware attacks ransomware gangs to stop attacking health orgs during pandemic trickbot named most prolific #covid malware coronavirus trojan overwriting the mbr a taxonomy of cyber-harms: defining the impacts of cyber-attacks and understanding how they propagate fbi official says foreign hackers have targeted covid- research uk's national cyber security centre (ncsc) and the us' department of homeland security (dhs) cybersecurity and infrastructure security agency (cisa) people's republic of china (prc) targeting of covid- research organizations why cybersecurity matters more than ever during the coronavirus pandemic data protection and covid- general data protection regulation (gdpr): principle (b): purpose limitation nhs contact-tracing app 'falls short of data protection law covid- information governance advice for ig professionals privacy in the age of medical big data balancing personal privacy and public safety in covid- : case of korea and france astrazeneca advances response to global covid- challenge as it receives first commitments for oxford's potential new vaccine covid- : collaboration is the engine of global science -especially for developing countries the danger of mainstream media infections with viral and fake information covid- : companies and verticals at risk for cyber attacks the implications of the covid- pandemic for cybercrime policing in scotland: a rapid review of the evidence and future considerations, ser. research evidence in policing: pandemics. scottish institute for policing research key: cord- -evz gwac authors: amirov, chingiz; howard, pat; kohm, catherine title: influenza pandemic planning: one organization's experience date: - - journal: healthc manage forum doi: . /s - ( ) - sha: doc_id: cord_uid: evz gwac this article highlights influenza pandemic planning by a geriatric facility in order to ensure preparedness for staff, clients and families. by describing our experience, we hope that other facilities that provide geriatric, long-term care services are able to advance their own pandemic plans. this article highlights influenza pandemic planning by a geriatric facility in order to ensure preparedness for staff, clients and families. by describing our experience, we hope that other facilities that provide geriatric, long-term care services are able to advance their own pandemic plans. cet article décrit la planification de la lutte contre une épidémie de grippe d'un établissement de soins gériatriques visant la préparation du personnel, des clients et des familles. forts de notre expérience, nous espérons que d'autres établissements qui assurent la prestation de soins gériatriques à long terme seront en mesure de faire progresser leurs propres plans de lutte contre une épidémie. his article describes the influenza pandemic planning undertaken by one health care institution. the facility provides geriatric services through a unique continuum of care, including an -story retirement residence, outpatient clinics, a -bed nursing home and a -bed complex continuing care hospital providing rehabilitation, palliative care and acute care. in this faith-based, academic health sciences centre fully affiliated with the university of toronto, over , staff, representing a variety of health disciplines and unregulated workers, are actively involved in care, research and education. since the last influenza pandemic in - , the risk of the next pandemic has never been greater than at present. experts at the world health organization advise that the next influenza pandemic is overdue. with h n avian influenza consistently advancing its geographical spread around the globe, the world has moved closer to the next pandemic. influenza pandemics usually cause abrupt surges in the number of people needing medical or hospital care, temporarily overwhelming health services. high rates of worker absenteeism can interrupt other essential services, such as law enforcement, transportation and communications, and impede business continuity and economic productivity. experiences during the outbreak of severe acute respiratory syndrome (sars) suggest that the associated social and economic disruptions will be amplified in this century's closely interrelated and interdependent system of trade and commerce. although neither the timing nor the severity of the next influenza pandemic can be predicted with any certainty, we know that the most reliable, predictable and expedient way to improve the defenses against pandemic influenza is to build on existing structures and mechanisms that have worked well in recent public health emergencies. this is the primary focus of a facility-level pandemic plan. many influenza pandemic planning guidelines have been prepared by federal and provincial health authorities. typically, these guidelines do not address the specifics of facility-level preparedness for a public health emer- catherine ann kohm, rn, ba, med., is the director of nursing at baycrest. previously she has managed departments such as utilization, emergency, admitting, pre-admission and social work and multicultural health at the university health network. currently, she is on the faculty at the university of toronto and york university. she is the recipient of several teaching awards and has published and presented in a variety of areas. gency, such as a pandemic influenza. federal, provincial and regional health authorities provide overall direction, guidance and coordination, while health care facilities provide the front-line response in terms of patient management, communication and surveillance. our organization has the additional challenge of planning to address the needs of a complex, geriatric long-term care facility. the key driver for getting started stemmed from our participation on the toronto academic health sciences network (tahsn) pandemic planning committee. the tahsn committee was preparing a manual to guide the member teaching hospitals in their response to an influenza pandemic. our facility identified that it was essential to prepare our own plan to address the unique needs of our organization. an effective facility-level response requires planning, at many levels. our planning started with the establishment of an influenza pandemic planning committee, composed of a broad representation from across the organization. the committee's ultimate goal was to prepare the organization to develop a planned response in the event of a pandemic. representation on the facility pandemic planning committee included medicine, nursing, infection prevention and control, occupational health and safety, allied health, pharmacy, purchasing, public affairs, information management, human resources, education and bioethics. it is important to note that this committee structure is useful for preparedness, when the plan is in development. for the actual response, the internationally recognized incident management system (ims) is an optimal structure to facilitate a well-coordinated response to pandemic or other emergencies. the ims is a north american standard, essential for management of any emergency incidents. in the united states and canada, ims is used extensively in the fire service and increasingly by police and emergency medical services. many hospitals and other health care providers are starting to implement ims within their organizations. the ims structure is built around five functions: command, operations, planning, logistics and administration. our approach was to develop a high-level plan for each area represented on the committee, followed by a detailed tactical plan, culminating in a table-top simulation exercise to test our plans and identify gaps. initially, the executive team established guiding principles and an overarching plan to guide the organization. an objective: "social distance" recommendations -develop recommendation aimed at increasing "social distance" for clients, staff and visitors at baycrest actions activity : present the concept of "social distance" and its role during influenza pandemic to the infection control committee and senior management committee, and have the concept endorsed as a basis for developing recommendations aimed at increasing "social distance" within baycrest in the event of pandemic. activity : present the concept of "social distance" and its role during influenza pandemic management of entities/sites where "social distance" would be a factor in the event of influenza pandemic to increase their awareness and get their support. activity : identify (map out) places of public gatherings or other similar "hot spots" throughout baycrest facilities where "social distance" would be a factor in the event of influenza pandemic. activity : alternatives to the ban and restriction of public gatherings are discussed with the management of entities/sites at baycrest where "social distance" would be a factor in the event of influenza pandemic. ethical framework was an important component to guide decision-making during a public health emergency that would impact our clients, families and staff. our next step was to ensure that the committee members had a comprehensive understanding of the pandemic influenza phenomenon. to achieve this, we began every meeting with an overview of the latest epidemiological information. initially, there was considerable anxiety due to extensive media coverage and fear of the unknown. this was mitigated through the use of humour, and reiteration of knowledge that we had gleaned from other meetings, journals, provincial and federal pandemic plans. the committee developed a common template for the high-level plan. each area was expected to develop a response to the various phases of the pandemic, ever mindful of the resources required during implementation. see figure for an example taken from the infection, prevention and control plan. each area presented its plan before the entire committee for discussion and input. this resulted in the identification of gaps and synergies between areas. each plan was entered into a common data base to allow access to all members. a cost centre was allocated to influenza pandemic planning to assist the groups in identifying required resources. as the plans neared completion, it was important to determine whether they were synchronized and would stand the test of an actual influenza pandemic. a real-life simulation would have been the most effective process to test our plans, but given the size and the complexity of the organization, it was decided that a table-top simulation would be the most practical and useful test of the plans. prior to the table-top simulation, a three-hour readiness session was held to prepare the teams. the goals of the readiness exercise were threefold: . to review all pandemic plans to ensure the teams knew and understood their role and responsibilities in each phase of a pandemic, . to identify additional gaps and synergies, and . to outline expectations for the upcoming table-top simulation. at the beginning of the readiness exercise, we reviewed our ethical framework and the guiding principles for pandemic planning. each group had someone assigned to record notes, which were collected at the end of the session and merged into a document for review by the influenza pandemic planning committee. evaluation results indicated that participants found the readiness exercise useful. the process of a table-top simulation is to allow participants to be immersed in their assigned roles, encouraging them to make decisions based on the information they receive during the exercise. the goals of this table-top simulation exercise were to test plans and identify gaps. two external facilitators with extensive experience in emergency exercise design were hired to assist with the process. meetings were held with the facilitators to familiarize them with both the organization and the facility's influenza pandemic plan, and finalize the script for the simulation. the exercise was to commence with a phase alert (world health organization) and then cover initial notification, establishment of the senior response team, coordination of response efforts and the beginning of a recovery plan. in order to gather diverse feedback, external observers were selected from a variety of health care institutions, the ministry of health and long-term care, public health, and emergency management services. two weeks prior to the exercise, detailed information was sent to the participants and the observers, clarifying their roles and outlining the objectives and agenda for the exercise. on the day of the exercise, there was a briefing breakfast with the observers to review their role expectations. the participant tables were organized under the headings: senior management, public affairs, resource support, logistics, the hospital, the home and supportive housing. approximately management and staff were involved in the simulation. it was very important to ensure that the participants were clear that this was a test of the plans, not a test of their knowledge or ability! the simulation, "exercise droplet," began with a briefing by the facilitator to orient the participants to the objectives of the exercise. participants were expected to react to the initial information that: "the director of emergency medicine in a downtown toronto hospital has been advised that the emergency department has quarantined a suspected case of type a (h n ) influenza, but the diagnosis is not yet certain." participants received subsequent inputs and messages over the three-hour period, with the information expressly simulating the first wave of the influenza pandemic. a copy of the facility's emergency manual and the pandemic response plans were available for reference. as in the readiness exercise, a staff person was assigned the role of recorder at each table to document all actions during the table top. the facilitator asked the participants to use their knowledge of their own facility and local resources to create a reality base for the selected scenario. "exercise droplet" passed exceedingly quickly. teams were immersed in their roles and the noise level in the room rapidly escalated. all participants were relieved and exhausted by the end of the session, and a debriefing and lunch concluded the experience. two methods were used to collect feedback following the table-top exercise: an immediate post-exercise debrief discussion and a structured survey distributed one week following the simulation. in addition, the facilitators provided a detailed written report on the exercise, summarizing strengths and weaknesses and providing recommendations. the feedback was tabulated, resulting in a list of suggestions for the influenza pandemic planning committee to consider. the following summarizes some of the insights from the evaluations and observers: what went well • holding a readiness session one month prior to the simulation was a valuable exercise, • the simulation was a very effective internal test of plans, and successful in identifying gaps and overlaps, • external and internal observers provided an objective view of the process and the feedback from a broad variety of perspectives was extremely useful. • the recommendation to implement the incident management system framework within the organization, with individuals targeted for key roles, will ensure common language and maximize coordination, • testing linkages with the broader community was a key piece that was missing. despite the efforts that the organization has devoted to influenza pandemic planning over the last two years, there remain many tasks and activities to be addressed. one of the first steps is to review the gaps identified by staff, external observers and facilitators. in addition to working on our plans with a renewed vigour, we have readjusted our original committee structure to more closely align it with both the ims structure and our internal organizational structure. we anticipate that the ongoing process of refining our plans will assist us in managing not only an avian flu outbreak should it occur, but will also be transferable to any public health emergency. avian influenza, including influenza a (h n ), in humans: who interim infection control guideline for health care facilities. manilla, philippines: who regional office for the western pacific. revised who strategic action plan for pandemic influenza toronto academic health science network. pandemic influenza planning guidelines who influenza preparedness plan. who, department of communicable disease, surveillance and response key: cord- -la sum authors: feldblyum, tamara v.; segal, david m. title: seasonal and pandemic influenza surveillance and disease severity date: - - journal: global virology i - identifying and investigating viral diseases doi: . / - - - - _ sha: doc_id: cord_uid: la sum continuous investments in influenza research, surveillance, and prevention efforts are critical to mitigate the consequences of annual influenza epidemics and pandemics. new influenza viruses emerge due to antigenic drift and antigenic shift evading human immune system and causing annual epidemics and pandemics. three pandemics with varying disease severity occurred in the last years. the disease burden and determinants of influenza severity depend on circulating viral strains and individual demographic and clinical factors. surveillance is the most effective strategy for appropriate public health response. active and passive surveillance methods are utilized to monitor influenza epidemics and emergence of novel viruses. meaningful use of electronic health records could be a cost-effective approach to improved influenza surveillance the recent infl uenza pandemic in caused by infl uenza a/h n reassortant with high human-to-human transmissibility, demonstrated the unpredictable nature of emerging viruses and importance of continuous surveillance. during the - infl uenza season, the h n virus infected approximately million persons and caused an estimated , hospitalizations and , deaths in the usa [ ] . this novel virus caused severe morbidity and mortality in pregnant women [ - ] and younger adults with % of deaths occurring in persons younger than years of age [ ] . in addition to the human toll, annual infl uenza epidemics and pandemics carry substantial economic consequences in health-care utilization costs, intervention costs, and reduced productivity. the cost of annual infl uenza epidemics in the usa is estimated to range between $ and $ billion [ ] . individual risk factors for severe outcomes of infl uenza infection vary between seasons and are associated with circulating infl uenza virus types and subtypes, as well as with individual demographic characteristics, such as age, ethnicity, and clinical conditions, such as asthma, diabetes, cardiovascular, lung, and neurological diseases [ - ] . due to variations in infl uenza virus activity, the capacity to respond to seasonal epidemics and pandemics depends on the availability of accurate and timely information and swift and early identifi cation of pandemic and epidemic strains. the us national infl uenza surveillance systems include syndromic, clinical, and virologic monitoring. information on infl uenza-like illness (ili), infl uenza hospitalizations, infl uenza and pneumonia associated mortality, infl uenza-associated pediatric mortality, and laboratory testing of a subset of specimens from patients with ili to characterize the circulating viruses are reported. these surveillance systems are resource-intensive [ , ] and require sustained funding for epidemiologic and virologic information gathering at the national and local levels [ ] . enhanced and timely syndromic surveillance methods that use electronic health records (ehr) could improve the assessment of infl uenza medical and economic disease burden and associated risk factors leading to identifi cation of at risk population groups, targeted and appropriate public health interventions, and estimates of economic burden associated with the disease [ , - ] . ehrs capturing information using the international classifi cation of diseases, ninth revision, clinical modifi cation (icd- -cm) codes lend themselves to effi cient quantitative analyses and have been used in numerous epidemiologic studies and infl uenza surveillance [ , , - ] . with the growing focus of the us health care system on the meaningful use of electronic medical records, one of the practical applications is expanding biosurveillance and preparedness capabilities, such as surveillance of infl uenza severity and associated risk factors during seasonal epidemics and pandemics [ , ] . traditional infl uenza surveillance data are based on laboratory testing of a limited number of samples, case reporting by participating health care providers, hospitalbased primary data, and deaths reported by statistics offi ces [ ] . data extracted from electronic medical records can enrich reporting of risk factors for disease severity or clinical diagnoses, even in the absence of laboratory testing, and augment the traditional surveillance. in addition, monitoring patients ehrs may enable detection of disease outbreaks for which no laboratory diagnostics were requested including emerging pathogens and biothreat events [ ] . the timely reporting of information on circulating infl uenza viruses and the disease burden associated with seasonal and pandemic infl uenza is essential for optimal public health response, identifi cation of vulnerable populations, and for prevention and patient management strategies. large electronic datasets of hospital discharge records, such as the nationwide inpatient sample (nis), could provide information on risk factors for disease enhancing infl uenza surveillance methods [ , ] . the use of much larger more representative national population repositories from existing electronic medical records can potentially augment or replace small hospital case series studies often employed for assessment of infl uenza severity. every year, emerging and reemerging infl uenza viruses lead to tens of millions of respiratory infections and up to , fatalities worldwide. unpredictability of antigenic drift or antigenic shift leading to emergence of viral strains with limited or no immunity in human population results in variable disease spread and severity. a novel high pathogenicity virus adapted to human-to-human transmission could cause a global pandemic with millions of deaths [ ] . timely detection and reporting of disease in specifi c populations through an effective biosurveillance system is the most promising strategy for mitigating the impact from disease outbreaks caused by naturally occurring epidemics or bioterrorism events [ ] . infl uenza virus surveillance informs selection of the annual vaccine strains and guides antiviral therapy. monitoring infl uenza outbreaks is of particular interest because they represent a proxy for research of potential biothreat surveillance systems. early clinical symptoms of many biologic warfare agents such as aerosolized b. anthracis , tularemia, and smallpox resemble infl uenza like illness [ , ] . surveillance of infectious diseases can be conducted using passive or active approaches. active methods based on laboratory testing and case reporting are usually resource intensive and require ongoing reporting by participating physicians, hospitals, and laboratories [ ] . only a subset of specimens can be tested [ ] and cases are often underreported. passive syndromic surveillance methods may be less accurate but they are also less expansive and enable assessment of the disease spread and severity in the population. implementing syndromic surveillance based on signs and symptoms, diagnosis, and large volumes of other health related data for disease of interest can greatly improve the quality and timeliness of passive surveillance [ ] . information acquired integrating both methods can generate a more complete picture of an outbreak or an epidemic [ ] . in the usa, the national infl uenza surveillance is lead by the cdc as a collaborative effort of state and local health departments and laboratories, health-care providers, hospitals, and clinical laboratories. the data on circulating infl uenza viruses and the disease activity including incidence, morbidity, and mortality is collected year round, compiled, and published weekly with a - -week reporting delay [ ] . infl uenza virologic surveillance throughout the usa is conducted by approximately laboratories comprising the who and national respiratory and enteric virus surveillance system (nrevss) laboratory networks. they collect information on the proportion of infl uenza a and b positive respiratory specimens and determine infl uenza a subtypes. a subset of the infl uenza positive samples, especially if the subtypes cannot be determined by standard diagnostic tests, are sent to cdc for further characterization by gene sequencing to monitor emergence of novel viruses and antiviral resistance [ ] . the second component of the surveillance system is the illness surveillance network (ilinet) comprised of approximately , healthcare providers voluntarily reporting all outpatient visits and the number of visits due to infl uenza-like illness (ili) stratifi ed by age group. the percentage of weekly ili visits weighted to refl ect the population size of reporting states are compared to the national baseline of ili visits outside of infl uenza season to monitor ili activity levels in each state [ ] . vital statistics offi ces in participating us cities report the total number of deaths and the number of deaths caused by pneumonia or infl uenza (p&i) stratifi ed by age groups. statistical methods are used to calculate the weekly level of p&i mortality above the seasonal baseline or epidemic threshold. in , pediatric infl uenza-associated mortality for children - years of age became a nationally notifi able condition. infl uenza hospitalization network comprised of hospitals in over counties in states collects information from hospital records and reports on laboratory-confi rmed infl uenza hospitalizations for children and adults. the information on geographic spread of infl uenza activity is augmented by state and territorial health department epidemiologists' reports [ ] . in addition to the cdc surveillance systems, the armed forces operate the global emerging infections surveillance and response system (geis) to protect military personnel and their families [ ] . respiratory infections surveillance is one of the geis programs contributing to the global infl uenza surveillance network. the program leverages established laboratory and research facilities in host countries and collaborations with global partners. its activities are coordinated and information regarding circulating infl uenza viruses, disease burden, and epidemiology is shared with cdc, who, and host countries. the data is also used in research and for development of vaccines and diagnostics [ ] . international infl uenza surveillance is accomplished through the who global infl uenza surveillance network collaborating centers including the cdc. global infl uenza surveillance information is shared through the who flunet tool and it provides advance signals of infl uenza activity and trends, informs selection of annual vaccine strains, and enables member countries to better prepare for upcoming infl uenza season [ ] . in addition to the active surveillance efforts, alternative methods such as syndromic surveillance, electronic patient records from emergency room or ambulatory doctor visits, and hospital discharge records have been used for surveillance of infl uenza and other infectious diseases with growing frequency [ , , , ] . syndromic surveillance provides clues on disease patterns collected from multiple information sources such as emergency department visits, ambulatory health-care visits, calls to health information hotlines, internet health information seeking, and over-the-counter medication purchases. indication of potential disease outbreak from syndromic surveillance is usually available before laboratory test results are reported [ ] . essence, the electronic surveillance system for the early notifi cation of community-based epidemics is an example of syndromic surveillance system implemented by the department of defense (dod) to automatically download data from the electronic health records of military personnel and their families. the system captures information coded in accordance with the international classifi cation of diseases, ninth revision, clinical modifi cation (icd- -cm) standards from over , weekly outpatient visits to us military treatment facilities [ ] . it monitors disease outbreaks based on health care utilization patterns and uses icd- -cm codes to group diagnosis into one of the eight disease syndromes. another national electronic surveillance system, biosense, launched in and operated by the cdc collects and analyzes icd- -cm coded data from outpatient visits to health-care facilities and emergency departments, hospitalized patients, laboratory tests, and information on over-the-counter medications sold in pharmacies [ ] . although different studies reported variable utility of syndromic disease surveillance systems for local disease outbreaks, the majority of them indicated that it was useful for monitoring respiratory disease activity and the annual infl uenza seasons [ , , ] . sensitivity of icd- -cm based detectors of acute respiratory disease and infl uenza epidemics varied from to % for acute respiratory disease to % for infl uenza outbreak [ ] and specifi city ranged between and % [ , ] . sensitivity was found to be moderate and likely not suffi cient to detect a small disease outbreak, e.g., in the event of a local bioterrorism incidence. however, icd- -cm coded data can be useful for infl uenza surveillance when accuracy, completeness, and timeliness are carefully considered [ ] before using such data for decision making. for a comprehensive infl uenza surveillance system, it is critical to include hospitals that would collect epidemiological and virological information on severe cases. this data enables characterization of severe ili, identifi cation of at risk population groups, tracking of genetic changes in the circulating viruses, and serve as a monitoring tool for emerging pandemics [ ] . hospital based case series studies yield valuable information on risk factors for sever infl uenza during an ongoing or past infl uenza seasons. although these studies can inform vaccination and therapy decisions, majority of them have a limited sample size, are recourse intensive, and the results are not generalizable on the national level. the lack of this data became especially apparent during the h n pandemic when the disease incidence rate was very high resulting in declaration of phase pandemic while the disease severity on a national level was not ascertained [ ] . hospital-based electronic surveillance is a cost-effective approach to identify infl uenza season-specifi c populations at high risk for ili complications and fatal outcomes. detailed clinical information on each individual case is coded in patients' records and can be used to augment active surveillance in public health response planning and implementation [ ] . advances in information technologies enabled new global and national surveillance methods and real time information sharing among multiple stakeholders. monitoring indicators other than the traditional information captured by health-care providers can be a cost effective approach to augment respiratory disease surveillance. rise in purchases of over-the-counter cold medications, school absenteeism, internet health information searches, and utilization of health advice phone lines were shown to correlate with increased infl uenza activity [ ] . the rise in health information seeking preceded doctors' visits by about week and was also correlated with media coverage of the health concern [ ] . an approach to infl uenza surveillance monitoring ili health-seeking internet queries was launched by google and cdc during the - infl uenza season. the system analyzed logs of web searches related to ili information and reported data with only day lag instead of the usual delay of - weeks. the accuracy of the ili estimates was - % as compared to the actual disease incidence reported by cdc infl uenza surveillance [ ] . a health map web based data collection system was employed during the h n pandemic to monitor the internet, compile, and report infl uenza activity in geographically diverse locations through an interactive map. data was collected from news media, blogs, and other nontraditional sources as well as from the who, cdc, and the public health agency of canada. the median lag between reported and confi rmed cases ranged from to days with considerable variations between the countries infl uenced by public health infrastructure, political system restricting information, and media coverage. the nontraditional information sources may enable earlier detection of outbreaks and epidemics, expand population coverage, improve sensitivity of emerging diseases detection, and place the epidemic or pandemic in the context of the affected population [ ] . while electronic surveillance based on nonclinical data such as over-the-counter medication sales, school absenteeism, and health information seeking may provide preliminary signs of potential infection spread, prompt release of electronic health records (ehr) containing diagnosis and clinical outcomes can lead to a more informative and timely disease surveillance [ ] . increasing utilization of patient electronic records could play an important role in attaining public health objectives and complimenting other information sources. information from electronic medical records captured through surveillance platforms or stored in local or centralized databases has been used in numerous studies for monitoring disease incidence, prevalence, severity, risk factors, and medical care decisions. analyses of electronic medical records were employed to augment the traditional approaches [ , ] during respiratory seasons in the usa. standard surveillance was not suffi cient during the recent infl uenza h n pandemic when several states, including new york [ ] , wisconsin [ ] , and california [ ] implemented additional information gathering methods based on electronic medical records to gain a more complete understanding of the ongoing pandemic severity. ehr-based surveillance systems such as electronic medical record support for public health (esp) implemented in ohio and massachusetts and biosense were successfully used for analyzing icd- diagnosis codes, reporting notifi able disease cases, surveillance of ili, identifi cation of infl uenza or upper respiratory infection risk factors among hospitalized patients, and for monitoring diabetes prevalence, risk factors, and disease severity [ , ] . the results of infl uenza risk factor analyses based on icd- coded data overall agreed with earlier observations based on primary data collected through the emerging infections program during - infl uenza seasons [ ] and in manitoba, canada during h n pandemic [ ] as well as with laboratory confi rmed infl uenza hospitalizations reported to the cdc during the pandemic [ , , ] demonstrated that optimally selected icd- code groups can be used in an automated surveillance system drawing information from electronic medical records for accurate monitoring of infl uenza activity. in this study of the us air force personnel and their dependents outpatient visits the syndromic surveillance results correlated with the results of sentinel ili surveillance conducted by the cdc. placzek and madoff ( ) used administrative hospital discharge records to estimate the hospitalization rates and characterize patients hospitalized with ili during the seasonal fl u epidemics and the h n pandemic in massachusetts. they evaluated two sets ("maximum" and "minimum") of icd- diagnosis codes for their relevance and accuracy in identifying infl uenza-associated hospitalizations and disease severity and concluded the proposed minimum icd- criteria more accurately refl ected the actual infl uenza cases. icd- coded diagnosis alone or in conjunction with other electronic health data were used in monitoring of ili severity and risk factors [ , , ] , and for modeling early detection of local respiratory disease outbreak [ ] . this approach was adopted for other disease surveillance, such as sars [ ] , diabetes incidence and management [ ] , and pertussis [ ] . the study results suggest that timely ili surveillance is feasible using icd- -cm coded electronic medical records and emphasized the importance of the appropriate icd- -cm code selection for case defi nition for accurate assessment of disease activity and severity [ , ] . current infl uenza surveillance systems are resource intensive and provide limited information on patients at-risk for severe infl uenza. to date, no study has been conducted using a large sample of electronic health records (ehr) to examine the risk factors for infl uenza in hospitalized patients across the usa. larger data sets of ehrs will enable the creation of statistically signifi cant age-specifi c models of infl uenza severity and predict more representative infl uenza risk factors and vulnerable groups. a recent study utilized the nationwide inpatient sample (nis) which is a repository of eight million electronic hospital discharge records from , participating hospitals in over states representing approximately % of all us hospitalizations [ ] . this data source is maintained by the healthcare cost and utilization project (hcup) sponsored by the agency for healthcare research and quality (ahrq). results from the retrospective unmatched case-control study of nis patients hospitalized with infl uenza during the h n pandemic and severe a/h n - epidemic seasons confi rmed the utility of using an existing electronic resource to identify comorbidities and demographic risk factors for severity of clinical outcomes associated with pandemic and epidemic infl uenza viruses [ ] . the use of primary diagnosis icd- -cm codes .xx- .xx to correctly identify infl uenza hospitalizations from nis was verifi ed by comparing the temporal trends of monthly hospitalization counts identifi ed in nis records (table . findings from these studies demonstrate that large datasets of electronic medical records are an essential component of infl uenza epidemic surveillance. integration of icd- diagnosis codes into more complex disease detection algorithms can further improve the sensitivity and specifi city of surveillance systems based on electronic medical records [ ] . however, this approach is limited if electronic records are fragmented between different providers using different disease algorithms whereas the icd- codes even though potentially less specifi c are standardized among all users and may be more applicable to nationwide surveillance [ ] . further standardization of data coding and selection criteria, and interoperability among private and government surveillance efforts has the potential to enhance the electronic data quality and timeliness [ , ] . this methodology can be especially advantageous for public health applications as it uses routinely collected data and requires modest investments for maintenance and operation [ ] . infl uenza virus is a zoonotic pathogen causing annual epidemics and pandemics resulting in human toll and economic losses all over the world. infl uenza-associated morbidity and mortality are especially high among persons with chronic health conditions and usually among the very old or the very young [ ] . although the virus was identifi ed and isolated only years ago, infl uenza disease outbreaks can be traced back to middle ages and identifi ed by signs and symptoms, sudden start of the epidemic, and excess mortality in historical sources dating to [ ] . shope demonstrated in s that the infectious agent causing fl u in humans could adapt to other species and cause similar disease in swine. the infl uenza virus adaptability to the host immune system enables sustained human-to-human transmission and the emergence of novel viral strains [ ] . it also poses a challenge to the public health efforts to predict and control the annual infl uenza epidemics and pandemics. infl uenza viruses belong to the orthomyxoviridae family and are divided into three genera or types, infl uenza virus a, b, and c [ ] . infl uenza a viruses are further classifi ed into subtypes defi ned by one of the hemagglutinin and one of the ten neuraminidase subtypes present in the virus [ ] . infl uenza b viruses are not classifi ed into distinct subtypes but are divided into two genetic lineages, yamagata and victoria [ ] . it is an enveloped single stranded rna virus with a genome fragmented into eight segments encoding proteins. the surface glycoproteins hemagglutinin (ha) and neuraminidase (na) play the most important role in viral infection and transmission. ha attaches the virus to the target cell's sialic acids receptors facilitating the viral rna entry into the cell. the na enzymatic activity cleaves the sialic acid releasing the newly produced viral particles [ , ] . the annual epidemics are caused by infl uenza a and infl uenza b, but only infl uenza a can adapt to multiple hosts and emerge as a novel virus causing pandemics. antigenic drift due to mutations in ha and na genes allows the virus to evade preexisting antibodies in the human immune system conferring the pathogenicity and virulence. antigenic shift occurs when infl uenza viruses containing diverse ha and na subtypes coinfect the same host, triggering a reassortment event and producing progeny with genomic segments from both parental viral subtypes [ ] . wild birds are the natural reservoir for infl uenza viruses. sixteen hemagglutinin and nine neuraminidase infl uenza a subtypes were isolated from aquatic birds and only the most recent ha was isolated from fruit bats [ ] . according to the mixing vessel theory, pigs are considered the main mammalian host where the adaptation of an avian infl uenza viruses to human host and reassortment events occur [ ] . pigs' cell-receptors match both human and avian infl uenza, rendering them susceptible to infection with viruses from both hosts [ ] . infl uenza a viruses have been also isolated from other animals, including a horse, dog, cat, tiger, and leopard [ ] . infl uenza type b and c is rarely found in hosts other than humans, although infl uenza b has been found in seals and infl uenza c has been reported in swine and dogs [ ] . despite the investments in infl uenza research, surveillance, and prevention efforts, infl uenza virus remains a cause of respiratory infection in the usa and in the world. annual infl uenza-associated deaths in the usa range between , and , [ ] and, on the average, , are hospitalized due to severe disease [ ] . the variations in mortality can be attributed to difference in the circulating viral types and subtypes. the average mortality rates are . times higher during the seasons when infl uenza a(h n ) subtype is predominant as compared to seasons when infl uenza b or other infl uenza a subtypes are the predominantly circulating viruses. during a typical infl uenza season, severe illness and death occur most frequently among individuals years and older ( . %) or children younger than years of age [ ] . persons of any age with underlying health conditions are also at a greater risk for severe outcomes associated with infl uenza infections [ ] . infl uenza viruses are transmissible among humans via the respiratory rout. during seasonal epidemics and pandemics, each case transmits the virus at - day interval to . - . and . - . individuals respectively [ ] . the human-to-human transmission occurs in one of the three ways: direct contact with infected persons, touching object contaminated with the virus and then transferring it from hands to mucus surfaces of the nose or eyes, and inhaling virus-containing droplets produced by infected person when coughing or sneezing [ , ] . the effi ciency of infl uenza transmission aerosolized in droplets depends on the size of the droplet, viral concentration, and humidity. yang and marr ( ) demonstrated that the concentration of infectious infl uenza virus in cough droplets is inversely related to the relative humidity (rh) in indoor settings, while the droplet size is directly related to relative humidity. in a dryer environment, the smaller droplets tend to stay in the air longer, infecting larger number of sensitive hosts. in a humid environment, the virus in large droplets settles on objects (fomites) and can survive for several days. viable infl uenza viruses in mucus were detected on paper money bills after h and in some cases up to days [ ] . in temperate climates, infl uenza epidemics occur in a seasonal pattern during the colder months of the year, while in the tropical climates, infl uenza circulates all year round with patterns associated with rainy seasons. multiple reasons for this periodicity such as sunlight, temperature, humidity, human mobility, and contact rates, and functions of the immune system have been explored without arriving at a defi nitive conclusion [ , ] . yang and marr ( ) suggested that the winter seasonality can be partially explained by higher concentration of droplet-suspended infl uenza viruses in heated buildings due to lower humidity. other environmental factors, such as colder temperature and reduced ultraviolet radiation, are also independently associated with virus survival and seasonality. temperature and humidity also effect the human immune system, diminishing the blood fl ow and leukocyte supply in low temperatures while increasing viral shedding [ ] . lowen and palese ( ) confi rmed that cold and dry conditions facilitated viral transmission through aerosolized droplets, while warm or humid environment ( °c, % rh) prevented the viral spread. they proposed that seasonal pattern of infl uenza epidemics in temperate climate occurs due to viral transmission by aerosolized droplets, while year-round infections occur through fomites or direct contacts in tropical climate. the exception to this pattern was the spring outbreak of the swine-origin infl uenza a h n , which possibly could be explained by the increased frequency of transmission via direct contact due to the absence of human immunity to the novel antigenic strain. variations in temperature and humidity did not affect viral spread by direct contact [ ] . infl uenza pandemics are caused by novel viruses for which the world population has no immunity [ , ] . each of the six pandemics in the last years were caused by a different novel infl uenza a virus that has undergone antigenic shift, reassortment of gene segments encoding ha and/or na, and successfully adapted to the human host [ ] . however, of the multiple possible combinations between ha genes and na genes, infl uenza viruses with only three combinations (h n , h n , and h n ) have adapted to enable human-to-human transmission suggesting the presence of inherent limitations in viral ability to adapt [ , ] . of the documented pandemics, the most devastating occurred in - (the spanish infl uenza), causing more than , deaths in the usa and over million deaths in the world [ ] . the avian origin infl uenza a h n virus which caused the pandemic had a case-fatality rate of . %, with the majority of the deaths occurring among otherwise healthy young adults - years of age [ ] . the high mortality appeared to be associated with pneumonia caused by bacterial coinfection [ ] . world war i potentially contributed to the spread and severity of the pandemic. crowded conditions, increased stress, and malnutrition could have weakened the immune system of the troops while increased travel of the armed forces and civilians facilitated the spread of the virus throughout the world [ ] . the sequence data of the infl uenza a h n virus suggest that the virus was not a reassortant but rather all eight viral segments were novel with no prior immunity in the human population. in contrast, the viruses that caused the (h n ) and (h n ) pandemics were direct descendants of the infl uenza and evolved from the existing strains through reassortment events with genes from avian infl uenza viruses [ ] . the h n virus with two surface proteins new to humans caused the asian pandemic, resulting in approximately , deaths in the usa and two million deaths worldwide. the h n "hong kong'" virus was associated with , deaths in the usa and approximately , , excess deaths globally. the disease caused by the pandemic h n was relatively mild and the virus became seasonal and is circulating to date [ , ] . predictions that high pathogenicity avian infl uenza (hpai) h n would be the next pandemic strain were the subject of public health concern. the h n continues to spread, causing disease in poultry and occasional human infections through direct contacts with infected poultry. data pertaining to the h n iav strain adaptation to human host is limited, but it appears that human-to-human transmission has not occurred. meanwhile, a fourth generation swine origin descendant of the virus caused a pandemic in [ , ] . three strains of viruses, derived from birds, pigs, and humans, gave rise to the pandemic virus by antigenic shift, reassortment, and recombination in pigs [ ] . human infections with the novel triple reassortment swine origin virus pdm h n were fi rst detected in mexico and then in california in april of , followed by the declaration of public health emergency in the usa [ ] . due to the fast spread of the virus worldwide, the who declared infl uenza pandemic in june [ ] . despite the high transmissibility, the disease severity was moderate which is not typical of most pandemic strains [ ] . a distinguishing feature of the h n virus, also observed in previous pandemics, was the off-season timing for the start of the pandemic and young age prevalence among infl uenza cases, hospitalizations, and deaths. in mexico in the early stage of the pandemic, % of deaths were reported for patients -to -years-old [ ] . in the northern hemisphere, the majority of deaths, . - . %, occurred among adults - years and only . - . % of deaths were reported in adults older than years [ ] compared to a typical infl uenza season when estimated % of deaths occur in this age group [ ] . among hospitalized patients . % of fatalities occurred among adults - years of age during the pandemic while . % fatalities occurred among patients years and older during the preceding infl uenza season [ ] . underlying medical conditions contributed to disease severity in all age groups. cross-reactive immunity was found more frequently among persons older than years of age due to earlier exposure to infl uenza a/h n strains derived from the pandemic virus [ , ] . the impact of infl uenza epidemics or pandemics on the affected population has been associated with predominantly circulating viral types and subtypes and their relation to the preexisting immunity of the human host [ , ] . infl uenza infections may cause especially severe disease in populations already burdened with a high prevalence of chronic pulmonary conditions [ ] . galiano et al. ( ) suggested that the major determinant of infl uenza disease severity was host-related and included immune response, individual genetic background, and likely environmental factors surrounding human host and the virus. they based their hypothesis on the fact that a complete sequence of the a/fujian/ / -like h n virus isolates from cases that died and those who survived did not reveal any genetic differences that could be associated with disease severity or increased mortality [ ] . because the mechanisms by which viruses evolve and adapt to human hosts remain undetermined and the seasonal infl uenza disease continues to cause substantial public health threat, identifying the most vulnerable population groups in a timely manner remains a critical component of public health response. interventions to prevent or mitigate the impact of epidemics and pandemics include vaccination, antiviral drug therapies, and non-pharmaceutical methods. vaccination is considered the most effective prevention method because it creates herd immunity by protecting not only the vaccinated individual but also precluding the viral transmission to those who did not receive the vaccine. however, effective protection can be achieved only if the vaccine strains antigenically match the circulating viral strains [ ] . antiviral therapy is benefi cial, especially when a new viral strain emerges for which there is no vaccine. novel therapeutic technologies against infl uenza offer great promise such as the use of sirna and ribozymes delivered by intranasal spray or retroviral carriage [ ] . non-pharmaceutical methods include social distancing to reduce crowding and personal interactions and travel restrictions [ ] . infl uenza symptoms range from mild upper respiratory ailment to severe complications resulting in patient hospitalizations and in extreme cases, death [ ] . the symptoms of infl uenza-like-illness (ili) include fever, chills, sore throat, or cough [ , ] . depending on the circulating viral strains, diarrhea or vomiting may also be associated with infl uenza infection, especially in children [ ] . infl uenza may be diffi cult to diagnose based on clinical symptoms alone because the clinical presentation may be similar to other respiratory viral and some bacterial infections [ ] . presence of infl uenza virus can be confi rmed by laboratory testing. the disease severity can be characterized by outcome indicators such as hospitalizations, admissions to intensive care units, length of hospital stay (los), utilization of mechanical ventilators, and fl u-associated mortality [ , , , ] . on the average, the frequency of severe cases requiring hospitalization or resulting in death is higher during the seasons when a(h n ) viruses are predominant [ , ] . during the pandemic, an estimated . % of the pdmh n infl uenza cases required hospitalization and could be characterized as severe; approximately , of the cases or . % died [ ] . in a review of studies characterizing the disease severity in the beginning of the h n pandemic, found a wide range of hospitalization rates ( - . %), icu admission rates ( - . %), and fatality rates ( - . %) among infl uenza cases. the fatality rate was signifi cantly higher ( - . %) among patients admitted to the icu. a prospective study in canadian population measured the outcomes of severe infl uenza a (h n ) cases as mortality, length of stay (los) in an icu, and duration of mechanical ventilation. in this study of critically ill patients, % required mechanical ventilation, the median icu stay was days, and . % died within days [ ] . annual infl uenza vaccination is universally recommended in the usa as the most effective prevention method for children older than months of age and for all adults [ ] . vaccinating in advance % of the us population even with loweffi cacy vaccine in combination with school closure could be a cost-effective approach to reducing the disease burden [ ] . susceptibility to infl uenza and severity of the disease is affected by multiple factors including characteristics of the circulating virus strain, genetics of the host, prior infection history, comorbidities, age, and environmental factors [ , ] . higher proportion of younger adults aged - [ ] were more frequently infected during the h n pandemic than traditionally more vulnerable age group years or older during the seasonal infl uenza epidemics while pediatric mortality and morbidity was of a greater concern during the - season [ , ] . this unpredictability of the virus-host interactions and consequences to population's health underscores the need for continuous timely and informative infl uenza surveillance. multiple studies conducted during different infl uenza seasons demonstrated increased severity of infl uenza when chronic conditions such as asthma, diabetes, neurologic disorders, obesity, and cardiovascular disease are present in children and adults [ , , , ] . underlying health conditions, especially chronic lung and heart disease [ ] were more prevalent among the cases admitted to icu or those who died compared to other hospitalized patients diagnosed with infl uenza [ ] . in an international study of more than , hospitalized patients with laboratory confi rmed h n pdm infl uenza proportion of patients with underlying chronic conditions increased with disease severity and constituted . % of those admitted into icu and . % of those who died [ ] . during the pandemic, mortality was higher among individuals with underlying medical conditions regardless of their age [ ] . the presence of any chronic disease was also associated with infl uenza severity among hospitalized cases in the usa during the pandemic and preceding seasonal epidemics [ , ] . underlying health conditions including hiv, cancer, heart disease, lung and respiratory conditions, diabetes, neuromuscular and neurological disorders, obesity, and pregnancy were reported to be associated with increased risk for infl uenza infection or disease severity. however, results were often controversial or not confi rmed to be statistically signifi cant. slightly more than half of a sample from the nis hospitalization records ( . % in - and % in ) reported at least one underlying health condition assessed (fig. . ) [ ] . for both the h n pandemic and a/h n - epidemic seasons, the proportion of records with comorbidities among severe cases ( . % and . % respectively) and among those who died in the hospital ( and . %) was similar and signifi cantly higher than among the hospitalizations with moderate disease ( . and . % respectively). the hospitalized patients with any comorbidity had greater odds of severe seasonal and pandemic infl uenza (or = . and . respectively) and inpatient death (or = . and . respectively) [ ] . during the h n pandemic, a greater proportion of immunocompromised hiv-positive persons were hospitalized with infl uenza compared to hiv prevalence in general population but the h n pdm-associated disease severity and mortality were not substantially affected. in a us study of hospitalized patients with confi rmed pandemic infl uenza a h n , there was no statistically signifi cant difference between the proportion of immunosuppressed patients among those with pneumonia ( %) compared to patients without pneumonia ( %) [ ] . in low prevalence settings the severity of seasonal infl uenza does not appear to change signifi cantly in adults infected with hiv. however, in high hiv prevalence populations, infl uenza may pose a higher morbidity and mortality risk due to compromised immune functions and the presence of tuberculosis, hepatitis, and other comorbidities [ ] . in south african population with high prevalence of hiv among patients with confi rmed infl uenza a (h n ) infection referred to icu, . % were immunosuppressed due to either hiv or immunosuppressive therapy [ ] . cancer patients receiving chemotherapy or after hematopoietic cell transplant (hct) have suppressed immune functions and are susceptible to infections including seasonal or pandemic infl uenza viruses. infl uenza infection outcomes in hct recipients vary depending on the infl uenza virus type and subtype [ ] . studies comparing seasonal and pandemic infl uenza disease in children and adults undergoing cancer therapy found signifi cant differences in clinical symptoms at presentation and in clinical outcomes [ - ] . although children infected with h n were healthier at presentation and had fewer comorbidities they more frequently had pneumonia, stayed longer in the hospital, were more frequently admitted to icu [ ] , and experienced higher mortality ( % vs. %) due to complications compared to children with seasonal infl uenza infections. males were especially at high risk for developing pneumonia. timely antiviral therapy mitigated the infl uenza disease severity in children and adult recipients of hct [ , ] . chronic heart disease is a known risk factor for severe outcomes among persons with infl uenza-like illness. during the h n pandemic, heart disease was the second most prevalent medical comorbidity present in approximately % of reported deaths among adults and in almost % of fatalities among persons years or older [ ] . heart and lung disease were also frequent comorbidities with diabetes and kidney disease among the infl uenza case fatalities. in a dataset pooled from multiple countries in europe, asia, and america chronic heart disease was present in . % of all hospitalized patients with ph n infection, . % of icu admissions, and . % of deaths [ ] . lung diseases were the most frequently reported chronic conditions for the h n infl uenza case fatalities with the chronic obstructive pulmonary disease (copd) most prevalent in adults and asthma in children [ ] . regardless of asthma severity, its prevalence tends to grow with escalating infl uenza disease severity [ ] . infl uenza virus infection is known to exacerbate asthma and asthma is a known risk factor for infl uenza infection. it was the most frequently reported underlying medical condition in pediatric deaths associated with infl uenza a/ h n [ ] . the impact of asthma may also depend on the circulating infl uenza viruses. in a canadian studies of pediatric population hospitalized with infl uenza, children with pandemic h n infl uenza in were signifi cantly more likely to have asthma ( %) than those with seasonal infl uenza during the - seasons ( %) although there were no difference in severity or clinical presentation of asthma between the pandemic and seasonal pediatric infl uenza cases [ ] . asthma was also more prevalent among the children admitted to icu with ph n and developing ph n -associated pneumonia compared with seasonal infl uenza in - [ ] . patients with chronic lung and airways diseases such as copd are at a greater risk for severe morbidity and mortality associated with infl uenza infection. evidence suggests that bacterial coinfections in copd cases may further impact the disease severity. in a study of patients hospitalized with severe copd in italy, viral infection was detected in . % and viral-bacterial coinfection in % of patients hospitalized with copd exacerbation. infl uenza was one of the most frequently identifi ed infections adversely effecting lung function and extending hospital stay [ ] . although many national guidelines recommend infl uenza vaccination, there is only limited evidence that vaccine is effective in copd patients. however, some observational studies suggest that vaccine reduces both hospitalizations and mortality [ ] . the association between diabetes type and type and a greater risk for infl uenza associated complications may be explained by adverse impact of excessive blood glucose on immunity, as well as heart, kidney, and lung functions [ ] . infl uenza surveillance data in wisconsin and new mexico during the h n pandemic indicated that diabetes was the second most frequent comorbidity following asthma and was present in - % of hospitalized infl uenza cases [ , ] . van kerkhove et al. ( ) reported that diabetes was an underlying chronic condition in % of infl uenza-associated hospitalizations and . % of cases admitted to the icu in a sample representing countries with diverse populations and healthcare systems. diabetes was present in % of infl uenza a/h n associated fatalities in england [ ] , . % fatalities in a large international sample [ ] , and % of fatalities in new mexico [ ] . the higher proportion of diabetes in new mexico potentially could be due to a higher than % obesity among hospitalized patients older than years. diabetes prevalence is on the rise in the usa, especially among the aging population, reaching almost % prevalence among persons years of age or older [ ] . infl uenza surveillance and timely characterization of clinical disease course are important for potential prevention and treatment of diabetic infl uenza cases [ ] . neurological and neuromuscular disorders (nnmd) are risk factors for infl uenza infections possibly due to diffi culty clearing secretions from respiratory tract due to impaired or reduced muscle tone and lung function could lead to severe disease [ ] . persons with nnmd also may have an increased susceptibility to recurrent respiratory infection due to diminished ability to protect airways through cough [ ] and a higher risk (or, . ) of infl uenza-related neurologic complications such as seizures [ ] . in a study of infl uenza-associated pediatric deaths during the - infl uenza season, % of the children had neuromuscular or neurologic disorder [ ] . louie et al. ( ) further confi rmed that neurologic diseases with the potential to compromise respiratory function were present in more than % of severe infl uenza cases among children. nnmd were the most prevalent chronic diseases associated with respiratory failure in hospitalized children with laboratory-confi rmed infl uenza diagnosis followed by chronic lung and chronic heart conditions [ ] . a study of pediatric deaths reported to cdc during the h n pandemic showed that % of case fatalities had neurologic disorders. majority of the children also had additional comorbidities such as heart disease [ ] . adult patients who developed pneumonia as a consequence of infl uenza h n infection were more than twice as likely to have a neurological disease compared to patients who had no complications [ ] . neurological disorders found among patients hospitalized due to infl uenza included down syndrome, cerebral palsy, developmental delay, history of stroke [ ] , seizures, spinal cord injuries [ ] , neuromuscular disorders, hydrocephalus, and epilepsy [ ] . pediatric deaths due to pandemic infl uenza fi ve times exceeded the annual average number of deaths caused by seasonal infl uenza viruses during the fi ve proceeding seasons. neurologic disorders were the most frequent comorbidities found in infl uenza-associated pediatric deaths [ ] underscoring the importance of continues surveillance of disease severity and the need for timely characterization of risk factors during an ongoing infl uenza season. during the h n pandemic, obese individuals with body mass index (bmi) exceeding kg/m were at a higher risk for infl uenza infection; they were more likely to be hospitalized and were disproportionately represented among the patients in icus, those with longer duration of mechanical ventilation, longer hospital stay, and those who died compared with those who were not obese [ , , ] . in a study of california adults the prevalence of obesity and extreme obesity among infl uenza cases was . and . times higher respectively than the us population average. the odds ratio (or) for fatality among the extremely obese (bmi > ) patients was . - . [ ] . these fi ndings corroborated the results of kwong, campitelli, and rosella ( ) suggesting that obese individuals were at a greater risk for hospitalization than persons with normal weight during prepandemic infl uenza seasons with or = . and . , for individuals with bmi - . and ≥ respectively. the association between obesity and infection can be explained by impaired immune response or by strain of infection on respiratory system and reduced mechanical function of lungs and airways. obese persons consume high percentage of oxygen to maintain normal respiratory function; they have increased airway resistance and may suffer from hypoventilation and chronic infl ammation of the respiratory tract altering the immune function and the ability to respond to challenges to respiratory system [ , ] . the role of obesity as an independent risk factor may be diffi cult to ascertain, especially in studies with a limited sample size, as it is often directly correlated with other underlying health conditions (e.g., diabetes and heart disease) known to increase risk for infl uenza infections and severe outcomes [ ] . however, because more than % of adults in the usa [ ] and million worldwide [ ] are obese it may be a major contributor to excess morbidity and mortality associated with infl uenza and warrants further investigation. pregnancy has been reported as a risk factor for seasonal and pandemic infl uenza infections and severe disease outcomes using historical and current data. about % of pregnant women infected with infl uenza developed pneumonia during the and pandemics [ ] . pregnancy was reported to be a risk factor for infection with infl uenza and severe disease outcome during the infl uenza a/ h n pandemic as well. in a review of publications on h n pandemic epidemiology in the northern hemisphere, reported that . - . % of hospitalized cases were pregnant women and they comprised . - . % of icu admissions. compared to nonpregnant women diagnosed with infl uenza, they were seven times more likely to be hospitalized and twice more likely to have fatal outcomes [ ] . in a uk study of a population with an estimated % prevalence of pregnancy, % of patients hospitalized with laboratory confi rmed infl uenza h n were pregnant and the majority of them were in the second or third trimester. the case fatality rate ranged between and % [ ] . the rate of respiratory hospitalizations among pregnant women in nova scotia during non-pandemic infl uenza seasons between and was almost times higher for pregnant women than the year before they became pregnant [ ] . pregnant women with comorbidities such as asthma, anemia, and heart or renal disease were at the greatest risk for infl uenza-associated hospitalization. the fi ndings on infl uenza severity association with pregnancy were not consistent. in several countries as the level of disease severity increased the proportion of pregnant women diminished and the odds ratio for death among hospitalized pregnant women was < [ ] . interestingly, in a study of ili hospitalized patients during the - infl uenza seasons, pregnancy was protective against pneumonia (or . ), possibly due higher likelihood of hospitalizing pregnant women with severe respiratory infection [ ] . this observation was supported by a uk study reporting that maternal outcomes were no more severe that for nonpregnant women of similar age hospitalized for infl uenza [ ] . an increased susceptibility to infl uenza infection and severe disease among pregnant women could be partially explained by changes in immune response due to lower plasma levels of adiponectin regulating macrophage activity [ ] . an additional explanation could be psychosocial changes that may occur during pregnancy such as perceived increased stress, anxiety, and negative mood which also were shown to alter the immune functions and increase the risk for respiratory tract infections [ ] . in addition to clinical comorbidities demographic characteristics and socioeconomic conditions also can increase the risk for infl uenza infections. close human contacts in crowded housing during the infl uenza season, infl uenza vaccine uptake in a community, awareness of infl uenza transmission routs, and following the nonpharmaceutical prevention practices effect infl uenza virus spread and attack rates in population. the risk for infl uenza infection may also vary in individuals from different racial/ethnic backgrounds and age groups. historically, higher attack rates and more severe disease outcomes were observed among minorities since s including during the infl uenza pandemic [ , ] . in an analysis of infl uenza h n cases pooled from countries, van kerkhove et al. ( ) reported that indigenous populations and minority groups were disproportionately represented among hospitalized infl uenza cases and fatalities in canada, australia, and new zealand, while in mexico and thailand minority groups did not carry excess disease burden. in a canadian case-control study of laboratory-confi rmed ph n cases, % were represented by the first nation residents. the odds ratio was . for the first nation individuals being admitted to the icu compared to other ethnic groups even when controlling for socioeconomic status, age, residency settings, comorbidities, and time to treatment [ ] . similar results for infl uenza severity were observed in the usa where the risk for ph n infl uenza hospitalization in new mexico was . times higher among american indians, . times higher for blacks, and . times higher for hispanics compared to non-hispanic whites [ ] . surveillance data from states showed that the rate of mortality attributed to ph n was four times higher among the american indians and alaska natives (ai/an ) and they had the highest rate ( . %) of underlying health conditions than all other ethnic groups [ ] . higher proportion of pediatric hospitalizations among minorities was observed during the pre-pandemic seasons as well, including the - season [ ] and - when infl uenza a/ fujiian was the prevalent circulating virus [ ] . although the reasons for disparities in infl uenza susceptibility and severity among the racial and ethnic populations are not fully identifi ed several explanations have been proposed including socioeconomic status and resulting differences in living conditions, crowding, health behaviors, and access to medical care [ ] . cultural differences may affect utilization of available health care or vaccination uptake. difference in genetic susceptibility and higher prevalence of chronic conditions associated with increased risk for infl uenza disease severity may also impact the attack rates and the disease outcome in ethnic minority communities [ ] . traditionally populations at the extremes of the age spectrum, young children and older adults are the most vulnerable groups during seasonal infl uenza epidemics while pandemics exhibit a characteristic shift towards younger adults in infl uenzarelated deaths [ , , ] . persons younger than years of age accounted for a greater proportion of deaths during all three pandemics in the twentieth century as well as during the h n pandemic when young adults were at an increased risk for morbidity and mortality. age was an independent risk factor for severe disease outcomes and death. in a study of hospitalized infl uenza cases in washington state the odds of icu admission or death were . and . times greater among adults - years and - years of age respectively compared with children younger than years when controlling for other risk factors [ ] . the lower infl uenza incidence rate and mortality among adults over years observed during pandemics could be explained by antigen recycling mechanism, a partial protection due to earlier exposure to a similar virus [ ] . however, if infected, this age group had the highest mortality rate among the hospitalized patients [ ] potentially due to the presence of comorbidities, effect of medications, and bacterial coinfections. explanations for severe disease among young adults included antibody-dependent enhanced infection and strong infl ammatory response in the lungs leading to lung injury and ards [ ] . once infected with a novel infl uenza virus younger persons may retain long-lasting immunity better than older persons [ ] . during the seasonal infl uenza epidemics older adults and young children are usually at a higher risk for severe disease and death. the proportion of infl uenzaattributable deaths during the - infl uenza seasons in canada increased with age from % in - age group to % in persons years and older. the case fatality rate for infl uenza hospitalized patients increased from to % for population - years to years or older respectively and over % of deaths occurred in persons older than years of age [ ] . during the - season when infl uenza a fujian strain was predominantly circulating virus increased morbidity and mortality was observed among children younger than years of age [ , ] while children hospitalized due to severe infl uenza during the h n pandemic were signifi cantly older with a larger proportion older than years of age as compared to pediatric admissions during the pre-pandemic infl uenza seasons [ ] . developing immune system and absence of immunity to circulating viruses in young children and weakened immune response to vaccination among the older adults renders both groups especially susceptible to seasonal infl uenza infection [ , , ] . although the health conditions described in this chapter contribute to infl uenza virus susceptibility and severity of the disease, their prevalence and impact may vary during different infl uenza seasons. during the infl uenza pandemic, only one third of the , hospitalized cases representing countries had an identifi ed chronic clinical comorbidity while approximately two thirds of hospitalized cases and % of fatal cases did not have any identifi ed preexisting disease. for the infl uenza pandemic, the overall difference in demographic and clinical factors between the disease severity groups and moderate disease controls suggests that age, sex, race, and all clinical conditions of interest showed overall statistically signifi cant association with infl uenza severity. however, pregnancy was not associated with infl uenza severity for women of childbearing age [ ] . the differences of risk factors and clinical outcomes in different countries further highlighted the need for country-specifi c and global surveillance as well as data sharing internationally [ ] . timely information on circulating infl uenza viruses and the disease burden associated with seasonal and pandemic infl uenza is essential for optimal public health response, identifi cation of vulnerable populations, and for prevention and patient management strategies. susceptibility to infl uenza and severity of the disease is affected by multiple factors including characteristics of the circulating virus strain, genetics of the host, prior infection history, comorbidities, age, and environmental factors. the unpredictability of the virus-host interactions and consequences to population's health underscores the need for continuous timely and informative infl uenza surveillance. clinical surveillance is critical for identifi cation of at risk population groups which also may change depending on the circulating virus as well as for monitoring the disease spread in the population and severity. syndromic surveillance based on nonclinical indicators may contribute to a signal of epidemic spread and increase of cases. to better predict viral strains for effective vaccines and monitor novel emerging viral strains that could cause epidemics it is critical to continue and expand viral surveillance on an international level. while electronic surveillance based on nonclinical data such as over-the-counter medication sales, school absenteeism, and health information seeking may provide preliminary signs of potential infection spread, prompt release of electronic health records (ehr) containing diagnosis and clinical outcomes can lead to a more informative and timely disease surveillance. increasing utilization of patient electronic records could play an important role in attaining public health objectives and complimenting other information sources. cdc estimates of h n infl uenza cases, hospitalizations and deaths in the united states the comparative clinical course of pregnant and non-pregnant women hospitalized with infl uenza a(h n ) pdm infection a large, populationbased study of pandemic infl uenza a virus subtype h n infection diagnosis during pregnancy and outcomes for mothers and neonates infl uenza virus infection during pregnancy in the usa update: infl uenza activity-united states, - season the signature features of infl uenza pandemics-implications for policy introduction to the hcup nationwide independent sample (nis) national surveillance of pandemic infl uenza a(h n ) infection-related admissions to intensive care units during the - winter peak in denmark: two complementary approaches neurological and neuromuscular disease as a risk factor for respiratory failure in children hospitalized with infl uenza infection infl uenza burden for children with asthma age as an independent risk factor for intensive care unit admission or death due to pandemic infl uenza a (h n ) virus infection co-morbidities associated with infl uenza-attributed mortality integrating clinical practice and public health surveillance using electronic medical record systems biosurveillance: a review and update infectious diseases society of america. pandemic and seasonal infl uenza principles for united states action how to maintain surveillance for novel infl uenza a h n when there are too many cases to count code-based syndromic surveillance for infl uenza-like illness by international classifi cation of diseases, ninth revision. emerg infect dis identifi cation of infl uenza cases during the h n pandemic in massachusetts using population-based hospital discharge data pneumonia in us hospitalized patients with infl uenza-like illness: biosense combining free text and structured electronic medical record entries to detect acute respiratory infections meaningful use of electronic nis records for infl uenza severity surveillance the impact of infl uenza epidemics on hospitalizations overview of infl uenza surveillance in the united states syndromic surveillance for local outbreaks of lower-respiratory infections: would it work? detecting infl uenza epidemics using search engine query data detection and early identifi cation in bioterrorism events accuracy of icd- -coded chief complaints and diagnoses for the detection of acute respiratory illness. proceedings amia annual symposium a process evaluation of an active surveillance system for hospitalized - h n infl uenza cases evaluation of icd- codes for syndromic surveillance in the electronic surveillance system for the early notifi cation of communitybased epidemics global emerging infections surveillance & response system (geis) the global emerging infection surveillance and response system (geis), a u.s. government tool for improved global biosurveillance: a review of infl uenza surveillance and monitoring a time-series analysis of clostridium diffi cile and its seasonal association with infl uenza public health syndromic surveillance system syndromic surveillance and bioterrorismrelated epidemics comparison of syndromic surveillance and a sentinel provider system in detecting an infl uenza outbreak value of icd- coded chief complaints for detection of epidemics strategy to enhance infl uenza surveillance worldwide infodemiology: tracking fl u-related searches on the web for syndromic surveillance. amia annual symposium proceedings information technology and global surveillance of cases of h n infl uenza two distinct surveillance methods to track hospitalized infl uenza patients in new york state during the - infl uenza season comparison of patients hospitalized with pandemic infl uenza a (h n ) virus infection during the fi rst two pandemic waves in wisconsin factors associated with death or hospitalization due to pandemic infl uenza a(h n ) infection in california adult hospitalizations for laboratory-positive infl uenza during the - through - seasons in the united states correlates of severe disease in patients with pandemic infl uenza (h n ) virus infection hospitalized patients with h n infl uenza in the united states hospitalized patients with pandemic infl uenza a (h n ) virus infection in the united states nationwide surveillance of infl uenza during the pandemic ( - ) and post-pandemic ( - ) periods in taiwan obesity and respiratory hospitalizations during infl uenza seasons in ontario, canada: a cohort study enhancing infl uenza surveillance using electronic surveillance system for the early notifi cation of community-based epidemics (essence) pertussis hospitalizations among infants in the united states herpes zoster and postherpetic neuralgia surveillance using structured electronic data infl uenza virus evolution, host adaptation and pandemic formation a history of infl uenza historical perspective-emergence of infl uenza a (h n ) viruses the biology of infl uenza viruses types of infl uenza viruses reassortment and evolution of current human infl uenza a and b viruses a complete analysis of ha and na genes of infl uenza a viruses a distinct lineage of infl uenza a virus from bats the pig as a mixing vessel for infl uenza viruses: human and veterinary implications estimates of deaths associated with seasonal infl uenza-united states infl uenza-associated hospitalizations in the united states fatal cases of infl uenza a(h n ) in children: insights from whole genome sequence analysis the signature features of infl uenza pandemics-implications for policy transmission of infl uenza virus in temperate zones is predominantly by aerosol, in the tropics by contact transmission of infl uenza virus via aerosols and fomites in the guinea pig model survival of infl uenza virus on banknotes global infl uenza seasonality: reconciling patterns across temperate and tropical regions dynamics airborne infl uenza a viruses indoors and dependence on humidity mitigation of pandemic infl uenza: review of cost-effectiveness studies the persistent legacy of the infl uenza virus the genomic and epidemiological dynamics of human infl uenza a virus estimation of potential global pandemic infl uenza mortality on the basis of vital registry data from the - pandemic: a quantitative analysis infl uenza seasonality: underlying causes and modeling theories avian-to-human transmission of the pb gene of infl uenza a viruses in the and pandemics hong kong infl uenza pandemic: evidence for a smoldering pandemic the infl uenza pandemic of : lessons and implications department of health and human services. hhs declares public health emergency for swine fl u severe respiratory disease concurrent with the circulation of h n infl uenza epidemiological aspects of h n infl uenza: the accumulating experience from the northern hemisphere epidemiology of pandemic infl uenza a (h n ) deaths in the united states incidence of pandemic infl uenza a h n infection in england: a cross-sectional serological study high mortality from respiratory failure secondary to swine-origin infl uenza a (h n ) in south africa two residues in the hemagglutinin of a/fujian/ / -like infl uenza viruses are responsible for antigenic drift from a/panama/ / infl uenza infection and copd clinical characteristics and -day outcomes for infl uenza a (h n ) multistate surveillance for laboratory-confi rmed, infl uenza-associated hospitalizations in children implications for immunization recommendations assessing the burden of pediatric infl uenza in europe: the european pediatric infl uenza analysis (epia) project infl uenza-associated hospitalizations in the united states estimating the burden of pandemic infl uenza a (h n ) in the united states critically ill patients with infl uenza a(h n ) infection in canada prevention and control of infl uenza with vaccines the role of host genetics in susceptibility to infl uenza: a systematic review mortality and morbidity burden associated with a/h n pdm infl uenza virus: who is likely to be infected, experience clinical symptoms, or die from the h n pdm pandemic virus? fatal cases of infl uenza a in childhood risk factors for severe outcomes following infl uenza a (h n ) infection: a global pooled analysis risk factors for severe illness with pandemic infl uenza a (h n ) virus infection in china complications among adults hospitalized with infl uenza: a comparison of seasonal infl uenza and the h n pandemic infl uenza-associated pneumonia among hospitalized patients with pandemic infl uenza a (h n ) virus-united states infl uenza susceptibility, severity, and shedding in hivinfected adults: a review of the literature differences in clinical outcomes after infl uenza a/h n and seasonal infl uenza among hematopoietic cell transplant recipients risk factors for pandemic infl uenza a (h n )-related hospitalization and death among racial/ethnic groups in new mexico clinical features and outcome of infl uenza a (h n ) virus infections in children with malignant diseases: a case-control study characteristics and outcomes of pandemic /h n versus seasonal infl uenza in children with cancer risk factors and outcomes among children admitted to hospital with pandemic h n infl uenza comparison of children hospitalized with seasonal versus pandemic infl uenza a infections and airway infl ammation in chronic obstructive pulmonary disease severe exacerbations infl uenza vaccine for patients with chronic obstructive pulmonary disease type diabetes and pneumonia outcomes: a population-based cohort study. diabetes care pandemic infl uenza a (h n ) and mortality in the united kingdom: risk factors for death national diabetes fact sheet-diabetes ddt neurologic complications in children hospitalized with infl uenza: characteristics, incidence, and risk factors infl uenzaassociated deaths among children in the united states neurologic disorders among pediatric deaths associated with the pandemic infl uenza obesity and infl uenza association between h n infection severity and obesity-adiponectin as a potential etiologic factor a novel risk factor for a novel virus: obesity and pandemic infl uenza a (h n ) prevalence of obesity in the united states maternal morbidity and perinatal outcomes among pregnant women with respiratory hospitalizations during infl uenza season impact of infl uenza exposure on rates of hospital admissions and physician visits because of respiratory illness among pregnant women pneumonia in us hospitalized patients with infl uenza-like illness: biosense psychosocial factors and susceptibility to or outcome of acute respiratory tract infections racial and ethnic disparities in hospitalizations and deaths associated with pandemic infl uenza a (h n ) virus infections in the united states deaths related to pandemic infl uenza a (h n ) among american indian/alaska natives- states population-based surveillance for hospitalizations associated with respiratory syncytial virus, infl uenza virus, and parainfl uenza viruses among young children pandemic versus epidemic infl uenza mortality: a pattern of changing age distribution lone simonsen, president of sage analytica, inc., graciously donated the nis dataset used in our research study for which we are currently preparing a manuscript of our detailed results [ ] . key: cord- -vxk uqlc authors: fedson, david s title: influenza, evolution, and the next pandemic date: - - journal: evol med public health doi: . /emph/eoy sha: doc_id: cord_uid: vxk uqlc mortality rates in influenza appear to have been shaped by evolution. during the pandemic, mortality rates were lower in children compared with adults. this mortality difference occurs in a wide variety of infectious diseases. it has been replicated in mice and might be due to greater tolerance of infection, not greater resistance. importantly, combination treatment with inexpensive and widely available generic drugs (e.g. statins and angiotensin receptor blockers) might change the damaging host response in adults to a more tolerant response in children. these drugs might work by modifying endothelial dysfunction, mitochondrial biogenesis and immunometabolism. treating the host response might be the only practical way to reduce global mortality during the next influenza pandemic. it might also help reduce mortality due to seasonal influenza and other forms of acute critical illness. to realize these benefits, we need laboratory and clinical studies of host response treatment before and after puberty. an evolutionary perspective in public health has been important in explaining associations between different human phenotypes and chronic diseases [ ] . the same perspective might help us understand many forms of acute critical illness. it might also suggest better ways to manage critically ill patients. two recent studies of influenza virus infection and endotoxemia in mice have shown that survival is better before puberty than after puberty. these studies help explain the lower mortality in children compared with adults seen in the influenza pandemic and in many other types of acute illness. this difference is probably the heritage of human evolution. understanding the scientific basis for this difference suggests an alternative way to respond to the next pandemic. instead of relying on vaccination and antiviral treatment, we might be able to treat patients with inexpensive generic drugs that modify the host response to acute critical illness. unlike pandemic vaccines and antiviral treatments, these drugs will be available in any country with a basic healthcare system. if laboratory and clinical research convincingly demonstrates this approach works, it would benefit people everywhere. this idea has been discussed several times in the past decade [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the influenza pandemic is remembered because it killed as many as - million people worldwide: an estimated . % or more of the global population [ ] . remarkably, the mortality rate was much higher in younger adults than it was in children, giving rise to the familiar w-shaped pandemic mortality curve ( fig. ) [ , ] . a similar mortality pattern has not been described for subsequent pandemics ( , and ). some investigators have attributed high pandemic mortality in young adults to secondary bacterial pneumonia [ ] . this explanation is incomplete and unsatisfactory for several reasons. children were infected with the virus more frequently than adults ( fig. ) and they were almost certainly colonized with the same bacteria that were associated with bacterial pneumonia in adults, yet their pneumonia mortality rates were much lower [ , ] . more important, lower mortality among children compared with adults was not unique to the pandemic. children have lower mortality than adults due to infections caused by many bacteria (e.g. group a streptococcus, s. pneumoniae, s. aureus and m. tuberculosis) and viruses (e.g. mumps, varicella, poliomyelitis, epstein barr virus, hepatitis e, yellow fever, sars and smallpox). similar mortality differences have been seen in several other conditions (e.g. disseminated c. albicans infection, acute lung injury accompanying severe malaria, sickle cell chest syndrome, multi-organ failure following severe trauma, severe burn injury and febrile neutropenia) [ , ] . in short, lower mortality rates among children were not unique to the pandemic. most influenza scientists have sought to explain the mortality difference by studying the virus. numerous reports have shown that the virulence of individual influenza viruses differs markedly in laboratory models of infection. for example, influenza a (h n ) viruses are generally more virulent than h n viruses, and the virus (h n ) was more virulent than the ordinary seasonal h n influenza viruses seen today. antigenic changes in human influenza viruses are frequently reported over the course of a single influenza season [ ] , and in the mortality impact of the second pandemic wave in the fall was much greater than it was during the first wave the preceding spring [ ] . several investigators have sought to explain the greater mortality among adults in by studying influenza disease in human populations. during the influenza pandemic, children - years of age who were living in remote, isolated communities were often the only ones to survive [ ] . there is general agreement that pandemic mortality peaked in young adults, but it was much lower in adults years of age (fig. ) . their lower mortality is thought due to the protective effect of residual immunity following exposure to h n -like viruses that circulated before an h n -like virus (russian influenza) appeared in the early s [ ] . influenza virologists agree that antigenic priming following infection with these earlier h n viruses (known as 'original antigenic sin') provided some measure of long-lasting protection against the highly virulent h n virus that emerged in [ ] . accordingly, individuals born after the early s were exposed only to h n -like viruses and would have missed antigenic priming with pre- h n -like viruses. as young adults in , they were susceptible to infection with the new pandemic h n virus. influenza a viruses are categorized into two groups. group includes h , h and h subtypes, whereas group includes h and h subtypes ( figure a in ref. [ ] ). this phylogenetic understanding has informed recent age-specific analyses (based on individual birth year) of mortality patterns before, during and after the pandemic [ ] [ ] [ ] [ ] [ ] . worobey et al. have used a hostspecific molecular clock approach to demonstrate that high mortality in young adults may have been due to childhood exposure to a doubly heterosubtypic putative h n virus that circulated from to [ ] . they think that young children (but not infants) were protected by childhood exposure to a newly emerged (post- ) h variant or n antigens. miller et al. interpret the historical data more cautiously [ , ] . they agree with worobey et al that early life antigenic imprinting might have led to a dysregulated t-cell response that increased the risk of death following infection in with a new and antigenically dissimilar influenza virus. however, they question whether a new h virus emerged in the early s to replace the h virus that first appeared in . worobey et al have also analyzed cases and deaths due to h n and h n influenza. they have shown that ha imprinting was "the dominant explanatory factor for observed incidence and mortality patterns for both h n and h n " [ ] . for example, individuals born during the period when h n viruses circulated were protected against h n infection (both are group viruses) but were at increased risk of h n infection (a group virus) [ ] . however, individuals born during the - period (the h n era) were protected against h n infection (both are group viruses), whereas those born before (the h n era) were not. the importance of antigenic imprinting was also shown for the h n pandemic. individuals born before were exposed to seasonal h n viruses before the emergence of the new h n pandemic virus in . as older individuals, they experienced a lower incidence of ph n disease in than those born after [ ] . however, miller et al. have argued that early life h n virus infection may have actually increased the risk of death during the heterotypic h n pandemic [ ] . the importance of antigenic imprinting for human influenza is undeniable. 'first flu' may indeed be 'forever' [ ] , but whether antigenic imprinting is helpful or harmful for every individual is still an open question. a similar uncertainty has arisen about influenza vaccination. the doctrine of 'original antigenic sin' was developed following observations that influenza vaccination led to the anamnestic recall of antibodies to earlier influenza viruses [ ] . recent epidemiologic studies, however, suggest that repeated influenza vaccinations may lead to reduced vaccination effectiveness [ , ] . moreover, repeated infection of ferrets with h n viruses affects both the quantity and quality of their antibody responses [ ] . thus, there appear to be two sides to the host response following repeated influenza virus infections and vaccination. moreover, these observations leave open the larger question of whether antigenic interaction among influenza viruses is the only determinant of how an individual will respond to influenza virus infection. writing about the pandemic, ahmed et al. observed that "children were not protected from infection, but, for reasons that are as mysterious today as they were in , they were able to cope with the disease much better than their adult counterparts" [ ] . they added, ". . . this change in disease susceptibility occurs around the time of puberty, and it is possible that sex-associated hormones are involved in this transition" [ ] . in trying to understand the 'mystery' of greater mortality among young adults during the pandemic, scientists have studied influenza viruses and the human response to previous infection. in essence, they have asked 'why did young adults die?' they could also have asked 'why did children live?' [ , , ] . influenza scientists have never created an experimental model of the mortality experience seen in the . recently, however, suber and kobzik experimentally replicated the different susceptibility of children and adults to influenza-related mortality [ ] . they infected groups of c bl/ mice with influenza a(h n ) (pr ) virus. male and female mice were infected on either postnatal day (p , prepubertal) or postnatal day (p , pubertal). (in c bl/ mice, puberty usually starts on postnatal day p or p .) mortality was much greater in pubertal (p ) than in prepubertal (p ) mice ( fig. a and b) . deaths began to occur days following infection. by this time, pulmonary virus titers had fallen to levels much lower than they were on days and , and they were similar in prepubertal and pubertal mice ( fig. c) . high-dose, exogenous estrogen treatment is known to protect adult female mice infected with influenza virus [ ] . to determine the role of sex hormones in the prepubertal/pubertal mortality differences between p and p mice were not significant by the kruskal-wallis with dunn's multiple comparisons test. from ref. [ ] with permission difference, suber and kobzik castrated male and female mice on day p and infected them on day p [ ] . over the next weeks, mortality was reduced in castrated but not in sham-operated mice. they then blocked the onset of puberty in p -infected female mice by pretreating them (starting on day p ) with leuprolide, a gonadotropin-releasing hormone (gnrh) analog. leuprolide desensitizes gnrh receptors and decreases the secretion of gonadotropins, and this blocks the normal pubertal increase in estrogen. they also pretreated male and female p infected mice with acyline, a gnrh antagonist. both leuprolide and acyline pretreatment improved survival [ ] . in addition, when p -ovariectomized mice were infected on day p , estrogen treatment given - or - days following infection abrogated the protective effect of ovariectomy. protection was also reversed in castrated males by treatment with both estrogen and testosterone (normally, testosterone is converted to estrogen by aromatase). transcriptome profiling over the course of infection showed marked enrichment of estrogen, b-estradiol and estrogen receptor [ ] . for this reason, estrogen receptor blockade was carried out using fulvestrant. pretreating p -infected male and female mice reduced subsequent mortality, and when fulvestrant was given to females days following infection, survival was greatly improved. in addition, in older postpubertal male and female mice infected on day p , survival also improved when fulvestrant treatment was started days following infection [ ] . transcriptome analysis also showed increased expression of il- b in the lungs and blood leukocytes of pubertal (p ) mice days after infection [ ] . when pubertal mice were infected on day p and then treated with anti-il- b blocking antibody and days later, survival was greatly improved. early treatment on the day of infection, however, was not beneficial, suggesting that il- b activity was expressed differently at different stages of disease [ ] . as discussed above mortality rates in many infectious diseases are lower in children than they are in adults [ , ] , for this reason, joachim and kobzik studied mice with endotoxin (lps)-induced sepsis before and after puberty [ ] . the conditions for these experiments differed slightly from those in the influenza experiments [ ] ; all mice were female and postpubertal mice were given lps on postnatal days - , not earlier. prepubertal mice injected intraperitoneally with lps on day p - had significantly better survival than postpubertal mice h after injection (fig. a) , although endotoxin levels in the blood were similar in both groups (fig. b) [ ] . as in the influenza experiments, survival in prepubertal mice improved when the onset of puberty was delayed by pretreatment with estrogen ( days before and on the day of lps injection). similarly, in postpubertal mice injected with lps, blocking the onset of puberty by pretreatment with leuprolide (administered daily from prepubertal day p to postpubertal day p ) substantially improved survival. in addition, fulvestrant was administered to pre-and postpubertal mice to determine whether the increase in lps-induced mortality was specifically due to the onset of puberty or the lack of estrogen activity, but the results were indeterminate. finally, in lps-treated postpubertal mice, adoptive transfer of peritoneal cells (macrophages and b and t cells) harvested from lps-naive pre-and postpubertal mice had different effects on survival: mice that received cells from prepubertal mice had significantly lower mortality than those treated with postpubertal cells (fig. c) [ ] . investigators have presented many arguments for and against the use of murine models to explain aspects of acute critical illness in humans [ , ] . for comparative studies of puberty, mice present special problems; humans live much longer than mice and human puberty extends over several years, not a day or two as in mice. nonetheless, murine studies before and after puberty can be of considerable value. for example, estrogens have an mice were injected intraperitoneally with lps (salmonella enterica) and followed for days. mortality in mice injected with prepubertal peritoneal cells was significantly lower than it was in control mice or those that received postpubertal peritoneal cells. from ref. [ ] with permission important role in puberty and they can also modify the response to acute critical illness. kobzik et al. have shown that unlike other studies, estrogen treatment reversed protection against influenza mortality in prepubertal and castrated mice [ ] . these apparently contradictory findings might reflect the known pro-inflammatory activities of low-dose estrogens and their anti-inflammatory effects when higher doses are used [ , ] . suber and kobzik have shown that the different influenza mortality rates in pre-and postpubertal mice have nothing to do with previous exposure to influenza viruses and/or control of virus replication. this observation is critically important. although antigenic imprinting clearly influences human outcomes in both pandemic and seasonal influenza [ , - , , ] , differences in antigenic imprinting might not be the only explanation for better childhood survival during the pandemic. in attempting to understand the 'mystery' of better survival among children compared with adults during the pandemic, investigators have focused exclusively on infection with influenza viruses and ignored the better survival of children with other infectious diseases and noninfectious critical illnesses [ , ] . the better survival of prepubertal mice following endotoxin treatment shown by kobzik et al. suggests that this is a general phenomenon. long-lasting, age-specific antigenic imprinting seen with influenza is not known to occur with most other forms of acute critical illness [ , ] . instead, changes in the host response to critical illness associated with increased mortality appear to begin with the onset of puberty. it follows that factors associated with prepuberty might somehow contribute to the better survival of children compared with adults. infection with influenza viruses initially targets respiratory epithelial cells [ , ] . in response, myeloid and lymphoid cells mount a brisk pro-inflammatory response, often called a 'cytokine storm'. patients who develop severe illness are unable to control what becomes a systemically dysregulated immune response. after several days (usually a week or more), they develop evidence of immunosuppression [ , ] . death occurs in those who are unable to resolve their illness and restore homeostasis. the pathogenesis of acute lung injury, including severe influenza, involves (among other things) mitochondrial dysfunction [ ] , oxidative stress [ , ] , endothelial dysfunction [ , ] and molecular mechanisms (e.g. specific lipid mediators) that initiate the resolution of pulmonary and systemic injury and the restoration of homeostasis [ , ] . the evolutionarily conserved process of autophagy is central to the host response [ ] ; it contributes to both influenza virus replication [ ] and the evolution of influenza-related lung injury [ , ] . the host response to infection may involve mechanisms that enhance resistance (which reduces pathogen burden) or tolerance (which reduces the impact of infection) [ , ] . both resistance and tolerance are driven by a multiplicity of metabolic changes in immune and other host cells [ ] [ ] [ ] [ ] , some of which include estrogen signaling [ ] . some of these immunometabolic changes have been documented in mice with experimental influenza virus infection [ ] . the molecular mechanisms that account for the difference in the mortality rates of children and adults with different forms of acute critical illness (seen in humans and now replicated in mice) are largely unknown. working together, the endocrine, nervous and immune systems integrate and regulate the availability of energy. evolutionary biologists have developed the theory of life history, which emphasizes trade-offs in how energy is allocated to storage, activity, maintenance, and the anabolic activities of growth and reproduction [ ] . according to life history theory, the transition to puberty is accompanied by an overall switch in the allocation of energy from growth to reproduction. nonetheless, although this theory has given us a better understanding of changes in energy metabolism that occur over extended periods of time, it has yet to explain the sudden and intense increase in energy expenditure that accompanies the host response to acute critical illness or whether tradeoffs in energy allocation in critical illness are different before and after puberty. in outbreaks of seasonal and pandemic influenza, only a small number of individuals who are infected develop severe or fatal illness. this was true during the pandemic; although approximately one-third of the human population was infected, only a small proportion died. some of this protection is due to cd + t-cell immunity, especially immunity directed against the evolutionarily conserved np antigen [ ] . this immunity reflects previous exposure of populations to influenza virus antigens, but importantly it encompasses both group and group viruses, unlike antigenic imprinting discussed above. t-cell immunity does not prevent the occurrence of infection, but it modifies the course of illness, reducing virus shedding and in some instances limiting or preventing the occurrence of symptoms [ ] . inborn genetic variants can also account for life-threatening infections [ ] , but the susceptibility of most individuals probably depends more on variations in host defense mechanisms that are expressed only after infection has occurred [ , ] . the importance of these post-infection variations was demonstrated in ha-seronegative healthy young adults who were experimentally infected with influenza h n virus [ ] . (a similar study was undertaken with h n challenge infection [ ] .) following infection, peripheral blood cytokine responses were determined every six hours for the next five days. in nine subjects who developed symptomatic illness, there were early increases in cytokines associated with fever, leucocyte recruitment and markers of innate antiviral immunity, and some of these increases appeared as early as two days before the onset of symptoms [ ] . these cytokine findings were also demonstrated in a parallel genomic analysis. in contrast, the subjects who remained asymptomatic showed early and persistent down regulation of the same inflammatory markers. symptomatic subjects developed cytokine profiles similar to those that have been seen in patients who develop severe illness, while those who remained asymptomatic showed host responses indicating rapid control of infection. these findings suggested that the "inflammatory pathway an individual will follow is probably determined at (a) very early, even presymptomatic time" [ ] . which pathway is followed is probably determined (at least in part) by epigenetic factors [ ] [ ] [ ] . in a study of populations in sweden and japan during the early and late years of the th century, evolutionary biologists showed that the increase in the annual probability of death due to all causes was greatest during the second decade of life, not in later years (fig. ) [ ] . other studies have shown that stress differentially allocates energy resources between reproduction and immune function [ ] , and estrogens contribute to the energy trade-offs that help maintain homeostasis [ , ] . at least some of the mechanisms responsible for maintaining homeostasis during puberty are epigenetically regulated [ ] . numerous laboratory and clinical studies have described biological pathways that are associated with the susceptibility of neonates and the elderly to acute critical illnesses, but very few studies have compared host responses before and after puberty [ , ] . one such study documented the responses of weanling and adult ferrets following infection with the h n pandemic virus [ ] . compared with adult ferrets, weanlings developed much milder clinical illnesses and had less evidence of pulmonary damage, yet rapid virus clearance from the respiratory tract was seen in both groups. like adults, the immune responses of weanlings to infection were robust, but they were different. pro-inflammatory cytokine responses in the two groups were similar, but regulatory response genes for il- and tgf- were more highly expressed in weanlings [ ] . because influenza in ferrets closely mimics the disease in humans, this study suggests that the milder response to influenza in children compared with adults is due to a more strongly expressed regulatory response. very few studies have directly compared the cell signaling responses of children and adults to acute critical illness. nonetheless, in , surgeons reported two studies that directly compared the inflammatory responses of peritoneal macrophages harvested from the sterile abdomens of children and adults [ , ] . pro-and anti-inflammatory responses were elicited by exposing the macrophages ex vivo to endotoxin and il- . unlike adults, responses in children were dominated by an il- anti-inflammatory pattern. recent research has shown that dna methylation stably reduces the expression of il- in th cells [ ] . short-term reversal of this epigenetic mechanism can bring about an increase in il- gene expression. a decade ago, surgeons who were involved in liver transplantation in children and adults sought to better understand inflammatory responses in their patients by studying hepatic ischemicreperfusion injury in mice of different ages [ ] . they found evidence of less inflammation but greater autophagy in the livers of younger ( - -week old) mice compared with older ( - -week old) mice, and the response of younger mice was associated with greater nuclear retention of pparg activity. following pretreatment (for three days) of older mice with the pparg agonist rosiglitazone, their highly inflammatory response was changed to the less inflammatory response seen in younger mice, and this change was associated with the autophagy pattern seen in younger mice. it is important to recognize that in this study younger mice were not clearly shown to be pre-pubertal and treatment was given before, not after the ischemic episode. nonetheless, pre-treatment with rosiglitazone was able to "roll back" the damaging response of "adults" to the more benign response of "children". pparg agonists have important effects on energy metabolism, and there is considerable "crosstalk" among these agents (glitazones) and other drugs that also have immunometabolic activities (e.g., statins [ ] , ace inhibitors and angiotensin receptor blockers [ ] , metformin [ ] ) [ ] [ ] [ ] [ ] [ ] . these findings suggest that many if not all of these drugs could be used to change the host response of adults to that seen in children. the drugs would probably work better if given in combination rather than by themselves [ ] . for a severe infection like pandemic influenza, treatment with these drugs could improve an adult's tolerance of infection [ ] [ ] [ ] [ ] and might improve survival. the drugs might also have similar effects in children who develop life-threatening illness. ever since the emergence of highly virulent avian h n influenza in , virologists have warned of the possibility of a new and devastating influenza pandemic. in , epidemiologists provided an estimate of what global mortality might be if the next pandemic is like the one in [ ] . this estimate ( to million deaths) seems low because in pandemic mortality is thought to have been - million and today the global population is four times larger. a recent study from the institute for disease modeling estimates that during the first six months of a -like pandemic, almost million people could die [ ] . moreover, if the next pandemic is caused by an h n -like virus, which has a high case fatality rate, its impact on global mortality could be much worse [ ] [ ] [ ] [ ] . influenza virologists are now concerned about the possibility of an h n pandemic [ , ] . nonetheless, even in the absence of pandemics, yearly outbreaks of seasonal influenza cause appreciable mortality worldwide [ ] . most of these influenza-related deaths (pandemic and seasonal) occur in developing countries [ , ] . current strategies for national and global pandemic preparedness focus on influenza vaccination for populations and antiviral treatment for individuals [ ] . influenza virologists hope to develop universal influenza vaccines that will provide long-lasting protection, making it unnecessary to vaccinate against seasonal influenza each year [ ] . vaccination with a universal vaccine might conceivably provide protection against infection with a future pandemic virus. recent virologic studies, however, raise important questions about whether this strategy will work [ , ] . moreover, much of the world will lack the human infrastructure to guarantee administration of a universal vaccine [ ] . this means that for the foreseeable future, health officials responsible for pandemic preparedness will have to count on using conventional pandemic vaccines. unfortunately, none of these vaccines will be available during the first six pandemic months [ ] . moreover, when they eventually become available, it is unlikely they will be equitably distributed to low-and middle-income countries that don't produce their own influenza vaccines [ ] . antiviral treatment of individual pandemic patients could also be problematic. supplies of one of the drugs (oseltamivir) are limited and the drug is not widely used. there is also concern about the development of antiviral resistance. moreover, a recent report on patients hospitalized in china with laboratoryconfirmed h n influenza showed that although % of all patients were treated with oseltamivir, case fatality rates were still % [ ] . an alternative strategy for reducing pandemic mortality would be to develop effective treatments that target the host response of patients who develop severe illness [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . these drugs might have some effect on the development of symptomatic illness [ ] , but their potential impact on pandemic mortality would be far more important. agendas for laboratory and clinical research to evaluate their potential have been published in several articles ( table in reference , table in reference , and more generally in references and - ). although influenza scientists often regard host response treatment as an adjunct to antivirals [ ] , some of this research must be limited to generic drugs that target the host response because most of the world's people won't have access to antivirals but will have access to generics. these studies must go beyond documenting cytokine responses following infection and examine immunometabolic and epigenetic factors that affect (among other things) cellular immunity, endothelial function and energy metabolism [ , ] . all of these studies should include comparisons before and after puberty. treating the host response holds promise for not only reducing pandemic mortality but also for reducing the appreciable mortality associated with seasonal influenza and other forms of acute critical illness (e.g., ebola virus disease [ ] ). many of the candidate drugs are produced as generics in developing countries, and supply chains for their worldwide delivery are already in place [ ] [ ] [ ] [ ] [ ] . physicians are familiar with these drugs because they use them every day. if this treatment strategy were shown to work, it could be used in any country with a basic healthcare system. for a pandemic, treatment could start in all countries on the first pandemic day. influenza virologists have expanded our understanding of the molecular biology and epidemiology of influenza viruses. laboratory and clinical investigators have deepened our understanding of the host response to critical illness. evolutionary biologists have suggested that evolution provides insights that could help public health. all of these developments should shape the way we respond to the next influenza pandemic. charles darwin wrote ". . . observation must be for or against some view if it is to be of any service" [ ] . his view -the hypothesis that evolution is guided by natural selection -was supported by extensive observations made over several decades, and its explanatory power (i.e., 'service') has withstood challenge for almost years. the idea (hypothesis) of treating the host response to pandemic influenza was introduced in [ ] . its potential explanatory power has also been supported by experimental and clinical observations, although treating the host response has received little attention from scientists and health officials [ ] [ ] [ ] [ ] [ ] [ ] . yet in a practical sense this approach to treatment could be of great service (in darwin's word) if it could reduce global mortality during the next pandemic. kobzik and colleagues have shown age-specific differences in influenza mortality in mice before and after puberty that are not affected by previous infection (antigenic imprinting) with influenza viruses [ ] . considered with evidence from endotoxemic mice [ ] and other studies [ ] [ ] [ ] [ ] [ ] [ ] , their findings suggest that the mortality impact of pandemic and seasonal influenza and other forms of acute critical illness might be reduced by treating the host response. by reducing the damage caused by influenza in adults to the more tolerant response seen in children, treatment could in effect "roll back" evolution. physicians will inevitably be called upon to manage seriously ill patients during the next pandemic, but there is a real risk they will relive the experiences of physicians years ago [ , ] . this is sure to occur if influenza scientists and public health officials continue to reject the possibility that host response treatment could reduce pandemic mortality [ ] [ ] [ ] ]. if we are to take seriously the challenge of preparing for the next pandemic, it is self-evident that a "top down" approach based on vaccination and antiviral treatment, driven by the decisions of elite scientists, health officials and corporate executives, will not meet the world's needs [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . instead, an effective response must include a "bottom up" approach to individual patient treatment by ordinary doctors working in ordinary healthcare systems who use ordinary, widely available and inexpensive generic drugs that modify the host response. the studies reviewed here suggest that the biological basis for treating the host response reflects our evolutionary heritage. this idea might not be revolutionary [ ] , but its practical implications for health, equity and security during the next pandemic could be immense. consequently, investigators must undertake laboratory and clinical research to convincingly show whether it will be effective. if it is effective and is put into practice, it would represent a striking application of the idea of evolutionary public health [ ] . conflict of interest: none declared. evolutionary public health: introducing the concept pandemic influenza: a potential role for statins in treatment and prophylaxis commentary: from scarcity to abundance: pandemic vaccines and other agents for "have not" countries meeting the challenge of influenza pandemic preparedness in developing countries confronting the next influenza pandemic with antiinflammatory and immunomodulatory agents: why they are needed and how they might work treating influenza with statins and other immunomodulatory agents how will physicians respond to the next influenza pandemic treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and ebola clinician-initiated research on treating the host response to pandemic influenza protective immunity and susceptibility to infectious diseases: lessons from the influenza pandemic predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness was bacterial pneumonia the predominant cause of death in the - influenza pandemic? molecular epidemiology of a/h n and a/h n influenza virus during a single epidemic season in the united states geography may explain adult mortality from the - influenza pandemic the doctrine of original antigenic sin: separating good from evil vaccine-induced antibodies that neutralize group and group influenza a viruses age-and sex-specific mortality associated with the - influenza pandemic in kentucky age-specific mortality during the influenza pandemic: unravelling the mystery of high young adult mortality genesis and pathogenesis of the pandemic h n influenza a virus reexamining the evidence regarding circulation of a human h influenza virus immediately prior to the spanish flu potent protection against h h and h n influenza via childhood hemagglutinin imprinting searching for sharp drops in the incidence of pandemic a/h n influenza by single year of age pandemic paradox: early life h n pandemic influenza infection enhanced susceptibility to death during the h n pandemic first flu is forever imprinting of repeated influenza a/h exposures on antibody quantity and antibody quality: implications on seasonal vaccine strain selection and vaccine performance childhood tolerance of severe influenza: a mortality analysis in mice elevated b-estradiol protects females from influenza a virus pathogenesis by suppressing inflammatory responses characterising pre-pubertal resistance to death from endotoxemia genomic responses in mouse models greatly mimic human inflammatory diseases the future of murine sepsis and trauma research models induction of interleukin- beta (il- b) is a critical component of lung inflammation during influenza a (h n ) virus infection human influenza virus infections mitochondrial dysfunction in lung pathogenesis identification of oxidative stress and tolllike receptor signaling as a key pathway of acute lung injury the role of oxidative stress in influenza virus infection endothelial cells are central orchestrators of cytokine amplification during influenza virus infection the lung microvascular endothelium as a therapeutic target in severe influenza lipidomic profiling of influenza infection identifies mediators that induce and resolve inflammation treating inflammation and infection in the st century: new hints from decoding resolution mediators and mechanisms perpetual change: autophagy, the endothelium, and response to vascular injury autophagy induction regulates influenza virus replication in a time-dependent manner inhibition of autophagy ameliorates acute lung injury caused by avian influenza a h n infection activation of autophagy is involved in the protective effect of b-oestradiol on endotoxaemia-induced multiple organ dysfunction in ovariectomized rats disease tolerance as a defense strategy disease tolerance and immunity in host protection against infection unravelling the networks dictating host resistance versus tolerance during pulmonary infections km es jamieson am. surviving deadly lung infections: innate host tolerance mechanisms in the pulmonary system a guide to immunometabolism for immunologists mitochondrial dynamics at the interface of immune cell metabolism and function estrogen receptors regulate innate immune cells and signaling pathways metabolic pathways of lung inflammation revealed by high-resolution metabolomics (hrm) of h n influenza virus infection in mice endocrinology, energetics, and human life history: a synthetic model natural t cell-mediated protection against seasonal and pandemic influenza. results of the flu watch cohort study human genetic basis of interindividual variability in the course of infection distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges differential evolution of peripheral cytokine levels in symptomatic and asymptomatic responses to experimental influenza virus challenge temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection mitochondria and epigeneticscrosstalk in homeostasis and stress epigenetic and transcriptomic regulation of lung repair during recovery from influenza infection the key role of epigenetics in human disease prevention and mitigation human mortality improvement in evolutionary context metabolic stressors and signals differentially affect energy allocation between reproduction and immune function estrogens and the control of energy homeostasis: a brain perspective the emerging role of epigenetics in the regulation of female puberty differential pathological and immune responses in newly weaned ferrets are associated with a mild clinical outcome of pandemic h n infection a mouse model with age-dependent immune response and immune-tolerance for hbv infection endotoxin induces an exaggerated interleukin- response in peritoneal macrophages of children compared with adults il- beta induces an exaggerated pro-and anti-inflammatory response in peritoneal macrophages of children compared with adults locus-specific reversible dna methylation regulates transient il- expression in th cells activation of peroxisome proliferatoractivated receptor-gamma during hepatic ischemia is age-dependent pleiotropic effects of statins on the cardiovascular system effects of ace-inhibitors and angiotensin receptor blockers on inflammation metformin and inflammation: its potential beyond glucoselowering effect estimation of potential global pandemic influenza mortality on the basis of vital registry data from the - pandemic: a quantitative analysis innovation for pandemics h n virulent mutants detected in chickens in china pose an increased threat to humans estimates of global seasonal influenza-associated respiratory mortality: a modeling study the pathway to a universal influenza vaccine natural and directed antigenic drift of the h influenza virus hemagglutinin stalk domain evaluation of pre-existing antihemagglutinin stalk antibody as a correlate of protection in a healthy volunteer challenge with influenza a/h n pdm virus m the pandemic influenza preparedness framework: a visible procurement option for developing states? epidemiology of avian influenza a h n virus in human beings across five epidemics in mainland china, - : an epidemiological study of laboratory-confirmed case series statins, influenza vaccination and influenza the role of adjuvant immunomodulatory agents for treatment of severe influenza darwin and the scientific method influenza in : recollections of the epidemic in philadelphia herding, social influences and behavioural bias in scientific research: simple awareness of the hidden pressures and beliefs that influence our thinking can help to preserve objectivity revolutionary science key: cord- -mxkputbd authors: gautam, ritu; sharma, manik title: -ncov pandemic: a disruptive and stressful atmosphere for indian academic fraternity date: - - journal: brain behav immun doi: . /j.bbi. . . sha: doc_id: cord_uid: mxkputbd nan brain, behavior, and immunity journal homepage: www.elsevier.com/locate/ybrbi the zoonotic virus ( -ncov) has terrifically affected the world that it becomes even hard to breathe. the sharp pang of this pandemic ( -ncov) is exponentially sweeping across the world and is triggering chaos, fear, anxiety, and stress among the people (montemurro, ) . it may cause pernicious impacts on cognitive functions, and also inflict extensive neurological disruption (wu et al. ) . by april , , more than one million ( , , ) persons have been globally infected due to the convergence of this uncontrollable infectious disease. most of the global population has been depressed and threatened due to the exponential growth of infection and the increasing number of fatalities (covid- coronavirus pandemic, ) . to avoid the mass spreading of this pandemic virus, the decision regarding nationwide lockdown has been taken. no doubt, this will save the masses of life. however, this lockdown is also creating chaos and huge difficulties for the people (sharma et al., ) . the -ncov has shattered the lifestyle, daily routine, business, stock market and even the education system of the globe. the indian academic fraternity has been badly affected by this pandemic. due to scrupulous isolation measures and closedown of universities and colleges, academic fraternity is under insurmountable mental pressure which is raising the prevalence and rate of stress, anxiety and depression among them (charnsil and chailangkarn, ) . primarily, there is a great threat of being infected. the concern of family and friends is also intensifying the stress rate. furthermore, due to the dilemma of lockdown and to maintain the social distancing, the authorities have instructed the teaching fraternity to take their classes online (choudhury et al., ) . during this pandemic, it is very tough to prepare and deliver the quality lectures to the students and the situation gets worse when the teaching is online as most of the teachers have not been trained for the effective use of web resources for teaching. additionally, the teachers who are specialized in conventional teaching found it more difficult to cope with online methods. moreover, the level of frustration during this pandemic would be on the higher side for the old-aged and psychologically-disordered teachers as they are more vulnerable to contamination. the liability of online classes will further intensify the stress as they are not comfortable in using electronic gadgets and online resources. above all, some of the students are not serious in online teaching as the teachers have negligible control over students in online teaching. additionally, the teachers residing in the remote areas are more frustrated and depressed because due to unavailability or poor internet connection, they are not able to complete their tasks (zhang, ) . most of the adhoc and contractual teachers of different colleges and universities are also worried about their job and salary. the teachers employed in small-scale institutes don't get the proper salary and to manage the daily needs of their family they normally indulge in extra works like tuition or part-time job (evening shifts). this pandemic has shut down all the sources of their income. additionally, the level of stress and frustration is on the peak for the guest lecturers as they were paid on the basis of the lectures taken per day. the interruption in research activities during this outbreak is also being a reason of stress for the teaching community. due to the lockdown of colleges, universities the teachers and students (particularly science faculty) are not able to use the facilities of their laboratories. moreover, most of the teachers are not able to access online journals as they have institutional web access only. this pandemic has also significantly affected the mental state of the students. they are also in the dilemma of being infected with this unfortunate pandemic virus. the massive transmission of the fake news over social sites (whatsapp, twitter, facebook) and media has created chaos and stressful atmosphere for the students. the scary atmosphere is affecting the concentration level and the learning ability of the students. the training students (mca/mba/b.tech) who have joined their internship in different companies are not able to get the hand-on experience of the live projects. some of the research scholars (life and applied sciences) who have been carrying out their experiments in their institutional labs for the last couple of weeks and were about to finish their studies feel more frustrated as they have to re-conduct their experiments due to this lockdown. furthermore, different kinds of examinations have been postponed due to this zoonotic virus and there is complete uncertainty about the examination policies i.e. how and when it will be conducted. in addition to the regular examination, most of the competitive examination has also been aborted or postponed for which students were preparing for the last couple of months or even a year. the postponement of the examinations is also causing frustration and stress among the students. these different kinds of tensions disrupt the sleep time of the students which eventually decreases the body's immunity and hence makes them more susceptible to infection. some of the students have taken educational loan for their higher studies in abroad. the restricted transmission has delayed their joining process however; the cycle of monthly instalments is going on. therefore, there will be an excessive financial burden on the students which will indirectly be a cause of stress or anxiety among them. some of the researchers who have got the opportunity of post-doctorate fellowship in different international universities are under tremendous pressure about their future. several such scholars are under high financial burden as most of them have resigned their current jobs for this fellowship. the long prevalence of this pandemic may create different types of psychological disorders among teachers and students. the consequences of this pandemic can be worsened for psychologically weak students and teachers. finally, this pandemic has taught us that the subject of online teaching needs to be incorporated at the primary and higher level of education. additionally, all educational institutes need to periodically organize the workshops related to the use of online learning and teaching. likewise, a short course on stress management needs to be mandatory for all the students so that they can beat the stress in similar catastrophic events. above all, there is a need to be post-traumatic stress disorder and related factors in students whose school burned down; cohort study working from home under social isolation: online content contributions during the coronavirus shock covid- coronavirus pandemic the emotional impact of covid- : from medical staff to common people a chaotic and stressed environment for -ncov suspected, infected and other people in india: fear of mass destruction and causality nervous system involvement after infection with covid- and other coronaviruses thoughts on large-scale long-distance web-based teaching in colleges and universities under novel coronavirus pneumonia epidemic: a case of chengdu university supplementary data to this article can be found online at https:// doi.org/ . /j.bbi. . . . key: cord- -n sf ude authors: drake, tom; chalabi, zaid; coker, richard title: buy now, saved later? the critical impact of time-to-pandemic uncertainty on pandemic cost-effectiveness analyses date: - - journal: health policy plan doi: . /heapol/czt sha: doc_id: cord_uid: n sf ude background investment in pandemic preparedness is a long-term gamble, with the return on investment coming at an unknown point in the future. many countries have chosen to stockpile key resources, and the number of pandemic economic evaluations has risen sharply since . we assess the importance of uncertainty in time-to-pandemic (and associated discounting) in pandemic economic evaluation, a factor frequently neglected in the literature to-date. methods we use a probability tree model and monte carlo parameter sampling to consider the cost effectiveness of antiviral stockpiling in cambodia under parameter uncertainty. mean elasticity and mutual information (mi) are used to assess the importance of time-to-pandemic compared with other parameters. we also consider the sensitivity to choice of sampling distribution used to model time-to-pandemic uncertainty. results time-to-pandemic and discount rate are the primary drivers of sensitivity and uncertainty in pandemic cost effectiveness models. base case cost effectiveness of antiviral stockpiling ranged between is us$ and us$ per daly averted using historical pandemic intervals for time-to-pandemic. the mean elasticities for time-to-pandemic and discount rate were greater than all other parameters. similarly, the mi scores for time to pandemic and discount rate were greater than other parameters. time-to-pandemic and discount rate were key drivers of uncertainty in cost-effectiveness results regardless of time-to-pandemic sampling distribution choice. conclusions time-to-pandemic assumptions can “substantially” affect cost-effectiveness results and, in our model, is a greater contributor to uncertainty in cost-effectiveness results than any other parameter. we strongly recommend that cost-effectiveness models include probabilistic analysis of time-to-pandemic uncertainty. pandemic influenza events have occurred repeatedly throughout history (potter ) . the recent re-emergence of highly pathogenic avian influenza h n in and the less fatal but more transmissible h n swine influenza strain of have pushed pandemic influenza up the public health policy agenda. as a consequence funds earmarked for pandemic influenza preparedness have risen markedly over the past decade (united nations system influenza coordinator ) . correspondingly, the number of economic evaluation or costeffectiveness studies of pandemic influenza investment options has also increased. a recent systematic review by pérez velasco et al. ( ) indicates that there have been such studies to date. methodology for the economic evaluation of pandemic preparedness investments, and public health interventions generally, draws on methods developed for health technology assessment. methodological challenges raised by the more complex decision context of public health investment including pandemic influenza preparedness are still being identified and addressed (weatherly et al. ; drake et al. ) . uncertainty is a characteristic feature of a pandemic. there is a risk that an as yet unknown highly pathogenic and highly transmissible pathogen will emerge and cause substantial mortality and morbidity worldwide. we do not, and perhaps cannot, know when this will happen, how virulent or how infectious a novel pathogen will be. in general, healthcare economic evaluations make an implicit assumption of consistency in health burden. an analysis based on a clinical trial, for example, is only relevant to policy making if the evaluation context remains reasonably consistent over time. in contrast to this, a pandemic is a one-off event and although there may be similarities to previous pandemics it will nevertheless be fundamentally and unpredictably different. a key challenge for pandemic influenza health economists is to model prospectively; considering how future pandemic events could present differently from past events. sensitivity and uncertainty analysis are separate but related approaches for assessing the influence of input model parameters on the outcome result. these terms are sometimes used interchangeably but we use the concept of 'sensitivity' to refer to the degree of change in model output for a given change in a model input parameter. in contrast, 'uncertainty' has bayesian connotations and has been defined as 'any deviation from the unachievable ideal of completely deterministic knowledge of the relevant system' (walker et al. ) . we consider attributable model uncertainty in terms of the total imprecision in the model output due to imprecision in one or more parameter inputs (o'hagan and luce ; cooper et al. ; duintjer tebbens et al. ) . pandemic economic evaluations often consider a single base case pandemic scenario, then explore a small number of variations from this base case using univariate sensitivity analysis (e.g. eynard et al. ; halder et al. ) . pandemic 'uncertainty' is usually not given special attention and the parameters included in a sensitivity analysis vary between studies with pandemic attack rate, mortality rate and particularly time-to-pandemic, all omitted in different studies to-date. a more robust approach than a simple deterministic sensitivity analysis is to simulate a large number of scenarios, drawing new parameter results for each scenario according to predefined probability distributions. this method is known as 'monte carlo' sampling, and in health economics is increasingly used in probabilistic sensitivity analysis. however, monte carlo sampling (or its stratified version, latin hypercube sampling) can also be used for uncertainty analysis or even replace the deterministic base case scenario. many pandemic economic evaluations do take a probabilistic approach, including the first published study of this kind (meltzer et al. ). however, many subsequent studies present a single base-case scenario despite the choice of pandemic characteristics being somewhat arbitrary. time-to-pandemic-does it affect decision making? to a policy maker or public health planner, whether a pandemic occurs in or years makes a big difference in terms of investment choices and resource allocation. in all sectors, including health, the length of time before gains or losses are likely to occur is weighed in the decision making process. in economics, discounting is the practice of adjusting the value of future gains or losses to reflect their present day equivalent. this is applied to costs and, in many cases, to health impact and in theory reflects the time preferences of the population. when undertaking cost-effectiveness analysis of pandemic influenza investment options, there are four general ways to handle pandemic timing: ( ) retrospective-fixed time analysis. ( ) prospective-fixed time analysis. ( ) prospective-deterministic sensitivity analysis. ( ) prospective-probabilistic sensitivity or uncertainty analysis. time-to-pandemic uncertainty, does it matter? interestingly only a minority of pandemic economic evaluations to date include a sensitivity analysis of time-to-pandemic. within the pandemic economic evaluations included in the review by pérez velasco et al. ( ) , we identify four studies that include pandemic timing in a univariate sensitivity analysis (meltzer et al. ; siddiqui et al. ; lee et al. ; newall et al. ) , and a further three that model uncertainty in pandemic timing probabilistically (balicer et al. ; lugnér and postma a,b; carrasco et al. ) . siddiqui and edmunds ( ) found that pandemic timing is the second largest source of parameter uncertainty after mortality rate, while meltzer et al. ( ) find the results and implications for policy 'depend most [our emphasis] on the assumed probability of the pandemic', although they do not include this in the probabilistic analysis. to date, all probabilistic models assume a poisson stochastic process (a sequence of discrete events where the times between successive events are independent and exponentially distributed), expressed in some studies as a constant annual probability of a pandemic. the implicit assumption is that emergence of a pandemic event has a constant year on year probability driven by random mutation or re-assortment, which eventually produces an influenza strain that results in effective humanto-human transmission and thus has pandemic potential (webster ) . while viral mutation will be important, there are a range of socio-economic, environmental and ecological factors which may influence the emergence of a future pandemic (jones et al. ) . the probability of a pandemic event that arises from these complex factors may not be well characterized by poisson stochasticity. pandemic preparedness measures such as stockpiling of antiviral therapies or personal protective equipment require an upfront investment for an unknown benefit at an unknown point in the future. the aim of this study is to establish whether uncertainty in when a pandemic will next occur (henceforth 'time-to-pandemic') is important when evaluating whether pandemic preparedness activities are an efficient use of scarce resources. is calculation of a cost-effectiveness ratio sensitive to changes in assumptions of time-to-pandemic? is time-to-pandemic an important driver of total model uncertainty? we explore the importance of this uncertainty when using standard cost-effectiveness methods to evaluate investment in health system pandemic preparedness. we consider a case study of antiviral stockpiling in cambodia, a low-income country with many pressing demands on healthcare resources considered a hotspot for emerging infectious diseases (coker et al. ) . the comparison is 'no stockpile', and the evaluation perspective is from the medical provider. health impact is measured in disability adjusted life years (dalys), and costs are the cost of the antiviral stockpile. health gains resulting from the stockpile occur at a certain point in the future in the event of a pandemic and are therefore discounted, whereas the investment cost occurs in the present and so is not. this analysis is intended as a stylized decision scenario and is not intended as a cost-effectiveness analysis of antiviral stockpiling in cambodia. to analyse the impact of time-to-pandemic on model output, we use a simple pandemic event model to generate an incremental cost-effectiveness ratio (icer) for an antiviral stockpile. for a population ðmÞ a proportion ðhÞ is hospitalized due to the pandemic virus during the course of the pandemic. of these a further proportion f ð Þ dies from the pandemic disease. a quantity ðqÞ of antivirals are stockpiled at cost ðcÞ; for simplicity the cost of stockpile replenishment is not included. receiving an antiviral when hospitalized due to pandemic influenza reduces the risk of fatality by a proportion ðrÞ. we define a parameter set which is broadly representative of the cambodian context. the model structure is outlined as a probability tree in figure , and all parameters are detailed in table . the model was coded in the statistical software package 'r', version . . . the net health impact ðÁÞ in terms of dalys is calculated by subtracting total deaths in a baseline scenario from total deaths in an intervention scenario and converting to dalys using a conservative assumption of an average dalys lost per death. pandemic costs and consequences are adjusted to present day value using the discount factor ( þ discount rate) ðÞ and timeto-pandemic ðtÞ. the discounted health impact ðÀÞ is given by: the icer ð Þ is then given by: this highlights that the icer is proportional to the discount factor to the power of 'time-to-pandemic', clarifying the interaction between discount rate and pandemic timing. the presence of a power law helps to explain the extent to which uncertainty in discount rate and time-to-pandemic affects the icer. there is some debate as to whether health outcomes should be discounted (severens and milne ; bos et al. ) . this debate centres on whether the measure of health utility already incorporates a valuation of time. it seems reasonable that long duration illnesses such as hiv/aids do contain consideration of the value of future years. for pandemic or epidemic events where the disease duration is short but when the case occurs is uncertain, it seems likely that some form of discounting is needed to reflect time preferences. that is, given the choice, an individual would prefer to contract a highly pathogenic influenza in years rather than next year. the cost-effectiveness analysis considers the cost per daly averted for scaling up the antiviral stockpile by million courses. potentially serving % of the . million total population a stockpile of million courses is a substantial increase on the courses currently retained (data supplied by ministry of health, cambodia). to gather data on time-to-pandemic, we considered major pandemics in the last years and calculated the interpandemic period. information on possible earlier pandemic event years was not included as the veracity of some pandemic assumed between . % and % of the population would be hospitalized at some point during the course of a pandemic. case fatality proportion f uniform ( . - . ) lower: who severe pandemic threshold is % case fatality; however, this refers to the proportion of all cases which die. this is the case fatality proportion for hospitalized patients which we would expect to be higher. we assume a lower bound of % and upper bound of % case fatality. time-to-pandemic (years) t uniform all fitted to data in table dates is disputed (potter ) (pandemic dates and intervals are presented in table ). using the historical pandemic interval data we carry out a univariate sensitivity analysis to assess whether observed differences in the number of years between pandemics can substantially affect cost-effectiveness results. however, univariate analysis is limited because it does not account for interaction between the values of other model parameters. sensitivity to time-to-pandemic may be different given a different set of other input parameter values. we therefore use multivariate monte carlo simulation to sample parameter values from uniform distributions of six model parameters (time-to-pandemic, case fatality proportion, hospitalization proportion, discount rate, intervention cost and intervention effectiveness), repeating times to produce results from a wide range of parameter combinations. parameter 'importance' is assessed using elasticity and mutual information (mi) measures (described below). the purpose of this study is to determine whether uncertainty in the number of years before a pandemic occurs (time-topandemic) is important in cost-effectiveness analysis. for this reason, the analysis is designed as a 'challenge' model using large estimates of uncertainty in other model parameters to present the greatest challenge to the importance of time-topandemic. in most cases, little data exists to fit sampling distributions of the model parameters so in general uniform distributions have been used with ranges at logical or plausible limits. if pandemic timing uncertainty is shown to be important compared with large estimates of uncertainty in other pandemic characteristics then we can conclude that pandemic timing uncertainty is important to cost-effectiveness analysis of pandemic influenza preparedness. we use two measures to determine the importance of uncertainty in the time to the pandemic to the overall uncertainty in icer: mean elasticity and mi. although the potential value of the mi measure in health economics has been reported (coyle et al. ) , it is not commonly seen in the health economics literature. similarly, while elasticity is a concept commonly used in economics it is rarely found in healthcare economic evaluation. we describe both measures fully here for completeness. the elasticity of a parameter describes the extent to which an output changes given an incremental change in an input parameter. this is frequently used in economics to describe effect of demand given a change in price. using elasticity to measure parameter importance is a logical step from routine sensitivity analysis of economic evaluation, which commonly presents a change in icer given fixed univariate changes in an input parameter. standard univariate sensitivity analysis is useful in quantifying the impact of possible parameter changes on cost effectiveness. to compare the sensitivity of the icer to each parameter on equal basis, we normalize the univariate sensitivity analysis, producing a point elasticity for each monte carlo simulation. we take the mean of the point elasticities and report the mean parameter elasticity as a unit-less measure of parameter importance. the icer is a function of the parameters listed in table . in a general mathematical formulation if we denote the icer by y and the model parameters by ðx j , j ¼ . . . nÞ where n is the total number of parameters, then the icer can be represented as a non-linear function g of the n parameters: the normalized local elasticity measure is defined as: where the symbol @ denotes partial differentiation, and the elasticity is evaluated at x j ¼ x. È y, x j À Á is the proportional change in y due to a small proportional change in x j . the mean elasticity measure " È y, x j À Á is more appropriate to assess parameter sensitivity under uncertainty (where there is not a high degree of confidence in the expected value). this is given by coyle et al. ( ) : where n is the number of point-wise evaluations carried out within the range x j, min , x j, max  à , and the symbol means 'element of'. mi analysis is based on information and entropy theory (fraser and swinney ; veyrat-charvillon and standaert ; batina et al. ) , the origins of which lie in estimating the entropy of thermodynamic systems. its use has been advocated in the health economics literature (coyle et al. ) . the entropy hðyÞ of an uncertain variable y (such as the icer) is defined in continuous space by the following integral equation: where ðyÞ is the probability density function of y and ½y min , y max is the range of y (i.e. y min and y max are the lower and upper bounds of y, respectively). the mi between the icer ðyÞ and a variable on which it depends x j (e.g. case fatality proportion or time-to-pandemic) is defined by the following double integral equation: where the double integration is carried over the range of icer and the range of parameter x j , x j, min , x j, max  à and y, x j À Á is the joint probability density function of y and x j . Éðy, x i ) is the mi and can be interpreted as the amount of uncertainty that is reduced in y if the uncertainty in x i is removed (e.g. because of new information acquired on x i ) or alternatively the amount of information that y and x j share. in practice, discrete rather than continuous analysis is carried out. the counterpart equations to ( ) and ( ) in discrete space are: and where pðy ¼ yÞ denotes the probability that y ¼ y, and p y ¼ y, x j ¼ x À Á denotes joint probability that y ¼ y and x j ¼ x. from equation ( ), it can be shown mathematically (dragomir and goh ) that ðy, x j Þ ! , y, x j À Á ¼ if y is independent of x j and that ðy, x j Þ attains its maximum when y ¼ x i (i.e. y and x j are the same) or when y is a deterministic function of x j . this fits exactly with the interpretation given above of mi. in one extreme, if the icer is independent of a parameter then reducing the uncertainty of that parameter would not have any effect on the uncertainty of the icer. at the other extreme, if the icer depends on one parameter only, then reducing the uncertainty in the icer is maximized by reducing the uncertainty of the parameter to its minimum. we used the r package 'entropy' for mi calculations (hausser and strimmer ). variation in icer and parameter elasticity by parameter value. in the parameter uncertainty analysis outlined above a uniform distribution is used to model time-to-pandemic uncertainty (mean years, range - years). we relax this assumption in a secondary analysis of uncertainty by also running analyses with normal, poisson and gamma distributions. all distributions are fitted to the data on pandemic interval in table , using the fitdistrplus package within r (delignette-muller et al. ). the normal distribution is truncated at to prevent sampling of negative values. we use the mi to assess whether time-to-pandemic uncertainty remains important irrespective of sampling distribution choice. the world health organization recommends using a costeffectiveness threshold of - times the national gross domestic product (gdp) per capita (world health organization ); however, there are many limitations to using this rule including situations when funds originate from international organizations (drake ). nevertheless, we include an illustrative calculation of the proportion of simulations found to be 'cost effective' at a threshold of us$ per daly averted, the gdp per capita in cambodia (world bank ). the mean cost of the million course stockpile is us$ million (median also us$ m) with mean dalys averted (median: dalys averted), and a mean icer of us$ per daly averted (median: us$ per daly averted). note that the mean and median icer is calculated per monte carlo simulation not from the mean and median costs and dalys averted. figure shows the spread of simulation results on the cost-effectiveness plane. costs range uniformly between us$ and million while deaths averted are highly skewed with a small number of pandemic scenarios producing a high death toll. univariate analysis of change in icer adjusting for timing according to pandemic intervals from historical data is presented in table ; the range is us$ to us$ per daly averted. in the probabilistic analysis, parameter sensitivity and uncertainty are assessed by calculation of elasticity and mi, respectively (table ) . using both measures, the most 'important' parameters identified are discount rate and time-topandemic. these have an elasticity slightly greater than two, indicating that, on average, an increase in discount rate or time-to-pandemic causes a greater than proportional increase in the icer. all other parameters have a mean elasticity magnitude of indicating that a change in the parameter causes a roughly proportional increase or decrease (for negative elasticities) in the icer; that is an doubling of the parameter value causes the icer to double or halve, respectively. similarly, mi scores for discount rate and time-to-pandemic are two to three times larger than the other parameters, indicating a greater contribution to total uncertainty in the icer result. figure presents how icer and elasticity vary with each parameter. the first row of figure shows how change in input parameter (x-axis) affects the icer result (y-axis). each point represents a model simulation and skewness in the distribution of simulations reflects the relationship between the parameter and the icer. a loess mean regression line with % confidence interval is overlaid using the r package 'ggplot' (wickham ). the second row of figure also plots change in input parameter (x-axis) but this time against elasticity, outlining whether parameter point elasticity is dependent on the value of the parameter being measured or on other parameters. elasticity is measured for each monte carlo simulation, and each simulation probabilistically samples from six model parameters, so each elasticity measurement corresponds to a new model parameter set describing a new pandemic scenario. for the hospitalization proportion and the case fatality proportion elasticity is constant at À irrespective of their value at measurement or the value of other parameters. similarly, intervention cost has a constant elasticity of . elasticity for intervention effectiveness increases at greater parameter values but is independent of other model parameter values. the elasticity for discount rate and time-topandemic is dependent not only on their own parameter value but also on the value of the other parameter. that is, there is an interaction between discount rate and time-to-pandemic when assessing elasticity. the uniform sampling distribution for time-to-pandemic is replaced with gamma, normal and poisson distributions, repeating monte carlo simulations for each distribution type. mean icers for uniform, gamma, normal and poisson distributions are us$ , us$ , us$ , us$ per daly averted, respectively (table ). the proportion of prior for uniform, gamma, normal and poisson time-to-pandemic sampling distributions and corresponding icer output distribution. simulations cost effective at a willingness-to-pay of us$ per daly averted does not differ substantially with different timeto-pandemic sampling distributions and the contribution of time-to-pandemic to uncertainty in the icer remains high compared with other model parameters as measured by the mi. this can be seen in figure which presents the prior (time-topandemic) and posterior (icer) probability density curves. the shape of the posterior or icer probability density curve is consistent irrespective of the prior or time-to-pandemic distribution choice. the results of this analysis demonstrate that uncertainty in time-to-pandemic is important in pandemic cost-effectiveness models. both univariate and multivariate measures of elasticity found that in our model the icer was most sensitive to changes in time-to-pandemic and discount rate. similarly, mi analysis found that time-to-pandemic and discount rate were the principle drivers of uncertainty in the model results. uncertainty in pandemic hospitalization rate was also important, as would be expected. while time-to-pandemic is important the choice of sampling distribution was less so, with similar contributions to uncertainty resulting from uniform, gamma, normal and poisson distributions. pandemic cost-effectiveness models should either take a probabilistic (bayesian) modelling approach to incorporate uncertainty in time-to-pandemic and other pandemic parameters into the base case analysis or conduct a full probabilistic sensitivity analysis around a fixed base case scenario. the large amount of pandemic uncertainty in the model, which cannot easily be reduced, may mean that reducing uncertainty in other parameters, such as treatment effectiveness, offers minimal improvement to the usefulness of pandemic cost-effectiveness models. one additional aspect of the relationship between time-topandemic and cost effectiveness is that if year-on-year no pandemic occurs then the expected time to pandemic decreases and the expected cost effectiveness of investment rises. ironically there may be an inverse relationship between cost effectiveness and likelihood of investment in pandemic preparedness measures, i.e. decision makers are more likely to act on pandemic preparedness immediately following a pandemic and interest wanes with time. the consequence of discounting future health losses leads to a greater emphasis on the short term. should standard rate of time preference be applied to events with potentially catastrophic impact? are population time preferences in line with individual preferences? individual preferences can betray the public good as seen in individual vs social demand curves for vaccine uptake (fine and clarkson ) . if we take a long run perspective, individuals come and go, and so they have a clear timepreference, but the population remains. in effect the problem becomes philosophical; relating to the current generation's responsibility to future generations. this problem is mirrored in other population level challenges such as climate change, national debt accumulation or risk of redundant antibiotics resulting from widespread antibiotic usage. this analysis points towards the heavy impact that time-preferences of individuals has on these decision contexts. further work is needed to (re)establish norms for discounting in these contexts. central to this will be the question of whether time preferences are different when individuals make decisions as a community, whether time preferences differ with very high impact events and whether discount rates are indeed constant for long time-spans. this study has several limitations. the model is a simple decision tree and does not include more sophisticated model structures recommended in pandemic preparedness cost-effectiveness analysis (lugnér and postma a,b; drake et al. ) . however, this is not likely to be a significant problem as these approaches aim to more accurately assess the effectiveness of pandemic preparedness of interventions and therefore would be unlikely to lead to a lower estimate of the importance of time-topandemic. the model also only considers antiviral stockpiling as a pandemic preparedness measure. other pandemic preparedness options may not require upfront investment, such as social distancing measures in response to a pandemic and therefore time-to-pandemic would not be an issue. pandemic preparedness requires upfront investment and the benefits of this investment are only realized during the course of the next pandemic, an unknown number of years after the investment. we find that in the economic evaluation of pandemic preparedness investments the uncertainty in timeto-pandemic is a dominant factor in model uncertainty. mathematical models to assess the cost effectiveness of pandemic preparedness options should include probabilistic sensitivity or uncertainty analysis of time-to-pandemic. at the same time, steps should be taken to carefully consider the most appropriate approach to discounting the impact of future catastrophic events such as pandemics. cost-benefit of stockpiling drugs for influenza pandemic mutual information analysis: a comprehensive study discounting health effects in pharmacoeconomic evaluations: current controversies strategies for antiviral stockpiling for future influenza pandemics: a global epidemiceconomic perspective emerging infectious diseases in southeast asia: regional challenges to control comprehensive decision analytical modelling in economic evaluation: a bayesian approach measures of importance for economic analysis based on decision modeling fitdistrplus: to fit a parametric distribution to non-censored or censored data a counterpart of jensen's discrete inequality for differentiable convex mappings and applications in information theory priority setting in global health: towards a minimum daly value. health economics (early view online cost-effectiveness analysis of pandemic influenza preparedness: what's missing? uncertainty and sensitivity analyses of a dynamic economic evaluation model for vaccination programs influenza pandemic planning in switzerland-an economic perspective individual versus public priorities in the determination of optimal vaccination policies independent coordinates for strange attractors from mutual information cost-effective strategies for mitigating a future influenza pandemic with h n characteristics entropy inference and the james-stein estimator, with application to nonlinear gene association networks global trends in emerging infectious diseases economic analysis of pandemic influenza vaccination strategies in singapore investment decisions in influenza pandemic contingency planning: cost-effectiveness of stockpiling antiviral drugs mitigation of pandemic influenza: review of cost-effectiveness studies the economic impact of pandemic influenza in the united states: priorities for intervention cost-effectiveness of pharmaceutical-based pandemic influenza mitigation strategies a primer on bayesian statistics in health economics and outcomes research systematic review of economic evaluations of preparedness strategies and interventions against influenza pandemics a history of influenza discounting health outcomes in economic evaluation: the ongoing debate cost-effectiveness of antiviral stockpiling and near-patient testing for potential influenza pandemic animal and pandemic influenza: a framework for sustaining momentum mutual information analysis: how, when and why defining uncertainty: a conceptual basis for uncertainty management in model-based decision support methods for assessing the cost-effectiveness of public health interventions: key challenges and recommendations predictions for future human influenza pandemics ggplot : elegant graphics for data analysis world bank world health organization the authors would like to thank korbinian strimmer for advice on calculating mi using the r 'entropy' package and yoel lubell for comments on the study aims and methods. the work was supported by the german federal ministry for economic cooperation and development (bmz) as part of deutsche gesellschaft für internationale zusammenarbeit's (giz) german pandemic preparedness initiative. ethical approval for the wider project has been granted by the ministry of health in cambodia and the london school of hygiene and tropical medicine. no empirical data was collected for this study. this manuscript has not been published in whole or in part elsewhere. time-to-pandemic uncertainty, does it matter? none declared. key: cord- - wlpvmv authors: rubinić, ivan title: pandemic paradigm shift date: - - journal: nan doi: . /wusa. sha: doc_id: cord_uid: wlpvmv the surprising outbreak of an anticipated virus has exposed that the profit‐centered mode of production renders a dysfunctional society, with a high incidence of pandemic‐prone diseases. consequently, the global health crisis and subsequent economic collapse threatening the existence of billions reveal the ultimate market failure from both heterodox and radical theoretical viewpoints. the demise of markets and capitalist systems calls for a straightforward economic intervention and radical transformation of the way societal production is conceptualized. this paradigm shift must deprioritize economic growth driven by the omnipresent commodification of all social relations and must furnish a viable alternative provided by the political economy. the starting point for such fundamental change in the dominant discourse must be rooted in balancing between the needs and wants, and in creating an environment in which properly understood self‐interest would bring about a sustainable and equitable increase in societal well‐being. the coronavirus pandemic outbreak was the turning point that radically transformed social and economic lives across the globe. with detrimental presymptomatic interpersonal transmission, this novel and deadly virus has rapidly spread among the population and has postponed, until further notice, worldwide economic activity. due to the lack of effective antidotes, physical distancing becomes the last line of defense. this has effectively disabled the labor force from participation in the production process and, thus, has imposed economic lockdown of a hitherto unrecorded magnitude. soon after its emergence, the adverse effects of viral biohazard have disclosed that the dynamics of epidemic models have an enormous potential to outgrow its biological foundations and infect the societal material reproduction. the latter has major bearing in a crisis prone (marx, ) , highly financialized environment that prioritizes debt-led growth which, through a spread induced by debt-deflation spiral (fisher, ) , may cause an epidemic of "economic diseases" and initiate financial crashes. economic history has demonstrated that these "black swan events" are seldom. however, when they do occur, the compounded biological and economic effects are generating havoc with severe implications for societal reproduction. as such, these events are invariably the cause behind major economic disruptions that can overthrow the dominant mode of production. hence, it comes as no surprise that these effects exacerbate the existing and self-evident malfunctions of the capitalist system and are likely to spark the sharpest recession since the great depression. therefore, the current crisis with yet unknown, but undeniably long-lasting and devastating consequences, challenges the predominant set of economic beliefs and demands in-depth interdisciplinary scholarly attention. the publication by vidal ( ) points out, through a consensus among professionals, that the economic progress leading to the destruction of biodiversity, invasion of wildlife harbors, rapid urbanization, densely populated locales, and growing global interconnectedness, creates a favorable condition for the pathogen's cross-species transition. in accordance to jones, the released article concludes that the expansionary economic regime, through the disruption of the fragile balance between human and ecosystem health, generates "a hidden cost of human development." as a matter of course, where there exists a cost, there surfaces a need to approach the subject from the economic perspective. therefore, a prime concern of the pragmatic economist should be placed on answering the following four questions: where does the responsibility for this cost lie? what are the likely consequences of this cost going to be? which authority can structure the response plan, repayment scheme, and who is to bear the expenses? what are the larger theoretical and practical implications resulting from this socioeconomic turmoil? to that end, through the use of a narrative method, this study aims to furnish content to the premise that from both the heterodox and radical economic viewpoints: (a) the coronavirus pandemic must be considered a market failure, (b) the ongoing pandemic has the potential to beget a three-layer economic crisis, starting at a point of production, (c) the solution for the existing state calls for sizable supranational and/or national economic interventionism, and (d) the pandemic necessitates a shift from the profit-centered neoliberal paradigm toward the society focused on efficient, sustainable, and equitable development. the remainder of this exposition is structured as follows: the section positions the current health crisis within the well-defined economic analytical framework of market failure; the section explains the nature and the dynamics of the threefold economic crises, resulting from the expected spillover effects induced by the coronavirus; the section offers a number of remedies; the section endeavors to locate the sources for financing the expenses of an effective pandemic response plan; the section provides arguments in support of the claim that the current state of affairs necessities a fundamental paradigm shift; the section concludes. the proposition that naturally acquired herd immunity represents an antidote is an idea in the fashion of social darwinism, and one that failed miserably in the midst of the ongoing pandemic of the coronavirus. departing from socioeconomic natural selection, combined with the logic of the "laissezfaire," building immunity through contracting disease coincides remarkably with the ideology underlying market fundamentalism. with respect to the survival of the fittest and the preservation of the unrestricted order of free-market relations, the outlined rationale can be linked to the neoclassical economic paradigm brought about by the marginalist revolution (e.g., marshall, ; walras, ) . in sum, centered around the equi-marginal principle (see varoufakis, ) , the mainstream narrative seeks to reduce the complex social interaction to the optimization problem comprised of rational utility-maximizing agents and profitmaximizing firms. these are, restricted by budget constraints and scarcity of resources, in pursuit of their insatiable ends and unlimited growth. in such a theoretical framework, societal members are altering and adapting nature to fulfill their biological needs and derived wants via the production of use values. given the existing circumstances, the consumption of the use values produced tends to maximize, to the greatest extent possible, human needs and wants. in other words, the satisfaction received from the consumption of use values is what constitutes the utility maximization. this is the cornerstone of the neoliberal model in which the success of societal production is measured via economic efficiency and against the pareto ( ) optimality where, given the existing placement of resources, the advancement of any one individual can occur only at the expense of another. however, given that private and social interests often do not coincide, it is not a correct deduction from the principle of the "laissez-faire" that self-interest consistently operates in the public interest (keynes, ) . when the optimality conditions are not met, the allocation of resources suffers from pareto inefficiency, suggesting that each rational individual acts in their self-interest and the entire group is worse off as a result. as put by shiller ( , p. ) , "even completely rational people can participate in herd behavior when they take into account the judgments of others, and even if they know that everyone else is behaving in a herdlike manner. the behavior, although individually rational, produces group behavior that is, in a welldefined sense, irrational." provided that the cumulative efforts of selfish individuals do not transmute by interaction to the maximization of the social well-being, this is the equivalent of saying that there exists a market failure (bator, ) and a need for allocative improvement. the above-mentioned scheme is perfectly adept at explaining why the coronavirus has managed to reach a pandemic level with devastating consequences. in a broad sense, the outbreak of the global, viral infection discloses the ultimate market failure, becoming apparent as soon as it is recognized that the capitalist regime was systemically ill-prepared despite the fact that the risk of the pandemic-prone diseases was not merely hypothetical. the fact that the emergence of novel pathogens was not a matter of "if" but "when" is confirmed with striking precision within, among others, the pentagon's ( ) pandemic influenza and infectious disease response plan and global preparedness monitoring board's ( ) annual report. however, regardless of the reported shortage of ventilators, beds, and personal protective equipment, the provision of the needed public goods could not be accommodated under the market-led environment. the fundamental cause behind this underperformance lies in the basic feature of the capitalist system, which is confined to the instantaneous profit-seeking, and the role of government effectively downsized to the preservation of a level playing field. on these grounds, constantly threatened by competition, profit-motivated individuals could not risk betting on the "black swan event," corporations could not justify such an investment to their shareholders, and the government could not interfere because it would distort the supposed allocative superiority of the market mechanism. simultaneously, in a narrow sense, the nature of the coronavirus disease reveals a number of other failures. most obvious is the fact that only a fraction of the population has reaped the benefits of the economic development that has created conditions for disease transmission from animals to humans, thus generating a considerable cost not only to themselves but also to the billions of third parties. the second failure is the pandemic, having a disproportionately harmful impact on the elderly, relative to the total population. by acting in their self-interest, this suggests that the young people would jeopardize senior citizens and act against the group's broader interest. the third failure results from the information imperfections leading to overconsumption and irrational consumer choices. the particularly apparent case is hoarding personal protective equipment that gives rise to the shortage within medical facilities, where they are needed the most. the fourth example is the leaders in the position of power who can, as a reflection of self-interest or ignorance, impose nation-wide rules of conduct that may put entire populations in danger, for instance, through the herd immunity strategy and postponing the enforcement of state-wide lockdowns. the final case stems from the excessive price gouging and pandemic profiteering, the most apparent being the soaring of the prices of vital commodities, illicit trade, and the underground economy. these events are an unambiguous demonstration of malfunctioning markets, and the textbook representatives of the problems arising from public goods, negative externalities, information asymmetries, principal−agent relations, and noncompetitive markets. moreover, they are confirmation that, from the viewpoint of the capitalist mode of production, the pandemic generates unique type of market imperfection, which encompasses all of the aforementioned failures. even more crucial is that the pandemic reveals a nature-driven, fundamental phenomena which hierarchically underlies those failures, stemming purely from market relations. in effect, the coronavirus pandemic exposes duality between the free-market individualism and the collectivism of mankind. this opposition is founded on the claim that market relations are biased against social activities in favor of individual activities (hahnel, ) . in contrast, the emergence of the pandemic disease makes the success of individuals and the possibility for an effective response thoroughly dependent upon the actions of all other societal members. as is the case with all market failures, the latter implies that the individual arrangements (based on freedom and private property) cannot effectively solve the production conundrum resulting from the pandemic crisis. consequently, as indicated by the general theory of second best (lipsey & lancaster, ) , to curtail deficiencies of the market individualism in a theoretically coherent manner, overcoming the pandemic-led market inefficiencies undisputedly require resorting to collective action via straightforward and sizable government intervention. the current state of emergency is intimately connected to the failure generated by capitalism's preexisting condition and exacerbated by the present health crisis. in this regard, deliberate attention must be paid to appropriately differentiate between symptoms and disease. this fundamental misunderstanding of the crisis constitutes the shortcoming of advocates who claim that the ongoing crisis is keynesian in roots. however, although their concerns may be partly correct in observation, as will be shown, they are undeniably false in the foundation. the key to understanding this premise is recognizing that a pandemic and wartime cannot be compared for the simple reason that, in the former case, no economic activity can be carried out due to the interpersonal disease transmission caused by an exogenous health shock. in light of this, economists are faced with the radical reduction in production induced by the world-wide inability to employ the labor force in the production process. the absence of the productive factor and the consequential underproduction crisis, characteristic of the precapitalist societies, dictates the rebirth of the classical political economy. further support of such a claim is grounded in the fact that keynes' seminal model (keynes, ) rejects the classical labor market theory and considers that the insufficient level of effective demand, and not the aggregate demand-supply interaction, determines the unemployment level (sheehan, ) . therefore, the real source of concern is not primarily demand-side in nature. the real concern is related to avoiding, by all means necessary, the malthus' ( ) disastrous scenario of overpopulation from underproduction. at this point, the relevance of malthus' stance on the relationship between nature and mankind becomes essential. in his famous exposition, malthus shows that mankind is, only to a certain degree, master over nature. hence, when the existing circumstances disable the production of a desirable quantity of use values, the system is likely to reveal a specific type of the malthusian catastrophe. to paraphrase malthus ( , p. ): should the vices of mankind fail in (among other) the war of epidemics the population will be leveled with the food of the world. thus, malthus explicitly recognizes that the pandemics limits the possibility of societal reproduction to the disposable means of subsistence. for this reason, the basic societal attitudes toward nature as the provider of subsistence for mankind must adapt to this situation by restricting market antisocial bias (vices), which is self-destructive when confronted with the pandemic. thereupon, it becomes self-evident that the adequate response to the pandemic crises commands the government intervention, which must be directed toward the protection of the population's health, the circular flow of capital, and the economic productive capacities. simultaneous implementation of these tasks is pivotal because producing subsistence commodities is a basis, not only for their immediate consumption but for the process of societal reproduction (marx, ) . this is to suggest that both the physical and the material well-being are mutually indispensable constituent elements of the existence of mankind. only in the aftermath of the direct coronavirus threat or, in the worst-case scenario, concurrently with it, the crisis is expected to disclose its following layer. this layer will be related to the deadlock caused by the cost-minimizing, mass unemployment on the one hand (u.s. department of labor, ), and unparalleled accumulation of wealth on the other (oxfram, ). therefore, the secondary concern will be the economic (rather than pandemic) lockdown, which will be brought about by the danger of deflation caused by the macroeconomic demand insufficiency. given that the markets can only provide the commodities for which there exists an effective demand, the drop in aggregate demand begets a sudden tendency of the marginal efficiency of capital to decline. this, in turn, eliminates the capitalist incentive to invest, halts the production, and triggers the crisis. thus, resulting in keynes' ( ) abundance (oversupply) of capital or marx's ( ) overproduction of means of production employed in the self-expansion of value, originating from the contradiction between production and realization of the surplus value. where, both keynes and marx analyze a capitalist system in which labor is employed with the sole purpose to produce profits, that is, to increase marginal efficiency of capital, or to support the process of capital valorization, respectively. accordingly, a drop in the capitals' marginal efficiency lowers the capitalist propensity to consume (expand productive capacities) and the volume of investments, thus spiraling to further reductions in employment and effective demand. it must be emphasized that the pandemic did not hit a prosperous economy and has occurred at the time when the majority of global economic activity was slowing down (saad-filho, ). adding to the problem are the long trend of declining wages, lagging behind the rise in productivity, and low or even negative interest rates falling below the keynes' level of the marginal efficiency of capital or marx's entrepreneur's share of profit. moreover, induced by the recent fiscal austerity tenet, the impoverished state capacities have generated a present-day erosion of the public sector's (most notably medical) institutions and labor power crucial to overcome the coronavirus crises. hence the keynes' ( , p. ) prolific conclusion "…that the duty of ordering the current volume of investment cannot safely be left in private hands." given that markets are not functioning properly, in both keynes' liberal and marx' radical schemes, addressing the pandemic and economic lockdowns entails that the government must place restrictions on the free-market individualism. consequently, the government must redress the unemployment, deflation, and lacking investments, stemming from the declining wages, insufficient aggregate demand and consequential decrease in the capital's marginal efficiency. lastly, in reference to the work by aliber and kindleberger ( ) , it is imperative to stress that this crisis, promptly named the great lockdown, represents the first truly global economic contraction with yet unknown consequences in the modern history of manias, panics, and crashes. fueled through the unparalleled globalization, the shift from global overconsumption to global underconsumption, at a time of record-high commodification of societal interactions (milanovi c, ) and the ever-growing consumerism, will initiate the economic downturn of tectonic proportions. amplified by the excessive global inequality (stilwell, ) , distorted by the global core-periphery structural dependence (rubini c, ponikvar, & tajnikar, ), and challenged by the climate crisis (mazzucato, ) , the perplexity of the forthcoming slump exhibits a common problem which requires collective action. therefore, addressing the issue of economic life returning to normal implies that "business as usual" will be achievable only when the global value chains and production networks will be restored. this will be possible only when all countries will be safe to trade with, that is when they will no longer be in a health crisis. hence, it is not only desirable but also compulsory that the path toward a sustainable social order must be conceived on the administering of effective solutions across the globe, which represents a historically unprecedented challenge to mankind. there exists little doubt as to whether the exponential coronavirus infection impedes the supposedly indefinite economic growth as a neoliberal hallmark and necessitates putting at the forefront the government multidimensional intervention of proportional response. accordingly, combating the coronavirus pandemic brings government intervention into the sphere of preserving production and maintaining employment. conversely, if the intervention is directed against insufficient demand, even if induced by the pandemic crisis, the government is effectively coping with the conventional shortcoming of the malfunctioning free-market. in both cases, if the government wants to protect and improve collective well-being, it must do so first by setting its target goals, and second by choosing between various functions of social welfare, as these define the form of the government's collective action. once determined that the current state is a broad outcome of the misallocation of resources relative to the competitive ideal, the attention is shifted to the provision of counterforces. heavily influenced by mazzucato ( ) and tajnikar ( ) , the subsequent recommendations ought not to be considered as finite solutions but rather as building blocks for effective crisis management. in the first stage, the immediate response should be directed toward saving lives and preventing further spread of the coronavirus as a prerequisite for the preservation of the public interest in the long run. the continuation of production must be prioritized in all essential activities as well as in the activities where the health of the workers can be adequately protected. in this respect, in agreement with health professionals and union leaders, the government must ensure proper health standards and provide necessary personal protective equipment. the production of such equipment must be given priority over other activities. if necessary, the government should command or even temporarily nationalize private entities for this purpose. the government must ensure sufficient reserves of essential commodities, mobilize all available (public and private) health capacities to fight against the virus, and protect strategically important activities, such as food provisioning, police, firefighters, military, it, transport, energy, and delivery. amid the pandemic, health care must be readily available to all, free of charge. prices of basic commodities and services must be maintained to their precrisis levels. the government must ensure that all eligible activities switch to the on-line operational system to minimize interpersonal contact. the overall policies must be centered around the preservation of the employed workforce through temporarily banning layoffs. nonetheless, the distressed companies should receive a government guarantee and direct financial assistance with regard to the wages of the employed workforce unable to work due to the health crisis. moratoriums on evictions, bankruptcies, and debt repayments must be passed until the business, as usual, is restored. moreover, a flexible restructuring of the existing debt must be enforced with a reasonable grace period during which all late fees and interest charges do not apply. unemployed, precariously self-employed, economically dependent, and at-risk populations must receive a minimum basic income to overcome the period of mandatory physical distancing. additional assistance must be provided to the homeless. stock exchange transactions should be temporarily halted, practices such as short selling and stock buybacks, as well as activities leading to bank runs and panics, must be prevented. any kind of pandemic profiteering must be disabled, in addition to all individually profitable but socially counterproductive activities. dividends, bonuses, compensation packages, and similar payoffs should be severely limited. there cannot be legal entities who benefit from the pandemics, and those who find themselves in a favorable position must exhibit financial solidarity toward those affected most. alternatively, such fortunate entities should be subjected to excess profits taxation, generating the government's emergency revenues in times of crisis. even more so, those legal entitles and workers who will be unaffected or mildly affected by the health crisis should continue to cover their responsibilities toward the government regularly. conversely, legal entities that had to close temporarily should be freed from any financial responsibilities toward the government (e.g., taxes and concessions). all planned public projects must be halted (unless they are of strategic importance), and available budgetary expenses must be utilized against coronavirus, toward the preservation of production. the lacking resources must be secured through government channels, making it easier for households to retain their incomes and for businesses to resume production once the health lockdown ends. analogously, once these measures create a backbone for systemic stabilization, the second stage should focus on facilitating recovery as a response to the economic lockdown following rubini c the health crisis. in relation to this, society must determine public investments in vaccine development, as a priority. emphasis must be placed on reinstating all idle capacities, constituting a macroeconomic textbook example of reigniting the economic engine. this normalization must be conceived upon simultaneously achieving the aggregate goals against unemployment, deflationary tendencies, insufficient demand, and lacking investments. however, it bears mentioning that this fight must be initiated at the point of production, since the circular flow of capital, as a principal vehicle for a robust recovery, starts by employing the workforce in the labor markets. this is the reason why it is crucial to ensure the adequate protection of the workforce in the first stage, so that in the second stage the government can incentivize the employment and initiate the production process. this is to say that solving the crisis of classical economy is a precondition for proceeding with the heterodox or radical solutions related to the second stage. the government handouts and bailouts must be directed toward entities focused on value creation (instead of value extraction), where the previous practice of socializing losses while privatizing gains can no longer be tolerated. relatedly, deliberate attention must be placed on correcting the misalignment between private incentives and social returns. society must restore the balance between private rewards and social contributions so that, to the highest possible extent, the social contribution of each worker mirrors their private compensation (stiglitz, ) or that their reimbursement mirrors the value created (rubini c & tajnikar, ). the urgency of ameliorating this market failure is highlighted in the present crisis in which poorly equipped and overworked medical staff is often struggling financially while the majority of the "leisure-adverse" employers are seeking refuge in the safe zones. accordingly, at a great personal cost to themselves, the medical staff (as a representative of a much larger disadvantageous group of workers) obviously does not enjoy the fruits of their marginal productivity. inasmuch, the government's direct liquidity injections, where necessary, must be provided conditionally upon retaining an employed workforce and achieving sustainable and inclusive economic revival. these subsidies should be realized without intermediaries, in order to prevent the financial institutions from dampening the recovery, similar to that occurring after the great recession. if this alone will not suffice, in addition to the development of the above-mentioned safety net system, the government must take on the role of the employer of last resort. it should seek to employ jobseekers directly and incentivize, both through higher returns and through inflation, the employment of unused capital in production processes that ultimately serve to promote broader societal goals. preferably, the latter should be achieved through public-private partnerships and socially useful infrastructural investments. in connection to this, it is important to notice that direct employment by the government should be a priority over the unemployment compensation. this is simply because the later, as opposed to the former, generate expenditure without the production of value and the contribution to social wealth (wolff, ) . in specific circumstances, both private and corporate debt relief and collectivization should be considered. if implemented successfully, the government intervention would ensure high aggregate capacity utilization, raising both incomes and profits. concurrently, these measures would encourage consumer spending, prevent accumulation of unsellable inventories, increase the propensity to invest, and place the economy back on the path to recovery. last but not least, two crucial points bear mentioning. the government's actions must be transparently and thoroughly contemplated. the first wave of pandemic lockdown will increase government debt used to finance, among others, protective and health expenses, final consumption, and (un)employment benefits concurrently with a substantial decrease in budget revenues. therefore, when the second wave of economic lockdown takes place, the government's ability to finance crisis management will be extremely limited. for this purpose, governments should look for sources to finance expenses whenever possible, by lending capital within national financial markets. this would help in balancing out domestic savings and investments without causing disbalances of trade. otherwise, in the absence of adequate supranational payment arrangements, the disbalances of trade would be imminent if the government would borrow internationally. even though the overwhelming evidence shows that the increased government borrowing can confront insufficient demand, expansionary spending is severely limited in the fight against the pandemic production lockdown. this is because the health risk impediments to production, simultaneously targeting producers and consumers alike, must be primarily addressed through strict physical coordination before any monetary response can suffice. in reference to the global downturn, the third and most demanding group of remedies is dealing with the fact that ongoing crises must be addressed on a global scale. this is essential because the coronavirus pandemic deconstructs the globalization, meaning that focusing on the national solutions will not deliver a sustainable outcome (Žižek, ) . similar to the described inner-country scenario, it is important to recognize that the necessity of the collective response is not conditioned by virtue of cross-country solidarity. precisely the opposite, a global plan is paramount given that preserving the globalization is in the genuine interest of the capitalist market economy. even more so, since it is the irreversible outcome of the development of the productive forces, the globalization process must be protected at all costs. in relation to the latter, the rationale behind the dynamics of the inner-country solution must be modified to tackle global challenges ahead. generally speaking, combined with the globalization and rising inequalities, the coronavirus pandemic raises the need to address the problem through some form of a supranational authority. hence, it is self-evident that the nature of the threat requires a certain degree of a global healthcare network (smith, ) , universal health care, and a potent transnational system of detection and restriction of the spread of the pandemic-prone diseases. thereafter, it must be recognized that the contemporary mode of production originates from the economy of scale and the growth-led model, dependent upon international trade and globalized supply chains. from this, it follows that the nation-state remedies will fail to restore global value chains and production networks, without which there is no going back to pre-pandemic "normal". lastly, the lessons drawn from past global crises have shown that they tend to generate a dichotomy between an effective international lender of last resort and large-scale military conflicts (aliber & kindleberger, ) . this is ever more relevant within today's globalized world in which economic specialization has fueled country-wide production of exchange values rather than use values. resultantly, if there is no international trade, there is no realization of commodities. consequently, given that the prevailing comparative specialization has created countries with disproportional economic structures, the vast majority of them are dependent and cannot reproduce independently. the final result is a state in which certain countries, due to the insufficient demand, will have to cover the expenses of food destruction while those predominantly relying on the tertiary sector will struggle to make ends meet. apart from this, corresponding detrimental dynamics will take place within countries, between the wealthy and the impoverished. regardless of the fact that finding a cross-country compromise poses a difficult task, there exists no viable alternative to avoiding global standstill, given the lack of global cross-country cooperation. in other words, the unified supranational response through the effective international lender of last resort must absorb asymmetrical shocks and exhibit cross-country symbiotic solidarity when and where it is needed the most. coping with the catastrophic aftereffects of the great lockdown, which is likely to become the worst contraction in modern history, undeniably comes at great expense. the trillions that will be spent on violating conventional market rules are the finest indicator of the need for critically transcending the dominant discourse and unwavering beliefs in market efficiency. related to the sections and , both keynes and marx see the solution to this crisis in the process of capital depreciation, producing a capital shortage and creating a basic condition for an increase in its marginal efficiency (stojanov, ). an additional advantage of such a scenario is that it incentivizes investment spending and consumption of means of production as a safeguard from the capital's otherwise inevitable loss of value. consequently, the increase in marginal efficiency creates a foundation for recovery and the restoration of societal production. on these grounds, two things are certain. first is that the entire society must participate in covering the costs by respecting principles of vertical equity, horizontal equity, and ability-to-pay. second is that the fiscal policy is the most obvious instrument available. this entails that the costs must be disproportionally displaced toward those members of the society who can afford to pay them. this is where the present-day excessive inequality must be turned into a societal advantage through the deliberate use of the government's expansionary fiscal policy directed toward reinstating idle productive capacities. effectively, the costs related to the preservation of sufficient demand, pre-crisis level of employment, and continuous reproduction, to be financed via unbalanced government budget or direct injection of money, must be covered through the progressive taxation of income and wealth, or through the direct redistribution inflicted by the philanthropic altruism. coordinated by the progressive government, the needed policy toolkit should support socially useful public investment financed through solidarity among people. this means that structuring effective response arrangements requires transcending the mainstream view on solidarity as "interpersonal externality." if it is to beget success, by disproportionally affecting the wealthy and by restricting market-led individualism, the pandemic response plan will undeniably have to take the role of the great leveler. the key to a favorable outcome is the acknowledgment by both the power holders with vested interests and the rest of the society, that the pandemic as an external existential threat demands to replace the competitive market setting with synergic cooperation. accordingly, given the circumstances, the triumph should be built upon the economics of equitable cooperation, which has the capacity to generate a positive-sum and sustainable results. in this sense, it can be inferred that society needs to utilize solutions comparable to the time of the "great compression," during which progressive taxation and direct, large-scale government employment programs were used to develop modern welfare states after the second world war. in this context, it is imperative not to overlook that this theoretical proposition does not imply that the affluent members should contribute more merely out of solidarity. among others, their disproportional participation is crucial because they have asymmetrically benefited from the development leading to the pandemic, they have reaped disproportional benefits arising from publicly financed projects, and because they consume much more protection of their private property from the government than the rest of society. regardless of if the above stated refers to a national level or presently infeasible supranational level, from this assertion, it naturally follows that the pandemic paradigm shift is necessary if society is to make progress. the diagnosed pandemic predicament requires a radical overhaul of the presently inefficient patterns of production, distribution, exchange, and consumption. this is because confining to the narrow concept of pareto optimality proved unsustainable over the long run if production takes place for profit alone (stojanov, ) . given that the pareto principle does not permit comparing interpersonal utilities, it is hardly surprising that it is unable to deal with the coronavirus pandemic. hence, the pareto criterion must be rejected as the measure of economic efficiency (see hahnel, , p. ) . this is why the government must define an appropriate welfare function and impute value judgments, implement an innovative policy toolkit, and set up a new efficiency criterion to be used as the benchmark for the assessment of the success of societal achievements henceforth. therein lies the complex reality of the postpandemic restart which brings into question the basic postulates of economic science. thus, it becomes necessary to develop a theoretically coherent reform of economics by abandoning, or severely restricting, the prevailing market mantra which holds individual's profit motive to be the primary driver of societal production. toward that end, keynes and marx offer valuable insight into how this novel paradigm should be conceptualized. the mainstream paradigm has departed from robbins ' ( ) standard definition of economics as a cornerstone of a neoliberal optimization problem, studying human behavior as the relationship between ends and scarce means with alternative uses. having this in mind, the orthodox approach seeks to achieve economic efficiency weighted against pareto criterion, where ends are considered insatiable wants in relation to the purportedly limitless (in growth) human desire for consumption. this mainstream framework, in which the consumer is undeniably crowding out the citizen, is widely and rightfully refuted by nonorthodox economists. in this regard, keynes' ( ) constructive criticism places the focus on the hierarchy of wants, differentiating between absolute and relative class. building on the keynes' rationale, skidelsky ( ) argues that human behavior is bounded by absolute (biological) needs and relative (social) wants. hence, needs are limited by nature, with the lower bound being bare subsistence. contrarily, wants are made limitless by society, given that they are considered aspirational pathways to satisfy and maintain the insatiable desire for the individual's superiority relative to other members of society. on the other hand, marx's ( ) critique is derived from the fact that the principle of scarcity pays no attention to distributional implications innate to the capitalist mode of production. therefore, it is no wonder that the commodity production of profit-bearing exchange values is placed ahead of the production of use values intended to satisfy human needs. even though the theory suggests that the use values are the source of the exchange values, the usefulness of the latter is derived not from the commodity's immediate consumption but from their ability to bring profits once they are realized in the marketplace. given the massive distributional inequalities, this is the alternative of saying that the focus is cast on satisfying unlimited wants of those who can afford them instead of fulfilling even the most basic needs of others. this final result explicitly opposes marx's needs-centered distributional system apparent within a well-known aphorism "from each according to his ability, to each according to his needs!" (marx, , p. ) . since this framework advocates that the resources are scarce relative to wants and not needs, in both cases, the starting point toward building a better society is not rooted in the problem of scarcity, but in that of distribution. likewise, the problem must not be conceived upon fulling our insatiable wants but should be primarily focused on satisfying the basic needs. this erroneous discrepancy between abundance and scarcity, as well as between wants and needs, is created by society and therefore is to be restricted by society (skidelsky, ) . more generally, it is not a result of self-interest or greed as "permanent" features of human nature but is an inherent reflection of characteristic behavior that emerges from living under capitalist society (see. fine & saad-filho, ) , which subordinates the human needs of many to the profit motives of few. what governs the societal relationships is thus not a natural inequality but a historically specific social one in which relationships are not organized between equals. even more than that, it is governed by the dynamics in which socioeconomic interaction between people appears as the interaction between commodities. given that it is derived, established, or at least authorized by the consent of men, this is what rousseau ( ) considers a detrimental, instituted inequality constituting the core of the pluralist critique of capitalism. in line with all above mentioned, the conclusion drawn is that the great lockdown mandates a paradigm shift. the new economic paradigm must account for the consistent academic underpinnings provided by the heterodox and radical schools of economic thoughts, which furnish a powerful theoretical groundwork in favor of correcting the misalignment between needs and wants. as understood by rousseau ( ) , this notoriously difficult task is to be accomplished through the formation of a novel, tacit social contract bringing benefits to all parties involved and bringing about more equitable, sustainable, and symbiotic mode of societal production. however, appealing and relevant this fundamental economic reform is, until the labor becomes "…not only means of life but life's prime want" (marx, , p. ) , instead of reinventing the economic science, society must urgently reinforce the existing mode of production. here again, the coronavirus pandemics calls for a restriction of the market individualism, calls for economics of equitable cooperation, and calls for the appropriation of the self-interest properly understood (de tocqueville, ) . fortunately, the material conditions necessary to tackle these challenging socioeconomic realities already exist and should be, without delay, employed in two interchangeable and mutually reinforcing ways. the society should seek to maximize its needs by tying them to the interests of the owners of the private property. in this scenario, faced by the exogenous threat, the capitalists must recognize that maximizing societal basic needs instead of its wants, through the large-scale provision of the use values, is in their own self-interest as much as it is advancing the collective well-being. second, as stated previously, the remaining societal needs should be accommodated via the government's collective leadership, which restricts the private self-interest and fulfills the societal needs through a nonprofit, solidary economic environment. the bottom line is that the natural calamities overpower the economic pursuit of insatiable wants and confine the performance of the profit-motive primarily to the needs-based principle. therefore, the coronavirus pandemic sets the narrow limit for socially constructive, world-wide disaster management whose implementation becomes a matter of progressive practical politics and complementary technical economics. alternatively, uncompromised persistence on the claim that individual and societal interests are somehow mutually exclusive will generate a disservice to both. irrespective of the great lockdown's still nascent stage of crisis development, under any circumstances and regardless of what the preliminary outcomes may entail, several unequivocal and incontestable facts must be considered. first, the coronavirus is here to stay, it is likely going to mutate, and there is no ultimate safeguard against the recurrence of the multiple pandemic waves. second, the only possible trajectory that would position the world back toward a precrisis operating mode is the development of an effective and widely accessible vaccination, which may take years. third, given the current patterns of economic development, with adverse ecological impacts, the cross-species transition of yet unknown deadly pathogen cannot be excluded in the foreseeable future. fourth, the existing economic system is faced with its first truly global slump, threatening the existence of billions and severely hampering worldwide societal reproduction. given that the emergence of the coronavirus and the poorly managed supranational emergency state of preparedness are the straightforward results of market failure, it would be logically inconsistent to infer that the market's self-correcting mechanism can adequately respond to the mutually reinforcing crises of health, economic, and global lockdown. with that in mind, unrestricted by the ideologically downsized role of the government, the prevailing market paradigm, driven by the disconnect between securing the public health and the instantaneous profitability, has exposed a systemic incapacity to fulfill even the most basic societal needs. the consequential demise of the "efficient" free-market capitalist system brings back to the surface the paramount, collective struggle against the approaching socioeconomic havoc, based on the compelling case provided by the heterodox and radical schools of economic thought. the latter urgently requires the return of strong economic interventionism, which must (a) ensure sufficient funding for the vaccine invention and production of the supportive protective and medical equipment, (b) prevent the irreparable loss of social wealth and ensure the continuation of social production, as the precondition for social reproduction, (c) ensure that the pandemic response plan will beget global solutions, without which there cannot be sustainable recovery. the interconnected policy recommendations put forth by this study constitute absolute necessities whose costly implementation can be realized solely through the synchronized working of national and supranational authorities. while the supranational organizational scheme remains completely unclear, what is certain is that the massive financial burden of the great lockdown will have to be channeled toward those members of society who can afford to pay for them. hence, the conclusion that the excessive prepandemic economic inequality is both the cause behind and the cure for the current state of affairs, whereas the pandemic itself should become the new great equalizer. this inevitably results in the pandemic paradigm shift, conceptualized through the departure from the narrowly defined self-interest maximization toward a society which will put humans back into the economic equation and acknowledge that it is only by maximizing our collective interests that the society can find a way out of the crisis. this imminent change will profoundly affect the basic features of society, in which all segments of the preexisting socioeconomic arrangements must focus on putting the basic needs of the many ahead of the insatiable wants of a few. this restriction of free-market individualism for the purpose of preserving collective wellbeing is an appropriate course of action which must be taken into account as a platform for addressing all existential threats to society, inclusive of ecological and environmental crises. from this perspective, the great lockdown simultaneously poses an opportunity, as well as a challenge to mankind, who cannot allow itself the luxury of letting another serious crisis go to waste. ultimately, whether the crisis will beget a progressive change toward equitable and solidary collective or a turn towards destructive national movements, remains to be seen. however, until resolved, the clash between the coronavirus and humanity effectively disables what was, up until now, considered economically rational decision-making and what will largely determine the overall success of the fight between viral and economic reproduction. ironically, the success of the technologically advanced society and masters of artificial intelligence will be measured against one of the simplest life forms in existence. accordingly, the evolution of economic rationality rendering homo economicus with a properly understood notion of self-interest, is a fair price to be paid to secure life in a civilized society. ivan rubini c https://orcid.org/ - - - manias, panics, and crashes: a history of financial crisis the anatomy of market failure marx's capital a world at risk: annual report on global preparedness for health emergencies the abcs of political economy essays in persuasion the general theory of employment, interest, and money the general theory of second best an essay on the principle of population principles of economics critique of the gotha programme capitalist's triple crisis capitalism alone: the future of the system that rules the world world's billionaires have more wealth that . billion people usnorthcom branch plan : pandemic influenza and infectious disease response sectoral and technological analysis into the origins and determinants of the eurozone's economic inequality labour force exploitation and unequal labor exchange as the root cause of the eurozone's inequality coronavirus, crisis, and the end of neoliberalism understanding keynes' general theory how & how not to do economics lecture : unlimited wants, limited resources why coronavirus could spark a capitalist supernova the price of inequality the political economy of inequality validity of the economic thoughts of keynes and marx for the st century ne dovolimo, da bi zaprti v stanovanja ostali brez denarja in hrane! news release: unemployment insurance weekly claims foundations of economics: a beginner's companion destruction of habitat and loss of biodiversity are creating the perfect conditions for diseases like covid- to emerge elements of pure economics global capitalism: corona and capitalism: overlapping sicknesses pandemic! covid- shakes the world ivan rubini c (phd) presently holds the position of an assistant lecturer and researcher at the economics department of the faculty of law at the university of rijeka. he is a / urpe fellow working toward the advancement of the research in political economy, economic inequality, and economic theory. more details on his academic profile can be requested from dr.ivanrubinic@gmail.com.how to cite this article: rubini c i. pandemic paradigm shift. labor and society. ; - . https://doi.org/ . /lands. key: cord- -sabmw wf authors: el-shabrawi, mortada; hassanin, fetouh title: infant and child health and healthcare before and after covid- pandemic: will it be the same ever? date: - - journal: egypt pediatric association gaz doi: . /s - - - sha: doc_id: cord_uid: sabmw wf background: the novel corona virus disease (covid- ) current pandemic is an unpreceded global health crisis. not only infection of infants, children, and adolescents is a concern for their families and pediatricians, but there are also other serious challenges that should be properly identified and managed as well. main body: we have to identify and assess the different factors that have either direct or indirect effects on child health and healthcare due to covid- pandemic and focus on the serious effects. it is easily realized that there are many challenging problems associated with covid- with short-term effects that already appeared and need urgent solutions and long-term effects that are not yet well apparent and have to be searched for and properly addressed. conclusions: covid- crisis has lots of impacts on child health and child healthcare, not only from the medical aspect but also from the social, psychological, economic, and educational facets. all these adverse implications have to be identified and dealt with on individual bases approach in the short and long term. since reporting of the first index cases of infection with the novel severe acute respiratory syndrome corona virus (sars-cov- ) in wuhan (hubei, china) on december , the whole world has changed very rapidly and dramatically. on january , the world health organization (who) has declared the novel corona virus disease (covid- ) as a global health emergency, and shortly thereafter on march , it was declared as a pandemic [ ] . covid- pandemic proved rapidly to be a major international medical problem that has many sequences on infants, children, and adolescents. worldwide, concerted efforts must be exerted in order to identify the huge problems and impacts the pandemic has created that affect child health and child healthcare, and plan prompt solutions for them. all the news, reports, and experiences from the four corners of the world are indicating that infant and child health and healthcare systems before the covid- pandemic have been changed to variable degrees and will probably never be the same after the pandemic in many aspects for extended periods of mankind life. covid- is uncommon to cause marked clinical symptoms in healthy children as compared with adults. however, asymptomatic children are able to transmit the virus to their adult contacts, and very young infants and children (as well as those with underlying comorbidities) are at increased risk to manifest severe illness [ ] . covid- is a droplet infection that spreads rapidly to the unprotected contacts from an infected person. the infectious virus can persist on contaminated surfaces for variable times. the risk of transmission via touching contaminated paper is low, while respiratory and fecal specimens can maintain infectivity for quite a long time at room temperature. sars-cov- could exist in the air in poorly ventilated buses for at least min. absorbent materials like cotton are safer than non-absorptive materials for protection from viral infection [ ] . as children are less likely to present with serious symptoms, they may have nasal congestion, sore throat, muscular and bony aches, abdominal pain, vomiting, or diarrhea [ ] . in children, common circulating corona viruses can cause common cold symptoms such as fever, rhinitis, otitis, pharyngitis, laryngitis, headache, bronchitis, bronchiolitis, wheezing, pneumonia and, in up to % of cases, gastrointestinal symptoms (which are more common in children than adults) [ ] . some recent studies have shown that there is limited spread among children and from children to adults [ ] [ ] [ ] . the most common manifestations in infected adults include fever, tiredness, and a dry cough [ ] . in the majority of infected adults, the symptoms are mild, and more than % completely recover. however, the remainder may become seriously ill and some may die. more severe symptoms include difficulty in breathing, pneumonia, acute respiratory distress syndrome, and septic shock leading to multiple organ failure such as heart, liver, and kidney failure [ ] . until now, there is limited evidence that maternal vertical transmission can occur, and newborn infection if occurs is due to perinatal transmission rather than prenatal [ ] . it was also found that there is no transmission of the virus through breast milk; therefore, cessation of breast feeding from covid- -infected mothers is not recommended, and infected mothers are strictly advised to follow preventive precautions such as handwashing, cleaning the breast before feeding, and using masks during breast feeding [ ] . laboratory findings from children are rather similar to those in adults and include a white blood cell count that is typically normal or reduced with decreased neutrophil count and/or lymphocyte counts. thrombocytopenia may occur. c-reactive protein (crp) and procalcitonin levels are often normal. in severe cases, elevated liver enzymes, lactate dehydrogenase levels, as well as an abnormal coagulation and elevated serum ferritin and d-dimers have been reported [ ] . radiologic findings in children are similar to those of adults. chest radiography mostly shows bilateral patchy airspace consolidations mainly at the periphery of the lungs, peri-bronchial thickening, and ground-glass opacities. chest computed tomography (ct) scans mostly show airspace consolidations and ground-glass opacities [ ] . until now, there is no definitive evidence-based drug therapy for covid- neither in adults nor in the pediatric populations. current management for covid- is largely symptomatic and supportive care. supportive measures include sufficient fluid and caloric intake, antipyretics, oxygenation, anticoagulants, and prophylactic antimicrobial therapy to prevent superadded bacterial or fungal infections. the aim is to stabilize the clinical condition and prevent further deterioration as organ failure and secondary infections. it is better for children with mild symptoms to stay at home under medical supervision. if the child condition is deteriorating, then the child should be hospitalized as advised by the treating pediatrician [ ] . confirmation of the information credibility is essential for healthcare professionals and the public in general. during crisis, rumors and false stories, misleading information, and unreliable data are sadly shared via social media leading to a state of instability and uncertainty among the community members and causing mistrust in the healthcare providers [ ] . pediatricians and all other healthcare team must be cautious about starting therapies based on news or social media reports and should rely on trusted sources of evidence-based information from reliable credited sources of updated information and share those with the families in their care [ ] . it is equally important that families be aware that many of what is called sham remedies have been promoted to the public. many sham treatments have been widely disseminated on social media. these include, for example, drinking warm water, gargling with saline or garlic, drinking lemon juice with honey or black seeds, use of specific homeopathic or alternative medicines, and drinking specific alcoholic drinks. none of these remedies have been proven effective in prevention or treatment, and some have been shown to be harmful, and therefore, should not be recommended [ ] . healthcare facilities all over the world became suddenly overwhelmed by unexpectedly treating thousands of covid- patients at the same time. this has created marked congestion and an unpreceded chaos in the healthcare facilities especially in the populated regions. this has its adverse impacts and many people and particularly infants and children were and still (until the time of writing this manuscript) unable to get the proper medical care they actually need. suggested short-term measures have been proposed to the countries all over the world by the who in response to covid- pandemic. a comprehensive guidance to countries on the types of actions and adjustments needed to support the response [ ] . there is an urging challenge of how to provide the required healthcare needed by infants and children in due time and place avoiding the possibility to catch sars-cov- infection if they go to seek medical advice at hospitals or healthcare facilities. the mandatory precautions including the fundamental physical distancing and infection control requirements will affect the traditional routine medical care beside that many parents are afraid to leave homes or do not want to take their child to a medical care facility with a possibility to be infected from other sick children. therefore, care givers are encouraged to share their worries and information with their pediatricians via phone calls, e-mails, or other social media applications [ ] . telemedicine has been dramatically exploited in the past few months as a useful tool for long-distance clinical care more than -folds what has happened to it during the past decade. telemedicine can be used for education, counselling parents, and health management, and its role is professionally enlarging in many regions such as the usa and europe, but awaiting further regulatory approvals in other regions such as in egypt [ ] . telemedicine may be of limited practical application in some low-income countries where resources are limited due to technical, economic, cultural, or geographical factors, but yet it needs to be tried as an alternative to face-to-face communication to get the required medical advice especially in the straight forward medical problems and concerns. with appropriate attention and caution for some issues such as patient safety, confidentiality, and suspected missed clinical information, telemedicine can be an effective way to help patients during the present covid- pandemic [ , ] . it is estimated that millions of infants and children worldwide have just missed and will continue to miss their required essential vaccinations with a fear that some vaccine preventable diseases (vpd) may come back as measles and poliomyelitis. the who has stressed the importance of maintaining the essential health services during covid- pandemic and identified immunization as a core health service that must be offered to the target chirdren [ ] . special planning and extra ordinary efforts are required to be applied quickly for vulnerable pediatric populations at increased risk of morbidity and mortality as refugees and children under custody. however, it was advised that mass vaccination campaigns should be temporarily halted or postponed to follow recommendations on maintaining proper physical distancing and infection control precautions required to combat covid- transmission during such campaigns [ ] . covid- crisis has forced governments to close nurseries and schools as well as sports' clubs and gardens. it is not allowed to travel to areas where recreations can be practiced. children are not allowed to meet their friends and other relatives. they are locked down at their houses having the same repeated daily routine. similar to adults, children are likely to suffer anxiety, fear, and other psychological manifestations. children may experience negative feelings and thoughts such as fear of being hospitalized, taking injections up to a fear of their family member loss, or even their own death. this may present as behavioral disturbances, loss of appetite, sleep problems, nightmares, and many other stress-related disorders. the adolescents are also affected but to a lesser extent than children as adolescents seem to express an excellent ability to manage situations of insecurity and have a better adaptation with the changing circumstances [ ] . in the wake of the global lockdown, schools are closed. children are not only obliged to stay at home for longer hours and become more vulnerable to domestic violence and other sorts of child abuse, but also there is an anticipated decrease in reporting of child maltreatment cases which includes sexual, physical, and emotional abuse. adding other adverse factors as parental unemployment and economic burdens will be negatively reflected on providing a safe healthy environment for the children to stay in. it is clear now that the measures which have been taken to control the spread of covid- are causing what may be called a "secondary pandemic" of child neglect and abuse [ ] . the living conditions in refugee camps, crowded reception centers, or detention facilities are unfortunately a very suitable environment for covid- spread. there is lack of proper healthcare services and sanitary precautions beside the suboptimal physical and medical status of the children at such places. displaced children are among those with the most limited access to prevention services, testing, treatment, and other essential support. in addition, the pandemic and containment measures are likely to have negative consequences for their safety and education, which were pre-carious even before the outbreak of the disease [ ] . many families are struggling with their daily lives. parents and care givers being out of work or even have already lost their jobs during the pandemic do not have enough financial resources to cope with the many changes occurring. on the other hand, the basic needs of infants, children, and adolescents must be fulfilled. with the world economy sagging into recession, it is feared that this hardship will remain and probably increase over the coming months, if not years [ ] . being more vulnerable to catch infections, children suffering of chronic diseases are at high risk to get covid- infection. those children are suffering of marked decrease of their protective mechanisms and inner barriers to combat infections. not only that, but also if they developed covid- infection, there will be a potential increased risk of deterioration of their clinical status. prevention is the principal key factor for those children. they should not catch covid- at the first place. they must strictly stay at home avoiding any possibility to catch infection. if covid- infection is suspected, they must seek medical advice promptly. infants < year of age and children with certain serious underlying conditions appear to be at greater risk for severe disease. the most commonly reported underlying conditions in covid- pediatric patients were chronic pulmonary disease, cardiovascular disease, immunosuppression (e.g., related to cancer, chemotherapy, radiation therapy, hematopoietic cell or solid organ transplant, and high doses of glucocorticoids) [ ] . the overwhelming current covd- ongoing disaster should not make us forget other serious medical and surgical diseases and emergencies that children may suffer. pediatricians and pediatric hospitals must be prepared to provide rapid, efficient, and safe medical management accordingly. in its recent position statement, the international pediatric association (ipa) has strongly recommended that the primary care and hospital resources for children must be maintained during the current covid- pandemic, in order to ensure addressing the child and adolescent health priorities and providing required health management services for children with more severe covid- manifestations [ ] . the mandatory lockdown and inevitable social distancing measures due to the covid- pandemic has forced the governments in many countries to close nurseries, child care centers, schools, training centers, and higher education facilities as universities and institutions. these closures have affected millions of students worldwide not only retarding their educational aspects, but also adversely affecting their emotional status and well-being. whenever the schools are reopened, the protection of children and educational facilities is particularly important. precautions are necessary to prevent the potential spread of covid- in school settings; however, care must also be taken to avoid stigmatizing students and staff who may have been exposed to the virus [ ] . staying at home for long time and closure of sports clubs and lack of physical activities may eventually result in marked weight increase in children and adolescents and development of obesity problem with all its negative consequences. pediatricians have to alert parents and care givers for this increasing heath problem during lockdowns. on the other hand, in many developing countries, the opposite may occur; the economic adverse effect of covid- may result in marked decrease in the families' abilities to ensure enough food supplies for their children resulting in their suffering of undernourishment. nutritious food intake has to be offered to every individual. proper nutrition and hydration are vital for health these days. intake of more water and avoiding sugars are essential. children and adolescents should eat a variety of fresh and unprocessed foods every day to get enough vitamins and minerals [ ] . what is expected after covid- pandemic is over? the covid- pandemic caused an unpreceded disturbance in the global health systems. humanity is hopeful that it may come to an end sooner rather than later especially if an effective antiviral treatment(s) and/or vaccine(s) are developed rapidly. until that moment, prevention of infection and symptomatic and supportive treatment are the best to do. therefore, revising infant and child health and healthcare plans, and prioritizing the healthcare projects are essential and mandatory issues as the world will never be the same again. both globalization and urbanization that have been two of the world's most powerful drivers in the past few decades are anticipated to be reversed by covid- leading to increasing the distances among people and between countries due to border closures and restricted international travel [ ] . so far, the covid- crisis has had a great impact on child health and healthcare all over the world, not only from the medical aspect, but also from the social, psychologic, economic, and educational aspects. all these implications have to be identified and dealt with properly to avoid their short-and long-term consequences on an individual bases approach. world health organization (who). ( ) statement on the second meeting of the international health regulations ( ) emergency committee regarding the outbreak of novel coronavirus ( -ncov) china novel coronavirus investigating and research team. a novel coronavirus from patients with pneumonia in china stability and infectivity of coronaviruses in inanimate environments epidemiological characteristics of pediatric patients with coronavirus disease in china coronavirus infections in children including covid- : an overview of the epidemiology, clinical features, diagnosis, treatment and prevention options in children children and covid- . ( ) national institute for public health and the environment, ministry of health, welfare and sport spread of sars-cov- in the icelandic population ) maternal and perinatal outcomes with covid- : a systematic review of pregnancies q&a on covid- , pregnancy, childbirth and breastfeeding infection prevention and control during health care when novel coronavirus (ncov) infection is suspected covid- : how to be careful with trust and expertise on social media us centers for disease control and prevention (cdc). ( ) covid- databases and journals coronavirus disease (covid- ) advice for the public: myth busters ) health systems governance and financing & covid- available at global telemedicine implementation and integration within health systems to fight the covid- pandemic: a call to action in-person health care as option b virtually perfect? telemedicine for covid- guiding principles for immunization activities during the covid- pandemic the psycho-social effects of covid- on italian adolescents' attitudes and behaviors is a secondary pandemic on its way? institute of health visiting united nations high commissioner for refugees ( ) joint statement as covid- pandemic continues, forcibly displaced children need more support than ever us centers for disease control and prevention (cdc). ( ) coronavirus disease cdc covid- response team ( ) coronavirus disease in children -united states promoting and supporting children's health and healthcare during covid- -international paediatric association position statement world health organization (who). ( ) schools & covid- -control & prevention guide available at the world economic forum covid action platform. the post-covid- world could be less global and less urban springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations the authors stated no acknowledgement. both authors contributed equally in all steps of preparation of this work. the author(s) read and approved the final manuscript. the authors declared that they receive no funding whatsoever for this work. ethics approval and consent to participate not applicable the authors are giving their consent for publication. the authors declared that they have no conflicts of interest.author details faculty of medicine, cairo university, cairo, egypt. misr international university, cairo, egypt.received: june accepted: july key: cord- - x euj authors: nickol, michaela e.; kindrachuk, jason title: a year of terror and a century of reflection: perspectives on the great influenza pandemic of – date: - - journal: bmc infect dis doi: . /s - - - sha: doc_id: cord_uid: x euj background: in the spring of , the “war to end all wars”, which would ultimately claim more than million lives, had entered into its final year and would change the global political and economic landscape forever. at the same time, a new global threat was emerging and would become one of the most devastating global health crises in recorded history. main text: the h n pandemic virus spread across europe, north america, and asia over a -month period resulting in an estimated million infections and – million deaths worldwide, of which ~ % of these occurred within the fall of (emerg infect dis : - , , bull hist med : - , ). however, the molecular factors that contributed to the emergence of, and subsequent public health catastrophe associated with, the pandemic virus remained largely unknown until , when the characterization of the reconstructed pandemic virus was announced heralding a new era of advanced molecular investigations (science : - , ). in the century following the emergence of the pandemic virus we have landed on the moon, developed the electronic computer (and a global internet), and have eradicated smallpox. in contrast, we have a largely remedial knowledge and understanding of one of the greatest scourges in recorded history. conclusion: here, we reflect on the influenza pandemic, including its emergence and subsequent rapid global spread. in addition, we discuss the pathophysiology associated with the virus and its predilection for the young and healthy, the rise of influenza therapeutic research following the pandemic, and, finally, our level of preparedness for future pandemics. influenza viruses have posed a continual threat to global public health since at least as early as the middle ages, resulting in an estimated - million cases of severe illness and , - , deaths annually worldwide, according to a recent estimate [ ] . regional influenza epidemics occur on an annual basis, resulting in millions of illnesses and hospitalizations despite intensive vaccination and awareness programs [ , ] . moreover, influenza pandemics arise sporadically due to the introduction of an antigenically-distinct influenza a virus within a population, which can result in devastating effects on global public health and healthcare networks. the emergence of influenza subtype h n in , which ultimately resulted in an estimated - million deaths worldwide, would forever change the course of human history and will be discussed in detail in the following sections [ ] [ ] [ ] . the aims of this short review are to discuss: i) the emergence and spread of the virus; ii) the unique severity of disease in young, healthy individuals; and iii) the subsequent influence of the pandemic on influenza virus therapeutic and future preparedness. it is postulated that % of the worldwide population is infected by an influenza virus each year, resulting in a total economic burden of $ . billion usd [ , ] . as a testament to the significant toll posed by influenza on public health and healthcare systems, the us centers for disease control and prevention (cdc) estimated that from to , influenza infections resulted in . - . million illnesses and , - , hospitalizations annually in the us alone [ ] . it has been suggested that children are likely the primary transmitters of influenza [ ] . lethal influenza infections are primarily associated with high risk populations, including infants (< year), the elderly (> years), and individuals with pre-existing comorbidities, including chronic respiratory abnormalities, cardiac disease, immunodeficiency, and pregnancy [ , ] . mortality in children and young adults is generally low [ ] . symptoms manifest as a sudden high fever, headache, pharyngitis, cough, myalgia, nausea, vomiting, and fatigue, which generally resolve within days in healthy adults [ , ] . severe and/or lethal disease is typically associated with viral pneumonia or secondary bacterial infections in the lower respiratory tract [ ] . to be considered a pandemic, an influenza virus must: i) spread globally from a distinct location with high rates of infectivity resulting in increased mortality; and ii) the hemagglutinin (ha) cannot be related to influenza strains circulating prior to the outbreak nor have resulted from mutation [ , ] . it should also be appreciated that prior to the first isolation of a human influenza virus in , the cause of influenza outbreaks and pandemics could only be inferred based on physiological symptoms of disease, along with the speed and breadth at which illness was spread [ ] . as early as bc, hippocrates, the father of modern medicine, described the first known account of an influenza-like illness in his sixth "book of epidemics" [ , ] . here, he recounted an annual recurring upper respiratory tract infection characterized by pharyngitis, coryza, and myalgia which peaked around the winter solstice [ ] . this seasonal epidemic occurred in perinthus, a northern port town located in what is now turkey, and is referred to as the "cough of perinthus" [ ] . it has been suggested that potential pandemics may have occurred in and ; however, it is unanimously agreed that the first documented influenza pandemic occurred in , resulting in high morbidity [ , ] . the virus originated in asia, before spreading to africa, and then simultaneously spreading from both continents to europe. it reportedly spread across the entire european continent within months, before eventually reaching the americas [ , ] . two pandemics were recorded in the eighteenth century. the first began in russia in , eventually moving across the entirety of europe within months and, ultimately, across the known world over the following years [ ] [ ] [ ] [ ] . the second pandemic began in china in , before spreading to russia and, subsequently, across all of europe. interestingly, this second pandemic had a high proclivity for young adults [ ] . two major pandemics also occurred throughout the nineteenth century. the first began in in china, with subsequent spread to southeast asia, russia, europe, and north america and had a low overall mortality rate [ , , , ] . a second pandemic emerged in russia in and spread rapidly to europe and north america, circumnavigating the globe in just months [ , ] . the virus, suggested to be of subtype h n , reappeared at least more times in successive years resulting in an estimated million global fatalities [ , , , ] . four influenza pandemics have occurred over the past century ( fig. ) . the - spanish flu pandemic, subtype h n , resulted in an estimated - million deaths worldwide and will be discussed in detail in the following sections. the - asian flu pandemic, subtype h n , originated in china in february and spread throughout asia and then globally by the summer. case fatality rates were approximately . % with - million deaths worldwide [ , [ ] [ ] [ ] [ ] . just a decade later, the - hong kong flu pandemic, subtype h n , emerged in china in july and spread throughout europe, north america, and australia by early [ ] . although mortality rates were low, the pandemic would ultimately claim between , and million lives [ ] . in april , the - swine flu pandemic, subtype h n , began with nearly simultaneous outbreaks in mexico and the us, before spreading globally over the next weeks. while the - pandemic had a low associated case fatality rate, resulting in , deaths worldwide, it had devastating effects on global economies and healthcare networks [ , ] . conventionally, influenza pandemics result in the extinction of previously circulating virus strains; however, this view was complicated by events in . although h n was replaced by h n as the circulating strain following the - asian flu pandemic, a descendant of the virus "re-emerged" suspiciously in , likely as a result of a man-made event, and established itself as a co-circulating strain, along with the reassortant h n virus (following the - hong kong flu pandemic) [ , ] . the suspicious "re-emergence" of a descendant of the virus in has been postulated to have been the result of a man-made event. this hypothesis has gained traction, as both the ha and na of the re-emerged virus show incredible similarity to a reference virus, and it is unlikely that this strain was maintained in an animal reservoir for almost two decades without having undergone detectable mutation [ ] . in , a triple reassortment (made up of avian, swine, and human influenza genes) pandemic h n jumped from pigs to humans, resulting in the co-circulation of three influenza strains [ ] . the first wave of the pandemic one hundred years following its emergence, the origin of the pandemic influenza virus remains shrouded in mystery. the pandemic began early in the final year of the first world war. whereas prior pandemics had spread largely along trade routes, the global context of the war enabled greater viral spread facilitated by the mass mobilisation of military personnel and civilians [ , ] . this was further augmented by the poor health and sanitation conditions found within trenches along the frontlines of the war, facilitating disease transmission [ ] . public knowledge regarding the severity of the pandemic was hindered, as many news agencies were barred from writing about the global health threat, instead reporting solely on morale boosting subjects [ ] . however, as spain was a neutral party in the war, newspapers were able to report on the devastating effects that the pandemic virus was exhibiting in spain. thus, it was generally perceived that this devastating illness originated in spain, resulting in the pandemic being incorrectly labeled as "the spanish flu" [ ] . a century following its emergence, there remains a relative paucity of knowledge regarding the ancestry and regional origin of the virus. sequence analysis suggests that the virus was derived from an avian-like influenza virus and that all eight gene segments likely evolved in parallel [ , ] . analyses of influenza virus genome sequences also suggest that the initial entry of the precursor virus into human circulation began in and did not appear to have jumped directly from an avian source [ , , ] . however, improved understanding regarding the emergence of the virus, as well as factors (biological, social, environmental) that contributed to viral transmission and pathogenesis, have been vital to the development of current epidemic and pandemic influenza outbreak response efforts. descendants of the pandemic influenza virus strain have been the cause of almost every seasonal influenza a infection worldwide over the past century [ ] . additionally, each of the pandemics occurring in , , and were caused by descendants of the pandemic ( , , and ). circulation of h n was reinitiated in and has therefore been added to this timeline. grey arrows designate the circulating or co-circulating strains during the interpandemic periods influenza virus strain, earning the viral strain the nickname "the mother of all pandemics" [ ] . investigations concerning the origins of the first wave of the pandemic, beginning in march , have primarily focused on the us and china, though recently it has been suggested that the origin may have been an outbreak of a respiratory disease misidentified as pneumonic plague in china [ , , ] . humphries suggests that the dissemination of labourers from china to assist allied war efforts during this outbreak resulted in the inadvertent spread of the virus to europe [ ] . from to , the route of travel to europe for the labourers included checkpoints in singapore, durban, cape town, north africa, and canada. additional reports of the first wave of the virus in the spring of suggest that the pandemic originated with chinese workers at camp funston, kansas, where the workers began suffering from to day fevers, gastrointestinal symptoms, and general weakness [ , ] . within weeks soldiers had been hospitalized, and thousands more had received out-patient treatment [ ] . the illness was able to spread to other military camps within the us, before traversing the atlantic ocean via soldiers supporting allied operations in europe. the us army reported that from march-may , . % of us soldiers were hospitalized due to this unidentified respiratory illness [ ] . while illness rates were high during this initial wave, mortality rates were largely similar to seasonal outbreaks of influenza. spain reported that the mortality rates for pneumonia and influenza was only . % [ ] . although there was some acceptance that this new illness was indeed influenza, this was not generally accepted [ ] . radusin reported that although the physiological symptoms were similar to influenza, the illness was too mild and short-lasting with minimal complications for it to be influenza [ ] . infections began to subside in many regions by the early summer [ ] . the generally accepted lines of spread of the first and second waves of the virus are provided in fig. . in mid-august of , reports suggesting a second wave of this severe illness began to surface [ ] . in some regions, primarily northern europe, the period between the end of the first wave and the beginning of the second wave was incredibly short, making the two waves almost indistinguishable [ , ] . this second wave, occurring from september-november , was responsible for the majority of illnesses and fatalities associated with the pandemic. although the origins of the first wave [ ] continue to be debated, the origin of the second wave is generally agreed to be the harbour town of plymouth in southern england, which allowed the pandemic influenza virus strain to easily spread to the rest of the world [ ] . ships from plymouth were dispatched to freetown, sierra leone in august , which allowed the virus to spread across the african continent [ ] . new zealand soldiers, who stopped in freetown on their way to and from the war front in europe, facilitated transfer of the pandemic virus to new zealand [ ] . from plymouth, the virus also spread to boston, from which it was able to disseminate across the rest of north america resulting in > million fatalities over the ensuing four months [ , ] . this second wave spread globally throughout the fall of with illness seen first amongst military personnel and, subsequently, within the general population [ , ] . the second wave of the pandemic differed from the first in that much higher morbidity and mortality rates were reported, with the majority of all fatalities associated with the pandemic occurring during this wave [ ] . ultimately, the pandemic would result in an estimated million infections worldwide (~ / of the world's population at the time) and a case fatality rate > . %, more than times higher than any other pandemic [ , ] . as a testament to the severity of this second wave, during the fall of , the first - pages of spanish newspapers were filled with obituaries of those who had succumbed to the pandemic virus [ ] . further, reports from philadelphia, pennsylvania stated that across hospitals in the city, every hospital bed was occupied by patients with influenza [ ] . the pandemic was especially problematic in highly isolated communities where many individuals had limited contact with prior influenza strains, thus lacking any pre-existing immunity. for example, some inuit settlements reported case mortality rates as high as %, while certain communities in africa were completely decimated [ ] . interestingly, individuals who had been infected throughout the first wave seemed to be protected against this secondary wave, and recent analyses have suggested that these individuals had up to % protection throughout the fall wave [ , ] . a third and final wave of the pandemic appeared in most of the world in the early months of [ , , ] . this final wave generally overlapped the first wave in terms of regional distribution; however, it seemed to spare areas where the second wave had been especially severe. overall, morbidity rates were lower throughout this final influenza wave; however, mortality rates are believed to have been just as severe as the second wave [ , ] . three successive annual winter post-pandemic recurrences occurred following the third wave of the pandemic with continually decreasing mortality rates, in particular within those - years of age [ ] . classically, fatal influenza infections are primarily associated with the very young (< years) and the elderly (> years) resulting in a characteristic "u"-shaped mortality curve (fig. ) . interestingly, however, the - h n influenza pandemic mortality curve exhibits a "w"-shape due to excess mortality in young adults - years of age due to influenza-related illness. it has been postulated that the increased disease severity in young adults was likely associated with immune status due to the lack of pre-existing immunity in this population [ ] . further, more than % of fatal infections occurred in those < years of age and nearly % of all influenza-related deaths during the pandemic were in those aged - years [ ] . influenza and pneumonia fatality rates in those aged - years were more than times higher than in previous years and absolute risk of influenza-related death was higher in those < years of age than those > years old [ ] . it is still not fully understood why this occurred, but it is possible that an antigenically similar influenza strain circulated prior to , providing a level of protection against the novel h n pandemic strain to those born prior to [ ] . additionally, archaeserological and epidemiological evidence have shown that an h subtype influenza virus may have been responsible for the influenza pandemic, which circulated until the emergence of the pandemic virus, leaving those individuals who had not been exposed to an h subtype virus highly susceptible to the pandemic virus [ ] . it has also been suggested that the generation of an excessive inflammatory response ("cytokine storm") in healthy, young adults infected with the virus may have contributed to the excess mortality seen within this age group [ ] . recent in vivo studies with the virus have shown a marked upregulation of inflammatory cytokines, along with the suppression of important antiviral immune responses [ , ] . in addition, other influenza strains, such as fatal h n infections in humans, have also been associated with the deleterious consequences of an excessive inflammatory response [ ] . ultimately, the case fatality rate was so severe in young adults during the - pandemic that the average life expectancy rate in the us dropped by~ years [ ] . physiological symptoms of the pandemic virus generally lasted for days and were described as feeling cold, shivering, high fever, weakness, nausea, loss of appetite, pharyngitis, cough, and bloodshot eyes [ ] . in some patients, a short "rebound" to normal health would occur that was followed by an aggressive recrudescence of disease and, ultimately, death [ ] . similar to the pandemic, the majority of fatal infections resulted from respiratory complications. however, it has also been demonstrated that excess influenza fatalities during the - pandemic were associated with an acute aggressive bronchopneumonia (including epithelial and vascular necrosis, hemorrhage, edema, and bacterial-associated variant pathology within the lungs) and a severe acute respiratory distress-like syndrome associated with severe facial cyanosis [ ] . autopsies performed on preserved lung tissues in the modern era have revealed acute pulmonary hemorrhage and secondary bacterial infections associated with pulmonary lesions in nearly all the fatal cases examined [ , , ] . streptococcus pneumoniae was present in many cases; however, staphylococcus aureus, haemophilus influenzae, and streptococcus pyogenes also appeared to complicate fatal cases [ , ] . neutrophilic pulmonary infiltration was seen in cases of pneumococcal pneumonia, while cases of staphylococcal pneumonia were marked by multiple microabscesses infiltrated by neutrophils [ ] . however, alveolar cell damage was seen in each case along with pulmonary repair and remodelling [ ] . tissues from each of the fatal cases examined had similar pathologic presentation, independent of which pandemic wave they were associated with. despite the difference in mortality rates, each wave showed similar cellular tropism, infecting both type i and type ii pneumocytes, as well as the bronchiolar respiratory epithelium [ ] . a multitude of scientific and technological advances have occurred over the past century, allowing for a greater understanding of the dynamic relationship between the host and influenza viruses during infection. these advances, along with access to autopsy samples and the reconstitution of the pandemic virus, have facilitated a greater understanding of how the pandemic virus differs from other seasonal and pandemic influenza virus strains. moreover, technological advancements following the - influenza pandemic virus have facilitated the development of preventative measures, including vaccines and antivirals, to limit widespread illness due to influenza infections. the determination of the genomic sequence of the pandemic virus, and the subsequent reconstruction of the virus, has provided us with the opportunity to decipher the viral-and host-specific properties that contributed to the severity of the - pandemic. it has been demonstrated that in contrast to other influenza viruses, the pandemic virus is highly virulent and pathogenic in multiple animal species without prior adaptation [ , ] . while obvious knowledge gaps remain, in particular with respect to the origin of the virus and the molecular mechanisms (host and/or viral) underlying differential pathogenesis as compared to other influenza viruses, there have been considerable advances in our understanding of the pandemic virus. [ , ] . means with standard deviations are presented for the prepandemic mortality curve. adapted from taubenberger and morens [ ] since the isolation of the first human influenza virus in , researchers have worked to develop an effective influenza vaccine [ ] . current influenza vaccines are reformulated seasonally and provide protection against circulating influenza a and b viruses [ ] . the world health organization conducts worldwide surveillance studies throughout the year on currently circulating influenza strains, and thus recommends which strains should be included in each influenza vaccine [ ] . while the seasonal influenza vaccine is approximately % effective, this protection is dependent on the characteristics of the individual being vaccinated, including age and overall health, as well as the match between the strains included in the vaccine formulation and currently circulating strains [ ] . individuals who have been vaccinated are generally protected from illness and provide a measure of protection for those who are not able to be vaccinated due to their age or other health issues through herd immunity [ ] . there has also been increasing interest in the development of "universal" influenza vaccines designed to provide protection against a wide range of antigenically-distinct influenza viruses, including those currently in circulation and those that may emerge in the future [ ] . these will not be discussed in detail as recent reviews have provided excellent discussions of this topic [ ] [ ] [ ] [ ] [ ] [ ] [ ] . two major classes of antivirals have emerged for therapeutic treatment of severe influenza virus infections. adamantane antivirals target the matrix- (m ) surface protein, while neuraminidase (na) inhibitors target the na viral surface protein. adamantane compounds were the first licensed influenza antivirals and block the m ion channel protein from properly functioning, thus effectively blocking membrane fusion [ , ] . unfortunately, adamantane antivirals are only able to target influenza a viruses limiting their application for influenza b virus infections [ ] . further, more than % of influenza a viruses are resistant to this class of drugs due to the high mutation rate of the virus [ , ] . thus, the use of na inhibitors is recommended [ ] . na inhibitors block the na surface protein and prevent the release of progeny virus and infection of additional cells [ ] . while resistance to na inhibitors has been observed in some influenza virus strains, they are still highly effective in the majority of patients [ ] . studies have shown that both adamantane antivirals and na inhibitors provide protection against the virus [ ] . although outside the auspice of this commentary, it should be mentioned that advances in mechanical ventilation modalities, including non-invasive positive pressure ventilation, from the s onwards, have provided an additional support mechanism for treatment of severely ill patients [ ] . the routine clinical use of antibiotics in the early twentieth century also heralded a new era for combating influenza viruses. as a testament to this, excess influenza mortality declined significantly from to onwards [ ] [ ] [ ] . however, the widespread general administration of antibiotics has resulted in an escalating public health crisis due to multi-drug resistance. this has impacted the treatment of severe influenza infections, as methicillin-resistant s. aureus (mrsa) is the most frequently isolated bacteria from patients with severe influenza-bacterial co-infections in the us [ , ] and complicated up to % of fatalities during the pandemic [ ] [ ] [ ] [ ] . influenza preparedness and lessons for the future although it has now been a century since the start of the spanish flu pandemic, lessons from this global health catastrophe continue to inform modern-day pandemic preparedness. investigations of the pandemic, including those with the reconstructed virus, have allowed researchers, as well as the global public, to understand the mechanisms that underlie pandemic emergence and escalation to public health crisis. it also allows researchers to predict the potential public health risks which may be caused by new pandemic viruses. for example, sequencing of the pandemic virus revealed similarities in the h protein of the pandemic virus, allowing researchers to predict that a lack of protection, and thus a high mortality rate may be seen in healthy, young adults throughout the h n pandemic [ ] . thus, when vaccines were limited during the early stages of the pandemic, young adults were prioritized over the elderly, who demonstrated some degree of protection to this influenza strain, resulting in a lower mortality rate in young, healthy adults [ ] . the average age for laboratory-confirmed fatalities during the pandemic was years in the us, supporting this vaccine prioritization initiative [ ] . additionally, the awareness of the complications caused by secondary bacterial co-infections from the pandemic ensured that the medical community was aware of this threat throughout the pandemic, likely resulting in a reduced mortality rate due to severe influenza infections with complications [ ] . however, the pandemic, albeit milder than previous pandemics in terms of overall mortality, resulted in significant strains on global healthcare networks and economies [ ] . in canada, direct healthcare costs (including hospitalizations, outpatient visits, and therapeutics) related to the pandemic have been estimated at $ billion cad, with $ million cad related directly to hospital care [ ] . a computational modeling study by smith and colleagues suggested that direct costs related to illness would be between . - . % of gdp in the uk for pandemics ranging from low to extreme [ ] . further, the - severe acute respiratory syndrome outbreak resulted in~$ billion total gdp loss in toronto alone [ ] . this highlights the importance of pandemic preparedness beyond a healthcare-centric approach to one that also includes downstream economic effects. the - pandemic resulted in incredible improvements to public health as well as scientific advances. however, our current understanding of influenza viruses, and their ability to cause illness in humans is still in its infancy in many aspects, and further underlines our inherent need for continued influenza research. the identification of key molecular determinants involved in the pathophysiology of severe influenza infections will also assist drug discovery and development strategies, including insights on appropriate timing for administration of antivirals and/or antibiotics. the development of efficacious broader-spectrum or "universal" influenza vaccines is also of incredible importance. the emergence of novel highly pathogenic avian influenza (hpai) viruses, including h and h subtypes, are of particular concern due to their pandemic potential. circulating hpai viruses are of potential concern to global public health [ ] . asian lineage avian influenza a (h n ), which circulates in fowl, is rarely found in humans but has resulted in life-threatening cases when able to establish stable lineages [ ] and h n has resulted in sporadic human infections in china resulting in > infections with an estimated % case fatality rate since [ ] . because hpai viruses can arise from previously known low-pathogenicity viruses with only minor mutations, it is important to be vigilant concerning these potential pandemic viruses [ , ] . in spite of the public health advancements in the years following the - pandemic, including widespread access in the developed world to an efficacious influenza vaccine, influenza viruses remain a global public health threat. this pas year, there were > , reported influenza infections, influenza-associated hospitalizations, and deaths across canada [ ] . further, during the - influenza season, vaccination rates in those - years of age was only and % in those ≥ , both below the national vaccination target of % [ ] . these data suggest that our continued vigilance against influenza must not only include a "research"-driven focus but also include public outreach and awareness campaigns that increase the general understanding of the healthcare burden associated with influenza infections. estimates of global seasonal influenza-associated respiratory mortality: a modelling study influenza: the mother of all pandemics updating the accounts: global mortality of the - "spanish" influenza pandemic characterization of the reconstructed spanish influenza pandemic virus influenza: molecular virology the annual impact of seasonal influenza in the us: measuring disease burden and costs prevention cfdca: estimated influenza illnesses, medical visits, and hospitalizations averted by vaccination in the united states influenza vaccination in young children reduces influenza-associated hospitalizations in older adults a narrative review of influenza: a seasonal and pandemic disease the origin of pandemic influenza a history of influenza history and evolution of influenza control through vaccination: from the first monovalent vaccine to universal vaccines insights into infectious disease in the era of hippocrates -year evolution of the term epidemic the chronicle of influenza epidemics the diffusion of influenza: patterns and paradigms influenza in twentieth century practice hanbook of geographical and historical pathology. london: new sydenham society pandemic influenza - ; a study in historical epidemiology influenza diffusion in european history: patterns and paradigms reviewing the history of pandemic influenza: understanding patterns of emergence and transmission transmissibility and geographic spread of the influenza pandemic the next influenza pandemic: can it be predicted? the emergence of pandemic influenza viruses summary report on the asian influenza epidemic in japan public health and medical responses to the - influenza pandemic global mortality impact of the - influenza pandemic estimated global mortality associated with the first months of pandemic influenza a h n virus circulation: a modelling study antigenic similarity of influenza a (h n ) viruses from epidemics in -- to the influenza pandemic: lessons for and the future the spanish flu--part ii: the second and third wave paths of infection: the first world war and the origins of the influenza pandemic the spanish flu--part i: the first wave evidence of an absence: the genetic origins of the pandemic influenza virus the influenza virus: a killer comes into view the site of origin of the influenza pandemic and its public health implications death from pandemic influenza during the first world war: a perspective from personal and anecdotal evidence. influenza other respir viruses understanding influenza backward the influenza pandemic: insights for the st century back to the future: lessons learned from the influenza pandemic reconstruction of the influenza virus: unexpected rewards from the past re-emergence of fatal human influenza a subtype h n disease the origin and virulence of the "spanish" influenza virus autopsy series of cases dying before and during the influenza pandemic peak lethal synergism between influenza and streptococcus pneumoniae what can we learn from reconstructing the extinct pandemic influenza virus? universal influenza vaccines: to dream the possible dream? universal vaccines and vaccine platforms to protect against influenza viruses in humans and agriculture is it possible to develop a "universal" influenza virus vaccine? outflanking antibody immunodominance on the road to universal influenza vaccination is it possible to develop a "universal" influenza virus vaccine? potential target antigens and critical aspects for a universal influenza vaccine is it possible to develop a "universal" influenza virus vaccine? potential for a universal influenza vaccine is it possible to develop a "universal" influenza virus vaccine? immunogenetic considerations underlying b-cell biology in the development of a pan-subtype influenza a vaccine targeting the hemagglutinin stem overcoming barriers in the path to a universal influenza virus vaccine influenza m proton channels mechanism of drug inhibition and drug resistance of influenza a m channel influenza neuraminidase inhibitors: antiviral action and mechanisms of resistance. influenza other respir viruses trend of influenza mortality during the period - influenza epidemic, england and wales, canada, and the united states a study of excess mortality during influenza epidemics in the united states, - critically ill children during the - influenza pandemic in the united states critical illness from pandemic influenza a virus and bacterial coinfection in the united states bacterial coinfection in influenza: a grand rounds review pulmonary pathologic findings of fatal pandemic influenza a/h n viral infections lung pathology in fatal novel human influenza a (h n ) infection centers for disease c, prevention. bacterial coinfections in lung tissue specimens from fatal cases of pandemic influenza a (h n ) -united states preliminary estimates of mortality and years of life lost associated with the a/h n pandemic in the us and comparison with past influenza seasons the impact of the h n pandemic on canadian hospitals the economy-wide impact of pandemic influenza on the uk: a computable general equilibrium modelling experiment national response to (sars): canada. in: who global meeting what will the next influenza pandemic look like emergence of a highly pathogenic avian influenza virus from a low-pathogenic progenitor public health agency of canada. / seasonal influenza vaccine coverage in canada textbook of influenza vital statistics rates in the united states: - . washington: office ugp vital statistics rates in the united states: - . washington: us government printing office not applicable. availability of data and materials not applicable. authors' contributions men and jk conceived of the ideas presented herein and made substantial contributions to the drafting and revising of the manuscript. both authors read and approved the final manuscript.ethics approval and consent to participate not applicable. not applicable. the authors have declared that they have no competing interests. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- -kdsv v e authors: chathukulam, jos title: the kerala model in the time of covid : rethinking state, society and democracy date: - - journal: world dev doi: . /j.worlddev. . sha: doc_id: cord_uid: kdsv v e kerala, a small state in south india, has been celebrated as a development model by scholars across the world for its exemplary achievements in human development and poverty reduction despite relatively low gdp growth. it was no surprise, then, that the covid pandemic that hit kerala before any other part of india, became a test case for the kerala model in dealing with such a crisis. kerala was lauded across the world once again as a success story in containing this unprecedented pandemic, in treating those infected, and in making needed provisions for those adversely affected by the lockdown. but as it turned out, this celebration was premature as kerala soon faced a third wave of covid infections. the objective of this paper is to examine kerala’s trajectory in achieving the success and then confronting the unanticipated reversal. it will examine the legacy of the kerala model such as robust and decentralized institutions and provisions for healthcare, welfare and safety nets, and especially the capacity of a democratic state working in synergy with civil society and enjoying a high degree of consensus and public trust. it will then examine the new surge of the virus and attempts to establish if this was due to any mistakes made by the state or some deficits in its model of “public action” that includes adversarial politics having a disruptive tenor about it. we will conclude by arguing that the kerala model is still relevant, and that it is still a model in motion. the covid- pandemic that descended upon us suddenly, rapidly spreading across the whole world, has been wreaking havoc on our lives and established habits. it is challenging us to interrogate and rethink many taken-for-granted ideas about our lives and institutions-the relationship between the individual and society, the meaning and value of sociality and communitas, of the common good, and perhaps above all the institutions that serve, govern and constrain us. our focus here is on the institution of the state, the critical actor in dealing with this pandemic. an important fact that has emerged in the wake of this global outbreak is that different states and political regimes behind them responded to the pandemic in very different ways with clearly different outcomes. a seemingly counterintuitive fact that has become clear is that some rich and powerful states (the us and the uk) have emerged as poor performers in effectively responding to the pandemic-in containing the infection by such timely measures as testing and isolating the infected, and in reducing fatalities by providing adequate health care in well-equipped medical centers. on the other hand, there are some relatively poor, so-called under-developed countries and regions, such as vietnam (the economist, ), cambodia and the small state of kerala in india (a state within a state) which have emerged as success stories with a record of early and effective interventions, of controlling the spread of the virus, healing the infected and reducing the death rate. this is a notable and significant fact despite later reversals and second and third wave of covid infections in some of these cases, including that of kerala. this article focuses on the "kerala model" of managing the pandemic. this small state in the south-west coast of india has been well known for nearly half a century for its "model" or pattern of development that achieved high levels of social and human development and rapid reduction in chronic poverty and endemic deprivations despite low economic growth and income (cds, ) i . the "kerala model" ii that has been studied by researchers since the mid- s, is once again in the news across the world as a relative success story in containing the pandemic despite economic constraints and other vulnerabilities such as its dense population iii and constant exposure to foreign contacts iv . indeed, some of these observers see kerala's pandemic management as a decisive test of the the objective of this paper is twofold: to highlight the ways in which kerala handled the pandemic and to analyze the structural and systemic factors behind the state's success. we will especially focus on the state and kerala's model of an effective and vibrant democracy and "public action" in the words of dreze and sen. we argue that while kerala was blessed with good and efficient leaders during this crisis, the more important factors behind kerala's success have been robust institutions of state and governance built over many years with the capacity to take timely and effective measures in handling the crisis. we further examine the unexpected reversal and the rise of third wave of covid infections in an attempt to identify what, if any, mistakes may have been made by kerala and if so if these were due to any deficits inherent in the kerala model. we argue kerala may have made a mistake in relaxing-even abandoning-the rules for the entry of a large wave of nrks returning to the state, and for isolating, testing and tracing these returnees, as kerala had successfully done earlier. while recognizing the unknown and unpredictable nature of this new virus (still being studied by experts) we also identify what may be some deficits in the model such as its tradition of public action that includes adversarial politics having a disruptive tenor about it, especially at a time of impending and contentious election. we argue further that states like kerala which have handled the crisis well have generally been relatively effective models of social democracies in which the state and its institutions work in relative synergy with society and representative social institutions. the paper is organized in four parts. this introductory part is followed by part i which describes the trajectory of the pandemic crisis, timely and effective steps kerala took in managing the pandemic, and then failed to anticipate and prevent a third wave. it also examines deficits in the model that may have been behind the state's failure to prevent a third wave. kerala's adversarial and competitive politics gave birth to public action which in turn laid the foundation for kerala model of development. however, competitive and adversarial politics may have its limitations especially when it comes to managing pandemics like the present one. kerala should have adopted a healthy combination of competitive and adversarial politics and a consensus based democratic approach to tackle the pandemic. part iii analyses the structural and systemic factors behind kerala's relative success, focusing especially on the capacity of the state and its institutions acting in synergy with society. part iv concludes the paper by reflecting upon the kerala experience and attempting to draw some generalizations about the capacity of "effective democracies" such as kerala to eliminate endemic poverty and chronic hunger in contrast to india's abysmal failure in making any serious dent into its record in these as it continues to be home to the single largest pool of chronically poor and hungry people in the world. we suggest that the roots of these lie in a major democratic deficit in the indian system--failed or weak public action, including rational-legal social movements and popular organizations, the space for these increasingly filled by communal, caste and nativist movements (tharamangalam, ) . it also discusses about the dominance of adversarial and competitive politics as the reason of kerala's failure to contain the covid pandemic in its third wave. how did kerala combat this virus better than india and many other countries? through what means? much of the answer to this question is public knowledge by now; for example, italy and the uk were battered by covid in the earlier phase of the pandemic outbreak since they did too little and were too late to take measures to contain the virus by testing, isolating and treating those infected and it resulted in devastating consequences. today, italy, uk, spain or much part of the europe are slowly recovering from the onslaught of the pandemic. the us, the world's richest and most powerful nation, was also confronting this crisis with early denials followed by confusing pronouncements and frequently changing policy initiatives by its authoritarian president even as the virus has spread rapidly turning cities like new york into epicenters of the pandemic. brazil's response to covid has also been a terrible one. india took some bold steps to contain the deadly pandemic by enforcing a stringent nationwide lockdown, but with little consultation, planning or provisioning in place to address the consequences of such a lockdown in a country with high levels of poverty, hunger, homelessness, weak health infrastructure and migrant laborers concentrated in its many urban centers. despite three successive lockdowns, india failed to control the spiraling surge in new covid infections viii . india which is slowly emerging from the lockdown in a phase to phase manner has overtaken brazil and usa and has become the global epicenter of covid pandemic. to see how and why kerala has been effective, we describe a few of the steps it has taken in a short time, then examine the policy priorities and values as well as the institutional structures that enabled kerala to act quickly to battle the pandemic-all of these the legacy of the "kerala model" over a period of time. although, kerala flattened the infection curve during the first two phases of covid ix , it failed to contain the surge in infections in the third phase. kerala's strategies in containing the pandemic in the first and second wave of infections gave way to premature celebrations and it instilled a sense of false safety in the minds of people. the fear factor went completely missing and with the easing of the lockdown people paid little attention to observe physical distancing, hand washing and even wearing masks. deal to collate and handle the health data of those quarantined xi . the major allegation was that the data was collected without the informed consent of the people and the deal lacked strong data protection clauses xii . the government version was that such an exercise was carried out to help medical officials and doctors to make a well-informed choice about possible hospitalization in the case of those quarantined. since the confidential data was collected under the deal made with the us company, questions were raised as to why the government did not disclose any details in the public domain regarding the deal. opposition parties xiii also questioned the rationale behind single handedly appointing the us based sprinklr company that too without putting a global tender for the same. since the cm also manages multiple portfolios including the department of information technology, the controversial deal was enough to rake up a political storm that too in the midst of the pandemic. the logic behind approaching a foreign company when kerala has institutions like centre for development of imaging technology (c-dit) xiv and kerala state it mission xv which are capable of handling big data analytics also raised doubts regarding governments decision. even the government at the centre led by bharatiya janata party (bjp) came down heavily on the state government for inking such a pact with a big data analytics company like sprinklr, when the country has central agencies like national informatics centre (nic) xvi which could easily handle the task assigned to the sprinklr. meanwhile, the kerala government defended its position citing that it took the decision to effectively analyze the covid data quickly. the government version was that it resorted to such a deal as it feared kerala might see an unprecedented jump in covid infection, following the easing of lockdown. it also stated that the ownership of the data lies with the kerala government and not with the sprinklr, which temporarily hosted the data in its server. the state government also said that strong data protection clauses were added to ensure the data privacy. however, the opposition parties weren't satisfied with these explanations and the reluctance of the cm to address the controversy openly added more fuel to the fire xvii . meanwhile, the government constituted a two-member committee to look into the matter. on april there was an outpouring of resentment over kerala government's stand. this unexpected move was dubbed as reluctance to accept more people coming by repatriation flights since the government feared that it will lose control over the fight against the pandemic. the opposition parties including congress, indian union muslim league (iuml) and bjp capitalized the public resentment against the stand of the governments. the opposition parties knew anything involving nrks would be a highly sensitive issue in the state since it has been surviving with the support of the remittances xxvii by overseas workers. it gave the opposition parties an opportunity to exploit the public anger and position themselves as true advocates of nrks. kerala will go to assembly elections next year and keeping it in mind, the ruling ldf, has been trying its best to turn the health crisis into an incredible opportunity to revive its political fortunes. the udf have dubbed the covid management as a mere public relations stunt with an eye on the forthcoming assembly elections. the opposition parties including bjp have accused the ldf for the spike in the infections as the government was too busy with marketing its covid story to international media and conducting debate series called kerala dialogue. the opposition parties in the state have always been skeptical about the kerala model of handling covid pandemic. the criticism by the opposition parties even had misogynistic undertones xxviii . the opposition accused that the health minister was not interested in saving lives and mocked her with misogynistic epithet. xxix however, the segregation of the infected and non -infected returnees from abroad did not happen due to technical difficulties and reluctance of the central government to conduct testing on expatriates boarding aircrafts from overseas. so, state government had no other go but to come up with an alternative strategy, where multi-layer screening facility was set up in airports for returnees xxx .again, on june , the cm wrote to the prime minister to seek the help from the central government to provide facilities for conducting covid test for expatriates returning to kerala via chartered flights. but this move was also met with stiff opposition and criticism from opposition parties and nrks xxxi . in july, a new trend emerged where covid infections through "contact" and local transmission xxxii started to surge in the state with more cases of community spread than imported cases. on july , kerala confirmed its first "covid super spreader" xxxiii incident in the coastal village of poonthura and pulluvila in thiruvanthapuram, the capital of kerala xxxiv . in poonthura and pulluvila, people blocked vehicles of police and attacked health workers. the residents in poonthura and pulluvila alleged that due to stringent lockdown measures they were not even allowed to venture out of their house to buy essential items from shops nearby. the residents complained that no shops in their vicinity were allowed to open and the men in uniform allegedly went around threatening and using bad words against the fishermen coming out of their homes. in addition to that a team of commandoes were but first, a brief overview of kerala and its specific characteristics will be helpful in providing a better context for this discussion. kerala is one of states in india, one of the smallest, but the most densely populated with million people nestled between the arabian sea and the hill ranges of the western ghats xxxvi .kerala is the only state in india without the historically, kerala has had close trade and cultural links with the outside world across the arabian sea; christianity and islam made their substantial presence here in the very early centuries of the founding of these religions making the state one of the most multireligious and multi-cultural. the past few decades saw a mass exodus of kerala's young people seeking employment outside the state, especially in the arabian gulf, but also in europe and north america. the remittances sent by these workers amount to about one third of kerala's state domestic product xxxviii (krishnan, ) . note also that there is a substantial number of migrant workers from other indian states (called "guest workers" by the kerala government) who fill local vacancies at the lower levels of the labor market, attracted by the higher wages and better social security in kerala. in addition to all this, unprecedented income growth and easily available bank loans in recent years have also spurred an exodus of kerala students seeking technical and higher education abroad, not only in the west but even in some remote parts of china and central asia, new destinations for those seeking medical and other degrees at relatively low cost. it is noteworthy that this small state now has four international airports facilitating the high volume of international travel. it is not surprising, then, that kerala was the first state to experience the covid- infection. indeed, the virus was initially brought by keralites returning from wuhan and italy xxxix . how, then, did kerala react to the sudden crisis? the first point to be highlighted here is that kerala may have been among the best prepared states/regions in the world to face this crisis. one reason for this is that it had the experience of successfully handling three crises in the past two years, a very serious nipah epidemic in and two outbreaks of kerala also failed to make use of the vast potential of alternative medical streams like ayurveda and homeopathy in treating covid . meanwhile, as the covid infections have alarmingly increased, the government has started promoting ayurveda as a way of boosting the immunity of the population xlvii . however, government has made it clear that diagnosis, medication and treatment of covid will only be done through scientifically-backed modern medicine. another criticism against kerala was that it was not testing enough. critics point out that kerala was testing less and thus it had relatively few cases earlier. in fact, whether kerala was testing enough was a cause of concern. however, in the beginning kerala, in march, the state was testing the most, followed by maharashtra. kerala with a population of million people conducted tests per million and maharashtra at that time conducted samples per million people. but in mid -april, when covid infections were slowing down in kerala, the aggressive testing strategy was relaxed. there had been allegation that kerala started testing asymptomatic and people with mild symptoms at a later stage. but as on september , , kerala has ramped up its testing from , to , tests per day. critics also argues that kerala invested its energy more in contact tracing than in testing which led to the drastic situation the state is facing now. second, kerala took early steps in monitoring and enforcing the rules of isolation. it has also harnessed and deployed modern technology such as surveillance by drones identifying locations of social gatherings, use of "geofencing" xlviii to enforce quarantine, and location tracking devices to create spatiotemporal maps for re-tracking movements of those infected. government resorted to surveillance technology to track the spread of the covid and to monitor people placed under quarantine. government was forced to resort to technology-based monitoring as the number of lockdown violators and those evading quarantine were increasing in the state. geofencing technology was one among them. what is behind kerala's success, some unique factors specific to kerala, a kerala exceptionalism? this is a complex question, and it is possible to highlight some unique historical and social factors, mentioned above. but our focus here is on institutional and cultural factors that are comparable and amenable to empirical investigation. from this perspective we will highlight the legacy of the "kerala model of development" that has created what some political scientists have called an effective or vibrant democracy (heller, ) , itself the legacy of "public action", as explained by dreze and sen lxxiv . this latter concept includes a proactive and interventionist state that responds to popular demands for basic social security, and a mobilized and politically conscious society that puts pressure on the state and holds it to account. how kerala evolved into such a state, at least close to this ideal, has a relatively long history. when kerala was born as a new state in india in by combining the two princely states of travancore and cochin and the british ruled region of malabar, all the three regions, especially the first two, had a half century old history of anti-caste and social reform movements followed by trade union and socialist movements, these resulting in a mobilized, and a socially and politically conscious population. the new state's first democratically elected government was formed by the communist party of india (cpi), the first time a communist party came to power in a free and multi-party election anywhere in the world lxxv (desai, ) . this government did not last long in a highly contentious political on the negative side, it is important to note two points here. first, the left parties abandoned such critical radical programs as land redistribution. they did enact and implement tenancy reforms that successfully abolished predatory landlordism. the traditional landless classes, of whom the vast majority were (still are) the dalits, received only their house sites or kudikidappu land leaving them where they had been for centuries, landless laborers, now turned into modern types of casual wage laborers lxxix (tharamangalam, ) . second, even the limited distribution of house sites, the most radical among indian states, required organized struggles and intense participation of mass organizations, especially of landless workers. the newly gained home ownership, however limited, did succeed in bestowing a certain sense of dignity to the former hutment dwellers who could no longer be evicted from their houses at the whims of the landlords. we have argued above that the two key elements in the kerala model are ( ) an interventionist state committed to pro-poor policies, and ( ) a mobilized society that engages the state through well-organized mass organizations and parties. in this section we discuss the way in which these two elements have interacted to create and maintain a certain synergy, a "virtuous" relationship. we suggest that this may be critical in understanding why kerala has succeeded where many others such as guatemala, nicaragua, and sri lanka have not been so successful. in examining state-society relations, scholars use different analytical lenses such as "equilibrium," "balance," "synergy," and "state-in-society." we find joel migdal's concept of state-in-society is particularly useful for it shows the state as embedded in society and constructed by social forces, on the one hand, yet enjoying relative autonomy and the capacity to mold and even manipulate social forces and social groups, on the other. .while the state can enjoy relative stability over a period of time, being a system of institutionalized practices, beliefs, and rules, every state is ultimately precarious and vulnerable as an arena in which contesting and changing social forces are continuously at play. we argue that kerala has been successful in maintaining a balance between state and society and among a variety of social groups and organizations. by this we do not mean an equilibrium imposed by some invisible hand, but a synergy created and maintained by institutionalized mechanisms capable of accommodating differences and resolving conflicts. as noted above, in kerala the process involved accommodation and compromise among various interest groups, mediated by rational-legal, modern institutions of the state as well as political parties and other organizations. this is not to suggest that this "virtuous" relationship has been unproblematic, or without dilemmas, strains, or contradictions or that it will be sustained indefinitely and can now be taken for granted. in fact, such a relationship is always precarious and a delicately negotiated one since democratic participation involves and requires critics of a given regime and even political opposition, and states and societies must negotiate inevitable conflicts of interests among social classes and groups. our argument has only been that kerala has not only been successful in maintaining a healthy balance but has, in fact, enhanced the "virtual relationship" between state and society in the context of confronting the four successive crises of floods and epidemics, and that the state's response to the latest and more ferocious covid pandemic, may have been a final test of the "kerala model". unlike the earlier crises, which were of short duration, the covid pandemic is likely to take longer time to resolve. it is therefore a crucial test of resilience of the kerala model. kerala's navodhanam was, indeed a revolution in hope -giving new hope to people who formerly lived without hope, accepting their fate as inevitable and/or unchangeable. kerala historian robin jeffrey (jeffrey, ) has noted, for instance, that by the s large numbers of people in kerala had enthusiastically embraced the belief that they had "entitlements", a concept that figures prominently in the writings of amartya sen. the social reform movements campaigned vigorously for the rights of the lower castes to education. an early associate of sree narayana guru, padmanabhan palpu lxxxi said on the subject: "we are the largest hindu community in kerala. without education no community has attained permanent civilized prosperity. in our community there must be no man or woman without primary education" lxxxii (ramachandran, ) . it is not accidental that universal access to education (first primary and then secondary and even post-secondary) became an issue of high priority in kerala both in terms of public demand and public policy. a notable aspect of mass participation, especially important in health care, has been the pivotal role of "women's agency" (women's empowerment in terms of literacy, education and health, promoting general achievements in human development indicators such as imr, child nutrition and health), as explained by amartya sen (sen, & and ( dreze and sen, the unprecedented covid pandemic has shaken our taken-for granted "common sense" in many respects. kerala which successfully contained the covid in the first two waves of infections is now struggling to contain the pandemic in its third wave. the kerala model of managing and containing covid , which was lauded once across the globe is now looked upon with skepticism. it is also a cautionary tale for the government, media and public at large against celebrating covid success models. kerala's biggest advantage was its robust healthcare system and participatory mode of governance or social democracy when it came to handling the pandemic. however, the pandemic has showed that even a participatory social democratic state face challenges in managing crises and ensuring basic security to all. we will conclude with a brief reflection on the concept of entitlement, made famous by nobel laureate amartya sen in many of his writings but especially in his classic study of famines (sen, ) . his now famous, but somewhat unexpected conclusion was that famines in the modern world are not caused by shortage of food, but by "entitlement failure" lxxxiii . as a corollary to this he also argued that self-governing democracies in the modern world have no famines for the obvious reason that such a government, responding to the needs of the people who elected them, and working in synergy with its citizens and civil society organizations has the knowledge, capacity and the will to take timely and effective steps to obtain and move food to the needy. one of the notable successes of india's sovereign democracy has been the elimination of the periodic famines that had been a recurring feature of colonial india. the country has been free of famines since the s; for the past few decades india has been not just selfsufficient in food supply, but has a substantial surplus, some of it often rotting or eaten by rats in ill-equipped public storages. but here comes india's famous paradox of "hunger amidst plenty" in contrast to kerala, a food deficit state which has eliminated such hunger. as cogently argued by patrick heller, effective democracies put re-distributive pressure on the state. if so, it should be obvious that india fails this test; india is just not an effective democracy --in sharp contrast to kerala which is. atul kohli, who has extensively studied these issues in india supports this conclusion (kohli, (kohli, , (kohli, , (kohli, & . he addresses the class basis of the indian state even better. according to him the redistributive capacity of the indian state, always low, declined even further during the post-reform period. this latter period, he says, has been marked by a shift in the character of the indian state from "a reluctant pro-capitalist state with a socialist ideology to an enthusiastic pro-capitalist state with some commitment to inclusive growth" (kohli, ).he asks if and how democratic politics can counter class power and if "…democracy and activism of the poor (can) modify this dominant pattern of development " (kohli, ) .he sounded an optimistic note as he was writing at a time when popular demands had led to such beneficial legislative measures such as the mgnregs lxxxvi and the national food security act lxxxvii which were beginning to show some success. but the indian state has shifted once again under the bjp which combines even more right-wing economic policies with the ideology and project of hindutva, a militant form of majoritarian hindu nationalism that moved from the fringes of indian society and politics to its mainstream in a short period of time (tharamangalam, ) .no wonder the figures for poverty and hunger are showing no decline as has happened in other southern countries, especially india's own poorer neighbors such as nepal and bangladesh. lxxxviii meanwhile, it is indeed encouraging to see that a few states such as kerala, goa and the so called tribal states mentioned above have continued to follow more promising paths with easily visible outcomes in terms of their social development. we can only hope that the lessons learned from kerala and other states and countries for their best practices during the covid pandemic will continue to resonate with the people of india and the world as they may be re-thinking and re-imagining a better world for the post-covid era. they admitted that they hurled abuses at the health officials and scoffed at them, but residents added that they were forced into doing such activities based on misleading information given to them by external forces. they also said that they have apologized to the health officials in this regard. (interviews with residents on july, lxiii in the wake of nationwide lockdown, guest laborers were housed in shelters in the state. with the easing of the lockdown, many of these the guest labourers are returning to their homes each day. the community kitchens served the guest laborers, the elderly, the homeless, the destitute, and the sick. lxiv a poverty eradication and women empowerment programme of government of kerala why have covid- cases surged in kerala? the hindu -year-old woman in kerala beats covid- in nine days india coronavirus: how kerala's covid success story came undone. bbc news poverty, unemployment and development policy: a case study of selected issues with reference to kerala this is kerala's ayurveda prescription to fight coronavirus and keep infections down. the print congress wins first round over sprinklr deal. the new indian express five years of participatory planning in kerala: rhetoric and reality the sen in the neo-liberal developmental programmes of kerala state formation and radical democracy in india the capabilities approach in the vernacular: the history of capability building in kerala india: development and participation an uncertain glory: india and its contradictions indian development: selected regional perspectives embedded autonomy: states and industrial transformation state-society synergy: government and social capital in development bringing the state back in on our minds: how a southern indian state crushed its coronavirus outbreak. the new york times new delhi: promila & co. in collaboration with the institute for food and development policy limits to kerala model of development: an analysis of fiscal crisis and its implications. thiruvananthapuram: centre for development studies planning commission global hunger index: the challenge of hunger and climate change. welthungerhilfe; and dublin history of kerala: prehistoric to the present do political regimes matter? poverty reduction and regime differences across india social capital as product of class mobilization and state intervention: industrial workers in kerala the labor of development: workers and the transformation of capitalism in kerala degrees of democracy: some comparative lessons from india a virus, social democracy, and dividends for kerala. the hindu land to the tiller: the political economy of agrarian reform in south asia democracy and development in india state and redistributive development in india poverty amid plenty in the new india state-directed development: political power and industrialization in the global periphery row over senior congress leader's "covid rani" remark on kerala health minister foreign remittance, consumption and income. thiruvananthapuram: akg centre for research and studies community kitchen live data state power and social forces: domination and transformation in the third world between euphoria and scepticism: ten years of panchayati raj in kerala taking solidarity seriously: analysing kerala's kudumbashree as a women's sse experiment a study on domestic migrant labour in kerala covid services-norka how a south indian state flattened its coronavirus curve. the diplomat report of the committee for evaluation of decentralized planning and development. government of kerala a decade of decentralisation in kerala: experience and lessons india coronavirus: why celebrating covid- 'success models' is dangerous. bbc news kerala cm's principal secretary removed for alleged connection to gold smuggling accused. the indian express a survey on ageing scenario in kerala senior citizens of india: emerging challenges and concerns indian development: selected regional perspective office of the registrar general. ministry of home affairs(mha). government of india the sample registration system (srs) statistical report in india is carried out by the office of registrar general & census commissioner a store promised buyers cashback of rs , if they got coronavirus within hours of purchase. vice prevalence of risk factors of non-communicable diseases in kerala, india: results of a cross-sectional study education in kerala's development: towards a new agenda carry 'coronavirus -free' health certificate to enter india if flying in from italy, south korea. times of india cm ducks' questions on sprinklr deal. the hindu the coronavirus slayer! how kerala's rock star health minister helped save it from covid- . the guardian kerala could lose rs , cr. in remittances as over lakhs register to return from abroad. the print historical hurdles in the course of the people's planning campaign in kerala, india agrarian class conflict: the political mobilization of agricultural laborers in kuttanad the perils of social development without economic growth: the development debacle of kerala rejoinder" to respondents to the symposium understanding kerala's paradoxes: the problematic of the kerala model of development medical team cornered by mob in kerala covid- hotspot, coughed at, abused. the indian express facebook, twitter followers not impressed by kerala cm pinarayi vijayan's pressers of late. the new indian express kerala sasthra sahitya parishad virus kerala: a portrait of the malabar coast lxv kudumbashree, . on august , authors of this research paper interacted with women who provided support to community kitchens (interview on august , ). lxvi a model that contains multiple centers of sourcing and delivering food, but with a "hub" that coordinates the activities and provides a central point of contact to all the clients. lxvii at present there are a total of janakeeya hotels are functioning in kerala. these days demand for janakeeya hotels are also rising. as per records, , , meals have been provided through these hotels. on july , authors of this research paper interacted with women who manage janakeeya hotels and some of them expressed their doubt towards the sustainability of the hotels. (interview on july , ). lxviii a good example of this is sourcing community-based disaster management plans (cbdms) already prepared by a large number of gram panchayats (village level governments) in the aftermath of the two earlier floods.these plans are based on extensive ward-based data on shelter management, hospital infrastructure, technical resource persons, and trained health workers. this valuable resource is now being used for the fact- lxxxiii take the example of the bengal famine of which killed over million people. sen asks why these million (mostly the rural poor) died while others were well fed, yet others hoarded food and/or exported food out of bengal. the answer has to be sought in the system of food distribution and resource allocation, a complex social, cultural, political and especially legal system. those who starved were the ones who were excluded from access to food in this system, at the center of which was a "war economy" that determined and controlled such access, i.e., "entitlements" to food. lxxxviii it is noteworthy that the best performing indian states in enhancing human development and reducing poverty also include some in the north east such as manipur and nagaland. we would suggest that the critical factor behind the difference between these so-called "tribal" states and the politically powerful, but socially backward north indian states (also the main base of the bjp and the hindutva movement) is the relatively weak presence (if any) of caste in the former and its entrenched and all-encompassing nature in the latter. a second factor may be the early lead of these north east states in literacy and education, mostly due to missionary activities. key: cord- - spglmzf authors: polšek, dora title: huremović d, editor. psychiatry of pandemics: a mental health response to infection outbreak: springer international publishing ; pages; isbn - - - - (e-book), isbn - - - - (softcover) date: - - journal: croat med j doi: . /cmj. . . sha: doc_id: cord_uid: spglmzf nan this book, dealing with a specific and so far underdeveloped field of psychiatry, is intended for a general audience interested in the overall mental health implications of a pandemic. although parts of the text can be understood by non-medical readers, the sections focusing on medication and specific symptoms could be harder to follow without a medical background. the series of chapters was envisaged as an all-encompassing review of the available research in the narrow niche of psychiatric consequences of a pandemic. serendipitously, the book was published before the outbreak of covid- , and at several places forebodes the emergence of a disease x, explaining the reasons that increase the odds of this scenario. today, several months later, it sounds as a feeble voice of a prophet, drowned by the noise of the actual coronavirus pandemic. the book starts off by giving a brief historical background of the most widely known pandemics, so as to underline the limited information that has been available to science today. several key reasons for knowing so little about mental health consequences of witnessing and surviving a pandemic are listed. for example, after the spanish flu the shock and horror of losing - million lives in a year had subsided so unusually quickly that the pandemic was dubbed the "forgotten pandemic. " this and other observations provide food for thought amid the information overload related to the current global situation. the text goes on to cover cultural, sociological, technological, legal, and managerial aspects of a pandemic, including surprising topics such as the analysis of the psychology behind the zombie apocalypse fantasy, as well as a point-by-point guideline for treating health care staff working with infectious patients. the authors give considerable attention to the impact of social distancing and quarantine on mental health, citing research papers showing a higher incidence of depression, posttraumatic stress disorder, and other anxiety disorders in patients admitted to intensive care units, family members of infected patients, and health care workers. many explanations presented in the book might seem intuitive and already known to the reader. however, the book's value lies in diligent and thorough fact-checking, as well as patient and unbiased data presentation, that stand in sharp contrast with shallow and sensationalistic style of most of the articles we are served daily in our news feeds. several chapters give an overview of psychiatric treatments and presentations of well-known illnesses. although in line with the all-encompassing goal of this book, the information given is too simplistic for a clinical expert but too complex for a non-specialized audience, and seems out of place. the limitation of the new and exciting field described in this book is the specificity of every pandemic when it comes to the affected population, pathology, incubation period, infectivity, mortality, and cultural context, so the conclusions drawn can be only sign posts for new solutions in an actual pandemic. however, this book provides a good review of different approaches necessary to deal with psychologic issues arising amid and in the aftermath of a pandemic and could be a compelling read for the interested audience. pandemics: health care emergencies key: cord- - lb y authors: rusch, valerie w.; wexner, steven d. title: the american college of surgeons responds to covid- date: - - journal: j am coll surg doi: . /j.jamcollsurg. . . sha: doc_id: cord_uid: lb y nan the covid- pandemic abruptly and perhaps irrevocably changed the way we live, conduct our business affairs, and practice medicine and surgery. in mid-march , as covid- infections escalated exponentially across many areas of the us, the centers for disease control (cdc), the surgeon general and the american college of surgeons (acs) recommended that hospitals and surgeons postpone non-urgent operations in order to provide care to covid- patients. [ ] [ ] [ ] it quickly became obvious that the covid- pandemic presented unprecedented medical challenges. acs leadership including the board of regents and officers (appendix) worked with the acs executive director (dr david hoyt) and staff to rapidly organize a response to the covid- crisis. the aim of this effort was to support acs members and fellows, as well as the broader medical community, in continuing to provide optimal patient care. because other similar public health crises could arise in the future, we report the measures taken by the acs to respond to the covid- pandemic. as the covid- pandemic spread rapidly from asia to europe and on to north america, a lack of national preparedness became obvious in many countries, including the us. one of the most urgent needs was the rapid dissemination of accurate information regarding the care of covid- patients. physicians and surgeons were initially forced to confront an overwhelming medical crisis via informal electronic exchange of anecdotal experience. therefore, the acs leadership convened a covid- communications committee (ccc) to provide timely, relevant and comprehensive information through an acs covid- one of the first and most important acs initiatives was the creation of guidelines for the selection of patients needing urgent operations (including some cancer procedures) during the immediate, temporary suspension of non-urgent surgery. the acs worked with surgical leaders across disciplines and throughout the country to create appropriate guidelines that were quickly referenced by the centers for medicare and medicaid services (cms), and many surgical societies and health care systems. [ ] [ ] [ ] [ ] as the covid- pandemic started to wane in may , a similar process was undertaken to create guidelines for the safe resumption of elective surgery, again accompanied by close communication with cms. [ ] [ ] [ ] [ ] in addition to inclusion in the bulletin and posting on the acs website, dissemination of these guidelines was amplified through webinars, and press releases and interviews. starting in mid-march , each division of the acs rapidly undertook specific measures to respond to the covid- pandemic. although space precludes discussion of all of these activities, we highlight some of them here. the indefinite and immediate national curtailment of non-urgent surgery had a dramatic financial impact on many practices which was most acutely felt by surgeons in private practice. at the suggestion of one of the regents (dr james elsey), a practice protection committee (ppc, appendix) was established to collaborate closely with the staff of the acs washington dc office, to advocate for support of surgical practices and provide fellows with accurate and up-todate information. the ppc meet weekly by video conference to identify critical advocacy issues and information that needed to be disseminated to acs fellows, including insurance coverage for telehealth services, financial assistance programs for surgical practices, questions to consider in consulting tax advisors, and accommodations for student loan forgiveness. the ppc was instrumental in selecting topics to be included in the bulletin and also led a webinar (attended by surgeons) in mid-april to provide education to surgeons on financial issues. as they do every day, staff from the acs washington dc office played an essential role in advocating for the support of surgical patients and practices through regular communication with cms and nearly daily communication with the white house covid- task force. with the approval of acs leadership, they submitted on behalf of the surgical coalition (a large group of surgical societies) several letters to congress regarding federal financial assistance programs and legislative initiatives that were key during the covid- crisis. cancer programs the acs cancer programs including the commission on cancer (coc) played a pivotal role in responding to the covid- pandemic. cancer patients faced the dual risk of having their cancer diagnosis and treatment delayed and, as a highly vulnerable population, of contracting covid- . through its multidisciplinary membership, the coc was able to rapidly develop disease-specific guidelines for triaging cancer patients for treatment and to define what elements in cancer staging and care could be modified to reduce the risks of covid- infection. as noted above, these guidelines were posted on the acs website and immediately disseminated through multiple media channels and webinars, each of which were attended by to , interactive participants. the coc emphasized that the immediate needs of cancer patients during the pandemic should take top priority and that most cancer operations could not be considered "elective" or non-urgent. the coc, which is responsible for accrediting approximately cancer centers across the us, specified that centers should not be held accountable for practice deviations implemented to protect patients from covid- . similarly, as the incidence of covid- started to wane in late april , the coc drafted guidelines for the progressive resumption of more elective cancer care. as the covid- pandemic developed across the us and most health care institutions banned professional travel, the cot made the difficult decision to convert the annual spring cot meeting and the atls (advanced trauma life support) global symposium to virtual meetings. the cot made special accommodations to support trauma centers including a one-year extension of all trauma center verifications and a delay in the deadlines for data submission to the trauma quality improvement program (tqip). the cot also provided access to the atls and asset (advanced surgical skills for exposure in trauma) videos and educational materials for just-in-time trauma training for surgeons who were deployed to cover trauma calls. the second focus of cot was to provide resources to support trauma systems. with help from members of the cot disaster committee and trauma systems committee, a guidance document was published to support trauma medical directors in maintaining trauma center access and care during the pandemic. to ensure that governmental and healthcare system leaders understood the importance of preserving the trauma system and the need for regional coordination to support the distribution of patients and resources among hospitals, the cot published a statement on the importance of these issues which was then widely distributed through state and federal advocacy teams. modeled on experience in south texas and washington state, the cot developed a guidance document for setting up a regional medical operations center and worked closely with the fema (federal emergency management agency) healthcare resilience task force to promote this approach and identify potential sources for funding. the infrastructure described in this document , not only supported the ability to manage the surge of covid- pandemic patients but also the healthcare system's response to future outbreaks and mass casualty events. in addition, the cot worked with trauma registry vendors and tqip participants to collect confirmed and suspected covid- cases via icd- diagnosis codes in order to understand the impact of pandemic on trauma care and account for those challenges when conducting riskadjusted benchmarking. the regional structure of the cot in every us state and canadian province and many countries worldwide, provides an opportunity for lessons learned to be shared around the globe. for example, a webinar for the trauma health system in saudi arabia presented by dr eileen bulger, chair of the cot, on the acs guidelines garnered , attendees and the new york city cot shared a summary of their lessons learned through the acs website. the acs division of research and optimal patient care houses all the quality improvement programs in the acs, which include all the verification/accreditation programs as well as all the clinical data registries (eg nsqip and tqip). given the several decades of experience in creating and maintaining clinical data registries, the acs leaders decided to address the paucity of covid-related data by collecting data, with the overarching goal to support a better understanding of covid- . several clinical data developments at the acs during the pandemic were achieved -both in the current acs registries, and also the development of a new registry, aptly named the acs covid- registry. the following is a brief description of the achievements, which were described and messaged through the acs newsletter. importantly, there was a substantial response by hospitals who subsequently registered to participate in the registries. the purpose of this newly developed registry was to collect key data on all covid- patientsboth non-operative and operative patients. it was developed with the input of several expert clinicians at several sites in different "hotspots" who were in the midst of treating covid- patients. in addition to patient demographics, variables were designed to allow ease of data collection and based on relevant severity predictors, admission information, hospitalization information, therapies used, discharge information, as well as other factors. all patients ages and older were eligible. data were collected from hospital admission through discharge. participation in the registry is free of charge. all hospitals worldwide were invited to participate. at the time of this writing, the registry was released and hospitals have joined and are collecting data. we continue to communicate with health care providers and facilities through the newsletter to provide registry updates and to invite more to join in this important initiative. the acs houses several registries (nsqip, tqip, mbsaqip, peds nsqip, ncdb). by way of an example, the national surgical quality improvement program (nsqip) is a risk adjusted outcomes clinical data registry. it provides amongst the most accurate risk-adjusted surgical outcomes. the inpatient and post discharge surgical outcomes of covid patients across settings remains largely unknown. hence it was decided to add a covid variable into the programthus a risk adjusted (including covid) outcome may be evaluated and benchmarked. this will be important given the single institution publications that have reported high mortality and complication rates. in addition to nsqip, other acs registries are also adding covid related variables. given the rigor and high-level accuracy of data collection in the acs registries, we hope important data will be collected that will help in our diagnoses, treatments, and decisionmaking for these patients. as with the covid- registry, communicating the covid relevance of the current acs registries through the newsletter was important for the readership to know and understand -both in terms of participation, but also in terms of understanding some of the important things the acs and its membership are performing to combat this pandemic. the acs has a long history of partnering with the us military. in , the acs and us department of defense (dod) created a formal relationship designed to bring lessons learned from military conflicts to the civilian sector and to assist military personnel in maintaining surgical readiness between times of conflict. an excellent example of this collaboration was the dod's response in deploying , -bed hospital ships to new york city and los angeles and in building mobile field hospitals in multiple cities including new york, chicago, new orleans and hartford. in addition, military medical teams provided care in civilian hospitals. conclusions through an intensive and cohesive group effort by acs staff, leadership and fellows, the college has successfully managed the unprecedented challenges of the covid- pandemic and supported its members in continuing to provide high quality patient care. the response by the acs was multifaceted but was based first and foremost on providing surgeons around the world a single source of easily accessible and highly reliable information. in the us, the acs also served as a steadfast advocate for surgeons' practice needs at the state and federal level and for measures aimed at supporting optimal patient care. this approach provides a template for managing future such crises should they arise. all crises of this scope offer opportunities for learning and behavioral change. in the remarkably short span of months, the world changed radically. the covid- pandemic has irrevocably opened opportunities for working remotely via electronic platforms including, telemedicine, a greater ability to work from home, to hold even large meetings electronically, the expansion of virtual methods for training surgeons, and virtual site visits for programs needing acs accreditation / verification. in the midst of stress, loss and grief, there are also many future opportunities which the acs is now striving to bring to fruition. appendix. factsheet: state action related to delay and resumption of "elective" procedures during covid- pandemic covid- : recommendations for management of elective surgical procedures covid- : guidance for triage of non-emergent surgical procedures coronavirus updated: new information on elective surgery, ppe conservation and additional covid- issues cms releases recommendations on adult elective surgeries, non-essential medical, surgical, and dental procedures during covid- response healthcare facility guidance: summary of recent changes joint statement: roadmap for resuming elective surgery after covid- pandemic association of american medical colleges. important guidance for medical students on clinical rotations during the coronavirus (covid- ) outbreak accreditation council for graduate medical education additional education: cross-specialty summit on the impact of covid- pandemic on surgical training emergency restructuring of a general surgery residency durng the coronavirus disease pandemic: the university of washington experience orthopaedic education during the covid- pandemic pracitcal implications of novel coronavirus covid- on hospital operations, board certification, and medical education in surgery in the usa doctors and nurses are already feeling the psychic shock of treating the coronavirus factors associated with mental health outcomes among health care workers exposed to coronavirus disease the mental health consequences of covid- and physical distancing. the need for prevention and early intervention the american college of surgeons. covid- guidelines for triage of cancer surgery patients acs guidelines for triage and management of elective cancer surgery cases during the acute and recovery phases of coronavirus disease (covid- ) pandemic american college of surgeons committee on trauma. maintaining trauma center access and care during the covid- pandemic: guidance document for trauma medical directors assistant secretary for preparedness and response. establishing medical operations coordination cells (moccs) for covid- federal emergency management agency (fema) letter to emergency managers requesting action on critical steps how to partner with the military in responding to pandemics -a blueprint for success key: cord- -upj mvzn authors: hwang, e. shelley; balch, charles m.; balch, glen c.; feldman, sheldon m.; golshan, mehra; grobmyer, stephen r.; libutti, steven k.; margenthaler, julie a.; sasidhar, madhu; turaga, kiran k.; wong, sandra l.; mcmasters, kelly m.; tanabe, kenneth k. title: surgical oncologists and the covid- pandemic: guiding cancer patients effectively through turbulence and change date: - - journal: ann surg oncol doi: . /s - - - sha: doc_id: cord_uid: upj mvzn background: the covid- pandemic has posed extraordinary demands from patients, providers, and health care systems. despite this, surgical oncologists must maintain focus on providing high-quality, empathetic care for the almost million patients nationally who will be diagnosed with operable cancer this year. the focus of hospitals is transitioning from initial covid- preparedness activities to a more sustained approach to cancer care. methods: editorial board members provided observations of the implications of the pandemic on providing care to surgical oncology patients. results: strategies are presented that have allowed institutions to successfully prepare for cancer care during covid- , as well as other strategies that will help hospitals and surgical oncologists manage anticipated challenges in the near term. perspectives are provided on: ( ) maintaining a safe environment for surgical oncology care; ( ) redirecting the multidisciplinary model to guide surgical decisions; ( ) harnessing telemedicine to accommodate requisite physical distancing; ( ) understanding interactions between sars cov- and cancer therapy; ( ) considering the ethical impact of professional guidelines for surgery prioritization; and ( ) advocating for our patients who require oncologic surgery in the midst of the covid- pandemic. conclusions: until an effective vaccine becomes available for widespread use, it is imperative that surgical oncologists remain focused on providing optimal care for our cancer patients while managing the demands that the covid- pandemic will continue to impose on all of us. devastating consequences of the covid- pandemic, over . million americans will be diagnosed with cancer this year, and over , will die of their disease. thus, until an effective vaccine becomes available for widespread use, it is imperative that surgical oncologists remain focused on providing optimal care for our cancer patients, while managing the demands that the covid- pandemic will continue to impose on our health system and our providers. to this end, a panel of editors of the annals of surgical oncology were invited to reflect upon those strategies that have allowed institutions to successfully prepare for cancer care during covid- as well as others that will help hospitals and surgical oncologists manage the expected challenges at the intersection of covid- and cancer care. a summary of key measures that have established a framework from which to address these issues is provided, as well as additional strategies for managing resumption of surgical care in cancer patients. the panel provides perspectives on: ( ) creating a safe environment for surgical oncology care, ( ) redirecting the multidisciplinary model to guide surgical decisions, ( ) harnessing telemedicine to accommodate requisite physical distancing, ( ) understanding interactions between sars cov- and cancer therapy, ( ) considering the ethical impact of professional guidelines for surgery prioritization, and ( ) advocating for our patients who require oncologic surgery in the midst of the covid- pandemic. establishing a covid taskforce the initial action of most medical centers' response to the covid- pandemic was to create a multidisciplinary taskforce (''incident command center'') including executive leadership, infectious disease experts, and department leaders to provide oversight, create policy based on available scientific evidence, and allocate resources for managing the crisis. further, the taskforce is typically responsible for communicating a unified message regarding the evolving pandemic across the organization, which is critical for caregiver wellbeing and safety. utilizing a realtime dashboard developed for the purposes of managing the approach to the covid- pandemic, the taskforce sets organizational priorities in a rapidly changing environment. this has resulted in tiers of care for our oncologic patients, providing a framework for which patients should be treated with standard treatment pathways during the covid- pandemic versus those who should be considered for alternative pathways of care. one critical role of the taskforce has been to engage with other regional leaders to share best practices in a rapidly changing environment. for example, a weekly new jersey-wide cancer program teleconference was organized, with participation from many of the cancer programs across the state representing all the largest healthcare systems. the teleconference afforded all the programs the opportunity to share common experiences and best practices as well as set treatment standards informed by national guidelines but tailored to some of the unique challenges in the state. as another example, hospitals across boston have coordinated a regular meeting to exchange utilization and capacity data as a strategy of balancing load and minimizing the likelihood of implementing crisis standards of care asymmetrically across hospitals. while such strategies were considered advisable in the past, they are now an essential part of regional strategy for healthcare delivery. a fundamental focus on safety in the hospital and the clinic was an early and essential step for minimizing risk of exposure to all patients and caregivers, especially for those who needed oncologic care. the pandemic has forced most institutions to limit activity at the hospital and clinics to the most essential tasks to reduce potential viral transmission and enhance efforts to achieve social distancing for patients and staff. in some countries, including italy, there have been coordinated efforts to segregate either entire hospitals or hospital units for covid- patients, allowing physical separation of patients with greatest transmission risk from those who are most vulnerable. special training in biosafety measures has been required, and protocols have been put in place in every hospital, clinic, and cancer center to optimize the safety of caregivers in these areas. distancing requirements have led to an increased need for electronic communication devices such as smartphones and laptops, which have been provided to patients with covid- infection to enhance remote communication between patients and caregivers and family members while limiting exposure. enhanced cleaning protocols should be implemented in these areas and other ''hot spot'' areas including the emergency department and occupational health. protocols and dedicated teams have been created for safe patient transport and response to acutely deteriorating patients. the pandemic has required that the number of access points to the hospital and clinics be significantly reduced, and if available, thermal cameras have been used to assess all people entering-patients, visitors, and caregivers-for potential covid- infection. in many hospitals, no visitors are allowed; in others, the number of visitors allowed has been significantly restricted. prior to in-person visits at hospital clinics, patients are now contacted by telephone and screened for symptoms of potential covid exposure or infection, with those reporting possible symptoms being directed to testing areas and then triaged accordingly. among cancer patients, the european society of medical oncology (esmo) guidelines recommend testing for covid infection prior to chemotherapy infusions, although it is acknowledged that shortage of tests preclude this strategy at many hospitals. employee travel has been restricted in most institutions to reduce exposure of caregivers to covid- in high-risk areas; and at a minimum, employees are required to disclose travel upon return so that appropriate testing or quarantine may be implemented. in response to the covid- pandemic, organizations have enacted plans centered around ''caring for patients'' and ''caring for caregivers'' core values of healthcare organizations around the world. the downstream effect of protecting healthcare workers who care for patients with cancer is a reduction in potentially life-threatening covid- infections in our immunosuppressed cancer patients. new tools and resources have been required to support unfamiliar models of work for caregivers. reassignment of clinicians has been required to meet the evolving demands of the pandemic, in particular at ambulatory respiratory care clinics, covid- inpatient floors, and icus. rapid retraining of caregivers to fill critical positions which are outside of their traditional scope of practice have been accomplished via web-based platforms. live intranet-based courses have been developed covering topics which include icu workflow, update of covid- treatment protocols, management of sepsis and acute respiratory distress syndrome (ards), and ventilator management. some states have provided healthcare workers with civil liability protection, recognizing the need for many to work outside their area of specialty. creative work hour scheduling is one effort that attempts to minimize exposure among healthcare team members. for example, some hospitals have created teams of physicians within a specialty who rotate coverage for hospital and clinic patients (a and b teams). team a provides in-person care in the hospital and clinic, while team b provides care using digital platforms from remote locations. team a and b switch roles on a weekly basis. such scheduling strategies are intended to limit the spread of infection at the workplace within a group of specialists and staff. the mean asymptomatic period during incubation time is . days; and following high-risk exposures and a -day monitoring period, the estimate for missed cases is . per , , thereby providing theoretical support for a weekly rotation schedule. simultaneous cross-coverage of infusion, clinic, and in-hospital patients by medical oncologists is another strategy to reduce the size of the required in-hospital physician workforce to reduce their potential exposures. this is feasible given the overall reduction in patients at the hospital due to triage. a large percentage of those providing indirect patient care (secretarial support and administrative services) are generally enabled to work from home via secure digital platforms. this too requires rapid training of these staff and, in many instances, provision of hardware. access of caregivers to protective equipment (ppe) has clearly emerged as essential for maintaining a safe workforce. ppe use education has been one of the most challenging aspects of managing communications. over the course of the pandemic, recommendations from the who and cdc have changed and have often not taken into account local shortages of certain types of ppe. to rapidly disseminate correct use of ppe and assessment of patients with respiratory symptoms, electronic communication through the covid- intranet site has been utilized. preservation of ppe while simultaneously providing a safe environment for caregivers has been critically important. protocols have been established and shared with caregivers via the covid- intranet site for extended use and limited reuse of n masks and eyewear for those in high-risk environments. in addition, modified donning and doffing protocols for safe recycling are shared via the covid- intranet site. in many centers, caregivers have been provided a storage bag for repeated n use during the day. at the end of a shift, the storage bags are discarded, and n masks are placed in designated collection bags for resterilization. large-scale reprocessing of masks using hydrogen peroxide vapor has been approved by the us food and drug administration and is currently being utilized to establish a backup stock of ppe for emergency use in some areas. reduction of in-person meetings is in alignment with the goal of physical distancing. meetings within healthcare organizations have uniformly been transitioned to virtual meetings using secure digital platforms. for caregivers with direct patient contact and without a way to self-isolate at home, on-site or hotel rooming may be provided to limit exposure of a caregivers' family members during the pandemic. for the care of patients with covid- . many guidelines for resource allocation have been proposed, including one from the american college of surgeons, and they are covered in more detail below. for patients undergoing planned essential cancer operations, covid testing should ideally be performed within h of the planned procedure; however, few hospitals have had access to sufficient numbers of tests to incorporate this into their testing algorithm. for asymptomatic patients that test negative for covid- , anesthetic and surgical procedures are conducted under standard operating protocols. for patients who test positive for covid- , surgical procedures are delayed when possible, both to minimize exposure to healthcare workers and to reduce postsurgical risk. for those patients who test positive for covid- , whose symptoms are consistent with covid- infection, or in whom testing is not available or possible (e.g., emergent cases), enhanced or management protocols must be in place to reduce viral exposure to anesthesia, surgical, and nursing teams (table ) . significant levels of psychological stress, including depression, anxiety, and insomnia, have been documented among healthcare workers involved in the care of patients with covid- . to proactively address this, hospitals have looked to provide resources, including professional coaching, courses focused on wellbeing and resilience, and stress management, through virtual support groups. virtual exercise classes are also being offered to assist caregivers with maintaining physical fitness during the period of physical distancing. closures of schools and daycare centers have created an additional barrier for healthcare employees to report to work away from home. hospitals and medical centers do not operate daycare centers large enough to accommodate children for all their employees. moreover, even an attempt to scale up on-site facilities runs at odds with institutional goals of social distancing. for many employees, the ability to work from home and simultaneously provide childcare serves as a workable solution. for others, hospitals have contracted with vetted reputable outside organizations to provide childcare support at reduced rates for their employees. health systems have taken decisive measures to ensure the safety and wellness of their most important resources: their staff and patients. the actions that the pandemic has required of all healthcare systems have helped to address some long-standing issues and may allow hospitals to emerge from this challenge as stronger and more effective institutions. the multidisciplinary approach is a familiar cornerstone of cancer treatment, and repurposing this framework during the covid- pandemic allows care teams to continue to provide patient-centered cancer care with excellent outcomes, while effectively pursuing institutional priorities such as patient and staff safety, social distancing, and conservation of resources including ppes. in response to the covid- pandemic, many cancer centers have expanded the multidisciplinary team model to help manage oncologic care (table ). many guidelines for surgical oncology triage have been advanced during the covid- pandemic by professional societies and hospitals. , [ ] [ ] [ ] [ ] [ ] however, guidelines appropriate for one hospital or region may not be appropriate for another, given that hospitals and regions are in different phases of the pandemic. in addition, the appropriateness of some guidelines shifts as the impact from covid- changes over time. it is thus appropriate and essential to leverage multidisciplinary teams to develop care pathways, provide recommendations for individual patients, triage when necessary, and redesign workflows. some small studies have reported dual concerns for cancer patients of both increased risk of contracting the viral illness and higher rates of surgical morbidity and mortality among affected patients. , while evidence is still limited, such studies underscore the need to balance the numerous competing concerns including patient safety, health system resources, everchanging hospital mitigation strategies, optimal cancer treatment, and consideration of patient comorbidities. bartlett et al. have provided an early overview of key surgical considerations that must be taken into account broadly for all cancers as well as for specific cancer types. multidisciplinary discussion is collaborative and incorporates the specific risks and benefits from the perspectives of different specialties. surgeons will consider risks of exposure to covid- from an operation, adequacy of blood bank supplies, potential need for a precious icu bed postoperatively, and risks to staff including nurses and anesthesiologists. radiation oncologists will consider the risks to patient and staff and challenges faced by some patients undergoing radiation therapy in a setting in which visitors are not allowed. medical oncologists will consider avoidance of immunosuppressive treatments and use of regimens that can be administered at home. all team members will consider treatment efficacy, impacts of potential treatment delays, risks of travel, the number of required trips to the medical center, and challenges of clinical trial participation. as multidisciplinary teams converge to balance these competing priorities, several key areas merit careful consideration (fig. ) . in medicine, every action has inherent risks and benefits, and this balance may be shifted during the covid- pandemic. one must consider whether the recommended cancer care and potential exposure to covid- places the patient at higher risk than delaying care in favor of quarantine until the pandemic has eased. in some patients, delay of their cancer treatment may be in their best interest. patients that harbor the novel coronavirus may have poor outcomes during treatment, in particular if rendered immunocompromised secondary to cancer therapy. as a result, the multidisciplinary team must consider nonstandard approaches to treatment. the covid- pandemic has forced flexibility and thinking outside the box when considering treatment options for each patient. algorithms in cancer care are vital to consistent outcomes, but strict adherence to treatment algorithms cannot singularly override consideration of many covid- -related priorities. patients will be naturally anxious about the suggestion of a delay in their cancer treatment. they may be provided with reassurance that a multidisciplinary team has determined that the planned delay will not impair overall outcome and that the risk of a poor outcome from covid- exposure is greater than the risk of treatment delay. it is important to review with the patient the treatment plan and rationale for the recommendations as well as schedule regular updates as resources and capacity change within the health system. a new diagnosis of cancer confers a level of psychological stress on every patient, and the covid- pandemic poses additional emotional stress. thus, multidisciplinary teams should also be prepared to recognize patients who are struggling to manage their mental health and provide interventions for relief. defining urgency of ambulatory care in a multidisciplinary manner may allow some patients to have their appointments safely delayed. each cancer disease program should develop priority categories based on individual demographics, imaging and pathology reports, and tumor phenotype. teams must determine the order in which patients should be seen and by which team members. in addition, treatment teams may determine which patients can be effectively managed using a telehealth platform. for example, one strategy involves new patients with operable cancers being seen in person by a surgeon, and a medical oncologist providing consultation remotely, minimizing the number of direct encounters with the patient. in each case, the patient and their family are reassured that they will receive safe, effective, and time-sensitive care in this changing environment. multidisciplinary meetings to establish treatment recommendations for each patient should be accompanied by clear documentation of the treatment recommendations and the disciplines present during the discussion. published society guidelines should be used as resources whenever possible to guide management recommendations. emergence following the covid- surge requires the same intensity of planning and resourcefulness that was initially required to address this crisis. planning for resumption of surgical cancer care requires the development of patient priority categories based on urgency of intervention, postoperative resource requirements, and projected availability of these resources across the institution. in italy, one of the first countries to suffer from devastation and resource constraints from the pandemic, a simple four-tier prioritization schema incorporating urgency, tumor factors, and patient factors was instituted successfully, providing an effective and transparent process. establishing a priority list of patients with delayed operations requires communication not only within a cancer disease group but also across disease groups to truly optimize resource utilization. the multidisciplinary approach is again emphasized, recognizing the importance of integrating additional information such as nurse staffing levels, blood bank supplies, and icu beds. there are active efforts by both the national cancer institute (nci) and international groups to examine the impact of surgery in both covid- -confirmed patients and patients with cancer affected by delay of surgery or radiation that will yield important insights into outcomes in these affected cohorts (e.g., the uk national institute for health research global health research institute nct ). these studies will provide additional evidence on the effect of surgical delay and nonstandard management of cancer on cancer outcomes. there has never been a time when patient communication has been more vital as during the present covid- pandemic. conversations with patients, in particular about treatment delay, are difficult but essential, especially as the long-term consequences of treatment delays are often not well established. a multidisciplinary approach allows for more uniform and consistent messages to patients. conveying consensus among team members to a patient helps alleviate their anxieties, in particular when treatment recommendations do not adhere to standard established guidelines. the use of a multidisciplinary approach provides an organized rational framework to allow mitigation of the impact of covid- without compromising the excellent outcomes that have been achieved in cancer care. moreover, it can be an effective tool to manage patient safety while reallocating resources. albert einstein famously said: ''in the midst of every crisis, lies great opportunity.'' it may be more pragmatic to consider that a crisis accelerates inevitable change and that the opportunity presented in the midst of the covid- pandemic lies in examining burgeoning medical technology. ''telemedicine'' is an encompassing term which refers to the exchange of medical information through electronic communications. these technologies have gained widespread attention, but adoption has not been universal, noting significant barriers associated with the expenses of implementation, reimbursement challenges, and specific services that require an in-person visit for a physical examination or imaging and labs. for many patients, limitations are based on a lack of access to a computer/mobile device as well as lack of broadband access in more rural areas. in , only . % of physicians worked in practices that used telemedicine, and rates for surgeons were even lower ( . %). however, with the covid- pandemic, interest in and use of telemedicine has accelerated to slow community spread of the virus and limit exposure of other patients and staff members while providing essential non-covid healthcare. even before the pandemic, telemedicine was being evaluated for much-needed oncology services secondary to national shortages of cancer specialists and limited access to subspecialty care for patients in rural or underserved areas, including a patient's ability to obtain second opinions or a provider's ability to discuss cases at a multidisciplinary tumor board meeting. efforts such as the extension for community healthcare outcomes (echo) project, an evidence-based method that links interdisciplinary specialists with community-based practitioners using web conferencing technology, were being implemented across specialties to enable better management of complex conditions locally, including a focus on cancer care. for surgeons, uptake of telemedicine was being considered in the preoperative and postoperative phases of care. many studies found that, for selected conditions, preoperative diagnosis via telemedicine was as accurate as interventions carried out in conventional clinics. better incorporation of ''store-and-forward'' (table ) for imaging studies, pathology reports, and other medical records will improve the efficiency of real-time telemedicine visits and add to patient satisfaction. in many ways, this mirrors the steps needed for specialty consultation appointments, since these components of a patient's file are collected and forwarded for review in advance of seeing the patient. substituting a virtual visit for an in-person meeting with a surgeon in advance of a scheduled operation has yet to be implemented broadly and would need to account for issues around or scheduling to allow first-time in-person meetings in the preoperative area and then questions around tenets of the informed consent process. indeed, the role of telemedicine for surgeons is not well studied, and the extent of implementation is unknown but has most certainly been accelerated by the pandemic. other implications of preoperative telemedicine visits have yet to be evaluated robustly, taking into account issues of data security and patient privacy as well as broader implications for the patient-doctor relationship, including the patient perspective on the benefits (and downsides) of a virtual preoperative visit. postoperative assessments conducted by telemedicine, mainly for drain care or wound assessments, could decrease the burden of ambulatory clinic visits. further, a handful of studies showed that patient satisfaction with virtual visits compared favorably with usual care, noting a reduction in ''unnecessary'' trips to see their doctors, with attendant savings in costs associated with travel and time away from work. for postoperative care, many surgeons were already using telephonic check-ins or communication via patient portals embedded in electronic medical records as postoperative hospital stays were becoming shorter. common uses are already in place for discussion of pathology results and postoperative symptom management. beyond the perioperative phases of care, there is tremendous opportunity in evaluating a role for telemedicine in other aspects of oncology care. one major area that many experienced as a relatively seamless transition during covid- pandemic was videoconferencing platforms for team conferences and tumor boards. for hospitals facing resource constraints (e.g., ppe), which precluded all but highly selected elective surgical cases, the need and desire for consensus-driven decision-making was more apparent than ever, especially given considerations for triage and alternate treatment strategies. indeed, some have noted greater conference participation as virtual platforms were made available, heralding a welcome change for many. during the pandemic, many ambulatory clinic visits for interval oncologic surveillance were converted to telemedicine visits rather than being postponed. however, for many of these ''routine'' follow-ups, concomitant needs for imaging and labs precluded wholesale transition of these appointments to a virtual platform since a visit to a medical facility was still required for tests which serve as an adjunct to physical examination. as patients were heeding to social distancing and sheltering in place, research staff were reassigned to work remoting to the extent possible, putting accrual for clinical trials and nonessential in-person research visits on hold unless a virtual format was able to be developed and implemented {reference aso pawlik et al. covid article in press}. indeed, the fda issued guidance recommending ''alternative methods for assessments, like phone contacts or virtual visits''. under the waiver authority and coronavirus preparedness and response supplemental appropriations act, the centers for medicare and medicaid services (cms) expanded the scope of and payments for telemedicine service on a temporary and emergency basis, effective march , . prior to this, medicare only covered limited telemedicine visits and placed restrictions on qualified beneficiaries (patients) and originating site, such that the patient had to live in a designated rural area and had to receive the service at an established medical site (table ) . to specifically allow for home-based telemedicine, many prior requirements were eliminated. importantly, reimbursement parity for telemedicine visits was addressed, noting that medicare will make payments at the same rate as regular in-person visits. for other types of services such as virtual check-ins or e-visits, patients must have an established relationship with the physician and follow established time intervals following or preceding another evaluation and management (e&m) service or procedure. these services include brief communications and can include an array of communication technology modalities, such as telephone or use of online patient portals. with the need to quickly move to provide care while minimizing risks during the covid- pandemic, about half of state medical boards issued temporary waivers or allowances for in-state licensure requirements related to telemedicine (since the usual requirement is that physicians engaging in telemedicine are licensed in the state in which the patient is located). in addition, many states changed regulations around patient consent and medicaid billing to rapidly enable the provision of care via telemedicine. this has led to rapid uptake of virtual visits using various insurance carrier-based platforms as well as stand-alone (third-party vendor) products. waivers have been variable in terms of coverage determinations for audiovisual versus audio-only (e.g., telephonic) visits and synchronous versus asynchronous services (table ). in some states, services refers to a patient location (''originating site'') staffed by an on-duty medical professional who acted as a local facilitator. established medical sites included clinics, hospitals, or certain other types of medical facilities with a local facilitator who helps transmit information using digital assessment or monitoring devices as part of a telemedicine visit distant site refers to the location of the licensed provider who is rendering telemedicine services. where applicable, facility fees may be covered and reimbursed in addition to professional fees for the service provided that would normally require an in-person visit such as writing prescriptions, including those for controlled substances, were waived as well. as with most change efforts, due consideration should be given to how to achieve ''sticky change'' in post-covid times. interestingly, the future of telemedicine seems assured since the accelerated advances being made (and which continue to be made) during the pandemic are unlikely to dissipate and appear to have been widely embraced. of course, there will need to be an overarching assessment of alignment between health systems' strategic goals and continued promulgation of telemedicine. ease of use, quality of care, and satisfaction with virtual encounters will need to be assessed on both the provider and patient side. physicians may appreciate increased flexibility with visits, possibly allowing for more visits in a given day and removing inefficiencies that are created by last-minute cancellations and over-crowded clinics. however, real work will need to be done to assess barriers and facilitators so that telemedicine services are as effective and efficient as possible. from a workflow perspective, early lessons (and indeed, lessons on the frontline) include rapid ascertainment of technology skills, not only to be facile with operating the selected platform but also to allow for patient engagement and rapport while managing screens and the electronic medical record. patients who had a preappointment orientation appear to be better prepared for telemedicine encounters, which allowed for more focus on the appointment and not the associated technology. issues which are likely to require immediate attention at a national level are evaluation of the emergent/temporary cms policies including state-level licensure and regulatory decisions put into place during the pandemic. payment rates for telemedicine services may need to be revised since the current list of covered services is limited. if homebased visits continue, issues around reimbursement of facility fees, for both the originating and distant site (table ) , will need to be evaluated to ensure that costs around supporting the technology infrastructure are covered and that there is fair reimbursement for the services provided. expansion of telemedicine services may create opportunities for savings under episode-based bundled payments. technology barriers which had previously been raised will resurface, including issues with bandwidth for rural residents and functional technology platforms for data collection and secure, health insurance portability and accountability act (hipaa)-compliant communications. forward thinking about healthcare disparities is also warranted, understanding that lack of access to technology may exacerbate inequities. the experience with covid- in europe and asia has established that a cancer diagnosis places a patient at much higher risk for morbidity and mortality and perhaps at higher risk for sars-cov- infection. [ ] [ ] [ ] for example, patients with lymphoma, leukemia, and lung cancer on active therapy can suffer mortality as high as %. it is critical, therefore, to minimize the risk of sars-cov- exposure for patients with a cancer diagnosis, especially those receiving active cancer treatment. absent a vaccine or medications that can block viral entry, the only tools available at the moment are physical separation and ppe. the use of immunotherapy for the treatment of cancer is now considered mainstream. the number of patients with common epithelial cancers treated with immune checkpoint inhibitors (ici) has been increasing, especially for patients with tumors of the lung, head and neck, kidney, and melanoma. with respect to the administration of checkpoint inhibitors (anti-ctla- and anti-pd- /pd-l ), there are essentially two major concerns that have been described. first, pulmonary toxicities from ici can either confound or exacerbate manifestations of covid- . lung toxicity from ici can be life threatening. the incidence of icirelated pneumonitis can be as high as % with combination therapy. while this is not the most common adverse event seen with ici therapy, it is the most lethal with a mortality approaching %. since patients with covid- can manifest an immune pneumonitis, it can be a challenge to discern whether such patterns on chest x-ray (cxr) or computed tomography (ct) scans are due to iciinduced toxicity or a manifestation of covid- . it is also not known whether the combined morbidity of ici-induced pneumonitis and covid- -related lung injury are additive or synergistic with respect to mortality. this is particularly important since autoimmune pneumonitis is treated with steroids, whereas sars-cov is not. a second issue is related to the apparent similarity between the appearance of cytokine release syndrome in some patients receiving icis and a similar ''cytokine storm'' seen in patients with advanced covid- . both appear to be the result of the release of highly active cytokines such as il- as well as t cell activation, and there is evidence that immune hyperactivation mechanisms may be in part responsible for covid- severity. the potential for an exacerbation of covid- -related cytokine storm in the event of a cytokine release syndrome reaction to ici (or car-t cell therapy) is at least of hypothetical concern. fortunately, cytokine release syndrome is a rare morbidity of ici, and cytokine storm a late manifestation of covid- . therefore, the risk of the two overlapping would seem to be small. while the potential for increased morbidity of ici in the setting of covid- should be carefully evaluated, concern should not prevent the administration of these potentially highly active agents in those cancer patients who can derive a significant benefit. clinical judgement and a risk-benefit assessment must be individualized for the patient. radiation therapy typically requires daily visits to the treatment center for multiple weeks, thereby putting patients and staff at risk of covid transmission. strategies are considered to deliver fractionated radiation in fewer doses. the goal of alternative radiation treatment schemes is preservation of clinical efficacy while reducing the number of daily treatments by increasing the dose per fraction. guidance for alternative approaches requires adherence to acceptable radiobiological parameters and clinical tolerability. patients treated with thoracic radiotherapy may develop pneumonitis that could be confused with severe acute respiratory syndrome caused by this novel coronavirus. ct scan and clinical course should help differentiate these conditions. the onset of radiotherapy-induced pneumonitis is much slower than covid- pneumonia, which typically develops rapidly over days; and chest ct findings observed with covid- pneumonia may be diagnostic: ground-glass opacification, consolidation, bilateral involvement, and peripheral and diffuse distribution. lung cancer presents a particular challenge in the setting of covid- ; lung cancer is the most common cancer type in the usa, and therefore the risk of contracting sars-cov- in the setting of lung cancer is significant. whether the modality employed is surgery, chemotherapy, radiation, or immunotherapy, the potential for exacerbation of lung inflammation and its impact on lung function is real. , absent covid- , patients with lung cancer are already at risk of pneumonitis, postprocedure infection, and loss of lung capacity based on comorbidities, smoking, and as a result of the modalities employed to treat their tumors. principles of maintaining lung function through oncologically sound resections that still preserve lung volume such as video-assisted thoracoscopic surgery (vats) take on an even greater degree of importance. methodologies to deliver fractionated radiation to a confined area of the chest, such as intensity-modulated radiation therapy (imrt) and proton beam therapy, are important to consider to reduce injury to normal lung tissue. for lung cancer patients with known sars-cov- or active covid- , consideration of delay in radiotherapy for a few weeks until symptoms resolve and inflammation subsides is important. while risks and benefits of immunotherapy have already been discussed, it is important to note that these strategies play a particularly important role in the modern multimodality management of lung cancer. risk-benefit assessment is therefore of paramount importance in this patient population. management of head and neck cancer patients is more complicated during the covid pandemic. those treating these patients are at increased risk of transmission through aerosolized particles, mucus, and blood. operations involving any portion of the upper aerodigestive tract pose an increased risk of covid transmission to those in the operating room. a high rate of transmission to otolaryngologists was reported in china, italy, and iran, with reports of morbidity and death. planned radiation therapy should be delivered without delay when possible. each month of delay in treatment is associated with a % increase in mortality. for patients with other advanced-stage malignancies, questions often arise as to whether cancer therapy can be safely postponed. this decision must be based on a number of factors, including cancer type, stage, and alternative to standard regimens that have some evidence of efficacy. while these decisions are individualized, some general principles apply. if treatment can be delayed based on indolent histology or early stage, then that is a reasonable option. for some regimens, a switch from iv to an oral route alternative may be possible, or it may be feasible to administer iv medications at home. alternatively, iv chemotherapy dosing schedules that are every weeks rather than weekly should be considered when appropriate. it may be reasonable to shorten adjuvant therapy based on reasonable extrapolation of clinical trial data, or even completely eliminate adjuvant therapy if the survival benefits are very small. careful risk-benefit assessments must be made. in many patients, delay or at-home options will not be feasible. for such cases, patients should be carefully monitored, protected from exposure if they are not sars-cov- positive, and appropriately isolated from other patients if they are. for patients with active covid- requiring active therapy for a cancer diagnosis, agents that can exacerbate the pulmonary sequelae of covid- should be avoided until symptoms of the infection have resolved. agents that can result in immunosuppression should be avoided when possible. the current covid- pandemic has led several professional societies to provide guidance for cancer care for patients in anticipation of a public health crisis. , these guidelines utilize limited available data and common-sense approaches to reduce the risks to patients and healthcare workers while optimizing healthcare resources in anticipation of the crisis. in fact, the three ethical duties of healthcare leaders include the duty to plan, the duty to safeguard, and the duty to guide. the guidelines are particularly relevant in decisions of triage, which are ethically the most challenging, when we switch from patient care ethics to public health ethics. however, guidelines to cope with an emerging pandemic, when based on limited evidence such as case reports and poorly controlled studies, are fraught with ethical concerns, some of which are discussed below (fig. ) . the greatest risk of guidelines is that they may be flawed or wrong for the individual patient. in the instance of covid- , this risk is particularly concerning. the perceived risk of harm to cancer patients with covid- undergoing surgery comes from small case series, which are relatively poorly designed studies. publications in high-impact journals trying to rapidly disseminate information can falsely elevate the perception of higher quality of evidence. guidelines are rarely updated expeditiously, which is necessary for a rapidly evolving disease. when guidelines are inflexible (''should,'' as opposed to ''may''), they can compromise individual patient preferences, affect policy including insurance coverage, lead to redistribution of resources, or be misused by specific advocacy groups. while most members of guideline committees are experienced clinicians, their local experiences will temper their recommendations. hence, an expert from new york ( cases/ , people) might have a completely separate assessment of the public health crisis than an expert in texas ( cases/ , people). most importantly, guidelines are designed to account for perspectives other than those of the patient, including those of the healthcare system, the lawmakers, national societies, and business leaders. this can obviously disadvantage the individual patient who is advocating for his or her own health. additionally, guidelines can encourage and embed institutionally, ineffective, harmful, or wasteful practices. examples of such interventions include prophylaxis with hydroxychloroquine and routine antibody testing without validated tests. guidelines can be extremely helpful in reducing variance and providing guidance in times of crisis but, if flawed or based on poor evidence, can lead to wasteful and harmful practices. numerous conflicting guidelines can be frustrating for healthcare personnel, especially when they interfere with an autonomous doctor-patient relationship. additionally, guidelines tend to be simplistic (binary yes/ no, likert scale-based triage systems) and may not allow for the nuances of individualized care required for patients. these generally do not allow for iterative sequencing of care and shared decision-making with patients and their families, both of which form the backbone of surgical oncology. this can lead to significant moral distress for physicians, specifically cancer surgeons. postponing time-sensitive operations or diverting patients to less effective pathways and reducing accrual to potentially life-saving clinical trials are specific circumstances that can add to the distress of the healthcare team. such guidelines can place clinicians in a position of being judged unfairly by their peers or the health system and pose theoretical malpractice risks when clinicians do not adhere to them. the financial ramifications of guidelines that create delays to surgery whenever feasible cannot be understated, especially for solo practitioners and small practices, who may lose their livelihood based on triaging patients and diverting them towards alternative treatments. finally, the quality of cancerspecific outcomes can be adversely impacted by poorly designed or overly generalized guidelines. healthcare systems are affected by the beneficial and harmful effects of guidelines in a public health crisis. triage and diversion of cancer care away from surgery can have a profound impact. cancer surgery remains one of the pillars of a cancer center. guidelines that impose reduced utilization of cancer surgery can dramatically impact the goals of the institution through creation of new financial, logistic, and administrative burdens. furthermore, longterm acceptance of altered practice patterns through habit rather than evidence even after the crisis has passed could well prolong patterns of care that are in neither the patient's nor the institution's best interests. policies that create barriers to cancer research during the covid- epidemic may disadvantage patients and investigators even after the crisis has passed. patient and staff safety are of paramount importance. however, through the turmoil and human suffering created by the covid- pandemic, it is easy to lose sight of the fact that million people will die from cancer this year alone. moreover, successes in cancer research can have a dramatic impact on millions of people. patients may derive benefit from participation in even early-phase clinical trials. continued collection of biospecimens-in particular during the pandemic-is the backbone of future breakthroughs in discovery of targets and biomarkers. clinical guidelines and institutional policies have necessarily been drafted quickly and with limited data to improve patient and public health outcomes and reduce harm to patients, healthcare providers, and society. it is important to recognize the limitations of these guidelines, continually reassess their validity, and modify or discard those that do not demonstrate their value with scientific scrutiny. surgical oncologists find themselves as primary advocates for patients who are in need of cancer operations during this pandemic. physician and hospital leaders as well as policymakers must understand the important needs of cancer patients, whose diagnosis, staging, and treatment depend upon the timely availability of surgical care to maximize a successful outcome. otherwise, they become a statistic of ''preventable death,'' just the same as an individual facing severe attack from the covid- virus infection. for most types of cancer, there is solid evidence of a window of time of approximately - weeks from the time of diagnosis to definitive surgical treatment. published reports provide evidence that survival rates are diminished for patients whose definitive operations are delayed beyond this window. [ ] [ ] [ ] patient safety during this pandemic is clearly of paramount importance; but safety is a two-edged sword. safety derived from pursuit of institutional goals of social distancing, conservation of hospital resources, and preservation of ppes are undoubtedly important. however, the safety of cancer patients is of particular concern when treatment is put on hold in face of a progressive disease process; delays in standard treatment may compromise their chances for survival. identification of a medical middle ground that best addresses the multiple needs is appropriate. cancer surgery generally does not fall into the category of emergency surgery (unless there is a life-threatening condition), nor is it in the category of elective surgery (similar to a hernia repair). rather, most operations in cancer patients may be categorized as time sensitive and essential. nevertheless, policies issued by many state departments of public health or implemented by hospitals require postponing elective surgery during the covid- pandemic but recognizing the need for emergency surgery to proceed. hospital committees, licensing boards, and policymakers have not uniformly integrated the important circumstance of cancer patients with surgically treatable disease and the need to give priority access to these patients. patients who complete neoadjuvant therapy also find themselves in need of an operation that is time sensitive. the appropriate window for operation following neoadjuvant therapy in many cases is well defined and relatively small (e.g., neoadjuvant chemoradiation therapy for rectal cancer). thus, gaps in time between the completion of appropriate course of neoadjuvant therapy and operation may impact survival statistics and may impact operative morbidity and mortality. nonetheless, there are other situations in which the window of time for operation is much larger following neoadjuvant therapy (e.g., hormone-sensitive breast cancer or low-grade prostate cancer). reliance on multidisciplinary teams to provide recommendations on delays carries many advantages, as outlined above. another approach involves the development and use of a scoring system for triage. as an example, emory university healthcare created a surgical prioritization tool based on patient age, cancer type (if present), and the time after which delay will either impact patient survival or result in an irreversible compromise in outcome that impacts patient function. the scoring tool is built into a database that allows tracking, storing, filtering, and sorting of the pending cases to help construct operating room schedules at the various hospital sites based on medical prioritization and is modified by any local resource constraints (or availability, icu availability, bed availability, blood availability, etc.). this technology has limited the bias inherent to these complex decisions, while creating an efficient method for scheduling and prioritizing these cases. sars-cov- infection and the covid- pandemic have created unprecedented challenges for delivery of cancer care. the human toll caused by the covid- pandemic is overwhelming and has claimed almost , lives worldwide at the time of this writing. however, we must also remember that million people worldwide will die of cancer this year alone. it is incumbent on individual providers and the healthcare system to deliver optimal cancer treatment while working within government and institutional policies appropriately designed to reduce infections, ensure sufficient resources, and provide safety for patients and healthcare staff. this involves supporting a healthy workforce, leveraging multidisciplinary teams to triage effectively, innovating new solutions for patient care and communication, and advocating for our cancer patients as well as cancer operations as appropriate. policies and guidelines developed in response to the pandemic should be continually reassessed to ensure they remain loyal to their objectives under careful scrutiny. the pandemic has been a catalyzing force which will result in tremendous and lasting change in healthcare delivery; the opportunity must be seized to address many of the serious problems in healthcare that may be less intractable than we believed prior to covid- . disclosures the authors have no conflicts of interest to disclose. surveillance, epidemiology, and end results program what to expect: oncology's response to coronavirus in italy cancer patient management during the covid- pandemic the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application personal protective equipment during the covid- pandemic-a narrative review where thousands of masks a day are decontaminated to battle the virus. the new york times marriott donate free hotel rooms for medical workers responding to coronavirus crisis. usa today covid- : elective case triage guidelines for surgical care factors associated with mental health outcomes among health care workers exposed to coronavirus disease managing cancer care during the covid- pandemic: agility and collaboration toward a common goal recommendations for the surgical management of gynecological cancers during the covid- pandemic-francogyn group for the cngof covid- pandemic: surgical oncology patient care management of cancer surgery cases during the covid- pandemic: considerations american college of surgeons. covid- guidelines for triage of cancer surgery patients thoracic surgery outcomes research network inc. covid- guidance for triage of operations for thoracic malignancies: a consensus statement from thoracic surgery outcomes research network framework for prioritizing head and neck surgery during the covid- pandemic early estimation of the case fatality rate of covid- in mainland china: a data-driven analysis sars-cov- transmission in patients with cancer at a tertiary care hospital in wuhan, china clinical characteristics of covid- -infected cancer patients: a retrospective case study in three hospitals within wuhan, china a combined approach to priorities of surgical oncology during the covid- epidemic the use of telemedicine by physicians: still the exception rather than the rule the use of telemedicine in surgical care: a systematic review fda guidance on conduct of clinical trials of medical products during covid- public health emergency medicare telemedicine health care provider fact sheet federation of state medical boards. states modifying requirements for telehealth in response to covid- cancer care delivery challenges amidst coronavirus disease- (covid- ) outbreak: specific precautions for cancer patients and cancer care providers to prevent spread covid- and cancer: what we know so far risk of covid- for patients with cancer controversies about covid- and anticancer treatment with immune checkpoint inhibitors radiological findings from patients with covid- pneumonia in wuhan, china: a descriptive study pulmonary pathology of early-phase novel coronavirus (covid- ) pneumonia in two patients with lung cancer head and neck cancer care in the covid- pandemic: a brief update aao-hns position statement: otolaryngologists and the covid- pandemic the relationship between waiting time for radiotherapy and clinical outcomes: a systematic review of the literature ethics and resource scarcity: asco recommendations for the oncology community during the covid- pandemic ethical framework for health care institutions responding to novel coronavirus sars-cov- (covid- ) guidelines for institutional ethics services responding to covid- . the hastings center clinical guidelines: potential benefits, limitations, and harms of clinical guidelines cancer patients in sars-cov- infection: a nationwide analysis in china timing and delays in breast cancer evaluation and treatment impact of delay to surgery on survival in stage i-iii colon cancer time to surgery and colon cancer survival in the united states publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -qn i cdj authors: zheng, lei; miao, miao; gan, yiqun title: perceived control buffers the effects of the covid‐ pandemic on general health and life satisfaction: the mediating role of psychological distance date: - - journal: appl psychol health well being doi: . /aphw. sha: doc_id: cord_uid: qn i cdj background: ways to maintain good health during a pandemic are very important for the general population; however, little is known about the impact of the coronavirus disease (covid‐ ) on individuals’ life satisfaction and perceived general health. this study aimed to examine the effects of covid‐ on life satisfaction and perceived general health and reveal the buffering effect of perceived control on coping with covid‐ . methods: we collected , participants’ data from pandemic‐affected provinces in china and obtained regional epidemic data of the same provinces. we employed a moderated mediation model with both individuals’ self‐report data and regional epidemic data to verify the hypotheses. results: psychological distance mediated the relationships of regional pandemic severity with perceived general health and life satisfaction. perceived control moderated the detrimental effects of regional pandemic severity through the moderating effects of regional pandemic severity on psychological distance, as well as the moderating effects of psychological distance on life satisfaction. conclusions: our findings indicate that perceived control may act as a protective factor buffering the psychological impact of the pandemic on general health and life satisfaction. psychological distance can serve as a mediator that explains how the covid‐ pandemic impacts perceived general health and life satisfaction. the coronavirus disease has been rapidly spreading worldwide after it was first reported in wuhan, china, in december . in march , the world health organization (who) declared the disease a pandemic and that it was in phase , suggesting that the pandemic is a widespread human infection. as covid- spreads easily through ordinary human interactions, the pandemic is not only a serious threat to public health but also causes psychological changes in individuals (qiu et al., ) . thus, social-psychological assistance has been regarded as an important measure in the crisis governance of covid- in china (chen et al., ; duan & zhu, ) . however, compared to mental problems, maintaining positive psychological status, such as in perceiving general health and life satisfaction, is critical for people during the pandemic. surprisingly, it is unclear how the covid- pandemic is impacting people's perception of general health and life satisfaction, as well as how social-psychological protection against the pandemic can be provided. therefore, the present study aimed to address these issues by analysing integrated individual-level self-reported data and regional-level epidemic data in china. the negative psychological outcomes of the covid- pandemic have attracted considerable attention. one prominent aspect which has been widely studied is mental health (chen et al., ; duan & zhu, ; xu et al., ) . in fact, a pandemic often causes feelings of distress and anxiety, according to previous studies (bults et al., ; wong, gao, & tam, ) . in this pandemic, per cent of respondents reported psychological distress in a chinese national study (qiu et al., ) . therefore, researchers highlighted the public's urgent psychological needs during the pandemic (liu, zhang, & wang, ; pfefferbaum & north, ) . in contrast to psychological problems caused by the pandemic, there is scant knowledge regarding the positive psychological outcomes, which contributes to the development of a good life and building a well-functioning society (seligman, steen, park, & peterson, ) . for the general public, maintaining health and life satisfaction during a pandemic is very important. previous studies have revealed that the severe acute respiratory syndrome (sars) outbreak had a considerable impact on individuals' perceived general health and life satisfaction (lai, bond, & hui, ; lau et al., ; main, zhou, ma, luecken, & liu, ) . in fact, considering the importance of psychological intervention in the prevention and control of covid- (chen et al., ; duan & zhu, ; qiu et al., ) , it is extremely important to help people-especially those living in areas where the pandemic has spread-to cope with psychological changes. however, as the existing research has mainly focused on mental health issues resulting from the pandemic, more research exploring the psychological effects of the covid- pandemic on perceived general health and life satisfaction among residents of pandemic-hit regions is necessary. the psychological effects of a pandemic often vary across regions and the negative effects are stronger in regions that are severely affected than in those that are less affected. in particular, people residing in severely affected regions have reported high levels of anxiety and low levels of subjective well-being compared to individuals from more mildly affected regions (kim, ; lau et al., ; wong et al., ) . therefore, given the detrimental effects of the covid- pandemic on psychological outcomes, people may report less perceived general health and life satisfaction in more severe pandemic regions than that in milder pandemic regions. actually, people tend to feel closer to the virus in severely affected regions. this is in line with psychological distance, which refers to the subjective experience that something is close or far away from others, including other persons, events, time periods, and hypotheticality (liberman & trope, ) . as the possibility is also a type of psychological distance (liberman & trope, ) , it affects individuals' subjective perceptions as well as their responses to risks (chandran & menon, ; jones, hine, & marks, ; lermer, streicher, sachs, raue, & frey, ) . as the number of confirmed cases indicates the pandemic's severity (reed et al., ) , an increase in the number in nearby places may be related to the perception of being infected. this will eventually result in decreasing the perceived psychological distance. as subjective distance from a disease has been reported to impact psychological reactions (kim, ) , a recent study found that people who perceived a small distance from death reported low levels of life satisfaction (gerstorf, ram, r€ ocke, lindenberger, & smith, ) . therefore, when people are residing close to infected places, they feel a closer psychological distance from the virus and thereby perceive low levels of positive psychological outcomes, such as life satisfaction and perceived general health. perceived control psychological factors are becoming increasingly important in alleviating the negative effects of pandemics and increasing the government's capacity to deal with disasters (li, yang, dou, & cheung, ; pfefferbaum & north, ) . among these, perceived control was reported to moderate the relationship between the perceived severity of covid- and mental health problems (li, yang, dou, & cheung, ; li, yang, dou, wang, et al., ) . in particular, perceived control has been found to significantly affect both life satisfaction and perceived general health (ferguson & goodwin, ; hofmann, luhmann, fisher, vohs, & baumeister, ) . according to the theory of perceived control, this term refers to an individual's perceived capacity to handle or prevent a certain incident, and the individual differences in sense of control are closely associated with successful coping during stressful situations (lachman, ) . according to prior studies, a sense of control can be a factor enhancing a person's capacity and competence in handling outcomes, thereby leading to effective techniques for coping with stressors and increased life satisfaction and health (alonso-ferres, imami, & slatcher, ; drewelies et al., ; hofmann et al., ; lachman, ; thompson & prottas, ) . additionally, a sense of control alters an individual's perception of their capacity to handle the environment, which changes their perception regarding a threat (witt, proffitt, & epstein, ) . in particular, people with high perceived control feel closer to positive targets and perceive greater distance from negative targets (han, gershoff, kirmani, & dalton, ) . therefore, a sense of control may lead to a further distance from negative objects such as the pandemic, which further results in a high level of perceived general health and life satisfaction. according to previous studies, the covid- pandemic has negatively affected both physical and psychological health in regions where it has spread (pfefferbaum & north, ; qiu et al., ; xu et al., ) . in addition to mental problems, ways to maintain life satisfaction and perceived general health are equally important for the general population living in pandemic-affected regions. however, to the best of our knowledge, few studies have attempted to investigate the effects of the covid- pandemic on life satisfaction and perceived general health. considering the differences in pandemic severity across regions in china, we propose the following hypotheses. hypothesis . regional pandemic severity negatively predicts perceived general health and life satisfaction among citizens in pandemic-affected regions. although some studies have examined the effects of the covid- pandemic on psychological outcomes, little is known regarding the possible mechanisms underlying the above-mentioned process. according to the psychological distance theory, regional pandemic severity may alter the perceived psychological distance, thereby reducing perceived general health, and life satisfaction. therefore, hypothesis . psychological distance mediates the effects of regional pandemic severity on both perceived general health and life satisfaction. psychological factors have become increasingly important for controlling this pandemic (duan & zhu, ; pfefferbaum & north, ) . in particular, perceived control has been demonstrated to have a protective function for mental health during the covid- pandemic (li, yang, dou, & cheung, ) . therefore, we propose the following: hypothesis . perceived control moderates the psychological effects of regional pandemic severity on perceived general health and life satisfaction. specifically, the impact of regional pandemic severity on perceived general health and life satisfaction is stronger for individuals with lower perceived control. lastly, given the protective function of perceived control in disasters (pfefferbaum & north, ), a sense of perceived control not only alters individuals' perception regarding a threat (han et al., ; witt et al., ) , but also helps individuals cope with the threat (infurna & gerstorf, ) . according to the literature, high perceived control increases the psychological distance from a negative target (han et al., ) , which may in turn help individuals in coping with the covid- pandemic and further lead to high levels of perceived general health and life satisfaction. in addition, many studies have reported that a sense of control is a key protective factor during adversity (infurna & gerstorf, ) , suggesting that people with high perceived control tend to successfully cope with the threat, even when they perceive a close psychological distance from the disease. therefore, perceived control may moderate the relationship either between regional pandemic severity and psychological distance or between psychological distance and the outcomes. therefore, we proposed the following hypotheses: hypothesis . perceived control moderates the psychological effects of regional pandemic severity on psychological distance from covid- . in particular, the impact of regional pandemic severity on psychological distance is stronger for individuals with low levels of perceived control, compared to those with high levels of perceived control. hypothesis . perceived control moderates the effects of psychological distance on life satisfaction and perceived general health. in particular, the relationships between psychological distance and outcomes (i.e. life satisfaction and perceived perceived control and covid- general health for individuals) are weaker for individuals with low levels of perceived control, compared to those with high levels of perceived control. hypothesis . perceived control moderates the mediating effects of psychological distance on life satisfaction and perceived general health ( figure ). in particular, the mediating effects of psychological distance are stronger for individuals with high levels of perceived control, compared to those with low levels of perceived control. this study recruited , participants from provinces of china using an online survey platform. their average age was . ae . years. there were men and , women respondents. none of them were confirmed cases, but nine of them reported that they were suspected cases. in addition, participants had completed high school education, had completed junior college education, held bachelor's degrees, and held master's or doctorate degrees. all participants provided informed online consent, and the study design was approved by the ethics committee of the first author's university. only those participants who provided online consent were enrolled in this study; these participants were debriefed using an online page and were compensated with rmb ( . euro) after completing the survey. life satisfaction. this was assessed using a single item, similar to the methodology of a previous study (kobau, sniezek, zack, lucas, & burns, ) . the participants were asked to indicate their levels of life satisfaction on a scale of to , wherein = extremely dissatisfied and = extremely satisfied. the statement was: "overall, how satisfied do you feel with your current life? means extremely dissatisfied and means extremely satisfied." perceived general health. this was also assessed using a single item, which was taken from a previous study (main et al., ) . the participants were asked to indicate their attitudes toward their recent health status on a scale of to . the statement was, "overall, your present health status is_____, where means bad, means normal, means good, means very good, and means extremely good." psychological distance. this was measured using two items, which were adopted from the concept of psychological distance (liberman & trope, ) . individuals were required to report their perceived psychological distance from the pandemic on a scale ranging from (extremely near) to (extremely remote). the statements were: "how much distance do you perceive between yourself and covid- ?" and "how much distance do you perceive between yourself and the people infected with covid- ?" pearson's correlation between the two items was . . regional pandemic severity. this is usually determined using two main factors: clinical severity and transmissibility (reed et al., ) . in this study, the regional number of confirmed covid- cases was used as the regional pandemic severity index, as the number of confirmed cases has been linked to regional pandemic severity. these data were obtained from the website of the national health commission of the people's republic of china. this study used the data from the day on which the survey was conducted ( february ). perceived control. this was measured using the perceived control scale (whitaker, miller, & clark, ) . the scale comprises five inverse items: "i have little control over the things that happen to me", "there is really no way for me to solve some of the problems i have", "sometimes i feel that i'm being pushed around in life", "there is little that i can do to change many of the important things in my life", and "i often feel helpless in dealing with life problems." each item was scored on a -point likert scale ( = "strongly disagree" to = "strongly agree"). the responses were reverse recoded so that higher scores indicated high levels of perceived control. cronbach's alpha was . for this sample. perceived control and covid- as people are residing (nested) in regions with different levels of pandemic severity, those in the same region are more similar in the perception of the pandemic than people residing in other regions. in other words, participants were intraclass correlated within their residing regions in this data. in such cases, the hierarchical linear model (hlm) is commonly used for a nested data structure (stephen & anthony, ) . therefore, we conducted an hlm with the regions of china as clusters; psychological distance, life satisfaction, and perceived general health as individual-level variables; and regional pandemic severity as the region-level variable. first, to estimate the intraclass correlation, we analysed a null model in mplus . . second, in model , we performed hlm with the dependent variables (life satisfaction and perceived general health), and control variables (including age, sex, education level, suspected case, and group size). third, regional pandemic severity and perceived control were entered as predictors with random intercepts in model to test the direct effects of regional pandemic severity. the effects of the random slope of perceived control were included in the latter model (i.e. model ) for testing the cross-level moderation. fourth, in model , we tested the mediation effect of psychological distance on the relationships between regional pandemic severity and outcomes with both random intercepts and random slopes. the random mediation effects were tested with the monte carlo approach in r . . (preacher & selig, ) . fifth, a cross-level moderation model with random slopes was used to estimate the moderating effect of perceived control on the relationship between regional pandemic severity and psychological distance. last, we tested the random moderating effect of perceived control on the relationships between psychological distance and outcomes in model . table shows the participants' demographic statistics and the correlation matrix of the variables in this study. in the null model, the results indicated that the intraclass correlation coefficients were . for psychological distance, . for life satisfaction, and . for perceived general health, respectively. as shown in table , after controlling for . ** (À. **) À. + (À. **) . (. ) À. ** (À. **) . (À. ) note: +p < . ; *p < . ; **p < . . regional pandemic severity was measured by the number of confirmed cases at the province level-the number was transformed by logarithm with base , below the regional pandemic severity was the raw number of confirmed cases; sex: other covariables in model , regional pandemic severity was negatively associated with life satisfaction (b = À . , se = . , p = . ), but was insignificantly related to perceived general health (b = . , se = . , p = . ) in model . therefore, h was partially supported. next, the results of the mediation model showed that regional pandemic severity had a negative effect on the psychological distance from covid- (b = À . , se = . , p < . ), which subsequently led to low levels of perceived general health (b = . , se = . , p < . ) and life satisfaction (b = . , se = . , p < . ). according to h , the mediating effects were both significant (perceived general health: effect size = À . , se = . , p = . , % ci [À . , À . ]; life satisfaction: effect size = À . , se = . , p < . , % ci [À . , À . ]), suggesting that regional pandemic severity affects individuals' life satisfaction and perceived general health through psychological distance. to test the moderating effects of perceived control, the present researchers first tested whether perceived control directly moderates the effect of regional pandemic severity on outcomes. the results of model demonstrated that perceived control insignificantly moderated the effects of regional pandemic severity on perceived general health (b = . , se = . , p = . ) and life satisfaction (b = À . , se = . , p = . ), which does not support h . subsequently, according to h , the results of model indicated that perceived control moderated the effects of regional pandemic severity on psychological distance (b = . , se = . , p = . ; table ). as shown in figure a , the effect of regional pandemic severity on psychological distance was greater among individuals with low levels of perceived control (b = À . , se = . , p < . ) than those with high levels of perceived control (b = À . , se = . , p = . ). next, the results of model indicated that perceived control moderates the effects of psychological distance on life satisfaction (b = À . , se = . , p = . ), but not for the effects of psychological distance on perceived general health (b = À . , se = . , p = . ). therefore, h was partially supported. in particular, regarding the effects of psychological distance on perceived general health, there were no significant differences found across the levels of perceived control ( figure b ). however, the effects of psychological distance on life satisfaction were greater among individuals with low perceived control (b = . , se = . , p < . ) than among those with high perceived control (b = . , se = . , p = . ; figure c ). finally, this study examined whether perceived control moderates mediation effects of psychological distance. the results of the moderated mediation model showed that among people with low perceived control, the psychological distance mediated relationships between regional pandemic severity and perceived general health (effect size = À . , se = . , p = . , % ci [À . , À . ]), and between regional pandemic severity and life satisfaction (effect size = À . , se = . , p < . , % ci [À . , À . ]). however, for people with high perceived control, the effects of psychological distance on both perceived general health (effect size = À . , se = . , p = . , % ci [ . , À . ]) and life satisfaction (effect size = À . , se = . , p = . , % ci [ . , À . ]) were insignificant. according to h , perceived control buffers the psychological effects of regional pandemic severity by moderating the mediating effects of psychological distance in the relationship between regional pandemic severity and outcomes (i.e. perceived general health and life satisfaction). in the covid- pandemic, it is quite important to maintain life satisfaction and the general health of the public. the results indicate that psychological distance can serve as a mediator in the relationship between regional pandemic severity and life satisfaction, and regional pandemic severity and perceived general health. in addition, perceived control can act as a protective factor against regional pandemic severity by moderating the mediating effects of psychological distance. in particular, the regional pandemic severity adversely affects psychological distance when people have low perceived control, which in turn can lead to low levels of both life satisfaction and perceived general health. this is consistent with the results of previous pandemic studies, which reported that pandemics led to considerable negative psychological outcomes (main et al., ; pfefferbaum & north, ) , and perceived control promoted successful coping, which led to life satisfaction and perceived general health (lachman, ; prenda & lachman, ) . it is noteworthy that this study recruited participants from regions in china during the severe phase of the covid- pandemic. the regions that our study sampled reported . per cent of the confirmed cases ( , people) of the total number in china and covered . per cent of the chinese population ( , million people). therefore, our results revealed the relationship between figure . perceived control moderates the effect of regional pandemic severity on psychological distance. note: regional pandemic severity was measured by the number of confirmed cases at the province level, and the number was transformed by logarithm with base ; the moderating effects were significant for figure a and figure c but not for b. environmental threat and psychological outcomes among people who resided mainly in the affected regions in china during the covid- pandemic. the present study provides empirical evidence that covid- pandemic severity at the regional level had a direct impact on individuals' life satisfaction after controlling the covariables. this result is consistent with the psychological effects of sars on subjective life satisfaction (lau et al., ; maunder et al., ) . the present study found that the covid- pandemic can create psychosocial burdens for ordinary citizens, thus resulting in decreased subjective life satisfaction. the present study did not find a direct association between regional pandemic severity and perceived general health. however, we found that the regional pandemic severity could affect individuals' perceived general health by shortening their psychological distance from the virus. in particular, people reported lower levels of perceived general health when they perceived a closer distance to covid- . consequently, the regional pandemic can lead to psychological changes related to perceived general health. our findings suggest that individuals who live in severely affected pandemic regions are more likely to perceive poorer general health, which indicates that more attention to this detrimental effect is needed in the future. our findings revealed the detrimental effects of the pandemic on people's positive psychological outcomes. positive psychology-contrary to mental health problems-focuses more on individuals' health and well-being that not only enhance daily life for individuals but also contribute to well-being (seligman et al., ) . therefore, it is necessary for the crisis management department to direct more attention toward positive psychological intervention programs for ordinary citizens living in pandemic-hit regions. it is noteworthy that this study found the mediating role of psychological distance in the relationship between the severity of the covid- pandemic and psychological outcomes. in particular, people living in areas with a large number of confirmed covid- cases perceived a closer psychological distance from the virus. this is in line with previous studies that the distance between self and sars affected the level of anxiety (lau et al., ; wong et al., ) . additionally, the present study found that people who perceived a close psychological distance from covid- reported low levels of life satisfaction and perceived general health. this is consistent with previous studies wherein people reported less life satisfaction when they perceived the threat at a close psychological distance (gerstorf et al., ) . consequently, the regional threat (i.e. regional pandemic severity) alters the subjective distance from the virus, which can subsequently change people's life satisfaction and perceived general health. our findings that psychological distance mediated the relationship between regional threat and mental outcomes can be further generalised to other highly infectious diseases. previous research has reported that environmental factors affect an individual's reactions through organismic variables (luqman, cao, ali, masood, & yu, ) . in this study, regional pandemic severity was measured from the regional epidemic data, and large numbers of confirmed cases represented higher environmental risks of infection. we believe that regional pandemic severity can be regarded as an environmental factor and can impact individuals' mental health through organismic variables such as psychological distance. according to the present study's findings, perceived control can serve as a protective factor against the psychological effects of covid- . in particular, perceived control was found to enhance the participants' capacity to deal with stressors and alter the subjective experience of environmental stressors (alonso-ferres et al., ; lachman, ; li, yang, dou, & cheung, ) . this study found that perceived control could moderate the mediating effect of psychological distance, in which perceived control not only buffers the detrimental effects of regional pandemic severity on psychological distance, but also alleviates the negative impact of psychological distance from covid- on perceived life satisfaction. our finding that perceived control can moderate the relationship between regional pandemic severity and psychological distance is consistent with previous studies. people with high levels of perceived control feel psychologically further from the disease (han et al., ) , which helps them successfully cope with the pandemic and improve their perceived general health and life satisfaction (alonso-ferres et al., ) . therefore, people with higher levels of perceived control are more likely to feel psychologically further from the current pandemic, which in turn increases their feelings of life satisfaction and general health. previous studies found the moderating role of perceived control in the associations between pandemic severity and mental health problems (li, yang, dou, & cheung, ; li, yang, dou, wang, et al., ) . however, the present study provides the empirical evidence that perceived control can alter the relationship by moderating the relations between regional pandemic severity and positive psychological outcomes (e.g. life satisfaction). given the adaptive function of perceived control in mental health (lachman, ) , the present study demonstrated that perceived control can moderate the psychological impact of the covid- pandemic by moderating the impact of the covid- pandemic on psychological distance and moderating the impact of psychological distance on life satisfaction, thereby improving mental health outcomes. our overall findings not only support the main effects of perceived control on perceived health and life satisfaction but also demonstrate its buffering effect on adjusting psychological outcomes among people living in pandemic-affected regions (alonso-ferres et al., ; lachman, ) . covid- continues to spread globally; ways to maintain good health are becoming important for the general public. our finding revealed that psychological distance explained the relationship between regional pandemic severity and psychological outcomes. programs for increasing psychological distance from the virus may help improve the general public's life satisfaction and health in pandemic-affected regions. for example, social distancing and isolating suspected people may be a way to promote increased psychological distance for the general public. our findings significantly contribute to understanding the adaptive function of perceived control against the psychological impact of the pandemic. enhancing perceived control is a possible approach for helping individuals cope with the psychological effects of the covid- pandemic . prior research has found that perceived control improves as uncertainty decreases (zachariae et al., ) . therefore, in terms of crisis governance, public communication regarding uncertainty related to the pandemic will be important. an objective description of the pandemic transmission and severity will benefit regional stability as well as global pandemic prevention and control. there are some limitations in this study. first, it employed a cross-sectional design, in which causal interpretations among self-report measures are impossible. however, we included an objective index, which is more convincing in determining a causal relationship. in addition, some correlations were low but reached significant levels due to the large sample size. although a large sample size usually leads to more reliable results with greater precision and power, more solid evidence is needed to provide support for the relations among these variables. further research should address these issues through longitudinal studies or experimental designs. second, both perceived general health and life satisfaction were assessed using a single item, which may not have been sufficiently comprehensive. additionally, although the measurement of perceived control has been used in previous studies (whitaker et al., ) , these items involve the components of lack of control. to further clarify the impact of perceived and lack of control during pandemics, we recommend that future studies select a more comprehensive measurement that assesses both perceived control and lack of control. third, covid- has been declared a global pandemic by the who. however, our cohorts were restricted to majorly affected regions, especially eastern and central china. given the cultural differences among regions in china, which may limit the generalisation of the study's findings, future studies should consider the cultural differences among populations when examining the psychological effects of the covid- pandemic. untangling the effects of partner responsiveness on health and well-being: the role of perceived control perceived risk, anxiety, and behavioural responses of the general public during the early phase of the influenza a (h n ) pandemic in the netherlands: results of three consecutive online surveys when a day means more than a year: effects of temporal framing on judgments of health risk mental health care for medical staff in china during the covid- outbreak the more we are in control, the merrier? partner perceived control and negative affect in the daily lives of older couples psychological interventions for people affected by the covid- epidemic optimism and well-being in older adults: the mediating role of social support and perceived control decline in life satisfaction in old age: longitudinal evidence for links to distance-to-death when good things feel closer and bad things feel farther: the role of perceived control on psychological distance perception yes, but are they happy? effects of trait self-control on affective well-being and life satisfaction perceived control relates to better functional health and lower cardio-metabolic risk: the mediating role of physical activity the future is now: reducing psychological distance to increase public engagement with climate change the effect of psychological distance towards a disease on health communication well-being assessment: an evaluation of well-being scales for public health and population estimates of well-being among us adults perceived control over aging-related declines: adaptive beliefs and behaviors the role of social axioms in predicting life satisfaction: a longitudinal study in hong kong the sars (severe acute respiratory syndrome) pandemic in hong kong: effects on the subjective wellbeing of elderly and younger people thinking concretely increases the perceived likelihood of risks: the effect of construal level on risk estimation self-control moderates the association between perceived severity of the coronavirus disease (covid- ) and mental health problems among the chinese public chinese public's knowledge, perceived severity, and perceived controllability of the covid- and their associations with emotional and behavioural reactions, social participation, and precautionary behaviour: a national survey traversing psychological distance individual diversity between interdependent networks promotes the evolution of cooperation by means of mixed coupling empirical investigation of facebook discontinues usage intentions based on sor paradigm relations of sars-related stressors and coping to chinese college students' psychological adjustment during the beijing sars epidemic long-term psychological and occupational effects of providing hospital healthcare during sars outbreak mental health and the covid- pandemic advantages of monte carlo confidence intervals for indirect effects planning for the future: a life management strategy for increasing control and life satisfaction in adulthood a nationwide survey of psychological distress among chinese people in the covid- epidemic: implications and policy recommendations positive psychology progress: empirical validation of interventions hierarchical linear models relationships among organizational family support, job autonomy, perceived control, and employee well-being reconceptualizing adolescent sexual behavior: beyond did they or didn't they? family planning perspectives tool use affects perceived distance, but only when you intend to use it anxiety among university students during the sars epidemic in hong kong. stress and health pathological findings of covid- associated with acute respiratory distress syndrome association of perceived physician communication style with patient satisfaction, distress, cancer-related self-efficacy, and perceived control over the disease we acknowledge the partial financial support from the scientific research fund from fuzhou university (gxrc ), the fujian social science foundation for education product (jas ), and the ministry of education (moe) of the people's republic of china project of humanities and social sciences ( yjc ). key: cord- - kxi fd authors: baker, joseph o; martí, gerardo; braunstein, ruth; whitehead, andrew l; yukich, grace title: religion in the age of social distancing: how covid- presents new directions for research date: - - journal: sociol relig doi: . /socrel/sraa sha: doc_id: cord_uid: kxi fd in this brief note written during a global pandemic, we consider some of the important ways this historical moment is altering the religious landscape, aiming our investigative lens at how religious institutions, congregations, and individuals are affected by the social changes produced by covid- . this unprecedented time prompts scholars of religion to reflect on how to strategically approach the study of religion in the time of “social distancing,” as well as moving forward. particularly important considerations include developing heuristic, innovative approaches for revealing ongoing changes to religion, as well as how religion continues to structure social life across a wide range of contexts, from the most intimate and personal to the most public and global. although our note can only be indicative rather than exhaustive, we do suggest that the initial groundwork for reconsiderations might productively focus on several key analytical themes, including: epidemiology, ideology, religious practice, religious organizations and institutions, as well as epistemology and methodology. in offering these considerations as a starting point, we remain aware (and hopeful) that inventive and unanticipated approaches will also emerge. as we write this, the world remains mired in a global pandemic, with the rates of infection from a novel coronavirus continuing to rise. covid- is still a new and inadequately understood upper respiratory infectious disease, with a rate of mortality that is high enough to have killed over , people to date globally. with delays in testing in some locations and insufficient knowledge, official estimates are still being corrected; nevertheless, the spike of known infections in march of moved national governments around the world to close businesses, places of worship, and schools-essentially, any arena where people gathered in substantial numbers. by the end of april, the united states alone had reported over one million cases of covid- , and by the end of may, amidst the accumulation of infections, mortality in the united states reached a grim milestone of , deaths. by the time this paper is published, infections and deaths in the united states and elsewhere will not just be higher. they will be significantly higher. in this brief note, we consider some of the ways that the global pandemic is altering the religious landscape, aiming our investigative lens to how religious institutions, congregations, and individuals are responding to the social changes wrought by . where should our analytical attention be focused? the ongoing coronavirus pandemic, the related public health measures taken to mitigate the spread of the disease, and the varied public responses to the virus have far-reaching social implications. religious institutions, communities, practices, beliefs, and identities present a particularly rich area for social scientific study, especially given the centrality of face-to-face and intimate gatherings typically associated with nearly all religious practices and traditions. further, the death and mourning wrought by a pandemic would typically result in an increase in face-to-face gatherings and religious rituals; but given the need for social distancing and the necessity of adapting interaction to these constraints, the pandemic is triggering an increased need for religious traditions while at the same time significantly altering the expressions of those traditions. how religious institutions manage death and mourning-two of the social moments religious leaders and institutions are most central to during normal times-is a strategic location for viewing some of the ongoing changes to religion. in this we can see how the "demand" for religious ritual, comfort, and support is presumably increased by the pandemic, while simultaneously the "available supply" of religion (in the form it is expected) is drastically decreased. so too the changes to levels of existential risk and the associated patterns of social engagement brought about by the pandemic offer social scientists numerous opportunities to explore important theoretical and practical questions regarding how conditions of change and uncertainty relate to private religious beliefs and practices. while the health risks of debilitation and death draw immediate attention, controversy rages on about how to handle the threat of covid- . among the most basic points of dispute is the economy. the segregation of health issues into doctors' offices and hospitals, the relative isolation of severe illnesses, and the fact that the majority of people are either asymptomatic or as yet unaffected by the virus have prompted much attention on the economic impact of local, state, and federal governmental responses to the pandemic. for months, the slowing of the economy due to the sanctions on in-person gatherings and mandates to shelterin-place has resulted in millions of people being financially affected by closings, furloughs, and layoffs, with sharp increases in unemployment. immense pressure exists to "re-open the economy" out of a desperation to keep businesses running and to re-hire workers, with the use of "phases" to indicate the types of activities that could result (i.e., : bare essentials of food, health, and utilities; : limits on room capacity and enforced social distancing; : continued sanitization and expansion of social boundaries). the wearing of masks has been strongly encouraged, although selectively enforced and inconsistently modeled by political leaders. and mainstream news and various social media sources often add to polarization and obfuscation about re-opening the economy, resulting in decidedly split judgments on which experts are valid, which solutions are viable, and which practices are needed to address the pandemic. likewise, calls to re-open the economy have been interwoven with demands to re-open churches, and restrictions on in-person gatherings that have limited religious services have been opposed as limiting "essential" social services, and hence as an infringement of religious liberty. the pandemic raises a number of important analytical considerations for researchers, from intra-individual and interactive, to larger organizational and cross-national implications. at a minimum, religion scholars will want to pay attention to how religious professionals have altered their leadership to accommodate social distancing, switching to a largely remote working environment. while the social spaces of many congregational leaders are shrinking considerably, other religious professionals have been called upon to play expanded roles. for instance, chaplains "usually do [their] work quietly, around the margins. but with the pandemic, their work has moved to the center of the american religious experience" (cadge ) . however, perhaps a broader re-imagining is possible in this moment. just as the circumstances surrounding the pandemic have caused many people to rethink such systemic issues as racial inequality, health care provision, and the role of education in a thriving society, the mandated "pause" might allow religion scholars the time and space to more thoroughly revamp the study of religion in the twenty-first century, and to develop innovative approaches to understanding how religion continues to shape people's lives (see figure ). one critical way religious institutions and individuals will be central to analyses of the pandemic is as an "independent variable" (smilde and may ) , including as a vector of disease transmission (conger et al. ). multiple instances have been documented of religious gatherings operating as "superspreading events," including cases in washington (hamner et al. ) , oregon (cline ), california (bizjak et al. ) , arkansas , and west virginia (nazaryan ) in the u.s. religious gatherings have also been identified as important sites of virus transmission in germany (boston ) and south korea (shin et al. ) . while most congregations followed state orders to close, some resisted such orders, staying open and risking arrest. still others innovated by developing "drive-in" church services that likely still posed some dangers to the health of attendees. the centrality of intensive interactive rituals for producing the communal benefits of religion (e.g., social support, emotional catharsis, perceived healing) ensures that there will be persistent tension between many religious groups' desire for in-person gatherings and the social distancing requirements necessary to limit the spread of covid- . to the extent that religious individuals and their related groups believe in-person collective experiences are essential to their religiosity, social identity, and well-being, they may continue in-person gathering to the limits of (or even beyond) social distancing policies. at the same time, social connections among members within congregations may lead to the urging of doctor visits, care for symptoms as they emerge, and practical assistance for medical bills, making congregational participation a potentially important factor in treating and overcoming disease (see benjamins et al. ) . a central consideration on this topic is the extent to which different religious traditions and worldviews emphasize particular orientations, such as individualistic versus collectivist orientations, care for the vulnerable, and neoliberal economics. sorting out the different ways that religion relates to the spread of disease and care for the sick stands as an opportunity for researchers in the field of religion and health to contribute to the wider body of knowledge about the pandemic. although religion is never truly an "independent variable" because of its historical and ongoing relationship to other facets of social life, particularly race/ethnicity, social class, and gender (wilde ) , it is nonetheless critical to investigate and document how religion influences behavioral patterns that are directly related to disease transmission and mitigation. likewise, in the case of the united states, the reciprocal and intensifying relationship between religion and partisanship ensures that (margolis ) , to the extent that public policies and actions toward covid- are politicized, religion is a critical consideration for a full understanding of social distancing actions (or inactions). religion will also likely be assessed as a complex system of beliefs that are shared and contested. a key consideration here is religion and science, for which a number of issues are immediately notable for both quantitative and qualitative study. central among these are whether and how religious identity, beliefs, and practices relate to behaviors undertaken (or avoided) in response to social distancing requirements, such as avoiding gatherings, vaccine hesitancy, or wearing face masks, to name but a few. for example, wearing masks has become figure . topics for researchers of religion to consider in relation to the covid- pandemic. a strong point of contention, with some insisting that masks are ineffective and unnecessary (as long as one has enough faith and courage). those who refuse to wear masks include many who believe mask wearing bows to the dictate of "the state," and therefore restricts a person's god-given freedom. coupled with this, many believe that mask wearing bows to the dictates of science, which is viewed as unreliable, especially in contrast to the strength of one's own spiritual devotion for providing unseen, and therefore miraculous, protection. already, there is evidence emerging that religious views are consequentially connected to following (or ignoring) such social distancing practices (hill et al., forthcoming; perry et al., forthcoming) . notably, these patterns fall along distinctively gendered lines in relation to religion (smothers et al., forthcoming) . at least four dimensions of religiosity are worth exploring in regard to their connection to social distancing behaviors: ( ) certainty of beliefs, ( ) perceptions of invulnerability, ( ) collectivist versus individualist orientations, and ( ) the centrality and intensity of collective rituals. certainty and exclusivity of an ideological framework can relate to the distrust of authority from other institutions, such as science or medicine ). an important contextual consideration is the extent to which these aspects of religion are connected to social dynamics of race (see yukich and edgell ), and how the differential racial impact of the pandemic may therefore be connected to religiosity in ways that differ along racial and ethnic lines. another important contextual consideration, at least in the united states., is the increasing politicization about views about science and religion (o'brien and noy, forthcoming). further, public opinion about the pandemic and social policies for mitigation cannot be fully understood without consideration of multiple aspects of religiosity and worldview. approaching religion in the pandemic from a different angle, the responses of clergy and religious elites to the hardship of the pandemic provide ample opportunity for systematic studies of multiple dimensions of ideology, including theodicy, the relation of particular religious traditions to scientific authority, and in some cases claims and experiences of miraculous healing. the analysis of official rhetoric and communications offers an opportunity to look at how representatives of different traditions frame suffering and death in the face of widespread injustice and tragedy. in the sense that theodicy provides a crucial window into the larger ideology of traditions (berger ), comparative and in-depth qualitative analyses hold much promise for revealing important connections between religious groups, their practices and experiences, and their larger cultural environments. beyond religious elites, popular assessments of rumors about what is true also warrant focused attention from researchers. weber's (( weber's (( ) interest in different forms of authority, including charismatic authority, places questions about the social construction of "truth" squarely in the realm of sociology of religion. religion scholars might, for example, examine the proliferation, consumption, and spread of conspiracy theories about the pandemic. although not necessarily related to formal religion (although sometimes they are), conspiracy theories contain a number of quasi-religious elements (bader et al. ; robertson ) , and social scientists studying religion can assist with evaluating the relative diffusion, as well as the patterns and consequences, of conspiracy theories. conspiratorial beliefs about the pandemic have already been spliced into existing conspiracy subcultures, such as the ones spun by alex jones or the anonymous online denizens of qanon (frenkel et al. ) . importantly, acceptance of conspiracy theories has consequences for political behavior (oliver and wood a) , health behaviors such as vaccine resistance (oliver and wood b) , and general social well-being, including trust in other people and the purchasing of firearms out of fear (bader et al. ). scholars of religion should not overlook this aspect of the pandemic, but rather contribute positively to this area of research. it is worth noting that secularity will also be related to social distancing attitudes and behaviors, and should be studied accordingly. we are focusing here on aspects of religion, but secular attitudes and identities should be considered from a similar perspective. religion will also continue to be analyzed as a set of emerging and established practices (ammerman ; wuthnow ) . thinking about religion as the object of analysis and its role in disease transmission, a clear and consequential way that the pandemic has changed religion is the suspension of in-person religious gatherings, and the corresponding need to engage in "socially distanced" forms of interactive religious services and rituals. religious groups have used a wide range of technological innovations to fill the void left by in-person gatherings, from teleconferenced seders to drive-in church services broadcast on radio stations, and increasingly in video chat memorial services. how long such mediated substitutions are necessary for interactive rituals remains an open question depending on groups' locations, orientations toward social distancing measures, and congregants' levels of fear and reticence about interactions in public spaces. even when congregations do return to face-to-face gatherings, there may be changes to interaction rituals, particularly those involving physical contact, singing, and ingestion. five possible implications of these changes can be seen in: ( ) the privatization of religiosity; ( ) asynchronous consumption of and participation in religious services; ( ) a shifting of conditions in the religious environment to favor groups that are already technologically advanced and adequately staffed to facilitate technologically-mediated religious innovation and distribution; ( ) religious organizations and their civic engagement with the local community; and ( ) conflicts between religious groups and local, state, and federal governments regarding social gatherings. a notable consequence of the pandemic may be further advancing the preexisting processes toward the privatization of religiosity (e.g., chaves ; houtman and aupers ). even for those continuing to participate in their religious communities remotely via mediated interaction, a qualitative shift toward the privatization of religious practice necessarily occurs. the long-term consequences of these shifts will depend on the extent and length of social distancing requirements, as well as whether and how people reintegrate physical co-presence within religious communities after social distancing requirements are reduced. while we can reasonably expect an acceleration of pre-existing trends toward religious privatization as a result of the covid- pandemic, the degree and expressions of this privatization remain to be seen and documented. the pandemic may also accelerate trends associated with secularization. to the extent that religious participation is habit based and interrupted by social distancing, it may facilitate the exit of some from active religious participation. so rather than a v-shaped pattern in religious participation after the easing of social distancing, returns to religious practice may well not reach their pre-pandemic levels. undoubtedly, some of this will be a transition to the privatization of religion, but some will also likely simply be declining levels of religiosity. generating adequate measures to map the extent of privatization versus secularization will be a key consideration for researchers. a related consequence is the increasing production and consumption of religious services and rituals via asynchronous communication. a primary example of this trend is the vast reduction of the annual hajj to mecca in , the first time this pillar of islam has been curtailed since the mid- s (hubbard and walsh ) . more generally, by removing the physical co-presence of group services, music, and rites, a foundational element of the positive affect produced by efficacious interactive rituals is removed (collins ) . in essence, the durkheim (( durkheim (( ) pathway to collective effervescence is substantially and negatively altered. while not all emotion is removed, an important shift has taken place that removes groups' abilities to generate shared rhythm and mood (on the positive side of generating group cohesion), and severely reduces or removes groups' abilities to police participation and norms (on the negative side of the social dynamics that create group cohesion) (see draper ; wellman et al. ) . so, while individuals may passively consume religious interactions or individually engage in rites and sacraments, the longer-term aspects of group cohesion and the accompanying social identities it generates are imperiled. beyond the experience of worship itself, the ability to mobilize and recruit volunteers for the practical needs of religiously motivated ministries, as well as generating financial contributions, are also challenged when members are deprived of the opportunity to interact face-to-face. encouraging use of digital platforms for charitable giving will also become much more important. notably, this places particular challenges on poorer individuals and religious congregations, where members' access to electronic forms of capital transfer may be limited. as charitable giving is re-directed from in-person to remote, organizations with a larger cache of financial resources have considerable advantages for long-term survival and success by virtue of their ability to weather potential downturns in financial giving, although the challenge of fundraising is a constant concern, even for seemingly stable organizations mulder and martí ) . related to the shift toward mediated communication for interactive rituals, groups and organizations that already emphasized the use of such technologies before the imposition of social distancing requirements have a clear competitive advantage for the maintenance of their organizations compared to groups who were more heavily reliant on face-to-face interactions. streaming services, both live and recorded, have become more common recently, and many congregations had already invested in the equipment and personnel to provide access to their services remotely. regarding communal rituals such as weddings, technology has been used to allow small in-person gatherings while providing remote participation for broader networks of family and friends. similarly, in relation to bereavement and death, online options have opened to conduct funeral services that allow involvement and interaction through video. organizations' access to capital resources will affect their ability to upgrade communication technologies to substitute for face-to-face gatherings during periods of social distancing. the pandemic also provides an opportunity to examine the role of religious organizations in social support for communities' members. for both the medical and economic hardships wrought by the pandemic and related social distancing measures, religious groups and individuals are playing important roles for formal and informal social support. for example, we know that religious congregations have been important sources of immediate assistance, from food pantries to supplemental funds to assist with costs associated with housing, medicine, and transportation. the changing landscape for religious nonprofits and local social service provisions organized through congregations are key domains for changes in the dynamics of formal social support. for informal social support, the provisions put in place by denominational organizations and local congregations to care for members during times of physical and financial hardship warrant explicit attention from researchers. conversely, the limitations placed on faith-based organizing and political engagement by social distancing should also be carefully documented. for instance, in light of a surge of protests connected to the "black lives matter" movement spurred on by the death of george floyd on may th, , there is evidence that the lull in congregational activity allowed logistical space for church leaders to redirect their energies toward mobilizing their ministries to participate in protests that publicly advocate against racial injustice. thus, an intriguing and unintended consequence of closed church services may have been allowing for the expansion of community and civic engagement beyond sanctuaries (see beyerlein and ryan ) . finally, at an institutional level, there are a number of opportunities for examining interesting and consequential issues involving the intersection of religion and law. thousands of religious groups received forgivable loans of up to million dollars through the paycheck protection program, which was part of a -billion-dollar economic stimulus package; support that some groups have strongly criticized. the u.s. roman catholic church alone gained at least $ . billion in this taxpayer-backed aid (and may have even exceeded $ . billion; see dunklin and rezendes ) . early reports also raised questions as to whether different religious groups were equally likely to receive support. the urge to re-start worship services given the pragmatic issues of accepting donations and the mobilization of volunteers for all sorts of ministries and services accomplished through the congregation have prompted aggressive calls for religious exemptions for church gatherings. on one end, some churches have insisted on a drive-in church option to ensure proper distancing and provide access to services for those without the technological means to access services remotely. on the other end, most churches who insist on continuing to meet physically have stated their intent to sanitize sanctuaries, provide masks, and generously space seating. some churches have sued their state governments, insisting that congregations are "essential businesses" and citing "religious liberty." indeed, there appears to be a resonance between those who agitate for re-opening the churches and those who agitate for re-opening the economy-a christian libertarian affinity that insists open churches and businesses are what is needed to keep america strong (see martí a martí , b . whether and how religious organizations, groups, and individuals are restricted from particular practices in order to limit the spread of disease necessarily raises points of tension about the legal parameters of religious freedom. accordingly, there will likely be waves of court cases across national, state, and local contexts dealing with issues related to social distancing and the rights of religious expression. some of these issues have already been taken up by high courts, such as the south bay united pentecostal church v. newsom ( ) case, where the supreme court of the united states denied injunctive relief to a church in california that did not want to follow social distancing restrictions on public gatherings. soon after, churches in california filed suit in federal court challenging the governor's ban on singing in houses of worship (calvary chapel of ukiah et al. v. newsom et al.) . many other similar cases will undoubtedly follow, and documenting how and why the legal boundaries surrounding religious freedom are remade in the ongoing and eventually post-pandemic landscape provides ample opportunity for meaningful study (see bennett ; wenger ) . a final consideration for social scientists studying religion during and after the covid- pandemic concerns methodology, and to an extent, the broader epistemology undergirding the study of religion. methodologically, many of the most vital tools available for studying religion, particularly those that are qualitative in orientation, are restricted by the need for social distancing. ethnographic, observational, and interview methods are all severely constrained by the reduction of in-person gatherings and the limitations on face-to-face interaction. of course, these are the precisely the methods that are needed to document the ongoing changes to structure and meaning of religion. consequently, researchers must be innovative in their use of digital technologies for the application of qualitative analyses, including but not limited to the use of online archives, digital ethnography, and alternative interview formats. in addition, the use of unobtrusive measures may become especially important as we seek to examine materials without the ability to observe as much in situ (see webb et al. ) . beyond the need to be methodologically innovative and resourceful, the changes to the social contexts of religion that we have detailed above also raise important epistemological and theoretical considerations for the sociology of religion. as religious adherents' definitions of worship and ritual life undergo reconsideration and change, researchers should pursue these emerging epistemologies by creatively tracking them. cutting-edge work in the field, such as the focus on "lived religion" (ammerman ; mcguire mcguire , , has already raised many of these questions. now, however, such considerations about the meaning of religion in the contemporary world-and how we should approach it as researchers and theorists-can no longer be ignored. rather than being prescriptive, this note is intended as an encouragement to our colleagues. given that covid- emerged as a public health crisis only a few months ago, sociologists of religion are only beginning to grapple with the many unanticipated and unseen dynamics of this global phenomenon. these happenings were playing out as most social scientists were also moving their professional lives into quarantine, taking on new roles, getting trained in social distancing practices, and managing the radical uncertainty of their work and home lives. as the circumstances of the pandemic normalize, as acceptable risks and potential vaccines emerge, and as the ability to secure analytical focus returns, there is no doubt that clever, insightful, and not-yet-fully apparent means of analyzing and revealing profound structural patterns will emerge. even as we are mournful of the suffering and tragedy the world continues to endure, we are hopeful that the creative and capable researchers who comprise our field will find ways to add their voices to the emergent understanding of how the world has changed in light of covid- , and perhaps better prepare us for the many unknowns of our collective future. our discussion here is neither comprehensive nor exhaustive, and no one can foresee all the ways that religion will influence and in turn be affected by the ongoing pandemic. we anticipate that the list of topics brought into new relief by the ongoing pandemic will grow ever-larger over time. still, we hope the considerations we have outlined are the beginning of productive dialog in the field. sacred stories, spiritual tribes: finding religion in everyday life fear itself: the causes and consequences of fear in america crusading for moral authority: christian nationalism and opposition to science religion and preventive service use: do congregational support and religious beliefs explain the relationship between attendance and utilization? defending faith: the politics of the christian conservative legal movement religious resistance to trump: progressive faith and the women's march on chicago infected with coronavirus at sacramento church. congregation tells county 'leave us alone more than in germany found to be infected with coronavirus after church's services the rise of the chaplains american religion: contemporary trends church tied to oregon's largest coronavirus outbreak interaction ritual chains churches were eager to reopen. now they are confronting coronavirus cases religious interaction ritual: the microsociology of the spirit catholic church lobbied for taxpayer funds, got $ . b the elementary forms of religious life surge of virus misinformation stumps facebook and twitter high sars-cov- attack rate following exposure at a choir practice-skagit county the blood of christ compels them: state religiosity and state population mobility during the coronavirus (covid- ) pandemic the spiritual turn and the decline of tradition: the spread of post-christian spirituality in western countries the hajj pilgrimage is canceled, and grief rocks the muslim world high covid- attack rate among attendees at events at a church -arkansas from politics to the pews: how partisanship and political environment shape religious identity american blindspot: race, class, religion, and the trump presidency capital and the cathedral: robert h. schuller's continual fundraising for church growth individual sensory experiences, socialized senses, and everyday lived religion in practice the glass church: robert h. schuller, the crystal cathedral, and the strain of megachurch ministry west virginia sees coronavirus outbreaks in churches political identity and confidence in science and religion in the united states medical conspiracy theories and health behaviors in the united states culture wars and covid- conduct: christian nationalism, religiosity, and americans' behavior during the coronavirus pandemic ufos, conspiracy theories and the new age: millennial conspiracism how a south korean church helped fuel the spread of the coronavirus causality, normativity, and diversity in years of u.s. sociology of religion: contributions to paradigmatic reflection the gendered religious response to state action on the coronavirus pandemic unobtrusive measures, revised edition the sociology of religion, translated by ephraim fischoff high on god: how megachurches won the heart of america religious freedom: the contested history of an american ideal complex religion: interrogating assumptions of independence in the study of religion what happens when we practice religion? textures of devotion in everyday life religion is raced: understanding american religion in the twenty-first century key: cord- -hcj jmbm authors: myers, kyle r.; tham, wei yang; yin, yian; cohodes, nina; thursby, jerry g.; thursby, marie c.; schiffer, peter e.; walsh, joseph t.; lakhani, karim r.; wang, dashun title: quantifying the immediate effects of the covid- pandemic on scientists date: - - journal: nan doi: nan sha: doc_id: cord_uid: hcj jmbm the covid- pandemic has undoubtedly disrupted the scientific enterprise, but we lack empirical evidence on the nature and magnitude of these disruptions. here we report the results of a survey of approximately , principal investigators (pis) at u.s.- and europe-based research institutions. distributed in mid-april , the survey solicited information about how scientists' work changed from the onset of the pandemic, how their research output might be affected in the near future, and a wide range of individuals' characteristics. scientists report a sharp decline in time spent on research on average, but there is substantial heterogeneity with a significant share reporting no change or even increases. some of this heterogeneity is due to field-specific differences, with laboratory-based fields being the most negatively affected, and some is due to gender, with female scientists reporting larger declines. however, among the individuals' characteristics examined, the largest disruptions are connected to a usually unobserved dimension: childcare. reporting a young dependent is associated with declines similar in magnitude to those reported by the laboratory-based fields and can account for a significant fraction of gender differences. amidst scarce evidence about the role of parenting in scientists' work, these results highlight the fundamental and heterogeneous ways this pandemic is affecting the scientific workforce, and may have broad relevance for shaping responses to the pandemic's effect on science and beyond. by mid-april , the cumulative number of deaths due to covid- had reached approximately , with nearly , deaths per day in the u.s. and , deaths per day in europe . throughout the u.s. and europe, schools and workplaces were typically required to be closed and restrictions on gatherings of more than people were in place in most countries . for scientists, not only did this drastically change their daily lives, it severely limited the possibilities of using traditional workspaces as most institutions had suspended "non-essential" activities on campus [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . to collect timely data on how the pandemic affected scientists' work, we disseminated a survey to u.s.-and europe-based scientists across a wide range of institutions, career stages, and demographic backgrounds. we identified the corresponding authors for all journal articles indexed by the web of science in the past decade, and then randomly sampled , u.s.-and europebased email addresses (see si s for more). we distributed the survey on monday april th, , about month after the world health organization declared the covid- pandemic. within one week, the survey received full responses from , individuals who self-identified as faculty or pis from academic or non-profit research institutions. respondents were located in all states in the u.s. ( . % of the sample, figure s a ), countries in europe ( . % of the sample, figure s b ), and were affiliated with the full spectrum of research fields listed in the survey. for more on the response rate, sampling method, and a comparison to a national survey of doctorate-level researchers, see si s . motivated by prior research on scientific productivity [ ] [ ] [ ] [ ] [ ] , the survey solicited information about scientists' working hours, how this time is allocated across different tasks, and how these time allocations have changed since the onset of the pandemic. we asked scientists to estimate changes to their research output-the quantity and impact of their publications-in coming years relative to prior years. we also solicited a wide range of characteristics including field of study, career stage (e.g., tenure status), demographics (e.g., age, gender, number and age of dependents in the household), and other features (e.g., institution closure and whether the respondent was exempt from any closures). details on the survey instrument are included in si s , and table s reports summary statistics for all the respondents used in the analyses. to understand the immediate impacts of the pandemic, we compare the reported level and allocation of work hours pre-pandemic and at the time of the survey. figures a and b illustrate two primary findings. first, there is a sharp decline in total work hours, with the average dropping from . hours per week pre-pandemic to . at the time of the survey (diff.=- . , s.e.= . ). in particular, . % of scientists reported that they worked hours or less before the pandemic, but this share increased nearly six-fold to . % by the time of the survey (diff.= . , s.e.= . ). second, there is large heterogeneity in changes across respondents. although . % reported a decline in total work hours, . % reported no change, and . % reported an increase in time devoted to work. this significant fraction of scientists reporting no change or increases in their work hours is notable given that . % of respondents reported their institution was closed for non-essential personnel. to decompose these changes, we compare scientists' reported time allocations across four broad categories of work: research (e.g., planning experiments, collecting or analyzing data, writing), fundraising (e.g., writing grant proposals), teaching, and all other tasks (e.g., administrative, editorial, or clinical duties). we find that among the four categories, research activities have seen the largest negative changes. whereas total work hours decrease by . % on average, research hours have declined by . % (teaching, fundraising, and "all other tasks" decrease by . %, . %, and . %, respectively). comparing the share of time allocated across the tasks ( figure c -f), we find that research is the only category that sees an overall decline in the share of time committed (median changes: - . % for research, % for fundraising, + . % for teaching, and + . % for all other tasks). overall, these results indicate that scientists' research time has been disrupted the most, and the declines in time spent on the other three categories are mainly due to the decline in total work hours. furthermore, correlations suggest that research may be a substitute for each of the three other tasks (see si s . and figure s ). still, despite the large negative changes in research time, substantial heterogeneity remains, as . % reported no change and . % reported spending more time on research. the sizable heterogeneity begs the question as to what factors are most responsible for the observed heterogeneous effects among scientists. to unpack the varied effects of the pandemic, we first examine across-field differences. figure a depicts the average change in reported research time across the different fields we surveyed. fields that tend to rely on physical laboratories and time-sensitive experiments -such as biochemistry, biological sciences, chemistry and chemical engineering -report the largest declines in research time, in the range of - % below pre-pandemic levels. conversely, fields that are less equipment-intensive -such as mathematics, statistics, computer science, and economics -report the lowest average declines in research time. the difference between fields can be as large as four-fold, again highlighting the heterogeneity in how certain scientists are being affected. these field-level differences may be due to the nature of work specific to each field, but may also be due to differences in the characteristics of individuals that work in each field. to untangle these factors, we use a lasso regression approach to select amongst ( ) a vector of field indicator variables, and ( ) a vector of flexible transformations of demographic controls and pre-pandemic features (e.g., research funding level, time allocations before the pandemic). the lasso is a datadriven approach to feature selection that minimizes overfitting by selecting only variables with significant explanatory power , . we then regress the reported change in research time on the lasso-selected variables in a post-lasso regression, allowing us to estimate conditional associations for each variable selected (see si s ). comparing figure a and b, we find that the contrast between the "laboratory" or "bench science" fields versus the more computational or theoretical fields is still significant in the post-lasso regression, indicating that differences inherent to these fields are likely important mediators of how the pandemic is affecting scientists. although we cannot reject a null hypothesis of no change, there is also suggestive evidence of an increase in research time for the health sciences, possibly due to work related to covid- . importantly, we also find that most of the variation across fields is diminished once we condition on the individual-level features selected by the lasso, which suggests a large amount of heterogeneity is due to these individual-level differences. indeed, the standard deviation of the twenty field-level averages of reported changes in research time is . %. by contrast, the standard deviation of the individual-level residuals from these fieldlevel averages-that is, how much each individual's response differs from the average in their field-is . %, indicating there is substantial variation across individuals even within the same field. to illustrate the raw individual-level variation, we measure the average change in reported research time across demographic and other group features ( figure c ). given the persistent gender gap in science - , we include interactions with the female indicator to explore potential gender-specific differences. we find that there are indeed widespread changes across the range of individual-level features we examined. yet, when we use the lasso and regression to control for the field differences documented in figure a , we find marked changes in the relevance of certain individual-level features. figure d plots the post-lasso regression coefficients associated with the demographic and careerstage characteristics and reveals four main results. first, career stage appears to be a poor predictor of the impacts of the pandemic, as conditional changes in research time for older versus younger and tenured versus untenured faculty are statistically indistinguishable. second, scientists who report being subject to a facility closure also report only minor unconditional differences in their research time ( figure c ), and this feature is not selected by the lasso as a relevant predictor for changes in research time. third, there is a clear gender difference. holding field and all other observable features fixed, female scientists report a . % larger decline in research time (s.e.= . ). fourth, child dependent care is associated with the largest effect. reporting a dependent under years old is associated with a . % (s.e.= . ) larger decline in research time, showing a substantially larger effect than any other individual-level features. reporting a dependent to years old is also associated with a negative impact, ceteris paribus, but that decline is smaller than the decline associated with dependents under years old. this is consistent with shifts in the demands of childcare as children age. having multiple dependents is associated with an additional . % decline (s.e.= . ) in research time. overall, these results are consistent with preliminary reports of differential declines in female scientists' productivity during the pandemic , . our findings further indicate that some of the gender discrepancy can be attributed to female scientists being more likely to have young children as dependents ( . % of female scientists in our sample report having dependents under the age of , compared to . % of male and other scientists, s.e. of diff.= . ). for further results related to the other three task categories, see si s . . to estimate the potential downstream impact of the pandemic, we also asked respondents to forecast how their research publication output in and -in terms of the quantity and impact of their publications-will compare to their output in and . we randomly assigned respondents to make a forecast for one of six possible scenarios where they were to take as given the duration of the pandemic to be , , , , , or months from the time of the survey. for more on how we use this introduced random variation and adjust scientists' forecasts to account for underlying trends in publication output, see si s . . figure a plots the distribution of the estimated changes in publication quantity and impact due to the pandemic. we find that, on average, quantity is projected to decline . % (s.d.= . ). for comparison, prior estimates show that in the biomedical sciences, receiving a grant of approximately one million dollars from the national institutes of health raises a pi's short run publication output by - % , , suggesting that a projected decline of % is not negligible. moreover, the decline in output is not limited to quantity, as impact is projected to decline by . % on average (s.d.= . ). to understand which scientists are most likely to forecast larger declines in their output due to the pandemic, we repeat the lasso-based regression approach using these forecasts as dependent variables. these analyses uncover two notable findings ( figure b ). first, all of the features selected as relevant are related to caring for dependents. as in the case of research time, reporting a dependent under years old is associated with the largest declines. second, gender differences in these forecasts appear attributable to differential changes associated with dependents. reporting a -to -year-old dependent is associated with a . % (s.e.= . ) and . % (s.e.= . ) lower forecast of publication quantity and impact, respectively, but only for female scientists (see si s . for the field-level results). we find that most of the same groups currently reporting the largest disruptions to research time also report the worst outlook for future publications. the correlations between reported change in research time and forecasted publication output are . for quantity (p-value < . ) and . for impact (p-value < . ). while understanding the relationships between time input and research output is beyond the scope of this study, we repeat the analysis, including the changes in reported time allocations to test if they moderate the effects we observe. we find that, while the post-lasso regression coefficients associated with the selected demographic features generally become smaller, a statistically significant relationship remains in most cases even when conditioning on the (lasso-selected) change in research time. this suggests the forecasted declines associated with reporting young dependents are not simply explained by the direct change in time spent on research ( figure s ). we further investigate how these publication forecasts may depend on the expected duration of the covid- pandemic by plotting the (randomized) expectation shown to the survey respondent against the estimated net effect of the pandemic ( figure c) . a linear fit indicates that, for every month that the pandemic continues past april , scientists expect a . % decrease in publication quantity (s.e.= . ) and a . % decrease in impact (s.e.= . ) due to the pandemic. these marginal effects may appear small relative to the others documented in this paper, but it is important to note that they are on a similar scale as economic forecasts for the u.s. and europe, which (as of may ) project economic declines in the range of . - . % per month ( - % for ) . still, these results could also reflect uncertainties or errors inherent to these forecasts, or strong personal beliefs about the timeline for the pandemic that are not easily swayed by the survey's suggestion. our results shed light on several important considerations for research institutions as they consider reopening plans and develop policies to address the pandemic's disruptions. the findings regarding the impact of childcare reveal a specific way in which the pandemic is impacting the scientific workforce. indeed, "shelter-at-home" is not the same as "work-from-home" when dependents are also at home and need care. because childcare is often difficult to observe and rarely considered in science policies (aside from parental leave immediately following birth or adoption), addressing this issue may be an uncharted but important new territory for science policy and decision makers. furthermore, it suggests that unless adequate childcare services are available, researchers with young children may continue to be affected regardless of the reopening plans of institutions. and since the need to care for dependents is by no means unique to the scientific workforce, these results may also be relevant for other labor categories. more broadly, many institutions have announced policy responses such as tenure clock extensions for junior faculty. of u.s. university policies we identified that provided some form of tenure extension due to the pandemic, appeared to guarantee the extension for all faculty (see si s . for more). institutions may favor such uniform policies for several reasons such as avoiding legal challenges. but given the heterogeneous effects of covid- we identify, it raises further questions whether these uniform policies, while welcoming, may have unintended consequences and could exacerbate pre-existing inequalities . while this paper focuses on quantifying the immediate impacts of the pandemic, circumstances will continue to evolve and there will likely be other notable impacts to the research enterprise. the heterogeneities we observe in our data may not converge, but instead may diverge further. for example, when research institutions begin the process of reopening, there may be different priorities for "bench sciences" versus work that involves human subjects or that requires travel to field sites. and research requiring international travel could be particularly delayed; all of which could lead to new productivity differences across certain groups of scientists. furthermore, individuals with potential vulnerabilities to covid- may prolong their social distancing beyond official guidelines. in particular, senior researchers may have incentives to continue avoiding inperson interactions , which historically facilitate mentoring and hands-on training of junior researchers. the possibility of a resurgence of infections suggests that institutions may anticipate a reinstatement of preventative measures such as social distancing. this possibility could direct focus toward research projects that can be more easily stopped and restarted. funders seeking to support high-impact programs may have similar considerations, favoring proposals that appear more resilient to uncertain future scenarios. lastly, although we have focused on two of the denser geographic regions of scientific output in this study, the pandemic is having a substantial impact on research worldwide. in the coming years, researchers may be less willing or able to pursue positions outside of their home nation, which may deepen or alter global differences in scientific capacity. future work expanding our understanding of how the pandemic is affecting researchers across different countries, at different institutions, and in different points of their life and career could provide valuable insights to more effectively protect and nurture the scientific enterprise. the strong heterogeneities we observe, and the likely development of new impacts in the coming months and years, both argue for a targeted and nuanced approach as the world-wide research enterprise rebuilds. . kitchener, c. women academics seem to be submitting fewer papers during coronavirus. 'never seen anything like it,' says one editor. https://www.thelily.com https://www.thelily.com/women-academics-seem-to-be-submitting-fewer-papers-duringcoronavirus-never-seen-anything-like-it-says-one-editor/ ( the study protocol has been approved by the institutional review board (irb) from harvard university and northwestern university. informed consent was obtained from all participants. figure s reports the results from a similar exercise focusing on fieldlevel differences. we find the same three fields associated with the largest declines in research time -biochemistry, biology, and chemistry -also forecast the largest pandemic-induced declines in their publication output quantity, ceteris paribus. c. average estimated changes in publication outputs per the randomized duration of pandemic respondents were asked to assume for their forecasts (either , , , , , or months from the time of the survey, mid-april ). .......................................................................................................................... ........................................................... s additional results .................................................................................................................................... spent on different tasks ................................................................................ -research tasks by groups ............................................................... forecast results ................................................................................. ................................................................................ s supplementary tables ........................................................................................................................... s supplementary figures ......................................................................................................................... s references for supplementary information ......................................................................................... to compile a large, plausibly random list of active scientists, we leverage the web of science (wos) publication database. the wos database is useful for two reasons: ( ) it is one of the most authoritative citation corpuses available and has been widely used in recent science of science studies - ; ( ) among other large-scale publication datasets, wos is the only one, to our knowledge, with systematic coverage of corresponding author email addresses. we are primarily interested in active scientists residing in the u.s. and europe. we start from million wos papers published in the last decade ( - ). in an attempt to focus on scientists likely to still be active and in a more stable research position, we link the data to journal impact factor information (wos journal citation reports), and exclude papers published in journals in the bottom % of the impact factor distribution for its wos-designated category. we use the journal impact factor calculated for the year of publication, and for papers published in , we use the latest version ( ). we then extract all author email addresses associated with papers. for each email address in this list, we consider it as a potential participant if: ( ) it is associated with at least two papers in the ten-year period, and ( ) the most recent country of residence, defined by the first affiliation of the most recent paper, is in the u.s. or europe. we have approximately . million unique email addresses after filtering, with about , in the u.s. and , in europe. we then randomly shuffled the two lists separately and sampled roughly , email addresses from the u.s. and , from europe. we oversampled the u.s. as a part of a broader outreach strategy underlying this and other research projects. we recruited participants by sending them email invitations through with the following text: we build on field classifications used in national surveys such as the u.s. survey of doctorate recipients (sdr) to categorize fields in our survey, aggregating to ensure sufficient sample sizes within each field. the notable additions we make to the fields used in these other surveys are to include: business management, education, communication, and clinical sciences. these fields reflect major schools at most universities and/or did not immediately map to some of the default fields used in the sdr (i.e., the "health sciences" field in sdr does not include medical specialties). out of a total of , emails sent, approximately , emails were directly bounced either due to incorrect spelling in the wos data or the termination of the email account. in hopes of soliciting a larger sample, we also undertook snowball sampling by encouraging respondents to share the survey with their colleagues as well. overall , individuals entered the survey and , continued past the consent stage. of those that did not, were not an active scientist, post-doc, or graduate student and thus not within our population of interest, did not consent, and did not make any consent choice. when a respondent continued past the consent stage, we asked them to report the type of role they were in. out of the , consenting responses, there , responses from faculty or principal investigators (pis), , responses from post-doctoral researchers, from graduate students in a doctoral program, and from retired scientists. of the remaining respondents were some other type of position and another did not report their position. this yields an estimate of a response rate of approximately . %. first, our low response rate may reflect the disruptive nature of the pandemic, but it also raises concerns for generalizability of our results. however, after we received feedback from the initial distribution that many individuals had received the email in their "junk" folder, we became concerned with our distribution being automatically flagged as spam. based on spot-checking of five individuals that we ex-post identified as being randomly selected by our sample, and who we had professional relationships with, found that in four of the five cases the recruitment email had been flagged as spam. we know of no systematic way of estimating the true spam-flagging rate (nor how to avoid these spam filters when using email distributions at this scale) without using high-end, commercial-grade products. additionally, as with any opt-in survey, there may be correlations between which scientists opt-in and their experiences about which they want to report. for example, scientists who felt strongly about sharing their situation, whether they experienced large positive or negative changes, may be more likely to respond, which would increase the heterogeneity of the sample. furthermore, there may also be non-negligible gender differences that arise not due to actual differences in outcomes but due to differences in reporting known to occur across genders [ ] [ ] [ ] [ ] [ ] . for our analyses, we focus entirely on responses from the sample of faculty/pis. from the full sample of pis, we retain respondents who reported working for a "university or college", "nonprofit research organization", "government or public agency", or "other", and excluding responses from individuals who report to work for a "for-profit firm". we also restrict the sample to respondents whose ip address originated from the united states or europe (dropping , responses from elsewhere). we then drop observations that have missing data for any of the variables used in our analyses: responses do not report their time allocations, do not report their age, do not report the type of institution they work at, and do not report their field of study. altogether, this amounts to dropping observations. given the relatively small subset of our sample dropped due to missing data, we do not impute missing variables as this introduces unnecessary noise . the summary statistics for the final sample used in the analyses are reported in figure s and the geographic distribution of respondents is shown in figure s . to estimate the generalizability of our respondent sample, we use the public microdata from the survey of doctorate recipients (sdr) as the best sample estimates of the population of principal investigators in the u.s. the sdr is conducted by the national center for science and engineering statistics within the national science foundation, sampling from individuals who have earned a science, engineering, or health doctorate degree from a u.s. academic institution and are less than years of age. the survey is conducted every two years, and we use the latest data available ( cycle). for this comparison, we focus only on university faculty in both our survey and the sdr. we also constrain our sample to only include fields of study with a clear mapping to the sdr categories. the sdr focuses only on researchers with ph.d.-type degrees, and so it does not capture researchers with other degrees still actively engaged in research (i.e., researchers with only m.d.s). this means we exclude "architecture and design," "business management," "medicine," "education," "humanities," and "law and legal studies." figure s compares respondents between our sample and the sdr sample. figure s a illustrates differences on demographics and career-stage features, including raw differences as well as those adjusted by field. we find only a small difference in age and no difference in partner status. our survey oversamples on female scientists, those with children, and untenured faculty. these differences persist after conditioning on the scientist's reported field. that we ultimately find female scientists and those with young dependents to report the largest disruptions suggests that these individuals may have been more likely to respond to the survey in order to report their circumstances. the geographic distributions are relatively similar, with slight oversampling of west and undersampling of south. lastly, we find a significant but small oversampling of u.s. citizens. we also compare the distribution of research fields (fig. s .b) . overall the distributions are relatively similar. we appear to oversample most significantly on "atmospheric, earth, and ocean sciences" and "other social sciences." while we undersample most significantly on the biological sciences, "mathematics and statistics," and "electrical and mechanical engineering". there does not seem to be a clear pattern with these field-level differences, as we undersample fields that ultimately report being across the spectrum of disruptions (i.e., mathematics and statistics reports some of the smallest disruptions, and the biological sciences are amongst the most disrupted). the unconditional changes reported by each group of scientists is informative of how the pandemic affected researchers overall. but it does not allow us to infer whether groups reporting larger or smaller disruptions are doing so for reasons inherent to that group (i.e., the nature of work in certain fields, or the demands of home life unique to certain individuals) or because the individuals that select into that group tend to also be disrupted for unrelated reasons. this motivates a multivariate regression analysis to explore whether changes associated with a group of individuals change after conditioning on other observables. however, selecting which of an available set of covariates (or transformations thereof) to include in a regression is notoriously challenging. the lasso method provides a data-driven approach to this selection problem by excluding covariates from the regression that do not improve the fit of the model , . when using the lasso, our general approach is to include a vector of indicator variables for the fields or demographic/career groups of interest, along with an additional set of controls. when focusing on differences across fields, we include the demographic/career variables in the control set, and vice versa. the control variables common to all lasso-based analyses are: pre-pandemic level of time allocations and totals, pre-pandemic share of time allocations, pre-pandemic funding estimate, and indicators for the type of institution (academic, non-profit, government, or other) and the location (state if in u.s., country if in europe). to make minimal assumptions about the functional form of the control variables, we conduct the following transformations to expand the set of controls: for all continuous variables we use inverse hyperbolic sine (which approximates a logarithmic transformation while allowing zeros), square and cubic transformations, and we interact all indicator variables with the linear versions of the continuous variables. we perform the lasso using the lasso linear package in stata © software. we use the defaults for constructing initial guesses, tuning parameters, number of folds (ten), and stopping criteria. we use the two-step cross-validation "adaptive" lasso model where an initial instance of the algorithm is used to make a first selection of variables, and then a second instance occurs using only variables selected in the first instance. the variables selected after this second run are then used in a standard post-lasso ols regression with heteroskedastic robust standard errors. we are interested in the effect of the covid- pandemic on research output. as an initial estimate of what this effect could be, we asked respondents to forecast how their research output in and will compare to their prior output in and . this framing was chosen for its simplicity; however, it does not provide a direct estimate of the pandemic effect. for this effect, we could have asked how the respondent expects their output to be in and compared to what they would otherwise expect their output to have been in and had the pandemic not occurred. clearly, this is more complicated. but since we chose the simpler framing, we must account for some underlying factors before arriving at figures closer to what scientists think the effect of the pandemic will be (or our estimates thereof). these raw year-to-year forecasted changes in publication outputs will be influenced by four major factors: ( ) changes due to the pandemic to date; ( ) anticipated future changes due to the pandemic; ( ) the respondent's expectations about how long the pandemic will last; and ( ) regular trends in the evolution of publication output across different individuals and fields (e.g., if female scientists have continually been increasing their number of publications produced each year, then in the absence of the pandemic we might expect this trend to continue into the near future). again, we are primarily interested in ( ) and ( ). to overcome ( ), we randomly assign respondents to make forecasts for one of possible scenarios where they were to take as given the duration of the pandemic to be either , , , , , or months from the time of the survey. in some analyses, we condition on this variable to control for variation due to perceptions about the length of the pandemic. in others, we explore the effect of these different perceptions directly to infer how scientists perceive disruptions may evolve as the pandemic does or does not continue to persist. with respect to the issue of differential trends across individuals and fields, we first note that the time scale we are concerned with (approx. years) is small enough that we expect the majority of individuals to not change in terms of their observables. this is because all of our time-dependent observables used in the analyses are based on groupings of years. still, to more quantitatively address this issue, we use historical data and another lasso-based regression model to project scientists' publication output in and , using their observable features from the survey and publication data since . our assumption is that these projections can approximate what scientists would have forecasted in the absence of the pandemic--they provide a crude counterfactual. given the short timeframes involved, and the rich observable data we possess, we hypothesize that the room for significant biases or deviations are small relative to the acrossindividual variation. due to data quality limitations, we are only able to connect % of respondents to their publication records, but a comparison of observables indicates that there are no meaningful differences between those scientists connected to their publication record, and those not (see figure s ). since we observe the variables used in these projections for all respondents, we can project out trends for all scientists in our sample. while the measurement of publication quantity is straightforward, the measurement of quality or, as it was asked in the survey, "impact" is not. following a long line of science of science research , we use citation counts as the best available proxy for quality. we follow the state of the art in terms of adjusting and counting these citations in a manner that does not conflate across-field differences . the lasso-based projection proceeds as follows. first, we demean the publication measures at the year level. this is because we do not want to attribute aggregate year-to-year variations across the entire sample to actual changes in net output, since these fluctuations can very plausibly be linked to changes in the web of science (wos) coverage over time, and we are much more concerned with differential trends amongst different fields and/or different individuals. next, we use the lasso to select which of the observables are the best predictors of publication counts and citations. the major difference between this lasso-based approach and the others used in this paper is that, here, we interact all observables with flexible time trends (i.e., squared, cubic, and inverse hyperbolic sine transformations of the year variable) to allow differential trends across groups. finally, we project out these expected output measures as a function of the selected covariates and their corresponding coefficients from a post-lasso ols regression. importantly, we project out of sample just two years so that we have estimates of the counterfactual trends for and . with these estimates of respondents' counterfactual forecasts in hand, we then simply subtract them from scientists actual reported forecasts to arrive at our estimate of scientists' forecast of the "net effect" of the pandemic. figure s plots the distributions of the unadjusted forecasts and these net effects for both the quantity and impact measures. the adjustment does not substantially change the distribution, but we are more confident in these estimates as "pandemic effects" for the aforementioned reasons. figure s plots the reported changes in research time (y-axes) against the reported changes in time allocated to the other three task categories (x-axes). the figures are binned scatterplots, and linear fits of the data suggest that research may be a substitute for the other categories. a % increase in fundraising, teaching, or all other tasks is associated with a decline in research by . % (s.e.= . ), . % (s.e.= . ), and . % (s.e.= . ), respectively. we lack exogenous variation in the data that can clearly shift the time allocated to one (or a subset) of tasks, so we cannot identify the extent to which these correlations reflect actual substitution patterns or unobserved factors. though the magnitudes and precision of these relationships suggests further investigations are certainly warranted to better understand how scientists allocate their time. figure s a and s b replicate figures b and d from the main text, respectively, instead using each of the other three task categories for the dependent variable. for the analysis focused on fields (fig. s a) , no clear patterns emerge with respect to changes in time spent fundraising or teaching. reported time changes in teaching may be due to a combination of reasons. first, during the pandemic, the demand for these activities is likely relatively stable (e.g., most academic institutions have moved classes online, but there are few reports of suspension of classes); and second, impacts due to the transition to online teaching may have taken place earlier, hence not captured by our survey. there is evidence that clinical science and biochemists are spending an increasing amount of time on the "all other tasks" category, which could plausibly be due to a redirection of effort directly towards pandemic-related (non-research) work. for the analysis focused on demographic groups (fig. s b) , we find that scientists reporting a dependent under years old tend to also report larger declines across all task categories. this result is consistent with an unsurprising hypothesis that these dependents require care that leads scientists to decrease their total work hours. the fact that there does not appear to be any substitution away from research towards these other categories for these specific individuals with young dependents suggests the association is driven by factors inherent to having a dependent at home, and not that these individuals also tend to select alternative work structures that has them performing less research and more of other tasks. figure s recreates figure b from the main text, but using the field-level lasso approach. forecasted changes in output are almost entirely confined to publication quantity (as opposed to impact), with the same fields of biology and chemistry that reported the largest declines in research time also forecasting the largest declines in publication output, here in the range of - % relative to what would have been expected otherwise. notably, some fields expect to publish more because of the pandemic, again highlighting the heterogenous experiences scientists are having due to the pandemic. figure s recreates figure b from the main text, but while including the reported changes in time allocated to each of the four task categories (in addition to the pre-pandemic reported time allocations as before). again, we find a similar set of dependent-related variables to be most predictive of forecasted publication changes, even though the reported change in research time is also selected as relevant by the lasso. for comparison, the forecasted disruption associated with a dependent under years old ( . % decline expected publication count) is approximately the same magnitude as the implied effect associated with a % decrease in research time. using internet searches, we attempted to identify university-level tenure clock extension policies put in place as a result of the covid- pandemic. while not a comprehensive list, we identified policies for universities, encompassing both public and private, small and large institutions. of the universities, have automatically applied a tenure clock extension to all faculty, with individuals having the ability to opt out - ; require applications but are automatically approved [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . four universities have not established unilateral policies [ ] [ ] [ ] [ ] . instead, they have either created a separate application process or added covid- -related impact to the list of reasons a faculty member may apply for an extension. table s . summary statistics. summary statistics for the main survey sample. "mean, with pubs." and "mean, miss. pubs." report the averages for the sub-samples that can and cannot be connected to their publication record in wos, respectively. the "t-stat" column reports the tstatistic from a test of mean differences between these two sub-samples. the two wos-based variables are "pub. quantity (number) since " (the sum of the author's number of publications in the wos record), and "pub. impact (eucl. citations) since " (the field-demeaned euclidean sum of citations to the author's publications in the wos record ). figure s . geographic distribution. plots respondent locations in u.s. (a.) and europe (b.), aggregated to preserve anonymity. figure s . comparison to u.s. university-based sdr respondents. summary statistics for demographic variables and fields common to both our survey and the u.s. survey of doctoral recipients (sdr). all comparisons are based on u.s.-located faculty or pis at universities or colleges that report affiliation with a field of study present in both surveys (note: all fields present in the sdr are present in our survey, but not vice versa). a. describes the sample averages for both samples and the mean differences in both the raw data ("diff.") and after adjusting for the different composition of fields in each sample ("diff., field adjusted") b. plots the share of respondents in each sample that affiliate with each of the fields common to both surveys. (*** p< . ; **p< . ; *p< . ) a. b. figure s . publication changes, raw and inferred pandemic effects. plots the distribution of changes to publication output. blue lines indicate publication quantity, red lines indicate impact. solid lines indicate the raw responses from the survey (which asked only about changes in publication output from - to - ), and dashed lines indicate our estimates of the implied effect due to the covid- pandemic based on the removal of group-specific trends in publication output. see the methodology section for more. figure b from the main text, also including the scientists' reported changes in time committed to each of the four task categories. the error bars indicate % confidence intervals, and only variables selected in the corresponding lasso selection exercises are included in the post-lasso regression. the coefficient corresponding to the " %change time, research" variable indicates the percent change in the scientists' forecasted quantity or impact associated with a % increase in the change in reported research time. for example, we estimate that scientists who reported a % larger decline in their research time forecast that the pandemic will cause them to produce . % fewer publications in - . covid- ) deaths. our world in data policy responses to the coronavirus pandemic science-ing from home how research funders are tackling coronavirus disruption safeguard research in the time of covid- coronavirus outbreak changes how scientists communicate the pandemic and the female academic early-career scientists at critical career junctures brace for impact of covid- how early-career scientists are coping with covid- challenges and fears how covid- could ruin weather forecasts and climate records productivity differences among scientists: evidence for accumulative advantage research productivity over the life cycle: evidence for academic scientists the economics of science faculty time allocation: a study of changeover twenty years incentives and creativity: evidence from the academic life sciences regression shrinkage and selection via the lasso regression shrinkage and selection via the lasso: a retrospective web of science as a data source for research on scientific and scholarly activity increasing dominance of teams in production of knowledge quantifying long-term scientific impact atypical combinations and scientific impact highly confident but wrong: gender differences and similarities in confidence judgments boys will be boys: gender, overconfidence, and common stock investment trouble in the tails? what we know about earnings nonresponse years after lillard, smith, and welch measurement error in survey data response error in earnings: an analysis of the survey of income and program participation matched with administrative data flexible imputation of missing data regression shrinkage and selection via the lasso regression shrinkage and selection via the lasso: a retrospective how to count citations if you must extension of the probationary period for tenure-track faculty due to covid- disruptions harvard offers many tenure-track faculty one-year appointment extensions due to covid- extending the reappointment/promotion/tenure review timeline covid- and tenure review response to covid- disruption: extension of the tenure clock. the university of alabama in huntsville memo on tenure-track probationary period extensions due to covid- . university of virginia office of the executive vice president and provost extension of tenure clock in response to covid- rule waivers: tenure clock extensions, leaves of absence, conversions, dual roles extension of the tenure-clock guidelines for contract extension and renewal. iowa state university office of the senior vice president and provost tenure clock extension due to covid- disruption faculty promotion and tenure tenure-track faculty: extension of tenure clock due to covid- . the ohio state university office of academic affairs promotion/tenure clock extensions due to covid- -faculty one-year opt-in tenure clock extension covid- guidance for faculty: extensions of tenure clock probationary period extensions for tenure-track faculty. the university of texas at austin office of the executive vice president and provost tenure rollback policy for covid- we thank alexandra kesick for invaluable help. this work is supported by the air force office of scientific research under award number fa - - - , national science foundation sbe , and the alfred p. sloan foundation g- - and g- - . key: cord- -x kl bx authors: lee, connal; rogers, wendy a. title: ethics, pandemic planning and communications date: - - journal: monash bioeth rev doi: . /bf sha: doc_id: cord_uid: x kl bx in this article we examine the role and ethics of communications in planning for an influenza pandemic. we argue that ethical communication must not only he effective, so that pandemic plans can be successfully implemented, communications should also take specific account of the needs of the disadvantaged, so that they are not further disenfranchised. this will require particular attention to the role of the mainstream media which may disadvantage the vulnerable through misrepresentation and exclusion. in this article , our focus is on the central role played by communication in a public health emergency such as a flu pandemic, and th e ethical issues that arise from communication in this context. the two main eth ical issues d iscussed here are the need for effective communication, in order to ensure compliance with and therefore successful implementation of flu plans , and the need for communication strategies that do not exacerbate existing inequalities in the community. we will argue that ethical communication must be both effective and just. a flu pandemic will pose major threats to health and safety and has the potential to disrupt normal life in a variety of ways . measures such as case isolation, household quarantine, school or workplace closure and restrictions on travel figure prominently in many flu plans.p these measures will be requir ed to reduce the risks of contagion, leading to limitations on citizens' usual liberties. compliance from the public is required for measures su ch as quarantine and social distancing to be effective . whilst there is debate about the level of compliance required for effective containment of infection. " there is th e ri sk that non-compliance with restrictive measures from very small numbers of individuals may spread infection . it has been predicted, for example, that border restrictions and /or october internal travel restrictions must be more than % effective if they are to delay spread of infection by more than to weeks. given the types of liberty-limiting arrangements that a pandemic will bring, it is important to recognise the potential for pandemic plans to be undermined by individuals and groups failing to comply with directives . one manner in which this is likely to occur is through an illinformed populace. if people are unaware of what is to be expected and how to respond appropriately, then there is the risk that pandemic plans may be undermined by a lack of co-operation from the public. inadequate communication during the sars epidemic has been identified as one factor associated with the genesis of panic in the community and weakened co-operation and support from the public. another manner in which non-compliance may occur is through some people and groups viewing directives and government orders as unrepresentative or illegitimate. measures such as quarantine may be jeopardised by a refusal to comply with directives seen to lack fairness or authority. therefore, effective communication with the public is important for ensuring, to the extent possible, that all individuals both understand what is required of them and see restrictive measures as legitimate and worth adhering to. international communication guidelines draw attention to the need for communicators to understand existing public beliefs, opinions and knowledge, thus contributing to the public's involvement, or sense of involvement, in the planning and implementation process. effective communication alone, however, cannot guarantee that the public will comply with directives, as people may act in selfinterested ways not consistent with pandemic plans. effective and efficient communications should therefore be seen to be necessary but not sufficient for implementing pandemic plans. further, communications should not only be efficient and effective but also just. in the following sections, we argue for ethical pandemic communications that overcome barriers to accessing information and avoid inequalities imposed by current media arrangements. avoiding unnecessary harms caused by a lack of information can help to prevent greater disadvantage to the worst off. firstly, however, it is important to outline the role of communications in pandemic planning. communication can take many different forms . of these, the media has been recognised as having a key role to play in effective implementation of a plan in the event of a pandemic outbreak. the world health organisation, for example, specifically identifies the role of the media and draws attention to the need for public officials to utilize the press as a means of communicating with the public. ( ) public knowledge. communication strategies should aim at increasing public awareness about what is involved in a pandemic. the media should playa central role in informing the public of the content of pandemic plans, as well as contributing to the public's ( ) public rationality. in terms of creating and maintaining a social climate of rationality , it will be important that media information regarding risks and potential rationing of resources is not overplayed or sensationalised and is proportional to the actual threat at hand, thereby avoiding unnecessary public alarm. as thomas may points out, developing a communications infrastructure designed to accurately convey information can go a long way to mitigating crises created through fear. ( ) equity. there will be an ethical imperative to recognise and address inequalities in communications. if inequalities in access to information are not addressed , then there is the concern that some groups and individuals will miss out on vital information . as it may take only one ill-informed individual to spread disease, reaching every available person should be a priority in the event of a pandemic. inequalities in control over the mainstream media pose a potential threat to pandemic plans. as we discuss below, exclusion, m isrepresentation and stigmatisation of groups and individuals by the press may lead to a climate of non-compliance , thereby jeopardising the welfare of the whole population. ( ) inequalities in access to information. with regard to access to information, people vary both in their ability to receive information and to act on this. addressing inequalities in access therefore requires making information directly accessible for the public and ensuring that information is sensitive to the varying needs and interests of different individuals and groups in society so that it is information that people have the capacity to act on. we have identified three ethical issues that should be recognised and addressed in overcoming inequalities in access to information. these are: barriers to accessing information; voluntary versus involuntary lack of access to information; and provision of information that is relevant to people's capacities. (a) barriers to accessing information. many influenza plans are available on internet sites. this is inadequate communication from an ethical point of view, as it places the burden of responsibility on individuals to access information.p in planning for a public health crisis such as a pandemic, there needs to be more than a formal capacity to access necessary information. this should necessarily involve a concerted effort by governments and authorities to ensure that information reaches people in forms that are readily accessible.p including but not limited to the mainstream media. inequalities in access to information may be due to a range of factors such as geographic isolation, disabilities related to visual or hearing impairments, or decreased access related to long or irregular working hours . whilst these inequalities may not be in themselves unjust, they are inequalities that affect access to information and have the potential to jeopardise successful pandemic planning. there is a strong moral imperative to address and rectify inequalities in access that arise from involuntary circumstances. if some individuals are unable to comply with directives because their capacity to access information has not been considered, there is an ethical duty to ensure that people are not unnecessarily harmed when they could have been protected if given appropriate information. overcoming all inequalities in access may not be possible, however, if we include inequalities resulting from voluntary actions, such as never watching or listening to the news or reading mail delivered to the home. overcoming voluntary refusals to accept information may require significant, costly and overly burdensome interventions in people's lives, and therefore not be as morally justifiable as overcoming involuntary barriers. addressing the issue of access must also take into account what kinds of information are most important for individuals to receive. we suggest that this must involve adequate consideration of how capable people are of understanding and acting on directives. this requires a match between the content of the information, including instructions for action, and the resources and capacities of the recipients of that information. there is an ethical imperative to ensure that the varying information requirements of the population are adequately considered.vt during the build up to hurricane katrina, for example, the community received information advising them to leave new orleans or seek refuge in the superdome stadium. however, this information did not take into account the varying capacities of groups and individuals to act upon the directives given. this type of advice did not assist already vulnerable groups (such as people in poor health or with disabilities) who lacked the resources to abandon their property in the absence of insurance and assurances that they would be adequately taken care of. in this case the information available to the less well-off in new orleans was neither relevant nor particularly useful given the realities of people's circumstances. perhaps more importantly, the effect was to widen inequalities, as those who were well enough off to comply fared better than those who were not so able. communication during a pandemic must be sensitive to how capable people are of acting on information important to their health and well being, and the likely compounding effects on existing inequalities. it could be argued that it was not the nature of information distributed in the case of katrina that was the problem; rather, it was the poor socio-economic circumstances of much of the population together with the lack of other necessary resources. however, it is important to note that in the subsequent media reports , there was stigmatisation of those who had not complied with the advice, with the implication that much of the ensuing human disaster was the fault of the victims themselves, rather than anything else such as lack of capacity to follow the advice. in situations like this, the lack of appropriate information for the disadvantaged is exacerbated by media communication that is not sensitive to the capacities of people to act on that information. we will now look at inequalities in control over media content and give a brief account as to why addressing these inequalities is necessary for achieving compliance and avoiding extra injustices in the event of a pandemic. ( ) inequalities in control over media content. in the event of a pandemic, inequalities in access to and control over the media may cause a number of problems, limiting the successful implementation of pandemic plans . this is critical when, as for example in australia, media ownership is concentrated in the hands of a few whose interests do not overlap with the role of communication outlined above. not everybody in society has the freedom to engage in and influence media discourse. in terms of the ability of individuals and groups to engage in the public forum, rawls' theory of justice is helpful for making an important distinction between liberty and its value. liberty, according to rawls, is the complete structure of the liberties of october citizenship, whilst the worth of liberty is the value a liberty has for individuals and collectives depending upon their ability to advance their ends. for example, the value of freedom of speech is worth more to a radio-based 'shock jock' with the means of advancing their point of view than to an unemployed person lacking the capacities and opportunities to advance their interests through the media. mainstream news favours the interests and values of those with a stake in the media business ahead of any competing ethical principle such as the public interest or reducing inequities. here we take stakeholders to include advertisers, audiences, and those who work directly for media firms . as a result, the content of news stories, particularly within the commercial press, is typically slanted towards the interests of stakeholders, with consequent disenfranchisement of non-stakeholders . there are two main ways in which the mainstream media can have a negative impact on those who lack power and influence over the press: misrepresentation and exclusion of nonstakeholders. (a) misrepresentation of non-stakeholders. in the event of an influenza pandemic, media misrepresentation of the interests and claims of nonstakeholders, in particular the least well -off sections of the community, may be problematic. there is a risk that individuals and groups who protest current arrangements may be presented to audiences as disruptive and unhelpful to the situation. this has the potential to weaken compliance levels during a pandemic. the misrepresentation of some groups may lead the public at large to view these groups as troublesome, leading to further marginalisation. if this occurs, then it is unlikely that these groups or individuals will embrace the notion of 'civic duty', which is an important aspect of accepting liberty-limiting arrangements."? it will be concerning from an ethical standpoint if misrepresentative media coverage facilitates discrimination against certain groups, as happened in canada where there was public boycotting of chinese business interests after the outbreak of sars was linked to a chinese national.l" thus it is not difficult to imagine that in the event of a pandemic, certain groups will be treated less than fairly by the media, such that the public will also treat these groups unfairly. overall this inequality in representation of points of view , claims and interests is likely to impact negatively on pandemic plans. the interests of non-stakeholders are not well represented in the mainstream media. this means that in a pandemic, their information needs may be largely ignored, and their interests unnoticed, by the wider society.t? the exclusion of some groups may lead to a lack of understanding about the legitimate claims of these groups. this will be damaging for pandemic plans, particularly if certain groups have justified claims. for example, it may be that arrangements for dealing with a pandemic are actually harmful for some individuals or groups.s? a greater likelihood of infection in communities that lack infrastructure could lead to demands for extra resources in the event of a public health crisis. if the claims and view points of these groups are excluded from the press, then wider society simply will not understand what those claims and views are and how they might contribute to more effective handling of pandemics. it is important to note here that we do not want to develop an account of how the media ownership model could, or in fact should, be restructured in order to overcome the problems that we have identified. rather, we see it as important to highlight the specific problems that arise with current media arrangements that will, in the event of a flu pandemic, harm the vulnerable, despite any public perceptions that a privately owned press is a free and independent press. it is of course possible that privately owned media may act out of self-interest to promulgate effective communication, or be persuaded to act with benevolence. however, we suggest that more concrete action from pandemic planners and governments will be necessary to ensure that communications are equitable. having outlined how mainstream media may undermine pandemic planning, we now look in more detail at the effect that media bias may have on disadvantaged groups and individuals. living conditions and community infrastructure both have a bearing on how susceptible to infection a given community may be, or how well prepared and equipped a given community is to deal with infection.v' situations of socio-economic disadvantage facilitate transmission of infectious diseases, as we have seen to date with the patterns of emergence and transmission of both sars and bird flu. given the potential for increased burden of disease amongst the disadvantaged, it may be particularly harmful for the effective implementation of pandemic plans if less well-off sections of the community and vulnerable groups are not given a voice through the media. this increased vulnerability to infection places a disproportionate amount of responsibility on the disadvantaged to act in ways that will not spread illness, adding to the moral imperative to support these groups through equitable communications. the increased risk of infection faced by disadvantaged groups is likely to put them in a position whereby they become subjects of news. given the above concerns regarding the fair representation of disadvantaged communities in the media, a pandemic may create a climate of news coverage that misrepresents,stigmatises and excludes the disadvantaged or vulnerable. we already have experience of this, for example, with news stories regarding hiv/ aids in the s that contributed to stereotypical and harmful perceptions of the homosexual community, as well as leading to a lack of understanding by society at large as to how the virus is contracted.v' the potential for a pandemic outbreak to make the worst off even more worse off must be a consideration in structuring an ethical approach to communications. as the main communicative force in our society, the media will playa central role in communicating the ethical underpinnings of arrangements and decisions; as such the media will contribute to and influence how the public perceives the fairness of measures such as priority vaccination and distribution of resources. as well, the press will influence the public's judgement of how well state directives protect or have protected the public from harm. however, inequalities in control over media content suggest that the public may well be given a biased interpretation of the effectiveness of a given plan in safeguarding the collective interests of society, with the risk that pandemic reporting will favour the interests of wealthier sections of the community. in the event of an influenza pandemic, already vulnerable groups and communities will not only be in a position of greater risk with regard to infection, existing inequalities in media communications and infrastructure will further compound their vulnerability. by addressing these inequalities, it is possible to identify an ethical approach for communications about pandemic plans. in tum, addressing inequalities in communications means that pandemic plans are less likely to be undermined by groups and individuals not complying because their information needs have been ignored and their interests and points of view have not been fairly represented. box lists four features of ethical communications strategies. box : features of ethical communication strategies . equity in access to information . active redress of existing media inequities . decrease extra burdens on disadvantaged . increase information, legitimacy and trust taking these into account, we believe it is possible to implement pandemic plans with greater efficiency, effectiveness and compassion. we suggest that if policy makers and pandemic planners attend to inequalities in communication, this will help to avoid unnecessary disaster and spreading of disease, and also ensure that disadvantaged individuals and groups are not made more disadvantaged in the event of a public health crisis, as occurred in new orleans. endnotes earlier versions of this paper were presented at the th world congress of bioethics, beijing, china, august - , , and the australasian bioethics association annual conference, brisbane, july - , . we are grateful for comments received at these conferences, and from the anonymous reviewers. monitored, especially with respect to prospects for providing fair benefits to , and avoiding undue burdens on, disadvantaged groups, so that corrective adjustments can be made in a timely manner". for example, see th e european un ion public health in flu enz a website that offers access to flu plans detailing containment strategies , including liberty limiting arrangements: http:j jec.europa.eujhealthjph_threatsjcomjinfluenzaj influenza_en.htm reducing the im pac t of the next in fluenza pandemic using household-based public health in terventions stra tegies for mitigating an in fluen za pandemic the public's response to se vere a cute respiratory syndrome in toronto and the united states world health organisation, outbreak communication guidelines medical countermea sures for pandemic influenza: ethics and the law see for example the who outbreak communication guidelines, op . cit. , p . , which emphasise the rol e of trust and transparency in successful implementation of pandem ic plans clin ical decis ion m aking d u ring public health emergencie s : ethical con si de rations public co m m u nication, risk pe rception , and the via bility of preventa tive vaccina ti on against co m m u nicable d is ease s preparin g for an infl uenza pandem ic com mu nicati ng the risk s of bioterrori sm and other eme rge ncies in a d iverse society: a case stu dy of special populations in north dakot a afte r the flood oxford uni versi ty pr es s it will be important for people to accept liberty-limiting arrangem en ts, and this ofte n in volve s the public viewing co m pliance a s a civic resp on s ibility or duty. see for example the tor onto join t centre for bioethics pandemic influenza working gr oup rep ort, stand on guard for thee -ethical co nside rations in pr ep aredne s s planning for pandemic influenza , tor onto see al so sc hram j , 'how po pu lar percep tion s of ris k fro m sars are fermentin g dis crimination exp loring jou rnalis m ethics , sydney: un ivers ity of new south wal es pres s the bellagio sta te me n t of principle s h ighligh t s the n eed to m ake available accurate, u p-to -date and easily und erstood in for mation about avian and huma n pa ndem ic infl uenza for d isa dvantaged gro u p s . in particula r , prin ciple v states key: cord- -axio zna authors: van, debbie; mclaws, mary-louise; crimmins, jacinta; macintyre, c raina; seale, holly title: university life and pandemic influenza: attitudes and intended behaviour of staff and students towards pandemic (h n ) date: - - journal: bmc public health doi: . / - - - sha: doc_id: cord_uid: axio zna background: in a pandemic young adults are more likely to be infected, increasing the potential for universities to be explosive disease outbreak centres. outbreak management is essential to reduce the impact in both the institution and the surrounding community. through the use of an online survey, we aimed to measure the perceptions and responses of staff and students towards pandemic (h n ) at a major university in sydney, australia. methods: the survey was available online from june to september . the sample included academic staff, general staff and students of the university. results: a total of surveys were completed. nearly all respondents ( . %, / ) were aware of the australian pandemic situation and . % ( / ) reported either "no anxiety" or "disinterest." asian-born respondents were significantly (p < . ) more likely to believe that the pandemic was serious compared to respondents from other regions. . % ( / ) of respondents had not made any lifestyle changes as a result of the pandemic. most respondents had not adopted any specific behaviour change, and only . % ( / ) had adopted the simplest health behaviour, i.e. hand hygiene. adoption of a specific behaviour change was linked to anxiety and asian origin. students were more likely to attend the university if unwell compared with staff members. positive responses from students strongly indicate the potential for expanding online teaching and learning resources for continuing education in disaster settings. willingness to receive the pandemic vaccine was associated with seasonal influenza vaccination uptake over the previous years. conclusions: responses to a pandemic are subject to change in its pre-, early and mid-outbreak stages. lessons for these institutions in preparation for a second wave and future disease outbreaks include the need to promote positive public health behaviours amongst young people and students. in april , severe cases of pneumonia preceded by influenza-like illness were noted to occur in mexico and then north america. a novel influenza a (h n ) virus was identified as the cause and it rapidly evolved into a pandemic. cases of the strain were first identified in australia in early may and soon appeared across the country [ ] . as of february , there have been , confirmed cases and deaths in australia. while this pandemic has been moderate or milder than previous pandemics such as the spanish flu of - , similarities can be drawn between the two in regards to the median age of cases. in australia, the median age of confirmed cases is years [ ] universities therefore have the potential to become explosive, centrifugal outbreak centres due to their large young adult population, high levels of close social contact and permeable boundaries. during a pandemic or disease outbreak, the proportion affected may exceed the seasonal norm of one-third of the student population [ ] . as sites of transmission, they may have a negative impact on the larger communities in which they are embedded. additionally, student behaviour is often divergent from non-student adult populations [ ] . hence, understanding of and outbreak management in such institutions are essential to minimise the impact of pandemic influenza in both the institution and its surrounds. university settings are unique given the permeability of their boundaries and the groups, and the activities within the institution that affect social contact between its members. both of which have the potential to affect behaviours and perceptions. this survey was conducted to examine the understanding of and attitudes towards pandemic (h n ) amongst students and staff at the university of new south wales (unsw), sydney, australia and their behavioural intentions during this pandemic. the cdc recommends that institutions of higher education balance the goals to minimize morbidity and mortality from pandemic influenza with the goal of minimising educational and social disruption [ ] . between april th and september th , ten broadcast emails were sent out by the director of the university health service to staff and students. contained in the emails was information on the: ( ) h n situation; ( ) modes of spread and common symptoms; ( ) recommended health advice consistent with both the who and national recommendations; and ( ) contact information for the relevant health departments [ ] . posters developed by the commonwealth department of health and ageing and unsw were placed in high traffic areas and focused on: ( ) encouraging faculty, staff and students to stay at home if symptomatic (i.e. with a fever, cough, and runny nose) and to protect each other; ( ) cough/sneeze etiquette (i.e. "cover your mouth and nose when you cough and sneeze" and "dispose of used tissues in the bin) and ( ) hand hygiene (i.e. "wash your hands properly and regularly"). data was collected from the june - september, coinciding with the peak of the pandemic in australia. an anonymous online survey was designed to assess the knowledge, attitudes and perceptions of pandemic (h n ) , which was referred to by its vernacular alternative, "swine flu". the survey was piloted on june th with three students and three staff, representative of the members of the study population, and modified accordingly. the final version assessed: ( ) demographic characteristics; ( ) awareness, perceived personal risk and anxiety; ( ) recent influenza-related behaviours changes; ( ) intended behaviour in the event of various scenarios at unsw and ( ) compliance with different community interventions. in regards to the behaviour changes, we included four changes (cancelling social plans, avoiding busy public places, cancelling/postponing travel plans and not using public transport) that were related to avoidance behaviour and not recommended by the government and five changes (buying hygiene products, receiving the seasonal influenza vaccine, using online resources for teaching and learning and stockpiling necessities) that were related to recommended behaviours. the recommended behaviours questions were adapted with permission from a study undertaken by rubin et al [ ] . the sample comprised of both academic and non-academic staff (i.e. administration, it and other support staff) and students at unsw in sydney, australia. participants accessed the final questionnaire via a link on an online newsletter available to all unsw staff and students, and via an online information gateway. emails were also sent to the heads of each faculty, informing them of the survey. consent was implied upon completion and submission of the questionnaire. submitted surveys were collated in a directory and deidentified prior to analysis. participants were offered the chance to win a $ cash prize upon completing the survey. ethics approval was granted by the university of new south wales human research ethics committee. the quantitative data on the completed survey was collected in microsoft excel. openepi (version . ) was used to calculate [ ] , proportions, % confidence intervals and χ tests for significance. alpha was set at the % level. we used logistic regression to compute odds ratios to evaluate the association of demographic variables and attitudes and beliefs. a total of unsw staff and students aged ≥ years completed the online survey between the june and september . the overall response rate was . % ( / ) and most respondents were young ( - years, . %, / ) and born in australia ( . %, / ) ( table ). academic and general staff members were both overrepresented in our sample ( . %, / , x = . , p < . ; . %, / , x = , p < . respectively) compared to the actual proportions employed at unsw ( . %, / and . %, / respectively). students were underrepresented ( . %, / , x = , p < . ) compared to the proportion of internal students at unsw ( . %, / ). most respondents ( . %, / ) reported that they had heard about the australian pandemic situation. whilst . % ( / ) believed that it was serious, . % ( / ) said that they were "not anxious" (figure ) and a further . % ( / ) reported "disinterest". of the respondents who felt they were likely to contract pandemic influenza ( . %, / ), . % ( / ) believed the infection would adversely affect their health. towards the end of the survey period and the end of winter, the percentage reporting "no anxiety" increased and the proportion of respondents who believed that the pandemic was "serious" significantly decreased (or, . [ % ci, . - . ); p < . ) ( figure ). perceptions of susceptibility significantly decreased with the decline of laboratory-confirmed cases in australia (or, . [ % ci, . - . ]; p = . ). asian-born respondents were significantly more likely to believe that the pandemic was serious (or, universities are not immune to natural or manmade disasters, and past experience with these have illustrated the importance of continuity during and after these events [ , ] . in an influenza pandemic, such institutions must maintain a balance between academic continuity, with infection control and minimising morbidity [ ] . in contrast to pre-pandemic and early pandemic findings in australian communities [ , ] , most of the university population surveyed were not anxious about the australian pandemic situation nor did they think it was serious. younger respondents (aged - ) were most likely to believe they were not susceptible to pandemic h n , despite being the most affected group in previous influenza pandemics. following the resurgence of media coverage of "swine flu" in australia, we did measure a significant rise in anxiety, perceived susceptibility and seriousness. this however declined with the approach of spring and the decline of laboratory confirmed cases of influenza a (h n ) in nsw [ ] . this illustrates that public perception of a pandemic is unstable, especially when the severity and natural progression cannot be accurately predicted. if requested by authorities, most respondents in our cohort were willing to undergo isolation if suffering from influenza-like-illness (ili). of concern was the high proportion of students who indicated that they would still attend university with symptoms. in the event of an exam or assessment deadline, their proportion tripled. such behaviour is detrimental for both students and the community, for in addition to spreading the pandemic virus, students with ili are also likely have reduced academic performance by up - % [ ] . absenteeism from university was higher in respondents who had indicated making a lifestyle change, implying the practicality of encouraging general positive health behaviour in this population. along with encouraging students to self-isolate in the case of illness, there must be ongoing education about the importance of infection control, especially when anxiety rates and risk perceptions are low. health messages need to educate students about the impact of the illness on their studies, and universities should emphasise their illness/misadventure assessment policies during disease outbreaks. online resources such as lecture recordings and forum tutorials allow for off-campus education, and can provide continuity of learning for students undergoing isolation. however in our study, few respondents had adopted the use of online teaching or learning resources as a result of pandemic influenza (h n ). this may be due to a number of factors including: ( ) the apparent mildness of the pandemic; and/or ( ) the lack of promotion by the university to use these resources. it was encouraging to see that students were very willing to continue university schooling via online resources, indicating the potential for expanding the existing unsw online teaching resources. while it was encouraging that students would undertake online courses, we found very little support for an online teaching method among the academic staff members. reluctance to use online resources was associated with increased age, and may be due to unfamiliarity with or resistance to technology. in preparation for an outbreak, universities should focus on creating additional support for technologies that allow faculty and students to continue their teaching and learning activities which minimise disruption. online recordings, virtual learning environment, blogs, web conferencing and discussion forums should all be utilised to assist in the delivery of lessons. having a contingency and communication plan for teaching key sections may provide the needed continuity for students and faculty. training must be provided in the pre-pandemic periods to minimise disruption. we found that most respondents had not made any lifestyle changes or undertaken any specific behaviour change despite receiving information from the university. this may be attributed to the mildness of pandemic (h n ) . this finding supports both the pre-pandemic and post-sars findings on the dose-response relationship between outbreak severity and the responses to it [ , ] . of the respondents who did indicate behaviour change, increased hand hygiene was the most common. it would therefore be beneficial and at minimal cost for institutions such as universities to provide extra hand-washing facilities and posters encouraging compliance in communal areas and computer labs. universities could also boost hygienic practices by openly distributing small bottles of hand gels or tissue packets to staff and students on campus. close to % of our respondents stated that they were 'very willing' to receive a hypothetical pandemic vaccine. as the survey period ended before the vaccine became available, we were unable to follow up participants to ascertain if they did receive the vaccine. in australia, the h n vaccine was not released until september , by which time, virus activity was very low. a recent national survey [ ] , found that although % of the australian cohort was aware of an available pandemic vaccine, less than % had received the vaccine. we can therefore expect similarly low vaccination rates in our cohort. the survey also identified that uptake of the h n vaccine was three times as high in those aged years and over ( %) than in those aged - years ( %), with no statistically significant difference between males and females [ ] . we found that respondents who had received seasonal influenza vaccinations in the past were significantly more likely to accept the pandemic vaccine then their non-vaccinated counterparts. these findings are consistent with several recent studies on pandemic vaccine uptake [ , ] . providing the vaccine through clinics or university health facilities should help bolster vaccine uptake, especially for international students, who may not have access to free healthcare. of the participants surveyed, asian-born respondents were the most likely to be anxious about the australian pandemic situation, rate the situation as serious, undertake specific behavioural changes and comply with public health measures. it could be hypothesised that these respondents, their families, friends or members of their communities may have been exposed to previous infectious disease situations such as sars and avian influenza [ , ] . if not exposed, at the least these respondents have lived in countries where their governments have had to deal with these situations, leading to stricter infection control standards and higher levels of media exposure. interestingly, asian born respondents who have been settled in australia for longer periods were less likely to have made any lifestyle changes compared to their counterparts who have been in the country for only short amount of time. it would appear that living in australia dilutes the tendency to adopt behavioural changes, and it would be beneficial for future studies to identify aspects of australian culture which influence health behaviours. we acknowledge that this study has several limitations. these include: ( ) the survey was restricted to the unsw student, general and faculty staff, mostly highly educated sydney residents; ( ) the electronic format of the survey may have excluded persons without internet access; ( ) we did not defin what "requested by the authorities meant" so it was open to the respondents interpretation and ( ) the survey was not translated into other languages. however, english is the dominant language used in both teaching and communication and unsw relies heavily on electronic communication with its campus population to disseminate other unrelated information in english. there was no established measure of influenza protective behaviour, as most of the survey items were developed prior to the publication of the cdc guidance for responses to influenza for institutions of higher education [ ] . the declining number of participants who accessed the online survey towards the end of the survey period likely restricted analysis of how responses to the pandemic change over time. from the study results, several key messages should be drawn. firstly, risk perceptions and anxiety are low and will remain so unless there is a major shift in the virus. this will continue to impact on compliance or uptake of mitigation strategies. secondly, more effective health communication and management is needed to promote self-isolation and infection control in the event of illness especially amongst students. these students are unlikely to adopt behaviours that are unknown to them. therefore the focus should be on handwashing and cough etiquette. lastly, universities must invest in online teaching resources and training during inter-pandemic periods. there also needs to be greater recognition for the need for online assignment submission and examinations to ensure minimal disruption to the students. national centre for immunisation research and surveillance of vaccine preventable diseases (ncirs), the children's hospital at westmead and discipline of paediatrics and child health australian government department of health and ageing: pandemic (h n ) australian department of health and ageing: australian influenza surveillance report no colds and influenza-like illnesses in university students: impact on health, academic and work performance, and health care use on the use of college students in social science research: insights from a second-order meta-analysis cdc guidance for responses to influenza for institutions of higher education during the - academic year public perceptions, anxiety, and behaviour change in relation to the swine flu outbreak: cross sectional telephone survey openepi: open source epidemiological statistics for public health pandemic policy and planning considerations for universities: findings from a tabletop exercise. biosecurity and bioterrorism: biodefense strategy, practice, and science pandemic influenza in australia: using telephone surveys to measure perceptions of threat and willingness to comply the community's attitude towards swine flu and pandemic influenza australian government department of health and ageing: pandemic (h n ) predicting the anticipated emotional and behavioral responses to an avian flu outbreak longitudinal assessment of community psychobehavioral responses during and after the outbreak of severe acute respiratory syndrome in hong kong adult vaccination survey provisional topline results for h n vaccination uptake. canberra: australian government department of health and ageing acceptance of pandemic (h n ) pandemic influenza vaccination by the australian public does receipt of seasonal influenza vaccine predict intention to receive novel h n vaccine: evidence from a nationally representative survey of world health organisation: avian influenza: assessing the pandemic threat. world health organisation severe acute respiratory syndrome (sars) pre-publication history the pre-publication history for this paper can be accessed here submit your next manuscript to biomed central and take full advantage of: • convenient online submission • thorough peer review • no space constraints or color figure charges • immediate publication on acceptance • inclusion in pubmed, cas, scopus and google scholar • research which is freely available for redistribution authors' contributions dv/hs participated in the design of the study and survey, undertook the distribution and collection, performed the analysis and drafted the manuscript. mlm participated in the design of the study and survey, assisted with the analysis and reviewed the manuscript. jc/crm participated in its design and coordination and helped to draft the manuscript. all authors read and approved the final manuscript. raina macintyre receives funding from influenza vaccine manufacturers gsk and csl biotherapies for investigator-driven research. these payments were not associated with this study. the remaining authors have no competing interests. key: cord- - ikkl hk authors: wilson, christopher; jumbert, maria gabrielsen title: the new informatics of pandemic response: humanitarian technology, efficiency, and the subtle retreat of national agency date: - - journal: nan doi: . /s - - - sha: doc_id: cord_uid: ikkl hk digital communication technologies play an increasingly prominent role in humanitarian operations and in response to international pandemics specifically. a burgeoning body of scholarship on the topic displays high expectations for such tools to increase the efficiency of pandemic response. this article reviews empirical uses of communications technology in humanitarian and pandemic response, and the ebola response in particular, in order to propose a three-part conceptual model for the new informatics of pandemic response. this model distinguishes between the use of digital communication tools for diagnostic, risk communication, and coordination activities and highlights how the influx of novel actors and tendencies towards digital and operational convergence risks focusing humanitarian action and decision-making outside national authorities’ spheres of influence in pandemic response. this risk exacerbates a fundamental tension between the humanitarian promise of new technologies and the fundamental norm that international humanitarian response should complement and give primacy to the role of national authorities when possible. the article closes with recommendations for ensuring the inclusion of roles and agency for national authorities in technology-supported communication processes for pandemic response. recent decades have seen a dramatic rise in global pandemics. from the sars pandemic in , to avian influenza in , h n in , ebola in , and the appearance of the zika virus in latin america in , these developments are inextricably bound up in modern socio-technical developments and processes of globalization. advances in global air travel, agricultural technology, urbanization, and pollution all facilitate the appearance and spread of contagious diseases (see wolfe ; ramalingam ) . simultaneously, new media and technologies have also come to play a profound role in the way that global pandemics are identified, traced, understood, managed, treated, and perceived. digital communication technologies play an increasingly significant role in different aspects of global pandemic response, presenting novel opportunities to mitigate risks and enhance response efficiency. in doing so, they also confound traditional domains of information and communication practices in pandemic response (mager ) and introduce a novel collection of international and transnational actors to areas that have traditionally been the purview of national authorities. the capacity of digital communications tools to process, systematize, and make sense of large amounts of data has attracted the attention of practitioners, policy makers, and scholars alike (brownstein et al. ; tusiime and byrne ; wesolowski et al. ; zwitter and hadfield ; meier ; holeman et al. ) , and has raised significant expectations regarding their use in pandemic response in particular (odugleh-kolev ) . these expectations are countered by an emerging critical scholarship concerned with the novel risks that accompany humanitarian technologies (sandvik et al. (sandvik et al. , comes ) , how communication technologies impact power relationships between national and international actors in humanitarian crises (burns ; letouzé et al. ; mcdonald ) , and the ways in which new technologies are both constituted by, and contribute to reshaping social practices in a given society (amicelle et al. ) . with the exception of work by ihlen and levenshus' ( ) on technology in crisis and risk management and roberts and elbe's ( : ) on syndromic surveillance systems, however, the role of digital communication tools in pandemic response has received scant critical attention. this article contributes to filling that gap by conceptualizing the broad variety of ways in which digital communication technologies are brought to bear in global pandemic response. a three-part conceptual framework for informatics is constructed on the basis of empirical examples from recent pandemic responses and contemporary policy debates, drawing on the ebola response in particular. this model highlights how the application of new communication technologies in pandemic response is often accompanied by an influx of novel actors and convergence of previously distinct activities within single technological platforms or institutional operations. applying a critical reading of knowledge politics to these dynamics emphasizes the potential of new technologies to complicate global pandemic response, and the associated risk of relocating decision-making and agency outside of national authorities' spheres of influence. this article is organized in five sections. following this introduction, a second section describes the literature upon which the conceptual framework for pandemic informatics is developed. the third section presents that framework and describes each of its three components in detail. the fourth section notes two underlying dynamics that are consistently cited in conjunction with the use of digital communications in pandemic response: the introduction of novel actors and convergence of activities in single technological platforms and across organizational entities. the final section concludes by noting the significant challenges that this poses for effective coordination of pandemic response between national and international actors, and elaborates on the tendency of technologically driven informatics to decrease national authorities' sphere of influence in pandemic response. reflecting on seminal and watershed humanitarian policy for humanitarian coordination, the article concludes by suggesting that the roles and authority of national actors be explicitly designed in workflows for internationally coordinated pandemic response, and identifies preliminary measures through which this might be pursued. this conceptual exercise draws on descriptions of digital technology deployment in several contexts and from a variety of sources. in addition to academic research, this includes liberal reference to the so called "grey literature" produced by humanitarian implementing agencies, think tanks and volunteer groups, as well as descriptions of humanitarian communication in popular press and in online media maintained by civil society organizations and other commentators. while such sources are not subject to significant quality or review standards, and often lack the detail found in other types of literature, they tend to describe a much wider variety of activities, and do so without the significant time lag that accompanies peer reviewed research. often, activities and initiatives described in organizational reports, popular media, or ngo blogposts represent novel combinations of activities only anticipated in scholarly work and add a depth and richness to the scope of activity conceptualized in this article. the current analysis is grounded in response to the ebola pandemic, as arguably the most globally active and thoroughly documented example of pandemic response. accordingly, second section uses examples of digital technology innovation from the ebola response to construct a preliminary framework, with an emphasis on the incentives and objectives for using technological tools and strategies. the third section will then present each component of that preliminary framework in detail, using examples from other pandemics and from response policy more generally to validate and refine the framework. a great deal has been written about how communication technologies were used in the global response to west african ebola, including academic articles (odugleh-kolev ; tulenko ; sacks et al. ; sandvik et al. ; harman and wenham ) , assessments of multinational and non-governmental response (acaps ; adams et al. ; dubois et al. ; smith ) , and case studies documenting specific instances of technology use or country communication processes (nethope global broadband and innovations alliance ; acaps ; levine et al. ) . the most comprehensive overview is provided by fast and waugaman's ( ) -page report for usaid, "fighting ebola with information," which provides a starting point for this article's conceptual framework. after briefly describing the types of activities covered in fast and waugaman's report, an argument is made for re-categorizing and assessing those activities according to the objectives they pursue, which provides an initial basis for the framework developed in this article. fast and waugaman provide a thorough account of how information and technology were mobilized in the west african ebola response, based on case analysis, literature review, and over interviews. their analysis includes a typology of technology tools commonly utilized in the response ( - ) and nine in-depth case studies of specific information flows that relied on digital tools to facilitate response ( - ). these case studies include descriptions of activities, technological tools, actors involved, outcomes, challenges, and objectives and provide a useful starting point for drawing conclusions about the breadth of activities utilizing digital communications tools. fast and waugaman organize and present their case studies by virtue of the differences the integration of digital technologies enabled, such as increasing the diversity of information flows (e.g. "up" for data collection, as well as horizontally among peer groups, and back "down" through feedback loops) among a greater plurality of actors (e.g., frontline health workers, citizens, governments, and "remote" responders) ( ). the organizing principle here is a spatial understanding of coordination across pandemic response. connecting and coordinating actors that would otherwise not have exchanged information is certainly one of technology's most prominent contributions. a close read of these case studies, however, reveals a number of additional functions and objectives and allows for a more nuanced assessment of their impact. the liberian sms-based initiative, mhero, for example, was structured not only to connect frontline workers and governments, but also explicitly "aimed to strengthen the government's health information system […] and to provide critical information to support health workers on the frontlines of the crisis" ( ). the ebola community action platform (ecap) did not aim only to connect response organizations and extension workers, but more accurate information on the state of contagion and response was quickly leveraged towards public health messaging via billboards, radio, posters, handouts, and "person-to-person drama activities at the community level" ( ). these examples are notable not only for the breadth of actors they engage, but for the deliberate piggybacking of novel objectives and efficiencies, and the same dynamic is discernable across all of fast and waugaman's nine case studies. this matters. the way in which objectives are articulated and claimed has consequences for how responsibilities are allocated and priorities made in humanitarian response (burns ; mcdonald ) . in much the same way as the power asymmetries implied by humanitarian technology are often eclipsed by a presumption of technology's democratizing potential to re-distribute power (sandvik et al. : ) , fast and waugaman's preliminary mapping of digital information flows posits connectivity as an immediate and obvious benefit to pandemic response, without assessing the ways in which it asserts and reinforces power relationships. as the sociologists would have it, however, technological tools and political instruments "are less inert intermediaries than partly autonomous actants that contribute to orientating actors' behaviours" (amicelle et al. ) . novel connectivity in pandemic response inevitably structures relationships of power and responsibility in a messy field, asserting and assigning influence and roles in humanitarian response. critical scholars have described these dynamics as "knowledge politics" (burns ). the degree to which actors are able to influence these knowledge political assertions and assignments, we term informatics discretion, relies significantly on their participation, capacity and expertise in the types of information and communication modalities at issue (elwood ) . reconceptualizing digital information flows in pandemic response according to their objectives allows for a close reading of the ways in which this occurs and the implications it has for pandemic response coordination. a careful review of fast and waugaman's nine case studies suggests at least three broad categories of objectives that manifest themselves consistently across different modes of connectivity. digital communications in fast and waugaman's case studies are leveraged to determine the way in which ebola was spreading and the nature of risks posed by the pandemic, in order to coordinate activity among different types of response actors, including national authorities, international humanitarian aid workers and front-line health care providers, and in order to communicate with the general public regarding health risks and appropriate behavior to mitigate those risks. in order to test and refine these broad categories, they were assessed in the context of the broader literature on west african ebola response, and in the broader context of pandemic response and humanitarian policy, including grey literature and popular media, as described above. convenience sampling and citation tracing were used to identify relevant academic literature, while scans of the websites of civil society groups identified in academic research were used to identify sources in grey literature and popular press. when distinct objectives or efficiencies were described in the context of digital information flows, these were grouped according to the above categories. those categories were then refined into a three-part conceptual model of informatics in pandemic response, which is described in the following section. the previous section's review of objectives and efficiencies driving the use of digital communication technologies in ebola response suggested three broad categories: (a) diagnostic efforts, through which the characteristics and spread of infectious diseases are assessed in order to inform treatment and response; (b) risk communication practices, through which communities and individuals are informed about pandemic risks in an effort to mitigate those risks and curb contagion; and (c) coordination processes, through which different actors involved in pandemic response are allocated roles and responsibilities, in an attempt to maximize the efficiency of their work and avoid superfluous or parallel efforts. this section provides detailed description of these categories, validated and refined through reference to other contexts. it should be noted that some of these categories recall established fields of study. risk communication and coordination activities are relatively well delineated in scholarly work and policy documents (see plough and krimsky ; akl et al. , respectively) , while our understanding of diagnostic efforts combines a variety of activities occurring across the spectrum of response, from health surveillance, to the identification of the pandemic and clarification of symptoms, to contact tracing and contagion modeling. it should be emphasized that our objective here is not to recount or re-conceptualize established fields of practice, but rather to sketch the different mechanisms and patterns through which technology and information are deliberately employed, and to question the consequences this has for governance and power relationships in pandemic response more generally. this first component groups diagnostic activities related to collecting, systematizing, and processing information about a disease outbreak, and mapping its spread and associated needs, which we term diagnostics. this constitutes diagnosis at a societal level, and should not be confused with the medical diagnosis of individuals. the analysis of information has been central to understanding, anticipating and responding to infectious diseases at least since john snow became the "father of modern epidemiology" by drawing dots around a map of london water pumps during the cholera epidemic in (hempel ) . in the humanitarian context, collecting information is central to the implementation of an efficient response, including situational information, needs assessment, and operational information (king ; van de walle et al. ). this corresponds with humanitarian practice which has traditionally assumed the "information imperative" to be central to the humanitarian imperative-that is, the need to collect as much relevant information as possible, to enhance evidence for decision-making basis and improve efforts to assist people suffering in crisis contexts (bui et al. ; darcy and hofmann ; miller et al. ; saab et al. ) . scholars have explored a number of ways in which technology improves humanitarian diagnostics, including the use of mobile phone network data for human mobility mapping and contact tracing (tatem et al. ; aslam et al. ; wesolowski et al. ; gittelman et al. ; bharti et al. ; bengtsson et al. ) , and big data or social media scraping for contagion modeling (brownstein et al. ; chunara et al. ) . such techniques allow humanitarian actors to extract information, diagnosing needs and epidemiological trends without direct contact with affected populations. other applications of digital media for diagnostic activities introduce completely different actors. novel initiatives in response to the ebola pandemic in - include hackathons organized in western capitals to map resources for west african response, and western non-governmental organizations (ngos) that provide communication-based outbreak models to multinational humanitarian organizations (sangokoya ; moore ; dittus et al. ) or build geographic information system (gis) maps for national authorities (timo lüge ). early work is even underway to develop artificial intelligence responses to combat the spread of infectious diseases, by using multiple sources of publically available data to algorithmically predict the appearance and spread of disease (barron ). such innovative approaches are compelling and have attracted an understandable amount of interest and optimism, not in the least due to perceived gains in efficiency. novel collaborations and web-based health surveillance systems have regularly been quicker than the world health organization (who) to publish reports on epidemic outbreaks (anema et al. (anema et al. : (anema et al. - , and jennifer gardy, a senior scientist at the british columbia centre for disease control, has argued that epidemics are always essentially a race between the spread of info and spread of virus, and that technology has given scientists a critical edge (edmunds ) . whether or not such approaches are inherently more efficient, they are noteworthy for their inclusion of novel actors. this is perhaps most apparent in web-based initiatives such as wiki systems, which are used to facilitate collaborative pandemic modeling among geographically disparate scientists (kno.e.sis ), or the humanitarian data exchange, which through the leadership of a traditional humanitarian agency, was used to coordinate data sharing between a diverse group of actors, including local ngos and remote volunteer mapping communities (verhulst ; fast and waugaman : ) . though not solely dependent on digital media, a similar dynamic is visible in the proliferation of global health networks, such as goarn (global outbreak alert and response network) and promed (program for monitoring emerging diseases), which combine the efforts of national and international civil society and regulatory bodies, to surveil health risks internationally through a mix of traditional and digital media, and which to some degree eclipse the traditional roles of international and national health regulatory bodies (ramalingam : - ) . the second component we identify is risk communication, which we understand as the processes of communicating the risks associated with a pandemic outbreak, primarily to relevant and potentially affected publics. it is a widely recognized field of practice defined by the american national academy of sciences as: an interactive process of exchange of information and opinion among individuals, groups, and institutions. it involves multiple messages about the nature of risk and other messages, not strictly about risk, that express concerns, opinions, or reactions to risk messages or to legal and institutional arrangements for risk management. (cited in covello et al. : - ) . the interactive character referenced in that definition is the subject of some debate. in their handbook on global health communication, editors waisbord and obregon argue that the field of global health communication is characterized by a theoretical split, which places a preference for behavior change and unidirectional approaches against critical theories of participatory engagement (waisbord and obregon : - ). civil society and practitioner rhetoric tends to link participatory communicative models with technological advances, framed in normative terms that are highly critical of traditional, less participatory approaches in the humanitarian and development sectors (chao ) . this normative perspective is also assumed by several scholars (kaiser ; abraham ; maxwell et al. ; gillman ; Özdamar and ertem ; madianou et al. ) , and participatory approaches to risk communication have been argued to improve outcomes and efficiency. odugleh-kolev ( ) argues that a structural and interactive understanding of risk communication is particularly important in pandemic response, where coordinated, functional, and systemic communication is implied in activities such as assessing transmission risk and mapping contagion patterns in rural communities ( ). participatory approaches to risk communication tend to incorporate diagnostic activities, since digital media technologies facilitate simultaneous broadcast and collection of humanitarian information, at marginal cost, as will be discussed below. for clarity, this analysis focuses on risk communication implemented nationally or sub-nationally, targeting communities potentially affected by pandemics, and disregard the international role of for instance social media in risk communication. in doing so, we can identify at least three ways in which digital media are used intentionally to bolster risk communication strategies. again, responses to the ebola outbreak of are illustrative: firstly, digital media was expected to expand the reach and interactivity of risk communications. the use of new media technologies, particularly mobile phones, is often expected to dramatically increase the reach of risk communication to rural and remote communities, as well as front line health providers. mobile penetration rates in developing countries were estimated to have surpassed % at the time of the ebola outbreak (wesolowski et al. ) , and a review of ebola response in nigeria cited mobile-delivered training to health workers as "vital" for promptly declaring the country "free of ebola" (west : ). digital media also allow for scaled co-creation of health communication content, such as programs to produce videos together with youth infected with ebola in sierra leone, as a means of addressing stigmatization and developing trust networks among affected populations (zuckerman ). secondly, digital media allow for feedback and interaction to be integrated into risk communications. a project called u-report, led by the united nations children's fund (unicef), combines mobile phone-based surveys with opportunities for user feedback and was used to channel infection reports and concerns regarding public health activities in liberia during the ebola outbreak (muah et al. ) . similarly, the international conglomerate ibm combined outgoing radio communications with interactive short messaging system (sms) functionality to implement interactive risk communications surrounding ebola in sierra leone (bell, ) . some studies suggest that these affordances were particularly effective when targeting health communication to specific sub-groups (ems and gonzales ) . finally, digital media are sometimes expected to obviate institutional and resource limitations on the development of media platforms and content production for public health authorities. that digital media is faster and cheaper to produce and disseminate than paper is widely recognized. in addition, participatory content creation such as the sierra leone video program described above can effectively outsource some degree of communications work, as do content creation efforts which move beyond specific communities and aim to engage "the crowd" in generating content. such approaches have been pursued in generating both platforms and content for risk communication, either through international volunteer communities or institutionalized global health networks, or initiated by third parties, as in a series of hackathons organized in new york to develop mobile apps for spreading information about ebola in affected countries (sangokoya ) . the third component we identify is coordination, which is a persistent challenge and polemic in the humanitarian sector (stephenson ; bisri ). the introduction of new actors and new technologies promise to mitigate this challenge, even as they contribute to it in novel ways. ramalingam ( ) notes that the contemporary governance system for international diseases incorporates at least five different types of actors (intergovernmental organizations, national governmental organizations, non-governmental organizations, private foundations, and public/private partnerships and consortia), whose activities are marked by competition and lack of collaboration (ibid - ). he argues that this institutional disarray, when coupled with other socio-economic developments and trends of globalization, poses a threefold governance challenge to global health: the challenge of capitalizing on the diversity of actors, the challenge of bringing traditional actors up to speed with innovative organizational and technical approaches, and balancing the incentives and responsibilities of individual countries in treating diseases that do not respect borders (ibid ). simultaneously, timely, accurate, and appropriate information is widely regarded as a cornerstone for effective humanitarian coordination (bui et al. ; miller et al. ; saab et al. ) and digital media are often expected to dramatically enhance the coordination potential of information (moss and townsend ) . the most remarkable applications of digital media to coordination informatics for pandemic response are likely the creation and activation of global health networks, mandated to surveil infectious diseases internationally and alert regarding their outbreak. these networks have at least partially filled a coordination gap for identifying and initiating responses to global pandemics (see burkle et al. ) , but coordination in the implementation of specific response remains largely lacking. volunteer and technical communities (v&tcs) represent another prominent example of the coordination challenges posed by novel actors in humanitarian response. volunteer communities are composed of thousands of individuals around the globe who are moved to contribute time and energy to humanitarian response efforts virtually and remotely, often by collecting or processing humanitarian information such as incident reports or spatial data over social media. though different communities vary significantly in their membership, degree of organization and formal relationships with humanitarian coordinating bodies, their integration into a field marked by seasoned professional field staff and conservative information management is consistently marked by cultural and institutional tensions (harvard humanitarian initiative ). officially and institutionally this is visible in the challenges that surround the development of ethical codes of conducts for digital humanitarians (meier : - ; resor ) or the development of an activation protocol through which ocha is to include the standby task force (svt, one of the most prominent v&tcs) in humanitarian response operations (burns ; gorp ). in ebola response, v&tcs were particularly prominent in establishing novel information exchange platforms, such as a skype channel for coordinating data collection and identifying data gaps (fast and waugaman : - ) , though there is some evidence that lack of integration into formal coordination mechanisms actually "contributed to gaps in awareness of existing tools and duplication of effort" (ibid ). this dynamic recalls of other instances where the introduction of digital tools complicates rather than facilitates humanitarian efforts (bui et al. ; miller et al. ; saab et al. ) , and is consonant with the more general assessment that the uncoordinated introduction of novel actors into ebola response exemplifies "wider dysfunction in the provision of global health security" (harman and wenham : ). tapia et al.'s ( ) two case studies on humanitarian coordination offer a possible explanation for the failure of information systems to lead to enhanced coordination despite explicit efforts. on the basis of a careful literature review and analysis of two humanitarian coordinating bodies, they examine "the instrumental use of it as a mechanism by which ngos collaborate" (ibid ) and identify an important distinction between it-driven coordination efforts that are conceptualized as technical or informational challenges, and those that are conceptualized as organizational or process challenges, which they describe as more formidable. tapia et al. conclude that coordination efforts with modest goals and modest demands on organizational processes are likely to be more successful and increase opportunities for successively more progressive coordination efforts (ibid ). according to this logic, it would be reasonable to expect that digital media coordination would be most successful when it did not demand changes in organizational practice (i.e., coordinating actors who are already inducted in the use of specific media and coordination efforts that do not require changes to data formats or data collection procedures). this section describes two novel tendencies revealed by the above distinctions: the influx of novel actors that accompany and drive the use of new technologies in pandemic response, and the tendency of new technologies to compound previously distinct activities and workflows within single platforms or single institutional operations. new informatics introduce a host of actors and intermediaries not traditionally included in pandemic response and coordination. the ways in which this influx interacts with traditional structures for pandemic response can be considered according to a sandwich model, in which interaction is introduced from above and from below. the bottom slice of the sandwich in this metaphor is interaction with affected populations, where novel informatics present at least two types of challenges. firstly, social media and big data introduce promising new sources of information on which to base decision-making in pandemic response, but for whose meaningful use humanitarian organizations tend to lack the institutional and technical capacity, and national authorities even more so (harvard humanitarian initiative ; odugleh-kolev ; smith ; read et al. ) . simultaneously, the participatory ethos of new technology encourages humanitarian organizations and government authorities alike to deliberately engage affected communities in the design, implementation and evaluation of humanitarian response (kaiser ; maxwell et al. ; gillman ; Özdamar and ertem ) , yet poses a number of non-trivial hurdles to meaningful engagement. here too, technical capacities tend to be weakest with national governments, necessitating partnership with international organizations to invest in participatory interventions. infrastructural requirements and issues of access and representativity can also frustrate intentions to utilize participatory technologies. in a humanitarian context, political realities can often be the most meaningful obstacle, even when all issues of capacity, infrastructure, and access are surmountable. for all these reasons, national authorities are rarely in a position to unilaterally dictate the ways in which new technologies are leveraged to interact with affected populations. informatic challenges at the top end of the sandwich arise from the (sometimes unsolicited) engagement from novel international actors. of particular note are v&tcs and digitally native civil society organizations that are small, nimble, and eager to disrupt established practice. these actors present fundamental challenges to humanitarian coordination by their very engagement. because they do not fit neatly into traditional humanitarian coordination mechanisms, yet tend to demand attention and heighten expectations, novel international actors at the top level of pandemic informatics are a powerful force for asserting knowledge politics in informatics of response. the information flows described by fast and waugaman illustrate not only information exchanges in this sense, but fundamental assertions and negotiations about what kind of information is relevant and where and by whom those decisions are made. the moments at which this happens are not regulated by traditional policies of humanitarian coordination or cluster mechanisms, but occur in the practical application of technologies to knowledge and information, what some scholars have termed moments of closure in humanitarian knowledge politics (burns ). in some instances, international informatics are efficiently structured to serve national authorities. the introduction of data and information clearing houses presents opportunities for national authorities to assert control of national agendas, for example, such as when the humanitarian data exchange enabled guinean ministries to track training of infection prevention and control training efforts in the country (fast and waugaman : ) . this dynamic appears exceptional in a chaotic response environment marked by a "myriad of actors with no clear role or leadership" (harman and wenham : ) , however. a pandemic response context where "many of the information collection systems that organizations set up during the response were not linked to national systems or national capacity" ( ) necessarily reinforces the capacity and agency of international actors, and often novel actors, at the expense of national authorities' influence over response processes. it is also worth noting informatics practices that transcend this two-level model. most clearly in opposition to the agency of national authorities is the introduction of "hidden actors", such as application developers, producers of hardware or network managers with de facto influence over humanitarian data during its collection and processing (see gillman : ). equally notable are instances in which international actors bypass engagement with the traditional response environment altogether. in some instances, this appears to occur exclusively at the international register, with little or no contact with any in-country actors. examples include international networks of scientists collaborating to improve diagnostic tools (eclipse ), or hackathons organized in foreign capitals to develop data models or applications for implementation in pandemic response (sangokoya ; gordon ; lodato and di salvo ) . such initiatives raise serious questions about opportunity cost and efficient use of resources. to summarize, digital communication technologies and information flows introduce a host of novel actors to pandemic response. traditional humanitarian actors may experience this at the top level through the novel engagement of international actors, or at the bottom level through pressure to engage with affected populations and their data. in each instance, the influx of novel actors carries a risk for decision-making authority and agency to be moved into novel fora, further outside the influence of national authorities. this may not occur in an absolute sense; indeed, the role of national governments in driving ebola response strategies has been significant (dubois et al. : ) . yet the potential for exclusion merits careful consideration, particularly given the already pronounced tendency for agency of national authorities to be limited by the militarization of humanitarian response (sandvik ) and the increasing prominence of international ngos in public health service provision (prince ) . such dynamics are particularly vulnerable in the contexts of pandemic and crisis response, and reviews of the ebola response have also noted how decision-makers' identities shape response strategies (dubois et al. : ) . the application of digital technologies has undoubtedly opened up a host of opportunities for decision-making by novel actors. this may occur in situations where national authorities enjoy a limited role, such as the network communications of global watchdog networks in which ngos, scientific communities, international health networks and government agencies contribute to multiple digital communications streams and daily webinars to coordinate disease surveillance and response (ramalingam : - ) . it may also occur in digital for where there is no direct participation by national authorities, or in situations where national authorities lack the basic technical capacities to engage in a natural coordinating role, such as when "a host of academics, private philanthropists and technology companies" lobbied telecom companies for access to call detail records in order to develop their own response strategies (sandvik et al. : ) . though there are some cases in which novel actors and information practices support a stronger role for national authorities in pandemic response and a greater capacity to exercise agency and decision-making in the design and implementation of that response (ramalingam : - ; fast and waugaman : - ) , but this appears rare and the conditions under which it occurs are unclear. the overwhelming picture is one in which technologically driven informatics exacerbate coordination challenges (kim ) , driving the enactment of knowledge politics outside formal structures of humanitarian clusters and beyond the influence of national authorities. though the boundaries between diagnostic activities, risk communication, and response coordination were perhaps never entirely clear, these areas have traditionally been institutionally and procedurally distinct. digital communications' affordances and functionalities make it increasingly possible to combine activities from these areas in single processes. this recalls theories of technological convergence, in which the increasing capacity of media tools to integrate multiple functionalities corresponds with broader shifts in markets and genres (kim ) . as described by henry jenkins (huerta and tsimring ) : our cell phones are not simply telecommunications devices; they also allow us to play games, download information from the internet and receive and send photographs or text messages. any of these functions can also be performed through other media appliances. one can listen to the dixie chicks through a dvd player, car radio, walkman, computer mp files, a web radio station or a music cable channel. fueling this technological convergence is a shift in patterns of media ownership. whereas old hollywood focused on cinema, the new media conglomerates have controlling interests across the entire entertainment industry ( ). a detailed exploration of how these dynamic maps onto humanitarian technology exceeds the scope of this article, but we feel justified in arguing that there are at least two comparable dynamics. first, we will use the term digital convergence to refer to the ways in which technology enables a concentration of diverse tasks in single platforms and workflows (the same platform conducting a range of tasks). second, the examples cited in this article consistently exemplify how this type of convergence is coincident with what we term operational convergence, whereby specific types of information and communication management tasks are distributed across novel institutional and organizational groups of actors (same tasks conducted by a range of actors). below, we briefly describe four examples that demonstrate how this can occur in pandemic response. these examples are not explored in depth, but are meant to illustrate the consistent interplay of convergence with digital media and the injection of novel actors across a variety of humanitarian settings. the first example is what ramalingam terms "watchdog and knowledge networks" ( ), understood as networks involved in the "early detection of disease, characterization of the disease, and subsequent reporting and communication directed to decision makers in governments, international bodies and other key audiences" (ibid - ). especially instructive is ramalingam's analysis of goarn, the global outbreak alert and response network. as an "operational arm" of the who and network of networks that together surveil the outbreak and spread of infectious diseases, goarn functions as a de facto coordination mechanism for international and national actors engaged in pandemic response. the scope of goarn's activity in this regard is impressive, having responded to over outbreaks in over countries between and , and the network has played a crucial role in the sars outbreak in and the avian influenza outbreaks of . notably, the efficiency and scope of goarn's activities is explicitly attributed to the fact that coordination and information exchange occur across a diverse digital infrastructure that supports text messaging, email, and web-based applications, all of which are employed in tandem to ensure the right knowledge and information get to where they are needed at the right time, and importantly, allows a two-way exchange of information across the network ( ). notably, the diverse communications between national authorities, who staff, ngos, and scientific institutions are consolidated in a coherent institutional framework and through weekly webinars. this process interoperates diagnostic and coordination, feeding them directly into the establishment of response protocols, including protocols for risk communication, which are in many instances executed by the same actors that provided diagnostic information, by virtue of their capacity for rapid, two-way communication with populations. though it is unclear the degree to which this operational convergence of such tasks diminishes the agency of national authorities in a general sense, it is reasonable to expect that the inclusion of multiple actors decreases governments' scope for top down control. this may often be for the better in terms of effective response, as is likely the case with sars in , when goarn's access to digital communications platforms facilitated the supply on non-governmental diagnostic information, which likely contributed to acknowledgement of the outbreak by the chinese government. assisted contact tracing provides a second example. contact tracing is the epidemiological practice of identifying the individuals who have come into contact with infected individuals, in order to map the spread of a disease (huerta and tsimring ) . in , a private company named odisi developed a platform for "assisted contact tracing" (act), which digitized this process through the use of integrated voice recognition software. individuals in ebola-affected communities were able to report their contacts using mobile phones and then received follow-up messages regarding care and updates on the ebola response. this digitized approach increased the efficiency of data collection by eliminating the need for human interviewers, and also allowed the integration of other types of data (paper and mobile data), which increased the platform's diagnostic capacity dramatically. though the platform was designed and implemented as a diagnostic tool, the affordances offered by digital media quickly presented other opportunities. the automated registry of exposed individuals was quickly adapted for risk communication purposes via sms follow-up messages, and the digitization of rapid analysis of data promptly positioned the act platform to play a coordinating role among parallel diagnostic initiatives. here, we see a clear digital convergence of diagnostic and risk communication activities on a mobile phone platform, at the discretion of a private company. a third example is offered by u-report, a free sms-based polling tool launched in uganda in through a civil society partnership in order to monitor the quality of human rights and governance in the country, with a focus on polls related to human rights. in early , platform users noted early signs of the outbreak that would later come to be known as "nodding sickness" and would claim over lives in the following months. u-report did not have a health mandate and did not solicit these early epidemic reports, but received them because the communication platform was already in place and integrated into the communication habits of users. in this sense, the presence of a digital media infrastructure very much conditioned the implementation of a diagnostic tool, which promptly provided a site for national coordination, as u-report collaborated with the ministry of health and the who to develop and implement a -stage communications and mobilization plan. here again we see the digital and operational convergence of diagnostic activities and risk communication activities by national authorities with the support of international organizations. notably, while national authorities are directly engaged in both sending and receiving content, they do not have direct control of the operational and financial processes that support the initiative. fourth and lastly, the humanitarian data exchange (hdx) was established by the un office of coordination for humanitarian affairs in , in an effort to improve and coordinate access to humanitarian data. the ebola crises page collected data sets from un, governmental, civil society, and private sector data sources and invited users to contribute their own data to the site. the page also featured maps and visualizations developed in collaboration with private charitable foundations and private businesses. as such, the site represents a near seamless integration of all the components of pandemic informatics. it directly served the needs of independent diagnostic efforts by providing access to quality humanitarian data; it performed a coordinating function by establishing standards and expectations for the use and production of humanitarian data, and visualizations and graphics created by the community were incorporated into the hdx gallery for download and use in independent risk communication efforts. here, we see convergence between digitally enabled coordination efforts, deeply rooted in multilateral humanitarian institutions, and the diagnostic processes that they enable. unlike the examples above, the question of who engages with the hdx and how is not significantly pre-determined. the platform is designed to be open, and to the extent that contributors are invited and approved by ocha, it is reasonable to expect that it is open to national authorities. to the extent that technological capacity still limits national authorities from engaging with the platform, convergence of diagnostic and coordination activities nonetheless consolidates what we can call informatic discretion outside their spheres of influence. what is striking about these examples is not necessarily the fact that activities related to different informatic components interact; that has to some degree perhaps always been the case. what is striking is the degree to which they do so automatically, as conditioned by digital media, and within the purview of the actor driving the technological and informatic innovation. this is almost never national authorities, due to capacity issues described above. to the extent that reliance on technology and the introduction of novel actors drive informatic discretion beyond the influence of national authorities, this phenomenon is likely to be exacerbated by instances of technological and operational convergence. this analysis has reviewed the ways in which digital technologies have been deployed in humanitarian pandemic response, and proposed a three-part conceptual model for assessing these informatics according to the objectives that are pursued. doing so revealed two consistent and interrelated consequences: -the influx of novel actors from both affected populations and from the international register engenders novel fora for asserting knowledge politics, influence, and informatic discretion in response. these fora support the increased engagement of novel actors, but are often inaccessible to national authorities due to limits on technical capacity and political position. -the efficiency of technologically driven informatics tends towards technological and operational convergence, in which multiple types of activities are collapsed into single platforms or institutional processes. convergence has the effect of further consolidating sites for informatic discretion beyond the influence of national authorities. these two dynamics are concomitant and mutually reinforcing. each is directly enabled by the introduction of novel technological tools and strategies to pandemic response, but also facilitates the other (novel actors tend to be the ones who actually combine informatics functionalities, often without warning and through their own innovations), and complicates traditional pandemic response informatics in mutually reinforcing ways. it is tempting to anticipate a certain momentum at play. it is also tempting to frame this as a coordination problem. novel actors and models for participation strain the humanitarian system precisely because humanitarian roles and responsibilities are rigidly defined, but not immutable. the dynamics of convergence would, moreover, seem to promise significant increases for efficiency and coordination were obstacles to information sharing surmounted, and gaps in institutional cultures for using technology filled. but herein lies the challenge. though technology seems consistently to imply dramatic gains in humanitarian efficiency, it consistently frustrates efficient coordination, and despite millions of dollars spent, in the case of multi-lateral, large-scale coordination efforts around information, there have only been several very public failures (tapia et al. : ) . this is likely because the challenge manifest in these informatics is more fundamental, having to do with the ways in which institutions and organizations leverage technologies to assert knowledge politics "in ways that rely upon the differential influence and authority that is granted to particular forms of knowledge or representations" (barnett ) . without addressing the differential capacities and expertise that drive a propagation of knowledge politics beyond national authorities' spheres of influence, coordination exercises are unlikely to be anything more than exercises. in this scenario, a humanitarian technological context marked by exuberant expectations and a chaotic lack of coordination is problematic. more troubling is the underlying recession of national authorities from those fora in which knowledge and influence are asserted and contested. the tendency of international humanitarian response to sideline national authorities is not new. the possible exacerbation of this dynamic by new response informatics is, however, particularly problematic because the enthusiasm surrounding novel technologies so efficiently occludes the challenges that they pose to fundamental coordination norms of humanitarian coordination. there is wide agreement that international humanitarian intervention should complement and support national authorities' response as a temporary measure until the point at which national authorities are able to assume control over national processes, facilities, and infrastructure (jahre and jensen ; harvey and harmer ; ocha inter-agency standing committee ). the details of this relationship prompt arduous contention and debate in the context of traditional humanitarian coordination mechanisms, such as the un cluster system (harvard humanitarian initiative ; sandvik et al. ; mcdonald ) , and to a modest degree, in critical commentary on the application of humanitarian technology (sandvik et al. ). until they are equally visible in the discourses and planning processes that drive remote volunteering, university hackathons, mobile network-enabled contact tracing, and participatory mapping efforts, it is hard to imagine ways in which to reassert the agency and influence of national authorities in new response informatics. so what is next? there are at least three opportunities to begin addressing this. firstly, the degree to which digitally driven informatics exacerbate challenges to the agency of national authorities in the context of humanitarian coordination should be explicitly included in critical discourses that resist techno-optimism in the humanitarian sector. this involves expanding notions of responsible humanitarian technology, innovation and data-use to include reflections on how digital informatics impact the spheres of influence of national authorities in humanitarian response. it constitutes an additional type of risk to be considered when questioning the risks associated with humanitarian experimentation (harvey and harmer ) . secondly, established mechanisms for coordinating complementary and supplementary humanitarian support to national authorities in humanitarian response, including the un cluster system, should deliberately anticipate these dynamics and work to mitigate their effects. significant work is ongoing to improve the ways in which national and international actors interact in humanitarian response (unga ; oecd ; jahre and jensen ; odugleh-kolev ) . the policies and procedures that result from these efforts should include explicit processes for accommodating the types of novel actors, platforms and instances of convergence described above. explicitly identifying roles and sites for interaction with national authorities would have the twin benefit of providing entry points for those actors according to established coordination norms, and providing opportunities for technical capacity development to national authorities. lastly, prominent humanitarian coordination bodies that have significant experience using digital communication technologies and interacting with the novel actors they introduce, should facilitate structured interaction between these actors and representatives of national authorities, in an effort to identify good practices for reinforcing national agency in digitally-driven informatics. taken to their logical conclusion, relatively low-cost investments in events and joint trainings by organizations such as ocha, could easily lead to the production of credible and welcome guidelines for novel actors at the top of the informatics sandwich, which include an explicit role for national authorities, protecting their agency and influence in the design and implementation of response. this agency matters. a clear and meaningful role for national authorities is worth safeguarding in order to ensure efficient and appropriate response (unga ; oecd ; jahre and jensen ; odugleh-kolev ) , but also because it is essential for securing the sustainability and long term impact of health outcomes in the wake of pandemic response (odugleh-kolev ; (dubois et al. ). the conceptual model and critical analysis proposed here provide a preliminary lens with which to purse those ends. lessons from the pandemic: the need for new tools for risk and outbreak communication. emerg health threats j : ebola outbreak. communication: challenges and good practices the oxfam ebola response in liberia and an evaluation report for the disasters effectiveness of mechanisms and models of coordination between organizations, agencies and bodies providing or financing health services in humanitarian crises: a systematic review questioning security devices: performativity, resistance digital surveillance for enhanced detection and response to outbreaks the reliability of tweets as a supplementary method of seasonal influenza surveillance the empire of humanity : a history of humanitarianism using mobile phone data to predict the spatial spread of cholera remotely measuring populations during a crisis by overlaying two data sources comparative study on inter-organizational cooperation in disaster situations and impact on humanitarian aid operations digital disease detection-harnessing the web for public health surveillance a framework for designing a global information network for multinational humanitarian assistance/disaster relief an authority for crisis coordination and accountability moments of closure in the knowledge politics of digital humanitarianism rethinking big data in digital humanitarianism: practices, epistemologies, and social relations creating bottom-up tech tools to fight ebola social and news media enable estimation of epidemiological patterns early in the haitian cholera outbreak technology innovation and big data for humanitarian operations risk communication, the west nile virus epidemic, and bioterrorism: responding to the communication challenges posed by the intentional or unintentional release of a pathogen in an urban setting according to need?: needs assessment and decision-making in the humanitarian sector analysing volunteer engagement in humanitarian mapping: building contributor communities at large scale the ebola response in west africa: exposing the politics and culture of international aid tweenome on film: excellent video on crowdsourcing killer outbreaks geographic information science: emerging research on the societal implications of the geospatial web subculture-centered public health communication: a social media strategy fighting ebola with information: learning from the use of data and information flows in the west africa ebola response. united states agency for international development humanitarianism in the age of cyber-warfare: towards the principled and humanitarian emergencies a new source of data for public health surveillance: facebook likes data science for a better world gorp afv ( ) integration of volunteer and technical communities into the humanitarian aid sector: barriers to collaboration governing ebola: between global health and medical humanitarianism disaster relief . : the future of information sharing in humanitarian emergencies international dialogue on strengthening partnership in disaster response : bridging national and international support: challenges for national authorities the medical detective : john snow and the mystery of cholera digital technology for health sector governance in low and middle income countries: a scoping review contact tracing and epidemics control in social networks digital dialogue: crisis communication in social media coordination in humanitarian logistics through clusters promise and practice : participatory evaluation of humanitarian assistance a repertoire approach to cross-platform media use behavior humanitarian knowledge management summary about social media research in disaster/emergency response systems the law, politics and ethics of cell phone data analytics ) mhealth compendium. united states agency for international development issue-oriented hackathons as material participation gis support for the msf ebola response in guinea the appearance of accountability: communication technologies and power asymmetries in humanitarian aid and disaster recovery mediated health: sociotechnical practices of providing and using online health information targeting and distribution in complex emergencies: participatory management of humanitarian food assistance ebola: a big data disaster -privacy, property, and the law of disaster experimentation new information technologies and their impact on the humanitarian sector lessons: west africa ebola disaster forensics: leveraging crisis information systems for social science how the tech sector can help stop ebola accessed may ocha inter-agency standing committee iasc reference module for cluster coordination at the country level. office of the high commissioner for humanitarian assistance what will it take to move risk communication into the twenty-first century? the paris declaration on aid effectiveness and the accra agenda for action models, solutions and enabling technologies in humanitarian logistics the emergence of risk communication studies: social and political context introduction: situating health and the public in africa. historical and anthropological perspectives mac ginty r ( ) data hubris? humanitarian information systems and the mirage of technology the neo-humanitarians: assessing the credibility of organized volunteer crisis mappers catching the flu: syndromic surveillance, algorithmic governmentality and global health security building global bridges: coordination bodies for improved information sharing among humanitarian relief agencies introduction of mobile health tools to support ebola surveillance and contact tracing in guinea evaluating ebola: the politics of the military response narrative do no harm: a taxonomy of the challenges of humanitarian experimentation humanitarian technology: a critical research agenda hacking ebola re)building health systems in west africa: what role for ict and mobile technologies? making humanitarian relief networks more effective: operational coordination, trust and sense making coordinating humanitarian information the use of mobile phone data for the estimation of the travel patterns and imported plasmodium falciparum rates among zanzibar residents reflections on the ebola crisis: health worker perspectives information systems innovation in the humanitarian sector use of technology in the ebola response in west africa humanitarian information management and systems theoretical divides and convergence in global health communication. obregon/the handb glob heal commun using mobile technology to improve maternal health and fight ebola: a case study of mobile innovation in nigeria the viral storm: the dawn of a new pandemic age. allen lane zuckerman e ( ) new media, new civics? governing big data authors' contributions cw contributed to the design of this research, desk review, and writing of the manuscript. mgj contributed to the design of this research, desk review, and writing of the manuscript. both authors read and approved the final manuscript. the authors declare that they have no competing interests. key: cord- -tt p uue authors: xue, lan; zeng, guang title: global strategies and response measures to the influenza a (h n ) pandemic date: - - journal: a comprehensive evaluation on emergency response in china doi: . / - - - - _ sha: doc_id: cord_uid: tt p uue as an infectious respiratory disease, influenza is prone to cause pandemics for its fast mutation, easy dissemination, susceptibility to humans, and its elusive nature in terms of treatment. three influenza pandemics occurred in the th century which caused huge losses worldwide. analysis by the who, after the global peak in the winter of , there were no signs of any further widespread dissemination of the virus, thus proving the end of the influenza pandemic. nevertheless, the organization warned that entering the post-pandemic period didn't mean the influenza a virus would disappear completely, as epidemic outbreaks were still likely to occur in some regions. additionally possibilities of virus variation were evident and so countries were advised to be on alert during this time. in response to the threat of a global influenza pandemic, the who as per the international health regulations (ihr ) , put a large amount of work into global prevention and control efforts, and also adjusted prevention and control strategy priorities to fall in line with this global influenza outbreak. countries worldwide have been proactive in their responses to the who's strategies and recommendations. in order to tackle possible influenza pandemics and minimize losses, in the who published its official guidance, the influenza pandemic plan: the role of the who and guidelines for national and regional planning, which was then later revised in and , respectively. in the revised who global influenza preparedness plan, an influenza pandemic was divided into six different phases: phases - are interpandemic, i.e., no new influenza viruses have been detected in humans but an influenza virus subtype is circulating among animals and could potentially pose a threat to humans; phases - consist of the pandemic alert phases where a new influenza virus has been detected in humans but its spread among humans remains limited; phase is the warning phase, declaring that the new influenza virus has spread widely across human populations. in its revision of the pandemic influenza preparedness and response, the who retained the use of a six-phase approach, but made some changes to the criteria. phases - are characterized by the transmission of an influenza virus among animals and few humans, and correlate with preparedness, including capacity building and response planning activities. phase is characterized by sustained human-to-human transmission of an influenza virus, while in phases - the virus becomes widespread and prevalent among humans. phases - clearly signal the need for response, prevention, and control measures. during the post-peak period, pandemic activity drops, but there are still possibilities of recurrent outbreaks, before levels finally return to those seen in seasonal influenza periods. these plans from the who were made mainly based on the threat levels from the highly pathogenic avian influenza (h n ), which are much different from the threats posed by influenza a (h n ) in , and which are not likely to be the same as future influenza threat levels. these documents have nevertheless played a crucial role in pandemic response efforts and have provided some basic guidance that can be utilized in the outbreak of any infectious disease. the pandemic influenza preparedness and response also summarized the lessons learned from coping with sars and the highly pathogenic avian influenza, which will be a great asset in responding to future outbreaks of infectious diseases. on may nd, , the who published its first ever list of countries and laboratories with the capacity to perform pcr (polymerase chain reaction) testing used to diagnose the influenza a (h n ) virus in humans, which was updated and re-published on may th, . the who's criteria for diagnostic capabilities are: "scoring % in the last two or more who external quality assurance programme panels (eqap) received by the laboratory; or scoring % in the last panel and having a history of consistent results for earlier panels." on the list published were institutions in countries which were able to perform pcr to diagnose the influenza a (h n ) virus in humans. in response to the outbreak and spread of influenza a, in the initial stages of the pandemic, the who began working on various alert and preparedness plans. on april th, , the who held an emergency meeting, swiftly determining the severity of the pandemic situation and announced that it constituted a public health emergency of international concern. on the evening of april th, , the who raised the influenza pandemic alert level from phase to phase , and again to phase on the evening of april th. level was raised to phase , the highest level the who has declared in the past years-signalling the onset of a global influenza pandemic. on august th, , based on its global assessment, the who removed the phase alert level and announced that the world was moving into the post-pandemic period. while adjusting pandemic alert levels, the who proposed that countries stay flexible in tailoring their specific response measures to their local epidemic situations, and warned that influenza a (h n ), as highly infectious as it is, would continue to do harm in the infected countries and could potentially spread to more countries. as the virus continued to spread in the southern hemisphere, which was at that time entering winter, the risk of its combination and mutation with other local epidemic influenza viruses increased, and so the international community was still required to closely monitor the situation. in the early days of the pandemic, the who's influenza pandemic assessment team published its assessment results on may th, , in which a comparison was made with the and pandemics. the assessment came to the following conclusions: this was a new subtype of the influenza a virus; the influenza a (h n ) virus was likely to become more contagious than seasonable influenza viruses; differences in clinical symptoms were related to the patient's overall health situation; young people were more susceptible to the virus; the mortality rate was expected to be far lower than the pandemic; and there were still many uncertainties surrounding the pandemic. after the pandemic tapered off, on april th, the international health regulations review committee held its first meeting in geneva to assess the global response and the functioning of the ihr in relation to the pandemic, as well as to summarize related experiences and lessons learned. the assessment work is still under way and completion is expected in may . in addition to its preparation and alert efforts, the who also strengthened pandemic monitoring and introduced a series of strategies and measures relating to pandemic response, treatment, vaccine development, inoculation, and distribution. director-general's opening statement at virtual press conference. h n in post-pandemic period. beginning on april th, , when it first published information on the outbreak of human swine influenza in the u.s. and mexico, the who continually released pandemic and epidemiological information to the globe with the intention of facilitating international communication and sharing. from april th through july th, , during the early days of the pandemic, every day or every other day, the who published new laboratory-confirmed cases and deaths in affected countries, and at the same time it closely tracked the global transmission of influenza a (h n ). as the pandemic developed, who experts considered that as far as pandemic risk monitoring and response strategies were concerned, continued laboratory virus testing to all patients was no longer necessary, as it could overburden laboratories and thus influence their capacity in caring for critically ill patients and other unusual circumstances. on july th, , the who announced that countries affected by the epidemic were no longer required to report new confirmed cases, and recommended that attention be placed on monitoring influenza viruses and unusual epidemic events. but countries where influenza a was not present still needed to report cases as they were discovered. after april , although the increasing rates of the fatality were on the decline and the pandemic activity remained relatively low, the who continued the monitoring of the pandemic and remained in close contact with public health experts in countries across the globe in order to determine whether the virus activity had returned to levels and patterns normally seen for seasonal influenza. global pandemic activity had remained low over the past few months, and there was little evidence of higher pandemic influenza activity than what was normally caused by the seasonal influenza. the transmission of the influenza a virus still persisted in the southern hemisphere, but it was still impossible to determine if countries there had transitioned to levels and patterns expected for seasonal influenza. therefore, the who continued conducting epidemiological monitoring of the global pandemic situation and reported on relevant information. zhang ( after the outbreak of influenza a (h n ), the who consulted related pharmaceutical manufacturers about developing vaccines, encouraging worldwide support of influenza a (h n ) vaccination production. the organization also collaborated with drug authorities in related countries ensuring that newly developed influenza a vaccines met as many safety standards as possible. meanwhile, the organization helped china in efficiently obtaining live strains of the influenza a (h n ) virus, which accelerated the country's research and development of relevant vaccines and drugs. while ensuring an adequate amount of seasonal influenza vaccines were available, the who also initiated research and development for influenza a (h n ) vaccinations in the early stages of the pandemic. given that global limited production capacity for antiviral drugs and influenza vaccines could never meet the healthcare needs of . billion people, the who recommended governments to have clear and targeted prevention and control measures to avoid waste of resources. on july nd, , a meeting of the world's health ministers was held in mexico to assess the influenza pandemic and discuss countermeasures and inoculation distribution. at the meeting, who director-general margaret chan called for international collaboration and solidarity, while stressing that special attention must be paid to high-risk groups like pregnant women and patients with chronic diseases. the who also called on vaccine manufacturers to provide them a certain amount of free vaccines so as to help developing countries better cope with their epidemics. in response to the ongoing global pandemic, the who stressed the importance for countries to carry out inoculations and to set forth three goals for their vaccination strategies, i.e. ensuring the normal operation of national healthcare systems, lowering morbidity and mortality, and minimizing possibilities of community-level outbreaks. to ensure continued normal operations of healthcare systems, the who recommended medical workers first be vaccinated, then pregnant women, patients aged six months and older with such chronic illnesses like asthma and obesity, healthy people aged - , healthy children, healthy people aged - , and people aged and older-in that exact order. the who also urged pharmaceutical manufacturers to produce vaccines at full capacity, to ensure fair distribution among developed and developing countries. countries such as china, italy, france, the united states, germany, the united kingdom, norway, sweden, finland, australia, and japan took steps to vaccinate domestic residents, based on their own epidemic situations, healthcare resources, and ability to acquire vaccines. some of the countries placed orders for more vaccines in order to cope with potential outbreaks. , response strategies varied widely across countries (see a detailed description in the next section) because each was faced with outbreaks and developments with different characteristics, in addition to political, economic, and cultural dissimilarities, especially in their public health systems which varied in both management and operation. while developed countries already had fairly effective response measures in place thanks to their advanced economic and social development as well as robust healthcare systems, some developing countries with poor economic foundations and weak public healthcare had a much harder time dealing with public emergencies. therefore, they had an even harder time in dealing with influenza a (h n ). after the pandemic broke out, countries showed varied responses to the who's recommended response strategies and measures; in particular developing countries that had greater reliance on these strategies and measures as well as technical assistance from the who, were much more proactive. there is no doubt that the who played a crucial role in helping countries worldwide-especially developing ones-in coping with the pandemic, whether it is pandemic monitoring, clinical diagnosis and treatment of the virus, or vaccine development and distribution. however, because this pandemic originated in north american countries, taking into account the political, economic and cultural differences between countries as well as their different response capabilities, the who was also faced with new challenges like how to provide tailored guidance to developed and developing countries. the purpose of this guidance was to increase the effectiveness of related strategies and measures, mitigate and contain the spread of the pandemic, and minimize the negative effects of the virus on society and populations. such targeted guidance was not particularly prevalent in their guidance regarding response strategies and measures as the requirements placed on developed countries were quite low, resulting in an overall devaluation of said proposed strategies and measures. therefore, when confronting similar public health emergencies in the future, the who should present more pertinent strategies and tailored measures which could play greater roles in pandemic preparation and response. the outbreak in late april of influenza a (h n ) in several north american countries quickly attracted attention in related countries. responding promptly to the crisis, government agencies and related departments in multiple countries immediately initiated public health emergency mechanisms and put into action a wide range of prevention and control strategies and measures. considering the serious economic, social, and public health consequences that could happen due to the outbreak, coping with the pandemic would demand participation, coordinated preparation, and enhanced collaboration from governments and different departments. some countries specifically established unified leadership bodies and related mechanisms to deal with the pandemic, while others did so through existing government bodies or departments. for example, countries like the united kingdom, india, japan, and mexico set up a special coordination and management mechanism, and established an emergency decision-making, command and coordination body which was directed by the heads of government with the guidance and participation of relevant agencies. the british government specifically established a ministerial committee consisting of related government departments to strengthen inter-departmental communication and coordination and ensure the formulation and execution of preparation and response policies. the indian ministry of health and family welfare established the inter-ministerial task force and joint monitoring group for ai/pandemic to direct and coordinate the national response to the pandemic. france's public health emergency mechanism was run by the "inter-ministerial risk group" with dr. shashi khare. pandemic influenza a h n : preparedness & response in india. cdc new delhi. http:// . . . /linkfiles/rce_day _h n _india-dr_shashi_khare.pps. the responsibility of decision making, situational tracking, and publicity, and the minister of the interior acted as the lead and was responsible for approving and initiating such decisions. japan established the new influenza response headquarters directed by the prime minister, and transformed the risk management center's information liaison office under the prime minister's official residence into the official residence's liaison office for directing and coordinating national pandemic response efforts. mexico, whom in the past responded to public health emergencies mainly through direct government interventions and temporary emergency groups, established the national committee for health security (cnhs) for analyzing, monitoring, and assessing the security issues of national health policies and for proposing relevant policies. the united states, australia and some other countries didn't specifically establish a governing body in response to the pandemic. after its incorporation in into the united states department of homeland security (dhs), the federal emergency management agency's (fema's) responsibilities were expanded from natural disaster response to counter terrorism and pandemic diseases. the fema director, appointed by the president, reports directly to the secretary of homeland security and may, in response to a crisis, be summoned by the president to attend ministerial-level meetings and take part in the decision-making process. after the influenza pandemic outbreak in , the united states launched its standard emergency response procedures, which included close collaboration and coordination among the federal, state and local governments along with the private sector. the u.s. congress was charged mainly with funding public health efforts at the federal, state, and local levels, while it was the responsibility of the federal government to update response plans, strengthen the development and revision of community-based plans, and enhance response capabilities. the dhs oversaw the distribution of antiviral medications and the dissemination of pandemic information to the public. the u.s. department of health and human services (hhs), the executive body of pandemic preparation and response, was in charge of deploying, directing, and overseeing various response efforts, and they also completed the following: issued guidance on the influenza pandemic, provided technical, financial, and medical support to states, and based on pandemic analysis announced a national state of emergency. as the national public health institute under the hhs, the center for disease control and prevention (cdc) played a crucial role in virus monitoring, prevention, and control. similarly, australia established a mechanism in which an inter-agency committee under the leadership of the prime minister and the cabinet was in charge of determining the federal government's preparation and weissman ( . national and regional response strategies and measures response strategies as well as pandemic countermeasures, with state governments making and implementing relevant policies under the guidance of the federal government. whether or not a governing body was established for management of the pandemic, countries worldwide attached great importance to collaboration among government institutes and departments. for example, interim pandemic assessment reports by u.s. departments all mentioned that the timely response to, and rapid progress made in coping with the influenza pandemic, were due in large part to the clear divisions of labor and close collaboration among federal government institutes, departments, and state, and local governments. , the indian government also stressed that pandemic responsibilities did not fall solely on the health department, and that it was necessary for multiple departments to collaborate with one another; the following departments of india were involved in pandemic preparation and response: the ministry of finance which provided cash, budgets, risk management, and insurance; the ministry of commerce and industry which provided medical equipment; the ministry of road transport and highways which was charged with handling relevant transportation and communication issues; the ministry of defense and related military departments which was charged with public services, laws and regulations, security, and human rights; the ministry of information and broadcasting which guaranteed the transparency of strategic communication, the dissemination of information, etc.; the ministry of environment and forests and the ministry of health and family welfare which ensured biosafety, sanitation, wildlife conservation, etc. to effectively curb the transmission of the pandemic and its negative effects on society, many countries formulated a national strategy or plan against possible influenza outbreaks from - , outlining the duties and division of labor among government departments as well as their preparation and response strategies. their policies on influenza a (h n ) were generally built on these strategies. in , pursuant to the pandemic preparedness guidance published by the who, the united states developed the hhs pandemic influenza plan and the national strategy for pandemic influenza, according to which preparation and response strategies and measures would be chosen based upon phases that measured the pandemic's development. included in the documents are detailed provisions about the duties along with preparation and response strategies of related government departments and mechanisms, i.e.: inter-departmental collaboration, council of australian governments/working group on australian influenza pandemic prevention and preparedness. national action plan for human influenza pandemic. . sebellus ( a) . sebellus ( b). public risk communication, vaccine production and distribution, and the stockpiling of antiviral medications. in accordance with the who pandemic preparedness guidance, the united kingdom published their influenza pandemic contingency plan in , and their national framework for responding to an influenza pandemic in , which stipulated that strategies and measures for both preparation and response would be selected based upon pandemic phases. in , australia formulated the australian heath management plan for pandemic influenza and later revised it in , and it remains as the country's national-level health plan for an influenza pandemic. india formulated the influenza pandemic preparedness and response plan in , which was used as a foundation for prevention and control policies against influenza a (h n ). in , the mexican government issued the national preparedness and response plan for pandemic influenza, on which the country's prevention and control policies against influenza a were built. on may th, , the japanese government swiftly issued the action plan for measures against influenza a (h n ) to curb its domestic transmission. this plan contained response measures formulated according to four phases of distinct pandemic phases, i.e. occurrence overseas, early occurrence at home, infection expansion-spread-recovery, and stabilization. for countries across the globe, central governments primarily provided the funds for prevention and control efforts against influenza a (h n ), and these funds were made available to related departments in the different pandemic phases. during the initial period and at the peak of the pandemic, these funds were mainly used for stockpiling antiviral drugs; purchasing relevant equipment, facilities, protective supplies and other materials; establishing points of distribution for antiviral drugs; providing patients with free antiviral drugs; and carrying out pandemic monitoring. during post-peak periods, funds were mainly utilized to purchase unified influenza a vaccines from manufacturers, which were then distributed to the public with no charge. some developed countries also specifically established foreign assistance funds that provided developing countries both monetary and material assistance in combatting the pandemic. the united states congress invested heavily in pandemic prevention and control. in , the congress provided an appropriation of more than seven billion u.s. dollars (usd) for implementing the pandemic preparedness strategy. on april th, , the u.s. president received another appropriation of . billion usd from congress which was specifically designated for combatting the swine flu. in july of that year, congress provided . billion usd to be used as funds for emergency resource deployment and an additional . billion usd for emergency preparation and response against the influenza pandemic. in september, the congress went on to make million usd available to states and hospitals for carrying out vaccination programs. meanwhile, the united states agency for international development (usaid) provided mexico with five million usd in emergency aid funds, , sets of personal protective equipment for virus monitoring personnel, and tamiflu for , courses of treatment. additionally, the hhs provided countries with laboratory diagnostic kits, and donated to the pan american health organization (paho) medications for , courses of treatment in aid of latin american and caribbean countries. in australia, funds for prevention and control against influenza a (h n ) originated mainly from the federal government, which was used specifically for monitoring pandemic development, stockpiling and distributing antiviral drugs, training medical personnel, providing free vaccinations for citizens, and assisting developing countries with prevention and control efforts. the federal government spent million usd on antiviral drugs, . million usd on the purchasing of automatic detection equipment for the national influenza center and other public health laboratories, million usd on training general practitioners across the country, and million usd on a donation to the who which was used in aiding developing countries, especially those neighboring australia, with pandemic monitoring, detection, preparation and response. in the united kingdom, funds for responding to influenza a (h n ) came mainly from the british government; by january th, , the department of health had dispensed to the nation . million doses of pandemrix, an influenza vaccine developed by glaxosmithkline, and , doses of a baxter-developed vaccines. the indian government established a one billion rupee disaster response fund in accordance with the disaster management act, which was administered by the ministry of home affairs, and this disaster fund accepted donations from individuals and organizations. in addition, a national disaster fund was specifically established to finance disaster relief and recovery efforts. state governments also william corr ( established disaster response funds and relief funds in accordance with the law at the state and regional levels. mexico invested a total of million usd in influenza a (h n ) preparation and response, including the purchasing of drugs and vaccines, and the adoption of other prevention and control efforts. declaring a state of emergency helped the hhs prepare for and respond to the influenza pandemic, and prompted the food and drug administration (fda) to issue emergency use authorizations (euas) for the use of antiviral drugs and therapeutic tools-i.e. they approved the use of relenza and tamiflu as stockpiled antiviral drugs for prevention and control of the virus, rt-pcr for virus detection, and n masks, which protected pandemic-affected communities. on april th, , in light of the who's pandemic alert phases and its national pandemic situation, singapore raised their alert level in its five-level disease warning system from green to yellow, and again to orange the next day. to prevent the influenza virus from spreading into and circulating within their territories, many countries adopted strict inspection and quarantine measures in the early days of the pandemic. baggage and raw meat products from epidemic affected areas-were strictly quarantined; many airlines required their service staff to observe and question passengers suspected of illness, and when necessary, have them examined. american border officials between the united states and mexico also were required to examine the physical condition of travelers crossing the border and be prepared to take necessary measures. additionally, citizens were asked to stop all unnecessary travel into epidemic areas. australia also implemented strict border control, requiring all flights from the americas to report the health status of passengers on board before landing; any individual with influenza-like symptoms had to be assessed by australian quarantine authorities in order to determine if further treatment was required; eight major airports across the country were equipped with body temperature measuring instruments, and every incoming passenger was required to complete a health declaration card. india adopted pandemic monitoring measures at airports, sea ports, and inland ports across the country; all incoming passengers to the twenty two international airports were screened, especially those from epidemic areas or with influenza symptoms, who were then quarantined and treated for at least three days. medical personnel were trained in advance, and were required to wear masks, gloves, and protective clothing at work. influenza a (h n ) inspection standards and operational rules were formulated and implemented national widely at that time. japan's ministry of health, labor and welfare required all flights from mexico, united states, and canada arriving at the narita, kansai and chūbu centrair international airports be inspected while aboard the plane. local airports not included on the list of airports for quarantine measures, for example in niigata, akita and hiroshima, also decided to follow suit and expanded the scope of quarantine to include flights from south korea, hong kong, and some other countries and regions. japanese border inspection and quarantine authorities screened people from mexico, the united states and had cargo strictly quarantined, especially baggage and raw meat products from epidemic areas. while applying strict control measures against the importation of the virus, in the early days of the pandemic countries also began strengthening preparation capacity building. for example, in the united states, during the initial stage of the outbreak, the hhs dispensed medication from the strategic national stockpile enough to treat three million people, the department of defense (dod) separately readied enough medication for seven million soldiers, and the cdc allocated antiviral drugs, protective equipment, and testing kits. at the same time, the hhs provided training for medical personnel with the goal of enhancing their abilities in treating and handling the pandemic. the german government required each state to stockpile enough antiviral drugs to use for % of their populations. south korea increased budget spending so that by the end of october the country's had enough drugs stored for % of its population. in an effort to mitigate the spread of the virus, the indian government designated specific hospitals to treat influenza a (h n ) cases. to increase public awareness of the pandemic, countries developed large scale health education and communication projects. the u.s. cdc provided health recommendations to society, communities, clinical workers and other professionals, and launched an online live-broadcast health education program, "know what to do about the flu," to help strengthen the public's abilities in protecting themselves against the virus. the united kingdom updated pandemic situations and work priorities on a regular basis via an official government website, and provided technical support relating to virus prevention and treatment. india published a "public notice' through national media channels with the aim of disseminating knowledge and increasing public awareness of influenza a (h n ) prevention and control. the government also set up a toll-free service hotline to answer questions about the influenza pandemic. in japan, an information, education and communication campaign was launched targeting high-risk groups of people arriving at and departing from the country's international airports, and the ministry of health, labour and welfare opened an information window to answer questions from the public. as the pandemic developed and more cases emerged, it was found that the majority of cases were coming from local communities instead of from abroad. at this point in time, the continued use of containment strategies had been ineffective, and medical personnel were having to dedicate more time and energy to the increasing number of patients. according to the national response framework, the hhs in the united states needed to stockpile enough antiviral drugs for one-fourth of the country's population during the pandemic, and to prepare at least six million treatment courses during the pandemic's initial phase. in the spring of , the hhs allocated eleven million treatment courses that could be used for rapid response against the pandemic. the cdc and the fda also worked together to address potential options for treatment of severely hospitalized patients. in october, the hhs shipped an additional , bottles of the antiviral oseltamivir in oral suspension formula to anna schuchat ( a). . national and regional response strategies and measures states in order to mitigate a predicted national shortage. the fda worked closely with the cdc, the office of the assistant secretary for preparedness and response (aspr), manufacturers, and others to increase production and availability of personal protective equipment such as gloves, masks, and respirators. at the same time, the influenza (h n ) consumer protection team, established by the fda, put in place an aggressive strategy to combat fraudulent influenza products. the british secretary of state for health declared on july nd, , that the united kingdom's response efforts were transitioning from a "containment phase" to a "treatment phase." in order to cure patients more efficiently, the british government created a national stockpile by the purchasing of more antiviral drugs, and drug distribution centers were also established across the country, with the national health service (nhs) playing a leading role in treatment provisions. to relieve pressure on medical institutions, on july rd, , the british government launched the national pandemic flu service (npfs). the npfs was a self-help healthcare system which, through a dedicated website and call centers, provided people worried about flu-like symptoms with professional assessment services, including the suggestions on whether they should receive treatment or contact a general practitioner, etc. a person, if assessed as indeed having influenza a (h n ) symptoms, would be given an authorization number by the system, which he or she could use to pick up antiviral drugs from one of local distributions centers. the launch of this system effectively mitigated the pressure on primary healthcare institutions and allowed general practitioners to dedicate their attention to critically ill patients. in order to quickly detect and treat critically ill patients, and also to ensure an adequate number of hospital beds as the number of cases increased, the japanese government readjusted its guidelines on pandemic response efforts, and discarded the practice of classifying regions according to rate of transmission in that area. according to the revised guidelines, regular hospitals received patients infected with influenza a (h n ); all mildly ill patients were instructed to medicate and rest at home, rather than being hospitalized. for patients with asthma or other illnesses whom had contracted influenza a (h n ) and whose conditions were likely to worsen, a pcr (polymerase chain reaction) test or other influenza a virus test was performed, and effective antiviral drugs were administered as early as possible. when necessary, decisions would be made to get them hospitalized. japan gradually used the confirmed cases reported from a certain number of hospitals as estimations and predictions for that area's infected population. australia used antiviral drugs from their national medical stockpile to treat moderately and critically ill patients, especially those with severe breathing difficulties or those whose conditions were rapidly worsening. all medical personnel, who contracted influenza a (h n ) and developed moderate symptoms of jesse goodman ( infection, or were more prone to develop serious symptoms, were eligible for antiviral treatment. patients with fairly mild symptoms were encouraged to self-medicate. india issued clinical management guidelines, where the indian committee on infectious diseases published guidance on the screening and clinical treatment of laboratory-diagnosed cases of influenza a (h n ); the ministry of health and family welfare issued guidelines on family isolation, clinical examinations, and hospitalization by categories of influenza a (h n ) cases-where categories a/b patients were asked to be isolated and reduce contact with their family and others and category c patients required immediate hospitalization. all suspected cases were tested at the national institute of communicable diseases (nicd) in new delhi, or at the national institute of virology in pune, and then examined further at relevant laboratories. india currently has forty four laboratories dedicated to the early management of controlling confirmed cases. given the dynamic nature of the pandemic, involving each and every citizen in its mitigation became a very important part of global response efforts. to contain the pandemic, mexico mobilized a large force of police officers and soldiers to execute the following: distribute masks among citizens for free, shut down public places, cancel or delay large-scale events, halt teaching activities in all schools-including universities, primary and secondary schools, and kindergartens -in mexico city and in the state of mexico. on april th, , the mexican government declared a suspension of all nonessential public affairs and economic activities from may st through may th. moreover, the mexican government also adopted a wide range of measures to strengthen pandemic information communication and sharing, i.e.: reporting pandemic developments via media channels, setting up hotlines, launching influenza prevention websites, giving out leaflets on pandemic information that called for personal hygiene and increased public awareness of the virus. in the united states, the hss launched a one-stop influenza information website (www.flu.gov), which gathered information from regular media briefings conducted by the hhs and other federal agencies, and provided the public with scientific and effective information services. in collaboration with federal, state, and local partners, the hhs also developed a wide range of community-based intervention guidelines which were being evaluated simultaneously. the cdc and the dhs provided specific recommendations targeted to a wide variety of groups, including the general public, people with certain underlying health conditions, infants, children, parents, john and moorthy ( ) . national and regional response strategies and measures pregnant women, seniors, health care workers, workers in relevant industries, laboratory workers, and homeless people. with these recommendations, people were equipped to take appropriate action in reducing the transmission of the virus, especially in early autumn before vaccines were widely disseminated. the cdc also provided, and updated on a regular basis, scientific guidance on influenza prevention and control to schools, daycares, universities, large and small businesses, and federal agencies. these comprehensive guidelines provided not only advice on how individuals and institutions could protect themselves against the virus and mitigate its spread, but also recommendations for healthcare providers about the appropriate use of anti-viral drugs, especially in treating patients who were at the highest risk of suffering complications from the influenza. , in japan, after the alert level transitioned from an "overseas pandemic" phase to the heightened "early onset of a domestic pandemic" phase, the local governments of osaka and hyōgo prefectures required the following for areas where infections had occurred: gatherings and collective recreational activities be suspended, entertainment venues be temporarily closed, social service workers be required to wear masks, teaching activities of varying levels at more than one thousand educational institutions be suspended for one week, citizens avoid trips and gatherings, and business activity be reduced for the time being. in australia, patients with mild symptoms were allowed to stay at home as a means of isolation. with the rapid spread of the pandemic, the united states didn't take stock in counting cases, but instead focused on the evolution process of the virus. the united states' advanced and unique monitoring system for bacteria and viruses uses dynamic and standardized methods to collect data related to virus occurrence, virus developments, and basic medical trends, and employs national demographic data to compute virus incidence and describe its epidemiological characteristics. this system brings together and facilitates cooperation within the cdc, state health authorities, academic partners, hospitals and infection control centers. moreover, it contains special research platforms, i.e., socio-economic evaluations of disease risk factors, effects of the disease and vaccinations, data on resources for vaccine research and development, and data on approved vaccines. in australia, laboratory testing focused on critically ill patients, high-risk groups with severe diseases, and personnel in relevant institutions. monitoring was also conducted to see if any resistance or mutations of the virus had occurred. understanding that vaccinations were the best means for combatting the virus, countries focused a large amount of resources on vaccination development and inoculation methods. in its influenza pandemic preparedness and response plan, the hhs in the united states set two objectives for vaccine preparation : to stockpile twenty million vaccinations for key personnel, and to increase manufacturing capacity to cover the population in the united states, in other words, produce million doses within six months of the pandemic outbreak. immediately following the outbreak, the national institute of allergy and infectious diseases (niaid) subordinate to the u.s. national institutes of health (nih) began its research on the virus and vaccination development. in july , the niaid initiated a series of clinical trials on the effectiveness of newly developed vaccines. in september, the fda approved manufacturing for four vaccination types, which were then made available for distribution among the states. the federal government then identified priority groups for vaccination and formulated an inoculation policy. starting on october th, a national influenza a (h n ) voluntary inoculation program begun targeting high-priority groups including pregnant women; people between the ages of months through years of age; people aged years or older with chronic health disorders like asthma, diabetes and heart disease; and healthcare and emergency services personnel. during the two months that followed, vaccine manufacturers provided - million vaccination doses each week, an amount which reached roughly million by the end of . , according to statistics, the federal government ordered a total of million doses of the vaccine with the plans of vaccinating million people, and in the end million people were actually inoculated. on october st, , the united kingdom launched its national influenza a (h n ) inoculation program. the first phase of the plan provided the vaccine to the high risk population of fourteen million people, including critically ill patients, pregnant women, and healthcare personnel working in hospitals. soon afterwards, general practitioners across the country began encouraging people with health disorders or immunity problems, and pregnant women to get vaccinated. on december th, , the british government went on to include children ages six months to five years old in the vaccination program. in august , australia approved a national vaccination program and began providing free vaccinations to healthcare workers, pregnant women, and individuals with chronic health disorders who were susceptible to the virus. on september th, the australian government announced that all adults and children aged ten years and older could also receive free vaccinations. in may , the mexican government announced an appropriation of . million usd for the establishment of a dedicated committee composed of authoritative medical experts, and this committee's mission was to mobilize and coordinate research efforts for carrying out etiological, epidemiological, diagnostic reagent and vaccine research relating to influenza a (h n ). it was also responsible for providing policy recommendations on pandemic prevention and control and medical treatment options to the government. in july japan began distributing permits authorizing the utilization of influenza a (h n ) vaccines, and they also launched a national vaccination program. the first groups to receive it included healthcare personnel, police officers, as well as high-risk groups like pregnant women, patients with chronic diseases, and seniors. as influenza a (h n ) cases gradually declined, some countries readjusted their pandemic response levels as well as their measures for virus prevention, control, and treatment. countries set about making summaries and conducting evaluations while continuing their pandemic monitoring and information sharing. in , most regions across the globe saw a decline in influenza a (h n ) activity, and though in some regions the virus still sustained its intensity (level), the overall virus transmission dropped. additionally, it was discovered in most cases that the influenza a virus only caused mild infections, and that its virulence had not increased since it was first reported in april . effective vaccinations had been in circulation since november . it was for these reasons that the singaporean ministry of health decided on february th, , to downgrade its alert level from yellow to green. beginning in february , the united kingdom deactivated the national pandemic flu service (npfs), an act done in line with ensuring the operational response was appropriate to the threat level posed by the virus and also because general practitioners and primary care trusts could now manage the clinical mexico sets up special committee for influenza a (h n ) research. xinhuanet.com, may , . http://news.xinhuanet.com/world/ caseload by themselves. anyone concerned about flu-like symptoms were advised to contact their doctor for assessment, who could then issue an antiviral authorization voucher if needed. the npfs would be reactivated should the pandemic virus regained its virulence. starting on april st, , free antiviral medication from the national stockpile was no longer available to patients with influenza a (h n ). normal treatments and prescription charges were reinstated for those suffering from influenza. in june , the united states declared the end of the public health emergency. as confirmed cases declined and the spread of the virus continued to slow, the u.s. federal, state, and local health authorities began to readjust their response strategies. in addition to continued efforts in strengthening public health education and inter-agency collaboration, other measures included bolstering the vaccination campaign, strengthening virus monitoring, and continuing focus on virus mutations. as the pandemic developed in the united states, especially after the wide distribution of vaccinations to the public, some u.s. agencies and institutions evaluated the results of a range of their prevention and control measures. the purpose of these evaluations were to identify problems that existed in the national pandemic response measures, and correct them to better the response in the future. (upmc's) center for biosecurity held a conference to summarize important lessons learned from pandemic responses and raised policy suggestions in mitigating future infectious disease emergencies. on may - th, , the cdc, the national association of county and city health officials (naccho), and other stakeholders met to review the federal, state and local policies that had an impact on local health departments' pandemic detection, response, and recovery efforts. while modernized health care systems, antiviral drugs and vaccines represented the advantages of global response efforts this time around, factors like globalization and urbanization allowed the fastest transmission of any pandemic ever witnessed. after outbreaks occurred in multiple countries, governments worldwide immediately adopted a wide variety of proactive containment measures. while there were many successful responses, shortcomings were also exposed which incited doubt and controversy surrounding the pandemic. in regards to prevention and control measures, governments in most of the affected countries did not look lightly upon the pandemic, and they played leading roles in policy making, resource collection and allocation, as well as organization and coordination. firstly, governments identified and allocated prevention and control organizations and accountability mechanisms at the national level. as mentioned before, some countries such as the united kingdom and india specifically established bodies for comprehensive coordination in response to the influenza pandemic, while others like the united states-where established emergency response agencies were already in existence-launched their emergency response efforts upon the outbreak of the pandemic. the u.s. government then oversaw an organized response from varying agencies. secondly, countries developed national-level pandemic strategies or response plans as general outlines for prevention and control efforts. thirdly, funds for response efforts in most cases originated from the central government, where the capital was then allocated to appropriate departments based upon their responsibilities. lastly, central governments were in charge of across-the-board organization and coordination in all aspects of the response efforts, especially in the provision of services, drug supplies, and vaccinations, while at the same time playing a crucial role in communication and coordination with other social service organizations, businesses, and the general public. in the course of global responses to the sudden outbreak of the influenza pandemic, the who made good use of its expertise and networking strengths. with a global approach, the organization disseminated information, pushed coordination, and strengthened guidelines. it played an important role in coordinating and guiding countries' efforts to raise awareness, develop technical guidance, release pandemic information, develop vaccines, etc. most countries possessed an influenza prevention and control system comprised of a variety of collaborative relationships, i.e.: partnerships between central, provincial (state), and local governments, the private sector, and individuals, as well as international partnerships established through bilateral or multilateral collaboration. each party within this system had its function and standard operating procedures, with the division of labor already institutionalized; and in implementing specific prevention and control measures, these parties were expected to fulfill their expectations and duties as stakeholders. each stakeholder understood their role to play during the preparation, prevention, and control of the pandemic, and no major changes occurred in that respect during the pandemic. at the same time, capacity building and positioning was constantly being improved according to the different functions of each party. in addition to inter-departmental coordination and collaboration, countries like the united states also called upon the public for participation and global collaboration, which expanded collaboration as it brought in community and societal involvement. during different phases of the pandemic, countries emphasized the integration of comprehensive measures and key response issues, and efforts were adjusted according to the development of the pandemic. in the early phases, prevention and control strategies were "strict," as they focused largely on containment with inspection and quarantine measures. cases diagnosed early were treated in a timely manner to better the odds of developing a successful vaccination. at the spreading period of the pandemic, the focus shifted to clinical treatment of patients, alongside strengthening virus monitoring. during the post-peak period, while some countries quickly revised alert levels which reduced social impact, others had no readjustment mechanisms for policy changes in place which resulted in inefficient prevention and control. during this time, most countries recognized the importance of international collaboration. firstly, faced with the grim situation of a pandemic gripping the globe, affected countries followed the who's pandemic strategies and recommendations. combining the domestic situation with who's proactive policies and recommendations, most countries adopted relevant response measures. however, there were many countries that didn't adopt all of the who's policies and recommendation, nor did they follow all of the policy readjustments. instead in light of their domestic situation, governments formulated their own response strategies and measures. secondly, relatively close collaboration between countries did occur. due to the many uncertainties surrounding the occurrence and development of the influenza a (h n ) pandemic, the level of "appropriateness" of response strategies -i.e. were they considered "lax" or "strict," "ineffective" or "overreacting"became a major controversial point surrounding the pandemic prevention and control policy. on the one hand, based on their own pandemic situations, their preparation evaluation, and cost-benefit analyses, developed countries such as the united states, canada, the united kingdom, and france, adopted policies that focused more on treatment than on control. the united states, for example, in the early days of the pandemic considered influenza a (h n ) no bigger a threat than the seasonal influenza, so the government failed to take strict response measures, like quarantine and medical observation, which resulted in a spike in domestic infections. on october rd, the united states declared a national health emergency, sparking questions about the government's response efforts. while some critics questioned whether there indeed existed such an emergency, others argued that a state of emergency should have been declared from the very beginning. an article published in the new york times in early january , gave full recognition to the country's response strategy, insisting that apart from luck, the federal government's appropriate, rapid, and conservative response successfully contained the virus and minimized potential harmful effects it could've had on the economy. on the other hand, some countries began with strict measures and relaxed them later on, causing difficulties in latent response efforts. for example, countries like mexico declared a state of high alert immediately upon the outbreak, leading to a certain extent, a public panic. but after the who elevated the pandemic alert phase, the mexican government rushed to lower its domestic alert level in order to ease public anxiety. thus the public became careless, causing the increased transmission rate. moreover, media in japan, france and other countries exaggerated pandemic situations that embellished "the widespread transmission" of the virus in home countries through imported cases. people became panic-stricken and it became increasingly difficult to implement proper response measures. japan and other countries failed in resource management as they placed too much emphasis on border control and quarantine, and not enough on domestic control and detection, thus making it difficult to contain the spread of the pandemic. these actions also led to widespread criticism of government response efforts. though the who's role in the global pandemic response efforts was widely recognized, the organization also suffered criticism as there were varied opinions about the timeliness of alert level changes and their investments in personnel and equipment. reuters reported on april th, , that the who admitted to having problems in their response efforts, including its failure to communicate the uncertainty of the new virus before it swept the globe. some critics held that from the perspective of pandemic development, the influenza a (h n ) pandemic was not as dreadful as it was initially anticipated, and it was the who that created a global panic in its response-which caused an excess in vaccination stockpiling among some countries. some even suspected that the ihr emergency committee might have had an "affair" with some drug manufacturers and was suspected of helping them seek profit by deliberately exaggerating pandemic situations so that the who would raise its pandemic alert to the highest level. in response, on april th, , the who commissioned a panel of external experts to conduct an overall evaluation of the global response to the influenza pandemic in the hope of providing lessons for the future, and simultaneously to assess the global implementation of the ihr . the who's policy evaluation comprised three main parts, i.e. capacity and preparedness, pandemic alert and risk assessment, and response. on june th, , the who officially responded to and clarified such issues as to the influenza a (h n ) virus met the criteria for a pandemic, the severity of the pandemic, and related conflicts of interest. central people's government of the people's republic of china. who experts warn global h n pandemic still not over yet. http://www.gov.cn/jrzg/ - / /content_ .htm. who. the international response to the influenza pandemic: who responds to the critics. http:// www.who.int/csr/disease/swineflu/notes/briefing_ /en/index.html. there are no international standards for vaccine allocation in mitigating the global burden of disease. while the united states began vaccinating its citizens in early october after the fda approved on september th the marketing of influenza a (h n ) vaccines produced by csl, medimmune, novartis vaccines and diagnostics, and sanofi pasteur, mexico, which had been suffering a severer pandemic situation, was unable to launch a vaccination program until january . building a powerful global vaccine production infrastructure for influenza pandemics where countries and regions in need could acquire adequate vaccines at affordable prices became one of the hot international topics at this time. the who stated that although antiviral drugs used at that time to combat influenza enjoyed complete patent protection, the organization proposed that these drugs be acquirable in the cases of public health crises. the use of antiviral drugs was hit heavily upon in the who's guidance documents, but, given cost issues, the use of such drugs and vaccines had little operability in most middle and low-income countries. moreover, some international media held that the outbreak in the united states brought to the forefront the many flaws in their healthcare system, most notably the use of old-fashioned vaccine technology and excessive reliance on vaccine manufacturers abroad. a highly controversial event also occurred during vaccination distribution: the new york city department of health and mental hygiene decided to give the small amount of vaccine available in the early phases of the pandemic to big corporations on wall street such as goldman sachs and citibank, an act which experts believe only exacerbated public relation issues. vaccine production and distribution became a controversial focal point during prevention and control of the pandemic as it involved multi-faceted issues such as vaccine patents, mass psychology, and social justice. h n preparedness: an overview of vaccine production and distribution u.s. global health response to a novel -h n hhs' effort to provide science-based pandemic influenza guidance for the u.s. workforce lessons from previous influenza pandemics and from the mexican response to the current influenza pandemic h n preparedness: an overview of vaccine production and distribution pandemic influenza in india who director-general margaret chan says international community cannot afford to take influenza a (h n ) pandemic lightly preparing for the - influenza season h n influenza: monitoring the nation's response protecting the protectors: an assessment of front-line federal workers in response to the -h n influenza outbreak global surveillance during an influenza pandemic. version , updated draft assessing the severity of an influenza pandemic -h n influenza: hhs preparedness and response efforts characteristics of the india's public health emergency management system: from a perspective of influenza a (n h ) preparedness and response. global science, technology and economy outlook influenza a pandemic moves into a new phase, who changes way of epidemic reporting key: cord- - j fl authors: afolabi, michael olusegun title: pandemic influenza: a comparative ethical approach date: - - journal: public health disasters: a global ethical framework doi: . / - - - - _ sha: doc_id: cord_uid: j fl community-networks such as families and schools may foster and propagate some types of public health disasters. for such disasters, a communitarian-oriented ethical lens offers useful perspectives into the underlying relational nexus that favors the spread of infection. this chapter compares two traditional bioethical lenses—the communitarian and care ethics framework—vis-à-vis their capacities to engage the moral quandaries elicited by pandemic influenza. it argues that these quandaries preclude the analytical lens of ethical prisms that are individual-oriented but warrant a people-oriented approach. adopting this dual approach offers both a contrastive and a complementary way of rethinking the underlying socioethical tensions elicited by pandemic influenza in particular and other public health disasters generally. contemporary healthcare constitutes an instinctual and institutional response to the multifaceted cycles of health, illness, and disease. hence, the problems of diseases including infectious ones affect all and sundry irrespective of current "sick status". pandemic influenza is one such incident that afflicts all sectors of the society. it also raises questions and issues related to utility and equity, ensuring the protection of vulnerable individuals and groups in society, the need to exercise public health powers with respect for human rights as well as the just allocation of human and material resources. attending to these issues, however, juggles many kinds of personal, social, political, and professional interests against one another; thus, reflecting the traditional public health dilemma of fine-tuning individual against collective good. since the restrictive approach of individualism-driven moral lenses is unsuitable for people-centered quandaries, it seems pertinent to employ a people-centric moral lens to engage them. in this vein, the ethical prism of communitarianism and ethics of care seem apt. by examining and contrasting the core fabric of the communitarian and care ethics frameworks vis-à-vis the attendant dilemmas of pandemic influenza; this chapter attempts to tease out a broader ethical path towards engaging the challenges of pandemic influenza. to properly set the conceptual foreground essential to articulating the ethical features of pandemic influenza, however, it is important to elaborate the associated biological, social, and global dynamics. these parameters, as macphail recently argues, are exigent in the explication and engagement of pandemic or infectious disease outbreaks. there have been some speculations as to the origins of the influenza virus. it has been hypothesized that the virus originated from wild waterfowls and has only slowly evolved through multiple animal species including humans. but what is known about the disease caused by the virus-influenza-is that it is a febrile illness of the upper and lower respiratory tract, characterized by a sudden onset of fever, cough, myalgia, and malaise. pneumonia is a principal serious complication and local symptoms include sniffles, nasal discharge, dry cough, and sore throat. pandemic influenza outbreaks describe the rapid spread of influenza infection. whereas there is some conceptual controversy about the description and definition of pandemics, they generally refer to the dissemination of new infective diseases to which immunity has not been developed in a widespread manner across a significant part of the world. they could break out in nations with a large geographical size (such as china, india, and the united states) or when the number of affected nations are many. the pandemic nature of influenza is historically underscored by the - incident that killed an estimated million to million people. pandemic influenza is generally characterized by an alteration in the viral subtype (due to antigenic shift), higher mortality rates among younger groups, several waves of the particular pandemic, increased capacity of spread, and geographic variation in the impact of the outbreak. specifically, influenza pandemics occur when an influenza virus mutates or when multiple strains combine, or re-assort to produce strains to which there is no current immunity. novel outbreaks of the influenza virus occur either in large nations or across selected nations in close proximity. contemporary society experiences an increased development of new serotypes of several kinds of respiratory viruses because of the evolutionary potential afforded by the human population explosion and the great global increase in human mobility. in a manner of speaking, it seems that phds such as pandemic influenza outbreaks have evolved to become recurring features of the human experience. some insights into the biological features and processes that create pandemic outbreaks support this idea. influenza viruses belong to the orthomyxoviruses family. this comprises seven genera including influenza virus a, b, c, and d. although both the genus influenzavirus a and b affect humans and cause pandemics, influenza a has been the principal culprit in known outbreaks to the extent that four major pandemics have resulted from it ( - , , , and ) . however, genetic reassortment and exchange of influenza viruses between humans and animals generate antigenic shift, which periodically introduces new viruses to the human population. this, in addition to mutation and selection, produces antigenic drift that accounts for the year-to-year variations in influenza a subtypes. wild ducks, for instance, serve as the primary host for various influenza type a viruses that occasionally spread to other host species and cause outbreaks in such animals as fowl, swine, and horses. such outbreaks often lead to new human pandemics due to novel viruses infecting immunologically naïve people. a critical aspect of the emergence of novel virus strains is genetic variation and combination that occur at the hemagglutinin (ha) antigens (of which there are ) and neuraminidase (na) enzymes (of which there are nine) between and amongst human and animal influenza viruses. the subtypes of the ha and na surface proteins forms the basis for the classification of outbreaks. for example, the through virus was h n , the through virus was h n , the through outbreak was caused by h n , the virus was h n , and the outbreak was caused by h n ; while the most recent virus seen in eastern china in was h n . all of these traditional and new influenza viruses cause pandemics of differing proportions but more are projected to occur. this projection is well supported by the scientific community. however, it is not known when any will occur or whether it will be caused by the h n avian-derived influenza virus, newer subtypes like h n , or completely novel subtypes. virologists like webster and govorkova argue that given the number of cases of h n influenza that have occurred in humans (more than ) with a mortality or death rate of more than %, it would be prudent to develop robust plans for dealing with such pandemic influenza and its (expected) new variations. such plans, however, necessarily demand attention to the associated ethical dynamics. regardless of the specific subtype of human or animal-derived influenza outbreaks, the public health challenges and the moral quandaries are essentially the same. a critical biological feature of influenza lies in its mode and pattern of transmission. this revolves around its capacity to evolve and become airborne-transmissible between and amongst human beings. the influenza virus transmits from person to person primarily in droplets released by sneezing and coughing. some of the inhaled virus lands in the lower respiratory tract, the primary site of disease marion russier et al., "molecular requirements for a pandemic influenza virus: an acid-stable hemagglutinin protein," proceedings of the national academy of sciences , no. ( ) . pp. pp. - anna v cauldwell et al., "viral determinants of influenza a virus host range," journal of general virology , no. ( ). pp. - . couch. p.; shah. p. . cauldwell et al. p. . miller et al. pp. - shah. p. . rebekah h borse et al., "effects of vaccine program against pandemic influenza a (h n ) virus, united states, - ," emerging infectious diseases , no. ( . pp. - . cauldwell et al. p. . macphail. p. . robert g webster and elena a govorkova, "h n influenza-continuing evolution and spread," new england journal of medicine , no. ( ) . pp. - . russier et al. pp. - being the tracheobronchial tree, and sometimes the nasopharynx. largely because breathing is an essential biological need of human beings and partly because human-human associations are an inevitable part of reality, this biological feature of influenza viruses makes everyone vulnerable and susceptible to infection. specifically, crowds of people facilitate viral transmission by enabling sharp upticks in the rate of transmission. the virus also circulates for longer periods in infected persons. the biological features of influenza and its mode of transmission elicit some observations. one, pandemic influenza is not a single disease for which a single and specific therapeutic intervention that will be effective all the time can be developed. in other words, while there is a general approach to engaging this public health disaster, specific interventions will usually vary by each outbreak. this gives an existential and evolutionary advantage to the influenza virus over human communities. it also engenders a disaster dynamic in the sense that every outbreak becomes "sudden" and potentially associated with large human casualties. secondly, it shows the common vulnerability to which the local and global human community are subject vis-à-vis the ease of spread of the viral infection. thirdly, the biological features of pandemic influenza demonstrate how a collective response (human material, scientific etc.) is key to engaging its social and other attendant consequences. the importance of this last remark will become clearer against the backdrop of the social and global features of pandemic influenza outbreaks, a. theme addressed in the next section of this chapter. an influenza pandemic has the potential to cause more deaths and illnesses than any other public health threat. pandemic influenza a h n were reported. also, the h n outbreak recorded a death rate of %, and the recent h n outbreak caused human infections and deaths. in the united states, the estimated potential threat of pandemic influenza is . million deaths, million sick people, and nearly million hospitalizations, with almost . million requiring intensive-care units. global estimates are higher. for instance, the "spanish flu" caused an estimated - million global deaths. it has been projected that a recurrence of the influenza strain would probably result in the death of - million individuals. these data show that substantial numbers of deaths are an inevitable consequence and feature of pandemic influenza. however, death itself often brings about certain social consequence including the death of some of the most gifted members of the society. sir william osler, one of the pioneers of scientific medicine, died of complications arising from influenza in . influenza was cited by the german war general, erich von ludendorff, as a significant reason for why the initial gains of their last offensive faltered and ultimately failed during world war . from a biological perspective, influenza exploits naïve immune systems which tend to over-respond to the influenza virus. as such, young and promising adults constitute a large part of vulnerable victims. in this regard, potential contributions to societies are nipped in the bud, young widows and widowers emerge as well as a lot of orphans. for instance, , children were orphaned due to the outbreak in new york city. influenza also spread within households soon before or after the onset of symptoms in primary infected patients. another associated social feature of pandemic influenza is the closure of schools with an attendant truncation of learning and educational opportunities, depending on the length of the outbreak. while some of these social features are local and exert localized effects, human beings as social animals with the aid of the increased means of locomotion transmit some of the local features into a global experience. the pandemic of influenza which occurred during a time of much less globalization spread to the united states within - months of its detection in china while the pandemic spread to the u.s. from hong kong within - months. it is estimated that the burden of the next influenza pandemic will be overwhelmingly focused in the developing world. however, the epidemiological notion well-known to public health experts that infectious diseases can predicate outbreaks in neighboring places and nations implies that even so-called developed societies cannot be spared as long as the current interpenetration of people across the globe remains. the influenza outbreak, for instance, spread to countries and caused a total of , cases of infection. in short, in a globalized world, infectious diseases travel in nodes of human, material, and animal networks. data from sporadic studies suggest that influenza may be fairly prevalent in africa, albeit sub-clinically. it may, therefore, have a considerable impact on morbidity and mortality on the continent should a combination of factors create a virus that is viable enough to cause a pandemic. this will have far-reaching consequences for the continent due to the material and human resource constraints, lack of preparedness plans as well as the very limited bio-therapeutic capacities that are currently available to produce vaccines. it may likewise create the dispersal of a virus novel to other continents that have experienced typical outbreaks. geographical location plays a major role in public health, and disasters including health disasters are unique in that each affected region of the world has different social, economic, and health backgrounds. as such, while there is a global spread, the nature of each local context and how it responds shapes pandemic influenza in some key ways. first, the nature of the "disseminating" nation influences how infection spreads elsewhere. for example, china's slow reaction to the sars outbreak as well as its limiting of access to patients and other relevant information hhs, "hhs pandemic influenza plan." p. b . , no. ( ) . p. eric k noji, "public health issues in disasters," critical care medicine , no. ( ) . p. s . seemed to have deepened the global intensity of that crisis. in other words, how a local public health disaster is handled shapes the local severity and how it spreads elsewhere. on the other hand, well-handled local health crises positively influence the possible impacts on contiguous nations. in this vein, radest notes that canada's rapid and coordinated response to the sars outbreak significantly limited its spread and impact in the united states. the above examples echo the interconnectivity of the modern world and show how a course of action in one place, however passive, may significantly influence the course of events in another for good or bad. it supports the idea that contemporary health in the twenty-first century is now inevitably and inherently global with respect to infectious diseases. at the heart of these remarks, however, is the possibility of utilizing different networks of human interconnectivity to actively foster the global good. in other words, learning about how people connect and relate at different levels (individually, communally, institutionally et cetera) and learning about the chief actors and players in such a relationship nexus may provide a powerful tool for driving global public health agenda. yet, integral to such a process is how responses to pandemic influenza are framed and implemented locally as well as their attendant limitations. this theme is addressed in the next section. the human instinct for self-preservation has, at the social plane, always resulted in some institutional responses to diseases, whether rudimentary, barely adequate, or sophisticated. in the context of phds, responses are shaped by the nature of the specific disaster, where it is taking place, and what human, material, pecuniary and technological resources are available to deal with the given emergency situation. for instance, the united states prioritizes building a system that ensures stable and economically viable vaccines to engage influenza outbreaks. countries that lack the same kind of resource will clearly prioritize other approaches. however, the general approaches to pandemic influenza are therapeutic and non-therapeutic in nature. this section briefly examines them. pandemic influenza outbreaks, like most diseases, have elicited some biopharmaceutical responses geared towards mitigating its disastrous effects. due to the changing biological and social dynamics associated with the outbreak, social as well as scientific responses are always evolving to keep up. nevertheless, the therapeutic measures fashioned to combat pandemic influenza fall into two groups. these are preventive measures involving the use of anti-viral drugs as well as vaccination. in the past, drugs like rimantadine and amantadine were used as prophylaxis against influenza a. but drug resistance has increasingly been observed to these m -ion channel-blocking agents. today, drugs of choice are mainly tamiflu (oseltamivir) and relenza (zanamivir). black et al. noted that early anti-viral intervention during the pandemic helped reduce the doubling time in the early stages of the outbreak. the linkage between antiviral use and reduction in clinical severity and influenza infectiousness is generally supported in the extant literature. hence, treatment of clinical cases with anti-viral agents constitutes the first-line of engagement for pandemic influenza and these drugs are employed to control or contain pandemic outbreaks long enough for vaccines to be made. yet, drugs like oseltamivir and zanamivir, usually neuraminidase inhibitors, can only help reduce transmission if given within a day of the onset of symptoms. on the contrary, delay in symptoms diagnosis, as well as intervention, favors infection dissemination. nevertheless, antiviral agents for influenza offer some protection to families and households once infection has been detected. in clinical trials, antiviral treatments have been shown to be efficacious in preventing infection, hence, slowing down transmission as well as limiting the severity of the disease. but the effectiveness of neuraminidase such as oral oseltamivir and inhaled zanamivir at reducing mortality is uncertain. in addition, there is some evidence of side-effects. for instance, in adults as in children, oseltamivir increases the risk of nausea and vomiting. also, treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced. resistance to these anti-viral drugs has also been reported, even in people who have never been previously treated with them. ultimately, the success of antiviral prophylaxis critically depends on the identification of index cases in households, pre-schools, schools, and other institutional settings. this clearly highlights the importance of personal, social, and institutional cooperation in relation to dealing with the associated challenges. on the other hand, vaccination as one of the most effective and cost-saving strategies for ameliorating infectious diseases offers a protective approach to limiting and/or curtailing the social and economic consequences of pandemic influenza. two types of vaccines are generally used. trivalent inactivated vaccine and live attenuated influenza virus vaccine, both of which contain the predicted antigenic variants of influenza a(h n ), a(h n ), and b viruses. borse et al. estimated that vaccination program against influenza prevented , - , , clinical cases, - , hospitalizations, and - deaths. they also reported that the national health effects of vaccination were greatly influenced by the timing of vaccine administration and the effectiveness of the vaccine. similarly, ferguson et al. estimated that during a global outbreak, vaccination at the rate of % of the population per day would need to begin within months of the initial outbreak. but this is not feasible under current vaccine technologies. this pragmatic challenge would, however, create a biological and social climate in which infection may flourish in a logarithmic manner. the recurring antigenic variation in influenza viruses which leads to the frequent emergence of new infectious strains increases the likelihood of continuous outbreaks. this and the capacity of the influenza virus to acquire amino acid changes in its viral proteins implies that each outbreak will demand novel vaccines. this often delays the possible response time, again creating a window where infection can readily spread, locally and globally. for instance, it will take at least months from identification of a candidate vaccine strain until production of the very first vaccine during an outbreak. this biological fact makes it difficult to stockpile influenza vaccines ahead of outbreaks and, by consequence, limits the preparedness efforts geared towards confronting the public health challenges and moral quandaries. it is important to note that vaccines have some limitations. for instance, they are not entirely safe public health interventions, especially when specifics are examined. this fact has increasingly come to light in relation to vaccines against pandemic influenza. besides sore arm and redness at the injection site as well as red eyes which have been reported in earlier vaccine trials, there has been some association between increased incidence of narcolepsy in children and the use of the aso -adjuvanted vaccine for pandemic h n influenza in scandinavian countries. in addition, anecdotal reports of fetal deaths occurring shortly after vaccination emerged in and raised public health concerns about vaccine safety. another shortcoming associated with vaccination generally is vaccine failure, which often creates a false sense of protection in recipients while allowing the continued spread of infection. in relation to pandemic influenza specifically, vaccine failure was recently reported by manjusa et al. in people of years and above as well as those who have been vaccinated against seasonal influenza. this is quite troubling partly because vaccine failure vis-à-vis pandemic influenza vaccines has been little studied, and partly because there are countries like the united states where seasonal flu vaccine shots are almost the norm. another dimension to vaccine failure relates to the variation of influenza virus clades. nelson et al. recently reported that nigeria, côte d'ivoire, and cameroon exhibit more variable patterns of influenza virus seasonality, hence, there is a possibility of variants evolving locally within west africa. this, they further argue, undermines the assumption that a vaccine matched to globally dominant lineages will necessarily protect against these local lineages. this notion further raises the question of whether the immune system of populations living in tropical african hhs, "hhs pandemic influenza plan." p. b . environments would react similarly to a vaccine developed mainly for populations restricted to certain geographical areas of the world. on this note, in the possible event that someone originally from any of these nations were present in a pandemic influenza scenario outside african shore, the likelihood of their benefiting from vaccination seems slim. hence, a significant offshoot of vaccine failure in relation to pandemic influenza (especially if newer studies show more negative results) will be the reluctance of people to receive vaccines for seasonal flu and those developed for pandemic influenza outbreaks. these have unsettling public health and moral consequences. one way of engaging the limits of influenza vaccines involve creating a vaccine type that is capable of eliciting cross-protective peptides/epitopes that would be effective against different variants. but this is very difficult. besides the scientific technicalities, producing vaccines for pandemic influenza is not a cheap venture. for example, meltzer, cox, and fukuda estimated in that it would cost the united states about $ . billion to contain pandemic influenza. whereas the economic burden of influenza in lower-and middle-income countries involves direct costs to the health service and households and indirect costs due to a loss in human productivity, these countries also have limited financial capacities to pursue pandemic influenza vaccination as a public health tool. the impacts of the ensuing disease burden from such a constraint will not be locally confined, as it will ultimately seep into the trans-national and global terrains. in summary, the major and, perhaps, insurmountable constraint to vaccination as a tool for engaging pandemic influenza lies in the logistic challenge of producing a pandemic vaccine from scratch, conducting pre-clinical testing as well as generating billions of doses within a very short time for global distribution, which may, however, not work across all nations. but considering the limitations associated with antiviral drugs as well as vaccines in relation to combating pandemic influenza, some form of non-therapeutic approach is necessary, at least as some adjunct to mitigate the overall impact of pandemic influenza on the local and global human community. the next section addresses this theme. yazdanbakhsh and kremsner. p. e . the non-pharmaceutical and non-therapeutic approaches to pandemic influenza revolve around measures such as case isolation, school or workplace closure, restrictions on travel, quarantine as well as contact tracing. for instance, school closure is a non-pharmaceutical intervention often suggested for mitigating influenza pandemics. the logic behind this lies in the notion that children are important vectors of transmission, more infectious, and susceptible to most influenza strains than adults. it is also tied to the idea that high a contact rate in schools fosters transmission of infection. this approach, according to cauchemez and colleagues, may bring about an estimated % reduction in peak attack rates. however, this reduction will be hindered if children are not adequately isolated or if the policy is not well implemented. whereas school closure may only bring about a small reduction in cumulative attack rates, it can foster a substantial reduction in peak attack rates. closure of schools may, however, increase anxiety and create a crisis, as was observed in france during the outbreak. closure of workplaces is another non-pharmaceutical intervention for pandemic influenza. it may be warranted by the degree of the outbreak in which businesses shut down at their own discretion, and for their own safety, as was seen during the - outbreak. however, it may also be warranted by government policy. either way, business closure incurs huge economic costs, pecuniary, and other consequences for the different people tied to and/or dependent on the affected businesses or their services and goods. different forms of quarantine measures are also used to mitigate the spread of infection during an influenza pandemic. for instance, isolation and quarantine of infected patients allow some containment of infection which consequently slows down viral transmission. ultimately, quarantine contributes towards reducing the overall costs and impact of an outbreak. some medical experts see household quarantine as the most effective social distance measure, provided the level of compliance is good. yet, quarantine-at least on a general note-does not always work. for example, maritime quarantine was one of the measures employed in west africa to engage the influenza outbreak as well as interning the ill. however, historians like heaton and falola note that these approaches yielded meager success in relation to quelling the spread and virulence of the pandemic. measures such as cancellation of non-essential public gatherings and restrictions on long-distance travel might help to decrease influenza transmission rates as well as overall morbidity, their effectiveness has not been quantified. the nature of pandemic influenza, the therapeutic and non-therapeutic approaches, and the associated limitations generate some moral concerns. the next section discusses this. ethical issues arise during outbreaks of pandemic influenza. some of these are directly tied to the nature of the virus, some in relation to human responses, some to the social responses, and others to how different human beings respond differently to the several challenges elicited by the pandemic. bioethicists have underscored the critical need to reflect on the ethical issues raised by the specter of pandemic influenza outbreaks. however, what may and what may not be feasible to do will never be clear enough if these ethical quandaries are not clearly explicated. hence, this section seeks to clarify the moral quandaries elicited by pandemic influenza and show the core connecting strands that resonate amongst them. generally, contexts of uncertainty are tied to the evolving nature of knowledge. tannert et al. opine that uncertainty occurs because the more the human community gains insights into the mysteries of nature, the more they realize the limits of their knowledge about how things are. these limitations, they note, make it impossible to foresee all the associated future effects and implications of situations and decisions with certitude. in relation to medicine, jean daly notes that the art of medicine seeks to abolish uncertainty. regardless of the good intentions and telos of medicine, the stark reality is that this task has hardly been achieved. contexts. james marcum contends that uncertainty is largely a part of medicine because of the variability of the underlying biology. uncertainty is not new in the realm of science. however, in the context of public health disasters uncertainty has a strong pragmatic dimension which can influence courses of actions and decisions in multiple unfavorable ways. for example, it occurs during pandemic influenza outbreaks and generates many concerns. in this vein, borse et al. note that the public health community cannot accurately predict the arrival of a pandemic. indeed, a great deal of uncertainty occurs in relation to estimating the potential impact of a pandemic such as influenza. this scenario stifles preparedness efforts, especially in resource-constrained countries where there are often competing social needs to be met with limited budgets. however, the two main uncertainty issues embedded in pandemic influenza involve the nature of the virus and the types of responses available to engage outbreaks. on the one hand, the influenza virus undergoes constant variation in its antigens, creating new infectious strains. the virus also acquires amino acid changes in its proteins. these scenarios increase the likelihood of pandemic outbreaks. however, the question of when, where, and of what magnitude the outbreak will be is never clear-cut. worst-case scenario analysis based on the - pandemic provides no insight into the probability of an influenza pandemic in the next , , or years and how serious such an outbreak might be. this scientific uncertainty or paucity of precise knowledge ignites some social uncertainty and may prompt moral inertia in relation to the level of preparedness and the ability to mitigate the various possible ramifications of an outbreak, when it does occur. this backdrop of uncertainty creates at least three possibilities: over-preparedness, ample preparedness, and under-preparedness. assuming the level of risks remains constant, over-preparing for a pandemic will undoubtedly involve the committing and expenditure of more human and material resources to an outbreak. this will create a sense of waste (to decision and policy makers) after the incident and may affect the resources that will be committed to future outbreaks. the right amount of preparation will help curtail an outbreak while under-preparedness will barely help curtail an outbreak. however, if the level of risk increases, over-preparing may help curtail a pandemic whereas what was hitherto ample preparedness as well as what was hitherto not enough will enable the full range of the effects of a pandemic outbreak to be felt. " ibid. , no. ( ) . p. . kuby. p. . murray et al. pp. - . in other words, the changing nature of the virus demands a constant readjustment of the level of preparedness without a reliable frame of reference with the attendant possibility of some inevitable social harm. not surprisingly, scholars like peter doshi argue that there is a need for evidence-based ways to address hypothetical scenarios of non-zero probability such as the notion that novel influenza pathogens acquire increased virulence during successive "waves" of infection. the scientific uncertainty associated with health disasters such as pandemic influenza may, however, tempt government officials to attempt some form of a cover-up, hence, raising trust issues. for instance, during the cholera outbreak in naples, italian officials paid newspapers and reporters not to report the outbreak. chinese officials tried to keep the sars outbreak a secret. saudi officials, likewise, tried to silence the virologist who discovered the coronavirus in and ultimately forced him to resign from his position. incidents like these have the tendency to dissuade social cooperation during public health emergencies like influenza and have the potential to weaken the overall success of public health interventions. on the other hand, there is a lot of uncertainty surrounding the therapeutic and non-therapeutic approaches adopted vis-à-vis pandemic influenza. it is uncertain, for example, if neuraminidase antiviral drugs really cut down mortality when implemented as the first line of defense. this may create some sense of hesitation in relation to using them. secondly, it is uncertain who and who will not develop some of the associated side-effects. these factors, at a pragmatic level and for less rich nations, may dis-incentivize prioritization of funds for antiviral drugs. uncertainty likewise plays out in the context of influenza vaccines. for instance, only a small amount of any vaccine can be stockpiled because the scientific and public health community can hardly be sure of the efficacy of any given vaccine prior to an outbreak. this is due to possible vaccine failure which will make a new outbreak not amenable to the biological effects of hitherto effective vaccines. hence, vaccines are generally not produced until the new virus strain causing a pandemic is isolated. also, there is uncertainty over who will be at highest risk of infection and complications. this creates a dilemma of some sorts with the potential that a class of the people who need vaccines may not get enough, while another class of people who will benefit less from vaccination gets too much. another kind of uncertainty is linked with possible side-effects of vaccines. while some incidence of narcolepsy was reported in children after the use of aso -adjuvanted h n influenza vaccine in scandinavian countries, and there have been anecdotal reports of fetal deaths doshi. p. . shah. pp. - . hhs, "hhs pandemic influenza plan." p. s - . kotalik. p. . emanuel and wertheimer. p. . dauvilliers et al. pp. - occurring shortly after the vaccination ; it is not clear if these safety issues are one-off events or may recur for other pandemic vaccines. responding to influenza vaccine safety signals during a pandemic constitutes a scientific and public health policy issue since decision-makers must balance the immediate consequences of disease against uncertain risks. one of the consequences of the therapeutic uncertainties associated with pandemic influenza is the validity of administering potentially ineffective antiviral drugs with side-effects or vaccines that may cause harm to people. another is the validity of withholding such drugs and vaccines because it may not be useful for some class of people, or because some people may experience certain degrees of side-effects. these issues raise concerns about human rights and whether or not they may be violated through these courses of actions, or by any other course of action associated with handling a pandemic influenza outbreak. the universal declaration of human rights and the international covenant on economic, social and cultural rights documents enunciate the rights of "everyone to the enjoyment of the highest attainable standard of physical and mental health". hence, it is perhaps more than ever taken for granted that there are rights-related obligations that society, as well as healthcare providers, owe patients as well as those that may potentially fall sick. since everybody is theoretically a potential victim of ill-health depending on time, placek and social or physiological circumstances, individuals can appeal to a rights-based rhetoric to garner positive action from government and healthcare professionals in relation their health. the morality of such a claim stems partly from governments' moral obligation to their citizens and partly from the fiduciary obligations that health professionals have towards fostering the health of patients (and potential patients) in a fashion that preserves their rights as human beings. many moral concerns related to human rights come to the fore in the context of pandemic influenza outbreaks. the first is related to the limited number of vaccines that can be available for each outbreak (due to reasons outlined in the preceding section) and the best sharing formula to use. whatever adopted formula in a given place or situation, some people who may benefit could be excluded. for instance, pandemic influenza often generates a high number of sick people over a large geographic area who will need care at the same time. while this "need" begins at the local plane, it may evolve to be regional and/or global depending on the extent and severity of an outbreak. hence, the human and material resources of healthcare will be rapidly depleted and overwhelmed. since the needs of everyone cannot be met under such a scenario, there is usually some need to ration available resources. in fact, vaccines are hardly enough during pandemics, and rationing is generally considered as the ethical option. yet, the contemporary interconnection between health, the right to health and human rights implies that withholding vaccines from some people who might be potential victims of a pandemic outbreak may be a human rights violation. on the other hand, administering antiviral drugs to non-vaccinated at-risk people helps reduce the severity of illness. during disaster scenarios, the goal remains saving lives but a pandemic scenario in which - % of the population can fall sick within a very short time often demands some type of prioritization of resources. this is partly because keeping some sets of people alive, especially health workers will ultimately help society keep more people alive during a public health disaster. for instance, the traditional view is that prioritizing the vaccination of front-line healthcare workers can help reduce staff absenteeism as well as help prevent them from becoming vectors of viral infection. this is often justified by the logic that a phd situation such as pandemic influenza often makes health professionals work outside their normal scope of practice, put in extra hours, cover for ill workers, accept great risks as well as incur other situational unexpected responsibilities and supererogatory duties. although adults aged years or older, pregnant women, and people of any age with underlying medical conditions are at high risk of pandemic influenza and its associated complications, the notion that death is more tragic in children and young adults as opposed to elderly persons, perhaps, because younger persons have not had the chance to live and develop through all stages of life and accomplish their dreams has made some ethicists argue for the prioritization of vaccines to younger people. yet, if persons are inherently born with human rights and do not have to earn rights, such an idea tends to revamp the rights to health of some class of people at the expense of others. indeed, notions such as this echo the idea that mainstream bioethical issues tend to be far-flung from the values of ordinary people and often irrelevant to the decisions they experience in their encounter with healthcare. in other words, an empirical approach which takes into consideration what people would want when faced with this thorny dilemma rather than an armchair speculation ought to influence the criteria for rationing vaccines. one of the non-therapeutic responses to pandemic influenza is the isolation and quarantine of infected patients. whereas a visibly infected and sick person may have just a little objection to quarantine (after all, such a state mirrors the ambulatory limitations that most disease states naturally impose on people), it is often problematic for other categories of people. in this vein, isolation and quarantine raise concerns about the acceptability of confining people and preventing them from engaging in some of the social activities they otherwise would have loved. whereas restriction of movement is ethically problematic, it is equally problematic to allow person a who may be infectious to roam free, thereby potentially infecting other persons who may also (without the imposition of some restriction) further spread infection. it is clear from the foregoing that pandemic influenza challenges and raises some moral concerns regarding the rights of people, preempting the need to balance them against what is the optimal good of the society. but embedded in these reservations is the demand for autonomous living, broadly conceived. whereas this has been associated with western contexts, concerns about rights violations in relation to quarantine measures are not confined to the west. sambala and manderson recently commented about how ghanaians and malawians perceive public health interventions including quarantine as being intrusive. but this perception seems to run contrary to the cultural norm of most african people. in relation to this strand of thought, shah notes that during epidemics, the traditional attitude of the acholi people of uganda involves working together to isolate the sick, mark homes of the sick with long elephant grass, warn outsiders not to visit affected villages, and refraining from potentially infection-transmitting practices including sexual intercourse. this suggests at least two things. one, in traditional african societies there may be some fairly general consensus about the need to adopt mutual and social cooperation for the overall benefits of the society in engaging collective threats. secondly, it shows how the global village has increasingly penetrated and fragmented societies that were once non-individualized in orientation. but it seems that societies have been affected differently by the globalizing current of individualistic logic. for instance, macphail whereas europeans and americans generally view quarantine during influenza as almost worthless, asians such as hong kongers, expect it as the norm during health disasters, and demand it. this probably shows how strong an influence the communal-oriented confucian idea still exerts in that country. in the context of pandemic influenza outbreaks, over-emphasizing individualism and the attendant call for autonomy (even when such does not cohere with social interests) overlooks communal values and the relational nature of social interactions. it likewise ignores the complex nature of pandemic influenza and how it plays out in an equally complex web of this global age and how people more or less are susceptible to the harms of public health disasters regardless of their proximity. it has also contributed, as lachman argues, to a reduction in the fear of infectious diseases by increasing the emphasis on patients' rights, giving rise to a dangerous complacency that may do great damage to the goals of public health. one of the ways to address the attendant dangers inherent in this almost pervasive trend is recognizing the vulnerabilities even to far-flung harm that is fast becoming an integral aspect of contemporary life. vulnerability-in different forms and facets-plays out in pandemic influenza, as in other public health disasters. traditionally, belonging to the human community or occupying specific facets of life constitutes sources of vulnerability. but the state of being susceptible to harm by the actions and activities of other people or by parts of nature such as viral organisms is also a potential source. in addition, the state of vulnerability may ensue from a range of social, economic, and political conditions. in the context of pandemic influenza, the naturalistic, socioeconomic, epistemic, political, and biological dimensions of vulnerability arise. on the one hand, humans located in pandemic-prone cities or countries and other human beings linked to the global community by technological means of transportation (such as air travel) or non-technological ones (such as migrating birds) are generally vulnerable to influenza outbreaks. the likelihood of a novel strain of influenza outbreak occurring in a country such as china (for instance, jiangcun in guangzhou) where large numbers of people, birds, and swine mingle freely in certain markets is very high ; hence, making the local population and consequently the people of such a nation more vulnerable. macphail, the viral network: a pathography of the h n influenza pandemic. pp. - . bennett and carney. p. . peter j lachmann, "public health and bioethics," the journal of medicine and philosophy , no. ( ) . p. . henk ten have, "vulnerability as the antidote to neoliberalism in bioethics," revista redbioética/unesco , no. ( ). p. . on the other hand, the strength of health systems reflected by availability of experts, economic and technical resources will vary the extent of pandemic-related vulnerability which different societies will experience. in addition, it is widely believed within the scientific community that influenza pandemics can hardly be halted, but they can be delayed. therefore, the "ignorance gap" that occurs during pandemic influenza outbreaks creates a context in which some of the preparatory strategies will inevitably fail (due to no fault of anyone), thereby leaving some people less protected. in relation to the socioeconomic dynamics, it is estimated that most influenza pandemic-associated deaths occur in poor countries or in societies with scarce health resources which are already stretched by extant health priorities and challenges. farmer and campos underscore the need for bioethics to engage the growing problem posed by the gap between rich and poor nations, and how such a course of action reflects social justice. politically, communist nations such as china present unique dimensions to the vulnerabilities of pandemic flu as they may control critical information traffic and access to patients, thereby deepening the crisis situation, or misrepresenting it, and thereby subjecting the rest of the connected world to avoidable risks. the biological make-up of human beings both make them vulnerable to becoming infected with influenza virus as well as make them good vectors of dissemination. for instance, the virus has a surface molecule that enables it to attach firmly to cells in the mucous membranes of the respiratory tract, preventing it from being swept out by the ciliated epithelial cells. but breathing is a normal aspect of human existence, and the oxygenation of the human blood and other oxygendependent biochemical processes of the human body rely on it. yet, the combination of these factors facilitates the ready transfer and exchange of the influenza viruses amongst people, especially when they are in close proximity. the foregoing shows how susceptibility and vulnerability to infection during pandemic influenza reflect a combination of factors. how these combine in specific localities and regions will, therefore, determine the extent of an outbreak. it is also clear that some amount of control can be exerted on minimizing some of these factors. for instance, the use of face mask (to limit infection acquisition and spread), transparency (to combat political bottlenecks), and monetary aid (to help poor nations) will exert some preventive effects on infection transmission, hence, limiting the overall burdens and severity of an outbreak. since everyone may not receive the same level of healthcare for various reasons during a public health disaster (depending on time, place, and category of persons such as adults, the aged, or children), questions about justice and what is just in the context of a pandemic outbreak arise. pandemic outbreaks exacerbate extant inequalities to the extent that certain groups of people face disproportionate risks and impacts of disease. this obviously seems unfair, especially if pre-pandemic actions that would have ameliorated the situation were not done. for instance, school closure in certain districts may interrupt educational opportunities or growth of some children, and business closures will lead to financial losses. since such restrictions may not apply to every region of the nation, these measures may seem unfair to those affected, knowing that other children continue to have access to education, and other people continue to run their businesses. if this characterizes the feelings of some of the people affected by these restrictions, then it is reasonable that some form of compensation may be required to foster optimal compliance to the public health measures that are to implemented. indeed, bioethicists like michael selgelid and søren holm make explicit arguments for some form of compensation to people who suffer financial and other losses due to compliance with public health directives issued during influenza outbreaks. although compensation may not be a problem in more affluent nations where other educational stimulus and business tax breaks may help alleviate any temporary pandemic-associated losses, poorer countries will find it hard to compensate people for any such losses. rationing also raises issues about justice in terms of how vaccines (if available) will be shared during an influenza pandemic. given the limited amount of supply available globally, and locally in a developed economy like the us, distributing the limited supply will require determining priority groups. for people not to feel a sense of being left out during local vaccine administration, it is better to have debated and developed a preparedness plan with the consensus of the local populace. resolving vaccine distribution on a global scale will, however, involve very complex sets of factors. for instance, will countries who supply most of the technical and financial resources to develop such an influenza vaccine demand that the needs of her people be prioritized as opposed to the needs of nations that have contributed little or not at all? even if such a question were not explicitly raised, will it be fair to distribute vaccines equally if every country or affected region has not made significantly even contributions? these are unsettling questions that are bereft of simple answers. some ideas stand out when all the ethical issues generated by pandemic influenza are closely examined. four of these ideas demand attention. the first is the need to help people. secondly, the nexus of relationship that exists between people henk ten have, vulnerability: challenging bioethics (routledge, ). pp. - . michael j selgelid, "promoting justice, trust, compliance, and health: the case for compensation," the american journal of bioethics , no. ( emanuel and wertheimer. p. . and the influenza virus and the changing nature of what is known as well as what can be done to help people under such constraints will limit the help some people may ultimately get during an outbreak. thirdly, the threat of an outbreak presents different risks which vary by context, time, and place. lastly, regardless of the different situational dynamics that pandemic influenza presents locally, regionally, and globally; its threat will affect everyone to varying degrees. since nations theoretically care about their people, it is only reasonable that a people-centered approach offers a useful way to engage the moral quandaries elicited by pandemic influenza outbreaks. the subject matter of diseases is human populations. in fact, the preoccupation of medicine remains the amelioration of the distress of people technically referred to as patients. if a people-centric approach constitutes a viable way of engaging the ethical issues embedded in pandemic influenza scenarios, one way to glean a sufficiently nuanced angle on such an approach will involve turning to ethical lenses that are, in principle, people-oriented. two principal examples of such ethical prisms are communitarianism and ethics of care. this section briefly explains each of these moral lenses, and how each may help engage the ethical issues generated by pandemic influenza. the communitarian moral lens adopts a people or community-centric perspective to moral issues. applied to public health, it offers a population-centered approach which best reflects the philosophy of public health in terms of its commitment to doing the most for the greatest number of people in a society or within a social context. bioethicists like stephen holland regard the communitarian lens as useful since it aims at realizing collective interests. this same idea offers a strong justificatory argument for adopting it in relation to public health interventions. communitarianism pays attention to the social sphere, institutions, and interrelationships in relation to moral judgments that will inform public health policy and practice. its ethos provides an alternative to the dominant atomistic lens of individualism which operates via the logic of self-protection and the unbridled macphail, the viral network: a pathography of the h n influenza pandemic. p. . stephen holland, public health ethics (polity press, ) . pp. - . pursuance of self-interests. it holds that the social nature of life and institutional and social relationships should inform moral thinking, and by implication, the process of determining appropriate courses of actions should lie within the social space. to be sure, the communitarian notion appeals to the historical traditions of communities or people who share customs, ideals, and values ; and thus prioritizes common threads of thought and practices within specific communities as a strong moral basis for justifying decisions that pit different individual and social interests against one another. there is an important phenomenological aspect of communitarianism. for people raised within the traditional family structure-father, mother, children, and relatives-the family unit constitutes a micro-community which generally socializes the child into a community-oriented way of reasoning. while the strength of such an orientation is expressed in different measures by different individuals, it also provides the cognitive platform for balancing and pursuing personal interests in a feedback loop with the collective interests of other family members. yet, the ultimate measure of what level of community-oriented reasoning an individual retains in adult life will depend on their education, social experiences, whatever meanings they draw from these, and how these parameters are brought to bear in the context of specific decisions and choices. this reality partly explains the multiple versions and interpretations of communitarianism, which tends to mar its conceptual and theoretical coherence. it also partly explains why community values are not generally shared by all. communitarians advance three different types of claims: descriptive claims which stress the social nature of people; normative claims which celebrate the value of community and solidarity, and a meta-ethical claim which emphasizes the idea that political principles should mirror "shared understandings'. two of these dynamics-the normative as well as the metaethical-are important in relation to engaging the ethical issues elicited by pandemic influenza. the significance of the meta-ethical dimension of communitarianism is its capacity to help drive and ground public health policies. this is especially so considering the reality that community and living together in today's fragmented and individualistic world is generally seen ever less as a necessity and assumes the dimensions of a choice as the default state. hence, these two facets will be examined in relation to their possible insights and pragmatic importance vis-à-vis engaging the quandaries associated with influenza outbreaks. healthcare focuses on helping sick people regain optimal health and healthy people maintain good health. pellegrino and thomasma remark that medicine seeks to foster social flourishing as well as the medical good of society. if this is true, and if the end of the communitarian moral lens is to ensure the survival of the society by promoting the interests of people over the selfish interests of individuals, then how can this approach help engage issues of uncertainty, vulnerability, human rights and justice? this can come through appropriate educational policies and approaches carried out prior to and during influenza outbreaks. it is not known when and in whom influenza therapeutic interventions such as antiviral drugs and vaccines may cause side-effects. it is also not known when an outbreak will occur or the attendant magnitude. since public health disasters are classless in terms of who will and who may not be affected, the scenario of uncertainty affects every segment of people in the local communities and nation. hence, health workers, government officials, the rich, the poor, the educated and illiterates and other possible stratification of society are potential victims. a communitarian ethos is useful in at least two ways in relation to dealing with the uncertainties associated with pandemic influenza. generally, it can-with the right pre-disaster public education-help ensure that people understand the unavoidable scientific and knowledge-related gaps in preparedness policies and specific plans put together to engage a specific outbreak. this will help avoid or minimize blame, since scapegoating during disease outbreaks causes different shades of disruption and target important actors including health workers. in fact, the better educated the public is about the challenges of stockpiling vaccines, the more cooperative they will likely be to the vaccine-supply challenges that arise during an outbreak. a communitarian ethos may also help engage the real and possible harms that may ensue due to the therapeutic uncertainties associated with pandemic influenza. these harms arise from the uncertain nature of what is knowable about a pandemic virus before it strikes as well as the biological limits of the therapeutic arsenals often produced within a very narrow time window. this is also generally tied to the reality that new health interventions including drugs and vaccines come with the possibility of some adverse events, which may be linked to the chemical/biological/physical components of the product, to genetic susceptibilities in certain individuals, or to edmund d pellegrino; david c. thomasma, "the good of patients and the good of society: striking a moral balance," in public health policy and ethics, ed. michael boylan (springer, ) . pp. - . shah. p. . environmental triggers. keeping the public aware of this fact before and during an outbreak as well as emphasizing that accepting these risks (though uncomfortable at the individual plane) will serve to ensure the society overcome a pandemic should help garner some level of support critical to ensure proper compliance. since people are born with inherent human rights and do not have to earn them, it is hard to justify trumping the rights of some for the sake of public health. this is especially so if the people whose rights may be inhibited or violated do not consent to the process. to avert this, a discursive approach involving inclusive deliberations is essential. in this vein, the communitarian lens can help foster dialogue as well as call for the need to reward people for the sacrifices they may or will bear on behalf of the community and the society. for instance, guaranteeing that some compensation will be paid for financial losses incurred through workplace closure as well as apt public education about the nature, purposes, and conditions of quarantine facilities will help convince people that such temporary rights-related inconveniences are for the benefits of the overall society. in relation to vulnerability and justice, the communitarian lens can help clarify the different kinds of social, biological, and natural vulnerabilities that face different people in different contexts. for example, it can offer a way of making the important distinction between general vulnerability that people will experience as human beings, vulnerability based on age, and occupational vulnerability seen in health professionals. based on these distinctions, it can help underscore how context-specific cooperation will help ensure the overall success of the countermeasures adopted to engage a given pandemic. critical to this, however, is the moral currency of trust. trust shapes how the public evaluates risks and benefits. it also influences the acceptance of prescribed public measures to mitigate present or perceived risks. effective risk and crisis communication depend on public trust in the government during a pandemic. as such, a higher level of trust will influence a more positive level of social compliance. van der weerd and colleagues corroborated this in their empirical study of the pandemic in the netherlands. in addition to trust, transparency in terms of how priorities will be made in terms of the allocation of vaccines as well as antiviral agents, and decisions pertaining to school and/or workplace closures is important. even in western climes, public health experts have sometimes pointed out the paucity of transparency in ethical reasoning and the scanty explicit ethical justification for pandemic-related policies. obviously, an atmosphere of trust and transparency will be conducive to discussing and addressing issues related to local justice. this is especially relevant in relation to less wealthy nations or countries with weak institutions. for instance, it will be hard to garner cooperation in hitherto abandoned communities by appealing to communitarian ethos without addressing extant disparities in the social fabric as well as the healthcare system. if human beings are located in particular communities but are willy-nilly part of a global community, how well the vulnerability and justice-related issues are locally addressed will influence the extent of their regional and global dynamics. this echoes the notion that badly managed local issues associated with pandemic influenza will pose more challenges and burdens at the regional and global levels. since every nation lacks an equal capacity to deal with the local burdens of pandemic influenza, it is necessary for wealthier nations to rally around poorer ones. indeed, the transcontinental nature of health disasters including pandemic influenza and sars underscores the urgent need to strengthen how the global community deals with emerging infectious diseases, and how novel visions of global solidarity and cooperation will be key in such an endeavor. this constitutes a preventive stance and falls well within the traditional agenda of public health. this approach is also a reasonable economic and health security choice as it will statistically cut down the possibility of global and transnational infection dissemination. while the communitarian ethos as argued above offers some insights into how to flexibly engage the moral dilemmas generated by influenza outbreaks, its application in non-community-oriented contexts potentially raises some difficulty at the institutional and individual planes. such possible difficulties, however, call for a global but locally nuanced moral framework. that theme, however, will be addressed in chap. . for now, the rest of this chapter will explore another people-centric moral lens, care ethics, in relation to resolving the quandaries of pandemic influenza. in addition to the communitarian lens, the ethics of care perspective (eoc) constitutes a people-centric method of attempting to resolve ethical issues. whereas it sometimes arrives at the same conclusions reached by traditional bioethical approaches, employing it as a complimentary approach to the moral quandaries generated by pandemic influenza should yield additional nuances and insights visà-vis resolving the associated moral concerns. care ethics emphasizes varying degrees of care within relational contexts ranging from the personal sphere to the realm of moral strangers. hence, it is an other and people-centric moral lens. it has henk ten have, global bioethics: an introduction (routledge, ). p. . peter a singer et al., "ethics and sars: lessons from toronto," british medical journal , no. ( ) . pp. - . edwards, "is there a distinctive care ethics?" p. . been applied to diverse relational contexts including everyday lives, professional practices, social and public policies, as well as international relations. for scholars like steven edwards, ethics of care uses a distinct ontological commitment to realize its outcomes as well as justify its stance. it is an attempt to re-conceptualize and renegotiate the moral landscape in order to give room for a plurality of values. some have argued that the removal of friendship with its altruistic emotional sequelae and the subversion of virtue ethics from the sphere of morality were some key factors that warranted the moral change which birthed the ethics of care framework. while eoc is also linked with gender-based morality which undergirded campaigns for equal employment opportunities between the sexes, legal rights, reforms of family life and sexual standards, and better education ; scholars like noddings have pointed out that it is broader and deeper than feminist ethics. to be sure, one of its major impetus is the call for the expression of higher capabilities. care ethics also encapsulates a spectrum of ideas. for kittay, care constitutes an "achievement term" such that caring occurs only when specific acts of care have been carried out. in this vein, intentionality would not qualify as part of the baggage of care rhetoric. this obviously has some pragmatic appeal. most people, for instance, would only appreciate care if it helps contribute towards relieving their current distress. yet, caring may also constitute a general attitude and an orientation which may provide appropriate background conditions for shaping responses to others' needs and states of distresses. also, one may care but situational constraints may limit how a caring impulse may translate into pragmatic ends. therefore, that someone simply "lacked opportunity" to show care as apostle paul writes in his epistle to the philippians does not necessarily indicate the absence of care. hence, caring cannot be reduced only to materialistic terms. one way to distinguish the general caring orientation from specific acts of care is to refer to each as "caring about" and "caring for" respectively. care ethics locates morality within the ambiance of family, friends, and colleagues, and ultimately towards the public sphere. it rejects the independent and atomistic notion of the self and champions an inter-dependent and inter-related view. this approach grants eoc a psychological gestalt to which people brought up in caring relationships, at least in the early phases of their lives, can readily identify with. it thus partly appeals to kohlberg's theory of moral development. here, the emphasis is put on the foundational roles of trust and its place in fostering a deepened sense of reciprocity within a social context of inequality. not surprisingly, some ethicists describe caring as the primary virtue which offers a general account of right versus wrong actions as well as political justice. whereas the informal social contract idea underlies inter-personal and stateindividual relationships, the care ethical lens may be applied to the personal sphere as well as social institutions due to its multiple ways of situating relationality. indeed, eoc focuses on attentiveness and sensitivity to the needs of others and offers a moral compass for teasing out delicate boundaries between obligation-based ethics and responsibility-based ethics. as such, it seeks to transcend the depersonalized realm of asking "what obligations do i have to mr. x" to the humane realm of asking "how can i help mr. x" in scenarios of moral crises. since caring embodies an activity, a set of activities or a labor of care from one person to the other, it presupposes that the capacity for receiving care will be present in the recipient(s) of care. public health disasters including pandemic influenza with their myriad of ethical and pragmatic challenges create a spectrum of needs and contextual dependencies which some people will have to meet, directly and indirectly. it thus creates different types of carer versus cared-for relationships between and amongst victims, atrisk people, health workers, and government officials. since it is a foundational nexus like these that underlie the caring ethic, it will be insightful to examine how the ethics of care moral lens may help resolve the moral dilemmas elicited during pandemic influenza outbreaks. osuji. p. . whereas tirima recently argued that ethics of care is irrelevant to addressing the moral imperatives in disaster scenarios because it only builds off on relationships and, therefore, requires some proximity between the caring moral agent and the cared-for victim, such a stance is flawed for at least three important reasons. firstly, care ethics can, through relevant public policy, positively influence how victims of disasters are cared for. secondly, contexts of duty exist between some of the players and victims of disasters which form the basis of a relationship of caring. for instance, healthcare professionals incur fiduciary duties to at-risk people, victims of a public health disaster as well as the general populace that may potentially be infected and infect others. thirdly, if the care ethical prism emphasizes how individuals may offer help "in scenarios of moral crises, then it should be relevant in health scenarios where different kinds of conflicting moral emergencies occur. the application of care ethics to specific disaster contexts such as influenza outbreaks, however, requires elaboration. specifically, this needs some explication with reference to issues of uncertainty, vulnerability, human rights and justice. whereas the dilemma of uncertainty that arises during pandemic influenza affects everyone, it will affect different sets of people differently. for instance, the biological uncertainties associated with an influenza outbreak are not known to the same extent by public health experts, health workers, the literate, and illiterate members of the society. caring about the potential practical consequences that may result from the attendant "ignorance" gap should, therefore, involve sharing as much useful information as possible between and amongst the different rungs of people. the relational context, in this regard, may be situated and realized through professional associations, institutional contexts, public announcements through media outlets and patienthealth professional interactions. kunin et al. recently reported on how primary care physicians helped pass on important pandemic-related information to out-patients during the pandemic in israel. this, they concluded, helped enhance the success of the national pre-pandemic preparedness plans. indeed, during public health disasters, the speed at which information is needed by policymakers may be faster than is usually possible through traditional mechanisms of research dissemination. this scenario makes information sharing a norm; even possibly those provided by preliminary research findings. humans instinctively show care to other humans in need. while this caring instinct has been socially modified and conditioned in some parts of the world where individualistic tendencies run rife, some communal-oriented cultures give room for a freer expression of the instinct of care. the instinct of care may, however, be counterproductive in the context of phds. for instance, during pandemic influenza, sick and dying patients remain active carriers of infection, as such, will infect susceptible friends and relations who feel obligated to show care in relation to helping them. in other words, "unbridled" caring may increase the vulnerabilities elicited during pandemic influenza. yet, the care ethics moral lens may help modify and re-direct the caring impulse in a more socially useful way during a pandemic. the other-centric nature of the eoc lens implies that people should care not only about themselves but about others, perhaps, even moral strangers. how person a will care during a public health disaster will, however, differ from how b will choose to act in a manner that reflects care, depending on their levels of knowledge, resources available to them as well as their social and spatial location. in other words, how a healthcare worker will care professionally in the hospital context and supererogatorily in the non-hospital context will differ from how a lay member of the society can show care in a pandemic situation. however, appealing to the eoc may help facilitate the selflessness needed. if someone cares that their society survives an influenza outbreak, then they should be willing to play roles that will help bring about that goal. this will facilitate compliance with therapeutic measures such as vaccines and antiviral drugs as well as non-pharmaceutical measures such as contact tracing, quarantine, and workplace closure. collective adherence to these measures will help cut down the susceptibility and vulnerability of individuals, groups of people, and the society to the impact of influenza outbreaks. by enabling the willingness of people to subject themselves to the public health restrictions required to contain pandemic influenza and accept the potential risks and side-effects associated with vaccines and antiviral agents, the eoc approach may indirectly eliminate or downplay the human rights-related quandaries engendered by pandemic influenza. noddings has argued that attentiveness and responsiveness are exigent to rights, flowing from one person to the other. if this is true, then the eoc may help individuals adjust the emphasis they place on articulating their rights contextually during an influenza pandemic for the sake of the collective good. finally, an appeal to the care ethical lens may help address the moral quandaries associated with local justice. although some versions of care ethics hold the posi- ns crowcroft, lc rosella, and bn pakes, "the ethics of sharing preliminary research findings during public health emergencies: a case study from the influenza pandemic," eurosurveillance , no. ( ). pp. - . shah. p. . noddings. p. . tion that it is not possible to integrate and apply justice to care, such a limitation hardly applies to the context of a public health disaster such as pandemic influenza. for instance, the different conflicting priorities that arise during influenza outbreaks such as rationing of limited resources will be easier if some people are at least willing to forgo their interests for others. in non-familial carer and cared-for relationships involving at-risk government representatives and at-risk members of the society and familial relationships involving parents and children living in the same house, an appeal to a care ethical lens may help drive the moral sensitivity to the needs of others, enabling some vaccine-eligible persons (under the standard rationing criteria) to forgo their ration, preferring rather that other at-risk people (for example, ordinary people and younger family members) have them. this kind of selflessness approximates some form of humanitarian act in that person a decides to overlook their interests for others "without expecting rewards". however, because human beings naturally seek their own personal interests, there may be some difficulty in achieving this other-centric goal in as many people as possible in a public health disaster situation. this implies that the care ethical lens may have some limitations in relation to sufficiently engaging the ethical dilemmas raised by pandemic influenza in particular and other types of public health disasters, in general. that theme will, however, be addressed in chap. . during disasters, there is the utilitarian goal of doing the most good for as many people as possible with minimal harm. a people-oriented moral lens, this chapter argues, may be apt in accomplishing such an agenda. the chapter explored the strengths of the communitarian and care ethics moral lenses in relation to engaging the moral quandaries elicited during pandemic influenza outbreaks. because it is difficult to engage pandemic outbreaks with little prior preparation, these moral lenses become important since they can help people develop an other-centric orientation and sensitivity to the needs of others. to systematically drive the importance of a people-centered approach to pandemic influenza, this chapter explicated the biological make-up of the influenza virus as well as the social and global features of the associated pandemic. this helped underscore the local, regional, and global seriousness of pandemic influenza as a distinct type of public health disaster. the chapter went on to show how an barnes et al. p. . vawter, gervais, and garrett. p. . understanding of the social and biological dynamics of influenza has shaped the therapeutic and non-therapeutic approaches to engaging outbreaks. it also articulated some of the attendant limitations of pandemic influenza countermeasures including vaccines and anti-viral drugs. this chapter has also highlighted the ethical quandaries generated by influenza outbreaks. these are issues related to epistemic and social uncertainty, biological, social, geographical and political vulnerabilities, potential violations of human rights through some of the therapeutic and non-therapeutic countermeasures, as well as issues of local and global justice. against this conceptual background, the chapter pointed out how helping people is a central concern in pandemic influenza, and how the thorny ethical issues constitute difficulties encountered in accomplishing this goal. on that note, it showed how people-centered lenses such as communitarianism and ethics of care may be useful in engaging the associated practical and moral challenges. to clarify the importance of each of these approaches, the chapter elaborated each of these ethical lenses, and showed how each may help orient different players in the context of a pandemic influenza towards acquiring a sense of community and an other-centric sensitivity which will be essential to resolving the moral dilemmas as well as realizing the critical public health objective central to such a public health disaster. however, partly because there are limited grounds for deciding what the limits of practical reasoning will be ab initio, and partly because of the complexities and nuances that are associated with the global dimensions of the issues at stake in pandemic influenza situations, these ethical lenses may suffer some limitations. whereas this chapter has examined none of such limits, they will be engaged in chap. where the relational-ased global ethical framework will be formulated. biological features of novel avian influenza a (h n ) virus epidemiological consequences of household-based antiviral prophylaxis for pandemic influenza strategies for mitigating an influenza pandemic effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza a h n pdm virus infection: a meta-analysis of individual participant data influenza virus resistance to neuraminidase inhibitors containing pandemic influenza with antiviral agents vaccine-preventable diseases: an examination of measles and polio in nigeria vaccines for seasonal and pandemic influenza is there a distinctive care ethics? the ethics of care: personal, political, and global african traditional medicine: autonomy and informed consent their time: a history of feminism in western society care ethics and "caring" organizations moral boundaries pp is there a distinctive care ethics? unprecedented lead poisoning outbreak in zamfara, nigeria: a multidisciplinary humanitarian response to an environmental public health disaster in a resource scarce setting public ethics of care-a general public ethics challenges of the pandemic response in primary care during pre-vaccination period: a qualitative study exploring the technologies of laboratory science for social change: an examination of the nigerian healthcare system vaccine-preventable diseases: an examination of measles and polio in nigeria evidence and healthcare needs during disasters narcolepsy, a (h n ) pandemic influenza, and pandemic influenza vaccinations: what is known and unknown about the neurological disorder, the role for autoimmunity, and vaccine adjuvants non-pharmaceutical public health interventions for pandemic influenza: an evaluation of the evidence base beyond the dyad: exploring the multidimensionality of care ethics of care: critical advances in international perspective the great influenza: the story of the deadliest pandemic in history public health ethics: theory, policy and practice pandemics. in encyclopedia of global bioethics epidemiological consequences of household-based antiviral prophylaxis for pandemic influenza effects of vaccine program against pandemic influenza a (h n ) virus, united states liberalism and communitarianism: a misconceived debate household transmission of pandemic influenza a (h n ) virus in the united states closure of schools during an influenza pandemic viral determinants of influenza a virus host range are we professionals? a critical look at the social role of bioethicists america's forgotten pandemic: the influenza of the ethics of sharing preliminary research findings during public health emergencies: a case study from the influenza pandemic evidence-based medicine and the search for a science of clinical care increased risk of narcolepsy in children and adults after pandemic h n vaccination in france estimated global mortality associated with the first months of pandemic influenza a h n virus circulation: a modelling study a systematic review of the social and economic burden of influenza in low-and middle-income countries pandemic influenza vaccines a controlled trial of amantadine and rimantadine in the prophylaxis of influenza a infection the elusive definition of pandemic influenza is there a distinctive care ethics? who should get influenza vaccine when not all can? epidemiology and evolution strategies for mitigating an influenza pandemic seasonal influenza vaccines human rights discourse within global health ethics. in an introduction to global health ethics risk factors of influenza vaccine failure in - , - and - at baylor scott & white health (bswh) in central texas medical countermeasures for pandemic influenza: ethics and the law risk of fetal death after pandemic influenza virus infection or vaccination global explanations versus local interpretations: the historiography of the influenza pandemic of - in africa the ethics of care: personal, political, and global department of health and human services public health ethics should persons detained during public health crises receive compensation? neuraminidase inhibitors for preventing and treating influenza in adults and children influenza pandemic epidemiologic and virologic diversity: reminding ourselves of the possibilities preparing for an influenza pandemic: ethical issues challenges of the pandemic response in primary care during pre-vaccination period: a qualitative study liberalism and communitarianism public health and bioethics their time: a history of feminism in western society disasters, the environment, and public health: improving our response containing pandemic influenza with antiviral agents pandemic and public health controls: toward an equitable compensation system a predictable unpredictability: the h n pandemic and the concept of strategic uncertainty within global public health the viral network: a pathography of the h n influenza pandemic medicine and public health, ethics and human rights an introductory philosophy of medicine: humanizing modern medicine responding to vaccine safety signals during pandemic influenza: a modeling study the economic impact of pandemic influenza in the united states: priorities for intervention the signature features of influenza pandemics-implications for policy the influenza pandemic: insights for the st century estimation of potential global pandemic influenza mortality on the basis of vital registry data from the - pandemic: a quantitative analysis effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza a h n pdm virus infection: a meta-analysis of individual participant data multiyear persistence of pandemic a/h n influenza virus lineages in west africa vaccines for seasonal and pandemic influenza care ethics and "caring" organizations public health issues in disasters african traditional medicine: autonomy and informed consent conclusion: taking forward the debate rethinking community in the aftermath of communitarianism: outlines of a phenomenological path bioethics: catastrophic events in a time of terror molecular requirements for a pandemic influenza virus: an acid-stable hemagglutinin protein ethical problems in planning for and responses to pandemic influenza in ghana and malawi influenza virus resistance to neuraminidase inhibitors promoting justice, trust, compliance, and health: the case for compensation pandemic: tracking contagions, from cholera to ebola and beyond test of a trust and confidence model in the applied context of electromagnetic field (emf) risks ethics and sars: lessons from toronto lessons from africa: developing a global human rights framework for tuberculosis control and prevention africa: a practical guide for global health workers public ethics of care-a general public ethics the ethics of uncertainty vulnerability as the antidote to neoliberalism in bioethics the challenge of universal access to health care with limited resources ethics in a pandemic: a survey of the state pandemic influenza plans the good of patients and the good of society: striking a moral balance pandemic influenza preparedness: an ethical framework to guide decision-making with human health it'sa global thing": canadian perspectives on ethics in the global governance of an influenza pandemic unprecedented lead poisoning outbreak in zamfara, nigeria: a multidisciplinary humanitarian response to an environmental public health disaster in a resource scarce setting ethical issues in pandemic planning monitoring the level of government trust, risk perception and intention of the general public to adopt protective measures during the influenza a (h n ) pandemic in the netherlands allocating pandemic influenza vaccines in minnesota: recommendations of the pandemic influenza ethics work group pathogenesis of the pandemic influenza virus h n influenza-continuing evolution and spread influenza in africa public health ethics: an update on an emerging field biological features of novel avian influenza a (h n ) virus key: cord- - owsb bg authors: leung, gabriel m.; nicoll, angus title: reflections on pandemic (h n ) and the international response date: - - journal: plos med doi: . /journal.pmed. sha: doc_id: cord_uid: owsb bg gabriel leung and angus nicoll provide their reflections on the international response to the h n influenza pandemic, including what went well and what changes need to be made in anticipation of future flu pandemics. there is general consensus that the only predictable characteristic of influenza viruses and pandemics is their unpredictability [ ] . given such uncertainty, reasonable application of the precautionary principle should prevail in the responses. indeed many of the initial responses to the pandemic went well. once isolated, the pandemic virus strain was shared immediately, specific diagnostic assays were produced and distributed worldwide, antivirals were available in many countries, vaccine development started promptly, and clinical trials demonstrating vaccine safety and immunogenicity were conducted rapidly. there were many inherently favourable features of the pandemic itself, not all of which were immediately apparent (table ) . this was not spanish flu. the impact has been mostly confined to the health sector. but that impact has been significant and heterogeneous, with pressure experienced by primary and hospital care (especially intensive care and paediatric services). distilling descriptions of the impact of a complex public health threat like a pandemic into a single term like ''mild,'' ''moderate,'' or ''severe'' can potentially be misleading [ ] . certainly the experience of hospital clinicians indicated that this pandemic, sometimes described as ''mild to moderate,'' was not limited to only mild or moderate illness. many patients were severely ill and died, and undoubtedly, high-quality clinical management of patients with severe complications in intensive care units saved many lives of the critically ill, who often required prolonged hospitalisation [ ] . the epidemiology of this pandemic is different than for seasonal influenza epidemics, but not unlike previous pandemics. young people have been disproportionately affected in terms of hospitalisation and deaths compared to seasonal influenza in which complications and mortality are predominantly borne by the elderly [ ] . similarly, the risk to pregnant women has been higher than for seasonal influenza [ , ] , which was also noted in previous pandemics. the attributable premature mortality may remain unclear for some time. recent american analyses have estimated many more deaths than those officially reported with laboratory confirmation of infection and that years of life lost were equivalent to the pandemic. the lower bound of such estimates is equivalent to the annual burden caused by a typical h n seasonal epidemic in temperate climates [ , ] . the years-of-life-lost metric captures the impact of a different agespecific mortality pattern which death counts cannot. deaths involving the young and healthy incur many more potential years of life lost compared to those of older adults and of chronically ill individuals. there are also a number of ''firsts'' for the pandemic after an interpandemic period of more than four decades (box ). these brought both opportunities and challenges. under the auspices of the world health organization (who), the process of a global review by public health specialists from around the world has recently begun. they were nominated by national authorities and are led by an elected chair who assessed the handling of the swine influenza event among us military personnel at fort dix [ ] . here we offer some initial reflections on the first months of the present pandemic. considerable effort in recent years had been dedicated to preparing for surveillance during a pandemic and to incorporating modelling in planning in some countries. the pandemic virus was detected and isolated reasonably early, although too late for any attempt at containment. it remains unclear precisely when or where it first emerged, but the earliest human infections were detected in north america and the best estimates of the timing of emergence are variously mid-february from field epidemiology in southeast mexico or mid-january from a molecular clock model [ ] . situational awareness during the early phase allowed quick assessment by countries, notably those affected first (mexico, us, canada, and southern hemisphere temperate countries). the integration of clinical, laboratory, and epidemiologic data proved essential and gave important insights into disease severity, transmission dynamics, and anticipated impact of interventions. focused local or national studies with analyses shared through who or regional bodies proved more valuable than relying on collection of primary data for analysis in some regions [ ] . although there were modelling efforts underway, only a few governments incorporated such data for policy decisions. data from seroepidemiological studies have been limited, primarily due to the lack of routine influenza serosurveys, and the essay section contains opinion pieces on topics of broad interest to a general medical audience. technical challenges with the assays, interpretation, and validation of results. available serological data on prevalence or seroincidence of humoral immunity yielded age-specific attack rates that indicated a substantial proportion of asymptomatic infections and mild illnesses, similar to or greater than past pandemics and seasonal outbreaks. this was confirmed by a recent hong kong study showing the proportion of asymptomatic infection, secondary attack rates, viral shedding, and course of illness among household members were largely similar between infections with seasonal and pandemic influenza virus strains circulating during [ ] . the few published serosurveys revealed heterogeneities in infection rates among different groups and between different places [ ] [ ] [ ] . in particular there appears to be serological evidence of substantial preexisting humoral immunity among older adults, ranging from % ( : titre by haemagglutination inhibition in those years or over) [ ] to % ( : titre by microneutralisation assay in those years or over) [ ] in different studies. further data on population susceptibility by age or the availability of a rapid and accurate serological test could allow health services to further target vaccine efforts for subsequent waves, as has been done in a few countries [ ] . early on, some airports installed thermal screening and others asked travellers to declare fever or respiratory symptoms at disembarkation. the utility of these interventions has been repeatedly challenged [ ] , although if executed well could delay the start of community transmission by a few weeks [ , ] (table ) . similarly, during the early stages of global or local spread, quarantine, isolation, school closures, and other social distancing measures were variously implemented in some populations (e.g., mexico [ ] , western japan [ ] , uk), although most have not yet been formally evaluated and published [ ] . two exceptions are in hong kong and the uk. in the former, it was estimated that transmission fell by % when schools closed [ ] . in settings like hong kong, with the infrastructure and resources to implement such measures and n decisions regarding pandemic response during the exigencies of a public health emergency must be judged according to the best evidence available at the time. n revising pandemic plans-to be more flexible and more detailed-should wait for who leadership if national plans are not to diverge. surveillance beyond influenza should be stepped up, and contingencies drawn up for the emergence or re-emergence of other novel and known pathogens. [ ] but some countries attempted containment in phases and . some countries even instituted a ''containment phase'' using case-finding and various measures such as isolation and antiviral treatment of ill suspected and confirmed cases, and quarantine of exposed persons with or without antiviral chemoprophylaxis, while others never attempted or quickly moved from resource-intensive containment to mitigation [ ] . a preliminary evaluation of intensive containment undertaken in parts of the uk during its spring/summer wave of demonstrates how resource-and labour-intensive community containment could have been and also how even with a lot of resources the measures had to be abandoned [ ] . it is now recognised that the phrase ''containment'' was unfortunate and potentially misleading since at best the actions were only mitigating impact [ ] . this pandemic virus transmitted efficiently among children and at least one study has shown that school closures were associated with reduced population transmission when implemented early [ ] . closures appear to have stopped school outbreaks in western japan and might have also mitigated impact initially on the local communities [ ] . however, decisions on this intervention were contextually specific, dependent on feasibility and their potential downsides [ ] . in europe and the us the judgement was generally that proactive school closures would not be justified as a community mitigation intervention in the context of a perceived mild-to-moderate pandemic among the general population, and reserve plans for widespread closure have not been activated in most jurisdictions. however, local decisions were made to close schools in some areas as a response to prevent transmission and high attack rates among schoolchildren or simply where there was too much illness and absenteeism to sustain teaching [ , ] . personal protective interventions such as face masks, hand hygiene, and early isolation may have been beneficial in reducing transmission at the individual level in the home [ , ] , although household secondary attack rates during the pandemic were similar to those with seasonal influenza [ , ] . their population level impact remains to be assessed. there was much debate over whether to use conventional masks or respirators in health care settings. one well-conducted canadian trial on seasonal influenza virus transmission published during the pandemic suggested no additional advantage from n respirators [ ] . oseltamivir and zanamivir (and later peramivir in some countries) played a role in the mitigation effort, sometimes drawing on national stockpiles. except for japan, widespread use of antivirals had not been the norm previously. it became standard to recommend neuraminidase inhibitors for treatment of inpatients and high-risk outpatients, and in restricted circumstances for chemoprophylaxis. innovative delivery schemes were sometimes developed. those who fell sick in england could have a telephone assessment (taking pressure off primary care) and then if appropriate receive empiric oseltamivir treatment from a local pharmacist. in norway oseltamivir was made available ''over the counter.'' however in many european settings, reluctance remained among primary care providers to prescribe a drug they were unused to. another controversy was whether to offer oseltamivir to all those with symptoms or target those at higher risk for complications. the observational data so far suggest that early treatment with neuraminidase inhibitors have worked to reduce severe disease and have not been linked to significant adverse risks [ , ] . late clinical presentation and delayed initiation of antiviral treatment have been implicated with more severe complications worldwide, indicating gaps in identifying and treating patients before disease severity increases. while sporadic cases of oseltamivir resistance have been reported in association with a specific mutation (h y in neuraminidase), such oseltamivir-resistant viruses have rarely transmitted [ ] . indeed, the pandemic virus has remained genetically and antigenically stable so far. the core pharmaceutical preventive intervention was vaccines and this has box . a series of ''firsts'' about pandemic (h n ) n the first pandemic to emerge in the twenty-first century. it has been more widespread and remains ongoing, compared to sars. n the first pandemic to occur after major global investments in pandemic preparedness had been initiated. n the first pandemic for which effective vaccines and antivirals were widely available in many countries, thus requiring public health authorities to earn and retain the confidence of health care providers through whom such are usually distributed. n the first influenza pandemic to coincide with the ongoing hiv/aids pandemic and for which preliminary data do not suggest a substantial, disproportionate impact on hiv-infected patients. n the first pandemic that took place within the context of a set of international health regulations and global governance, which had not been widely tested until the present. n the first pandemic with early diagnostic tests that led to rapid diagnosis but also an early obsession in the media and of policymakers with having reports of the numbers of those infected. n the first pandemic with antivirals available in many countries that led to a hopeful expectation that the pandemic might be containable, leading to the preparation for and implementation of a ''containment phase'' in some places. n the first pandemic in which intensive care was available in many countries to treat critically ill patients, fostering an expectation that everyone could be treated and cured. n the first pandemic with a ''blogosphere'' and other rapid social media messaging tools that challenged conventional public health communication. been a particular focus for critics citing the uneven and suboptimal uptake across countries. development of a pandemic vaccine was a scientific success, but limited availability until after the autumn/winter wave had nearly peaked in the northern hemisphere contributed to lower coverage than anticipated [ ] . vaccination coverage depended on many factors, including availability, preordering, licensing and bureaucratic hurdles, logistics, convenience, and, most crucially, public and professional perceptions. this pandemic presented a particular risk communication challenge, since while infection usually results in mild illness, occasionally it is lethal, even in the young and previously healthy despite optimal treatment [ ] [ ] [ ] . in the absence of any excess risk of serious side effects compared to annual seasonal vaccines [ ] (despite the intensive effort to look for such) the benefits of immunisation far outweighed any potential down-sides at the individual level, particularly for those at higher risk for complications. notwithstanding such evidence, the cost of pandemic vaccines was considerable and a loss of public confidence has sometimes been triggered by unsubstantiated media reports of serious side effects with a ''new vaccine'' that utilised the same manufacturing technology as for years of seasonal vaccines. uptake among health care providers as role models has been mixed, as has their expression of the need for vaccination at all. this sometimes cast doubt in the minds of the public. conversely, pandemic deaths in young healthy people abruptly changed public perception (such as in canada, romania, and finland); supply and organisational issues then became crucial. another more fundamental criticism challenges whether vaccines should have been procured at all given an eventual surplus in the developed north. the unexpected finding that a single dose was immunogenic among all persons except for younger children, which reduced the required number of doses by half from the projected number needed in most countries, but this was not known in advance of countries placing vaccine orders. had there been ''overpreparation''? the prior worry had been the reverse -would there be sufficient production capacity to meet needs [ ] ? even in retrospect, and with the observed burden of the pandemic, a vaccine was clearly justified for countries where annual vaccines for seasonal influenza are routinely recommended. field and pharmacovigilance data so far have shown that these vaccines were immunogenic, effective, and very safe [ ] . however, the frailty was timing and availability. generally supplies came in later and in smaller amounts than forecasted, in part due to lower yield in growth of the vaccine virus strain than expected. reduce and delay community spread somewhat at the earliest stage to allow better preparation for mitigation response [ ] completely prevent entry of infected individuals due to suboptimal sensitivity and asymptomatic (including infected and within incubation period) or subclinical presentation [ ] many countries did not attempt these measures because of logistics, stage of pandemic [ ] or other cost-benefit considerations [ ] china hong kong sar japan personal protective measures (e.g., face masks, hand hygiene, cough etiquette, early self-isolation when ill) reduce risk of infection to self and close contacts (if self is ill and infected) [ , ] have not been evaluated whether they can provide significant populationlevel protection virtually all countries implemented these measures to varying degrees in health care settings according to the risk of the situation. almost all encouraged hand hygiene, cough etiquette, and early self-isolation most countries recommended adoption of hand hygiene, cough etiquette, and early self-isolation when ill, but use of face masks in the community was uncommon except in east asia. antivirals for treatment and chemoprophylaxis [ , ] mitigation: reduce illness severity and complications if administered early; reduce transmission from those receiving treatment; sometimes also used as chemoprophylaxis in high-risk circumstances provide significant population-level protection or allow containment attempts at source containment were not possible, as the pandemic was effectively already in who phase when what became the pandemic virus was first identified [ ] . initial observational studies suggest antivirals were successful when early treatment was administered canada germany hong kong sar japan uk us (these populations attempted the intervention initially but effort was not sustained towards the later stages of the pandemic) vaccines mitigation (a) at individual level by conferring immunity to infection in those at higher risk of severe disease or (b) at a population level by immunizing population groups especially those who are transmitting most (i.e., children) in most countries vaccine was not available early enough and/or arrived in insufficiently large amounts to achieve mitigation at a population level. greater population benefit may occur in the next season most of the orders arrived after the peak of the autumn/winter wave in the geographic north (whose countries had received most vaccines). therefore, judgement on their impact in averting serious morbidity and deaths may come only after the second winter. perhaps then, differential use by countries will allow for comparisons where there is good surveillance for severe disease and deaths. there have been claims of extraneous influence on the independent and objective judgment of expert advice that in turn influenced decision-making [ ] . these claims have been robustly countered as they relate to who's advisory and decision-making process [ ] . as harvey fineberg, chair of who's external review, pointed out, when assessing any allegations of impropriety or bias, or the perception of such, it would be important to distinguish between financial or other conflicts with potential pecuniary gains versus predispositions arising from an individual's background and experience. rather than aiming for a complete purge of any and all experts who had worked with vaccine manufacturers and received sponsorship, as these are often the very same group who possess the most relevant and useful expertise precisely because they have been closely involved in the research and development process, the focus should be on making the declaration of such interest wholly transparent and comprehensive according to a set of robustly established procedures that can withstand the strictest scrutiny. it is reassuring that who has honoured its commitment to making public the names and declarations of interest of the pandemic emergency committee when the pandemic was declared over on august . additionally, receiving advice should be differentiated from making decisions. the people entrusted with undertaking the latter task should then judge the validity of the advice rendered by experts, having taken into account their interest declarations. the decision makers should also be prepared to justify their actions. it is important to learn from our experience through the first year and beyond as we move into the new seasonal influenza [ , ] . it is theoretically possible, although unlikely, that the second winter of this pandemic will be worse than the first, as happened for the pandemic when transmissibility increased [ ] . equally, if the pandemic virus outcompeted the a(h n ) virus strains responsible for more intense seasonal epidemics, there may even be a diminution of disease burden in older people. as of this writing, seasonal influenza a (h n ) and b virus strains continue to cocirculate. antigenic drift in the h n virus is expected to occur in the future, especially under the pressure of so many people now being immune through infection or immunisation, although the timing is unpredictable. the pandemic virus is included in the trivalent seasonal influenza vaccine composition for both hemispheres. clear communication of public health messages will remain a particular challenge and not confusing what could happen (and should be prepared for) with what is most likely to happen. in assessing the pandemic response, decisions made during the exigencies of a public health emergency must be judged according to the best evidence available at the time. hindsight always gives perfect vision and using post-hoc information to evaluate prior decisions at best confuses and often produces unfair conclusions. preparedness plans will have to be revised in due time, after the many lessons learned have been gathered. this should be done quickly in case the worst is not yet over [ ] . however, rewriting plans should best wait for who leadership if national plans are not to diverge. a strong argument exists for making future plans more flexible and having extra descriptions including the many aspects of severity when a pandemic is emerging that then determine the consequential public health actions [ ] . broadening surveillance for a range of influenza a viruses among a wide range of animals (e.g., swine), not just in avian species, as well as strengthening the monitoring of seasonal influenza virus infections in humans will facilitate identification of novel influenza a viruses of pandemic potential, and earlier detection of the emergence of a pandemic virus. more broadly we should look beyond influenza and draw up contingencies for the emergence or re-emergence of other novel and known pathogens [ ] . one challenge faced initially in this pandemic was for timely collection and sharing of clinical data to inform optimal management of critically ill patients worldwide. establishing clinical research infrastructure prior to a pandemic and a central institutional review board will facilitate data collection and analyses [ ] , whether for the next influenza pandemic, sars outbreak, or next novel respiratory pathogen of global importance. clinical management of severe influenza disease should not be limited to the current antiviral regimen, and include the development of other therapeutics (e.g., novel antivirals and immunotherapy). ongoing improvements in the routine and timely monitoring of hospital admissions and deaths attributable to influenza, as well as representative serological surveys at regular intervals can provide epidemiological data with which to reduce uncertainty around the true burden of influenza and thus inform policy choices [ ] . assessment of the humoral and cellular immune response over time in a subset of vaccinated individuals could reveal how vaccine-induced immunity differs from natural infection, and whether cross-reactive responses to other influenza virus strains are modulated by the two types of immunological response [ ] . the latter could become important as the pandemic strain has already been cocirculating with other interpandemic influenza a virus strains in some parts of the world. greater access to antivirals and influenza vaccines worldwide is an ongoing challenge. although who secured pledges of million vaccine doses and monies for operations, and more than less-resourced countries have signed agreements with who for supply of vaccines, this gap remains. it is an indefensible fact that these vaccines started to flow to the poorer countries well after they began going to the countries with advance purchase arrangements. delivering timely pandemic influenza vaccination in countries without existing seasonal vaccine programmes is proving difficult. the longterm solution has to be improved surveillance, expanded monitoring of disease burden, and better prevention and control of influenza, including the development of seasonal vaccine use and production in all regions of the world [ ] . increased coverage of available bacterial vaccines (hib, pneumococcal) will help prevent secondary invasive bacterial coinfections with either seasonal or pandemic influenza. finally accusations of ''overreaction'' can be countered by the observation that investment in fire services or insurance is usually judged against their ability to respond to conflagrations. if the first test is a lesser fire, that experience should be used for improvements rather than as a reason to scrap the fire engines and cancel the insurance [ ] . influenza pandemics of the th century experience and lessons from surveillance and studies of the pandemic in europe writing committee of the who consultation on clinical aspects of pandemic influenza ( ) clinical aspects of pandemic influenza a (h n ) virus infection severe respiratory disease concurrent with the circulation of h n influenza pandemic influenza a(h n ) virus illness among pregnant women in the united states critical illness due to a/h n influenza in pregnant and postpartum women: population based cohort study estimates of the prevalence of pandemic (h n ) , united states preliminary estimates of mortality and years of life lost associated with the a/h n pandemic in the us and comparison with past influenza seasons the swine flu affair: decision-making on a slippery disease pandemic potential of a strain of influenza a (h n ): early findings comparative epidemiology of pandemic and seasonal influenza a in households incidence of pandemic influenza a h n infection in england: a cross-sectional serological study influenza a(h n ) seroconversion rates and risk factors among distinct adult cohorts in singapore cross-reactive antibody responses to the pandemic h n influenza virus entry screening to delay local transmission of pandemic influenza a (h n ) entry screening for severe acute respiratory syndrome (sars) or influenza: policy evaluation a clinical virological and epidemiological analysis what mexico taught the world about pandemic influenza preparedness and community mitigation strategies epidemiological characteristics and low case fatality rate of pandemic (h n ) in japan europe's initial experience with pandemic (h n ) -mitigation and delaying policies and practices school closure and mitigation of pandemic (h n ) , hong kong who interim protocol: rapid operations to contain the initial emergence of pandemic influenza the role of the health protection agency in the 'containment' phase during the first wave of pandemic influenza in england influenza pandemic: an independent review of the uk response to the influenza pandemic influenza (h n ) outbreak and school closure closure of schools during an influenza pandemic facemasks and hand hygiene to prevent influenza transmission in households: a cluster randomized trial household transmission of influenza a (h n ) virus after a school-based outbreak household transmission of pandemic influenza a (h n ) virus in the united states surgical mask vs n respirator for preventing influenza among health care workers: a randomized trial antiviral treatment for patients hospitalized with pandemic influenza a (h n ) the truth about tamiflu? neuraminidase inhibitors in pandemic a/h n flu interim results: state-specific influenza a (h n ) monovalent vaccination coverage -united states hospitalized patients with h n influenza in the united states pediatric hospitalizations associated with pandemic influenza a (h n ) in argentina mortality from pandemic a/h n influenza in england: public health surveillance study preliminary results: surveillance for guillain-barre syndrome after receipt of influenza a (h n ) monovalent vaccine -united states preparing for the next pandemic pandemic influenza a(h n ) breakthrough infections and estimates of vaccine effectiveness in germany conflicts of interest. who and the pandemic flu ''conspiracies the international response to the influenza pandemic: who responds to the critics. pandemic (h n ) briefing note how well are we managing the influenza a/h n pandemic in the uk? a new decade, a new seasonal influenza: the council of the european union recommendation on seasonal influenza vaccination estimates of the transmissibility of the (hong kong) influenza pandemic: evidence of increased transmissibility between successive waves emerging infectious diseases: a -year perspective from the national institute of allergy and infectious diseases early observational research and registries during the - influenza a pandemic studies needed to address public health challenges of the h n influenza pandemic: insights from modeling association between the - seasonal influenza vaccine and pandemic h n illness during spring-summer : four observational studies from canada global pandemic influenza action plan to increase vaccine supply we thank timothy m. uyeki of the us centers for disease control and prevention for substantial discussion and input. icmje criteria for authorship read and met: gml an. agree with the manuscript's results and conclusions: gml an. wrote the first draft of the paper: gml. contributed to the writing of the paper: gml an. contributed to the review from the experience of the pandemic in european countries: an. key: cord- -ovmko authors: sherman, allen c.; williams, mark l; amick, benjamin c; hudson, teresa j.; messias, erick l title: mental health outcomes associated with the covid- pandemic: prevalence and risk factors in a southern us state date: - - journal: psychiatry res doi: . /j.psychres. . sha: doc_id: cord_uid: ovmko the covid- pandemic has had a dramatic effect on the functioning of individuals and institutions around the world. this cross-sectional registry-based study examined some of the burdens of the pandemic, the prevalence of mental health difficulties, and risk factors for psychosocial morbidity among community residents in arkansas. the study focused on a period of gradual reopening but rising infection rates. the investigation included validated screening measures of depressive symptoms (phq- ), generalized anxiety (gad- ), trauma-related symptoms (pcl- ), and alcohol use (audit-c). a notable percentage of participants reported elevated symptoms on each of these outcomes. in separate multivariable analyses that accounted for a number of demographic and pandemic-related covariates, individuals who reported greater pandemic-related disruption in daily life, and those with a prior history of mental health concerns, were more likely to screen positive for depressive, anxiety and trauma-related symptoms. findings illuminate burdens experienced by community residents during a period of phased reopening, and offer a foundation for future screening and intervention initiatives. in the period since january , when the world health organization (who, ) and the us department of health and human services (health and human services, ) designated the coronavius disease (covid- ) as a public health emergency, the pandemic has had a sweeping impact on daily life for individuals around the world. the high transmissibility of the virus in conjunction with the lack of approved vaccines and limited therapeutics have contributed to an international public health crisis. communities have had to manage shortages of viral testing resources, diminished access to routine medical care, and sometimes conflicting preventative health recommendations. physical distancing provisions have constrained access to work and recreation. the jarring economic effects have left many individuals unemployed or with reduced incomes, and almost everyone has grappled with disruptions in normal routines. these widespread changes might contribute to a range of psychosocial difficulties, including social isolation, anxiety, uncertainty, and loss. there have been urgent calls for research regarding potential mental health effects of the covid- pandemic (holmes et al., ) . as yet, relatively little is known about responses among the general population in the us (liu et al, ; tull et al, ) , though work in this area is advancing rapidly. an initial wave of studies, mostly conducted in the immediate aftermath of the outbreak, suggested elevated levels of selfreported anxiety, depressive symptoms, and distress among community residents in china (e.g., huang and zhao, ; qiu et al. ; ren et al., ; tang et al. ; zhang and ma, ) and then in other countries such as italy (forte et al., ; germani et al., ) , spain (gonzalez-snguino et al., ) , germany (bäuerle et al., b; petzold et al., ) , india (varshney et al. ) , egypt (el-zoghby eta l. ), hong kong (choi et al., ) , and the us (liu et al. ; tull et al., ) . earlier studies similarly documented mental health sequelae following the severe acute respiratory syndrome (sars) coronavirus epidemic, though these data were derived largely from recovered patients rather than the broader community (gardner and moallef, ) . a larger, well-developed literature has focused on psychosocial responses to other types of community-level disasters, with findings pointing to consistent problems with depression and trauma-related symptoms, sometimes in tandem with other difficulties such as anxiety, substance use, and general distress (beaglehole et al. , lowe et al. pietrazk et al., ; tang et al., ) . the extent to which these difficulties might be associated with the evolving covid- pandemic in the us remains uncertain, and clearly there is a need for additional research. moreover, as yet very few investigations that have focused specifically on the experience of the general public during periods of phased reopening of businesses and institutions (tan et al., ) . such research would be especially important in communities experiencing increased infection rates, where residents have struggled with the dilemma of increased access and social interaction but also increased risk. another salient concern involves efforts to identify which individuals may be most vulnerable to psychosocial morbidity in response to the pandemic. it is recognized that periods of upheaval affect different individuals in different ways (mancini, ) . risk factors identified thus far in prior research regarding responses to the covid- pandemic included female gender, younger age, and a previous history of mental health concerns (bäuerle et al. b; el-zoghby et al., ; forte et al., ; germani et al., ; gonzales-sanguino, ; rossi et al., ; solomon and constantinidou, ; varshney et al., ) . specific aspects of the pandemic might be expected to increase vulnerability to distress as well, including viral exposure or infection, financial adversity, food insecurity, diminished access to healthcare, greater isolation associated with social distancing efforts, and increased disruption in daily life. different geographic regions have encountered notable differences over time in sars-cov viral infection rates and local government mitigation responses. the current study was a registry-based cross-sectional investigation regarding mental health responses to the covid- pandemic among community residents in arkansas. rural regions have been identified as among the populations of special interest (holmes et al., ) , though as yet rural areas of the us have not been studied. we sought to examine a number of clinically relevant psychosocial outcomes that might be adversely affected by a global traumatic event (i.e., elevated symptoms of depression, generalized anxiety, posttraumatic stress, and alcohol misuse), using validated self-report screening measures. additionally, we evaluated a range of demographic and situational risk factors that might intensify vulnerability to psychosocial morbidity. we anticipated that heightened levels of anxiety, depression, and posttraumatic stress would be associated with specific situational factors, including perceived viral exposure or infection, food and financial insecurity, reduced access to routine medical care, greater disruption in daily life, more stringent social distancing, and diminished daily structure. this was a cross-sectional registry-based observational study. the online survey was available for one month from may nd to june th , a period during which infection rates in arkansas increased significantly (centers for disease control and prevention, ) while the state progressively reopened (phase and early phase in arkansas). emailed invitations with links to the online survey were distributed to individuals in the arresearch registry, which is comprised of individuals who have expressed potential interest in research participation, and which varies widely with respect to rural vs. urban residence, socioeconomic resources, and racial/ethnic background. the registry is maintained by the translational research center at the university of arkansas for medical sciences (uams). individuals were included if they were age and older, resided in the state, and were listed in the registry as healthy community residents. an information form informed potential participants about study procedures, risks, and confidentiality provisions, and the return of the completed survey signified consent. the study was approved by the uams institutional review board with a waiver of documentation of written consent. the survey was administered using redcap, a secure web application for online research which allows participants to enter responses online (harris et al., ) . to enhance comparability across other studies in progress, instruments were derived as much as possible from those posted kroenke et al., ) was used to assess depressive symptoms. the reliability and construct validity of this screening instrument have been reported in multiple investigations (kroenke et al., , levis et al., . a cutoff score ≥ has shown a sensitivity of % and a specificity of % for major depression in a meta-analysis of findings derived from a variety of medical and nonmedical settings (levis et al., ) . the -item generalized anxiety disorder questionnaire (gad- ; spitzer et al., ) was used to measure generalized anxiety. studies in primary care patients (spitzer et al. ) and the general population (lowe et al. ) have supported the reliability and criterionrelated validity of this measure. in a meta-analysis, a cutoff score of demonstrated a sensitivity of % and specificity of % among individuals assessed in medical and community settings (plummer et al., ) . the -item ptsd checklist for dsm- (pcl- ; blevins et al., ) was used to evaluate trauma-related symptoms (blevins et al. ) . instructions were keyed to the covid- pandemic. research suggests good internal consistency and convergent validity in student and clinical populations. a cut-off value of has been viewed as an indicator of posttraumatic stress (blevins et al. ; bovin et al., ) . (our interest was in trauma-related symptoms; given the ongoing nature of the pandemic at the time of assessment no effort was made to assess temporal criteria for acute stress disorder or posttraumatic stress disorder.) the -item audit-c (bush et al., ) was used to assess alcohol use, as a secondary outcome. this measure has been widely used to screen for alcohol misuse. cut-off scores of ≥ for men and ≥ for women have been used as indices of heavy alcohol use (bush et al., ; bradley et al., ) . participants completed a brief form regarding demographic characteristics (e.g., age, gender, ethnicity, prior medical and mental health conditions, etc. year follow-up study (marel et al., ) . items inquired about covid- testing and perceived infection, using items adapted from the uas, and about perceived exposure and perceived covid- symptom severity, using items adapted from the atos. three items (coded no, yes, not sure) inquired about food insecurity (i.e., -worried that you would run out of food;‖ -ate less than you think you should;‖ or -went without eating for a whole day‖), and items asked about financial insecurity (i.e., missed or delayed payment of rent/mortgage and utility bills), using items adapted from the uas. eight items (coded no, yes, not sure) assessed social activity/distancing behaviors (e.g., -attended a gathering with more than people‖), using items adapted from the uas; these items were summed to create a total score. a series of items, created by the authors, assessed disruptions in daily life due to the pandemic (e.g., -trouble arranging for childcare,‖ -trouble staying involved with family/friends‖); each item was rated on a -point likert scale and summed to derive a total score. four single items, each with - response options, asked about other burdens, including illness or loss of loved ones due to covid- , and the impact of the pandemic on employment status, daily structure, and sheltering at home. additional items regarding healthcare assessed whether the pandemic had affected access to usual medical care, and whether participants had sought psychotherapy or psychiatric medication in response to the pandemic (each coded no, yes, not sure). finally, participants were asked about prior (pre-pandemic) mental health concerns, including a history of depression, anxiety, and ptsd diagnoses (each coded no, yes, not sure). descriptive statistics were used to summarize demographic variables and to characterize covid-related burdens. using established cut-off scores, we examined the frequency (percentage) of participants who screened positive for possible cases of depression (phq- ), generalized anxiety (gad- ), posttraumatic stress (pcl- ), and alcohol misuse (audit-c). preliminary bivariate analyses evaluated associations of elevated scores on the primary outcomes (i.e., scores above thresholds for depression, anxiety, and trauma) with demographic variables (e.g., age, ethnicity, gender, comorbidities) and situational risk factors (e.g., perceived exposure and infection, covid- symptoms, food and financial insecurity, access to routine medical care, pandemic-related employment changes, illness or loss of loved ones, reduced daily structure, social activity, and disruption in daily activities,), using t-tests, or chi-square or fisher exact tests, as appropriate. due to its non-normal distribution, a logarithmic transformation was used for the level of disruption in daily life; however, results were unchanged using the raw score, so the raw score is reported here for ease of interpretation. several variables were dichotomized for the analysis, including marital status (married/living with partner vs. all others), ethnicity (minority group vs. non-minority), number of comorbidities ( vs. or more), food insecurity (no vs. yes to any of items), financial insecurity (no vs. yes to any of items), perceived viral exposure (none vs. significant or prolonged exposure at work, in the community, or at home), perceived viral infection (no vs. yes or not sure), perceived covid- -related symptoms (none vs. mild, moderate, or severe), illness/death of loved ones (not affected vs. covid- illness or death of a loved one), pandemicrelated employment changes (no adverse changes vs. loss of job, loss of business, temporary lay-off, or reduction in hours/income), sheltering at home (sheltering and working at home and leaving no more than a few times per week vs. more frequent departures), and daily structure (few planned or scheduled activities vs. at least several planned/scheduled activities per week). separate multivariable logistic regression analyses were used to model associations of each outcome with demographic/situational factors that were significant in preliminary bivariate analyses. the data were checked for multicollinearity and residuals were examined. as partial adjustment for multiple comparisons p-values <. were considered significant. a total of individuals ( . %) responded to survey, completed the mental health measures and were included in the analyses, of who were sent emailed invitations. compared with those who not complete the survey, respondents were more likely to older (p =. ) and white (p =. ), and marginally more likely to be female (p = . ). data from ( . %) participants were missing for the pcl- (which was located at the end of the survey); individuals who did not complete this measure did not differ from those who did on any of the demographic or outcome variables (all p's >. ). missing data for all of the remaining variables was negligible (i.e., . %). sample characteristics are listed in table activities. the percentage who had experienced illness or death of a loved one from the disease was small (n = , . %). interestingly, in response to the stress of the pandemic, a number of participants reported that they had sought mental health counseling (n = ; . %) or had been started on psychiatric medication (n = , . %). bivariate associations of the primary mental health outcomes with demographic and situational factors are displayed in tables and . with respect to demographic correlates, younger individuals (all p's ≤. ), women (all p's ≤. ), and participants with lower family incomes (all p's ≤. ) were significantly more likely to screen positive for depression and anxiety (but not trauma symptoms), and those who reported a prior history of mental health diagnoses (all p's ≤. ) were more likely to screen positive on all three mental health outcomes. individuals with a greater number of medical comorbidities (p =. ), less education (p =. ), and those who were not married or living with a partner (p =. ) were significantly more likely to report clinically elevated levels of depressive symptoms. in bivariate analyses, participants who experienced greater disruption in daily life due to the pandemic (all p's ≤. ), and those who believed or suspected that they had been infected with the virus (all p's ≤. ), were significantly more likely to screen positive on all three outcomes ( this study offers an initial evaluation of mental health outcomes in response to the covid- pandemic among community residents in arkansas. findings provide novel information regarding the experience of individuals in a rural southern region of the us. additionally, this investigation is among the first to characterize a period of phased reopening, during which infection rates continued to grow appreciably. results indicate that a notable proportion of respondents experienced clinically elevated distress, as assessed by validated screening measures of depressive symptoms, generalized anxiety symptoms, trauma-related symptoms, and alcohol use. these levels would appear to exceed prevalence estimates derived from the general us population prior to the pandemic (kessler et al., ) , though the population estimates are based on diagnostic interviews rather than more provisional self-report instruments. findings suggest that mental health difficulties are a salient concern in the post-acute period of the pandemic-that is, during an interval of gradual reopening of businesses and venues within the state (phases and ) but progressively mounting cases of infection. (choi et al., ) reported that . to . % of participants had exceeded cut-off values for depression on the phq- or briefer phq- , and . to . % had exceeded thresholds for generalized anxiety on the gad- or gad- ; these estimates are in range with the values found here (i.e., . % for depression and . % for anxiety). prevalence rates were notably higher in an american study conducted with young adults earlier in the pandemic ( . % and . %, respectively), which is perhaps not surprising given the association between younger age and heightened distress (liu et al, ) . as yet, few studies have used any version of our measure of trauma symptoms (pcl- ); among those that have, findings have been quite variable but higher than our estimate of . % (gonzalez-sanguino et al., ; liu et al., ) . no comparisons are available as yet regarding our measure of alcohol use (audit-c). as anticipated, in bivariate analyses we found that younger participants, women, and individuals with lower incomes were more likely to screen positive for depression and anxiety (though not trauma symptoms), and those who had received a prior mental health diagnosis (i.e., mood disorder, anxiety, or ptsd) were at higher risk for all three psychosocial outcomes. . results regarding other demographic correlates have been inconsistent in prior research. we did not find strong effects for racial/ethnic background. nonetheless, given that minority groups face greater risks for covid- complications and mortality (khunti, ) , as well as broader inequities in healthcare, it seems clear that potential mental health sequelae in minority communities continue to merit close attention. consistent with hypotheses, several aspects of the pandemic were related to poorer outcomes in bivariate analyses. individuals who believed (or were unsure) that they had been infected were more likely to screen positive on all three mental health outcomes, and those who perceived that they had experienced physical symptoms of covid- were more likely to screen positive for depression and anxiety. (the number of participants who had received actual test results was too small to support meaningful analyses for viral status.) as anticipated, individuals who experienced food insecurity or financial insecurity were more likely to screen positive for depression and anxiety (with a non-significant trend for trauma symptoms). loss of income or employment was related to greater risk for depression and trauma symptoms. these results are a notable concern, given the breadth of the economic crisis precipitated by the pandemic, and underscore the need to address the mental health costs of economic turmoil. participants who experienced reduced access to routine health care were more likely to report elevated depression and anxiety symptoms. the gradual resumption of services by primary and specialty care clinics, facilitated in part by broader use of telemedicine platforms, might help diminish these concerns over time. fundamental changes in the fabric of daily life were also related to mental health difficulties. individuals who had the least structure in their daily lives, with fewer planned or scheduled activities to organize their day, were more likely to screen positive for depression and anxiety, while those who were more stringent in their efforts to shelter at home, seldom leaving their residence, were more likely to screen positive for depression and trauma symptoms. moreover, greater disruption in daily life (as reflected in difficulties caring for others for whom one is responsible, arranging childcare, sustaining activities or religious pursuits, maintaining valued connections with family and friends, etc.) was associated with greater likelihood of clinically elevated distress on all three outcomes. these findings are consistent with concerns that have been expressed about the adverse effects of ruptured routines, responsibilities, and social ties in the aftermath of the pandemic (holmes et al., ; tull et al., ) . multivariable analyses, which accounted for the effects of each of these demographic and situational risk factors, suggested that vulnerability to clinically meaningful depression was highest among individuals with a prior history of mental health problems, those who were unmarried, and those who experienced greater disruption in daily life due to the pandemic. risks for generalized anxiety were highest among community residents who had a prior mental health history, lower incomes, and who experienced greater disruption in daily life. similarly, the likelihood of elevated trauma symptoms was most pronounced among those with prior mental health diagnoses and greater disruption in daily life stemming from the pandemic. current results, in conjunction with findings from other studies reviewed here, suggest a need to marshal a range of pragmatic, accessible mental health services across the spectrum of care from prevention through screening and treatment. the need may be acute in view of an anticipated surge in demand for mental health care in response to the pandemic (figueroa and aguilera, ) , especially in regions such as arkansas struggling with protracted problems with disease mitigation, or those subjected to subsequent waves of infection. internet-based services are expected to play a major role; evidence supports the efficacy of interventions delivered on digital platforms (e.g., andersson et al., ) and smartphone applications (e.g., firth et al., ) . in the us and a number of other countries, barriers to billing for telehealth services have been reduced, but there remain racial and age-related disparities in digital literacy and access to technology (figueroa and aguilera, ) . there have been preliminary efforts to develop interventions specifically geared toward the challenges of the pandemic (e.g., bäuerle et al., a; figueroa and aguilera, ; sanderson et al., ; wei et al., ) , and these initiatives can be expected to grow. this study is among the first to examine mental health outcomes among community residents in arkansas, and one of the few investigations to use validated screening tools to evaluate these outcomes in the us. on average, the sample is older than those evaluated in many prior studies, which offers novel information about the experiences of individuals at increased risk for covid- -related mortality. the large sample, range of clinically relevant outcomes, and detailed attention to pandemic-related risk factors are among the salient features of the study. moreover, extensive efforts were made to select established measures that would allow for comparisons with future investigations. the study has important limitations as well. the cross-sectional design precludes any inferences about casual or temporal relationships (e.g., it is possible mental health difficulties contributed to greater financial insecurity or more stringent sheltering at home, rather than vice versa). further research is needed to examine changes in these outcomes over time, especially in view of the rapidly evolving nature of local infection rates, mitigation efforts, and economic disruptions. additionally, the sample was drawn from a research registry, and though it was racially, economically, and geographically diverse, it is not a representative sample of the population. women were overrepresented, which is common in survey studies (bäuerle et al., b; forte et al., ; germani et al., ; gonzaelz-sanguino et al, ) , and african americans and younger individuals were under-represented relative to the state population. the response rate was modest ( %), though in keeping with rates often observed in web-based community surveys (mcconnell et al., ; porter & whitcomb, ; sinclair et al., ) . to address these issues regarding selection bias and cross-sectional analyses, population-based studies using longitudinal designs would offer an important contribution at the next phase of research; such work is underway. scores on self-report screening measures are not the same as clinical diagnoses; in subsequent investigations it would be useful to include information derived from diagnostic interviews. finally, other variables that might be associated with mental health outcomes merit attention in future research, including level of media exposure, perceptions of personal risk, safety provisions associated with return to work, and attitudes toward vaccination. in sum, results suggest heightened levels of psychiatric morbidity during a period of reopening in response to the covid- pandemic, among community participants in a rural southern us state. individuals who struggle with greater interference in their day-to-day lives, and those with preexisting mental health difficulties, may be most vulnerable to mental health sequelae. author contributions: we declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted. the project described was supported by the translational research institute (tri), grant ul tr through the national center for advancing translational sciences of the national institutes of health (nih). the content is solely the responsibility of the authors and does not necessarily represent the official views of the nih. guided internet-based vs. face-to-face cognitive behavior therapy for psychiatric and somatic disorders: a systematic review and meta-analysis an e-mental health intervention to support broadened people in times of the covid- pandemic: cope it increased generalized anxiety, depression, and distress during the covid- pandemic: a cross-sectional study in germany psychological distress and psychiatric disorder after natural disasters: systematic review and meta-analysis the posttraumatic stress disorder checklist for dsm- (pcl- ): development and initial psychometric evaluation psychometric properties of the ptsd checklist for diagnostic and statistical manual of mental disorders-fifth edition (pcl- ) in veterans audit-c as a brief screen for alcohol misuse in primary care the audit alcohol consumptions questions (audit-c): an effective brief screening test for problem drinking covid- response, covid- case surveillance public data access, summary, and limitations depression and anxiety in hong kong during covid- impact of the covid- pandemic on mental health and social support among egyptians the need for a mental health technology revolution in the covid- pandemic can smartphone mental health interventions reduce symptoms of anxiety? a meta-analysis of randomized controlled trails the enemy which sealed the world: effects of the covid- diffusion on the psychological state of the italian population psychological impact on sars survivors: critical review of the english-language literature emerging adults and covid- : the role of individualism-collectivism on perceived risks and psychological maladjustment mental health consequences of disasters mental health consequences during the initial stage of the coronavirus pandemic (covid- ) in spain. brain, behavior research electronic data capture (redcap)-a metadata-driven methodology and workflow process for providing translational research informatics support secretary azar declares public health emergency for united states for novel coronavirus. health and human services website multidisciplinary research priorities for the covid- pandemic: a call for action for mental health science generalized anxiety disorder, depressive symptoms and sleep quality during the covid- outbreak in china: a webbased cross-sectional study prevalence, severity, and comorbidity of -month dsm-iv disorders in the national comorbidity survey replication is ethnicity linked to incidence or outcomes of covid- ? the phq- : validity of a brief depression severity measure accuracy of patient health questionnaire- (phq- ) for screening to detect major depression: individual participant data meta-analysis factors associated with depression, anxiety, and ptsd symptomatology during the covid- pandemic: clinical implications for us young adult mental health validation and standardization of the generalized anxiety disorder screener (gad- ) in the general population posttraumatic stress and depression in the aftermath of environmental disasters: a review of quantitative studies published heterogeneous mental health consequences of covid- : costs and benefits impact of covid- on substance use and access to services measure. matilda centre for research in mental health and substance use ströhle, . risk, resilience, psychological distress, and anxiety at the beginning of the covid- pandemic in germany resilience in the face of disaster: prevalence and longitudinal course of mental disorders following hurricane ike screening for anxiety disorders with the gad- and gad- : a systematic review and diagnostic metaanalysis the impact of contact type on web survey response rates a nationwide survey of psychological distress among chinese people in the covid- epidemic: implications and policy recommendations mental health during the covid- outbreak in china: a meta-analysis covid- pandemic and lockdown measures impact on mental health among the general population in italy the nature and treatment of pandemic-related psychological distress comparison of response rates and cost-effectiveness for a community-based survey: postal, internet and telephone modes with generic or personalised recruitment approaches prevalence and predictors of anxiety and depresson symptoms during the covid- pandemic and compliance with precautionary measures: age and sex matter a brief measure for assessing generalized anxiety disorder: the gad- is returning to work during the covid- pandemic stressful? a study on immediate mental health status and psychoneuroimmunity prevention measures of chinese workforce a meta-analysis of risk factors for post-traumatic stress disorder (ptsd) in adults and children after earthquakes covid- related depression and anxiety among quarantined respondents. psychol health psychological outcomes associated with stay-at-home orders and the perceived impact of covid- on daily life uas) coronavirus tracking survey, long form survey instrument-wave initial psychological impact of covid- and its correlates in indian community: an online (feel-covid) survey efficacy of internet-based integrated intervention on depression and anxiety symptoms in patients with covid- world health organization. who director-general's statement on ihr emergency committee on novel coronavirus ( -ncov). world health organization website impact of the covid- pandemic on mental health and quality of life among local residents in liaoning province, china: a cross-sectional study key: cord- -z j izi authors: ross, allen g.p.; crowe, suzanne m.; tyndall, mark w. title: planning for the next global pandemic date: - - journal: int j infect dis doi: . /j.ijid. . . sha: doc_id: cord_uid: z j izi in order to mitigate human and financial losses as a result of future global pandemics, we must plan now. as the ebola virus pandemic declines, we must reflect on how we have mismanaged this recent international crisis and how we can better prepare for the next global pandemic. of great concern is the increasing frequency of pandemics occurring over the last few decades. clearly, the window of opportunity to act is closing. this editorial discusses many issues including priority emerging and re-emerging infectious diseases; the challenges of meeting international health regulations; the strengthening of global health systems; global pandemic funding; and the one health approach to future pandemic planning. we recommend that the global health community unites to urgently address these issues in order to avoid the next humanitarian crisis. the west african ebola virus pandemic has shown us yet again that the world is ill prepared to respond to a global health emergency. this follows similar statements that were made after the h n outbreak in that ''the world is ill prepared to respond to a severe influenza pandemic or to any similar global, sustained and threatening public health emergency''. our response to the ebola zoonotic 'spillover' was delayed and as a result , people lost their lives in nine countries. the direct financial cost of the ebola pandemic was estimated to be in the vicinity of six billion us dollars and global economic losses over billion dollars. clearly there are lessons to be learnt from the ebola outbreak. in , following the severe acute respiratory syndrome (sars) pandemic, the international health regulations (ihr) were modified. while two thirds of the world health assembly countries have failed to comply with the regulations as of , and for the one third who say they did, there are serious concerns about the reliability of their self-assessment. now, with liberia declared free of ebola and declining incidence in sierra leone and guinea, these same regulations are once again being revisited after more than a decade. is this a futile exercise and should the ihrs be abandoned if they cannot be enforced by who and fulfilled by the world health assembly (wha) member nations? the national health systems in west africa, and for most low and middle income countries (lmics), would not meet ihr standards (despite claims by some member wha nations) and it is unlikely that following the ebola pandemic much will change. many have stated that who failed to respond to the current ebola epidemic in a timely manner but even if they did, would the outcome have been really that different? there were no drugs or vaccines available to treat and prevent the disease, thus quarantine, isolation and safe burials were the primary methods utilized to halt the spread of disease and were initiated by the afflicted nations themselves. it typically takes years if not decades to develop a vaccine or drug that will have public health impact. one only has to look at the countless billions that have been spent on trying to develop a vaccine for hiv, thus far without success. moreover, weak, malnourished, immunosuppressed populations living in poverty with little or no hygiene, sanitation or running water will always be highly susceptible to new emerging or reemerging infectious diseases. at 'ground zero' of the ebola epidemic it was believed that in , hungry children living in the remote guinean village of meliandou killed and ate infected fruit bats. , thus, what can realistically be done to prevent and contain future national epidemics from becoming global pandemics? we discuss a number of issues that urgently need to be addressed in order to plan, and possibly prevent, the next global pandemic. if one looks at the history of emerging or re-emerging infectious disease pandemics globally, on average they have appeared every decade but now, worryingly, the frequency between pandemics seems to be disturbingly shorter as evident with severe acute respiratory syndrome ( in order to mitigate human and financial losses as a result of future global pandemics, we must plan now. as the ebola virus pandemic declines, we must reflect on how we have mismanaged this recent international crisis and how we can better prepare for the next global pandemic. of great concern is the increasing frequency of pandemics occurring over the last few decades. clearly, the window of opportunity to act is closing. this editorial discusses many issues including priority emerging and reemerging infectious diseases; the challenges of meeting international health regulations; the strengthening of global health systems; global pandemic funding; and the one health approach to future pandemic planning. we recommend that the global health community unites to urgently address these issues in order to avoid the next humanitarian crisis. international journal of infectious diseases j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / i j i d human/host/reservoir interaction. weak malnourished populations in lmics serve as the breeding grounds for future pandemics ( figure ). for example, in metro manila, the most densely populated city in the world, approximately six million people live in slums with no piped water or toilets. according to who, million people in urban centres have no access to safe drinking water and over million lack sanitation. the un predicts that the world's urban population will double to over six billion by and most of the increase in density will occur in lmics. population density is directly correlated with the rate of transmission of respiratory and faecal-oral pathogens (e.g. mycobacterium tuberculosis, influenza, cholera, rotavirus, helminths). between and there were emerging infectious disease (eid) origins reported globally. figure illustrates some of the most recent eid epidemics. eids are primarily zoonotic ( %), originating in wildlife populations (e.g. hiv, sars, ebola, west nile virus, lyme disease) but bacterial pathogens have become increasingly of concern due to antibiotic resistance especially in the developing world. , multidrug-resistance (mdr) to mycobacterium tuberculosis, streptococcus pneumoniae and staphylococcus aureus are a global concern and gram-negative bacteria resistance to b-lactams is widespread. drug resistance to enteropathogens has also become a major global health challenge. mdr salmonella enterica typhi and s. enterica paratyphi are common in asia and sub-saharan africa, and there are increasing reports of reduced susceptibility to fluoroquinolones. campylobacter jejuni resistance to fluoroquinolones has become a concern in southeast asia, with rates of resistance of % reported from thailand. viral pathogens (e.g. ebola, makona variant (ebov), mers-cov, h n ) are also of concern due to their high rates of nucleotide substitution, poor mutation error-correction rate ability and capacity to quickly adapt to human hosts. table displays some potentially pandemic pathogens that should be under active global surveillance. the current outbreak of mers-cov in south korea is of grave concern given the case fatality rate is over %. surveillance of zoonotic diseases is largely based on detecting illnesses in humans who often serve as the sentinel species and dead-end hosts. apart from rabies, most national surveillance systems in the world do not monitor zoonotic diseases appearing in wildlife, yet % of zoonotic eids (e.g. anthrax, nipah virus, hantavirus, type a influenza, sars, mers-cov, ebola) come from this source. , many rna viruses have emerged and dispersed globally such as chikungunya virus, west nile virus and dengue virus. these three arboviruses alone have morbidity and mortality rates that far exceed those of the combined rates of sars, ebola and mers-cov. , thus, eid discovery efforts need to be directed toward reservoirs and vectors at the human-animal interface. the integration of human, veterinary, and agricultural medicine, as proposed by the 'one health' approach, should result in earlier warning of eids and provide us with a better opportunity to respond to potential spill-over threats. , moreover, targeting surveillance to regional hotspots of eids provides an evidencebased rationale for more appropriate allocation of global resources. the outbreak of ebola once again tested the revised ihr. according to gostin and friedman ( ) ''who fell short of its leadership responsibilities, and the ihr -the governing legal framework -displayed deficiencies''. the three west african countries involved (guinea, liberia, sierra leone) in the pandemic failed to comply with the ihrs capacity-building mandate and, to date, two thirds of wha member countries have failed to comply with the same regulations. , of the one third of the wha member nations that said they did comply, there has been no evaluation to verify their claims. , like the outbreak of h n in , the response raises questions regarding the extent to which the ihr can serve as a framework for global pandemic responses. , , if the wha member nations ( ) do not take the ihr core capacity-building requirements of disease surveillance, reporting, and response seriously, then why continue to use them as an international framework? in reality wha member nations from lmics see the regulations as an enormous obligation primarily developed to protect the health and welfare of developed nations. , during the ebola outbreak, controversy arose when american and spanish nationals were preferentially chosen to receive the experimental drug zmapp over west african nationals. moreover, when foreign medical staff became infected they were flown home for what was deemed superior medical care. clearly these ethical issues, which are well known by the wha member representatives, will impact on future ihr compliance. furthermore, member nations from lmics do not have the national capacity to adhere to ihr, given they have very weak infrastructure and poorly financed health systems. lmics must be given considerable financial and capacity building assistance or they will be unable to comply. these massive inequities must be addressed if we are to plan appropriately for the next pandemic. for most countries in the developing world it is difficult to improve their health systems to a standard that is similar to that of high-income countries. moreover, as mentioned, most lmic countries will not be able to establish core ihr capabilities without considerable donor support and international assistance for training, creating the necessary laboratory infrastructure for prompt diagnosis, and the technology required for 'real-time' reporting of epidemics. point of care screening tests for use in community health posts are increasingly available for rapid diagnosis of emerging pathogens and will shorten the time from presentation to treatment. however improvements and access to diagnostic technologies will need to be supported by the capacity to interpret and act on the findings. presently limited health-care dollars are spent on running tertiary national hospitals with little, or none, spent on preventive services, disease control or epidemic preparedness. however, most countries do have offices or departments for communicable disease control with the number of staff engaged in such full-time activities varying considerably. at the district/municipal level most developing countries have medical health officers and at the community level a considerable human resource of community health workers (chws). gostin and friedman ( ) have proposed a new global health framework with robust national health systems at its foundation and an empowered who at its apex. however, who has failed to provide the necessary leadership to coordinate global health emergencies on the ground and adequately support wha member nations to develop core ihr capacities. in september , the un assumed leadership of the ebola response and created the un mission for emergency ebola response (unmeer), the first un mission to respond to public health emergencies. in contrast with ihr recommendations, security council resolutions are legally binding for member countries. we now propose a new un centre for disease control (un cdc), potentially based in new york, to serve at the apex of a new global health framework with a number of new and existing regional cdcs reporting directly to it (figure ) . a proposed structure might be: national cdc departments reporting to their regional cdcs, and provincial/district/municipal cdc departments reporting to their national cdcs with community health workers at local health centres reporting to their municipal health officers. in sum, at the apex of our proposed global health framework would sit a new un cdc with security council authority and at the foundation, chws in local health centres. chws have transformed the health-care systems of many developing nations including bangladesh, india, ethiopia, and malawi and are absolutely crucial for future global security. on october th , world bank president, dr jim yong kim, has proposed a new pandemic emergency facility (pef). as stated on their website ''the world bank group is playing a lead role in conceptualizing the facility, working in coordination with international organizations, including the who, the private sector and other development partners. pef is a global financing facility that would channel funds swiftly to governments, multilateral agencies, ngos and others, to finance efforts to contain dangerous epidemic outbreaks before they turn into pandemics. financing from the pef will be linked to strong country-level epidemic and pandemic emergency preparedness plans, thereby incentivizing recipient governments and the international community to introduce greater rigor and discipline into crisis preparedness and reduce the potential for moral hazard. the pef is expected to cover a range of response activities such as: (i) rapid deployment of a trained and ready health care work force; (ii) medical equipment, pharmaceuticals and diagnostic supplies; (iii) logistics and food supplies; and (iv) coordination and communication. the pef would if the who contingency fund ( million us dollars) and the world bank pandemic emergency facility cannot be utilised to strengthen national health systems in lmics in order to meet ihrs core capabilities, then how can this be achieved? a multi-billion us dollar international health system fund has been proposed but considerable funding from both the private and public sector will need to be secured if the fund is to be successfully launched. the g , the european union, and philanthropic organizations will need to contribute. the implementation and monitoring of such funds at the national level will have to be carefully scrutinised and audited if the core capacities of the ihrs are to be achieved and maintained. ultimately lmic nations themselves will need to allocate health care dollars toward health prevention and epidemic planning. for many lmics this is not a priority and they are ill prepared to respond to epidemics on their own soils. building national capacity is the rate limiting step for global health security. if the international community fails to support this capacitybuilding initiative then this puts the world in a precarious situation with regard to future pandemics. it is well known in management circles that 'if one fails to plan then one should plan to fail'. with regard to pandemic planning, if we fail to build national epidemic capacities in lmics then we should plan to deal with a global pandemic in the not too distant future. however, in order to build such national capacity it will take considerable international political will that at the moment seems to be lacking. instead of allocating huge resources that 'react' to pandemics, funds must be earmarked to 'prevent' pandemics. this would include building national capacities of lmics and smart surveillance of eids in identified hotspots in the tropical and subtropical world. what are the likely organisms to cause a future pandemic and where will they originate from? zoonosis from wildlife represents the most significant global health threat of our time yet little funds are spent monitoring and identifying new zoonotic pathogens originating in wildlife. clearly a 'one health' approach is the way forward. pandemic preparedness and response-lessons from the h n influenza of a retrospective and prospective analysis of the west african ebola virus disease epidemic: robust national health systems at the foundation and an empowerd who at the apex report of the ebola interim assessment panel. who reference number: a / are we ready for a global pandemic of ebola virus? an audacious goal: the elimination of schistosomiasis in our lifetime through mass drug administration bat-filled tree may have been ground zero for the ebola epidemic outbreak of ebola virus disease in guinea: where ecology meets economy global trends in emerging infectious diseases urbanisation and infectious diseases in a global world surveillance for antimicrobial drug resistance in under-resourced countries enteropathogens and chronic illness in returning travellers surveillance and control of zoonotic agents prior to disease detection in humans factors responsible for the emergence of arboviruses ecology of zoonoses: natural and unnatural histories prediction and prevention of the next pandemic zoonosis the economic value of one health in relation to the mitigation of zoonotic disease risks the revised international health regulations: a framework for global pandemic response ebola in west africa: learning the lessons global health security: the wider lessons from the west african ebola virus disease epidemic health inequalities and infectious disease epidemics: a challenge for global health security the world bank. global pandemic emergency facility key: cord- -f v cih authors: paul, aneesh mathews; susanthomas, sinnu title: multifaceted covid- outbreak date: - - journal: nan doi: nan sha: doc_id: cord_uid: f v cih the time when everyone is struggling in the cruel hands of covid , we present the holistic view on the effects of this pandemic in certain aspects of life. a lot of literature exists in covid- , but most of them talk about the social and psychological side of the covid problems. covid- has affected our day-to-day life and its effects are extensive. most of the literature presents the adverse effect of the pandemic, but there are very few state-of-the-art approaches that discuss its beneficial effects. we see the multiple faces of the pandemic in this paper. to the best of our knowledge, this is the first review that presents the pros and cons of the pandemic. we present a survey that surrounds over effects on education, environment, and religion. the positive side of covid- raises an alarm for us to wake up and work in that direction. digital transformation in the marketplace. devaux et al. [ ] investigated the effects of hydroxychloroquine against sars-cov- virus. faridi [ ] has studied the effect of middle east respiratory syndrome coronavirus (mers-cov) that has caused havoc in saudi arabia in . the author has seen the effect of mers-cov on male and female in riyadh. the authors in [ ] , [ ] , [ ] , [ ] assessed the psy-chological stress of covid- on health workers. xiang et al. [ ] reported an overview of infected healthcare workers in china and italy during the early periods of the covid- . the authors in [ ] , [ ] , [ ] studied some social impacts of covid- . chakraborty and maity [ ] studied the covid- effect on the economy and global environment. ivanov [ ] predicted the impact of covid- on global supply chains. xu et al. [ ] studied the air quality index to see the effects of covid- on the environment. chinazzi et al. [ ] studied the effect of travel and quarantine influence on the dynamics of the spread of covid- . braun [ ] narrated examples of the situations of the poor during covid- . ahmed et al. [ ] highlighted the precarious position of postdoctoral fellows in academic positions due to covid- . staniscuaski et al. [ ] projected out the problems faced by academic mothers having many difficulties working at home during covid- . bouillon et al. [ ] discussed the positive side effect of coronavirus on air pollution. suicide rate has increased during the pandemic time [ ] , [ ] .the situation of covid- has diverse effects in india [ ] . in this paper, we study the multi-faceted effects of covid- on our planet. our contribution in this paper is threefold. ) the pandemic has affected the entire education sys-tem and a new era of distance learning has emerged. a review on various education systems during the pandemic is looked out. ) covid- has benefits in certain areas such as the environment. the environmental effects are discussed. ) overall change in religious practices has changed and we review these aspects in this paper. the remainder of this paper is organized as follows. section ii highlights the overall change in the education system during the covid- season, and discusses the social and psychological impacts of the pandemic. section iii presents the religious and environmental effects of coronavirus. section iv presents the conclusions of this paper. education system is one of the prime pillars in developing a nation. it constitutes an important ingredient in deter-mining the growth of a country. human development is an important determinant in a person's health and trade. the education system is severely interrupted in most of the countries since the outbreak of this pandemic across the globe. the schools, colleges, and universities are in the total closure mode. billions of academic learners became devoid of their knowledge acquisition during this pandemic. the teachers, students, schools, and families -all became a victim of this bitter truth. the world has gone under complete reorganization during this period be it any sector, the education sector is not left apart. the speed of the pandemic and the closure of schools was so fast that it was difficult to come up with a solution with all facilities. the closure of educational institutes will not only have short term impact, but leave a footprint on economic and societal components. there are number of areas in education that is affected by the pandemic: the landscape of higher education across the world is defined by the cross border movements of the students. globally every year there is an increase of % in the number of students studying abroad as shown in fig. . as per the unesco [ ] , the students enrolled for higher education for a period of typically a year to seven years. according to the statistics given by organization for economic cooperation and development (oecd), the in-ternational student population with demographic changes is likely to reach million by [ ] . most of the international students prefer either the united states, the united kingdom, germany, france, or australia for their higher education [ ] as shown in fig. . as per the statistics in , the top host countries involved in sending students to other countries include china, india, south korea, and france [ ] as shown in fig. . the pandemic has brought a sluggish impact on the movement of students across the border. the travel restrictions during lockdown and the fear of pandemic will affect the cash flow at the universities. parents are afraid to send their ward across any border in this situation. the universities in these countries are undergoing extreme pressure on student admission. if this problem persists, there is a possibility of decline in international higher education in the com-ing years. the pandemic has brought a devastating effect on the global education system. the pandemic has shrinked the world under their own home and hometown and cross border movements seem to be a threat to the life of an individual. ) online learning active learning is not only a source of fun but also a source of formation of cognitive social skills. carlsson et al. [ ] emphasized on the increase in cognitive skills with the total number of school days attended. the study carried out in sweden showed that crystallized intelligence can be aug-mented significantly by % of a standard devia-tion while attending ten days of extra schooling. the closure of schools for almost a month at the beginning of this pandemic can cause a trivial loss of % of the standard deviation. the pandemic has left the learning systems with no options other than embracing a distant or online learning. as per the statistics released by unesco [ ] , the pandemic has affected nearly . billion learners around the world. the recovery of the disruption of the learning process is essential to facilitate the continuity of the education system. when physical presence is a risky situation, an alternative has to be taken at various levels of learning. online learning is a new strategy embraced by the education system in this time of pandemic. the transition from active learning to passive learning was very rapid during this pandemic. the curriculum was not designed for passive learning, so the viewers are losing their interest in the content. the shift in developed countries to the online learning system does not pose any problem, but for developing and under-developed countries -it is a challenging situation. the rural areas of these countries do not have the basic infrastructure to facilitate the online learning. the pandemic has posed a threat to the overall development of the underprivileged in these countries resulting in shattering their economies. the video telephony softwares is being used for distant learning. the concept of keeping the electronic gadgets far from the children has been loosened even for a primary school going child during this pandemic. the online learning has removed the commuting time for the learners but on the other hand, made them addicted to electronics devices leading to many social, psychological, and physical disabilities. online learning brought a paradigm shift in one's own comfort zone. the hassle of traffic jams, pollution, queues, health problems, allergies is halted in this course of time. most of the learners are happy with the online learning system since environmental problems do not leave them void of attending classes. online learning has brought an end to the centuries old practice of chalk and talk. due to the sudden change to the online learning in the education system, the preparedness of the tutors was a concern. an inhibition of this sudden change was found in the tutors during the beginning phase. the course curriculum was not made for passive learning. the sudden shift in the teaching system with inadequate preparation from the learner side was also noticeable. teaching is a knack that everybody is not gifted with, so many tutors are not so effective in an online mode. in countries like india, where there is a huge shortage of technology savvy tutors, this model of learning would not work out. lack of infrastructure and resources in the rural parts of these countries is an obstacle for teachers for a complete preparation of imparting the knowledge. an unavailability of dedicated online platforms is posing a threat for outcome based education. the tutors are adjusting the platforms with the video telephony platforms. if the problem of pandemic persists, there is a need for creating dedicated learn-ing platforms. most of the schools and universities undergo the ad-mission process during the month of may-june for fall semester. due to the severity of the pandemic in many parts of the world, the admission process is hindered. the situation in the admission process is becoming alarming in the foreseeable future with the pandemic situation. traditional admission procedures would not take place in this season. new procedural strategies for admissions should be considered in order to fill the gap in this pandemic. some universities are not con-sidering taking any students the current academic year, while some are luring people with discounts. it is a crucial task for the students to decide which school they would like to attend without visiting respective campuses. the pandemic has forced people to create a virtual world of working at home. the virtual world cre-ates effortless paths to collaborate across the globe. the conferences, academic meetings, classes, and seminars have gone online leaving a space for academic collaborations. we see a lot of unprecedented collaborative work globally among the educators [ ] during this pandemic leading to a loss in the travel economy. the cancellation of universityfunded international travel for conferences, blanket bans on any international travel for spring break, canceling study-abroad programs [ ] made different academicians closer virtually. collaborations serve a larger purpose as an individual and also as an organization [ ] . there are lots of scope for online conferencing platform business. the concept of education will be reformed envisaging the global collaboration. globally, the collaboration has brought a new direction to certification courses and degrees. these collaborations fulfills the need of each other while dividing the work in chunks. the pandemic has brought a halt to the organizational structure making a scarcity in the manpower. the universities are facing challenges to recruit new students, and faculty during this pandemic. the retention is also questionable. the recruitment for the faculty is a worrisome issue for the administration when the risk of losing students is hovering around them. when survival of many institutes is a burden for them, the recruitment of new faculty members increases their load. due to the recession in the corporate sector, the recruitment process for the students is a great disaster. the job offers have been withdrawn creating a havoc in the student community. the global outlook of the pandemic would massively devastate the livelihoods in the entire world. fig. the consequences of a sudden shift in the learning system brought a slowdown to the world economy. the international students from china and india constitute . % and . % of the total international students in the usa higher education sector. the travel restrictions during the pandemic would cut down the admission process leading to an economic burstdown. the conveyance to the institutes are at a halt causing recession in the travel sector. all the learners cannot afford to stay near their institutes, so they stay far and face a time-consuming and costly commute [ ] . students spend approximately £ a month for commutation to their academic institutes. pandemic has saved the pocket of students in higher education. in countries like india, private schools and private vehicles charge a heavy conveyance fare for the commutation. the pandemic has given relief to the parents. same time, the train services and the road services are hit badly. cashflow in these services reduced leading to an economic crunch in these sectors. the students use to take long commutes to the institutes taking away their well-being [ ] . they are deprived of their sleep and exercises. to commute long distances, students get up early and the daily routine is hampered. lack of daily exercises make them obese which is a major cause of concern among the youngsters. students carry a heavy load of bags on their backs to the school in countries like india. carrying school bags are back breaking work to the students. heavy loads of school bags have deleterious effects on the spine of children [ ] . many measures are taken to reduce the amount of school baggage, but it was all at a minuscule level. the online learning during the pandemic season turned out to be a heavy relief to the students carrying heavy school bags. being in a well-being state is an important aspect of human being. we tend to give rest to the body if it is not in a position to commute. the learners refrain from going to class if they are not well. the pandemic situation takes off all the health issues and helps in smooth learning of classes. the students are free to learn from their home in any physical condition. the structure of the learning system is based on various assessment procedures. the students are assessed based on the merit system. the pandemic hit the world during the key assessment period cancelling many exams. the cancellation of exams would have a long-term consequence on the ca-reer of the student. first, the internal assessment and then the public examinations were cancelled. the grades at the end of the academic year were predicted according to some undefined rules influ-encing the privileged students. education system is shifting to an online assessment system that can cre-ate measurement errors. these errors in an abrupt assessment would increase the differences between the privileged and under-privileged students in the future. the labour market would face the dire consequences of inefficient assessment scores. the entrance exam in higher education is a worst hit in assessment procedures. the entrance exams to top universities are either postponed or cancelled. the exam agencies are coming up with alternative solutions in consultation with the international in-stitutes. ) strike free education education system is at stake be it teachers strike or any other political strike. these strikes prevent students from attending classes. according to the study at argentina [ ], days of teachers strike there is a decline of years of education by : % in an academic year. the teacher strike has a negative effect on student learning and their overall achievement [ ]. frequent political strikes or hartals impact the overall education system. according to the statistics in kerala, india [ ], there would be one hartal in every four days leading to disruption in the holistic coverage of prescribed syllabus. the online education system is not affected by any sort of socio-political disruptions. education system in the virtual platform eased out the disturbances due to the strike. the education aspects during the pandemic impacted the family in many ways. a) the education system comes with mid day meals for the underprivileged in countries like india and the pandemic situation has taken the bread out of the mouth of some children. children from poor families would come to school with the greed for getting a one time meal. if the pandemic persists, then there is a high chance of drop-outs from the school. moreover, it would be a tremendous challenge to keep up the motivation of the underprivileged children after the pandemic. b) most of the parents in the pandemic era are working from home. it is difficult for most of the parents to handle domestic pressure and work pressure at home. working parents are juggling with children and working at home. global home schooling would pro-duce disparities depending on the ability of the family members to help their children learn. the inequality in each student skill set would overall affect human capital growth. c) the unprecedented learning system needs assistance of basic infrastructure for its smooth conduct. power supply and internet connectivity are the essentials needed without disruption. to avail these resources at home and keep the student without stress is a burdensome work for the parents. in developing countries, it is a difficult situation to maintain the resources around the clock. d) women take care of the children and rela-tives at home when compared to men. they are more insecure in their jobs. women are struggling with their household obligations and work during the pandemic. the juggling between children at home and work would reduce their opportunities and earnings at the workplace. women have to work harder in order to compensate for the workload and at an increased stress during this period. the study says that many women have left their job during the pandemic due to the imbal-ance in the worklife. covid is a disaster that would widen the gender inequalities. studies reveal that there is an increase of % in usage of electronic gadgets by the impressionable minds. gadget addiction is one of the major drawbacks of the online learning system. irritational behavioural patterns are observed in the students during this pandemic. the long time exposure to electronic gadgets are making them obese. an attachment towards gadgets creates a space for emo-tional imbalances in their personality. students have confined themselves into their own territory keeping them away from the societal component of life. studying and living together with their companions under one roof increases their social abilities but lockdown has created a void space for problem solving and decision making skills. social unawareness and lack of cognitive skills would be more visible. these skills improve their employability, productivity, health, and well-being in the future, and ensure the overall progress of the nation. people around the world are worried about the undergoing changes in the climate. the global temperature is a major concern for many environmen-tal changes. the last five years ( - ) were recorded as the hottest years. globally °c temperature has increased since the last century. an increase in per capita gross domestic product (gdp) is proportional to global warming. a study conducted by [ ] shows the environmental degradation and co emission has increased with the economic growth and more production [ ] . according to the census in , the countries with the highest co emis-sion in the world is shown in fig. . we see that the environmental degradation increases with the increase in production for economic growth. a lot of measures were taken to reduce the hazardous emis-sion, but a substantial decrement was not possible. the co or greenhouse gas disturbs the natural regulation of temperature in the atmosphere and leads to global warming and climate change. humans manipulated nature according to his whims and fancies that resulted in paradoxical im-reduced by % or . gigatonnes (gt) which is equivalent to a decade earlier data. there was an average decline of % energy demand per week during full lockdown and an average of % decline in partial lockdown countries. an unprecedented decline in demand for various fuels is seen during the pandemic as shown in fig. . the crisis of pandemic is paving a way for clean energy transitions. this decline in co emission is unprecedented and would be temporary, unless there is a resilient effort to change the structure. balances. humans are responsible for the emission of the greenhouse gas in the atmosphere over the last years. covid is the only disaster that has come as a boom to the environment. the major sources of co emission are energy, agricultural processing, land use changes, industrial processing, and other waste. electricity and heat is generated by burning fossil fuel, coal, and natural gas. a total of . % greenhouse gases are emitted while burning these fuels and are the leading cause for tempera-ture regulation. industries emit . %, transporta-tion - . %, agriculture processing - . %, land use change - . %, and industrial processes- . %. distribution of different sources of greenhouse gas are shown in fig. . before the arrival of pandemic, it was difficult to control the industrial and transportation emission. an impossible action of putting a halt on these hazardous sources was done overnight. accord-ing to estimates published by international energy ) vibration in the earth crust high frequency seismic waves are propagated into the earth mainly due to the activities of the human. the seismic noise renders the real time estimate of population dynamics. the covid pandemic period is the longest seismic noise quiet period ever recorded. according to the royal observatory of belgium [ ], the seismic noise of the earth during the pandemic is not prevalent, reducing the vibration of the earth by %. the vibrations are reduced by one-third of the normal activity during the lockdown. it becomes easy for seismologists to detect the movement in the earth crust without much of an expedition. the construction projects in some countries were at complete hold during the initial stages of the lockdown. the availability of the workforce and the site constraints halted some of the projects. construction activities create an adverse impact on the environment. the burning of fossil fuel, noise, and the waste of the construction contribute to the regulation of the temperature in the environment. the halt in construction reduced the amount of pm by three times in the month of april . air pollution is recorded highest in many cities of india. the annual average pm . concentration during the lockdown was much better than the safer limit [ ], [ ], [ ] , [ ] as shown in fig. . under the banner of economic growth, entire industrial and other waste is dumped into the rivers making it difficult to breathe. the aquatic species are becoming extinct due to the pollutants in the river. india is at the top of river pollution. ganges river is the most populated river in the world. the present pandemic has come as a blessing in disguise for rivers. the water pollution has decreased con-siderably during covid period. the waters from the rivers in india are tested during covid and the results provoke us to take measures to clean the rivers. the ph levels, the conductivity level, dissolved oxygen (do), and the biological oxygen demand (bod) of the water is reduced during the lockdown period [ ] . a betterment in standards of drinking water was seen during the lockdown period as shown in fig. . pandemic season was a lockdown for mankind, but on the contrary animals were liberalized. humans were away but animals took over the deserted cities and towns. animals took the advantage of the drop in human activity and came out to explore and play in the public places. scavengers are not around to shoo them away giving a space for wildlife to thrive. mallard ducks, wild deers, herd of goats, troop of monkeys, kangaroos, gangs of turkeys, and many others are taking human spaces. road mortality was a threat to the wildlife population [ ] . the mortality has reduced to % due to less traffic on roads in the usa. less roadkill reduces the ecological imbalances. some animals have successfully adapted to live alongside humans and their survival is dependent on them. an absence of human activity endangers some wildlife species. some governments mobilize funds to feed and preserve these animals, and the lockdown hindered their progress. according to the livestock census of , there are around million stray dogs in india. these dogs are fed by ngos or leftovers from restaurants. the closed restaurants and the restrictions in the movement made these stray dogs starve. the sustenance of the people in rural places of poor countries became difficult during the pandemic. people are driven to take extreme steps for their livelihood through poaching. the illegal hunting of endangered species in african continent is a threat for the wildlife society. according to study conducted by traffic, the wildlife poaching in india has increased twice during the pandemic pe-riod. it has increased from % to % during the lockdown period. it may turn disastrous and pave a way for another pandemic. humans struggled from recent pandemics such as aids, ebola, mers, and sars that came as an effect of consumption of animal meat [ ] , [ ] . it becomes the responsibility of the wildlife conservation society to prevent any pandemic in the future. due to the clean air and lockdown, non-covid diseases are at steep decline in countries prone to all pollution. the behavioural changes during the lockdown has brought a decline in insurance claims by % in india. waterborne infectious diseases and respiratory related diseases are being recorded as lowest during the pandemic time. the claims on deadly diseases such as cancer has turned down by % as per the statistics of the insurance companies in india [ ] . due to decrease in vaccination [ ] and disruption in the hospital services, there is a possibility of an outbreak of other diseases. religion makes people follow different practices and form socio-cultural groups. each culture recorded in human his- ) wildlife effects tory practised some organized system of beliefs and prac-tices. we tend to see very few people practicing faith in normal life. for some it seems absolutely mandatory but for some these are obnoxious practices. religion and faith is an integral part of people's lives worldwide, even though it is increasing. religious practices were hampered during lockdown. various aspects of religion during lockdown are discussed in detail: religion is a predominant factor for satisfaction in life, on the contrary the religious tensions can be annoying [ ] and affect the economic growth of the country. religious fervency is vigorous in most secularized countries [ ] . the polarization towards targeted groups increased in many countries during the earlier stage of the pandemic [ ] . since the cases of the virus were aggravated by the religious gathering in some countries, we could see religious bigotries coupled with the pandemic. the virus has morphed itself into an anti-community virus [ ] , [ ] . the bigotries and xenophobia towards different sects of people can be seen in different countries as shown in fig. . prayer meeting in france, and many more [ ] , [ ] , [ ] . the pandemic spread in various countries was sparked by religious gatherings as shown in fig. religion and politics are a crucial part of life and covid- has acquainted the human life without these jargon words. the places that culminated religious polarization at the earlier stages of the pandemic were felt at peace in the later stages of the pandemic. everybody came out in unison to curb this pandemic through their services. charity works and social commitment was seen at large during the pandemic. the role of religious practices in spreading covid- was predominant [ ] , [ ] . the religious lead-ers surpassing the mass gathering orders became a source of virus carriers in the entire nation. some of the early covid outbreaks were traced back to religious gatherings such as daegu church in south korea, bnei-brak in israel, oom in iran, tablighi-jamaat in india, tabligh-e-jamaat in malaysia, many people are fervent in religious practices such as visiting places of worship, mass gatherings, religious celebrations, and many more. all these practices are hindered during the pandemic. entire paradigm shift was seen in the religious fraternity. the religious holidays and celebrations were practiced at home. the key moments of rituals were experienced in their own home. religious leaders were bound to ask their followers to stay at home during pandemics. they started releasing double the amount of messages for the community to cope up with the stress during the pandemic. the religious organizations started doing more charita-ble services. people started living with faith rather than religious places. social distancing would be the most tricky in places of worship. the survey concludes that the public has become comfortable staying at home and practising their faith till the resumption of the normal situation [ ] . religious leaders are challenged to foster and to bring their services and communities together in these trying times from a distance. the online platforms were used to connect to the community during religious ceremonies. during the pandemic time, the searches for prayer have skyrocketed in google search engines. many spiritual and therapeutic activities, such as yoga, meditation, martial arts, and conscious dance classes have gone online during this pandemic. these temporary solutions are not sustainable solutions as they need physical relationships with people. the places of worship is a source of income for many religious leaders and the common man. these sources of income are hindered by the pandemic. life without religious practices also hit livelihoods of businesses around the places of worship. a loneliness during the pandemic times created furore among the individuals. people were compla-cent in their comfort zone but they were kicked out of that with hopelessness and despair. adapting to a new environment with a u-turn in an individual's life was a difficult task. life is fragile during pan-demic time but increase in spirituality and faith be-came a vital part of their life. religion is considered as a source of solace in terms of pain and scepticism. the role of prayer in the current pandemic situation among the general public is noteworthy [ ] . there was an increased interest ever recorded in search of prayer as per the daily data recorded from google for countries. according to tearfund covid prayer public omnibus research [ ] conducted in the uk during the lockdown period gauged the responses to spiritual practices. the statistics was conducted on , uk adults aged + and shows that nearly half ( %) of uk adults pray regularly and a quarter ( %) of uk adults attended online religious service during lockdown. one in twenty uk adults ( %) who attended religious service have never gone to church and twothirds ( %) of uk adults agree that prayer changes the world. generally, religion is more appealing to the older generation, but during the lockdown period the reli-gious revival was seen in younger ones. the highest number of quran apps from google playstore was downloaded during pandemic [ ] . irrespective of any religion, everybody started seeking hope in their faith and started praying for various topics as shown in fig. . we humans have gone through multiple virus pandemics in different times. pandemic came with human devastation but with times we came over it. covid- is a disaster in many aspects of life, but in some it has proved a blessing. this paper describes the multiple faces of virus outbreak. we have looked upon a few possible areas of life which have been affected by covid- such as the educational sector, environmental sector, and religious sector. the areas where it is a boom leaves a space to ponder on the living standard of human beings. lot of effort was taken with respect to some serious problems on the earth, but everything was in vain and it was noticed that there was a sudden break in these problems during a pandemic. once the pandemic is over, there is a call by the earth to make it a better healthy living place. comparative pathogenesis of covid- , mers, and sars in a nonhuman primate model effects of covid pandemic in daily life rolling updates on coronavirus disease (covid- ) predicting covid- in china using hybrid ai model a weakly-supervised framework for covid- classification and lesion localization from chest ct deep learning covid- features on cxr using limited training data sets accurate screening of covid- using attention based deep d multiple instance learning dual-sampling attention network for diagnosis of covid- from community acquired pneumonia diagnosis of coronavirus disease (covid- ) with structured latent multi-view representa-tion learning wearable sensing and telehealth technology with potential applications in the coronavirus pandemic easyband: a wearable for safety-aware mobility during pandemic outbreak the impact of covid- on consumers: preparing for digital sales a comprehensive review of the covid- pandemic and the role of iot, drones, ai, blockchain, and g in managing its impact new insights on the antiviral effects of chloroquine against coronavirus: what to expect for covid- ? middle east respiratory syndrome coronavirus (mers-cov): impact on saudi arabia the psychological im-pact of covid- pandemic on health care workers in a mers-cov endemic country occurrence, prevention, and management of the psychological effects of emerging virus outbreaks on healthcare workers: rapid review and meta-analysis epidemic on medical staff in china: a cross-sectional study mental health impact of covid- pandemic on spanish healthcare workers the impact of novel coronavirus sars-cov- among healthcare workers in hospitals: an aerial overview covid- : disease, management, treatment, and social impact mitigating the psychological effects of social isolation during the covid- pandemic loneliness and social isolation during the covid- pandemic covid- outbreak: migration, effects on society, global environment and prevention predicting the impacts of epidemic outbreaks on global supply chains: a simulation-based analysis on the coronavirus outbreak possible environmental effects on the spread of covid- in china the effect of travel restrictions on the spread of the novel coronavirus (covid- ) outbreak the moment to see the poor the precarious position of postdocs during covid- impact of covid- on academic mothers coronavirus and exceptional health situations: the first disaster with benefits on air pollution can we expect an increased suicide rate due to covid- ? uncomfortably numb: suicide and the psychological undercurrent of covid- covid- pandemic: mental health and beyond -the indian perspective facts and figures: mobility in higher education study abroad statistics: convincing facts and figures online learning during the covid- pandemic centre for monitoring indian economy long school commutes are terrible for kids the effects of teacher strike activity on student learning in south african primary schools kerala suffers hartal every each one burns rs -crore hole in state's economy economic growth and carbon dioxide emissions? quieting of high-frequency seismic noise due to covid- pandemic lockdown measures air pollution dropped % in bengaluru during lockdown air quality in chennai during lockdown -do we have clues to mitigate air pollution reduction in water pollution in yamuna river due to lockdown under covid- pandemic impact of covid- mitigation on wildlife-vehicle conflict prioritizing zoonoses for global health capacity building-themes from one health zoonotic disease workshops in countries anthropogenic drivers of emerging infectious diseases insurers see up to % fall in non-covid medical claims who and unicef warn of a decline in vaccinations during covid- religious polarization, religious conflicts and individual financial satisfaction: evidence from india religious polarization: contesting religion in secularized western european countries india: infections, islamophobia, and intensifying societal polarization new center for public integrity/ipsos poll finds most americans say the coronavirus pandemic is a natural disaster statca of increase in anti-asian sentiment, attacks covid- and religious congregations: implications for spread of novel pathogens religion and the covid- pandemic god and covid- public health response to the initiation and spread of pandemic covid- in the united states high covid- attack rate among attendees at events at a church-arkansas have prayers changed in lockdown? people of faith answer in crisis, we pray: religiosity and the covid- pandemic tearfund covid prayer public omnibus research how coronavirus is leading to a religious revival key: cord- -ym ce ux authors: chawla, sonam; saxena, shailendra k. title: preparing for the perpetual challenges of pandemics of coronavirus infections with special focus on sars-cov- date: - - journal: coronavirus disease (covid- ) doi: . / - - - - _ sha: doc_id: cord_uid: ym ce ux covid- , arising from novel, zoonotic coronavirus- , has gripped the world in a pandemic. the present chapter discusses the current internationally implemented pandemic preparedness strategies succeeding/recommended to curb the covid- threat to humankind. the updated phase-wise categorization of a pandemic as recommended by the who is described, and associated innovations in surveillance, response, and medical measures/advisory in practice across the globe are elaborated. from a bird’s eye view, the covid- pandemic management relies on revolutionizing the disease surveillance by incorporating artificial intelligence and data analytics, boosting the response strategies—extensive testing, case isolation, contact tracing, and social distancing—and promoting awareness and access to pharmaceutical and non-pharmaceutical interventions, which are discussed in the present chapter. we also preview the economic bearing of the covid- pandemic. the present-day pandemic spotlight on covid- (coronavirus disease- ) was earlier placed on zika virus, h n , severe acute respiratory syndrome (sars), chikangunya, middle east respiratory syndrome (mers), and ebola. the "advancements" of the human race-increased urbanization, global travel, changes in land use, and fervent exploitation of the nature-are also the prime reasons for zoonosis and emergence of novel infectious diseases such as above (madhav et al. ; ahmed et al. ) . this rapid emergence of novel infectious diseases transmitting from surrounding animal life to humans and then from human to human, traveling quickly across the globe can trigger worldwide public health emergency situations, as prevalent today (https://www.who.int/dg/speeches/detail/who-director-general-sopening-remarks-at-the-media-briefing-on-covid- - march , http://www. emro.who.int/fr/about-who/rc /zoonotic-diseases.html). the world health organization (who) declared covid- a pandemic on march , . mesh database defines pandemics as-"epidemics of infectious disease that have spread to many countries, often more than one continent, and usually affecting a large number of people." such emergencies compromise human health, society, economics, and politics-a case in point: the covid- pandemic is forecasted to cost the global economy one trillion us dollars (https://www.ncbi.nlm.nih.gov/mesh/? term¼pandemics, https://news.un.org/en/story/ / / ). as against the earlier guidelines of who where it classified a pandemic into six stages, the revision in pandemic descriptors and stages stands today as follows: • predominantly animal infections, few human infections. this corresponds with the stages - of earlier classification, starting with phase where the virus is in its animal host and has caused no known infection in humans, phase where zoonosis has occurred and the virus has caused infection in humans, and phase where sporadic cases or clusters of infectious disease occur in humans. humanto-human transmission is limited in time and space and is insufficient to cause community-level outbreaks. • sustained human-human transmission. corresponds with the stage of the classical description wherein animal-human and human-human transmissions have sustained a community-level outbreak. the risk for pandemic is greatly increased. • widespread human infection or the stage - from the classical description where the same identified virus has caused a community-level outbreak in another country in another who region. • post-peak period where there exists a possibility of recurrence of infection. • post-pandemic phase when the disease activity is seasonal (https://web.archive. org/web/ /http://www.who.int/csr/disease/influenza/ gipa aidememoire.pdf, https://www.reuters.com/article/uk-china-health-who-idukkcn i pd). at the time of writing this chapter, coronavirus- (cov- )/covid- , though originated in wuhan, china, the first case being reported in november , had pervaded africa, americas, europe, south-east asia, eastern mediterranean, and the western pacific nations with , confirmed cases of covid- and claimed lives, globally (https://www.who.int/docs/default-source/coronaviruse/situa tion-reports/ -sitrep- -covid- .pdf?sfvrsn¼ _ ). europe was declared the new epicenter of the pandemic on march , . the number of new cases in china though declining and is believed to be in post-peak stage, the numbers are alarmingly increasing worldwide (https://www.nbcnews.com/health/ health-news/europe-now-epicenter-pandemic-who-says-n ). who and other leading epidemiology organizations unanimously agree on the indispensable role of pandemic preparation and planning at global and national levels to mitigate through the present public health emergency of covid- and any future outbreaks. pandemic preparation is not a job of single individual or organization. it requires inputs from each person susceptible to the infection agent as well as policy makers at national and international levels, frontline healthcare providers, infrastructure developers and maintenance personnel, pharmaceutical industry and researcher community, and so forth. moreover, the pandemic preparedness plan needs constant reviewing and improvisation (https://www.ecdc.europa.eu/ en/seasonal-influenza/preparedness/why-pandemic-preparedness). in line with the magnitude of the covid- pandemic, worldwide action plans have been activated on national and international levels. the united nations' strategic preparedness and response plan (sprs) against covid- , in layman terms, is designed to control human-human transmission, preventing outbreaks and delaying spread; provide optimal care for all patients; and minimize the impact on healthcare systems and socioeconomic activities. under sprs each nation is assessed for risk and vulnerability, and the resource requirements to support the country to prepare for and respond to covid- are estimated. several nations are well placed to implement this action plan with minimal support. however, otherwise partners are to be introduced to facilitate implementation of measures where there is a gap in capacity, on either a national or a subnational level, in additional support to national governments. thus, an extensive analysis and identification of an affected nation's gaps and needs shall be the basis to develop a covid- country preparedness and response plan (cprp). these cprps will need constant monitoring and reviewing using indicators charted in the sprp and updated as the situation evolves (https:// www.who.int/docs/default-source/coronaviruse/covid- -sprp-unct-guidelines.pdf). grossly, the extent of success of each pandemic action plan stands on the following pillars: • surveillance of coronavirus- and covid- infection: characterization of the virus, infection modes, diagnosing and detecting infection, contact tracing, annotation of data from confirmed cases, predicting mass infection outbreak, keeping a count, and estimation of mortality. • response management: bulk production and supply of protective/preventive pharmaceutical interventions or non-pharmaceutical interventions. • facilitating timely medical help: access to hospitals/healthcare providers, personal and public hygiene, disinfection, and quarantine services. • lesson learning from the present outbreak of covid- to facilitate future action plans and preparedness. hereafter we discuss the present salient strategies under the aegis of the covid- pandemic preparation plan, globally, which are helping the humankind mitigate through this emergency. we also discuss the impact of covid- on world economy and its bearing on future preparedness plans. as defined by the who, surveillance during pandemics is defined as "the ongoing collection, interpretation and dissemination of data to enable the development and implementation of evidence-based interventions during a pandemic event" (https:// www.who.int/influenza/preparedness/pandemic/who_guidance_for_surveil lance_during_an_influenza_pandemic_ .pdf). the present-day key worldwide surveillance activities against covid- include: (a) detection of coronavirus- and verification of covid- (b) risk and severity assessment (c) monitoring the pandemic the rapidly expanding array of pcr/reverse transcriptase pcr-based diagnostics which are quick and efficient in identifying the virus (pang et al. ; lake , https://www.finddx.org/covid- /) are basic requirements for surveillance at every phase of the pandemic for identifying and segregating the infected from non-infected and risk assessment, as well as monitoring recurrences and seasonal disease activity. covid- diagnostics have been discussed previously in this publication. an emerging exciting field of disease surveillance is infectious disease modeling and incorporation of artificial intelligence. notably, these are predictive techniques applicable to each of the three facets of disease surveillance (siettos and russo ) . a classical epidemiological surveillance parameter is quantitation of r (r nought, basic reproductive number) using mathematical models (https:// wwwnc.cdc.gov/eid/article/ / / - _article). r is a crucial metric indicating that on average the number of new infection cases are generated by a confirmed infection case, i.e., the potential transmissibility of an infectious disease. r of covid- infection is estimated as - . in the early phase, as even the asymptomatic patients or with mild pneumonia extruded large amounts of virus . important characteristics of r are: • it is a dynamic number and changes with -each stage of the disease -with interventions, e.g., vaccination, antivirals -precautionary measures such as personal/community disinfection, social distancing, and travel restrictions • with the knowledge of r , one can predict: -new cases expected on a daily basis, and hence facilitate arrangement of healthcare services and interventions locally -outbreak size and the dates of peak infection of the pandemic -probable decline timeline -the extent of vaccination coverage required to prevent future outbreaks • an r > indicates that each infected individual is transmitting the disease to more than new individual, and the infection is spreading increasingly. r ¼ indicates stable transmission and r < indicates the decline in disease transmission ( fig. . ). the aim of pandemic action plans is to monitor and depreciate the r . for instance, the median daily r in wuhan declined from . a week before the introduction of travel restrictions (january , ) to . one week later. the study used a stochastic transmission model of cov- transmission with four datasets from within and outside wuhan and estimated how transmission in wuhan varied between december and february (kucharski et al. ) . the most prominent mathematical model of covid- infection is the seir (susceptible-exposed-infected-recovered) model put forth by wu and coworkers and also endorsed by the who. this model estimates the size of epidemic in wuhan between december and january and forecasts the extent of domestic and global public health risks of taking into account for social and non-pharmaceutical prevention interventions. it is a compartmental model comprising four compartments and the individuals comprising the sample population move through each compartment-"susceptible" (not immune to infection) and get infected from other infection individuals and move to the "exposed" compartment for the incubation period. hereafter the infectious individuals move to the "infected" compartment and eventually to the "recovered" compartment after the disease has run its course, and they now have some immunity (fig. . ). the changes in the population in each compartment are estimated using ordinary differential equations to simulate the progression of an infectious disease. the critical parameters associated with this model are: • force of infection (λ) is the rate at which susceptible individuals are exposed. it depends on the transmission rate (β). • incubation rate (e) is the rate at which exposed people become infectious. • recovery rate (γ) is the rate at which infected individuals recover from the infection. through this model, it was predicted that the r was . , each confirmed case infected - other people, and the epidemic doubling time was . days. also, the size of the outbreak in wuhan was estimated to be up to , people (statistical uncertainty presented at % credible intervals). most striking feature of this model was that it took into account the travel data from and to wuhan over the period of study. thus, it was able to predict that multiple major chinese cities-guangzhou, beijing, shanghai, and shenzhen-had already imported the infection to trigger local epidemics. it also recommended that controlling the transmissibility by - % could eventually rein the local epidemics, and a control of % would phase out the epidemics . the application of artificial intelligence (ai) in close conjunction with technology in pandemic surveillance has demonstrated manifold advantages in surveillance activities as exemplified by china and other severely hit nations during the present covid- outbreak. ai, data analytics, and technological support amalgamated to facilitate: • track and forecast community outbreaks: bluedot is a canadian ai company using natural language processing and machine learning algorithms to monitor news outlets, worldwide official healthcare reports in several different languages, and air-travel data and flag the mention of contagious or novel diseases such as coronavirus. importantly this is followed by scrutiny by epidemiologists and thus also has a component of human analytics. bluedot alerted its clients to the potential outbreak in wuhan, china, on december , , days prior to the who recognized it as an epidemic (https://bluedot.global/products/). chest computed tomography (ct) scans have been endorsed as a primary diagnostic tool for covid- (ai et al. ). ali-baba group's research academy has developed a deep-learning ai-enabled system that can diagnose covid- in s with % accuracy and hence possibly automate the diagnosis activity in the face of overburdened healthcare systems. the ai system identifies an infectious individual based on the chest ct scans. the algorithm has been trained with data and ct scans from nearly confirmed coronavirus cases from across china. it can be used to track the efficacy of treatment during the course of infection as well as rapidly diagnose covid- (https://www.alizila. com/how-damo-academys-ai-system-detects-coronavirus-cases/). • implementing public hygiene guidelines: risk communication in places of potential communication is critical to alert the public and implement mass hygiene measures such as use of sanitizers and face masks when in public places. google trends was used in taiwan to monitor the public risk awareness following the first imported case of covid- which correlated with the increased search keywords "covid- " and "face masks." moreover, search for "handwashing" increased coinciding with the face mask shortage. high to moderate correlations between google relative search volume and covid- cases were evident in several major cities of taiwan (husnayain et al. ) . similarly, in china an ai-based company sensetime has developed a "smart ai epidemic prevention solutions"-a quick and effective system based on facial recognition and thermal imaging to screen for individuals with fever in a crowd without physical contact and hence preventing transmission. it can also monitor if any individual is wearing a face mask or violating the quarantine rules (https://www.sensetime.com/en/news/view/id/ .html). health code, a chinese government monitoring system, for which users can sign up through alipay or wechat, assigns individuals a color code (red- days self-quarantine/yellow- days self-quarantine/green-free movement) based on their travel history, time spent in outbreak hotspots and exposure to potential carriers of the virus. the software can be used to check the color of an individual on entering their identity numbers. • characterization of the cov- and vaccine/therapy development: the genome detective coronavirus typing tool is a web-based, user-friendly software application that can identify the novel severe acute respiratory syndrome (sars)-related coronavirus (sars-cov- ) sequences isolated in the original outbreak in china and later around the world. the tool accepts sequences per submission, analyzing them in approximately min. this tool facilitates tracking of new viral mutations as the outbreak expands globally, which may help to accelerate the development of novel diagnostics, drugs, and vaccines to stop the covid- disease (cleemput et al. ). google's ai platform deepmind-based protein structure prediction tool alphafold has predicted and released the d structures of several understudied proteins of the cov- as an open source. these can be useful in designing antivirals/vaccines against covid- in future outbreaks (jumper et al. ) . in summary, the new-age pandemic surveillance using ai, data analytics, mathematical modeling of infectious diseases, and risk prediction has significantly contributed to the management of the present covid- pandemic and is laying the foundation for future improvisation of the pandemic action plans. critical issues to be addressed while recruiting laboratory diagnostic services during the novel covid- pandemic are: • the authenticity of the diagnostic tool in light of the novelty of the coronavirus- • bulk of samples to be processed • the ease of obtaining the sample for use in the diagnostic tool the coronavirus causing covid- was first isolated from a clinical sample on january , , and within weeks, several reliable and sensitive diagnostic tools were developed and deployed. by mid-january, the first rt-pcr assays for covid- were accessible in hubei. the viral sequences and pcr primers and probe sequences were open-sourced and uploaded to public platforms by the centre for disease control, china. by february, there were ten kits for the detection of covid- approved in china by the national medical products association-six were rt-pcr kits, one isothermal amplification kit, one virus sequencing product, and two colloidal gold antibody detection kits (https://www.who.int/docs/defaultsource/coronaviruse/who-china-joint-mission-on-covid- -final-report.pdf). as of today, when the disease has assumed pandemic proportions, the volume of diagnostic tools needs to be multiplied, and hence, the united states food and drug administration (usfda) has provided regulatory relief to several testing companies like thermofisher, hologic, and labcorp under the emergency use authorizations, to facilitate ease of diagnosis. also it is keeping a tight watch on fraudulent companies claiming to sell interventions against covid- (https://www.fda.gov/ emergency-preparedness-and-response/mcm-issues/coronavirus-disease- covid- ). moreover, the world's first crispr (clustered regularly interspaced short palindromic repeats)-based diagnostic kit has been developed for covid- by mammoth biosciences, usa, and university of california. notably, the diagnostic kit is a simple strip-based assay and is easy to use and allows rapid detection without the need of transporting samples over long distances. the kit is still under approval evaluation by the fda (https://www.medrxiv.org/content/ . / . . . v ). nose and mouth swabs, the most widespread samples for cov- diagnostics, require trained personnel to procure samples. however, the study by to and coworkers recommends saliva as an easy-to-procure, noninvasive sample not requiring any trained personnel in covid- screening. they detected cov- in out of patient samples and also could trace the declining titers post-hospitalization . additionally, a long-term goal of evolving the diagnostics for this novel disease is to develop a prognostic marker of covid- . although it is too soon to say, qu and coworkers have proposed platelet counts and platelet to lymphocyte ratios as prognostic marker to distinguish between severe and non-severe patients. severe patients had higher platelet peaking and platelet to lymphocyte ratio correlating with deranged chest ct and longer hospital stays against the lower platelet peaks and platelet to lymphocyte ratios and lesser hospitalization stay (qu et al. ). vaccines and antiviral drugs are the prophylactic and therapeutic measures against a viral disease cov- . on march , , pfizer inc. and biontech announced to co-develop and distribute a potential mrna-based coronavirus vaccine which is likely to enter clinical testing by the end of april (https://www.pfizer.com/ news/press-release/press-release-detail/pfizer_and_biontech_to_co_develop_poten tial_covid_ _vaccine). however, in pandemic scenarios of new infectious diseases such as covid- , vaccine supplies will be limited or nonexistent at the early phase in lieu of the novelty of the disease and the unpredictability of the pandemic occurrence. thus, vaccines cannot be stockpiled, and production can only start once the novel virus has been recognized. with the current state-of the-art, the first doses of vaccine are not likely to become available in the early months of the pandemic. however, the pandemic action plans have accounted for forward planning to increase the likelihood that the vaccine will progressively become available as the pandemic unfolds. importantly, national or regional priorities need to be fixed in the action plan for the rational use of the building/limited supply of the novel vaccine. also, production and use of vaccines during the inter-pandemic period will influence their availability during a pandemic. thus, improving the infrastructure and logistics for vaccine production, administration, cold-chain, and professional training with the novel vaccines are important to avert/cruise through future outbreak events. the who advisory on prioritizing the population groups are as enlisted in descending order. however, the priorities need tailoring in each country/region according to local needs and epidemiological circumstances. recommended prioritizing of the groups is as follows: • healthcare workers and essential service providers • groups at high risk of death and severe complications requiring hospitalization • individuals (adults and children aged more than months) in the community who have chronic cardiovascular, pulmonary, metabolic or renal disease, or are immunocompromised • persons without risk factors for complications (https://www.who.int/csr/ resources/publications/influenza/ _ _ _a.pdf) antivirals are a crucial adjunct to vaccination as a potential strategy for managing covid- . several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to establish their efficacy and safety against covid- . it is important to establish a regular supply chain of antivirals and a high surge capacity in the face of cov- pandemic and future outbreaks. antivirals have a significant impact in reducing morbidity and mortality in light of unlikelihood of availability of vaccine against in early phases of pandemic. it is important to evaluate the non-interference of the antiviral interventions with the eventual vaccination, as well as the epidemiology of the group of individuals most seriously affected. it is also advisable to make available the information about the performance characteristics, side effects, and costs of antiviral therapy to public. also the commonly used neuraminidase inhibitors in influenza pandemics are ineffective in the case of cov- mediated infection and outbreaks (pang et al. ; dong et al. a , https://www. who.int/csr/resources/publications/influenza/ _ _ _a.pdf). the incorporation of antiviral therapy can be categorized as a prophylactic and for treatment use. as with vaccines, prioritizing of groups for antiviral therapy is advised as follows: • essential service providers, including healthcare workers (prophylaxis or treatment). especially, healthcare providers are in a position to be in direct contact with infectious individuals and are thus entitled to priority antiviral therapy. other community services such as those responsible for vaccine manufacture and delivery and personnel responsible for enforcing law and order and public safety. • groups at high risk of death and severe complications requiring hospitalization. the goal of prophylaxis or treatment here is to rein the mortality and morbidity. thus, high-risk persons living in the community outbreaks, seriously ill hospitalized patients, patients for whom a potential cov- vaccination is contraindicated are prioritized. • persons without known risk factors for complications from covid- . here the approach is generally therapeutic and aims to rein the morbidity and rationalize the use of healthcare resources such as antibiotics. though, the logistics of this strategy are extensive and expensive (requires large quantities of antivirals and access to healthcare service providers), it is most likely to limit the economic and social destabilization associated with a pandemic (monto ; henry , https://www.who.int/csr/resources/publications/influenza/ _ _ _a.pdf). a major step in ensuring bulk supplies of antivirals and vaccines is the setting up of medical stockpiles as a part of the pandemic preparedness plans. the usa has constituted a strategic national stockpile which is the nation's largest supply of potentially life-saving pharmaceuticals and medical supplies-antibiotics, chemical antidotes, antitoxins, vaccines, life-support medication, iv administrations, airway maintenance supplies, and other emergency medical and surgical items, for use in a public health emergency severe enough to deplete the local supplies. the facility also houses a data bank of other stockpiles and supply agencies, so that any emergency requirements can be procured in the shortest possible time (https:// www.phe.gov/about/sns/pages/default.aspx). healthcare personnel, maintenance of hygiene and disinfection during pandemics • rapid facilitation of treatment/prophylaxis, hospital centers, quarantine centers • caring for the patients as well as the health service providers to ensure uninterrupted care • communicating awareness about public and personal hygiene and implementing measure to ensure personal and public hygiene in the face of a highly infectious disease causing novel virus, china has successfully executed an ambitious, swift, and aggressive disease containment effort in the history of mankind. the laudable of its responses to facilitate timely medical care for infected was construction of two dedicated hospitals- -bed huoshenshan facility and the -bed leishenshan hospital in weeks (https://www.wsj.com/arti cles/how-china-can-build-a-coronavirus-hospital-in- -days- ). moreover, it ensured coordinated medical supplies, reserve beds were used and relevant premises were repurposed medical care facilities, and prices of commodities were controlled to ensure the smooth operation of the society (https://www.who.int/docs/ default-source/coronaviruse/who-china-joint-mission-on-covid- -final-report.pdf). ensuring the care of the medical service providers is a key response strategy to warrant efficient care for the general public. under the china's response plan, the healthcare workers were facilitated with personal protective equipment. nosocomial infections accounted were reported to be nearly from hospitals across china. the majority of this nosocomial infection ( %) were reported from hubei. a deeper contact tracing indicates infection of the healthcare worker from households than the workplace and were pinpointed to the early stages of the epidemic when understanding of the covid- transmission and medical supplies were limited (https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mis sion-on-covid- -final-report.pdf). in fact a novel infection control system for averting nosocomial infections of covid- was proposed by chen and coworkers, titled "the observing system." designated personnel called "infection control observers" were appointed by the department of infection control and nursing in guangdong second provincial general hospital who underwent training to familiarize infection control requirements in the negative pressure isolation wards. the wards were under camera surveillance and the infection control observer monitors medical staff in real-time via computer monitors outside the ward. the observer ensures normal operation of the negative pressure isolation wards, supervise the implementation of disinfection, ensure a sufficient supply of protective materials, arrange specimens for inspection, and relieve anxiety of the medical personnel while treating patients . personal and public hygiene/disinfection implementation is a key step to control transmission and prevent community outbreaks. good hand hygiene and respiratory hygiene have been aggressively promoted by who worldwide in this covid- pandemic. the basic personal and public hygiene practices are depicted in fig. . . fig. . the basic personal and public hygiene practices a key parameter to consider while disinfecting in households and public places hence avoid contact with infected surfaces is the estimation of decay rates of cov- in aerosols and on various materials composing the surfaces. it has been estimated that cov- in an aerosol (< μm, similar to those observed in samples obtained from the upper and lower respiratory tract in humans) was viable for up to h, up to h on copper surfaces, up to h on cardboard, and - days on plastic and stainless steel (van doremalen et al. ). on the basis of these findings, disinfection protocols can be set up for public places/medical facilities depending on the surfaces involved, and even in households' frequently touched surfaces like door handles, slabs, and tables be disinfected. the exponential transmission of cov- -starting with few infectious individuals with covid- quickly increasing manifold in a geographical location within a short time-is a recurring observation (dong et al. b , https://www.who.int/ emergencies/diseases/novel-coronavirus- /situation-reports, https://www.ecdc. europa.eu/en/publications-data/download-todays-data-geographic-distributioncovid- -cases-worldwide). figure . depicts the exponential surge in new confirmed cases per day plotted against time lapse post outbreak. the highly implemented global covid- management strategies of social distancing, travel restrictions, implementation of personal and public hygiene (non-pharmaceutical interventions), and pursuit of pharmaceutical interventions aim to delay the peaking of the outbreak, avoid burden on the healthcare infrastructure and personnel to ensure quality care for all in need, and rein overall mortality and declined health effects. this phenomenon has been described as "flattening of the curve" and is much shared on social media platforms facilitating awareness in the public (https://www.cdc.gov/flu/pandemic-resources/ pdf/community_mitigation-sm.pdf). hereafter, we discuss the key, successful globally adopted strategies for covid- management. it is a non-pharmaceutical infection prevention and control intervention to avoid or control contact between infectious and uninfected individuals to rein the disease transmission in a community eventually culminating into decreased infection spread, morbidity and mortality. the individuals infected with cov- shed the virus from their respiratory tract during the early infection stage when there are minor clinical manifestations leading to the extensive community transmission. while practicing social distancing, each healthy individual behaves like an infected individual, self-restricting contact with others. the main advantage is gleaned when an individual in incubation period/early infectious stage of covid- restricts coming in contact with other healthy individuals. this strategy involves the policymakers, and strict advisories/orders are issued under the pandemic action plan to restrict public gatherings and events, shutting down of educational institutes/offices/restaurants, avoiding nonessential travel and use of public transport, maintaining a distance of m at least between two individuals, restricting visit to hospitals, and avoiding online shopping. additionally, the elderly and individuals with hypertension, cardiovascular disease, diabetes, chronic respiratory diseases, and cancer are at a higher mortality risk (https://www.mohfw.gov.in/socialdistancingadvisorybymohfw. pdf, https://onlinelibrary.wiley.com/doi/pdf/ . /ijcp. ; zou et al. ) . the who director-general at a media briefing on covid- on march , , recommends testing of any suspected case, isolation to break the chain of transmission, and contact tracing for the prior days the subject came in contact with and then testing them as well (https://www.who.int/dg/speeches/detail/who-director-gen eral-s-opening-remarks-at-the-media-briefing-on-covid- % d% d- -march- ). a case in point-south korea carried out , covid- tests until march , -second highest across the world trailing behind china (https:// ourworldindata.org/coronavirus-testing-source-data), combined with strict social distancing implementation and is now seeing a fall in the number of covid- cases (https://ourworldindata.org/grapher/daily-cases-covid- -who?time¼ .. & country¼kor, https://www.sciencemag.org/news/ / /coronavirus-caseshave-dropped-sharply-south-korea-whats-secret-its-success). social distancing combined with case isolation and contact tracing has demonstrated its effectiveness in controlling the transmission from imported infection cases to the community transmission scenario (wilder-smith and freedman ). the relevance of case isolation and contact tracing are highlighted in a study by hu and coworkers where they have performed a clinical characterization of asymptomatic patientsconfirming infection by a laboratory-confirmed positive for the covid- virus nucleic acid from pharyngeal swab samples. the asymptomatic cases did not present any obvious symptoms while nucleic acid screening. about . % developed classical symptoms of fever, cough, and fatigue, during hospitalization; . % presented ct images of ground-glass chest and . % presented stripe shadowing in the lungs; . % cases presented normal ct image and had no symptoms during hospitalization, comprising the younger subset (median age: . years). none developed severe covid- pneumonia, and no mortality was observed. however, epidemiological investigation indicated at typical asymptomatic transmission to the cohabiting family members, which even caused severe covid- pneumonia. this study puts a spotlight on close contact tracing and longitudinally surveillance via virus nucleic acid tests. case isolation and continuous nucleic acid tests are also recommended (hu et al. ) . de-isolating of suspect cases where the first confirmatory test has returned negative is also an emerging issue of concern and needs improvement in testing capacity as well as strict implementation of social distancing during pandemic scenarios (tay et al. ). approaching january , , the daily risk of exporting at least a one covid- infected individual from mainland china through international travel exceeded %. for containment of the global spread of cov- and a covid- epidemic, china implemented border control measures-airport screening and travel restrictions, and were later also adopted by several other countries. wells and coworkers in their study in proceedings of natural academy of sciences used daily incidence data of covid- outbreak from china from december , , to february , , as well as airline network data, to predict the number of exported cases with and without measures of travel restriction and screening. the group put forth that the lockdown of wuhan and more cities in hubei province on january - , , averted export of more covid- cases by mid-february. however, it is to be highlighted that these travel restrictions and lockdown measures only slowed the rate of infection exportation from china to other countries. the global spread of covid- was based on most cases arriving during the asymptomatic incubation period. the authors recommend rapid contact tracing at the epicenter and at importation sites to limit human-to-human transmission outside of the location of first outbreak (wells et al. ). the covid- pandemic in today's times of excessive electronic connectivity and several social media platforms has a potential to alleviate the global mental stress levels. especially, if local myths and rumors are circulated in the already homequarantined population, restriction in fear of the disease can lead to additional mass hysteria. thus it is important to create awareness and dispel any negative myth, as put forth by the who in context of cov- (https://www.who.int/emergencies/ diseases/novel-coronavirus- /advice-for-public/myth-busters). some myths dispelled are: • covid- virus can be transmitted in areas with hot and humid climates or cold and snowy climates. cov- can be transmitted in all areas. • hot bath cannot prevent cov- transmission. • cov- is not transmitted by mosquito bites. it is a respiratory illness and respiratory hygiene is a key protective strategy. • heat generated from hand dryers is not effective against killing cov- on your hands. the only way to disinfect hands is washing with soap-water or alcoholbased sanitizers. • thermal scanners are effective in detecting only the elevated body temperatures. a confirmatory nucleic acid test is the most guaranteed test. • all age groups can be infected by cov- . elderly people and people with pre-existing medical conditions-asthma, diabetes, cardiovascular disease-are more vulnerable to exhibit severe covid- . thus, who advises people from all age groups to protect themselves by implementing good hand hygiene and respiratory hygiene. • sars-cov- is not a bioengineered organism arising out of manipulations from earlier sars-cov. andersen and coworkers have analyzed the genome sequence of the novel coronavirus- and compared it with several other zoonotic viruses. they claim that the viral-human point of contact-the high affinity receptor binding domain of cov- binding with the angiotensin-converting enzyme (ace ) of the target host-is acquired through natural selection. also they have shed light of probable animal host being rhinolophus affinis, as another virus ratg , sampled from a bat, is~ % identical overall to cov- (https:// www.nature.com/articles/s - - - ). the covid- pandemic can cause short-term fiscal distress and longer-term damage to the global economic growth. if we trace the economic trajectory of a pandemic: • early phase measures to contain/limit outbreak-shutting down of workplaces and public businesses, mobilization of healthcare supplies and surveillance activities, contact tracing, social distancing by isolation of contacts/quarantines incur significant human resource and staffing costs (achonu et al. ). • as the scale of the epidemic expands, new medical infrastructure will need to be constructed to manage building number of confirmed infected individuals, the surge in demand for medical consumables can increase the health system expenditures (herstein et al. ). • the quarantine and lockdown impositions disrupt trans-national supply chains, transportation industry, agriculture, entertainment, and travel industry. hoarding and black marketing of essential and medical commodities are expected. • behavioral changes during pandemic-avoiding association with other people to avoid infection-are the major determinant for economic impact of pandemics ( fig. . ) and not mortality. the behavioral change fear driven which in turn is driven by awareness and ignorance (burns et al. risk_jonas.pdf). • the high-income countries in scenario of a moderate pandemic can offset fiscal distress by providing official development assistance to affected countries and budgetary support. however, during a severe pandemic, a high-income country will also confront the same fiscal stresses and may be unwilling to provide assistance. on march , , worldwide , confirmed cases were reported, mortality was against , confirmed cases, and mortality of on march , when the covid- crisis was declared a pandemic (https://www.who.int/emergen cies/diseases/novel-coronavirus- /situation-reports). it is increasingly becoming evident that no region of the world will remain untouched by cov- invasion. however, pandemic preparedness is the key to tackle the present-day covid- health emergency worldwide. the rapid and effective enforcement of existing international and national action plans, as well as parallel review and improvisation, is facilitating the affected countries to contain transmission and possibly delay the peak of outbreak and mortality and garner recovery. it is notable that in the present pandemic scenario, innovative ai-powered surveillance, quick and strategic response actions-the trinity of testing-isolation-contact tracing, committed social distancing measures-travel restrictions, self-isolation, implementation of personal and public hygiene, and extensive mobilization of medical care facilities are helping the world mitigate through. the most insightful trend emerging from the global clinical and epidemiological data is that the identification of asymptomatic infected individuals is a crucial step to contain community outbreaks. for preventing future outbreaks of cov- infection, high-volume cutting-edge investigations are warranted in understanding the covid- pathology, cov- origin, biology, structural data of potential surface antigens, and precise anti-cov- antiviral therapies. although the global economy is suffering at the hands of cov- , it is important to review the current action plans and suitably improvise the future action plans to avoid potential recurrence. pandemics are unforeseen. national and international preparedness are crucial to tackle a pandemic. world over, humanity is grappling with covid- . the pandemic preparedness charter prescribed by international and national agencies to tackle covid- is evolving on the go. the key facets of pandemic preparedness emerging from global success and failure scenarios are: • active surveillance employing state-of-the art technology: -development of mathematical models for simulating the infection of cov- in a given country. the models can help predict the basic reproductive number which in turn facilitates monitoring the pandemic on day-to-day basis. -incorporation of contactless artificial intelligence-based technologies for mass thermal screening, track and forecast community outbreaks, implement public hygiene and use of masks, and contact tracing. • expanding the diagnose capacity/testing for cov- (the infectious agent) to catch any asymptomatic carriers, but at the same time ensuring: -precision of the test. -test is adaptable to processing bulk samples. -easy procurement of sample from suspected infected individuals. • management of bulk antiviral interventions and vaccines: -national or regional priorities need to be fixed for rational use of antiviral/emerging vaccines -prioritizing the population has been recommended: the healthcare workers and essential service providers are top priority. -medical stockpiles should be established. • promoting facilities for healthcare/healthcare workers and facilitating public disinfection and hygiene via: -rapid expansion of hospitalization facilities for treatment and isolation/ quarantine centers. -ensuring minimal nosocomial infections to the healthcare workers. -issuing and implementation of guidelines for ensuring good hand and respiratory hygiene. (continued) -public disinfection (and personal household as well) based on the established life of cov- on different surfaces. • globally successful strategies are: -social distancing and lockdowns to ensure minimal human-human contact. -travel restrictions to facilitate containment. -trifecta of test-isolate-contact tracing. • the economic cost of the covid- pandemic management is expanding due to: -disruption of economic activities due to implementation of social distancing via lockdowns. -battling the diseased and the increasing mortality. -diversion of resources to expansion of healthcare systems. -international and national relief funds are being constituted. -fiscal reliefs and aid from developed nations to the developing or underdeveloped countries can release the surmounting economic pressure. the financial impact of controlling a respiratory virus outbreak in a teaching hospital: lessons learned from sars does urbanization make emergence of zoonosis more likely? evidence, myths and gaps correlation of chest ct and rt-pcr testing in coronavirus disease (covid- ) in china: a report of cases evaluating the economic consequences of avian influenza initiation of a new infection control system for the covid- outbreak pii: btaa ) genome detective coronavirus typing tool for rapid identification and characterization of novel coronavirus genomes discovering drugs to treat coronavirus disease (covid- ) - ) an interactive web-based dashboard to track covid- in real time aerosol and surface stability of sars-cov- as compared with sars-cov- canadian pandemic influenza preparedness: antiviral strategy initial costs of ebola treatment centers in the united states clinical characteristics of asymptomatic infections with covid- screened among close contacts in nanjing - ) applications of google search trends for risk communication in infectious disease management: a case study of covid- outbreak in taiwan the alphafold team ( ) computational predictions of protein structures associated with covid- . deepmind website - ) early dynamics of transmission and control of covid- : a mathematical modelling study what we know so far: covid- current clinical knowledge and research nugent r (eds) disease control priorities: improving health and reducing poverty, rd edn. the international bank for reconstruction and development/the world bank vaccines and antiviral drugs in pandemic preparedness potential rapid diagnostics, vaccine and therapeutics for novel coronavirus ( -ncov): a systematic review platelet-to-lymphocyte ratio is associated with prognosis in patients with corona virus disease- mathematical modeling of infectious disease dynamics pii: ciaa ) de-isolating covid- suspect cases: a continuing challenge pii: ciaa ) consistent detection of novel coronavirus in saliva unique epidemiological and clinical features of the emerging novel coronavirus pneumonia (covid- ) implicate special control measures pii: ) impact of international travel and border control measureson the global spread of the novel coronavirus outbreak isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus ( -ncov) outbreak nowcasting and forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study sars-cov- viral load in upper respiratory specimens of infected patients key: cord- - l c my authors: rochwerg, bram; parke, rachael; murthy, srinivas; fernando, shannon m.; leigh, jeanna parsons; marshall, john; adhikari, neill k. j.; fiest, kirsten; fowler, rob; lamontagne, françois; sevransky, jonathan e. title: misinformation during the coronavirus disease outbreak: how knowledge emerges from noise date: - - journal: crit care explor doi: . /cce. sha: doc_id: cord_uid: l c my although the amount of information generated during this most recent coronavirus disease pandemic is enormous, much is of uncertain trustworthiness. this review summaries the many potential sources of information that clinicians turn to during pandemic illness, the challenges associated with performing methodologically sound research in this setting and potential approaching to conducting well done research during a health crisis. data sources: not applicable. study selection: not applicable. data extraction: not applicable. data synthesis: not applicable. conclusions: pandemics and healthcare crises provide extraordinary opportunities for the rapid generation of reliable scientific information but also for misinformation, especially in the early phases, which may contribute to public hysteria. the best way to combat misinformation is with trustworthy data produced by healthcare researchers. although challenging, research can occur during pandemics and crises and is facilitated by advance planning, governmental support, targeted funding opportunities, and collaboration with industry partners. the coronavirus disease research response has highlighted both the dangers of misinformation as well as the benefits and possibilities of performing rigorous research during challenging times. d uring times of uncertainty, it can be challenging to decipher which information is credible. watching major news channels early during the course of an evolving and breaking story, it is usually clear that the newscasters do not have complete information; however, this does not stop the constant flow of discourse to viewers. to fill this void, it is common for broadcasters to rely upon information that is not fully vetted, much of which ends up being incorrect once the entire story becomes clear. these same themes may occur during medical crises, most clearly demonstrated during infectious pandemics that elicit a primal fear in people, bringing forth images of blockbuster films in which novel viruses wipe out large swaths of the global population. a combination of fear and a lack of credible information in the early phase of an outbreak are the largest contributors www.ccejournal.org • volume • e to public hysteria. information is the best tool to combat hysteria, and as illustrated in the current infectious outbreak of severe acute respiratory syndrome coronavirus , in our digital media era, information is everywhere. the more important concern for clinicians and patients, similar to watching a breaking news story, in which information to believe and which to ignore. the ongoing coronavirus disease pandemic has demonstrated the volume of information that can be produced in a short period of time; this has been associated with both benefits (easier access for clinicians) and risks (misinformation). media sources including newspapers, magazines, and news shows have been covering this story with fervor. although the objectives of corporate news media include informing the public of the latest medical updates, they have an obligation to shareholders or private owners of selling more newspapers, magazines, or advertisements and the natural inclination to therefore stoke the fires of hysteria. certainly, some sources are worse offenders when it comes to this than others who take the time to more carefully vet sources. the amount of print and news media dedicated to covid- in the last few months is huge. tangible risks of misinformation should not be ignored, as they may lead to ill-informed health decisions ( ) including isolation orders, travel bans, population quarantines and even discrimination against travelers from certain countries or persons of certain ethnic origins. the use of unproven therapeutic or prophylactic interventions also introduces unnecessary risks and, unless they are used carefully in the context of an approved clinical study, increase the amount of noise thereby limiting our collective ability to discover new ways to treat patients. there are however benefits to digitalization of health media. based on experiences with previous outbreaks, for example, influenza a(h n ) pdm pandemic in , the world health organization (who) and other governmental organizations are better prepared. the who maintains a live and up-to-date covid- website which contains credible information on the outbreak (www.who.int/ health-topics/coronavirus). the u.s. centers for disease control and prevention website includes updates on virus status in the united states, travel restrictions, and a world map highlighting areas with covid- cases (www.cdc.gov/coronavirus). johns hopkins runs a website (www.gisanddata.maps.arcigis.com) that provides up-to-date and credible data describing the number of those infected broken down by severity and separated by country, as well as the number of deaths. these governmental and public health organizations sources of information should be considered most trustworthy, as they can be relied upon to avoid misinformation, and as such the public should be going here as their main source of information during the health crisis. perhaps unique to this pandemic, compared with others, has been the response from the medical community. although bedside practitioners are in need of data that will help them to better identify, risk-stratify, and treat affected patients, medical research often takes time. traditionally, research is deliberate, and producing trustworthy and methodologically sound results may not be as rapid as what is required. for example, according to pubmed, although over , citations related to h n influenza have been published since , the large majority ( , of these) were published after , over years following the major phase of the pandemic. major contributors to research delays include competing interests of investigators, regulatory barriers, time taken for protocol development, ethics approval, peer review and delays related to the publication process. this classic research model does not fit well with pandemic research, where there is a need for rapid information to fill gaps and address public concern. for covid- , some of these traditional delays have been circumvented (we will discuss how shortly), and as such, many of the major general medicine journals, including journal of american medical association (jama), new england journal of medicine (nejm), and the lancet have prioritized publications related to covid- . this has been facilitated at medical journals through invited content and expedited peer review processes. jama, the lancet, and nejm, for example, maintain a coronavirus resource center including research and multimedia content (www.jamanetwork.com/journals/jama/pages/coronavirus-alert), most as free online content. providing peer-reviewed and easily accessible content has helped to overcome some of the misinformation rampant in lay media. as of march , , unique citations related to covid- have been indexed in pubmed, in , and , in . this represents an enormous amount of scientific content for a disease that was first discovered in wuhan, china in mid-december. it remains to be seen, how valid and trustworthy the data from these publications will turn out to be, given the rapidity in which they were produced and the expedited peer review and editorial decision-making required to publish so quickly. there have already been some highly visible examples of dubious and scientifically questionable reports, even some that have been published and now corrected in highly reputable journals ( ) . the lesson is that not everything posing as trustworthy research truly is, and it is important to both support high-quality work, but also discourage and prevent work that is not trustworthy. also unique to this outbreak is the role social media has played in information dissemination and at times, propagation of misinformation ( ). twitter has become entrenched as an information source for both patients and clinicians ( , ) . although the platform is unique in allowing for engagement with experts and rapid discourse, the lack of scientific vetting and peer review ( ) can contribute to hysteria, rather than alleviating it. each day over , tweets are sent using the #covid hashtag (www. symplur.com) and this is increasing exponentially. filtering the knowledge from the misinformation in social media is extremely challenging, and probably a strategy to be avoided in times of pandemic. at the very least, if using social media, the focus must be on reliable sources presenting vetted information and avoiding conjecture and opinion. even this rule is not absolute, as we have seen dramatic cases of prominent individuals advocating for specific unproven therapies (e.g., hydroxychloroquine and azithromycin) leading to drug shortages and increased rates of toxicity. examples such as this reinforce the necessity of consistent and well-informed communication strategies in times when the risks of misinformation are significant. research during a pandemic or health crisis presents challenges beyond the usual difficulties surrounding research in the critically ill ( ) . most obviously, pandemic preparedness, planning and management requires time, resources and personnel. clinical researchers may be diverted to the bedside caring for affected patients or working with government and public health organizations to contain the outbreak. preliminary data from china suggests that mortality in wuhan (the center of the covid- outbreak with the largest number of cases) has been higher (> %) compared with other regions in china (around . %) and this has been hypothesized to be at least partly due to a shortage in healthcare providers ( ) . not only is researchers time diverted to clinical care but so are other resources including funding. governments are usually the largest research funder, especially in developed nations; however, these funds may be required during an outbreak to augment capacity through infrastructure or human resources investment. the most dramatic example of this was the government of china's investment in building a new , square foot hospital with , beds and icu beds, built in only days to care strictly for covid- patients. organizational stress has other collateral impacts on research capacity. research involving humans often requires regulatory or governmental support, especially if there are significant ethical, public health or safety concerns ( ) . more than likely, during times of institutional pressure, these regulatory pathways will be delayed, limiting the ability to get the approvals necessary to proceed. research ethics boards may mistakenly consider the emotional pressure on patients and caregivers during a health crisis as an unsuitable environment to conduct research, thereby enacting further delays and barriers to timely investigation ( , ) . safety concerns for research staff may keep them out of hospitals or limit their ability to enroll patients and capture study-related information. unfortunately, the greatest impact of health crises and pandemics and the most significant challenges with outbreak tracking occur in low-or middle-income countries (lmics), regions that are already well below capacity in terms of health and research infrastructure ( ) (fig. ) . lack of local or regional expertise in conducting methodologically rigorous research may require external collaboration, which is challenging in the setting of travel restrictions and which runs the risk of ignoring scientific input from lmic investigators and clinicians. this is all further complicated by a rapidly evolving landscape. within pandemics, the clinical situation often evolves day-to-day or week-to-week, a pace uncommon in the setting of traditional epidemiologic and clinical research. a research question or medical intervention that was relevant weeks ago may no longer be relevant by the time approval and funding are secured. as such, research priorities and approaches must be capable of responding nimbly and rapidly. this need for rapid information and rapid dissemination of trustworthy results is daunting and uncomfortable for most clinical researchers who are used to operating within extended timelines. the exponential increase in pubmed citations related to covid- over the last months is a testament to this rapid evolution in information. a we've learned time and time again, true salvation figure . countries judged to be most at risk for originating pandemic illness (red = high risk, orange = moderate risk, yellow = low risk). reference: global health security index (www.ghsindex.org). from pandemic times (e.g., ebola) will come only from well-conducted research informing prevention of disease with vaccines, use of prophylaxis, improving treatments, and mitigating diseaserelated consequences. although these barriers are significant, and clinical research during the health crisis is enormously complicated, this is the first outbreak in which rapid, potentially clinically useful research is being conducted alongside the pandemic response. at this time, approximately randomized controlled trials have been registered in clinicaltrials.gov, and more than in the chinese trials registry, investigating interventions such as antivirals (multiple), iv immunoglobulin (nct ), corticosteroids (nct ), antibiotics (e.g., azithromycin) (multiple), tocilizumab (nct ), sildenafil (nct ), thalidomide (nct ), immunotherapy (nct ), chloroquine (nct ), recombinant angiotensin-converting enzyme (nct ), thalidomide (nct ), biologic agents (nct ), mesenchymal stem cells (multiple), convalescent plasma (nct ), nitric oxide (nct ), vitamin c (nct ), traditional chinese medicine (multiple), and vaccines (nct ) in the treatment of covid- related illness. research funding bodies can help by prolonging funding periods, augmenting funding envelops to help overcome the barriers mentioned above, and considering funding pandemic research even outside pandemic times. over the coming months, the most significant issue facing clinicians caring for covid- patients will be to critically appraise the multiple research outputs and decide which to apply in clinical practice. for researchers conducting these trials, it is important to balance rapidity along with sound methodologic principles. this can be facilitated in a number of ways, which will be discussed next, including some direction on how best to incorporate new data into pandemic-based patient management. how might health researchers go about pursuing this in a timely manner? there are a number of strategies that have been employed to overcome some of the challenges associated with conducting research in this setting ( ) . pandemics related to respiratory viruses have occurred at regular intervals throughout history ( ) (fig. ) ; it is not a matter of if they will recur, but rather when. as such, rather than waiting until a pandemic occurs to build infrastructure, researchers may develop collaborative networks, initiate study protocols, and begin regulatory and ethical approval processes in anticipation of the next outbreak. then, when the inevitable pandemic occurs, research capacity will already be in place allowing for a facilitated response. the international severe acute respiratory and emerging infections consortium (isaric), a group which was formed in collaboration with international forum for acute care trialists (infact) umbrella, has followed this model ( ) . the group, which includes clinical research networks worldwide, was launched in following the h n pandemic with the plan to be ready for the next viral pandemic and with the goal of ensuring timely and efficient research in the setting of health crises related to emerging infection. as introductory work has been ongoing over the last few years, with the emergence of covid- , isaric is already prepared with whoendorsed case report forms, clinical characterization protocols to enable harmonious clinical and biological sample data collection, and clinical trial protocols that have been collated and endorsed by the entire research network (www.isaric.tghn.org). infact is also guiding the who on supportive and adjuvant care in severe viral disease through leadership within who committees, a great example of intensive care physicians leading the global response and research initiatives related to this pandemic. randomized, embedded, multi-factorial, adaptive platform trial for community-acquired pneumonia (remap-cap) is another example of an infact-led initiative that has positioned itself well to answer timely research questions during pandemic illness such as covid- (nct , www.remapcap.org). the unique study design allows for sequential investigation of a number of different interventions targeting pneumonia including specific antibiotics, antivirals, or corticosteroids, for example ( ) . in the setting of a pandemic, the adaptive design allows for evaluation of new interventions and multiple treatment options, even those specifically targeted to new or emerging viruses. this adaptive feature allows for trial infrastructure to be established and to even begin enrolling patients examining traditional interventions for pneumonia, while providing opportunity to change intervention mid-trial to more specific or relevant agents, targeted to specific emerging pathogens. for these reasons, the adaptive trial design is likely the optimal methodology for investigating different anti-covid interventions within the same design. in fact, the remap-cap team has already evolved their protocol to address covid- and will focus on treatment domains in study centers affected by the virus, including the evaluation of prolonged macrolide therapy, corticosteroid administration strategies, antiviral use, and interferon-beta. through central administration and wide-scale international recruitment, remap-cap is well-positioned to enroll a large number of geographically diverse patients; both crucial components to study a global pandemic. through the adaptive randomization, treatment arms that show the most promise or benefit along with the least amount of toxicity will see increased allocation of trial participants, while those with less efficacy or more toxicity will see decreased allocation ( fig. ) . similarly, the who has an adaptive trial planned assessing multiple interventions which may be efficacious in the setting of covid- and has developed a core outcome set to be used during pandemic research (www.who.int). given the rapidity of new research data associated with the covid- pandemic, the next question for bedside practitioners becomes which data are of sufficient quality and trustworthiness that it should inform clinical practice ( table ) . might we accept a lower threshold in the setting of health crises, as opposed to other settings ( ) ? clinical practice guidelines (cpgs) are often considered the gold standard for informing healthcare decisionmaking; however, traditionally, cpgs take years to produce, limiting their ability to impact knowledge translation during pandemic illnesses. to address this, guideline developers have attempted to provide rapid guidance documents, still produced using rigorous methodology, but often addressing questions of smaller scope, using larger teams to facilitate expedited recommendations, and frequently updated ( ) ( ) ( ) . there are a number of these rapid guideline efforts, some done using grading of recommendations assessment, development and evaluation methodology, currently underway addressing covid- with a couple having just recently been published such as the australia and new zealand intensive - ) . one of the risks associated with this constantly evolving research landscape, is that evidence, and subsequently best practice, is constantly changing. as such, it is not a surprise that these guidelines are not entirely consistent with one another, and risk quickly becoming out of date. this can be overcome through frequent reassessment of recommendations based on emerging evidence (living guidelines), which although crucial in this setting, represents an added challenge to be addressed. pandemics and healthcare crises provide extraordinary opportunities for the rapid generation of reliable scientific information but also for misinformation, especially in the early phases, which may contribute to public hysteria. the best way to combat misinformation is with trustworthy data produced by healthcare researchers. although challenging, research can occur during pandemics and crises and is facilitated by advance planning, governmental support, targeted funding opportunities, and collaboration with industry partners. the covid- research response has highlighted both the dangers of misinformation as well as the benefits and possibilities of performing rigorous research during challenging times. dr. rochwerg is supported by the hamilton health sciences early career research award. dr. lamontagne is supported by a fonds de recherche du québec -santé award. dr. sevransky's institution has received funding from the marcus foundation for a sepsis clinical trial. the remaining authors have disclosed that they do not have any potential conflicts of interest. for information regarding this article, e-mail: rochwerg@mcmaster.ca clinical decision making during public health emergencies: ethical considerations transmission of -ncov infection from an asymptomatic contact in germany social media and emergency preparedness in response to novel coronavirus tracking the flu pandemic by monitoring the social web twitter hashtags for health: applying network and content analyses to understand the health knowledge sharing in a twitter-based community of practice twitter as a tool for communication and knowledge exchange in academic medicine: a guide for skeptics and novices clinical research during a public health emergency: a systematic review of severe pandemic influenza management potential association between covid- mortality and health-care resource availability clinical research ethics for critically ill patients: a pandemic proposal social value, clinical equipoise, and research in a public health emergency ethics of clinical science in a public health emergency: reflections on the role of research ethics boards major issues and challenges of influenza pandemic preparedness in developing countries influenza pandemics: a historical retrospect isaric council: open source clinical science for emerging infections adaptive designs for clinical trials national ebola training and education center's special pathogens research network (sprn)'s medical countermeasures working group: evaluating promising investigational medical countermeasures: recommendations in the absence of guidelines developing who rapid advice guidelines in the setting of a public health emergency development of rapid guidelines: . gin-mcmaster guideline development checklist extension for rapid recommendations introduction to bmj rapid recommendations key: cord- -yjn sja authors: o'connor, daryl b.; aggleton, john p.; chakrabarti, bhismadev; cooper, cary l.; creswell, cathy; dunsmuir, sandra; fiske, susan t.; gathercole, susan; gough, brendan; ireland, jane l.; jones, marc v.; jowett, adam; kagan, carolyn; karanika‐murray, maria; kaye, linda k.; kumari, veena; lewandowsky, stephan; lightman, stafford; malpass, debra; meins, elizabeth; morgan, b. paul; morrison coulthard, lisa j.; reicher, stephen d.; schacter, daniel l.; sherman, susan m.; simms, victoria; williams, antony; wykes, til; armitage, christopher j. title: research priorities for the covid‐ pandemic and beyond: a call to action for psychological science date: - - journal: br j psychol doi: . /bjop. sha: doc_id: cord_uid: yjn sja the severe acute respiratory syndrome coronavirus‐ (sars‐cov‐ ) that has caused the coronavirus disease (covid‐ ) pandemic represents the greatest international biopsychosocial emergency the world has faced for a century, and psychological science has an integral role to offer in helping societies recover. the aim of this paper is to set out the shorter‐ and longer‐term priorities for research in psychological science that will (a) frame the breadth and scope of potential contributions from across the discipline; (b) enable researchers to focus their resources on gaps in knowledge; and (c) help funders and policymakers make informed decisions about future research priorities in order to best meet the needs of societies as they emerge from the acute phase of the pandemic. the research priorities were informed by an expert panel convened by the british psychological society that reflects the breadth of the discipline; a wider advisory panel with international input; and a survey of psychological scientists conducted early in may . the most pressing need is to research the negative biopsychosocial impacts of the covid‐ pandemic to facilitate immediate and longer‐term recovery, not only in relation to mental health, but also in relation to behaviour change and adherence, work, education, children and families, physical health and the brain, and social cohesion and connectedness. we call on psychological scientists to work collaboratively with other scientists and stakeholders, establish consortia, and develop innovative research methods while maintaining high‐quality, open, and rigorous research standards. the global impact of the coronavirus disease (covid- ) is unprecedented. by the june , in excess of million cases of covid- worldwide had been confirmed and covid- -related deaths were close to half a million. however, its impact should not only be measured in terms of biological outcomes, but also in terms of its economic, health, psychological, and social consequences. the covid- pandemic is unique with respect to the ongoing risks associated with the large numbers of infected people who remain asymptomatic, the impacts of the countermeasures on societies, the likelihood of second or third waves, and the attention it has received due to its global reach (particularly in high-income countries). the effects of the covid- pandemic will likely shape human behaviour in perpetuity. psychological science is uniquely placed to help mitigate the many shorter-and longer-term consequences of the pandemic and to help with recovery and adjustment to daily life. the immediate research response to covid- was rightly to focus resources on the transmission of covid- , identify biologics with which to treat those infected with the virus, and develop vaccines to protect populations. however, biomedical science can only go so far in mitigating the severe negative health, economic, psychological, and social impacts of covid- . the future availability of a vaccine currently remains uncertain; therefore, the primary weapons to mitigate the pandemic are behavioural, such as encouraging people to observe government instructions, self-isolation, quarantining, and physical distancing. even if a vaccine becomes available, we will still require changes in behaviour to ensure its effective delivery and universal uptake, so we need to prioritize research that will make the greatest contributions to our understanding of the effects of, and recovery from, the pandemic. the important contributions made by psychological scientists to understanding the impact of previous pandemics, including the ebola disease outbreak, severe acute respiratory syndrome (sars), and the middle east respiratory syndrome (mers), are welldocumented and mean we knew already a lot about public messaging and stress among frontline workers when the covid- outbreak began (e.g., brooks et al., , holmes et al., rubin, potts, & michie, ; tam, pang, lam, & chiu, ; thompson, garfin, holman, & silver, ; wu et al., ) . however, the unique features of covid- , including its virulence, the large proportions of people who remain asymptomatic but may still spread the virus (centre for evidence-based medicine, ), the stringent lockdown procedures imposed at pace on whole societies, and its global reach mean there is an urgent and ongoing need for social science research (world health organisation, ) . the collective and individual responses to severe acute respiratory syndrome coronavirus- (sars-cov- ) and to the introduction of measures to counter it have fundamentally changed how societies function, affecting how we work, educate, parent, socialize, shop, communicate, and travel. it has led to bereavements at scale, as well as frontline workers being exposed to alarming levels of stress (e.g., british medical association, ; greenberg, docherty, gnanapragasam, & wessely, ) . there have additionally been nationwide 'lockdowns' comprising physical distancing, quarantines, and isolation with the associated effects on loneliness, forced remote working, and homeschooling (e.g., hoffart, johnson, & ebrahimi, ; holmes et al., ; lee, ) . however, as well as having adverse psychological effects, the measures introduced to fight the pandemic may have led to positive social and behavioural changes. most obvious are the remarkable levels of compassion and support that have developed among neighbours and within communities as well as positive changes in behaviours such as hand hygiene, homeschooling, and physical activity. therefore, in addition to mitigating the negative effects of the pandemic, it is important to understand how any positive effects can be maintained as restrictions ease. there are, and will undoubtedly continue to be, inequalities in the effects of the pandemic and its aftermath; recognizing these vulnerability and resilience factors will be key to understanding how the current situation can inform and prepare us for dealing with future crises. of course, while we, as psychological scientists, are interested in the general effects of the pandemic, we are acutely aware of the fact that these effects disproportionately impact on different groups (box ). the issue of inequality is of central importance and runs through the research priorities that we describe below and it is a picture is emerging of covid- not as a single pandemic, but multiple parallel pandemics with some people facing numerous severe challenges and others experiencing few or none (williamson et al., ) . for those most vulnerable groups, the social, economic, and consequent psychological challenges of the pandemic are likely to be far-reaching and sustained. a clear priority for psychological scientists is to understand how best to help those in need and to consider the following factors in their research efforts. in western europe and the united states, the death rate among people with black, asian, and minority ethnic backgrounds is substantially higher than that of the general population. it is not known what is causing the disproportionate impact nor how it can be mitigated. psychological science is in a good position to explore the biopsychosocial antecedents and consequences of having a black, asian, or minority ethnic background in the context of covid- . individuals living in poverty face disproportionate challenges in relation to education, work, income, housing, and physical and mental health. for these most vulnerable groups, the social, economic, and consequent psychological challenges of the pandemic are likely to be far-reaching and sustained. moreover, an impending financial crisis means that people who have never before experienced hardships may suddenly find themselves in precarious circumstances. a quarter of people in the uk experience mental health problems every year, with particularly high levels in young people (mental health foundation, ) . the changed social conditions of the pandemic may increase the severity of mental health challenges, particularly when standard (face-toface) treatment and support are difficult to access. at the same time, pregnant women and those with existing long-term conditions such as transplant patients, cancer patients, and chronic obstructive pulmonary disease patients have been designated 'extremely vulnerable' and asked to self-isolate for long periods of time with uncertainties over access to support. those individuals who have recovered from covid- might also have new biological vulnerabilities, uncertainty over immunity post-covid- , and risk stigma arising from infection. individuals with disabilities, learning disabilities, special educational needs, and developmental disorders may also be more vulnerable due to the increased psychological challenges associated with shielding and self-isolation. the challenges generated by the pandemic vary markedly across the lifespan and will influence the nature of current and future psychological needs of different groups. many young people have struggled with reductions in direct social contact, decreased motivation, and uncertainty caused by disrupted training and education. adults have experienced multiple stresses as a consequence of intensified caring responsibilities, financial concerns, job uncertainty, and health conditions. for many older people, the greatest challenges have been social isolation, disruptions in access to health and social care, and coping with bereavement. in addition to the challenges surrounding age, there are emerging data to suggest that the effects of covid- may exacerbate existing inequalities for women. for example, women are more likely to be key workers and primary caregivers, thereby being exposed to higher levels of psychological and financial stress (fawcett society, ). the covid- pandemic is likely to have had a disproportionate impact on groups with low levels of social inclusion and/or those who traditionally have declined support services, such as people living in poverty, traveller communities, and people who are homeless. being separated from wider support networks may also be particularly difficult for those living in hostile households such as victims of domestic abuse and lgbt people living with family members who are unaccepting of their identity. many of those detained in secure settings have been exposed to marked changes in service delivery and reduced social contact, increasing their vulnerability to the psychological effects of the pandemic. surely not a coincidence that the murder of george floyd during a global pandemic prompted a global civil rights movement drawing attention to inequalities. in this position paper, informed by a group of experts and a survey (box ), we highlight the many ways in which psychological science, its methods, approaches, and interventions can be harnessed to help governments, policymakers, national health services, education sectors, and economies recover from covid- (box ) and other future pandemics (if they occur). specifically, we have identified the shorter-and longerterm priorities around mental health, behaviour change and adherence, work, education, children and families, physical health and the brain, and social cohesion and connectedness in order to ( ) frame the breadth and scope of potential contributions from across the discipline, ( ) assist psychological scientists in focusing their resources on gaps in the literature, and ( ) help funders and policymakers make informed decisions about the shorter-and longer-term covid- research priorities to meet the needs of societies as they emerge from the acute phase of the crisis. the methodology we employed to develop the main research priority domains is described in box , and the seven priority domains are outlined below and summarized in table . how does collective identification impact on social responsibility and adherence to anti-pandemic measures? one of the most striking aspects of the covid- pandemic has been the importance of social psychology to the outcomes. given the highly differentiated nature of susceptibility to the virus (box ), one might have expected many (especially the young and fit) to conclude that they have more to lose than gain by observing the rigours of lockdown and other preventative measures. if they had acted on such an individualistic calculus, then far more people would get infected and far more (especially the old and infirm) would die. however, on the whole, people did not act on the basis of such narrow self-interest, and the vast majority supported the lockdown (e.g., duffy & allington, ) . what is more, conversely, well-functioning social support is likely to confer resilience against the negative psychological impacts of the pandemic. finally, it is important that psychological scientists consider the interconnectedness of the above factors. for example, individuals who are young and from a bame background who are also from a less affluent socio-economic background may be disproportionately impacted by the educational, economic, and other consequences of the measures taken to contain and recover from the pandemic. similarly, many of the solutions to the problems posed by the pandemic involve the use of new technologies that assume the requisite skills, access to devices, and internet connectivity meaning that the 'digital divide' will likely have been exacerbated by the pandemic (ons, ). this paper outlines research priorities for psychological science for the covid- pandemic. in april , the british psychological society convened a core group of nine experts who met regularly for weeks in order to develop the research priorities. the nine experts represent broad areas of the discipline, namely biological, clinical, cognitive, developmental, educational, health, occupational, and social, and were assisted by a wider advisory group of psychological scientists (n = ) drawn from a range of uk higher education institutions and areas of research expertise. we also received input from two international experts. briefly, we used an iterative expert consensus procedure (e.g., merry, cooper, soyannwo, wilson, & eichhorn, ) to elicit and distil the judgments of experts on the research priorities for psychological science. unlike other consensus methods, which typically start with a list of priorities that are then ranked over the course of or meetings (e.g., fitch, bernstein, aguilar, burnand, & lacalle, ; mcmillan, king, & tully, ) , the present approach both generated and judged the priorities over hour long face-to-face meetings of the core group. consensus was achieved through discussion, and the experts were encouraged to discuss with the wider advisory group and their professional networks in between meetings. given the need to establish the priorities rapidly, a lengthy consultation process or an extensive review of all relevant scientific literatures was not possible. however, a brief online survey of psychological scientists was launched early in may with the aim of ensuring that the core and advisory groups had not missed any key research priorities, and to identify the highest ranked priorities in each of the broad areas of psychology to help inform the final wider-ranging research priority domains. the online survey had two components: first, participants were asked the open-ended question, 'please can you tell us what are your priorities for psychological science research in response to the covid- pandemic?' second, participants were asked to rank order the top five research priorities identified by the core group in each of the eight broad areas of the discipline (i.e., biological, clinical, cognitive, developmental, educational, health, occupational, social). the survey was distributed to psychologists via heads of uk psychology department email lists, the social media outlets of professional psychology networks (including the british psychological society), and snowball email methods by the expert and advisory group members. we received replies from psychological scientists representing all of the main areas of the discipline. respondents were . % female, . % were aged between and years, and . % self-identified as being from a minority group. the highest ranked research priorities in each of the broad areas are presented in table (see appendix for the full list of priorities). as a result of the time constraints, a detailed qualitative analysis was not possible for inclusion in this paper; nevertheless, the core group gave consideration to all of the free responses provided. overall, there were differing degrees of specificity, and respondents provided numerous, additional, and wellspecified research questions. however, at the broadest level, respondents' priorities coalesced around the question of how do we address the negative biopsychosocial effects of the covid- pandemic? the degrees of specificity related to population (e.g., people with black, asian, and minority ethnic backgrounds, children, people with low socio-economic status, people living with long-term conditions), type of intervention (e.g., service provision, environmental/social planning), methodology (e.g., qualitative, online, survey, laboratory-based), and setting (e.g., workplace, school, prison), but there was broad agreement. perceived personal risk bears no relation to whether people adhere to government instructions: whether or not one identifies with the broader community and hence acts on the basis of the risks to the community as a whole is the key driver (jackson et al., ) . so, getting people to think in collective rather than personal terms is critical to controlling the pandemic (reicher & drury, ) . or, in the rather more forceful terms of new york governor andrew cuomo: 'yeah it's your life do whatever you want, but you are now responsible for my life. you have a responsibility to me. it's not just about you . . . we started saying, "it's not about me it's about we." get your head around the we concept. it's not all about you. it's about me too. it's about we'. how can we nurture the development and persistence of mutual aid and pro-social behaviour? the significance of such 'we-thinking' is not limited to issues of adherence and social responsibility. the literature on behaviour in disasters and emergencies (drury, ) suggests that the experience of common fate in such events leads to a sense of shared social identity that in turn underpins solidarity and cohesiveness between peopleeven strangers. we have seen numerous examples of 'we-thinking' in the time of pandemic, which have played a key role in sustaining people through difficult circumstances. these range from neighbours knocking on doors to see whether people need help to over three million people contributing to more than four thousand mutual aid groups across the uk (butler, ) . so, how can we nurture such we-thinking in order to build mutual aid in communities and ensure it endures even after the acute phase of the covid- pandemic is over? what is the relationship between group membership, connectedness, and well-being? there is growing evidence of the role of group membership in sustaining both physical and mental health (haslam, jetten, cruwys, dingle, & haslam, ) . in addition to asking in general terms about how group identities are created, sustained, or else undermined in times of crises, we also need to investigate further the interface between group processes and health during and after periods of crisis. in other words: how can we keep people psychologically together even when they are physically apart and what is the relationship between face-to-face and virtual groups in terms of their health effects? more generally, that is not to say that all research priorities were covered in the original survey. two issues in particular stood out from the comments we received. the first was the importance of dealing with inequalities and differences between groups in the experience of the pandemic. the second was the need to address the positive as well as the negative developments coming out of the response to covid- . these were both incorporated into revisions of the paper and now occupy a much more central place than before. we are thankful to all those anonymous respondents whose comments helped improve our argument. a more rigorous, thematic analysis of these data is now available (see bps, c). the picture was very similar when respondents were asked to place research priorities identified by the expert group into rank orders. that is, broadly speaking, the priorities that received the highest rankings, irrespective of area of subdiscipline, were related to the need to address the negative biopsychosocial effects of the covid- pandemic. box : psychological science: methods, approaches, and interventions to help meet the immediate and longer-term covid- research priorities the future research landscape will be challenging due to the ongoing physical distancing requirements; however, psychological scientists are equipped with a broad range of methods, approaches, and interventions that will allow these research priorities to be met. some examples are as follows: internet-mediated research will be an important approach utilized by psychological scientists to collect data in the immediate post-pandemic phase and at longer-term follow-ups. internet-mediated research can be reactive (e.g., online surveys, online interviews) and non-reactive (e.g., data mining, observations from screen-time apps) and can be integrated with objective assessments of behaviour as well as with biological and social markers of physical and mental health. internet-mediated research can also be used to run experiments with online software available such as gorilla, psychopy, and e-prime. recent work has summarized the range of software for building behavioural tasks, and their efficacy in being used online (sauter, draschkow, & mack, ) . changes in the use of research methodologies may provide a catalyst for the formation of new collaborations and training to develop research skills in the psychological science community. at the same time, trust around data security and confidentiality will need to be built between researchers and the general public from whom we sample. however, in , more than an estimated million people aged - years in the european union reported they had not used the internet in the preceding months (eurostat, ) , and researchers will need to think creatively about conducting research projects remotely. for example, participants can have study materials delivered by post (e.g., salivettes for cortisol sampling or asking participants to self-sample), replacing face-to-face communication with telephone and/or video calls, and the use of personal protective equipment when collecting data. psychological therapies and behaviour change interventions can already be delivered remotely and evidence suggests that remote delivery does not necessarily mean inferior delivery (e.g., irvine et al., ) . urgent research is needed to translate interventions that are typically delivered in-person to telephone and online delivery modalities. psychologists are well-positioned to collect valuable qualitative data concerning people's relevant experiences, perspectives, and practices associated with covid- , which could inform psychologybased interventions to improve well-being and social cohesion. multiple participant-centred qualitative research methods can be rapidly deployed to elicit first-hand accounts from members of different communities, including (online) interviews, focus groups, and qualitative questionnaires, focusing on the psychological and social impact (jowett, ) . beyond the immediate term, qualitative data can be gathered longitudinally so that insights can be generated into the experiences of diverse groups over time, identifying salient crisis points and effective resolutions. implementation science is a branch of psychological science that is dedicated to the uptake and use of research into clinical, educational, health care, organizational, and policy settings. principles of implementation science can be used to help stakeholders navigate the extensive and unwieldy psychological science research literature. to inform policymakers and support professional decisionmaking about implementation, psychological research needs to be disseminated in an accessible format. one example of a well-regarded translational system is the us institute of education sciences what works clearinghouse (https://ies.ed.gov/ncee/wwc/), which provides reviews and recommendations about evidence-based practices for professionals working in educational settings. can we learn from this in order to improve the plight of socially isolated people as we emerge from the acute phase of the pandemic? under what conditions does unity and social solidarity give way to intergroup division and social conflict? finally, in addressing the positive potential of social psychological processes, we must not forget their darker side. 'we' thinking can all too easily slip into 'we and they' thinking, where particular groups are excluded from the community and then blamedeven an important feature of the covid- pandemic has been requested by government to provide psychological science expertise at pace. the inclination of many psychological scientists is to begin designing a new study or conducting a systematic review following preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines, but this does not meet the needs of policymakers. it would be valuable for psychological scientists providing expert advice to acquaint themselves with the terminology and procedures that are familiar to civil servants who are more likely to have use for a quick scoping review or rapid evidence assessment (collins, coughlin, miller, & kirk, ) rather than embarking on a time-consuming systematic review of systematic reviews (keyworth, epton, goldthorpe, calam, & armitage, ) . there are many challenges involved with conducting covid- -related research including dealing with vulnerable groups, giving due consideration to ethical concerns, as well as issues around running studies in the light of physical distancing requirements. therefore, having relevant patient and public involvement and including individuals with lived experience (as appropriate) in designing studies will be of paramount importance. psychological science has been leading the way in promoting and adopting open science principles and practices. nevertheless, psychological scientists need to ensure they balance the urgency of conducting covid-related research (during and in the recovery period) with ensuring research quality and open research practices. therefore, in order to help maintain quality, openness, and rigour, we urge researchers to endeavour to use registered reports, where possible (e.g., https://osf.io/rr/), or preregister their research hypotheses and analysis plans (e.g., https://aspredicted.org/) and make their data findable, accessible, interoperable, reusable (fair) recognizing the principle of 'as open as possible; as closed as necessary' (bps, a (bps, , b norris & o'connor, ) . moreover, we urge researchers to utilize pre-print servers, such as psyarxiv, in order to ensure their latest research findings are made publicly available rapidly and at no cost. we hope that openness will drive quality, but as yet there is no substitute for articles being peer-reviewed prior to wider acceptance by the scientific community. psychological science has responded swiftly to the covid- pandemic, but there is a danger of duplication of efforts and participant fatigue in the proliferation of online surveys, experiments, and focus groups that have arisen. we need to harness the ongoing efforts of psychological scientists worldwide in a coordinated effort on the scale of the large hadron collider (cern, ) to deliver truly evidence-based interventions to help societies emerge from the covid- pandemic. this will include cross-cultural research to understand why mortality rates, mitigation measures, and adherence to government instructions have differed so markedly between countries. finally, we urge researchers to register their research studies and findings on international repositories (https://osf. io/collections/coronavirus/discover). attackedfor the crisis. thus, un head antonio guterres has warned of a 'tsunami of hate' unleashed by the pandemic (davidson, ) . this hate and violence can take different forms: of anti-authority riots as in france (willsher & harrap, ) , or of racist violence against minorities as in india (mazumdaru, ) . in sum, insights from social psychology can be a valuable resource in a crisis; it can bring people together and generate constructive social power. but equally, it can set people apart and create problems that endure well beyond the crisis itself. it is evidently of the greatest importance to understand the processes that determine whether people unite or divide in hard timesand notably to understand the role of leadership, which has been so significant and so diverse in different countries during covid- . work environment and working arrangements consistent with previous pandemics (e.g., rubin et al., ) , the work-related challenges of the pandemic have been particularly high and widely recognized for health and social what is the impact of remote and flexible working arrangements on employee health, mental wellbeing, teamwork, performance, organizational productivity, and colleague/client relationships? what is the impact of social distancing in the workplace on employee health, mental well-being, teamwork, performance, organizational productivity, and colleague/client relationships? how can organizational resilience be developed to deal with the impact of covid- whilst supporting employees and protecting jobs? how will the covid- pandemic affect children's development? how will the covid- pandemic affect family functioning? how do school closures influence children's educational progress and well-being? what kinds of support improve long-term outcomes for children and young people? how can support services be effectively delivered to vulnerable children and young people, families, and schools? what are the immediate and longer-term consequences of covid- for mental health outcomes? what changes in approaches resulting from the pandemic need to be harnessed for the future? . physical health and the brain does covid- have neurological effects on the brain with consequences for mental health? what are the psychobiological impacts of the covid- pandemic on physical and mental health? how do we best apply existing theories and tools to promote sustained behaviour change among policymakers, key workers, and the public/patients? how do we develop new theories and tools to promote sustained behaviour change? care workers in direct contact with patients suffering the effects of covid- , leaving them vulnerable to trauma, fatigue, and other manifestations of chronic stress. what is unique about covid- is that changed working conditions and anxiety about infection have affected almost all employees, with particular challenges being faced by delivery workers, shop assistants, teachers, emergency services personnel, care home staff, transport staff, and social workers. the full economic severity of the covid-related restrictions is uncertain, although up to two million people could lose their employment in the uk alone (wilson, cockett, papoutsaki, & takala, ) . for those people still working, and those about to return to work, there are notable changes that will likely affect working practices in the foreseeable future. therefore, understanding the impact of the covid- pandemic on the work environment and new working arrangements is paramount to kick starting the economy and adjusting to daily life. what is the impact of remote and flexible working arrangements on employee health, mental wellbeing, teamwork, performance, organizational productivity, and colleague/client relationships? for many workers, particularly those in white-collar occupations, work took place entirely from home during the lockdown. it is possible that the lockdown will accelerate the general increase observed in home working practices (ons, ). a move to greater levels of remote working has clear economic benefits for employers (e.g., reduced estates costs). the flexibility to balance work and family life is also attractive to many employees (cf. strategic review of health inequalities in england, ). overall, the evidence points to positive benefits of remote working in terms of well-being (charalampous, grant, tramontano, & michailidis, ) , although these effects are not consistent. for example, it may lead to greater levels of professional isolation (golden, veiga, & dino, ). an increase in remote working will likely occur with a concomitant increase in the use of online technology to support communication and aspects of collaborative working. this has the potential to blur boundaries between work and home domains, resulting in negative impacts on well-being and productivity from work-home interference (van hoof, geurts, kompier, & taris, ) . greater use of technology may also be associated with different perceptual and cognitive demands that may affect productivity and wellbeing including social connections with work colleagues (e.g., mark et al., ) . what is the impact of physical distancing in the workplace on employee health, mental well-being, teamwork, performance, organizational productivity, and colleague/client relationships? until an effective vaccine is available, physical distancing rules will need to continue to be in place in work environments and we may experience multiple stay-at-home versus return-towork cycles. there is very little research exploring physical distancing and its effect on the general workplace, but returning to work will likely be both a welcome change and a potential stressor. while we have research from teams working in difficult and extreme environments (power, ; smith, kinnafick, & saunders, ) and research on professional isolation (golden et al., ) , this is an unprecedented opportunity to study adaptation across a breadth of individuals and organizational settings. how can organizational resilience be developed to deal with the impact of covid- whilst supporting employees and protecting jobs? the unprecedented demands that the pandemic has placed on organizations also offer a unique opportunity to understand how organizational resilience and preparedness for dealing with disruptions and emergencies can be developed. while a pandemic of this nature is rare, we can anticipate increasing periods of disruption due to covid- flareups and additionally, for example, in response to climate-induced events (e.g., recent australian fires, uk flooding), which are predicted to occur more frequently (banholzer, kossin, & donner, ) . although we know a lot about individual resilience, we know relatively little about organizational resilience, especially in the context of well-being and performance (taylor, dollard, clark, dormann, & bakker, ; fasey, sarkar, wagstaff & johnston, under review) and the ingredients such as the structures, processes, culture, and leadership that are essential for developing organizational resilience. parenting can be a challenging and anxiety-provoking experience at any time, but the covid- pandemic has brought these challenges and anxieties into sharp focus. for most families, the lockdown will represent the longest period of parenting they have experienced without ( ) the support of extended family members, friends, and childcare professionals; ( ) the routine of school and out-of-school activities; and ( ) any face-to-face social life outside the home. these changes in the social environment may have both negative and positive impacts on children and their families. at the most extreme end of the spectrum, the restrictions in place to combat the spread of the virus have been associated with worrying increases in domestic violence and child abuse. however, all families are likely to have experienced greater levels of stress (social care institute for excellence, ). the majority of carers with school-age children are dealing with homeschooling for the first time, and many carers are having to adapt to working from home while also looking after their children and older relatives. these pressures will be particularly acute for single-carer families. of course, such multi-tasking concerns apply only to carers fortunate enough to have maintained employment. it is important to support families during the current crisis, but also to understand the implications of these unprecedented changes in family life for family functioning and children's development as we emerge from the pandemic. how will the covid- pandemic affect family functioning? many effects of the pandemic on children's development are likely to be indirect, functioning through its impact on caregiving and family functioning. it is crucial for this research to include family members such as grandparents and non-resident parents and siblings. children in families who are already vulnerable due to domestic violence or abuse, social or economic disadvantage, or physical or mental ill health are likely to be most adversely affected. there is an urgent need for research to examine how these vulnerabilities moderate changes in family functioning post-pandemic and their impacts on the child. the ability to regulate behaviour and emotional responses is a key aspect of successful social interaction in individuals of all ages (e.g., baumeister & heatherton, ; kochanska, murray, & harlan, ) . family members may develop new self-regulation strategies as a result of having extended contact with the same restricted group of people. while such strategies may be adaptive, individuals facing extreme social or financial challenges may cope by psychologically distancing themselves from family members, ruminating on negative events, or engaging in behaviours that are harmful. understanding how adaptive and maladaptive self-regulation strategies change post-pandemic may prove useful in identifying individuals who need additional psychological support. school closures and social restrictions may provide a unique opportunity for family members to gain insight into each other's lives, potentially reducing disagreements and improving family functioning. research should investigate whether reporting such improvement during the crisis is associated with lower caregiving stress and better mental health. it is also important to study how families can maintain any positive aspects of functioning that have resulted from the pandemic as restrictions are eased. how will the covid- pandemic affect children's development? the effects of the pandemic will undoubtedly vary as a function of the child's age. while carers with young infants may have concerns about the negative impact of the lockdown on their babies' development, the infants themselves will be unaware of the abnormal nature of their social environment. optimal later development is predicted by caregivers' ability in the first year of life to see the world from the infant's point of view and respond appropriately to their cues (e.g., fraley, roisman, & haltigan, ; zeegers, colonnesi, stams, & meins, ) . the social restrictions do not obviously impede this type of infantcaregiver engagement, and young infants may therefore be least affected by the pandemic. older children who recognize the drastic changes in social contact may find transitioning back to pre-pandemic social behaviour difficult. it is therefore important to study how children and young people manage this transition and investigate whether the lockdown has raised the incidence of emotional and behavioural difficulties. studying the effects of the pandemic and its aftermath on particular groups that are known to be vulnerable to educational and health disadvantage (e.g., looked after children or children with developmental disorders) should be prioritized. positive effects of the pandemic on children's behaviour and social interaction are also anticipated. many children and young people will have found new ways to communicate with friends, entertain themselves, and keep themselves physically active. time away from school may have been spent learning new skills, developing new hobbies, or helping or supporting others. investigating changes in children and young people's empathy, altruism, theory of mind, creativity, innovation, problem-solving, and cognitive flexibility post-pandemic will help shed light on potential positive outcomes of the social restrictions associated with the pandemic. the challenges posed by the covid- pandemic have never been more evident than for the education and well-being of children and young people. in april , a third of the world's population were experiencing extended periods of lockdown with closure of schools and nurseries. parents, many of whom had work and other family responsibilities had to adopt the additional role of educator in home environments not set up for formalized learning. ad hoc arrangements were put in place at speed by schools with limited opportunities to develop clear definitions of learning activities, provide access to learning resources, and establish effective home-school communication. early surveys have shown wide variation in homeschooling arrangements, including stark differences between state and private schools in access to online learning and pupil-teacher communication (sutton trust, ) . there is a wealth of evidence about the factors that facilitate effective learning in schools, such as curricula and teaching strategies (hattie, ) . other studies have established that children's academic attainment and adjustment are predicted by higher caregiver education (erola, janolen, & lehti, ) and engagement in schooling (harris & goodall, ) . however, little is known on how to set up and deliver home education effectively under the unique conditions of the pandemic. while for some children the extended period at home is likely to have distinct positive benefits, research prior to covid- on substantial externally driven disruptions in schooling has shown adverse effects on child achievement and well-being (meyers & thomasson, ; sunderman & payne, ). the outcomes for the individual child are likely to depend on the capacity of families to step in and effectively support curriculum delivery at home. studies of other severe unplanned disruptions to schooling and family lives such as long-running strikes and natural disasters have shown greatest impacts on long-term educational and emotional outcomes for the most disadvantaged children (jaume & will en, ; masten & osofsky, ) . at particular risk of disproportionate adverse outcomes are children from families living in poverty, those receiving social care support, individuals with special educational needs and disabilities, and young people with mental health problems. there are high levels of concern that the recognized attainment gap for children from disadvantaged families (education in england: annual report . education policy institute) could be magnified by the pandemic conditions. there is an urgent need to identify and understand both the positive and negative factors that influence children's educational outcomes during and after the pandemic, and to use this knowledge to target support to those who need it most. the unanticipated consequences of the pandemic pose challenges for conventional designs depending on pre-intervention assessments. understanding its impacts on children's lives will require a robust body of research that draws on the diverse research methods of psychological science. this will require large-scale multidisciplinary data collection in addition to smaller-scale quantitative and qualitative approaches that will be vital for understanding the experiences of children, families, and professionals. some key questions to be addressed by this research are outlined below. in addition to collecting data on home-based support for learning, detailed contextual data are needed about social and environmental factors that are likely to interact in determining positive educational outcomes at particular educational phases (e.g., reading, writing, and maths in primary schools), as well as a range of mental health outcomes (e.g., anxiety, depression, self-harm, resilience). this will include research into the effect of social distancing on a range of social outcomes in children and young people (e.g., inclusion/ exclusion, friendships). what kinds of support improve long-term outcomes for children and young people? knowledge about the impacts of school disruptions on all children and young people will allow evidence-based interventions and resources to be targeted at those with greatest need. robust evaluations are required to scrutinize how interventions are accessed, by whom and with what degree of success. how can support services be effectively delivered to vulnerable children and young people, families, and schools? with reduced resources and restricted movement, professionals (such as practitioner psychologists) have had to adapt and develop new ways of delivering services. researchers in psychological science have a key role to play in working with practitioners and service providers to evaluate systems put in place for monitoring and delivering professional support during and in the aftermath of the pandemic. what are the immediate and longer-term consequences of covid- for mental health outcomes? there is expected to be an increase in mental health problems as a result of the covid- pandemic and the measures used to counter it. we already have evidence for the long-term mental health effects of previous pandemics and disasters (e.g., tam et al., ; thompson et al., ; wu et al., ) and an emerging literature on the near-term effects of covid- (e.g., ahmad & rathore, ; williamson et al., ) . but previous pandemics have been more localized and circumscribed making covid- different. social distancing, school closures, self-isolation, and quarantine have lasted longer than anything previously experienced. we know that these factors, together with financial uncertainty and concerns about health, are predictive of mental health difficulties, particularly anxiety. the current pandemic amplifies these factors and not only exacerbates problems in those with pre-existing mental health difficulties, but also increases the chance of new onset in those with no previous contact with mental health services. concerns about mental health effects may be particularly heightened for children, who have experienced high levels of disruption to normative developmental opportunities (including opportunities for social and outdoor play) and education, and potentially high levels of family stress (https://emergingminds.org.uk/cospace-study- ndupdate/). various poor mental health outcomes are also potentially associated with the disease itself. information about the long-term consequences comes from similar viruses such as sars and the mers. for example, many people who suffered from sars seemed to experience detrimental psychological effects even a year later (rogers et al., ; tam et al., ; thompson et al., ; wu et al., ) . therefore, we need to establish the immediate and long-term consequences of covid- on mental health outcomes in the population generally, but also in vulnerable, shielding, and self-isolating groups (box ). we urgently need to understand how all these factors interact and whether these consequences will require psychological interventions and supports not currently available. what changes in approaches resulting from the pandemic need to be harnessed for the future? even if the mental health consequences of this pandemic are not as predicted, we still expect increases in mental health problems. we know that mental health accounts for an increasing proportion of sick leave and that one in eight children and young people experience a diagnosable mental health problem (nhs digital, ) . childhood mental health problems often recur in adulthood (kessler et al., ) and are associated with physical health difficulties, poor academic, and occupational functioning, and are the primary predictor of low adult life satisfaction (layard, clark, cornaglia, powdthavee, & vernoit, ) . the increased prevalence will place a further burden on a mental health system that was already stretched and will increase waiting times and accentuate gaps in care. during the pandemic, mental health services rapidly changed. inpatients were discharged, even if they were detained in hospital because they were a risk to themselves or others. some people benefited, but we do not know how this reduction in bed use was managed. was it because the right supports and accommodation were provided? the move to remote contact in mental health services had been slow and of varied quality prior to covid- with challenges for both staff and service users. but the shift during the pandemic was swift, and although undoubtedly nhs staff felt pressure during the changeover, there now seems to be a steadier state. again, some service users may have benefited from this change with reductions in travel and, for some, better access to care and treatment. however, although the digital divide is reducing (robotham, satkunanathan, doughty, & wykes, ) , it remains highest in those who already have high unmet needs, including people in rural areas, those on lower incomes, people with lower levels of formal education, and older people. if remote working is tobe abeneficial part of an evolved mental health service, then we need to understand how to provide that 'webside' manner that will increase adherence and promote a therapeutic alliance. we also urgently need to evaluate the effectiveness of remotely delivered, digital interventions in the immediate and longer term. future interventions will need to be deliverable remotely, depending on local resources. for example, from an international perspective, many low-to-middle-income countries do not have high broadband penetration; hence, optimizing digital delivery that depends strongly on good internet connections will further widen the welfare gap. physical health and the brain the effects of covid- on health outcomes will be far-reaching and complex. for those falling ill, there are the direct consequences of the disease symptoms, such as respiratory failure in severe cases, alongside potentially direct viral effects on the brain. there are also more indirect population-wide effects of covid- pandemic-related stress and anxiety on physical and mental health, not only from the disease itself but also from changes in lifestyle including delayed treatment and screening for other known or suspected conditions. moreover, it is also likely that from an international perspective, in many lowto-middle-income countries, the pandemic will result in greater hunger/starvation, which will have severe impacts upon health. does covid- have neurological effects on the brain with consequences for mental health? at one level, covid- might alter mental health by the direct actions of the specific virus (severe acute respiratory syndrome coronavirus- ; sars-cov- ) on the brain. while neurological dysfunction is often described in covid- , including dizziness, and loss of taste and smell, these conditions are common to other respiratory tract infections and need not reflect a neurological disease per se (needham, chou, coles, & menon, ) . data from cerebrospinal fluid and post-mortem analyses will help resolve issues over the penetrance of sars-cov- . it is, however, known that the target receptor for sars-cov- is the angiotensin-converting enzyme- receptor (ace ). disruption of the blood-brain barrier during illness might enable entry of the virus, potentially aided by the presence of ace receptors in glial cells and brain endothelium. other potential routes of entry include the cribriform plate and olfactory epithelium, as well as via peripheral nerve terminals, permitting entry to the cns through synapse connected routes (ahmad & rathore, ) . at the same time, there is an array of immunological responses, including the cytokine 'storm' in severe cases, alongside non-immunological insults to the central nervous system provoked by covid- . the latter include hypoxia, hypotension, kidney failure, and thrombotic and homeostatic changes involving neuroendocrine function (needham et al., ) . together and separately, they may contribute to brain dysfunction in ways that vary with the severity of the infection, other underlying conditions (needham et al., ) , and the treatment for those other conditions (south, diz, & chappell, ) . largescale studies help confirm differential clinical risk factors for death following infection (williamson et al., ) , prompting genotype analyses, while noting that covid- might also induce epigenetic changes, including ace demethylation (sawalha, zhao, coit, & lu, ) . additional health concerns include post-viral fatigue and whether it might provoke a long-lasting syndrome. research consortia are initiating comparisons between populations that have or have not contracted covid- . challenges for psychological scientists include how to assess impacts on cognition and mental health, both in the short term and long term. a part of this challenge is how to deliver effective, online psychological testing (e.g., for 'shielded' populations), or to help follow-up large population cohorts, while not biasing the sample away from those least likely to use these platforms. an integral part of some investigations will be the inclusion of multiple neuroimaging methods, despite the era of distancing. just one of many questions would be the impact of covid- on mild cognitive impairment and its conversion to dementia. there is a premium on studying pre-existing cohorts (e.g., uk biobank, alspac), where retrospective, baseline data exist. such data are especially precious in the present landscape where everyone is, to some degree, affected by the pandemic. the power of these pre-existing cohorts will, however, be heavily influenced by the proportion of the population who contract covid- . what are the psychobiological impacts of the covid- pandemic on physical and mental health? despite the umbrella term 'stress' covering many different things, there is agreement that in its different forms, stress can lead to physiological changes (e.g., neuroendocrine, cardiovascular), with negative consequences for health (o'connor, thayer & vedhara, in press). three principal research questions can be identified: ( ) to what extent does pandemic-related stress, anxiety, and worry impact on biological mechanisms that influence health (i.e., hypothalamic-pituitary-adrenal axis regulation and cortisol dynamics, the autonomic nervous system, and gene expression) as well as on health behaviours (e.g., eating, sleep, alcohol consumption)? ( ) how best to counter their adverse effects? and ( ) how might such stress exacerbate existing medical and mental health conditions, and for how long? for all three questions, there will be considerable variations between groups and individuals (box ). one challenge will be to collate and verify relevant information, including that from 'smart' devices that can provide daily physiological data, activity information, and other measures of diurnal patterns, including sleep. one of the groups most likely to be negatively affected by stress is health care professionals. the pandemic may exacerbate the already high prevalence of secondary traumatic stress, burnout, and physical exhaustion among health care professionals, as well as impact on patient safety and medical error (e.g., dar & iqbal, ; figley, ; hall, johnson, watt, tsipa, & o'connor, ) , due to excessive workload and workplace trauma (e.g., itzhaki et al., ) . while resources such as support from managers and colleagues can help protect health care professionals against traumatic stress, the longerterm impact is likely to be substantial on individuals, their families, on the national health services and the wider care industry. amongst other groups of concern (box ) are those caring for a vulnerable relative or partner at home. one novel feature of daily life in the wake of the covid- pandemic in countries around the world are near-daily government briefings. one focus of these briefings is government instructions to the public as to how to behave. adherence to these and future instructions will be key to dealing with future crises. moreover, many sections above share in common the requirement that people adhere to instructions, whether it is practitioners delivering psychological therapies effectively over the telephone or employees continuing to maintain physical distancing at work. in the initial response to the pandemic, many governments instructed people to ( ) stay inside as much as possible; ( ) stay > m away from other people at all times; and ( ) maintain hand hygiene, among other measures such as wearing face coverings. the evidence suggests that public adherence to government covid- -related instructions worldwide has been high (ons, ), but it is not clear for how long people will continue to adhere to instructions that impinge on personal freedoms. what is clear is that there is a dearth of workers sufficiently trained to advise policymakers and to implement behaviour change interventions rapidly and at scale. the british psychological society's guidance on behaviour change is a good starting point for ensuring that instructions and messaging is clear (british psychological society, a). appointing chief behavioural science advisers to governments would ensure that cuttingedge psychological science advice is placed at the heart of policymaking. as people begin to emerge from the acute phase of the pandemic and the changes that were made to tackle it, it is important that psychological science is at the heart of ensuring that health-enhancing behaviours are sustained and that health-damaging behaviours are changed or prevented. there are numerous approaches to developing such interventions, including the behaviour change wheel (michie, atkins, & west, ) and intervention mapping (bartholomew eldrigde et al., ) , but they require the expertise of psychological scientists to deliver and to evaluate them (west, michie, rubin, & amlôt, ) . one of the main challenges now, and in the future, will be to ensure there is a workforce equipped with the competencies to develop behaviour change theory and tools that will bring about sustained changes in behaviour. taught post-graduate courses exist that could be scaled up and/or adapted to continuing professional development qualifications to meet this demand and help ensure that the changes in behaviour that will be required for the foreseeable future are sustained. how do we best apply existing theories and tools to promote sustained behaviour change among policymakers, key workers, and the public/patients? we sometimes forget that we have the theories and evidence for solutions that can be applied at pace to address novel problems. although we have never seen a lockdown before and so cannot predict what the outcomes will be directly, we do know what processes underpin adherence to instructions, and so can advise on the levers that can sustain adherence. in unprecedented and uncertain times now and in whatever the future might bring, the nature of psychological science allows us to make unique and invaluable contributions. if the covid- pandemic teaches us one thing, it is on the need to accelerate the translation of evidence from psychological science into practice. how do we develop new theories and tools to promote sustained behaviour change? at the same time, we should not forget the 'slow' approach to research (armitage, ) that involves addressing key research questions with multiple perspectives and methodologies, and accumulating such knowledge in prisma-guided systematic reviews. it is vital that continued investment is made into behaviour change research. only with this can we refine and develop the theories that best explain human behaviour (e.g., michie et al., ) . key research priorities include identifying which behaviour change techniques work best, for whom, in which contexts, and delivered by what means (e.g., epton, currie, & armitage, ) as well as how to counter the conspiracy theories and misinformation that arise during crises that seem to be aimed at derailing the very behaviours required to keep us safe and to reduce risk. in this position paper, we have set out seven research priority domains in which psychological science, its methods, approaches, and interventions can be harnessed in order to help governments, policymakers, national health services, education sectors, economies, individuals, and families recover from covid- . these are mental health, behaviour change and adherence, work, education, children and families, physical health and the brain, and social cohesion and connectedness. we have also highlighted that a clear overarching research priority relates to understanding the inequalities in the effects of the pandemic and recovery; recognizing the vulnerability and resilience factors that will be key to understanding how the current pandemic can inform and prepare us for dealing with future crises. we call on psychological scientists to work collaboratively with other scientists in order to address the research questions outlined, refine them and to adopt multidisciplinary working practices that combine different disciplinary approaches. an important next step will be to engage with wider stakeholders, potential users, individuals with lived experience, and beneficiaries of the research. addressing each of the research priority domains will benefit enormously from larger scale working and coordinated data collection techniques and the establishment of research consortia with their associated economies of scale. we also call on psychological scientists to further develop and adapt innovative research methodologies (e.g., remote testing and intervention delivery, online data collection techniques), while maintaining high-quality, open, and rigorous research and ethical standards in order to help with the recovery as we emerge from the acute phase of the crisis. how can we use biological markers to facilitate people's return to work? how do we link covid- -related biomarkers to existing population cohort databases? how do we address the negative biological impacts of the covid- virus on mental health? what are the impacts of covid- infection, treatment, and recovery on the brain? how do school closures influence educational progress, and physical and mental health outcomes for all children and young people? what 'homeschooling' practices are associated with positive educational and psychological outcomes? what is the effect of social distancing on a range of social outcomes in children and young people? what methods are used to track, monitor, and deliver local authority support services to vulnerable children and young people, families, and schools during lockdown, at transition back to school, and after return to school? how are educational and psychological interventions allocated, structured, delivered, and evaluated for children and young people in need, after schools have reopened? what is the impact of remote and flexible working arrangements on employee health, mental well-being, teamwork, performance, organizational productivity, and colleague/client relationships? what is the impact of social distancing in the workplace on employee health, mental well-being, teamwork, performance, organizational productivity, and colleague/client relationships? what managerial behaviours are most effective to manage remote working, possible mental health issues, job insecurity, and productivity? what is the risk of longer-term mental ill health among frontline staff after the immediate crisis? how can organizational resilience be developed to deal with the impact of covid- whilst supporting employees and protecting jobs? neurological manifestations and complications of covid- : a literature review changing behaviour, slow and fast: commentary on peters, de bruin and crutzen the impact of climate change on natural disasters planning health promotion programs: an intervention mapping approach self-regulation failure: an overview stress and burnout warning over covid- behavioural science and disease prevention taskforce. behavioural science and disease prevention: psychological guidance position statement on open data covid- research priorities for psychological science: a qualitative analysis the psychological impact of quarantine and how to reduce it: rapid review of the evidence covid- mutual aid: how to help vulnerable people near you. the guardian lhc the guide systematically reviewing remote e-workers' well-being at work: a multidimensional approach the production of quick scoping reviews and rapid evidence assessments: a how to guide beyond linear evidence: the curvilinear relationship between secondary traumatic stress and vicarious posttraumatic growth among healthcare professionals global report: virus has unleashed a 'tsunami of hate' across world, says un chief. the guardian the role of social identity processes in mass emergency behaviour: an integrative review the accepting, the suffering and the resisting: the different reactions to life under lockdown. the policy institute, king's college london unique effects of setting goals on behavior change: systematic review and meta-analysis parental education, class and income over early life course and children's achievement what do you use the internet for? defining and characterising organisational resilience in elite sport coronavirus: urgent call for uk government to support women and girls compassion fatigue: coping with secondary traumatic stress disorder in those who treat the traumatized the rand/ucla appropriateness method user's manual the legacy of early experiences in development: formalizing alternative models of how early experiences are carried forward over time the impact of professional isolation on teleworker job performance and turnover intentions: does time spent teleworking, interacting face-to-face, or having access to communication-enhancing technology matter managing mental health challenges faced by healthcare workers during covid- pandemic healthcare staff wellbeing, burnout, and patient safety: a systematic review do parents know they matter? engaging all parents in learning the new psychology of health: unlocking the social cure visible learning, a synthesis of over meta-analyses relating to achievement loneliness and social distancing during the covid- pandemic: risk factors and associations with psychopathology multidisciplinary research priorities for the covid- pandemic: a call for action for mental health science are there interactional differences between telephone and face-to-face psychological therapy? a systematic review of comparative studies mental health nurse's exposure to workplace violence leads to job stress, which leads to reduced professional quality of life the lockdown and social norms: why the uk is complying by consent rather than compulsion the long-run effects of teacher strikes: evidence from argentina carrying out qualitative research under lockdown -practical and ethical considerations. lse impact blog age of onset of mental disorders: a review of recent literature delivering opportunistic behavior change interventions: a systematic review of systematic reviews effortful control in early childhood: continuity and change, antecedents, and implications for social development what predicts a successful life? a life-course model of well-being mental health effects of school closures during covid- email duration, batching and self-interruption: patterns of email use on productivity and stress disasters and their impact on child development: introduction to the special section coronavirus: eu fears a rise in hostile takeovers how to use the nominal group and delphi techniques mental health statistics: children and young people an iterative process of global quality improvement: the international standards for a safe practice of anesthesia paralyzed by panic: measuring the effect of school closures during the polio pandemic on educational attainment (no. w ) the behaviour change wheel: a guide to designing interventions neurological implications of covid- infections mental health of children and young people in england - science as behaviour: using a behaviour change approach to increase uptake of open science stress and health: a review of psychobiological processes exploring the uk's digital divide coronavirus and the social impacts on great britain extreme teams: toward a greater understanding of multiagency teamwork during major emergencies and disasters the two psychologies and coronavirus. the psychologist do we still have a digital divide in mental health? a five-year survey follow-up psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the covid- pandemic the impact of communications about swine flu (influenza a h n v) on public responses to the outbreak: results from national telephone surveys in the uk building, hosting and recruiting: a brief introduction to running behavioral experiments online epigenetic dysregulation of ace and interferonregulated genes might suggest increased covid- susceptibility and severity in lupus patients coping strategies used during an extreme antarctic expedition domestic violence and abuse: safeguarding during the covid- crisis covid- , ace , and the cardiovascular consequences strategic review of health inequalities in england post- does closing schools cause educational harm? a review of the research. information brief covid- impacts: school shutdown severe acute respiratory syndrome (sars) in hong kong in : stress and the psychological impact among frontline healthcare workers psychosocial safety climate as a factor in organisational resilience: implications for worker psychological health, resilience, and engagement distress, worry, and functioning following a global health crisis: a national study of americans' responses to ebola work-home interference: how does it manifest itself from day to day? applying principles of behaviour change to reduce sars-cov- transmission opensafely: factors associated with covid- death in million patients in a paris banlieue, coronavirus amplifies years of inequality. the guardian getting back to work: dealing with the labour market impacts of the covid- recession. institute for employment studies coronavirus disease (covid- ) the psychological impact of the sars epidemic on hospital employees in china: exposure, risk perfection, and altruistic acceptance of risk mind matters: a three-level meta-analysis on parental mentalization and sensitivity as predictors of infant-parent attachment christopher armitage's contribution is supported by the nihr manchester biomedical research centre and the nihr greater manchester patient safety translational research centre. the views expressed in this publication are those of the authors and not necessarily those of nihr. armitage would like to thank professors madelynne arden and alison wearden for their support in writing. til wykes would like to acknowledge the support of her nihr senior investigator award. the set of priorities utilized for the survey of the psychological community.how do we increase adherence (and ability to adhere) to uk government covid- related instructions? how do we promote maintenance of positive behaviour changes and reverse negative behaviour changes resulting from covid- -related lockdown? how do we address the negative psychological impacts of the covid- pandemic? how do we maximize recovery from covid- for those infected with the virus? what is the impact of covid- -related stress on biological processes and health outcomes? what makes people adhere to anti-covid measures? what are the bases of anti-social behaviours such as stockpiling? how do mutual aid groups form and what makes them endure? when does social cohesion give way to scapegoating, prejudice, and intergroup conflict? what creates (or prevents) the potential for protests and collective disorder in the crisis? what are the long-term mental health effects of covid- ? what coping mechanisms are useful in reducing mental health problems during a pandemic? how do we provide beneficial remote psychological therapy and maintain therapeutic alliance? has discussion of mental health during the pandemic reduced stigma and discrimination in the community? people detained in hospital under the mental health act were discharged to free up bedshow was this possible? what are the impacts of covid- infection, treatment, and recovery on cognition, behaviour, and the brain? what are the drivers of covid- -related stress and its cognitive, neural, and physiological mechanisms and consequences? what are the perceptual and cognitive demands of digital and other alternative forms of communication and how do they impact on work and social connectivity? what factors influence the effectiveness of communication of scientific evidence and national guidance, and how do they influence behaviour? how do restrictions of movement, communication, and social support influence the cognitive, physical, and mental health of older individuals, and what factors lead to improved outcomes? how has the covid- pandemic affected parenting? how has the covid- pandemic affected children's development? how has the covid- pandemic affected family functioning? which factors moderate family members' response to the covid- pandemic? what support is most effective for families during the covid- pandemic? how do we assess biological markers of health and well-being remotely?continued key: cord- -ggrrbq u authors: ganguly, shuvadeep; bakhshi, sameer title: teleconsultations and shared care in pediatric oncology during covid- date: - - journal: indian j pediatr doi: . /s - - - sha: doc_id: cord_uid: ggrrbq u nan the recent coronavirus disease- pandemic (covid- ) presented a significant challenge in the effective care delivery for children with cancer across the globe. the data on clinical outcome of covid- in childhood cancer patients is limited with very few cases severe enough to require intensive care [ ] . still, keeping in mind the immunosuppressive nature of anti-neoplastic therapy and our evolving understanding of the disease, pediatric oncology services have to tread carefully between treating cancer and limiting covid- in this vulnerable population. with healthcare centres throughout the world grappling with covid- pandemic with resource optimization, all aspects of cancer treatment were adversely affected, including ancillary services like blood product availability [ ] . drawing on the early experience in italy, a consensus based guideline was formulated by international childhood cancer organizations to adapt treatment strategy of childhood cancer patients keeping in mind resource limitations during the pandemic [ ] . our centre is a government tertiary care healthcare institution, which was also concurrently designated as a covid- hospital during this pandemic. this led to manpower diversion thereby curtailing all aspects of non-covid- healthcare services. india also simultaneously instituted lockdown measures early in the pandemic which led to further difficulty for parents/caregivers to access timely care. our team formulated a multi-pronged strategy to adapt our treatment services considering these local challenges [ ] . initial triaging of patients and deciding intent of treatment was the cornerstone of the strategy. for children with palliative intent, hospital visits and intravenous chemotherapy were deferred as much as possible and oral metronomic therapy was administered wherever feasible [ ] . we also adapted our chemotherapy protocols for various solid malignancies utilizing oral therapy and deferring hospital visits as a temporary measure especially for families living far away from hospital [ ] . on the other hand, for aggressive malignancies like acute leukemia or non-hodgkin lymphoma (nhl) with curative intent, all efforts were made to institute or continue therapy according to protocol without any delay. proper multidisciplinary co-ordination was maintained and life-saving surgeries with curative intent for disease like bone sarcoma were carried out with all proper precautions during this pandemic period [ ] . we kept a significantly low threshold for testing any symptomatic patient for severe acute respiratory syndrome coronavirus (sars-cov- ) and isolate any positive cases at the earliest. over the course of last four months of this pandemic (april to july ), even with curtailing of healthcare services at our centre, new cases (age ≤ years) were registered and children with acute leukemia and lymphoma were started on therapy. among the children under our follow-up, children turned positive for sars-cov- with fatal outcome in two ( . %) of them; both these cases were having relapse/refractory cancer. unfortunately, another one of our patient committed suicide on fear of contracting covid- which underlines the excess of fear, stress, and stigma this disease has caused among common populace. during this pandemic situation, the government of india devised policies to strengthen telemedicine services and encouraged the adoption of digital healthcare [ ] . taking cue from the same, we contacted families/caregivers of a significant subset of routine outpatient oncology patients telephonically and also issued prescription via e-mail facility. support were provided to create e-mail facilities for families who were not well versed with technology by involving alternate family members. all childhood cancer survivors were followed up telephonically, advised to undergo investigations as per protocol locally, the reports of which were then evaluated via e-mail facility. this strategy of teleconsultation was also predominantly utilized for patients under non-intensive care like children with acute lymphoblastic leukemia/langerhans cell histiocytosis under maintenance therapy or patients on comparatively simpler protocols like hodgkin lymphoma. chemotherapy plans were decided after reviewing reports, and prescriptions were shared via e-mail. families were then advised to undergo chemotherapy at local healthcare institutions with pediatric facilities even including intrathecal drug administrations. during these last months, our team and patients' families readily adopted telemedicine services with number of teleconsultations rising from in month of april to in month of july . although there was a significant decrease in number of routine outpatient consultations ( % as compared to similar period last year), total children were managed on teleconsultation basis, which constitutes a sizeable . % of cumulative outpatient visits during this period. childhood cancer services in india is predominantly concentrated in few tertiary care institutes in first tier cities leading to inequitable and often delayed care [ ] . the extra-ordinary situation posed by this pandemic forced us to develop collaborative model to ensure continuity of care by involving local pediatric healthcare facilities, akin to the "shared care model" as practised in some western countries [ ] . being a tertiary care institution located at national capital, majority of families accessing our centre belongs to far away places [ ] . staying near the hospital during the whole treatment course and travelling regularly from their residential states for physical consultations during maintenance/followup period adds a significant indirect financial burden to an already prohibitive cost of cancer care for most of the families. although cost effectiveness was not formally analysed, we believe utilization of teleconsultation along with shared care model, wherever feasible, will go a long away in easing cost of care and reduce this burden of regular travel. during this pandemic period, we observed that majority of parents/caregivers were comfortable using e-mail for teleconsultations and were willing to continue the same even when the crisis abates. this is exemplified by the fact that families ( . % of all teleconsultations) sought re-consultation via e-mail rather than a physical visit even though travel restrictions have been eased currently. however, certain families faced problems procuring chemotherapeutic drugs at their local places of residence for which help, and logistic support were provided with help of philanthropic organizations. confidence of parents on local healthcare facilities is another concern which needs time to develop and evolve. our experience with telemedicine and developing this "shared care" model suggests that it is a feasible approach, and that even after covid- pandemic wanes away, this will perhaps remain as a healthy legacy of the pandemic. covid- in children with cancer in new york city impact of the coronavirus disease (covid- ) pandemic on pediatric oncology care in the middle east the covid- pandemic: a rapid global response for children with cancer from managing pediatric cancer patients in covid pandemic metronomic therapy in pediatric oncology: a snapshot. pediatr blood cancer chemotherapy adaptations in a referral tertiary care center in india for ongoing therapy of pediatric patients with solid tumors during covid pandemic and lockdown. pediatr blood cancer bone sarcoma surgery in times of covid- pandemic lockdown-early experience from a tertiary centre in india telemedicine practice guidelines, ministry of health and family welfare, government of india childhood cancer in india european survey on standards of care in paediatric oncology centres acknowledgements we sincerely acknowledge the dedicated efforts of entire pediatric oncology team of our centre especially nursing staff, dietician, data management professional and all supporting staff in formulating strategy and managing children with cancer during this exceptional pandemic situation. authors' contributions sb and sg conducted review, data interpretation and wrote the manuscript. sb will act as guarantor for this paper. conflict of interest none. key: cord- -upogtny authors: viboud, cécile; lessler, justin title: the influenza pandemic: looking back, looking forward date: - - journal: am j epidemiol doi: . /aje/kwy sha: doc_id: cord_uid: upogtny in commemoration of the centennial of the influenza pandemic, the american journal of epidemiology has convened a collection of articles that further illuminate the epidemiology of that pandemic and consider whether we would be more prepared if an equally deadly influenza virus were to emerge again. in the present commentary, we place these articles in the context of a growing body of work on the archeo-epidemiology of past pandemics, the socioeconomic and geographic drivers of influenza mortality and natality impact, and renewed interest in immune imprinting mechanisms and the development of novel influenza vaccines. we also highlight persisting mysteries in the origins and severity of the pandemic and the need to preserve rapidly decaying information that may provide treasure troves for future generations. initially submitted august , ; accepted for publication september , . in commemoration of the centennial of the influenza pandemic, the american journal of epidemiology has convened a collection of articles that further illuminate the epidemiology of that pandemic and consider whether we would be more prepared if an equally deadly influenza virus were to emerge again. in the present commentary, we place these articles in the context of a growing body of work on the archeo-epidemiology of past pandemics, the socioeconomic and geographic drivers of influenza mortality and natality impact, and renewed interest in immune imprinting mechanisms and the development of novel influenza vaccines. we also highlight persisting mysteries in the origins and severity of the pandemic and the need to preserve rapidly decaying information that may provide treasure troves for future generations. age patterns; history of epidemiology; influenza; mortality; pandemic; prior immunity one hundred years after the fact, the influenza pandemic remains one of the most important epidemics of the modern medical era; it was significant for its impact on both human health and the development of epidemiology and other medical sciences. still, as we mark its centennial, it is sobering to realize how little we understand about the origins and lethality of this unusual outbreak despite decades of intense multidisciplinary research. although it would be years before it was possible to fully characterize the virus responsible for the pandemic ( ), contemporaneous medical authorities put commendable effort into reporting detailed epidemiologic data on the progression of the pandemic that ranged from individual-level clinical records to aggregated city-level vital statistics ( , ) . in addition to quantitative epidemiologic data, there exist many anecdotal reports from clinicians, particularly those who served military populations, that have been mined to provide modern audiences a comprehensive account of the pandemic ( ). yet, many important questions remain about the evolutionary origins of the pandemic virus; the contribution of world war i and troop displacements to pandemic emergence and progression; the unique age profile of pandemic deaths, with its signature of high mortality rate among healthy young adults; the consequences of such a large mortality event on natality; and the heterogeneity of the pandemic experience around the world. such mysteries have captured the attention of the lay public and scientific community alike. in commemoration of the centennial of the pandemic, the american journal of epidemiology has convened a collection of articles that further illuminate the epidemiology of that pandemic and consider whether we would be more prepared if an equally deadly influenza virus were to emerge today. five of the articles touch on the origins of the pandemic virus, addressing the role of swine as mixing vessels in this and other pandemic events ( ), the age-specific mortality patterns of the pandemic ( ) ( ) ( ) , and prior population immunity ( ) . others include reports on geographic and social heterogeneities in the pandemic experience in which the authors describe the spatial diffusion of the pandemic in india and portugal ( , ) , the socioeconomic predictors of high mortality risk in sweden and globally ( , ) , and the consequences of the pandemic on us natality rates ( , ) . finally, commentaries address preparedness for future influenza pandemics ( , ) . the influenza virus is remarkable for its ability to infect a variety of animal species, from bats to birds to mammals. although successful cross-species transmission events may be rare, they play a key role in the genesis of new pandemic strains. nelson and worobey ( ) discussed different lines of evidence informing the origins of the virus, including the genetic make-up of the virus and other pandemic strains, the characteristics of influenza receptors across different influenza hosts, and the frequency of cross-species transmission events. they concluded that the pandemic virus must have emerged in mammals just before , most likely from the avian reservoir, with onward transmission from humans to swine. more broadly, a re-analysis of virologic data from the and pandemics, together with a modern understanding of the swinehuman interface, suggested a twist on the long-standing concept of swine as a "mixing vessel" for influenza virus. the authors proposed that swine should be viewed as a repository of historic human viruses rather than a conduit for reassortment of genetic material between avian and human viruses. van wijhe et al. ( ) returned to the question of the origins of the virus by exploring the epidemiologic imprint of the virus on danish mortality records, echoing recent work on immune imprinting ( ) ( ) ( ) . they identified several age breakpoints in pandemic mortality that were suggestive of the cycling of different influenza strains between the mid- th century and the pandemic. most notably, they argued for co-circulation of subtypes of influenza virus (carrying type i and ii hemagglutinin surface antigens) between and . as a result, persons born between and (aged - years during the pandemic) may have been primed by either hemagglutinin type, potentially explaining the intriguing age profile of pandemic mortality in adults. cilek et al. ( ) used a similar epidemiologic approach to explore the pandemic mortality patterns in madrid, spain. madrid is particularly interesting because a lethal pandemic wave was reported in the city in june , the earliest such event recorded. similar to other regions of the world, madrid experienced a signature pandemic pattern of higher mortality rates among young adults. however, seniors in madrid suffered equally high rates of excess influenza mortality. this is unlike the experience of the rest of europe and north america, where seniors were reportedly spared, presumably because of antigenic recycling (i.e., exposure to a related strain in childhood that conferred partial protection) ( , ) . this is an intriguing finding, and it will be important for future work to reconcile the well-accepted idea that a -like virus may have circulated in europe and north america in the second half of the th century, with the notion that madrid would have escaped this virus. to understand the unique epidemiology of the virus, it can be useful to document the experience of remote populations, in which prior immunity to influenza would be expected to be low because of less frequent circulation of the virus. rice ( ) built on a rich literature in this area to document mortality patterns in new zealand between and . he found that the s were a decade associated with high rate of influenza mortality in new zealand, despite the low global connectivity of this island in the era before air travel. he also noted that influenza mortality in was highest among young adults, with a more pronounced intensity in males than in females. these patterns are broadly consistent with the those among young adults in europe and the americas, pointing to the near universality of increased influenza mortality risk in this age group in . chuah et al. ( ) used seroepidemiology and structural equation modeling to answer the inverse question: how did early-life exposure to the pandemic virus impact how people responded to the pandemic, which was caused by an antigenically similar virus? they found evidence for immunologic priming from the virus in the oldest people they studied (individuals years of age or older) that impacted both baseline titers and vaccine response in . this work adds to a growing body of evidence that early-life exposures can have profound effects on immune response and mortality patterns decades after they occur ( ) . information about global connectivity in the th century is tenuous, and influenza records before are scarce. epidemiologic reconstructions of "modern" pandemics of the type presented here ( - ) provide indirect information on the exposures of populations that are now long gone, generating valuable hypotheses about influenza circulation patterns and disease dynamics well into the th century. such reconstructions offer precious insights into what influenza may have looked like years ago in a very different world and how long-term changes in human demography and mobility may affect disease dynamics ( ) . active research topics in the field of archeo-epidemiology include the search for predictors of influenza mortality, such as socioeconomic indicators or geography, and the drivers of influenza spatial diffusion. in articles in the present issue, the authors concentrated on the spatial diffusion of influenza, focusing on british india and portugal, countries that have been poorly studied in the context of the pandemic ( , ) . both studies revealed a highly heterogeneous spread of the pandemic and geographic variation in pandemic mortality impact, albeit at different spatial scales. although portugal as a whole was severely hit by the pandemic compared with other european countries, some provinces nearly fully escaped ( ). analysis of district-level mortality records in india revealed a northeastward wave of infection from september to november that was associated with climate and population density ( ) . diffusion was driven by long-distance jumps via the railroad network, superimposed on local diffusion between neighboring provinces. further, the authors found moderate heterogeneity in the mortality experiences of different indian provinces. spreeuwenberg et al. ( ) also made use of recently unearthed data from india to revisit the global mortality impact of the pandemic. india is a particularly important country for global burden estimation because it was the one most severely hit by the pandemic, with annual pandemic excess mortality rates that were -fold higher than those in denmark for instance ( ) . in the new study, the authors placed the burden of the pandemic at a much lower number than did previous work ( ) , in part by using more detailed data to better adjust for high background mortality unrelated to flu. the results of the portuguese study by nunes et al. ( ) echoed these conclusions-that careful analyses of more detailed data tend to decrease estimates of pandemic burden. the risk factors responsible for increased mortality and morbidity from influenza remain elusive, whether at the population level (e.g., effect of population density or weather on transmission) or the individual level (socioeconomic status, comorbid conditions, etc.). this is still an active area of contemporary influenza research, with direct applications to design targeted intervention strategies. in the present issue, bengtsson et al. ( ) explored the role of social class on pandemic mortality by linking individual death records with historical census data on occupation in a powerful study that captured the entire swedish population. the authors found that low-skilled or unskilled adults had higher death rates than did more skilled workers during the pandemic period relative to prepandemic years, whereas farmers (especially men) fared particularly well. social differences tended to be smaller in women, and there was no clear gradient between social class and mortality. the authors hypothesized that these social differences were linked to differential crowding in the workplace (hence an effect on transmission) rather than differences in income or nutrition. this is a topical issue because the effects of socioeconomic status and baseline health on influenza mortality are still debated today ( ) . researchers have long thought that the pandemic could have affected birth rates ( ) because of the large impact of this event on young adult mortality, the increased risk of severe flu outcomes during pregnancy, and a possible association between influenza infection and miscarriage. two papers in this issue address the topic of natality ( , ) . key questions here include the trimester of pregnancy during which the risk of death is highest for the mother and/or the unborn child and the impact of influenza on (increased) stillbirths and (decreased) live births. the duration of the pandemic effect on natality is also important because it informs the biological mechanism at play. if influenza impacts the probability of conception or fetal deaths, one would expect a temporary natality drop in the aftermath of the pandemic, followed by a rebound in births a few months later. in contrast, a high mortality rate among young women of childbearing age due to influenza infection would result in a long-lasting natality trough. dahal et al. ( ) explored these questions using individual birth and death certificates from arizona, where there was a drop in natality - months after pandemic mortality peaked. this was a temporary depletion, consistent with a detrimental effect of influenza early in pregnancy. in a larger study of populationlevel vital statistics in us states, chandra et al. ( ) found a % drop - months after peak influenza mortality, which they ascribe to a drop in conception during the period of intense pandemic activity. they also found a natality drop in the months after peak mortality, which they linked to excess preterm births and stillbirths due to influenza infections in the last trimester. interestingly, these patterns were also found in the aftermath of the influenza pandemic wave, albeit with a less pronounced effect. one reason we still look back at the pandemic years later is because doing so will make us better able to prepare for the future. the last articles of this collection are focused on preparedness for future pandemic threats ( , ) , building on the lessons learned in and later pandemics, and on new tools to protect populations, including the very active (but still elusive) topic of universal influenza vaccines. jester et al. painted an optimistic picture of progress made in influenza surveillance domestically and internationally, antiviral treatments, and robustness in the infrastructure for vaccine production ( ) . epstein reviewed the progress of the development of a broadly cross-protective flu vaccine, focused on conserved parts of the influenza virus, such as the matrix protein, nucleoprotein, the hemagglutinin stem, and various cocktail combinations ( ) . these vaccines offer promising broad protective effects against new influenza antigenic variants and could potentially be used in pandemic situations. however, some of the candidate vaccine formulations permit limited viral replication and may foster the emergence of escape mutants fit enough to cause disease. these features could have adverse epidemiologic consequences, and these risks need to be projected and monitored carefully. the pandemic is traditionally considered a worst-case scenario for pandemic preparedness, but there were many other pandemics before about which we know very little regarding mortality impact, circulating strains, or prior immunity. in fact, the pandemic has only recently drawn attention among epidemiologists ( , ) . most european and north american countries began formal collection of vital statistics in the mid-to-late th century, so that any pandemic predating can only be explored using church or cemetery records (or indirectly through reconstruction of modern pandemics). digitization of historic records is time consuming, data lack standardization, and information is generally limited to small populations. even with regard to the pandemic, crucial questions may never be answered, including which specific virus (or even subtype) circulated before and further back into the th century and what the population immunity profile was before the pandemic. the search for archival influenza specimens predating has remained elusive, and to our knowledge no archived sera exist from this period. in the absence of further virologic evidence, our understanding of the origins of the pandemic is limited to a handful of influenza virus sequences collected during may to november and to the epidemiologic signature of the virus in different populations. as nelson and worobey noted ( ), more work can be done in this area, particularly to explore the uracil content of post- viruses in different hosts, reconstruct their evolutionary trajectories, and better characterize host receptors and barriers to cross-species jumps. further, as rice ( ) and dahal et al. ( ) noted, a systematic analysis of the age mortality profiles of the pandemic in a sample of remote and wellconnected locations would be most useful, together with modeling of plausible biological hypotheses and immune histories most consistent with the data. databases, which are often crowdsourced or maintained by state health departments ( ) . further analyses of such data could shed light on the mortality profile of the pandemic in understudied locations and would also allow identification of family linkage and host genetic risk factors, which could be tested among descendants. many other library archives exist, although paper-based records rapidly decay and need to be digitized as quickly as possible. the detailed, sometimes freeform, notes typically kept by the scientists at the time mean that careful examination of these archives can sometimes yield surprising fruit. one such resource is the work of wade hampton frost, who was the first chair of the department of epidemiology at johns hopkins university and a critical figure in the fight against the pandemic. modern reanalysis of dr. frost's detailed work ( ) has already yielded abundant insights, and we included digital copies of his papers on the pandemic from the chesney archive in the web appendix (available at https://academic. oup.com/aje). the pandemic is remarkable for the large amount of extremely detailed epidemiologic data collected by public health officials ( , ), in part because it was an era that valued epidemiology, at a time when analytical approaches and knowledge of infectious agents were limited. these exquisitely detailed records have been particularly useful in the attempt to understand the pandemic retrospectively. as a thought experiment, we can imagine ourselves in : we may ask how scientists would look back at the large amount of data we archive on a daily basis in . on the one hand, much if not all of the modern data are digital, meaning that they do not run the risk of being destroyed by fire or floods and they can be more accessible to a wide audience, spurred by the open access movement. however, digital data can also be corrupted (intentionally or unintentionally) and disappear. much from the floppy-disk era has already been permanently lost, and it is unclear if modern cloud-based archives would survive a major disruption (whether technological or civil). further, even today, there is a systematic dearth of epidemiologic and molecular data from low-and middle-income settings (including data on the pandemic ( )). we are just beginning to scratch the surface of the intricate relationship between the influenza virus and the complex immune history of a host who has had repeated influenza exposures ( , ( ) ( ) ( ) ) . it is unclear whether we will be able to fully understand these interactions in the foreseeable future; in the meantime, population birth cohorts carrying important influenza immune histories disappear. we echo earlier calls for a time-stamped global repository of human sera and pathogen specimens, ideally together with epidemiologic information (biobanks) for current and future use ( ) . we also applaud the push by the us national institute of allergy and infectious diseases to fund international influenza birth cohort studies and help untangle the complex mechanisms of influenza immunity ( ) . if again confronted with a deadly flu pandemic, we would be in a better place than we were in because of the availability of drugs, vaccines, and antibiotics and the general improvements in health and nutrition. there are high hopes for the development of universal vaccines, but we need to keep in mind that influenza is a rapidly evolving virus that has a large and diverse animal reservoir and presumably many tricks in store. we can only anticipate another hundred years of very active, and always surprising, influenza research. structure of the uncleaved human h hemagglutinin from the extinct influenza virus preliminary statistics of the influenza epidemic influenza transmission in households during the pandemic the great influenza: the story of the deadliest pandemic in history origins of the pandemic: revisiting the swine "mixing vessel" hypothesis loose ends in the epidemiology of the pandemic: explaining the extreme mortality risk in young adults age-specific excess mortality patterns during the - influenza pandemic in madrid, spain influenza in new zealand before : a preliminary report investigating the legacy of pandemic on age-related seroepidemiology and immune responses to subsequent influenza a(h n ) viruses through a structural equation model the - influenza pandemic in portugal: a regional analysis of death impact spatiotemporal patterns and diffusion of the influenza pandemic in british india reassessing the global mortality burden of the influenza pandemic social class and excess mortality in sweden during the influenza pandemic natality decline and spatial variation in excess death rates during the - influenza pandemic in arizona, united states short-term birth sequelae of the - influenza pandemic in the united states: state-level analysis readiness for responding to a severe pandemic years after universal influenza vaccines: progress in achieving broad cross-protection in vivo potent protection against h n and h n influenza via childhood hemagglutinin imprinting re-examining the evidence regarding circulation of a human h influenza virus immediately prior to the spanish flu age-and sex-specific mortality associated with the - influenza pandemic in kentucky epidemiological evidence of an early wave of the influenza pandemic in new york city influenza epidemics in iceland over decades: changes in timing and synchrony with the united states and europe estimation of potential global pandemic influenza mortality on the basis of vital registry data from the - pandemic: a quantitative analysis global mortality estimates for the influenza pandemic from the glamor project: a modeling study natality decline and miscarriages associated with the influenza pandemic: the scandinavian and united states experiences transmissibility and geographic spread of the influenza pandemic age-specific excess mortality patterns and transmissibility during the - influenza pandemic in madrid, spain evidence for antigenic seniority in influenza a (h n ) antibody responses in southern china use of serological surveys to generate key insights into the changing global landscape of infectious disease the ghost of influenza past and the hunt for a universal vaccine this article does not necessarily represent the views of the national institutes of health or the us government.conflict of interest: none declared. key: cord- -q ce pi authors: nicholas, david; patershuk, clare; koller, donna; bruce-barrett, cindy; lach, lucy; zlotnik shaul, randi; matlow, anne title: pandemic planning in pediatric care: a website policy review and national survey data date: - - journal: health policy doi: . /j.healthpol. . . sha: doc_id: cord_uid: q ce pi abstract objectives this study investigates current policies, key issues, and needs for pandemic planning in pediatrics in canada. methods online pandemic plans from national, provincial and territorial government websites were reviewed to identify: plans for children and families, and psychosocial and ethical issues. a survey was administered to gather participants’ perspectives on the needs in pediatric planning, as well as important elements of their organizations’ and regions’ pandemic plans. a thematic analysis was conducted on qualitative survey responses. results the majority of existing plans did not adequately address the unique needs of pediatric populations, and mainly focused on medical and policy concerns. several gaps in plans were identified, including the need for psychosocial supports and ethical decision-making frameworks for children and families. similarly, survey respondents identified parallel gaps, in their organization's or region's plans. conclusions although many plans provide guidelines for medical and policy issues in pediatrics, much more work remains in psychosocial and ethical planning. a focus on children and families is needed for pandemic planning in pediatrics to ensure best outcomes for children and families. the impact of pandemic h n ( ) has raised public awareness of the threat of a severe influenza outbreak, as the public health agency of canada, provincial, and territorial bodies continue to bolster their contingency plans. in , severe acute respiratory syndrome (sars) revealed gaps in ontario's emergency response capability, and highlighted the need to prepare for future epidemics. the effects of this outbreak resulted in a total of probable cases and deaths in canada [ ] . sars heavily impacted the health care system in ontario and in affected areas across the globe. recent memories of this outbreak, coupled with the threat of pandemic h n ( ) warn of the impacts of a major outbreak in canada. accordingly, planning has become a pressing issue for stakeholders in government, industry and community. while the exact timing, pattern and impact of a future pandemic is unknown [ , ] , in canada an influenza pandemic could result in as many as . million people ( %) who become clinically ill, , ( . %) who require hospitalization, and up to , deaths ( . %) [ ] . such concerns have become a high profile public health issue, and fears of a potential global pandemic continue to grow. governments, policy makers, and health care providers (hcp), are planning for future pandemics, in part, based upon the lessons learned from sars. health canada [ ] has identified gaps in the response to sars that should influence current policies and planning. for example, there is still a need to address ethical concerns during a pandemic, for instance, governments may be required to infringe upon civil liberties to ensure infection control, and policy makers need to establish frameworks for decisionmaking to allocate scarce health care resources [ ] . a lack of coordination and communication, the poor management of resources, and the absence of a clear leadership structure within organizations and government also had a detrimental effect on the effort to control the sars outbreak [ ] [ ] [ ] . outside of canada, critical gaps have been identified in european union (eu) plans. these concerns include a lack of cooperation among eu countries and poorly delineated roles and responsibilities of central and regional health authorities. in addition, gaps exist in preparation for the impact on health care systems, the maintenance of essential services, and public health interventions to curb the spread of an epidemic [ ] . similar issues have been highlighted by researchers and planners world wide [ , ] . recently, pandemic h n ( ) has reignited these concerns about preparedness. in an effort to learn from sars and to prepare for a future pandemic, the government of canada has released the "canadian pandemic influenza plan for the health sector" [ ] . similarly, the majority of provincial and territorial governments have also released their regional plans [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] (see table for selected features of pandemic plans in various jurisdictions). these documents guide health planning and responses at provincial and local levels. government plans cover topics ranging from influenza surveillance, to the distribution of antiviral supplies, to communication and information dissemination. although these plans are designed to protect all canadian citizens, there continues to be a lack of dialogue or guidance to address the specialized needs of a pediatric population. children may require specialized supplies, medications, and treatment. they also require additional supervision and family support [ ] . additionally, pandemic planning for children and families is often addressed locally, with little coordination among the various levels of planning [ ] . this continued neglect of pediatrics, both by policy makers and researchers in pandemic planning, is problematic, as difficulties associated with psychosocial concerns or ethical decision-making are magnified for hcp, children and families [ ] . in this paper, we present both provincial and territorial policy statements as they relate to pediatrics based on a website review of plans. we also present the qualitative results from a survey administered to pediatric pandemic planning practitioners and policy makers. the goal of the project is to assess the comprehensiveness of existing pandemic plans in canada and to identify what professionals identified as important and needed in pediatric plans. there is little dialogue about ethical concerns in pandemic planning for pediatrics. as such, the literature about ethics in pandemic planning focuses primarily on adult care [ ] [ ] [ ] . thompson and colleagues have identified general values to guide care and policy for pandemic planning. these values include: the duty to provide care, equity, individual liberty, privacy, proportionality, protection of the public from harm, reciprocity, solidarity, stewardship, and trust [ ] . although these values are central to ethical planning and decision-making, many may be interpreted differently in pediatrics. for example, individual liberty does not apply to children in the same way as adults. compared to adults, children lack autonomy and parents must advocate and make health care decisions on their child's behalf. due to the lack of literature on this topic, policy makers must individually interpret the ethical issues in pediatric care. as such, policy makers who strive to maintain ethical care in pediatrics should be guided by ethical values, and stay aware of the needs of children and families. in this paper, participants identify situations where such ethical policy making must be implemented. in this paper, we present a website review of provincial and territorial pandemic plans with respect to pediatric policies. additionally, we present the qualitative results from a national survey on pandemic planning. websites of all canadian provinces and territories, and the public health agency of canada were reviewed to identify online and publicly available pandemic plans. each website was surveyed to identify the availability of a pandemic plan. subsequently, these plans were reviewed to assess their comprehensiveness and to identify unique plans for children and families, and psychosocial and ethical issues. the review was completed in june by a reviewer with a background in health policy. the reviewer used content analysis to record all references to pediatrics in a database. to verify this information, the plans were read by a second reviewer, and a search function was used to ensure that available pediatric plan information was included in the review. the web-based survey included open-ended questions that asked participants' opinions on the processes of planning, comprehensiveness and essential elements of pandemic plans in their organization or region. the survey was hosted by survey monkey (http://www. surveymonkey.com/), an online application that administers questionnaires to participants. this method was chosen to increase the response rate from participants across canada, particularly in more remote regions. an email with a link to the online survey was sent to potential participants between may and june . participants received a reminder email at and months after the initial request. the survey was available online in english and french. survey participants included individuals with expertise in pediatric care and pandemic planning, including: ( ) members of national, provincial and territorial pandemic influenza committees; ( ) professionals working in infection control and pandemic planning; and ( ) professionals working with children, youth and families in crisis. the participants were recruited using snowball sampling. email invitations to complete the survey were sent to individuals, with n = participants, with a response rate of . %. given this low response rate, the survey data presented is not intended to be representative. the demographic data, however, show that there are participants from all areas of pediatric care and pandemic planning. in addition, respondents from all provinces and territories participated in the survey (see table ). as such, the data identifies issues that are salient for participants who are interested and involved in the area, which may be important to consider in pandemic planning for children and families. open-ended survey responses were analyzed using qualitative data analysis software. a thematic analysis was conducted for each survey question using open coding. qualitative rigor was ensured through the use of referential adequacy, negative case analysis, and peer debriefing. government decision-makers have learned from sars, using this knowledge to plan for future pandemics, evidenced by the release of detailed pandemic plans. largely, however, the application of this knowledge to pediatrics has been lacking. specific references to pediatrics are seen in a minority of pandemic plans [ , , ] , but a greater focus on pediatrics has been noted in some recently released plans [ , ] . some plans do not acknowledge pediatrics as a need [ , , ] , while other plans suggest that the needs of this vulnerable population are being planned for, yet they do not articulate many concrete strategies to accomplish this task [ , , , [ ] [ ] [ ] . this omission of pediatric care in pandemic plans continues despite concerns of a potential outbreak, and the responsibility of governments to coordinate a pandemic influenza response for canadian children and families (see table ). governments with pandemic plans that address needs in pediatrics have solid contingency plans for medical and policy issues, but less so for psychosocial and ethical issues. medical components of plans focus on key issues such as: pediatric specific medical supplies; stockpiling of antivirals and vaccines; and differences in symptoms, triage, treatment and isolation [ , [ ] [ ] [ ] ] . policy issues included in current plans address needs for coordination with other agencies as well as the public. these issues are often coupled with guidelines on school closures [ , [ ] [ ] [ ] [ ] [ ] , [ ] [ ] [ ] [ ] , and only ontario's plan addresses child care provisions for hcp [ ] . chiefly, psychosocial and ethical concerns focus on communication [ , [ ] [ ] [ ] ] ; potential stressors for children and families [ , [ ] [ ] [ ] [ ] , , ] ; grief and bereavement counselling [ , , ] ; and family centred care [ ] . nevertheless, even these more thorough plans lack consideration of certain psychosocial and ethical issues, for example, 'how will decisions be made regarding children whose parents are unable to consent due to treatment?'. and 'how will children and families cope with these stressful events?'. many such concerns, relevant to pediatric patients, families and hcp, are not documented in pediatric pandemic plans. notably, the above mentioned plans all contain a pediatric specific focus; in contrast, a majority of plans do not thoroughly consider these issues and tend to focus on medical and policy matters in pediatrics [ ] [ ] [ ] [ ] [ ] [ ] , , ] . as a • notes that pediatric specific supplies will be needed • agencies must "determine support needed for orphaned children and the need for grieving and counselling services" • mentions different needs of children in terms of vaccinations, isolation, treatment • importance of supporting staff "through critical incident debriefing, grief counselling, child care support, etc." • children's/pediatric unit is one area in which the demand may increase markedly and continuing operation is crucial-health authority and facilities should consider these areas and determine which are critical to keep them operational result, many provinces may be under prepared to deal with the increased demand for pediatric services, especially the need for psychosocial and ethical supports. although many plans note differences in symptoms or treatment of children, and the need for school closures, still a number of these medical and policy needs are inadequately addressed and often psychosocial or ethical concerns are not touched upon at all. in fact, these issues present challenges often left unaddressed by government plans, resulting in a significant gap in pediatric pandemic planning. stakeholders in pediatric services and pandemic planning participated in this cross-canada survey and sharing written responses to open-ended survey questions, providing their suggestions for pediatric pandemic planning. participants identified four overarching themes about important needs in pediatric planning. main themes include: essential elements to a pediatric pandemic plan; importance of children and families in planning; importance of communication; and accounting for missing or rudimentary plans. participants identified plan elements they thought were central to any organization's pediatric pandemic plan. they identified concerns from resource allocation to ethical decision-making, illustrating the complexity and heterogeneity of these issues. participants provided a wide range of elements they thought should be included in a pediatric pandemic plan. many expressed the importance of child care measures during a pandemic. a variety of concerns pertaining to child care were identified, such as how to manage school and day care closures for working parents. by the same token, participants felt plans should provide support for hcp, in managing child care, family and job responsibilities, in addition to providing for occupational health concerns, including the psychosocial and physical well-being of hcp. moreover, participants felt that ensuring the availability of psychosocial supports for various stakeholders was also an essential plan element. they suggested that plans should make provisions to provide psychosocial supports for children, families, and hcp and their families. providing education and information were important to participants, to promote understanding and preparation during a pandemic. similarly, they identified communication with stakeholder groups as essential in a pediatric pandemic plan. participants felt that policies should provide guidance in infection control in pediatrics. coupled with these concerns, clinical guidelines were also identified as a central and complex issue in a pediatric pandemic plan. participants saw the need for treatment guidelines specific to pediatric populations, including guidelines for assessment and treatment, for children with an infected or absent parent or guardian, and for prevention, such as vaccination protocols. guidelines for the treatment of routine non-influenza health care cases were viewed as especially important to maintain care and to optimally treat the largest numbers of people. a participant stated, "we must have specific pre-set criteria on questions such as: when to stop performing elective surgeries, when to stop performing marrow and organ transplants, etc." resource allocation plans were a major concern, particularly for pediatric care, to ensure that resources are available for children and families during an outbreak. participants noted that community supports are required for stakeholder groups, for example, child care and psychosocial supports for children with an ill parent or guardian. another key issue was coordinating plans to include home care for those who are infected if hospitals are over capacity. a large portion of respondents also raised concerns about ethical decision-making during a pandemic, and the need for a framework for decision-making in pandemic plans. one respondent indicated the need for an ethical framework, specific to pediatrics: discussion/guidance [is needed] on ethical decisionmaking processes for the pediatric population. are these different than they will be for the adult population? will the philosophy of family centred care be impacted during a pandemic event? in essence, participants identified a range of issues that must be considered in pediatric pandemic planning, in order to manage the heavy burden an outbreak will place on health care systems and resources (see table ). participants were asked to identify missing elements in their organization's pandemic plan, and many responded with similar issues as when questioned regarding the key elements of a pediatric plan. these missing elements include: child care plans; communication and information sharing; ethical guidelines; needs of hcp (psychosocial, medical, workforce); organizational coordination; pediatric focus; continued plan development; post-pandemic planning; psychosocial needs; and resource planning and allocation. participants were asked to identify if their organization actively involved children and families in pandemic planning. those who responded affirmatively provided a range of strategies to incorporate the voices of children and families in plan development. such strategies include input from: family advisory committees, community organizations, family representatives, and research findings. consultation with children and families ranged from extensive involvement in planning, where a "family representative was involved as a key stakeholder on the steering committee," to minimal, such as consulting research studies on pediatric needs. conversely, participants who responded that children and families were not involved in planning provided a variety of explanations regarding why this occurred. these explanations include: pediatrics are not within the organization's mandate, the organization has a small pediatric population, plans are in development, and planners and staff are also parents. the most common response has that staff and planners are also parents, and that they can apply this experience to plan development. as an example, a participant stated, [children and families were] not [involved] to my knowledge, other than in the capacity that many of the people that have been involved in administrative or clinical care roles are also parents. they may have also been thinking in terms of being a parent. accordingly, based upon these survey responses, participants provided suggestions for, and noted barriers to, incorporating the voices of children and families in pandemic planning. participants provided information on preferred sources and methods of information dissemination during a pandemic. these sources include: business and industry, community organizations, government, hcp, professional organizations, the media, pandemic planning organizations, public health networks, schools and daycares. government was seen as a major source of information during a pandemic. one respondent suggested that, "information on the flu would be put together by those responsible at the ministry of health." methods of sharing information were varied, but largely web-based solutions were suggested by participants. participants also identified media (e.g. television, radio, print) and interactive information sharing (e.g. town hall meetings) as key strategies. survey respondents belonging to organizations without, or lacking a well-developed plan, were asked to identify why their organization was wanting in the area of pediatric pandemic planning. participants suggested that they were missing strong leadership in pediatrics and that this was a major factor contributing to a minimal or nonexistent plan. they felt that they had little guidance in what was required for pediatric pandemic planning. participants also expressed that they did not have access to resources for plan development, resulting in a "skeleton plan" focused on the adult population. lastly, not having adequate pediatric services or facilities within the organization or region contributed to the lack of a pediatric pandemic plan, as pediatrics was not a priority. while most respondents advocated pediatric planning, some participants were doubtful about the need for specific plans. these dissenting participants suggested that there are no unique pediatric issues to be addressed and that general plans are sufficient for pediatric care. other participants suggested that a pediatric plan was unnecessary because of a minimal focus on pediatrics, or due to a small pediatric population in their organization or region. the respondents who did not see the need for a specific plan provided responses such as, "my belief is that it should not be a separate plan-i would need evidence or rationale why a separate pediatric pandemic plan is required." on balance, the majority of respondents saw the need for a pediatric plan, but a substantial number of others did not see the implications or relevance of planning that is specific to children and families. participant responses indicate that pediatric pandemic planning is an important and salient issue across canada. based upon qualitative analyses of survey data, participants have provided important and useful feedback on the needs and essential elements in a pediatric pandemic plan, the importance of listening to children and families, the need for communication with stakeholder groups, and factors resulting in under-developed or missing plans. unfortunately, however, not all recommendations from participants are currently being implemented in provincial and territorial plans. this is exemplified in the congruence between what respondents felt were essential plan elements and the elements they identified as missing from their organizational or regional plans. there are clear and notable gaps in pediatric planning, both in terms of elements reported as missing by participants in their organizations' or regions' pandemic plans and in the parallel gaps in the provincial, territorial and national policy documents that were reviewed. for example, a lack of psychosocial and ethical policies in planning for pediatric care were identified as major gaps by survey respondents, and confirmed by our policy review. these discontinuities in identified key elements, and existing policies, point to the need for consideration of children and families at all levels of the planning process. moreover, this lack of pediatric specific considerations is noted in the perceptions of survey respondents who indicated that children do not have unique needs in the event of a pandemic and in the lack of policies across provinces and territories pertaining directly to the care of children and families. to address the needs of this population effectively, the authors suggest the incorporation of pediatric plans within broader provincial, territorial and national plans. the international literature on needs in pandemic planning notes the importance of cooperation and the need to identify roles and responsibilities in plans [ , ] . similarly, participants identified the importance of resource allocation, guidelines and communication in pediatric plans. it is clear that these issues are salient and must guide policymakers as they develop or update plans. based upon the web-based policy review, provinces with a combination of factors are often substantially more prepared based upon an analysis of their provided policies. for instance, british columbia's (bc) [ ] pediatric pandemic plan is a well-developed and readily available document which addresses the unique issues of children and families and touches upon some psychosocial concerns. likewise, bc is an example of a province with relative wealth, and a high population density in urban areas, for instance, bc reported the third highest population growth among the provinces during ( . per ) to reach a population of , , , one of the more populated provinces in canada [ ] . bc's major cities are easily accessible via commercial travel, and the province has welldeveloped health care and government infrastructure, all of which likely contribute to the resources available for the development of a pediatric pandemic plan. in contrast, northern communities appear to be at the greatest risk, given current rudimentary plans that are potentially influenced by a lower population density, few major cities, and a lack of reserve human, medical, supply, policy and financial resources. these disparities require greater consideration of factors influencing inequities in pediatric pandemic preparedness, including population density, socioeconomic status, relative isolation, and available resources. regardless of the factors that may influence the lack of pediatric contingency plans, there remains the possibility of severe outcomes for children and families in the event of an outbreak. it appears that greater attention and resources must be allocated to northern communities to ensure adequate preparation in the event of a pandemic. participants suggested that web based communication will be key in the event of a severe outbreak, allowing information to be distributed remotely [ ] . posting pandemic information on websites will be critical, as identified by survey respondents, to allow quick access to up-todate information. the majority of provincial, territorial and national pandemic planning bodies have responded to this method of information dissemination, in posting pandemic plans and information on their websites. public and political awareness of a potential pandemic has raised concerns over resource allocation and contingency planning, but in some jurisdictions, relatively little attention has been paid to planning in pediatrics. a review of the pandemic plans of the public health agency of canada, provincial and territorial governments has identified needs in pediatric planning. these issues and concerns were also supported by survey respondents, who are experts in pediatric care and pandemic planners, qualified to note such gaps in contingency plans. to overcome these gaps, a focus on the unique needs of children and families is required, while support and resource redistribution to less advantaged provinces and territories is needed to ensure the health and well-being of all canadians. consideration of the factors that influence pandemic preparedness (such as population density, affluence, relative isolation, and available resources) may be helpful to inform research and policy decisions. finally, the dissemination of information online, especially via government websites, is essential to communicate with the public during a pandemic. in brief, the findings presented here provide important suggestions to guide pandemic planning in pediatrics, in the hope that a pandemic response can ensure the safety of canadians. summary of probable sars cases with onset of illness from responding to pandemic influenza: a local perspective fortune favours the prepared mind: a national perspective on pandemic preparedness public health agency canada. the canadian pandemic influenza plan for the health sector learning from sars-renewal of public health in canada severe acute respiratory syndrome and critical care medicine: the toronto experience lessons learned from a provincial perspective ensuring a broad and inclusive approach. a provincial perspective on pandemic preparedness how prepared is europe for pandemic influenza? an analysis of national plans influenza pandemic preparedness action plan for the united states: update pandemic influenza preparedness in the asia-pacific region alberta pandemic influenza plan for the health system for health care professionals bc pandemic influenza preparendess plan preparing for pandemic influenza in manitoba pandemic influenza: preparedness guidelines for manitoba school divisions and schools (k- new brunswick pandemic influenza plan: for the health sector pandemic influenza: planning guidelines, roles and responsibilities for the health sector government of the northwest territories. pandemic influenza: contingency plan nova scotia health system pandemic influenza plan nunavut part of national pandemic preparedness effort developing healthy communities: a public health strategy for nunavut ministry of health and long-term care. ontario health plan for an influenza pandemic prince edward island pandemic influenza contingency plan for the health sector quebec pandemic influenza plan: health mission government of saskatchewan. public pandemic influenza plan press release: more cases of h n confirmed in yukon challenges facing pediatric preparedness the next influenza pandemic: will we be ready to care for our children? pediatric epidemic crisis: lessons for policy and practice development pandemic influenza preparedness: an ethical framework to guide decision-making preparing for an influenza pandemic: ethical issues moral principles for allocating scarce medical resources in an influenza pandemic report on the demographic situation in canada blogs and podcasts: a new generation of web-based tools for virtual collaborative clinical practice and education this research was funded by the canadian institutes for health research, funding reference number . key: cord- - jrvkk authors: craighead, christopher w.; ketchen, david j.; darby, jessica l. title: pandemics and supply chain management research: toward a theoretical toolbox date: - - journal: nan doi: . /deci. sha: doc_id: cord_uid: jrvkk the covid‐ pandemic paralyzed the world and revealed the critical importance of supply chain management – perhaps more so than any other event in modern history – in navigating crises. the extensive scope of disruption, massive spillover of effects across countries and industries, and extreme shifts in demand and supply that occurred during the covid‐ pandemic illustrate that pandemics are qualitatively different from typical disruptions. as such, pandemics require scholars to take a fresh look at what lenses offer understanding of supply chain phenomena in order to help supply chain managers better prepare for the next pandemic and foster transiliency (i.e., the ability to simultaneously restore some processes and change – often radically – others). to help scholars and managers achieve these aims, we offer an agenda for supply chain management research on pandemics by considering how the key tenets of well‐known and emergent theories can illuminate challenges and potential solutions. specifically, we consider how resource dependence theory, institutional theory, resource orchestration theory, structural inertia, game theory, real options theory, event systems theory, awareness‐motivation‐capability framework, prospect theory, and tournament theory offer ideas that can help scholars build knowledge about pandemics’ effects on supply chains as well as help managers formulate responses. this article is protected by copyright. all rights reserved the covid- pandemic was one of the most impactful events in modern history -it spread to over countries and territories around the world and induced the worst economic downturn since the great depression (international monetary fund, ) . while historically pandemics of this magnitude are rare, we only have to go back to 's h n outbreak to witness another example of pandemics' startling effects. given trends such as increased population, urbanization, and international travel, it is likely that another pandemic will occur. we highlight this reality, not as this article is protected by copyright. all rights reserved. alarmists, but rather as academics who believe business scholars must play a role in improving firms' ability to navigate these cataclysmic events. covid- brought to the forefront -more than any event in the last several decades -the importance of supply chain management. scholars and practitioners have long emphasized the importance of diagnosing and overcoming major supply chain challenges. for example, events such as port strikes, natural disasters, product safety problems, supplier bankruptcy, and terrorist attacks have all been carefully scrutinized for lessons about how to prepare for, manage, and respond to disruptions from both scholarly and managerial perspectives (e.g., craighead et al., ; bode et al., ) . despite the informative body of research and arsenal of company exemplars, neither fully prepared firms to effectively respond to the covid- pandemic, the "great lockdown," and the tidal wave of disruptions that plagued every industry and geographic region. we suggest that this is because pandemics qualitatively differ from typical supply chain disruptions along three interrelated dimensions: scope -a typical disruption is localized geographically and/or by sector. examples of the former include a port strike cutting off commerce in part of a country and a hurricane disrupting commerce in a specific region. an example of the latter is the / terrorist attacks, which disrupted various travel industries while farming and retailing pressed on after short pauses. in a pandemic, the whole world and all industries absorb impacts. spillover -a typical disruption often unfolds like a rock thrown into a lake -a large initial shock generally dissipates into minor ripples. in a pandemic, a torrent of roughly equivalent waves spills over from region to region and sector to sector. in response, governments adopt a war footing wherein they take steps such as closing borders, urging or dictating pivots to industry, and restricting individuals' freedom of movement. these actions are intended to mitigate effects, but some actually exacerbate the spillover. shifts -a typical disruption reshuffles the proverbial deck regarding supply and demandoften affecting one, but not the other. for example, a supplier's bankruptcy can result in a temporary loss of supply, but may have little, if any, effect on demand. in a pandemic, the force of disruption is strong enough to force supply and demand to extreme highs and lows. consider, for example, the nationwide panic buying of household items and the complete evaporation of new car purchases in the u.s. during the covid- pandemic. these dramatic shifts also occurred in the same product category as stay-at-home orders created skyrocketing demand for consumer-grade toilet paper (i.e., soft tissue on small rolls) but flushed demand for industrial-grade versions (i.e., large rolls that fit dispensers). while these dimensions are not intended as comprehensive descriptors of how pandemics differ from typical supply chain disruptions, they highlight significant points of departure. distilling lessons learned from the pandemic and anticipating a future one also requires a departure from the traditional scholarly emphasis on continuity and resiliency (e.g., azadegan et al., ; mena et al., in press). specifically, we suggest that companies need to foster transiliency (i.e., the ability to simultaneously restore some processes and change -often radically -others) to address pandemicinduced challenges. more simply, the concept of transiliency melds the concepts of resiliency and transformability. for example, a grocery store may need to restore its depleted products (i.e., resiliency) by improving its replenishment processes while simultaneously converting its operations (i.e., transformability) to mimic a 'quasi' distribution center by picking, packing, and delivering orders to curbsides or households. albert einstein famously proclaimed: "in the midst of every crisis lies great opportunity." for managers, the covid- crisis creates an opportunity to foster transiliency and thus better cope with the next pandemic. for scholars, the crisis offers an opportunity to help managers think and act in new and unfamiliar ways by revisiting the conceptual lenses used to understand supply chain disruptions. to help scholars capitalize on this opportunity, we create an agenda for supply chain management research on pandemics by considering how the key tenets of a series of well-known and emergent theories can illuminate challenges and solutions. in doing so, we hope to catalyze meaningful, impactful research that helps alleviate the next pandemic's impacts on supply chains. this article is protected by copyright. all rights reserved. tools enable craftspeople to accomplish tasks that they could not accomplish otherwise. as previously accomplished in research on best value supply chains (ketchen & hult, ) , new product development (wowak et al., ) , and sustainability (connelly, ketchen, & slater, ) , creating a toolbox of theories involves providing scholars with the means to generate new insights about a phenomenon of interest. in this section, we present ten theories and consider their implications for understanding supply chain behavior before, during, and after a pandemic. the set offered is a mix of theories that are well established in the supply chain literature and emergent perspectives that have not been leveraged much yet but seem poised to shed important light on pandemic-related challenges. in an effort to emphasize new ways of thinking, we steer clear of theories that have been extensively applied by supply chain researchers such as the resource-based view and transaction cost economics. we also recognize that other perspectives such as the behavioral theory of the firm, punctuated equilibrium, industrial organization, contingency theory, and evolutionary economics could help explain pandemic effects and the pursuit of transiliency. while we offer detailed consideration of ten theories, these others merit future attention as well. table summarizes the key tenets of each theory, highlights each theory's key insights for supply chain management research on pandemics, and proposes potential research questions. -------insert table about here ------- resource dependence theory (rdt) posits that firms depend on other actors in their environment for access to vital inputs such as materials, labor, and cash (pfeffer & salancik, ) . dependence creates uncertainty because the flow of resources from outside actors (e.g., suppliers) could stop due to those actors' wishes, failures, or both. firms respond by pursuing strategies and structures that reduce, minimize, or even eliminate their dependence on external entities. as such, rdt is a natural fit with supply chain research (e.g., jean, kim, & sinkovics, ; touboulic, chicksand, & walker, ) , that could transcend into the pandemic context (see table ). yet, pandemics' daunting effects may necessitate revisiting the dependence concept in at least two ways. first, while implemented strategies to manage dependencies may be effective in normal modes of operation, they may be ill-equipped to handle the hyper-time-sensitive nature of pandemics when the need for transiliency is heightened. resource dependence theory suggests that a firm's ability to respond to extreme shifts in supply and demand will be constrained by external entities who control the resources it requires (pfeffer & salancik, ) . thus, in the presence of an abnormal spike in demand, a critical bottleneck may surface. for example, during the covid- pandemic, hospitals' ability to respond to massive increases in demand for treatment was (initially) constrained by limited supplies of personal protective equipment (ppe) and ventilators. the spillover effects within a pandemic add complexity to managing these time-induced bottlenecks from resource dependencies. normally firms can center attention on a small set of key dependencies by attempting to reduce them or at least increase their predictability. this remains true during most disruptions as well. as a result of the spillover effects brought on by a pandemic, however, firms find themselves fighting a multi-front assault by an everchanging array of supply shortages and demand spikes. how can a firm juggle all of these interrelated dependencies to shape how well it fares during and after the pandemic? while this question will need to be examined by multiple studies and methods, the answers they provide could offer a great deal of promising insights. analytical research could provide important foundational insights by considering differences in scenarios wherein adjusting the parameters involved in one dependence relationship does or does not have a cascade effect on other dependencies. this article is protected by copyright. all rights reserved. second, while deployed structures to manage dependencies may be effective within typical supply chain contexts, they may have little merit during pandemics as dependencies, themselves, may evolve. for example, the extreme shifts in supply and demand that accompany a pandemic can alter power dynamics within supply chains, as firms become more or less dependent on external entities (pfeffer & salancik, ) . as an illustration, consider the power dynamics in a traditional retailer-supplier relationship. retailers are dependent on suppliers for access to brands and products, and suppliers are dependent on retailers for access to consumers. under normal circumstances, retailers enjoy a power advantage and wield this power to extract concessions from suppliers (huang, li, & mahajan, ) . during a pandemic, however, the balance of power shifts in suppliers' favor. in the midst of consumer stockpiling and unprecedented increases in demand, retailers are increasingly dependent on suppliers to keep shelves stocked. for example, during the covid- pandemic, walmart gave suppliers exemptions on its notoriously tight on-time, in-full protocol (souza, ) . to what extent emergent power relationships persist versus return to normal could be an overarching question worth answering. the resultant line of inquiry would seem to be central to the examination of transiliency in post pandemic periods. institutional theory suggests that firms bow to environmental pressures in an effort to earn legitimacy (dimaggio & powell, ) . legitimacy in turn is believed to allow a firm to more easily attract support from external actors such as buyers, suppliers, and governments. as various firms all pursue legitimacy, they start to resemble each other -a process called isomorphism (meyer & rowan, ) . bank branches, for example, share similarities such as well-dressed employees, conservative décor, and drive-through windows. within the supply chain context, researchers have examined how expectations of what constitutes legitimate behavior diffuse across supply chains and gradually become shared norms (e.g., bhakoo & choi, ; reusen et al., ) . this article is protected by copyright. all rights reserved. institutional theory's emphasis on the creation and demise of legitimacy fuels its value as a lens for understanding supply chain behavior during and after a pandemic (meyer & rowan, )see table . during a pandemic, firms are freed from a so-called 'iron cage' of expectations (dimaggio & powell, ) , and longstanding ideas of what is and is not legitimate are ignored as firms desperately respond to extreme shifts in supply and demand. for example, during the covid- pandemic, the 'lean' philosophy -a widely adopted, if not sacred, best practice since the swas called into question amidst rampant stockouts (jin & ellram, ) . after a pandemic subsides, institutional theory suggests two potential paths forward: either new conceptions of legitimacy will emerge or reinstitutionalization will occur as firms fall back into 'old habits' (davis-sramek et al., ) . because of the broad scope and dramatic shifts that accompany a pandemic, we expect that new conceptions of legitimate, successful behavior will emerge following a pandemic, resulting in some permanent transformations in supply chain processes. in the post-pandemic institutional environment, time-honored traditions such as lean operations will rise or fall on their own merits rather than being assumed to be legitimate. as such, we believe that studying the post-pandemic evolution -or revolution -of other mainstream supply chain strategies (e.g., global sourcing) would be a fruitful path to pursue. institutional theory also can shed light on changes in environmental complexity. firms typically face formidable pressures from only a limited number of actors (lu et al., ) even during most disruptions. during a pandemic, however, firms face a flurry of unpredictable pressures from numerous and diverse stakeholders, including government, supply chain partners, competitors, employees, consumers, and the media. for example, while target always exerts tough pressure on suppliers to deliver goods to its warehouses within tight windows (bose & layne, ) to appease consumer pressure, governmental actors normally are uninterested in suppliers' delivery performance. during covid- , however, the pressure shifted as the u.s. government called for stable supplies and full shelves to counter consumer hysteria and prevent further stockpiling. likewise, the u.s. government directed general motors to produce ventilators (rosevear, ) . during pandemics, firms may be asked to do more, but government pressures can also manifest in other ways. for example, a court ruling triggered the closure of amazon distribution centers in france due to the perspective that with "the punitive m euro per incident imposed by the court, the risk of accidently shipping non-essential items was too high" (forde, ) . to cope with heightened institutional pressures and unprecedented levels of uncertainty induced by a pandemic, firms will mimic the changes and processes implemented by other firmsparticularly industry leaders. such responses are mimicked not because of their efficiency or effectiveness but rather because they are viewed as 'safe' ways to proceed (dimaggio & powell, ). deephouse ( : ) insightfully recommended that "firms should be as different as legitimately possible" but, under pandemic conditions, it might be wiser to be as similar as possible until the crisis ends. overall, pandemics appear to foster changes in the nature of mimetic, normative and coercive pressures. as the general motors and amazon examples illustrate, studying whether and to what extent coercive pressures increase during a pandemic -as well as whether any increased pressures later persist or subside -would be enlightening. in crafting resource orchestration theory, sirmon, hitt, and ireland ( ) began by adopting barney's ( ) contention that strategic resources -assets such as a sophisticated supply network or stellar brand name that are valuable, rare, and difficult to substitute for or imitate -can give rise to sustainable competitive advantages. while barney's ( ) emphasis was theorizing about what effects strategic resources can have, sirmon et al. ( ) and sirmon et al. ( ) dug deep into understanding the processes by which these effects unfold. subsequently, performance management (koufteros, verghese, & lucianetti, ) and product recalls (ketchen, wowak, & craighead, ) have been examined from a resource orchestration perspective, but overall the theory remains underexplored within supply chain research. given the orchestration problems organizations experienced during covid- , pandemic research would be a great place to build momentum for this theory within supply chain research (see table ). resource orchestration theory suggests that three types of actions -structuring, bundling, and leveraging -accompany strategic resources (sirmon et al., ) . first, structuring refers to the "management of the firm's resource portfolio" (sirmon et al., : ) by accumulating (i.e., building), acquiring (i.e., buying), and divesting (i.e., selling) assets and capabilities. scholars should examine whether each of these actions plays a central role in creating transiliency during pandemics (e.g., what new resources are needed and how are they created?), but may also be used to examine longer term implications of the crisis. for example, the make-or-buy decision is a key consideration here as firms determine how much of their resource portfolio is built in-house versus contracted out to supply chain partners. owning the means of production offers control but also adds complexity, so many firms outsourced much of their resource portfolio in recent years. rampant shortages during the covid- pandemic may induce firms to rethink this approach in favor of increased selfsufficiency. modeling the balance of make-or-buy decisions that would allow firms to weather the extreme shifts in supply and demand in future pandemics could help managers determine how much of their resource portfolio should be moved back in-house. bundling refers to actions that bring together and integrate resources by stabilizing, enriching and pioneering processes, that tweak, extend or develop capabilities, respectively (sirmon et al., ) . for example, fedex became iconic by building a ruthlessly efficient supply chain alongside uniquely clever marketing and a culture centered on competitiveness that extended to its supply partners (hult, ketchen, & nichols, ) . while resource bundles are usually developed slowly and deliberately over time, the dramatic shifts in supply and demand induced by a pandemic force firms to bundle resources quickly and in ad-hoc ways. during covid- , amazon, for example, simultaneously altered its product mix toward essential items, onboarded tens of thousands of new employees, and abandoned its two-day delivery capabilities. in other words, the resource bundle this article is protected by copyright. all rights reserved. that had fueled much of amazon's previous success was completely reconfigured during the pandemic. understanding on-the-spot bundling's efficacy in responding to a pandemic as well as the effects of on-the-spot bundling on firms' longstanding resource bundles are important avenues for future research. in particular, scholars should examine whether the rapid bundling is driven by the flexibility of the underlying resources, adaptability of interfaces between resources, or both that create and enhance transiliency. in doing so, determining what (and how) firms stabilized, enriched, and pioneered capabilities would be valuable. leveraging refers to the actions taken to generate value from a firm's resources, including mobilizing (i.e., recognizing needed capabilities), coordinating (i.e., integrating resources), and deploying (i.e., using capabilities to support strategy) (sirmon et al., ) . during a pandemic, firms must not only rethink how they can generate value from their current bundling of resources but also what type of value they can create. for example, louis vuitton reconfigured its fashion workshops and cosmetics factories to produce much-needed masks, hospital gowns, and hand sanitizer during the covid- outbreak (seipel, ) . leveraging its production capabilities and distribution networks in this way may not generate value in the sense that it leads to a sustained competitive advantage for louis vuitton, but it generates value for society by helping to neutralize threats in the environment (barney, ) . after a pandemic, we expect that firms will restore some of their previous resource deployments, whereas others will be permanently transformed. further, as the louis vuitton example illustrates, synchronizing how resources are structured, bundled, and leveraged will be crucial to prepare for future pandemics (cf. sirmon et al, ; ) . according to research on population ecology, types of organizations survive or perish based on a process of natural selection that is beyond their control (hannan & freeman, ) ; this lies in contrast to theories such as resource dependence that are centered on willful adaptation. as population ecology thinking evolved, it increasingly emphasized the concept of structural inertia in explaining why many organizations cannot adapt to changing conditions (hannan & freeman, ) . just as a population of penguins would perish if placed in a desert, some firms cannot change enough to survive when conditions shift. for example, once-dominant blockbuster video was unable to adjust as streaming video became popular, and the firm collapsed. similarly, tens of thousands of restaurants were permanently closed due to covid- (maze, ) . within supply chain research, structural inertia has been used to explain why firms struggle to make major shifts, such as from mass production to customization (rungtusanatham & salvador, ) , despite the presence of conditions conducive to the latter. structural inertia appears to hold promise as a lens to examine why some types of firms fare better than others during and after pandemics (see table ). under normal conditions, small businesses fail more frequently than large firms due to resource constraints (hannan & freeman, ) . during a pandemic, this hazard is magnified because small businesses may not have the resources necessary to realize the level of transiliency needed for survival. this is illustrated, in part, by the u.s. government's attempt to help small businesses weather the covid- pandemic via a targeted loan program. larger firms gobbled up much of the initial funding that was intended for small businesses, leaving many of the latter suffering. indeed, an april survey found that % of small business owners expected to fail within six months (society for human resource management, ). yet, during the great shutdown, larger businesses were not immune to financial woes (e.g., j.crew filed for bankruptcy in may ) (tucker, ) . assessing the degree to which these firms struggled due to structural inertia before, during, and after the pandemic would be an intriguing research task. examining firms' structural inertia during and after pandemics through the lens of supply ecosystems is an appealing path (ketchen, crook, & craighead, ) . within an ecosystem, buyers and suppliers can become deeply intertwined, fostering a high level of interdependence. this interdependence can be a blessing, a curse, or both. for example, during the covid- pandemic, rise bar saw a dramatic increase in sales as consumers stockpiled non-perishable items like protein bars (dudley, ) . in response, amazon upped its suggested inventory levels, and rise bar began shipping the 'lion's share' of its available products to amazon (dudley, ) . such actions deepened the relationship between rise bar and amazon, but gave short shrift to rise bar's other retail partners. this is just one example of many whereby amazon strengthened its "competitive position in ways that could outlast the pandemic" (dudley, ) . to the extent that amazon now dominates the ecosystem, rise bar may become more vulnerable to the retail giant's whims over time and regret reducing its ties with other grocery chains when they needed rise bar the most. game theory aims to predict, given a set of rules, the strategies actors will use when interacting with each other (von neumann & morgenstern, ) . it assumes that actors are logical and will try to maximize their own payoffs. in one-time exchanges, selfish choices (i.e., 'defections') usually maximize outcomes. if actors interact repeatedly, however, game theory's 'shadow of the future' proposition suggests that each will act cooperatively because defections will attract future retaliation (bó, ) . building on these notions, game theory has been applied to buyer-supplier relations in order to predict, for example, optimal pricing and production quantities (cao & fang, ) , new technology adoption (zhu & weyant, ) , and distribution channel decisions (xia, xiao, & zhang, ) . game theory suggests that cooperation between firms with competing objectives is more likely during a pandemic because the costs of defection are much greater (see table ). during the covid- pandemic, for example, large grocery chains paid their suppliers faster to help suppliers stay solvent (creditsafe, ) . cooperation between competitors may also be warranted and, in some cases, requested by governments to adequately address a pandemic's impacts. during the covid- pandemic, norway temporarily suspended competition laws to allow rival airlines to coordinate routes in order to stay afloat and transport goods (terloar, ) . following a pandemic, the 'shadow of the future' proposition suggests that firms will be more likely to cooperate -or at least not act opportunistically -in order to prevent being 'punished' by buyers and suppliers in future pandemics (bó, ) . research is needed to understand the 'stickiness' of different types of coordination mechanisms (sahin & robinson, ) before, during, and after pandemics, such as whether the inevitable erosion of cooperation post-pandemic is linear or curvilinear and whether it is abrupt or gradual. while we expect greater cooperation, the scope, spillover, and shifts induced by a pandemic violate game theory's fundamental assumption that each actor knows the structure of the game (ross, ) . extreme shifts in supply and demand make it more difficult for firms to predict how buyers and suppliers will act and thereby place a premium on building transiliency. outside of the supply chain, government efforts to alleviate the scope of a pandemic's impacts continuously and unpredictably alter ground rules and thus disrupt how firms interact with one another. for example, during the covid- pandemic, several grocery chains had orders canceled or postponed by suppliers who were required to prioritize the u.s. federal emergency management association's (fema) orders (phillips, ) . this is in stark contrast to government's typically passive role within game theory as a 'third player' that enforces the rules and occasionally revisits them (ross, ) . experiments and simulations alike may be important tools for future research to test the sensitivity of game theoretic predictions to violations of the theory's assumptions brought on by a pandemic. real options theory focuses on how to make better decisions within uncertain situations. managers are believed to manage uncertainty by creating real options for themselves wherein they have the opportunity, but not an obligation, to make a bolder move as uncertainty is resolved (myers, ) . building a factory using a modular approach, for example, creates an option to expand the facility if demand requires it. given the inherent uncertainties within supply chains (flynn, koufteros, & lu, this article is protected by copyright. all rights reserved. ), real options thinking has been applied to information technology initiatives (tiwana, keil, & fichman, ; tiwana et al., ) , outsourcing (jiang, yao, & feng, ) , and other supply chain projects (hult, ketchen, & craighead, ) . pandemics create uncertainty at warp speed due to their scope, spillover, and extreme shifts in supply and demand. in preparation for the next one, managers should consider developing an arsenal of real options for navigating the associated uncertainties (see table ). real options theory offers six primary options -unlocking (aka growth), stage, deferral, scale, switch use, and abandonment (hult et al., ) -all of which potentially could be used to cope with the pandemicinduced challenges. for example, as covid- unfolded, companies attempted to use existing drugs (e.g., hydroxychloroquine, remdesivir) to treat virus symptoms (a switch-use option), expanded production of key medical supplies (a scale option), and terminated projects to allocate funds to address more pressing needs (an abandonment option). these actions appear to have been grounded in desperation rather than through the exercise of well-designed options, which may have limited their effectiveness. helping managers figure out which options to create before the next pandemic and to determine when the options should be exercised as the next pandemic unfolds represents a clear opportunity for supply chain scholars to contribute to theory and practice. we believe that the value of such options will vary considerably across industries and firms-as such future research should consider designs that center on breadth as well as depth. as scholars identify the best options to combat pandemics, they should not only consider each option's effectiveness in directly responding to the virus's threat but also the opportunities for transiliency each creates. for example, during covid- , many restaurants were forced to convert in-house dining operations to curbside and delivery operations (a switch-use option) because of government restrictions. as stay-at-home orders were relaxed, restaurants had to decide whether to maintain both types of operations or return to their original approach. real options thinking could allow for future pivots to be smoother. for example, in preparation for the next pandemic, this article is protected by copyright. all rights reserved. restaurants could create an overarching switch-use option (hult et al., ) by investing in contingency plans (e.g., how to convert in-house to delivery processes), training employees, and maintaining inventory of ambidextrous supplies (i.e., those that could be used in normal or pandemic modes of operation). to enable this transiliency, analytical research could focus on the optimal design, mix, and deployment of options while empirical research could explore whether the existing set of six primary options is adequate to cope with a pandemic's extreme impacts or if new types of options are waiting to be discovered. open systems theory's central premise is that organizations must obtain needed inputs from the environment and transform them into outputs that other actors will purchase (von bertalanffy, ) . organizations thus seek to establish and maintain an equilibrium between their inbound and outbound flows in order to achieve stability (katz & kahn, ) . dramatic happenings -the focus of event systems theory (est) -threaten this stability, which triggers changes to an organization's behaviors and features (morgeson, mitchell, & liu, ) . for example, the / attacks disrupted airport security operations, which prompted changes such as passengers having to remove shoes when going through the screening process. given its relative newness, est has not taken a strong hold in supply chain research, but its potential has been highlighted for scholars examining invasive events that alter firms and their supply chains, such as supplier-induced disruptions (reimann, kosmol, & kaufmann, ) and counterfeiting (craighead, ketchen, & cheng, ) . given its focus on events that are novel, disruptive, and critical (morgeson et al., ) and the resultant organizational changes, est is a natural fit for supply chain research on pandemics (see table ). in particular, scholars could embrace est's key change catalysts: event strength, space, and time. event strength centers on how salient the event is compared to the usual 'happenings' in the environment. est predicts, perhaps intuitively, that more salient events are more likely to trigger change. however, the level of change triggered by event strength is moderated by event space and time (morgeson et al., ) . event space focuses on how the effects of the event (i.e., not the event itself) spread, whereas event time focuses on the event's temporal aspects, such as its duration and trajectory. fortunately, the world has experienced only a few pandemics since the s (centers for disease control & prevention, a), but this infrequency has resulted in very few permutations of event space and time. while supply chain scholars should examine changes in response to previous pandemics to garner insights, est suggests that it is also important to examine a pandemic's space and characteristics in a 'forward looking' manner (morgeson et al., ) . for example, behavioral studies that center on decision making in juxtaposition with a pandemic's key event characteristics could help uncover likely responses from managers and policymakers. likewise, simulating pandemics with varying strength, time, and space characteristics could help managers vet current practices and make necessary preparations for the next pandemic. finally, empirical research using longitudinal data is well-suited to examine pandemic-induced changes given its ability to capture effect sizes and provide at least indirect evidence of causality. est may be especially useful for understanding how organizations can foster supply chain transiliency. one of est's key implications is that events "can beget new features…in addition to changing existing features" (morgeson et al., : - ) . that is, new policies and procedures implemented during a pandemic may continue even as operations return to normal and, in turn, become routinized over time. for example, during the covid- pandemic, 'fast fashion' companies were forced to move their design and manufacturing activities online whereby designers used digital prototyping to sample garments, prospective factories used virtual showrooms to showcase capabilities, and buyers placed orders from virtual lookbooks and digital fashion shows (roberts-islam, ). industry experts referred to covid- as a "catalyst for change" and predicted such digitalization would continue into the future. a key opportunity for supply chain researchers is this article is protected by copyright. all rights reserved. identifying which new features and changes to existing features should and should not endure following a pandemic. more broadly, should transiliency be a centerpiece of supply chain strategy post-pandemic, is its inherent value limited to times of crisis, or somewhere in between? we speculate that the answer to this will vary considerably across the various supply chain designs and strategies, environmental uncertainties, and industry clockspeeds. chen ( ) introduced the awareness-motivation-capability (amc) framework to describe, explain, and predict whether a firm will respond to an external threat and, if so, how. the theory contends that the likelihood and nature of responses are shaped by the degree to which a firm is aware of a threat, motivated to combat it, and capable of effectively countering it. most applications involve analyzing rivals' competitive moves and countermoves (e.g., chen, su, & tsai, ; upson et al., ) , but the theory recently has been extended to investigate whether and how a firm will respond to the implicit threat created when activist investors (i.e., investors who may want to force executives to act differently) take an ownership stake in the firm (shi et al., in press) . given the grave threat posed by pandemics, using the amc framework to shed light on responses appears to be a natural extension of the theory (see table ). some threats are explicit, while others are implicit (sinaceur & neale, ) . firms are more likely to be aware of the former, but the latter are often the more insidious dangers. past disease outbreaks involving sars and ebola had the potential to become pandemics, but early detection and preventative measures limited the scope of their effects. unfortunately, it appears that many firms failed to learn from these pandemic 'near misses' (e.g., dillon & tinsley, ) . as one chief executive officer put it, "maybe the covid- stuff caught everybody with their pants down" (motley fool, ). one research goal could be understanding why firms' awareness of potential pandemics either was too low or, if awareness was adequate, why this awareness did not trigger stronger preparation and contingency plans (goldschmidt et al., in press ). this article is protected by copyright. all rights reserved. a partial answer might lie in the second element of the framework. in the absence of strong motivation, a firm is less likely to respond to an implicit threat (chen, ) . firms must monitor a variety of outside threats and not all of them receive full attention. a firm might ignore or downplay the potential for a pandemic under a belief that the pandemic's effects would not spill over to its sector. another firm might be consumed by more explicit and immediate threats such as the bankruptcy of an important supplier, labor problems in a factory, untimely executive turnover, or an overseas competitor establishing a foothold in its home market. with so many risks to manage, perhaps a pandemic -a high impact, but low probability event -takes a back seat to more salient ones. thus, awareness of the threat posed by a pandemic increases the likelihood of a proactive response, but low motivation to respond makes a 'wait and see' approach more likely. looking to the future, firms are now keenly aware of pandemics and highly motivated to respond well if one emerges. given the monumental supply and demand shifts brought on by covid- as well as the scope of its effects and the spillover across regions and sectors, it is not surprising with the benefit of hindsight that firms' preparation of their supply chains was universally inadequate. chen ( : ) noted that "capability depends largely on strategic or resource endowments." because the normal ground rules are suspended under pandemic conditions, perhaps no type or amount of endowments is adequate to arm a firm with an arsenal of fully capable supply chain responses. this brings to the forefront the potential importance of coopetition (e.g., wilhelm, ) in which competing firms cooperate to realize an important outcome. during pandemics, the plethora of volatile, diverse environmental issues overwhelms the internal capabilities of most firms (i.e., prevents the achievement of requisite variety -cf. ashby, ) , suggesting that coopetition becomes a necessity rather than an option. for example, in the spring of , apple and google announced a plan to combine forces and develop contact tracing capabilities (sherr, ) . this initiative highlights the possibility that examining coopetition, particularly in terms of its ability to foster transiliency, would be a fruitful avenue. this article is protected by copyright. all rights reserved. prospect theory's focus is decision-making under uncertainty (tversky & kahneman, ) , which makes the theory well-suited for explaining supply chain decisions during and after pandemics (see table ). fundamental to prospect theory is the premise that how a problem is framed influences actors' decisions. in particular, describing a situation in negative terms will lead to riskier choices than if the same scenario is described in positive terms. in a highly relevant experiment, tversky and kahneman ( ) asked subjects to choose between alternative policies to combat a new epidemic. when likely outcomes were framed in terms of 'lives saved,' participants chose conservative options, but when the same outcomes were framed in terms of 'lives lost,' participants preferred aggressive, risky options. consistent with prospect theory, experimental findings suggest that supply chain managers will be risk-seeking and order more than the optimal amount when all possible outcomes involve losses (e.g., schweitzer & cachon, ) . to adjust for these risk preferences, firms normally implement various 'checks' and interventions in their ordering, replenishment, and inventory management processes (tokar, aloysius, & waller, ) . during a pandemic, however, we expect that supply chain managers' risk-seeking behaviors will not only be magnified but actually encouraged because of the enormity of the potential losses. knowing that positive and negative framing will nudge supply chain managers toward conservative and risky choices respectively, we expect that the best course of action is to consider both frames when making a decision. examining to what extent assigning a formal devil's advocate within discussions of these alternatives improves outcomes could be a useful research pursuit. in particular, research examining these frames in light of transiliency may shed light on why some processes are restored and others adapted. more generally, behavioral research using experiments (e.g., economics based, vignette based) appears well-suited to examining how framing as well as other behavioral influences/biases shape important pandemic-related decisions. this article is protected by copyright. all rights reserved. how prominent outsiders frame situations appears to be particularly important during a pandemic -such conditions offer extreme variation in potential outcomes and the presentation of these outcomes by government and media outlets varies greatly as well. for example, during the sars pandemic, the media was criticized for creating additional uncertainty (siegel, ) . similarly, during the covid- pandemic, media coverage varied significantly across countries and news outlets; some were accused of using 'sensationalist' or 'inflammatory' frames, whereas others were criticized for downplaying potential risks (radu, ) . framing alternatives in terms of potential gains may promote prevention behaviors (gallagher & updergraff, ), but such behaviors will be more conservative (tversky & kahneman, ) . during a pandemic, the use of loss frames may be warranted to galvanize managers to take the aggressive actions necessary to combat a pandemic's extreme effects. prospect theory is thus useful in understanding why supply chain managers are likely to underreact prior to the pandemic but overreact (e.g., hoarding behaviors) during the pandemic when "losses loom larger than gains" (kahneman & tversky, : ) . competition generally involves incremental accomplishments (e.g., poaching one supplier or customer from a rival) generating incremental gains (reductions in costs or increases in revenues, respectively). sometimes, however, competition takes the form of a tournament wherein there are large disparities in gains between winners and losers (connelly et al., ) . for example, in the mid- s, two supply networks headed by raytheon and lockheed martin competed for a -year, $ . billion contract to supply the u.s. army with training support (ketchen, ireland, & snow, ). raytheon's team won and collected all the money; lockheed was left to absorb the cost of preparing its bid and lick its proverbial wounds. firms entering such 'winner-take-all' tournaments must decide how much effort to devote to contending for the prize knowing that their investments will disappear if they lose. this article is protected by copyright. all rights reserved. tournament theory is well suited for analyzing buyer-supplier dynamics during a pandemic (table ) . on the supply side, extreme scarcity raises the stakes associated with acquiring needed items. rather than rationing goods across their customer base during the covid- crisis, some suppliers provided all available stock to preferred customers and left others empty handed. tournament theory suggests that the costs associated with losing (i.e., empty shelves and unhappy customers) will incentivize firms to improve their competitiveness in future tournaments (connelly et al., ) . post-pandemic, firms that were winners will need to figure out how to ensure they remain a preferred customer, while losers will need to figure out how to improve their standing. whether pandemic-induced tournaments foster collaboration or competition in post-pandemic buyer-supplier exchanges is an open question, but past evidence that major losses can induce aggressive behavior (e.g., harder, ; pfeffer & langton, ) points to the latter. prize spread is key to understanding behavior through a tournament theory lens (connelly et al., ) . some tournaments are winner-take-all as in the raytheon vs. lockheed martin example above, but others are structured more like a professional golf tournament or an automobile race wherein the first-place performer takes the proverbial lion's share of the rewards and others win logarithmically descending rewards. if the prize spread is too small (i.e., payoffs are distributed too broadly), firms' incentives to excel are low. if the prize spread is too large, firms may hold back effort because the costs of competing outweigh the likelihood of winning. a key challenge in designing tournaments is thus identifying prize spreads that maximize competitors' efforts (e.g., wen & lin, ) . during a pandemic, this challenge is even greater because the extreme uncertainty and associated risks make firms more sensitive to prize spreads (bloom & michel, ). an added twist that can redefine winning and losing during a pandemic is public shaming of winners. when almost a third of the initial relief funds intended for american small businesses during the covid- pandemic was quickly gobbled up by large, publicly traded companies, the tournament made losers out of thousands of small businesses that received no funds. in an unprecedented move, large companies such as ruth's chris steak house, potbelly, and shake shack returned their funds for redistribution to small businesses after being harshly criticized. analytical research could be extremely useful in identifying prize spreads that are optimized to get goods in the hands of the actors who need them during a pandemic, as well as estimating the effects of criticism on tournament winners' behavior. for example, how should the various governments distribute medical supplies across competing cities and states? during covid- , some states adopted a more selfish posture and hoarded certain resources. this leads us to wonder to what extent authorities should intervene when states are competing for scarce but valuable resources. confucius wisely observed that "the mechanic that would perfect his work must first sharpen his tools." in looking at our toolbox, and with acknowledgment that today's mechanics of theoriesi.e., researchers -include both women and men, we suggest that the theories can be sharpened to the degree they are applied to phenomena unique to pandemics. craighead et al. ( : ) argued for the importance of theoretical contextualization, defined as the "adaptation of the theory to the underlying industry situation," when using general theories (such as the ten theories in our proposed toolbox). we believe this is especially important for supply chain management research related to pandemics. without a strong pandemic context in the theorizing, scholars run the risk of merely tweaking extant supply chain management research when a greater change is needed. we thus call for research constructed around the realization that pandemic phenomena are qualitatively different that typical supply chain situations-whether in a normal or disrupted state. for example, in a typical disruption, companies quickly assess employees' physical wellbeing and the status of facilities and then move on to recovery. in a pandemic, employee safety needs to be monitored continuously. a lagged and unexpected downturn in employee health can shut a facility down, as smithfield experienced with their pork processing plants. in this case, an embedded switchuse option (enabling resource redeployment-cf., hult et al., ) such as the ability to transfer unique tooling to another plant would allow health assessment and recovery to coexist side-by-side on an ongoing basis. contextualizing a theory such as real options to account for the unique aspects of pandemics offers an added bonus-by examining rare and unique phenomena, scholars put themselves in a prime position to find a theory's boundaries, an important but elusive aspect of theory building (bacharach, ) . theoretical contextualization, and consequent sharpening of the tools, can be bolstered by capturing temporal and spatial aspects of pandemics. ketchen, craighead, and cheng ( ) stressed the importance of temporal capturing in supply chain management research wherein the theorizing captures the 'when' of examined phenomena. temporal capturing is an intuitive fit with pandemics-which evolve over time (centers for disease control and prevention, b)-thus enhancing the potential theory-driven insights for both scholars and managers (craighead, ketchen, & darby, ) . for example, researchers interested in resource orchestration theory could examine how companies bundled, structured, and leveraged their resources before, during, and after pandemics and thereby build understanding of how these resource shifts could be improved in the future. we described how amazon orchestrated its resources in response to covid- by altering its product mix toward essential items, onboarding tens of thousands of new employees, and abandoning its two-day delivery capabilities. as a pandemic subsides, when, how, and to what extent should a company return to the resource bundle that fueled much of its previous success? the spatial aspects of pandemics provide an additional interesting twist to this question. for example, because covid- unfolded differently across the us and around the world, to what extent did its geographic distribution play a role in amazon's orchestration shifts? while we recognize that theoretical contextualization, including temporal and spatial aspects, may come at the expense of generalizability , so be it-pandemics are important enough to warrant deep diving research. this article is protected by copyright. all rights reserved. the sharpening of the tools to foster a greater level of insight can also be accomplished with the synergy between the focal theory and (a) complementary theories; and (b) calibrated research designs. in many instances, master mechanics may find situations where the simultaneous use of multiple tools may be required to get the job done. likewise, scholars may find that a theory's effectiveness can be sharpened by another theory. for example, scholars embracing institutional theory to examine how companies deal with pandemic-induced shifts in government pressures to act (or not) may find that real options could play a role in dealing with the uncertainty surrounding those contexts. finally, ketchen et al. ( ) stressed the importance of theoretical calibration (i.e., the degree that the research design captures the theory's key tenets), which is an effective approach to hone the revealed insights. for example, event systems theory centers on event induced change so research designs capturing the before-after of key supply chain phenomenon would appear to be quite productive. in the aftermath of a monumental crisis, attention naturally turns to preparing for the 'next one' along with a profound universal hope that such preparations will never be needed. even if there were a guarantee that no more pandemics would arise in the foreseeable future, however, the covid- experience would still be worthy of attention from scholars and managers alike. for scholars, we outlined a series of theories that we believe are powerful tools for making sense of what happened, how organizations responded, and how supply chain structures and processes can be adjusted in case another pandemic arrives. meanwhile, managers can look to a timeless truth offered by the ancient greek philosopher plato: "necessity is the mother of invention." organizations experimented with new ideas and approaches -many used out of desperation -and some of these on-the-spot inventions can improve their transiliency regardless of what the future does or does not bring. thus, we end with a broad call for scholars to flesh out the transiliency this article is protected by copyright. all rights reserved. concept, both theoretically and empirically, and examine its explanatory value and boundaries within pandemic and interpandemic contexts. in thinking beyond the context of pandemics, one valuable facet of this inquiry could be examining how transiliency can help firms avert a crisis and quantify whether the benefits of crisis avoidance outweigh the costs of building transiliency. pfeffer, j., & langton, n. ( ) . the effect of wage dispersion on satisfaction, productivity, and working collaboratively: evidence from college and university faculty. administrative science quarterly, ( ) phillips, a. ( ). grocery stores seeking masks for 'essential' workers confront shortages, federal interference, accessed may , , available at https://www.latimes.com/politics/story/ - - /grocery-stores-masks-essentialworkers-shortages-federal-interference groups of firms who cooperate may be more likely to survive a pandemic than uncooperative ones the scope of a pandemic's impacts may be particularly troublesome for small firms and old firms who are slow to adapt how should government mitigation efforts be structured to enhance the likelihood that small firms will survive a pandemic? to what extent, if any, do a pandemic's extreme impacts accelerate the process of extinction for firms who were slow to respond to pre-pandemic pivots (e.g., the transition to e-commerce)? this article is protected by copyright. all rights reserved. to what extent, if any, do a firm's adaptation attempts during a pandemic influence its likelihood of survival following a pandemic? game theory -because firms strive to maximize payoffs, their actions can be predicted based on their interactions with other actors government efforts to alleviate the scope of a pandemic's impacts will alter the 'rules of the game' and thus how firms interact with one another extreme shifts in supply and demand will make upstream and downstream firms' moves more difficult to forecast and anticipate by what process and at what speed does cooperation between firms with competing objectives erode following a pandemic? how do the violations of the knowledge assumption brought on by a pandemic influence the sensitivity of game theoretic predictions? what mix of cooperation and competition helps firms achieve transiliency during and after a pandemic? real options theory -managers delay decision-making under uncertain conditions by creating options, then exercising or not exercising those options managers are more likely to exercise deferral, switch-use, and abandonment options in response to a pandemic staging options become more difficult to create and maintain during a pandemic, but they are potentially more useful under such conditions what types of options -new or existing -should managers create to foster transiliency in preparation for the next pandemic? under what conditions (i.e., when and how) should particular option types be exercised during a pandemic? this article is protected by copyright. all rights reserved. what is the optimal design, mix, and deployment of options during a pandemic? event system theory -novel, disruptive, or critical events are more likely to shape firm behaviors, and their effects may disperse widely across firms firms that experience huge swings in supply and demand during a pandemic are more likely to change their supply chain processes post-pandemic during a pandemic, firms that experience effects that cut across the entire end-to-end supply chain are more likely to foster transiliency how do event time and event space moderate the level of change triggered by a pandemic? how are supply chain managers and policymakers likely to respond to a pandemic given varying event characteristics (e.g., strength, time, space)? what changes in supply chain processes should be maintained and discarded following a pandemic? awareness-motivationcapability framework - the likelihood a firm will respond to an external threat is determined by its awareness of the threat, motivation to counter it, and capability to counter it prior pandemic experience will increase firms' awareness of a pandemic's impact and thus the likelihood they will respond individual firms are motivated to counter a pandemic's extreme impacts but are unlikely to have the capabilities required, thus encouraging coopetition what level of awareness is required to elicit a proactive response from firms pre-pandemic? how does firm motivation enhance or attenuate the effect of awareness on the likelihood of a proactive response? what level of cooperation between supply chain actors is required to effectively counter a pandemic's extreme impacts? this article is protected by copyright. all rights reserved. the framing of alternatives in terms of potential gains or losses shapes managers' risk preferences and decisions framing a pandemic's impact in terms of potential losses will increase the likelihood that managers will respond managers need to temper risk-seeking tendencies that the significant losses associated with a pandemic will encourage how can a pandemic's potential impacts be framed in order to improve supply chain managers' decisions? how does external framing (e.g., government and media) of a pandemic's potential impacts influence the likelihood supply chain managers will respond before versus during a pandemic? what 'checks' and interventions can firms implement to adjust for supply chain managers' risk preferences during a pandemic? tournament theory -how rewards are distributed among 'winners' and 'losers' shapes managers' decisions a firm will take more actions to maximize its chances of attaining pandemic-induced government bailouts when prize spreads are large pandemic-related uncertainty and the associated risks may require greater prize spreads to motivate firms to take actions that foster transiliency under what conditions do pandemic-induced tournaments foster collaboration versus competition in buyer-supplier exchanges? what level of prize spread optimizes the distribution of necessary goods during a pandemic? how do extreme losses during a pandemic influence firms' post-pandemic actions to maintain or improve competitiveness? an introduction to cybernetics supply chain disruptions and business continuity: an empirical assessment organizational theories: some criteria for evaluation firm resources and sustained competitive advantage the iron cage exposed: institutional pressures and heterogeneity across the healthcare supply chain the relationships among organizational context, pay dispersion, and among managerial turnover cooperation under the shadow of the future: experimental evidence from infinitely repeated games understanding responses to supply chain disruptions: insights from information processing and resource dependence perspectives target gets tough with vendors to speed up supply chain component procurement for an assembly supply chain with random capacities and random demand the continuum of pandemic phases competitor analysis and interfirm rivalry: toward a theoretical integration competitive tension: the awareness-motivation-capability perspective toward a "theoretical toolbox" for sustainability research in marketing tournament theory: thirty years of contests and competitions the severity of supply chain disruptions: design characteristics and mitigation capabilities goldilocks" theorizing in supply chain research: balancing scientific and practical utility via middle-range theory taking aim at theoretical and pragmatic impact: a call for actionable, insightful, and measurable research creditsafe data shows grocery chains paying suppliers faster during covid- pandemic understanding the present by examining the past: imprinting effects on supply chain outsourcing in a transition economy to be different, or to be the same? it's a question (and theory) of strategic balance how near-misses influence decision making under risk: a missed opportunity for learning the iron cage revisited: institutional isomorphism and collective rationality in organizational fields the amazon lockdown: how an unforgiving algorithm drives suppliers to favor the e-commerce giant over other retailers on theory in supply chain uncertainty and its implications for supply chain integration amazon extends distribution center shutdowns in france after losing appeal case health message framing effects on attitudes, intentions, and behavior: a meta-analytic review strategic sourcing under severe disruption risk: learning failures and under-diversification bias, manufacturing and service operations management the population ecology of organizations structural inertia and organizational change play for pay: effects of inequity in a pay-for-performance context an analysis of manufacturer-retailer supply chain coordination in cooperative advertising risk uncertainty and supply chain decisions: a real options perspective an examination of cultural competitiveness and order fulfillment cycle time within supply chains the great lockdown: worst economic downturn since the great depression drivers and performance outcomes of supplier innovation generation in customer-supplier relationships: the role of power-dependence valuate outsourcing contracts from vendors' perspective: a real options approach to prepare for the next 'black swan' event, supply chains should rethink 'lean prospect theory: an analysis of decision under risk the social psychology of organizations achieving research design excellence through the pursuit of perfection: toward strong theoretical calibration from supply chains to supply ecosystems: implications for strategic sourcing research and practice bridging organization theory and supply chain management: the case of best value supply chains strategic entrepreneurship, collaborative innovation, and wealth creation resource gaps and resource orchestration shortfalls in supply chain management: the case of product recalls the effect of performance measurement systems on firm performance: a cross-sectional and a longitudinal study deployment of supply chain security practices: antecedents and consequences a lot of restaurants are already permanently closed sourcing decisions under conditions of risk and resilience: a behavioral study. decision sciences institutionalized organizations: formal structure as myth and ceremony event system theory: an event-oriented approach to the organizational sciences wwe q earnings call determinants of corporate borrowing how global media covers the coronavirus responses to supplier-induced disruptions: a fuzzy-set analysis imitation of management practices in supply networks: relational and environmental effects designer and supply chain digital revolution: how covid- is changing the fashion industry general motors will help manufacture hospital ventilators to fight coronavirus game theory from mass production to mass customization: hindrance factors, structural inertia, and transition hazard flow coordination and information sharing in supply chains: review, implications, and directions for future research decision bias in the newsvendor problem with a known demand distribution: experimental evidence designer brand louis vuitton starts making masks, hospital gowns for coronavirus outbreak apple, google give a look at coronavirus tracking tech, promise more privacy protections portfolio spillover of institutional investor activism: an awareness-motivation-capability perspective false alarm: the truth about the epidemic of fear not all threats are created equal: how implicitness and timing affect the effectiveness of threats in negotiations managing firm resources in dynamic environments to create value: looking inside the black box resource orchestration to create competitive advantage breadth, depth, and life cycle effects survey: covid- could shutter most small businesses the supply side: delays, product scarcity challenge retailers, manufacturers norway temporarily suspends competition regulation for airlines information systems project continuation in escalation situations: a real options model the bounded rationality bias in managerial valuation of real options: theory and evidence from it projects supply chain inventory replenishment: the debiasing effect of declarative knowledge managing imbalanced supply chain relationships for sustainability: a power perspective coronovirus bankruptcy tracker: these major companies are failing amid the shutdown rational choice and the framing of decisions competitor analysis and foothold moves an outline of general system theory. british journal for the philosophy of science the theory of games and economic behavior optimal fee structures of crowdsourcing platforms managing coopetition through horizontal supply chain relations: linking dyadic and network levels of analysis toward a "theoretical toolbox" for the supplier-enabled fuzzy front end of the new product development process the impact of product returns and retailer's service investment on manufacturer's channel strategies strategic decisions of new technology adoption under asymmetric information: a game-theoretic model this article is protected by copyright. all rights reserved. key: cord- - b lenw authors: salenger, rawn; etchill, eric w.; ad, niv; matthew, thomas; alejo, diane; whitman, glenn; lawton, jennifer s.; lau, christine l.; gammie, charles f.; gammie, james s. title: the surge after the surge: cardiac surgery post-covid- date: - - journal: ann thorac surg doi: . /j.athoracsur. . . sha: doc_id: cord_uid: b lenw abstract background the covid- pandemic has dramatically reduced adult cardiac surgery case volumes as institutions and surgeons curtail non-urgent operations. there will be a progressive increase in deferred cases during the pandemic that will require completion within a limited time frame once restrictions ease. we investigated the impact of various levels of increased post-pandemic hospital operating capacity on the time to clear the backlog of deferred cases. methods we collected data from four cardiac surgery programs across two health systems. we recorded case rates at baseline and during the covid- pandemic. we created a mathematical model to quantify the cumulative surgical backlog based on the projected pandemic duration. we then used our model to predict the time required to clear the backlog depending on the level of increased operating capacity. results cardiac surgery volumes fell to % of baseline after restrictions were implemented. assuming a service restoration date of either june or july , we calculated the need to perform % or % of monthly baseline volume, respectively, to clear the backlog in one month. the actual duration required to clear the backlog is highly dependent on hospital capacity in the post-covid time period, and ranges from one to eight months depending on when services are restored and degree of increased capacity. conclusions cardiac surgical operating capacity during the covid- recovery period will have a dramatic impact on the time to clear the deferred cases backlog. inadequate operating capacity may cause substantial delays and increase morbidity and mortality. if only pre-pandemic capacity is available, the backlog will never clear. background. the covid- pandemic has dramatically reduced adult cardiac surgery case volumes as institutions and surgeons curtail non-urgent operations. there will be a progressive increase in deferred cases during the pandemic that will require completion within a limited time frame once restrictions ease. we investigated the impact of various levels of increased postpandemic hospital operating capacity on the time to clear the backlog of deferred cases. we collected data from four cardiac surgery programs across two health systems. we recorded case rates at baseline and during the covid- pandemic. we created a mathematical model to quantify the cumulative surgical backlog based on the projected pandemic duration. we then used our model to predict the time required to clear the backlog depending on the level of increased operating capacity. results. cardiac surgery volumes fell to % of baseline after restrictions were implemented. assuming a service restoration date of either june or july , we calculated the need to perform % or % of monthly baseline volume, respectively, to clear the backlog in one month. the actual duration required to clear the backlog is highly dependent on hospital capacity in the post-covid time period, and ranges from one to eight months depending on when services are restored and degree of increased capacity. cardiac surgical operating capacity during the covid- recovery period will have a dramatic impact on the time to clear the deferred cases backlog. inadequate operating capacity may cause substantial delays and increase morbidity and mortality. if only prepandemic capacity is available, the backlog will never clear. key words: cardiac surgery; covid- ; surgical capacity; coronary artery bypass grafting the covid- pandemic has resulted in dramatically lower adult cardiac surgery case volumes, as institutions and surgeons are following state and federal guidelines to curtail non-urgent operations. there will be a progressive increase in deferred cases during the pandemic that will require completion within a limited time frame once pandemic restrictions ease, in order to avoid excess morbidity and mortality [ ] [ ] [ ] . by definition, programs will have to achieve higher daily case rates than prior to the pandemic in order to service the excess demand. the postpandemic surge in adult cardiac surgery could overwhelm current hospital resources without proper planning. data were collected from four institutions across two health systems. each system included two large academic centers and two affiliated community cardiac surgery programs. first, we calculated a combined baseline case rate across centers, pre-pandemic, by quantifying all cases done from january to february , . inclusion criteria included any adult cardiac surgery case being performed in the operating room with a cardiac surgeon as primary or co-surgeon. heart and lung transplant, ventricular assist device, and transcatheter aortic and mitral valve replacements were included. primary extracorporeal membrane oxygenation (ecmo) cases and pediatric cases were excluded. next, we calculated the combined rate of cases during the early part of the pandemic. raw data was collected from march th through april th and this was used to extrapolate a new "pandemic" surgical case rate. march th was the day after the state of emergency was declared in the state of maryland. we calculated the number of patients that would have surgery deferred during the pandemic, and the length of time necessary to service the backlog in a timely fashion once restrictions were lifted. mathematical models were used to investigate the impact of the date that restrictions are lifted, and variable levels of hospital operating capacity on the time that would be required to address the backlog. to calculate the current backlog (b) on any given day (t), we developed the equation b = (r -r p ) (t -t ). this is the difference in the daily case rates multiplied by the number of days that difference had existed. t was then defined as the day that restrictions were eased and full operating capacity regained. next, the number of operating days necessary to perform all the backlogged cases, defined as backlog time (bt), was calculated. the model was designed to predict the length of time required to clear the backlog based on the amount of extra operating capacity a hospital could achieve. our prediction model defined t as the day the pandemic began, and t as the day restrictions were lifted. each hospital's post-pandemic daily case rate would be defined by an acceleration factor (a) multiplied by the original prepandemic case rate, r . the time required to clear the backlog of cases, bt, was then calculated. bt was defined by the equation bt = ( -r p /r ) (t -t ) / (a- ). the acceleration factor (a) represented how much surgical throughput a program could achieve above baseline. this factor would have to be greater than in order to incorporate some amount of deferred cases into the operating schedule in addition to baseline cases. cases were initially curtailed in early to mid-march and then more drastically in april as recommendations to postpone all but emergency operations became stronger. baseline total case rate for the four combined programs was adult cardiac surgery cases per month. during the pandemic that rate initially fell to , then to cases per month once full restrictions were implemented ( % of normal). during this time the number of deferred cases would be estimated to grow to by june and by july . this represents % to % of normal average monthly volume depending on the duration of the pandemic (figure ). the daily case rates were also calculated. we assumed operative weekdays per month. for the combined health systems, the average daily case rate pre-pandemic, defined as r , was . . the daily case rate during the pandemic, defined as r p , was calculated to be . (table ) . we also calculated the baseline and pandemic daily case rates for three broad categories of cases including coronary artery bypass grafting (cabg), open valve surgery, and transcatheter aortic and mitral valve replacements (tavr/tmvr) (figure ). combined cabg/valve cases were counted as cabg because we felt that the patient's coronary disease would often dictate more urgent triage (figure ). isolated valve cases were more likely to be deferred than patients with isolated or concomitant coronary disease. transcatheter cases were treated differently between the health systems. one system's transcatheter case rate fell from per month to cases per month, while the other system increased their transcatheter cases from per month to cases per month. this equated to approximately a % decrease in one system's transcatheter cases and a % increase within the neighboring system. this differential treatment of transcatheter cases partially mitigated the overall backlog accumulation. cabg cases and valves were triaged similarly by the health systems and these case rates fell by % and % respectively. next, we used our mathematical model to predict the number of cardiac surgery cases deferred during the pandemic, and the length of time required to operate on the backlog, dependent on the amount of increased operating capacity institutions could achieve. time to clear the backlog, bt, was calculated using our mathematical model (figure ). this was considered for the possibility of restored services on june or july with varied levels of case capacity (figure ). assuming services were restored june , the backlog could be cleared between - months, depending on degree of increased capacity. if services resumed july , the cardiac surgery backlog would be estimated to take between - months to clear according to the increased capacity achieved. progressively increasing the operating capacity had a dramatic effect on reducing the time to clear the backlog. if capacity is not increased above baseline (acceleration factor = . ), the backlog will never be cleared. in response to the covid- pandemic, adult cardiac surgery programs have dramatically curtailed operating activity, limiting cases to urgent and life-threatening emergencies. this slowdown has resulted in a growing backlog of adult cardiac surgery cases which will require surgical therapy in a finite time frame to improve quality of life and survival. our study analyzed the deliberate deceleration in adult cardiac surgery cases that has occurred at the two busiest cardiac surgical programs in the state of maryland in response to the covid pandemic. we observed a % drop in cardiac surgical volume, and subsequently a backlog that would require a monthly operating volume of % to % of baseline. since this would be challenging to accomplish in one month, we predicted that the amount of time necessary to clear the backlog would range from to months based on varied estimates of post-pandemic increased operational capacity. our data further suggest that deferred cardiac patients were triaged differently during the pandemic and that the composition of the waiting list is directly related to the triaging mechanism. as expected, isolated valve patients were preferentially deferred compared to patients with any coronary artery disease. we were surprised to see the differences in transcatheter case triage between the two systems. one system deferred the majority of transcatheter cases, while the other increased their rate, mainly tavr cases. although our data did not include reasons for triage decisions, this may have been due to differing thresholds for observing patients with severe aortic stenosis and uncertainty regarding best practice when deferring cardiac services. others have attempted to characterize the needs for surgical services after natural disasters by establishing a baseline surgical rate and then examining the incidence of injury during a disaster [ ] . a study of the nepal earthquakes in demonstrated an acute need for surgical therapy that was more than double the annual nepalese operating capacity, highlighting the need to be able to increase surgical capacity at critical times. another study focused on the aftermath of hurricane charley and found a thirty-two percent increase in adverse medical outcomes for patients with chronic medical conditions related to both increased demand and shortfalls in care delivery [ ] . similar to our investigation, these studies focused on increased healthcare demand following unpredictable events. our analysis differed because we analyzed the effect of an unexpected viral pandemic that necessitated a nearly % decline in surgical volume followed by an anticipated surge in surgical demand. our study is novel in that we prospectively attempted to predict system capacity needs in order to service the anticipated surgical surge. this will require local hospitals and health systems to examine capacity, set priorities, and plan for adequate hospital capacity to service the backlog of cardiovascular patients [ , ] . the global cardiac surgery response post-covid will be complicated by prior exhaustion of hospital supplies and human resources from the pandemic, and competition for resources and operating room availability with other surgical and medical subspecialties, which will also have backlogs. the recently published joint statement from the american college of surgeons and others provides guidance on when to safely reopen operating room capacity and includes recommendations for testing, personal protective equipment, and case prioritization [ ] . we believe that it will be important to maintain an incident command approach during the late phases of the covid epidemic as we transition to re-establishing, and increasing, our prepandemic workflow. planning should begin now, and crucially, prioritize patients with significant risks arising from delayed operations. the risks of deferring needed cardiac treatment have been previously demonstrated. reported mortality rate while waiting for surgical or transcatheter aortic valve replacement can be as high as . % at one month and . % at six months [ ] . for patients awaiting coronary surgery, median waiting list mortality rates of . % per month have been reported with mortality risk increasing % per month. additionally, % of patients experienced a myocardial infarction while on the waiting list [ , ] . we have attempted to estimate the resources required in planning for the post-pandemic surge in adult cardiac surgical volume. the capacity estimates for a given health system would depend on the percent increase in productivity targeted post pandemic. by utilizing our mathematical model, a health system could predict the time required for servicing their surgical backlog and adjust operating capacity accordingly. actualizing a plan to increase capacity may occur gradually and this will further increase waiting time for deferred patients. increasing capacity will also require proportional adjustments in resources such as operating rooms, icu and telemetry beds, and provider staff. for the majority of hospitals, or time is the most expensive resource. consequently, increasing icu and telemetry capacity to avoid operating room holds and cancellations is likely the most cost-effective approach to achieving increased throughput. the number of additional beds, nurses, and advanced practice providers needed can be calculated based on baseline resources. maximizing efficiency through early telemetry discharge, decreasing intensive care length of stay, level loading elective cases in the or, temporarily altering staffing models, and staggering cases can help increase throughput capacity [ , ] . another possible solution is to temporarily relocate some non-cardiac surgical cases to other facilities within a health system. in fact, maintaining the incident command center set up by many hospitals and utilizing some of the same workforce and bed solutions employed during the pandemic may be of value in delivering critical cardiac services in a timely fashion. our analysis has several limitations. firstly, we have assumed that historical rates of surgery will accurately predict future rates. this may be incorrect for several reasons. during the pandemic patients may be treated with alternative medical and interventional therapy, obviating the need for surgery. patients treated medically with symptomatic relief may decide not to pursue more aggressive treatment. other patients may be reluctant to incur out of pocket costs during this time of financial difficulty. additionally, there will unfortunately be some degree of attrition of patients from cardiovascular and covid-related mortality. the pent up demand could also accrue more slowly than calculated. cardiac surgeons sit at the bottom of a virtual funnel which begins with patients seeking medical care, referral to a cardiologist, diagnostic testing, and finally evaluation for surgery. each step along this pathway will be delayed during, and likely for some time after, the pandemic. delays would function as a governor on the acceleration of post-pandemic cardiac surgical demand. our study does, however, provide concerning data delineating a large group of patients with surgical level cardiovascular disease whose treatment has been necessarily deferred. our hope is that our modeling can be used to calculate the productivity increase necessary to treat patients in an acceptable time frame. further study could help better define the overall effects of a pandemic on the care of cardiovascular patients. although challenging and costly, early post-pandemic operating capacity will need to be greater than the original daily capacity to satisfy the pent-up surgical demand. not planning for post pandemic volume could result in a second wave of non-covid cardiovascular mortality. mortality on the waiting list for coronary artery bypass grafting: incidence and risk factors mortality while waiting for aortic valve replacement waiting times and prioritisation for coronary artery bypass surgery in new zealand surgical care required for populations affected by climate-related natural disasters: a global estimation medical interventions following natural disasters: missing out on chronic medical needs design of a model to predict surge capacity bottlenecks for burn mass casualties at a large academic medical center surgical subspecialty block utilization and capacity planning: a minimal cost analysis model roadmap for resuming elective surgery after covid- pandemic n.d balancing operating theatre and bed capacity in a cardiothoracic centre development and evaluation of a prospective staffing model to improve retention key: cord- - kmder authors: meyer, r. daniel; ratitch, bohdana; wolbers, marcel; marchenko, olga; quan, hui; li, daniel; fletcher, chrissie; li, xin; wright, david; shentu, yue; englert, stefan; shen, wei; dey, jyotirmoy; liu, thomas; zhou, ming; bohidar, norman; zhao, peng-liang; hale, michael title: statistical issues and recommendations for clinical trials conducted during the covid- pandemic date: - - journal: nan doi: nan sha: doc_id: cord_uid: kmder the covid- pandemic has had and continues to have major impacts on planned and ongoing clinical trials. its effects on trial data create multiple potential statistical issues. the scale of impact is unprecedented, but when viewed individually, many of the issues are well defined and feasible to address. a number of strategies and recommendations are put forward to assess and address issues related to estimands, missing data, validity and modifications of statistical analysis methods, need for additional analyses, ability to meet objectives and overall trial interpretability. the covid- outbreak emerging in china in december quickly became a global pandemic as declared by the world health organization in march . as of today, still only a few months into the pandemic, the disease and public health control measures are having very substantial impact on clinical trials globally. quarantines, site restrictions, travel restrictions affecting participants and site staff, covid- infections of study participants, and interruptions to the supply chain for study medication have led to operational problems, including difficulties in adhering to study protocols. trial sponsors have rapidly responded to this crisis, where the overriding primary concern has been to protect participant safety. some trials have been halted or enrolment suspended in the interest of participant safety. for ongoing trials, sponsors have implemented a variety of mitigations to assure safety of participants and address operational issues. the downstream effects of protocol deviations and trial conduct modifications lead to varying degrees of impacts on clinical trial data. the impacts, described in more detail in later sections, raise important statistical issues for the trial. in the extreme, trial integrity, interpretability, or the ability of the trial to meet its objectives could be compromised. intermediate to that, planned statistical analyses may need to be revised or supplemented to provide a thorough and appropriate interpretation of trial results. this paper offers a spectrum of recommendations to address the issues related to study objectives, inference, and statistical analyses. the major categories of impacts and mitigations are summarized in figure . the issues we discuss here largely involve ongoing trials, started before but conducted during the pandemic for non-covid- related therapies. many of the issues and recommendations will also apply to new trials. regulatory agencies have rapidly published guidance for clinical trial sponsors to address covid- issues (fda , ema a , b . the current paper is influenced by and expands upon these important guidance documents. the paper is organized as follows. in section we describe overall trial impact assessment. section considers assessment of impacts on the trial through the estimand framework. section summarizes recommendations for revised and supplemental analyses that may be needed for the trial, including the likely mechanisms of missing data and the recommended statistical approaches to address missingness. section outlines additional considerations for trial-level impact. a summary of recommendations is given in section . for trials impacted by the pandemic, assessing the change of the benefit/risk for participants is the first step in the decision-making process (fda ). all recommendations in this article presuppose that appropriate steps have been taken to assure participant safety. sponsors are advised to perform a risk assessment based on aggregated and blinded data to evaluate the likelihood of a trial to deliver interpretable results. it must start as a forwardlooking assessment in anticipation of effects not yet seen but with some likelihood to occur. it should continue throughout the conduct of the study in light of the evolving situation and accumulating data, considering regional differences in the infection status and pandemic-  determine what additional information needs to be collected in the study database or in the form of input from study investigators in order to adequately monitor, document, and address pandemic-related issues (feasibility to obtain such information and its quality may vary and this needs to be considered as part of the risk factors);  understand reasons for treatment or study discontinuation and the impact on planned estimands and intercurrent events;  evaluate extent of missing data and specific reasons for missingness;  assess changes in enrollment and in study population over time;  evaluate the protocol-specified assumptions and the likelihood that the trial would be able to achieve its goals;  ideally, verify the usability of data captured from alternative methods (e.g., virtual audio or video visits) before implementing them. such data may add more variability or not be interpretable;  determine any changes to planned analyses and analysis population definitions, or additional sensitivity analyses that need to be pre-specified prior to unblinding. based on the risk evaluations above, many sponsors have developed standardized metrics of trial operational status, such as rates of missed visits, discontinuations from treatment and study, protocol deviations, adverse events (aes), to reinforce a consistent approach to risk monitoring and assessment. such metrics are useful to identify trials that are more acutely impacted and to monitor the overall state of a portfolio of trials. the ich e (r ) addendum (ich, ) defines the estimand framework for ensuring that all aspects of study design, conduct, analysis, and interpretation align with the study objectives. it also provides a rigorous basis to discuss potential pandemic-related disruptions and to put them in the context of study objectives and design elements. for an affected trial, the first major question is whether the primary objective, and therefore the primary estimand, should target the treatment effect without potentially confounding influences of covid- . we recommend that for most studies started before the pandemic, the original primary objective should be maintained as designed, implying a treatment effect that is not confounded by pandemic-related disruptions. (for new studies, this definition of treatment effect may also be reasonable, but depends on many aspects of the trial design.) this does not automatically imply a broad "hypothetical estimand" with the same hypothetical scenario for all possible pandemic-related intercurrent events (ice). confounding may need to be addressed in different ways for different types of ices depending on the study context. we discuss this in section . our discussion is mainly geared towards considerations for the primary efficacy estimands, but similar logic can be applied to other study estimands. strategies for handling non-pandemic related ices should remain unchanged. here we discuss handling of pandemic-related ices only. the estimand framework allows for different strategies to be used for different types of ices and such estimands will likely be the most appropriate in the current context. ices should be considered pandemic-related if they occur as a result of pandemicrelated factors and are not attributed to other non-pandemic related reasons, e.g., treatment discontinuation due to lack of efficacy or a toxicity. pandemic-related ices of importance should first be categorized in terms of their impact on study treatment adherence (e.g., study treatment discontinuation) or ability to ascertain the target outcomes (e.g., death).  admitted to intensive care. * covid- related deaths and initiation of treatment for covid- infections may also be considered as ices if they occur after the completion of study treatment or after other non-pandemic-related ices and before the time point associated with the endpoint of interest. certain types of non-adherence to study treatment may not normally be considered as ices but may need to be in the context of the pandemic. for example, an ice of significantly reduced compliance or temporary treatment interruption may not have been anticipated at study design but could be now if considered likely due to pandemic-related disruptions. for some studies with significant pandemic-related treatment interruptions, the minimal duration of interruption expected to dilute the treatment effect could be defined. different strategies can be used for interruptions exceeding this duration as opposed to shorter interruptions. sensitivity analyses can be used to assess robustness of inference to the choice of cut-off. for time-to-event endpoints, it is tempting to define the minimally acceptable level of drug compliance on a participant level according to the observed exposure to study drug from the first dose of study drug until the event or censoring and exclude participants without a minimally acceptable level of compliance. however, such an approach could introduce immortal time bias and should therefore be avoided (van walraven et al, ) . a special consideration may be warranted for participants receiving experimental treatment for covid- regardless of whether they remain on study treatment. also, in studies where mortality was not originally expected, death due to covid- should be considered as a potential ice. most of the ice types listed against the "participant's adherence to study treatment" attribute in table (e.g., study treatment discontinuation) due to non-pandemic related reasons are likely addressed in the primary estimand prior to the pandemic. we recommend starting with an examination of whether the original strategy is justifiable when these ices occur due to the pandemic. if not, a different strategy should be chosen. we outline some high-level considerations in this respect.  treatment policy strategy, in which ices are considered irrelevant in defining the treatment effect, will typically not be of scientific interest for most pandemic-related ices because the conclusions would not generalize in the absence of the pandemic. for example, the treatment effect estimated under the treatment policy for premature treatment discontinuations caused by pandemic-related disruptions will reflect the effect of a regimen where discontinuations and changes in therapy occur due to pandemic-related factors (e.g., disruptions in study drug supply) which would not be aligned with the primary study objective. initiation of treatment for covid- infection after an earlier non-pandemic-related ice that was planned to be handled by the treatment policy strategy but prior to observation of an efficacy or safety endpoint will also need to be considered carefully and cannot simply be deemed irrelevant. under the treatment policy strategy, the estimated treatment effect may reflect the effects of infection and its treatment, which are presumably not of interest for the primary objective. a decision to use a treatment policy approach for pandemic-related ices may be justifiable if the percentage of participants with such events is low and this strategy was planned for similar non-pandemic related ices. this strategy may also be considered for handling ices corresponding to relatively short treatment interruptions. the treatment policy strategy should be avoided for pandemic-related ices of premature study treatment discontinuation in non-inferiority and equivalence studies, as similarity between treatment groups may artificially increase with the number of such events. similar considerations also apply to the composite strategy.  composite strategies, in which ices are incorporated into the definition of the outcome variable, are unlikely to be appropriate for most pandemic-related ices. for example, study treatment discontinuation due to pandemic-related disruptions should not be counted as treatment failure in the same way as discontinuation due to lack of efficacy or adverse reactions. a more nuanced consideration may be needed in studies of respiratory conditions, where covid- complications may be considered with a composite strategy as a form of unfavourable outcome. (see also a discussion on covid- related deaths further below.)  principal stratification strategy stratifying on a covid- related event (e.g., serious complications or death due to covid- ) is unlikely to be of interest for the primary estimand because it would limit conclusions to a sub-population of participants defined based on factors not relevant in the context of the future clinical practice.  while-on-treatment strategy may continue to be appropriate under certain conditions if it was originally planned for non-pandemic-related ices. this strategy is typically justifiable when treatment duration is not relevant for establishing treatment effect (e.g., treatment of pain in palliative care), but certain conditions may need to be considered, such as a minimum treatment duration required to reliably measure treatment outcomes.  hypothetical strategy, in which the interest is in the treatment effect if the ice did not occur, is a natural choice for most pandemic-related ices. this would especially apply to ices of study treatment disruption for pandemic reasons. for such participants, the hypothetical scenario where they would continue in the study in the same way as similar participants with an undisrupted access to treatment is reasonable. it is not necessary to assume a hypothetical scenario where such participants would fully adhere to the study treatment through the end of the study. rather, a hypothetical scenario may include a mixture of cases who adhere to the study treatment and those who don't adhere for non-pandemic reasons. discussions with regulatory agencies may be helpful to reach an agreement on the details prior to the final study unblinding. although estimation methods are not part of the estimand consideration, the ability to estimate treatment effects in a robust manner under a hypothetical strategy based on available data should not be taken for granted and should be assessed as the estimand definition is finalized. this aspect should be part of the overall risk assessment and decisions on the choice of the mitigation strategies. the discussion above highlights the need to capture the information associated with pandemic-related factors, such as those listed in table . this can be done either through designated fields in the case report form (crf) or through a detailed and structured capture of protocol deviations. an ice of death due to covid- requires careful consideration and the appropriate strategy depends on the disease under study and clinical endpoint. in disease areas with minimal mortality where death is not a component of the endpoint, a hypothetical strategy for deaths related to covid- infections may be recommended. for studies in more severe diseases where death is part of the endpoint, it is inevitable that more than one estimand will be of interest when evaluating the benefit of treatment for regulatory purposes. a pragmatic approach which includes covid- -related deaths in the outcome, i.e., which uses a composite strategy, is suitable if the number of covid- -related deaths is low or if there is a desire to reflect the impact of the pandemic in the treatment effect estimate. (see also the related section on competing risks analyses in section . . .) using a hypothetical strategy for deaths related to covid- infections will be important in evaluating the benefit of treatment in the absence of covid- (for example, when the disease is eradicated or effective treatment options emerge). it is acknowledged that such trials frequently include elderly, frail, or immunocompromised participants and it may be difficult to adjudicate a death as caused by covid- or whether the participant died with covid- . while treatment policy, composite, and principal stratification strategies may not be of interest for the primary estimand, they may be of interest for supplementary estimands when there is a scientific rationale to investigate the study treatment either in subpopulations of participants stratified based on covid- infection and outcomes and/or together with a concomitant use of treatments administered for covid- . for example, this may be of interest for studies in respiratory diseases or conditions suspected to be risk factors for covid- complications. the relevance of such estimands will also depend on the evolution of this pandemic, whether the virus is eventually eradicated or persists like seasonal flu. in the latter case, the reality and clinical practice are still likely to be different from the current crisis management conditions as the society and clinical practice adapt to deal with a new disease. in general, treatment condition of interest should remain the same as originally intended. however, operationally, the mode of treatment delivery may need to be changed due to pandemic-related reasons, e.g., treatment self-administered by the participant at home rather than in the clinic by a health-care professional. when such changes are feasible, they may be considered to reduce the frequency of visits to the clinic, and therefore reduce the risk of infection exposure. pandemic-related complications with study treatment adherence and concomitant medications should be considered as ices and handled with an appropriate strategy. the extent of such ices should be evaluated in terms of whether the treatment(s) received by participants during the study remain sufficiently representative of what was intended. this may include treatment interruptions, reduced compliance, and access to any background, rescue, and subsequent therapies planned to be covered by the treatment policy strategy. to align with the primary study objective, the target participant population should remain as originally planned, i.e., should not be altered simply due to the pandemic. protocol amendments unrelated to the pandemic to further qualify the study population should still be possible. the trial inclusion/exclusion criteria should also remain largely unchanged relative to those that would be in place in absence of the pandemic, except for the possible exclusion of active covid- infections. the clinical endpoint should generally remain as originally planned. in cases where alternative measurement modalities may be necessary during the pandemic, for example, central labs vs. local labs, remote assessments of questionnaires instead of in-clinic, etc., it must be assured that clinical endpoint measurement is not compromised and potential effects on endpoint variability should be assessed (see section . . ). in cases where pandemic-related ices, such as covid- deaths, are handled using the composite strategy, the definition of the endpoint may need to be adjusted. in cases of numerous delays between randomization and start of treatment, where the endpoint is defined relative to the date of randomization (e.g., in time-to-event endpoints), consideration may be given to redefine the endpoint start date to start of treatment. however, in the context of openlabel studies this may not be advisable. population-level summary describing outcomes for each treatment and comparison between treatments should remain unchanged, in general. in rare situations, a summary measure may need to be changed, for example, if the originally planned endpoint is numeric and a composite strategy is used for covid- deaths to rank them worse than any value in survived participants. in this case, a summary measure may be changed from mean to median. another example could be a hazard ratio (hr) from a cox proportional hazard regression, a summary measure of treatment effect commonly used for trials with time-toevent endpoints. if the assumption of proportional hazards is not satisfied, the estimated hr depends on the specific censoring pattern observed in the trial, which is influenced both by participant accrual and dropout patterns (rufibach, ) . external validity and interpretability of the hr needs to be carefully considered if censoring patterns are affected during the pandemic in ways that are not representative of non-pandemic conditions and if additional pandemic-related censoring depending on covariates such as the participant's age or comorbidities are observed. similarly, the validity of the log-rank test relies on the assumptions that the survival probabilities are the same for participants recruited early and late in the trial and that the events happened at recorded times. such assumptions may need to be assessed. supportive estimands with alternative summary measures could be considered (see e.g., boyd et al., ; nguyen and gillen, ; mao et al., ) . planned statistical analyses may need to be modified due to effects of the pandemic on trials. additional sensitivity and supplementary analyses may be needed to properly understand and characterize the treatment effect. depending on the trial, modifications in planned analyses may range from relatively minor, e.g., for trials with relatively low impact, to major, e.g. in settings where study drug administration and visits are severely disrupted by the pandemic. a general summary of analysis considerations is provided in table and detailed discussions are presented in subsequent sections. all planned modifications and additional analyses should be documented in the sap prior to data unblinding and in the clinical study report. additional post hoc exploratory analyses may also be necessary after study unblinding to fully document the impact of the pandemic and characterize the treatment effect in this context.  review all planned main and sensitivity analyses to ensure alignment with the revised estimand(s).  review / amend methods for handling of missing data, or censoring rules, to accommodate pandemic-related missingness.  summarize the occurrence of pandemic-related ices and protocol deviations.  summarize the number of missed or unusable assessments for all key endpoints.  summarize the number of assessments performed using alternative modalities.  summarize study population characteristics before and after pandemic onset. additional sensitivity and supportive analyses  plan additional analyses for sensitivity to pandemic-related missingness.  consider the need for additional, alternative summary measures of treatment effect.  consider exploring inclusion of additional auxiliary variables, interaction effects, and time-varying exogenous covariates in the analysis methods.  consider subgroup analyses based on subgroups defined by pandemic impact, e.g. primary endpoint visits before or after pandemic onset.  consider the need for evaluation of potential impact of alternative data collection modalities.  consider sources of data external to the trial, for example to justify use of alternative modalities.  plan for additional safety analyses. all planned efficacy analyses should be re-assessed considering the guidance provided in sections and in terms of handling of pandemic-related missing data (see section . ). the core analysis methodology should not change. however, depending on the revisions to the estimand, the strategies chosen for pandemic-related ices, and the handling of pandemicrelated missing data, some changes to the planned analyses may be warranted. additional analyses will frequently also be required to assess the impact of the pandemic disruption. special considerations may be needed for studies and endpoints where participant outcomes could be directly impacted by the pandemic, e.g., in respiratory diseases or quality of life endpoints. in studies where enrolment is halted due to the pandemic, sponsors should compare the populations enrolled before and after the halt. more generally, shifts in the population of enrolled participants over the course of the pandemic should be evaluated. baseline characteristics (including demographic, baseline disease characteristics, and relevant medical history) could be summarized by enrolment period to assess whether there are any relevant differences in the enrolled population relative to the pandemic time periods. shifts could be associated with regional differences in rates of enrollment because start and stop of enrollment is likely to vary by country as pandemic measures are implemented or lifted. sponsors should make every effort to minimize the amount of missing data without compromising safety of participants and study personnel during the covid- pandemic and placing undue burden on the healthcare system. whenever feasible and safe for participants and sites, participants should be retained in the trial and assessments continued, with priority for the primary efficacy endpoint and safety endpoints, followed by the key secondary endpoints. despite best efforts, sponsors should prepare for the possibility of increased amounts and/or distinct patterns of missing data. in the framework of ich e (r ), an assessment or endpoint value is considered missing if it was planned to be collected and considered useful for a specific estimand but ended up being unavailable for analysis. in case of ices that are addressed by a hypothetical strategy, endpoint values are not directly observable under the hypothetical scenario. such data are not missing in the sense of the ich e (r ) definition, however, they need to be modelled in the analysis, often using methods similar to those for handling of missing data. in the remainder of the paper, we will discuss methods for handling of missing data, and note that such methods can be useful for modelling unobserved data after ices, if the modelling assumptions align with the hypothetical scenarios chosen for addressing the corresponding ices. sponsors should assess and summarize patterns (amount and reasons) of pandemic-related missing data in affected trials. data may be missing because a) planned assessments could not be performed; b) collected data is deemed unusable for analysis, e.g., out-of-window; or c) data under a desired hypothetical scenario cannot be observed after an ice (e.g., censored). additionally, each pandemic-related missingness instance also has specific reasons and circumstances. at a high level, reasons for pandemic-related missing data could be structural (e.g., government enforced closures or sites stopping study-related activities) or they could be participant-specific (e.g., individual covid- disease and complications or individual concerns for covid- ). table outlines the aspects that together provide a comprehensive picture for assessing the impact of missing data and planning how to handle them in analysis. sponsors should, therefore, capture such information in the clinical study database as much as possible. the last two rows of table reflect circumstances similar to those that are considered in the context of ices (see table ). since missing data may occur both in the presence of ices (e.g., handled by a hypothetical strategy) and in the absence of ices (e.g., participant continues to adhere to study treatment but misses some assessments), we list them here as well. table . attributes of pandemic-related missing data. row summarizes reasons of missing data, rows - summarize related conditions that contribute to those reasons.  assessment missing due to a participant's premature discontinuation from the study overall for pandemicrelated reasons;  assessment missing due to missed study visits/procedures while a participant remains in the study (intermittent missing data);  assessment delayed (out-of-window) and deemed unusable for an analysis;  a composite score (e.g., acr in rheumatoid arthritis) cannot be calculated because some components are missing;  assessment deemed to be influenced by pandemic-related factors and deemed unusable for a particular analysis because the interpretability of the results may be impacted (e.g., in assessments of quality of life, activity/functional scales, healthcare utilization, etc);  recorded data cannot be properly verified or adjudicated due to covid- -related factors and deemed to be unreliable for analysis;  assessment performed after an intercurrent event intended to be handled with a hypothetical strategy and collected data are deemed unusable for this estimand. assessment accessibility  site (facilities or staff) unavailable to perform studyrelated assessments;  site/assessment procedure available but participant is unable/unwilling to get assessment done due to personal pandemic-related reasons. sponsors should also consider a potential for under-reporting of symptoms and aes during the pandemic due to missed study visits or altered assessment modalities, e.g., a telephone follow-up instead of physical exam. (see section . .) sponsors should also consider reporting patterns of missingness along several dimensions: over time (in terms of study visits as well as periods before and after the start of pandemic disruptions), with respect to certain demographic and baseline disease characteristics, as well as co-morbidities considered to be potential risk factors associated with covid- infection or outcomes, and across geographic regions. blinded summaries of missing data patterns prior to study unblinding may inform the choice of missing data handling strategies. it may be useful to compare missing data patterns from the current studies with similar historical studies, especially with respect to missingness in subgroups. after study unblinding (for final or unblinded dmc analyses), missing data patterns should be summarized overall and by treatment arm. although in most cases pandemicrelated missingness, especially structural missingness, would not be expected to differ between treatment arms, such a possibility should not be ruled out. in special circumstances, such as in an open-label study, missing visits may be related to treatment if the experimental treatment must be administrated at the site while the control treatment could be administrated at home, there may be more missing assessments in the control group. this may result in biased treatment effect estimates if mitigating strategies are not implemented. this could also be the case for a single cohort trial using an external control. sponsors should generally maintain the same approaches for handling of non-pandemicrelated missing data as originally planned in the protocol and sap. for pandemic-related missingness, appropriate strategies will need to be identified in the context of each estimand and analysis method. which strategy is most appropriate should be considered in light of the underlying context and reasons for missingness as shown in table and in alignment with the estimand for which the analysis is performed. three cases are described. ( ) when data are missing without the participant having an ice, i.e., participant continues to adhere to study treatment but has some endpoint values missing: the missing data modelling should be based on clinically plausible assumptions of what the missing values could have been given the fact the participant continues to adhere to study treatment and the participant's observed data. ( ) when data are modelled in presence of an ice: the strategy defined in the estimand for addressing that ice should be considered. provide an adequate selection of tools to deal with pandemic-related missingness (see e.g., molenberghs and kenward, ; nrc, ; ratitch, , mallinckrodt et al., ) . methods for dealing with missing data are often categorized based on the type of assumptions that can be made with respect to the missingness mechanism. using molenberghs and kenward ( ) 's classification of missingness mechanisms aligned with longitudinal trials with missing data, data are missing completely at random (mcar) if the probability of missingness is independent of all participant-related factors or, conditional upon appropriate pre-randomization covariates, the probability of missingness does not depend on either the observed or unobserved outcomes. (we note that in the framework of little and rubin ( ) , mcar is defined as independent of any observed or unobserved factors. this definition was subsequently generalized to encompass dependence on prerandomization covariates, also referred to as covariate-dependent missingness, and mcar is now used in the literature in both cases.) some types of pandemic-related missingness may be considered mcar, e.g., if it is due to a site suspending all activities related to clinical trials. consideration may be given to whether such participants should be excluded from the primary analysis set depending on the amount of data collected prior to or after the pandemic. for example, when all (most) data are missing for some participants, imputing their data based on a model from participants with available data would not add any new information to the inference, while excluding such participants is unlikely to introduce bias. when participants have data only for early visits before the expected treatment effect onset and the rest of the data are mcar, then including such participants in the analysis set may not add information for inference about treatment effect while adding uncertainty due to missing data. data are mar if, conditional upon appropriate (pre-randomization) covariates and observed outcomes (e.g., before participant discontinued from the study), the probability of missingness does not depend on unobserved outcomes. if relevant site-specific and participant-specific information related to missingness is collected during the study, most of the pandemic-related missingness can be considered mcar or mar. the definitions of mcar and mar mechanisms are based on conditional independence of missing data given a set of covariates and observed outcomes that explain missingness. the factors explaining pandemic-related missingness may include additional covariates and, in the case of mar, post-randomization outcomes. for example, missingness during the pandemic may depend on additional baseline characteristics, e.g., age and co-morbidities, as well as post-randomization pandemic-related outcomes, such as covid- infection complications. in the case of covariate-dependent missingness, regression adjustment for the appropriate baseline covariates is sufficient for correct inference, though this complicates the analysis model and the interpretation of the treatment effect for models such as logistic or cox regression where conditional and marginal treatment effect estimates do not agree. under mcar and mar, some modelling frameworks such as direct likelihood, e.g., mixed models for repeated measures (mmrm), can take advantage of separability between parameter spaces of the distribution of the outcome and that of missingness. in this case, missingness can be considered ignorable (molenberghs and kenward, ) , and the factors related only to missingness do not need to be included in the inference about marginal effects of treatment on outcome. this does not, however, apply to all inferential frameworks. multiple imputation (mi) methodology (rubin, ) may be helpful in this respect as it allows inclusion of auxiliary variables (both pre-and post-randomization) in the imputation model while utilizing the previously planned analysis model. multiple imputation with auxiliary variables may be used for various types of endpoints, including continuous, binary, count, and time-to-event and coupled with various inferential methods in the analysis step. the use of mi with rubin's rule for combining inferences from multiple imputed datasets may introduce some inefficiencies and impact study power, although some alternatives exist (see, e.g., schomaker and heumann, ; hughes et al., ) . for implementing a hypothetical strategy for covid- related ices in the context of time-to-event endpoints, regression models (e.g., cox regression) adjusted for relevant baseline covariates (in the mcar setting) or multiple imputation (in the mar setting) is recommended. competing risks analyses which treat pandemic-related ices that fully or partially censor the outcome, e.g., covid- related deaths, as competing events are not compatible with a hypothetical strategy. a further complication in the interpretation of competing risks analyses in this context is that participants are not at risk for the competing event from their time origin (e.g., randomization or start of treatment) onwards but only during the pandemic which is not experienced synchronously across the trial cohort. this compromises the validity of common competing risks analyses and prevents interpretation of results from such analyses to be generalized to the population. the implication of assuming specific missingness mechanism is that missing outcomes can be modelled using observed pre-randomization covariates or covariates and post-randomization outcomes (mar) from other "similar" participants, conditional on the observed data. for pandemic-related missingness, it is important to evaluate whether there are sufficient observed data from "similar" participants to perform such modelling, even if factors leading to missingness are known and collected. for example, if missingness and endpoint depend on age, and few older participants have available endpoint data, it may not be appropriate to model missing data of older participants using a model obtained primarily from available data of younger participants (possibly resulting in unreliable extrapolation). similarly, severe complications of a covid- infection may be due to these participants having a worse health state overall and modelling their outcomes based on data from participants without such complications may not be justifiable. additional assumptions about participants with missing data versus those with observed data may need to be postulated and justified, perhaps based on historical data. this is where the consideration of pandemic-related factors surrounding missingness, such as those mentioned in table , is important. pandemic-related missing data may need to be considered mnar if missingness and study outcomes depend on covid- related risk factors, treatment, and infection status but such data are not collected. the missingness mechanism may also be mnar if it depends on unobserved study outcomes. in the context of the pandemic, it may arise when participants with milder disease or lower treatment response are more inclined to discontinue the study or treatment and if their outcomes and reasons for discontinuation are not documented before discontinuation. analysis under mnar requires additional unverifiable assumptions but may be avoided through collection of relevant data. analysis of sensitivity to departures from mar assumptions should be considered, for example, models assuming plausible mnar mechanisms (see e.g., carpenter et al., ; mallinckrodt et al., ) . modifications to planned main analyses needed to handle pandemic-related missing data should be specified in the sap prior to study unblinding. see section . . for a discussion of sensitivity analyses with respect to missing data. additional sensitivity and supplementary analyses will frequently be required to assess the impact of pandemic-related disruptions on the trial. for non-pandemic-related events and missing data, the originally planned sensitivity analyses should be performed, but simply applying the pre-planned sensitivity analyses to both pandemic and non-pandemic ices and missing data may be problematic for three reasons. first, the objective to estimate treatment effects in the absence of a covid- pandemic may mandate different strategies for pandemic-related and unrelated events. second, as discussed in section . . , an mcar or mar assumption is frequently plausible for covid- -related events whereas this may not be the case for other missing data. third, sensitivity analyses to missing data could become excessively conservative if the amount of pandemic-related missing data is large. while a relatively large proportion of missing data could normally be indicative of issues in trial design and execution leading to greater uncertainty in trial results, that premise is tenuous when an excess of missing data is attributed to the pandemic. subgroup analyses for primary and secondary endpoints by enrolment or pandemic (see section . . ) period are recommended. if subgroup analyses are indicative of potential treatment effect heterogeneity, the potential for this to be rooted in regional differences should be considered. issues of multiregional clinical trials as described in ich ( ) may be magnified by the pandemic. in addition, dynamic period-dependent treatment effects could also be assessed in an exploratory fashion. for example, in models for longitudinal and time-to-event endpoints, one could include interaction terms between the treatment assignment and the exogenous time-varying covariate describing the patients' dynamic status during follow-up. however, results from such analyses may be nontrivial to interpret and generalize. more liberal visit time-windows may be appropriate for visits depending on the specific trial. sensitivity analyses should assess the robustness of results to out-of-schedule visits by either including them or treating them as missing data. a tipping point analysis (ratitch et al., ) may be used to assess how severe a departure from the missing data assumptions made by the main estimator must be to overturn the conclusions from the primary analysis. tipping point adjustments may vary between the pandemic vs. non-pandemic missingness and by reason of missingness. for example, one could tip missing data due to pandemic-unrelated missing data but use standard mar imputation for pandemic-related missing data. historical data may be useful to put in context the plausibility of the assumptions and tipping point adjustments. when main analysis relies on imputation techniques, sensitivity analyses can be done by using an extended set of variables in the imputation algorithm. when dealing with missing data in a context of intercurrent events handled with the hypothetical strategy, one could vary the assumed probability that the participant would have adhered to treatment through the end of the study vs that they would have had other non-pandemic-related events and impute their outcomes accordingly. for binary responder analysis, it is not uncommon to treat participants who have missing assessments as non-responders when a proportion of such cases is very small. for pandemic-related delayed and missed assessments, especially those occurring in absence of ices, it may be preferable to use a hypothetical strategy based on a mar assumption instead. however, anon-responder imputation for both non-pandemic and pandemic-related missing response assessments could be reported as a supplementary analysis. for time-toevent endpoints, we recommend the usage of interval-censored methods to account for cases where the event of interest is known to have occurred during a period of missing or delayed visits but the time to event is not precisely known in sensitivity analyses (bogaerts, komarek, and lesaffre, ) . alternative measurements of endpoints may be necessary during the pandemic period. a careful study-specific assessment is necessary to judge whether these alternative measurements are exchangeable with standard protocol assessments. ideally, exchangeability is established at the time of implementation based on information external to the trial. if not, blinded data analyses can support this, e.g. comparisons of the distribution of alternative measurements to the original measurement. however, if the validity of the new instrument has not been established previously, it will be challenging to rigorously demonstrate equivalence using data from the trial alone. if exchangeability can be established or assumed, the main estimator could include data from both the original and the alternative data collection. the sensitivity analysis would then include data collected according to the original protocol only and treat other data as missing. if the validity of the exchangeability assumption is uncertain, the opposite approach can be taken. modelling the interaction between treatment and assessment method can be undertaken as an alternate sensitivity analysis. outcomes it will be important to understand the pandemic effect on trial outcomes. there are several schools of thought on how this could be done. previous sections in this paper have described the need for collecting data describing how events such as missed visits and treatment interruptions can be attributed to the pandemic. these data are incorporated into definitions of pandemic-related ices and missing data, and the strategies for handling those in the analysis. statistical analyses of trial data will then be properly adjusted for pandemic effects. in many ways this is the ideal approach as it incorporates what is known for each participant directly into the analysis, and in a way that is very well understood. this is a standard approach to adjusting statistical analysis for inevitable perturbations in clinical trials. this approach has the disadvantage of needing to collect detailed data on pandemicrelatedness, which may not be feasible in some circumstances. another approach involves the use of pandemic time periods defined external to the trial database (e.g., to define pre-/during/post-pandemic phases as described in ema/chmp b). this approach requires the accurate and precise definition of pandemic periods. this is simpler to apply in single-country studies where the impact of the pandemic and local containment measures may be relatively homogeneous across participants. however, even for a single country, the pandemic may evolve in a gradual fashion, complicating the definition of pandemic start and stop dates, and the impact of the pandemic on study participants will likely not be homogenous. moreover, there may be several waves of infection outbreaks. the definition could prove even more challenging to implement in global trials because the start and stop dates of these periods and the impact of the pandemic on study participants may well vary by region. in practice, a standardized and pragmatic definition based on regionally reported numbers of covid- cases and deaths over time and/or start date and stop dates of local containment measures will likely be required. once pandemic periods have been defined, time-varying indicator variables for visits occurring during different pandemic periods could be incorporated as appropriate in statistical models or in ice definitions, as discussed previously. when this approach is used, the rationale for defining the pandemic start and stop dates should be documented. the situation is evolving rapidly and at this is point, it is not possible to provide definitive recommendation on the definition, implementation, and interpretation of these pandemic periods. in a third approach to generally assessing pandemic effects, each participant in the trial could be categorized according to the extent of pandemic impact on their treatment and assessments collected in the study database (details of protocol deviation, ices, missing assessments, pandemic-related reasons for discontinuation etc.). for trials with a fixed follow-up duration and minimal loss to follow-up, the categorization could be integrated in standard analyses, for example in defining subgroups for standard subgroup analysis. there is insufficient evidence currently to favour a single approach to this issue. sponsors are preparing to do at least the first two approaches, as these have been the subject of regulatory guidance. until we see how they play out and how the pandemic evolves, etc., it's sensible to consider multiple methods of summarizing pandemic effects. standard safety summaries will include all aes as usual. however, additional separate analyses may be needed for events associated with covid- infections and unassociated events, respectively, to fully understand the safety profile. the determination whether aes and, particularly, deaths are covid- related should be made during trial monitoring before data unblinding to avoid bias. in many situations, safety reporting will remain unchanged. however, disruptions due to the covid- pandemic may lead to increases in treatment interruptions, discontinuations and study withdrawals as well as the occurrence of covid- infections and deaths. hence, the estimands framework outlined in section could also be useful for safety analyses and we refer to (unkel et al, ) for a general discussion of estimands as well as time-to-event and competing risks analyses for safety. trials that require physical visits to adequately assess safety of the intervention will need to have maintained a schedule of physical visits to satisfy the requirement. generally addressing the potential for bias in collection of ae data is beyond the scope of this paper. exposure considering the compliance rate-or follow-up-adjusted analyses could be done, e.g., comparing the adjusted rates before and during the pandemic or with historical data. we don't have other methodological recommendations at this time, and more research is needed. the cumulative impact of missing data and revised statistical models discussed in the previous sections contribute to an overall study-level impact. the cumulative effect could alter the likelihood of meeting trial objectives, or even the interpretability of the trial results. sponsors should assess potential impact of missing data on several aspects and it may be important to reach agreement with regulatory agencies on some of these questions:  feasibility of planned estimation methods given the data expected to be available;  potential for bias in treatment effect estimation if there are important differences in missingness patterns across treatment arms;  study power for the primary and key secondary objectives;  interpretability of study findings;  adequacy of safety database due to potential reduction in total drug exposure time and potential for underreporting of aes;  adequacy of regional evidence required for regulatory submissions. as discussed in the previous sections, covid- related factors impact trial data in many ways with consequences for power of the study, probability of success, sample size or other aspects of the trial design. quantifying the potential effects of the various pandemic factors on trial results can be done through clinical trial simulations. the simulation models will depend on the factors used in the original trial design, and incorporate adjustments to estimands, missing data handling and analysis methods as discussed in sections and . to maintain trial integrity, the simulations should be informed only by blinded data from the study and the assumed values for the design parameters from external sources. variability and treatment effect estimates may be modified from their original values used in trial design. trial properties such as power and probability of success can be updated accordingly. sample size adjustment can be considered based on the simulation outcomes, or more extensive modifications of the trial design also may be considered such as change in the primary endpoint, analysis method, or addition of interim analysis with associated adaptation (posch and proschan ; kieser and friede ; muller and schaefer ) . such changes are challenging, and should be discussed with regulatory agencies, but can be considered if trial integrity is maintained. for some trials, it may not be feasible to increase sample size and the trial will fall short of enrollment target. given the extraordinary circumstances, we advocate more flexibility to consider methods for quantifying evidence across multiple trials and sources, including use of historical control arm data and real-world data, although sources and methodology for selection of such data would need to be planned and agreed with regulatory agencies in advance. if the observed treatment effect after data unblinding is meaningful but does not meet the statistical criterion due to covid- effects, the sponsor can evaluate whether the study results will be acceptable for registration on the basis of the accumulated evidence from the program; alternatively, whether the trial results could be used to define the inferential prior for a smaller follow up trial (viele et al ) . for a trial with a dmc, the sponsor should ensure that the dmc is well-informed of all measures taken to protect participant safety and to address operational issues. known or potential shortcomings of the data should be communicated. the timing of the regular preplanned safety interim analyses may need to be re-assessed. in addition, revised or additional data presentations may be needed. in some circumstances of interim analysis discussed in this section, a dmc may need to be established if not already in existence. there could also be circumstances related to participant safety where there may be a need to urgently review unblinded data, and establishing an internal dmc that is appropriately firewalled from the rest of the study team is recommended (e.g., studies without an existing dmc where it could take many months to organize an external dmc). efficacy interim analyses should be conducted as planned with information level (e.g., number of participants with primary endpoint or specific information fraction) as described in the protocol, which may cause a delay in the expected timeline. intermediate unplanned efficacy or futility interim analyses are generally discouraged unless there are safety and ethical considerations. however, if it is not feasible to reach the planned information level, altering the plan for interim analysis would need to be considered, for example with timing based on calendar time. in cases with strong scientific rationale for an unplanned interim analysis, the dmc should be informed and consulted on the time and logistics of the analysis. if an estimand, planned analysis methods, and/or decision rules have been changed to address pandemic-related disruptions and missing data, these changes should be communicated to the dmc and documented in the dmc charter. we do not generally advocate utilizing a dmc for operational risk assessment / mitigation process, to prevent influence of unblinded data on trial conduct decisions (ema/chmp , fda ). if the sponsor decides to involve the dmc, details should be clearly defined and documented in the dmc charter, including additional responsibilities of dmc members and measures to prevent introduction of bias. as we have discussed, the covid- outbreak continues to have major impact on planned and ongoing clinical trials. the effects on trial data have multiple implications. in many cases these may go beyond the individual clinical trial and will need to be considered when such results are included with other trial results, such as an integrated summary of efficacy or safety. our goal was to describe the nature of the statistical issues arising from covid- potential impact on ongoing clinical trials and make general recommendations for solutions to address the issues. the following are the most important findings and recommendations:  risk assessment, mitigation measures, and all changes to study conduct, data collection, and analysis must be documented in statistical analysis plans and clinical study reports as appropriate. some changes may necessitate protocol amendments and consultation with regulatory agencies (fda , ema a , b .  implications of the operational mitigations for the statistical analysis of the trial data should be considered before implementing those mitigations, especially for key efficacy and safety endpoints. validity and exchangeability of alternate methods of data collection require careful consideration.  the estimand framework, comprised of five key attributes, provides a pathway for assessing the impact of the pandemic on key study objectives in a systematic and structured manner and may be useful regardless of whether estimands are formally defined in the study protocol.  as much as possible, we recommend that original objectives of the trial be maintained; but some impact to planned estimands may be unavoidable. pandemicrelated intercurrent events will likely need to be defined to properly and rigorously account for unexpected pandemic effects.  planned efficacy and safety analyses should be reviewed carefully for changes needed to ensure that the estimators and missing data strategies align with updated estimands. additional sensitivity and supportive analyses will be needed to fully describe the impact of the pandemic-related disruptions.  sponsors should make every effort to minimize missing data without compromising safety of participants and study personnel and without placing undue burden on the healthcare system. priority should be on the assessments which determine the primary endpoint, important safety endpoints, followed by the key secondary efficacy endpoints.  most data that are missing due to pandemic reasons may be argued to be mcar or mar, especially if missingness is due to structural reasons, but additional considerations may apply, especially for certain diseases and participant-specific missingness.  sponsors should carry out rigorous and systematic risk assessment concerning trial and data integrity and update it regularly. the ability of trials to meet their objectives should be assessed quantitatively, taking account of the impacts on trial estimands, missing data and missing data handling, and needed modifications to analysis methods. european medicines agency committee for medicinal products for human use (ema/chmp guidance to sponsors on how to manage clinical trials during the covid- pandemic food and drug administration (fda) ( ), guidance for clinical trial sponsors: establishment and operation of clinical trial data monitoring committees guidance on conduct of clinical trials of medical products during covid- public health emergency, guidance for industry, investigators, and institutional review boards addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials general principles for planning and design of multiregional clinical trials survival analysis with interval-censored data: a practical approach estimation of treatment effect under non-proportional hazards and conditionally independent censoring analysis of longitudinal trials with protocol deviation: a framework for relevant, accessible assumptions, and inference via multiple imputation comparison of imputation variance estimators simple procedures for blinded sample size adjustment that do not affect the type i error rate aligning estimators with estimands in clinical trials: putting the ich e (r ) guidelines into practice estimands, estimators, and sensitivity analysis in clinical trials on the propensity score weighting analysis with survival outcome: estimands, estimation, and inference missing data in clinical studies statistical analysis with missing data a general statistical principle for changing a design any time during the course of a trial robust inference in discrete hazard models for randomized clinical trials the prevention and treatment of missing data in clinical trials clinical trials with missing data: a guide for practitioners unplanned adaptations before breaking the blind missing data in clinical trials: from clinical assumptions to statistical analysis using pattern mixture models multiple imputation for nonresponse in surveys treatment effect quantification for time-to-event endpoints -estimands, analysis strategies, and beyond bootstrap inference when using multiple imputation on estimands and the analysis of adverse events in the presence of varying follow-up times within the benefit assessment of therapies time-dependent bias was common in survival analyses published in leading clinical journals use of historical control data for assessing treatment effects in clinical trials group sequential and confirmatory adaptive designs in clinical trials we are grateful for the help of colleagues at each of our companies who have devoted much time to addressing these issues in their ongoing clinical trials. they have generously shared their ideas, and this manuscript has benefited from this broad input. we also thank the members of the "biopharmaceutical statistics leaders consortium" who brought the team of authors together and provided valuable input; and the associate editor and reviewers who provided extensive and helpful input within tight timelines. key: cord- - wck f authors: isaacs, david title: apocalypse perhaps date: - - journal: j paediatr child health doi: . /jpc. sha: doc_id: cord_uid: wck f nan unfolding of things not previously known or able to be known. the word has resonance for a pandemic which, by its very nature, involves an outbreak with an organism not previously known. in the bible's book of revelation, the apocalypse denotes the final destruction of the world (fig. ) . in common parlance, the word is often used to describe a massive catastrophe such as a world war. the link between a pandemic and the apocalypse is potentially petrifying. little wonder that pandemics engender panic. dates can be fateful. in chekhov's plays, people often die on their birthdays, a poignant dramatic device. william shakespeare died on his birthday. the exact starting date of the novel coronavirus pandemic covid- will never be known, but china informed the world health organization (who) about the disease on new year's eve, december . a few hours later and we might have called it covid- . transmission of severe acute respiratory syndrome (sars)-cov- , the virus that causes covid- , was accelerated by traditional travel of billion people for days before the chinese new year on january . the world has been preparing for a pandemic for decades and reacted swiftly to the - outbreak of sars and the h n influenza pandemic. however, the covid- pandemic has proved far more problematic than those two outbreaks. the mortality from sars was reportedly even higher than from covid- , but sars was controlled within months after infecting a mere people. in contrast, in fewer than months, sars-cov- has infected million people, killing over . sars-cov- is more infectious than sars because infected adults are infectious for anything up to days before they develop symptoms. if we can catch the disease from asymptomatic people, then every other adult in the world is a potential source of infection. the world is against us. no wonder passers-by keep their heads down and refuse to acknowledge our greeting or even smile back at us. while some countries have recommended or even mandated that every individual should protect themselves and others by wearing a mask in public, there is scant evidence of benefit. wearing masks in public arguably diminishes human connection just when physical distancing makes social connection most desirable. mask-wearing may frighten children and add to public fear. in his last novel, nemesis, pulitzer prize-winning american author philip roth describes the terror and panic caused by a fictitious epidemic of polio in in his home town of newark, new jersey. although allegorical, there are parallels with covid- , not the least being that polio too spreads silently from people who are infected but asymptomatic, a silent menace. responses to a pandemic are individual, dependent on personality and values. pessimists may predict doom and gloom; optimists may make light of the situation. nostradamus was not neutral. the doom-laden predictions of pessimistic 'catastrophisers' are coping mechanisms: if you predict the apocalypse, anything less is an improvement. human experience and response is contextual, varied and subjective and should not be unfairly judged. sometimes however, catastrophising can harm others in society. the damaging closure of australian schools, against the advice of the experts advising the chief medical officer brendan murphy, resulted from unresolved fears of parents and teachers, arguably fuelled by doomsayers prominent in the media. , unwarranted optimism may also be harmful; overly blasé people may fail to adhere to preventative measures, putting themselves and others at risk. when we feel threatened it is critical to know what and whom we can trust. trust is fragile in a pandemic when uncertainty is the norm. it would seem wise to heed the advice of health experts as regards how best to cope at a national level. , when the australian chief medical officer activated the pandemic emergency response plan, weeks before the world health organization declared a pandemic, the government was legally obliged to act. this has kept the pandemic under control in australia, avoided overwhelming the health-care system and kept the mortality low. in other countries, most notably the usa and the uk, expert advice was largely ignored, to disastrous effect. when it comes to personal protection, it would seem logical to listen and ideally trust the views of infection control experts. early stories of the deaths of health-care professionals in china, iran and europe understandably frightened their colleagues world-wide. infection control experts tried to offer reassurance that these deaths were almost certainly caused by failure to use personal protective equipment (ppe) rather than failure of ppe. but in a pandemic, 'almost certain' is not certain enough for all. some consultants have sought elusive 'certainty' by taking swabs to test for sars-cov- virus from all children admitted, despite a recommendation that wearing the same ppe would be appropriate, regardless of the result. fear of taking the virus home and infecting their family led some colleagues to request excessive ppe for themselves and their staff, potentially threatening supply. not judging people's motives does not preclude acting. inappropriate use of ppe jeopardises its availability for those most in need. inappropriate swabbing of children awaiting procedures can traumatise children, waste scarce resources and may delay urgent management. we should address harmful practices, preferably by civil negotiation, but if necessary by setting reasonable rules. data from china suggest that most transmission of sars-cov- occurred within households; nosocomial transmission to health-care staff was uncommon. a study screening symptomatic hospital staff in newcastle-on-tyne, uk found the same rate of sars-cov- infection in clinical and non-clinical staff. the authors conclude that staff were being infected through community transmission and that ppe was effective in protecting front-line health-care workers. humans often use war as a metaphor: the war against cancer: the war against drugs, the war against famine, the war against infection. people sometimes refer to broad-spectrum antibiotics (and cancer drugs) as 'magic bullets', an analogy as inaccurate as it is sinister. using the metaphor of war is a defensive manoeuvre which externalises the threat; in george orwell's classic novel , the dictator big brother invents an enemy state to fight against perpetually, thereby uniting his people. the war metaphor may resonate as we laud the courage of our front-line health-care workers, like heroic soldiers, going off to do battle. but war is scary, particularly to children, who are arguably at greater risk than adults of being scared by a pandemic. wars end in victory or defeat, with no middle ground. prevention is vital in limiting the spread of a pandemic; a war means diplomatic prevention has failed. at a time when world leaders want to blame each other for aspects of the covid- pandemic, the war metaphor is particularly menacing. in a pandemic, even more than in a war, solidarity is at a premium. we tolerate measures taken for public health reasons, such as restriction of movement and social contact, which infringe civil liberties under normal circumstances. if people fail to follow directions, some level of coercion, such as clearing beaches, may be needed and accepted by the public until viral transmission is controlled. there may be an expectation that we will shelve criticism of our government's response to the pandemic. where freedom of speech is valued, criticism may be tolerated. authoritarian regimes do not tolerate but suppress criticism. ophthalmologist dr li wenliang was made to sign a redaction saying he lied after alerting his colleagues in wuhan to the new respiratory disease; tragically, he died aged from covid- while trying to save others. more worrying are reports of medical workers in the uk being threatened with disciplinary action for raising workplace safety issues such as inadequate ppe. pandemics provide a concerning excuse for regimes to introduce new laws to silence critics which may not be repealed later. we should advocate that any measures that infringe civil liberties be proportionate and be reversed as the pandemic recedes. messaging is critical during a pandemic. the public should be informed regularly about progression of the pandemic, without increasing fear and engendering panic. people who are fearful need to feel their fears are not being dismissed or ignored. apocalyptic messaging may foment fear. reassurance without information to support optimism may paradoxically increase panic by raising doubts and losing trust. people who feel they have lost control of their destiny may be helped regain a measure of control. an example is to provide clear directions about how people can protect themselves and their family through physical distancing and hand hygiene. national pandemic responses vary depending on priorities: different leaders have prioritised saving lives and saving the economy differently. mental health is threatened by isolation, uncertainty and unemployment, leading to post-traumatic stress disorder, domestic violence, depression, and suicide risk. health-care staff are also at risk of mental health problems and moral injury. a one-size-fits-all approach can be disastrous in resource-poor countries, if physical distancing prevents employment, leading to starvation or prevents access to essential health services. hundreds of thousands have lost their lives. millions have been infected. the entire world has been affected. at present, many countries have started to relax their lockdown and allow survivors to try to resume their lives. for the survivors, the apocalypse is postponed. the pandemic is not over but the world lives on. now is a time for reflection: what did we do well, what should we have done better, how do we make the best of the current situation? there are positives as well as negatives to take from the pandemic. the environment has had a reprieve. initial unethical behaviour such as hoarding and profiteering has been offset by ethical human behaviour such as altruism and solidarity. let us emerge from this horrible pandemic sadder but wiser. ethical reflections on the covid- pandemic: the epidemiology of panic world health organization. who checklist for influenza pandemic preparedness planning. geneva: the organization learning from sars: preparing for the next disease outbreak: workshop summary presymptomatic sars-cov- infections and transmission in a skilled nursing facility do facemasks protect against covid- ? philip roth's story of a polio epidemic school closure and management practices during coronavirus outbreaks including covid- : a systematic review should i be worried about carrying the virus that causes covid- home on my clothes? ethical considerations for paediatrics during the covid - pandemic: a discussion paper from the australian paediatric clinical ethics collaboration characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention first experience of covid- screening of health-care workers in england offline: covid- -bewilderment and candour sars control and psychological effects of quarantine managing mental health challenges faced by healthcare workers during covid= pandemic has covid- subverted global health? thank you to mary cummins, chris elliot, annaleise howard-jones, stephen isaacs, ameneh khatami and anne preisz for helpful comments. editor-in-chief, children's hospital at westmead, sydney, new south wales, australia key: cord- - yxzj tw authors: chan, ho fai; skali, ahmed; savage, david; stadelmann, david; torgler, benno title: risk attitudes and human mobility during the covid- pandemic date: - - journal: nan doi: nan sha: doc_id: cord_uid: yxzj tw behavioral responses to pandemics are less shaped by actual mortality or hospitalization risks than they are by risk attitudes. we explore human mobility patterns as a measure of behavioral responses during the covid- pandemic. our results indicate that risk-taking attitude is a critical factor in predicting reduction in human mobility and increase social confinement around the globe. we find that the sharp decline in movement after the who (world health organization) declared covid- to be a pandemic can be attributed to risk attitudes. our results suggest that regions with risk-averse attitudes are more likely to adjust their behavioral activity in response to the declaration of a pandemic even before most official government lockdowns. further understanding of the basis of responses to epidemics, e.g., precautionary behavior, will help improve the containment of the spread of the virus. guarantee our survival. it is no coincidence that we are all well aware of the proverb "better safe than sorry". risk entails a complete probabilistic knowledge of something occurring, which allows a decision regarding what action to take. however, not only are we boundedly rational human beings ( ) subject to emotions ( ) such as fear, but the complexity of the environment and situation, the limited available information on contextual factors of other humans, or dynamic changes may not allow us to have a clear idea about the actual probability we face . in addition, calculating the probability of risk is not the same as actually perceiving it, and humans use less accurate heuristics to make judgments that also include perception of risk. our biases often disrupt our risk assessments in both positive and negative ways by limiting access to information (searches), limited cognitive understanding (noise), and through our own personal experiences. thus, subjective perceptions or emotional responses may be triggered by human traits or other factors. for example, we adjudge risk differently based on the physical distance between ourselves and the danger, i.e., we feel safer if the danger is further away, and we are less likely to continuously monitor it over an extended duration ( ) . this may work relatively well for traditional dangers like fires or floods, but the spread of a pandemic is invisible, and only media reports of those in hospital give any rough clue to its presence. as such, it is likely that we fail to correctly use local transmission (infection) rates as a guide of its proximity or distance to us and the level of threat it poses. risk as a feeling is less driven by actual probabilities and more by our instinctive and intuitive reaction to danger ( , p. ). risk-taking has often been classified as a stable personality trait ( ) , although situational or contextual factors can also matter (see, e.g., [ ] [ ] [ ] . an individual's risk type and their perception of risk are highly correlated, such that they interact to exacerbate the underlying risk type. that is: risk seekers are likely to have a worse perception of risk and not only are they willing to accept more gambles, but their estimations of the gambles are underweighted, leading to greater adoption of risk than the individual intended ( ) . in addition, we humans are also subject to framing biases, reacting differently depending on the way in which information is presented (e.g., positively or negatively, see ) . this framing can increase or decrease our willingness to take or avoid risk, especially where losses are concernedthe loss of life from contracting the virus is the ultimate loss. thus, preferences are not set in stone and are open to change, especially after we experience losses; i.e., an individual may be more risk-seeking following losses and risk-averse following gains ( , ( ) ( ) ( ) . feelings elicited during a pandemic have an impact on everyday activities ( ) and individuals are required to make trade-offs that are affected by their risk behavior. is it safe to go out shopping, to the park, to use public transportation etc.? what are the chances of getting infected? how do we need to respond? risk attitudes matter as individuals are aware that going into public places increases the possibility of being infected; if there was to be an infection, this would be subsequently regretted. risk-averse individuals may respond more to unfamiliar risks that are perceived as uncontrollable ( ) . during pandemics, states also may become more controllinghistorically, social mobility restrictions or regulations are common in pandemics. for example, anti-plague regulations banned funerals, processions, sale of clothing, and gatherings in public assemblies, all of which reduced opportunities for trade, and imposed severe penalties when those rules were not followed. community bonds might be destroyed if people lose the opportunity to, for example, grieve, pay final respects, or assemble ( ) . the level of social mobility in our current situation is interesting, as during this phase there is no real treatment or vaccination, which means that citizens need to rely on precautionary behavior. as the reality of the covid- outbreak emerged, we saw that states started to introduce social distancing and isolation measures to deal with the pandemic and the lack of a vaccine. in this article, we take a look at key social or human mobility factors related to retail and recreation, grocery stores and pharmacies, parks, transit stations, workplaces, and private residences. to measure risk-taking attitude, we use the global preference survey ( , ) , which analyzed risk at the country level by combining experimental lottery choice sequences using a staircase method (choice between a fixed lottery in which individual could win x or zero and varying sure payments) and self-assessment based on the willingness to take risks (see method section for more details). we then extended this data to obtain regional level information. exploring how risk attitude affects social mobility at the regional level is interesting as risk behavior can be seen as the product of an interplay between individuals, actions of others, and the community or social environment ( ) . risk is therefore deeply embedded in specific sociocultural backgrounds ( ) , with country and geographical differences in risk-taking reported by scholars such as ( ) (e.g., higher risk-taking values in africa and the middle east while western european countries are relatively risk-averse). in the context of a pandemic where a population is attempting social isolation or are in lockdown, we see that shopping behaviors change (drop) and large swathes of the workforce have lost their jobs, which means that the entire population has been directly affected by the pandemic if not the virus. it is therefore interesting to explore how citizens' responses to an epidemic are driven by risk attitudes or preferences at the community or regional level. in particular, we are interested in how individual behavior responses to global announcementssuch as the covid- outbreak classification as a pandemic by the who can be shaped by risk attitudes. we suggest that people in risk-taking environments may be less likely to respond and engage in behavioral change which reduces risk. we are also interested in comparing situations with higher or lower opportunity costs in human mobility. the opportunity costs of staying home are defined as the cost incurred by not enjoying the benefit of going out (benefits associated with the best alternative choice). for this, we explore differences between weekdays and the weekend. as many individuals are still working during the week, even while being at home, there is more psychological pressure to be active during the weekend, which increases the opportunity costs of staying at home. not going out requires more psychological costs to fight against previously formed habits, as it is difficult to abandon the way in which we are accustomed to act. we therefore hypothesize that regions with higher risk attitudes are less likely to follow precautionary strategies when opportunity costs are higher and are therefore are less likely to deviate from their outside activities during the weekend relative to the baseline. lastly, we also examine whether people adjust their behavior when living in a population with a larger proportion of older people at greater risk of more serious illness from contacting the virus. we expect that regions with a higher share of over individuals would show a greater reduction in mobility. in particular, risk-averse regions may display stronger mobility deviations from their original baseline (stronger reduction). we examined the relationship between the changes in human mobility during the outbreak of coronavirus disease and the average risk preferences of individuals in countries (with regions from countries with subnational regions data) . our main goal is to see if individuals in areas with higher (lower) levels of willingness to take risks are less (more) likely to reduce their exposure to social interactions by going to public places between feb and may . the outcome variables measure the daily changes (in percentage) in location visits compared to the median value of the same day of the week in the -week baseline period, during january and february . to see whether mobility changes are related to risk tolerance, we first regressed the each of the six mobility measures on risk-taking preference, namely, retail & recreation, grocery & pharmacy, parks, transit stations, workplaces, and residential. in each regression, we controlled for whether the day is a weekend, an indicator distinguishing our sample time period by the day when the world health organization (who) declared the covid- outbreak a pandemic ( march ) , the total number of confirmed cases per , people, number of days since the first confirmed coronavirus related death in the country , percentage of population over , population density (per squared km of land area), percentage of urban population, average household size, unemployment rate, per capita income (in logs), daily average temperature, and a set of indicators on government responses that covers recommending and requesting closure of school, workplace, public transport, stay at home, cancellation of public events, and restriction on gatherings and internal movement ( ) . consequently, our results regarding risk attitudes can be interpreted as independent of government lockdown measures. to this end, we employed a random-effects linear model to estimate the linear effect of risk-preference on mobility and linear interaction effects of risk and other covariates, namely, pandemic declaration, weekend, and the share of population over . as expected, we see an overall reduction in visits to all localities for almost all regions other than residential places, particularly in the earlier weeks in the sample period (see fig. ). interestingly, a large proportion of observations showed an increase in visits to parks, even in the earlier phase. examining the general relationship between risk attitude and the change in mobility in the entire sample period, we find some evident relationship to two most control variables report the expected effect on change in human mobility. specifically, there is a reduction in outings and an increase in staying home as severity increases, such as after the who declared coronavirus outbreak a global pandemic, increase in the number of case per population (except for parks and residential, in which the relationship is positive and significant at % level and not significant, respectively), and most lockdown measures (see supplementary table s ). we also find that, on average, there is a greater reduction in visits to retail and recreational places (β=- (table s ). markers represent the daily change in visits to the six locations for each region during the entire sample period , with different colors showing observations over time (from most blue (first week of the sample period) to yellow (middle of the sample period) to most red (last week of the sample period)). does the pandemic declaration increase the effect of risk-attitude? we examine the interaction between willingness to take risks and pandemic declaration to assess if the effect of risk-taking on mobility is evident. we find evidence suggesting the declaration is a strong for visualization purpose, we excluded the jammu and kashmir (india) region. moderator of the risk-mobility effect. it is relevant to note that the declaration of the pandemic precedes lockdown measures of most governments. we see that the reduction in outdoor activities (or increase in staying home) can be observed before covid- was declared a pandemic by the who, especially for visits to places classified as retail and recreation, transit stations, and workplaces (see fig. . we find that, with respect to risk preferences, the changes to visitation patterns (compared to their respective baseline) are relatively greater for areas with lower average willingness to take risk, following the pandemic declaration. specifically, we find the reduction in visits to grocery and pharmacy, transit stations, and workplaces prior to declaration is negatively correlated with willingness to take risk. however, interrogating the interaction terms between risk-taking and pandemic declaration revealed a more interesting nonetheless, the findings in our robustness checks (table s ) suggest that visits to grocery and pharmacy also decreased significantly after the pandemic declaration, which is also in line with the estimate obtained from table s . behavioral pattern; that is, the additional reduction in out-of-home activities after the declaration is much more dramatic for areas with more less risk-tolerating individuals. we found a statistically significant interaction effect on each of the outcome variables except for residential places (retail and recreation: β= . fig. ). it is also important to note that the pre-and post-declaration change in visitation pattern differences are smaller for higher risk-tolerance areas and vice versa, indicating that areas with higher average risk-taking are less likely to respond to the negative change in environmental status. the six panels show the predicted percentage change in visit to locations classified as retail and recreation, grocery and pharmacy, parks, transit stations, workplaces, and residential, compared to the respective baseline values, before and after who declared covid- as a pandemic on march , over average individual risk preference. estimates are obtained from table s , for illustration, predicted changes are calculated over five points of the risk-taking variable (at the st , th , th , th , and th percentiles of the distribution), which we categorized into five levels of willingness to take risk: very low, low, neutral, high, and very high, respectively. mobility patterns weekdays vs. weekends. next, we examine whether the tendency to change the frequency of visits to different localities during weekdays and weekends is mediated by risk attitude. as fig. table s in si appendix). moreover, we find that the mediation effect is more apparent after the declaration of pandemic, suggesting the effect manifests alongside severity. specifically, we reran the analysis including the interaction between the risk preference-weekend mediation effect and pandemic declaration dummy (triple interaction term). we visualized the results in fig. , showing the difference in average marginal effects of weekends (in contrast to weekdays) before and after the pandemic announcement, over levels of risk-taking (pre-and post-declaration average marginal effects of weekends is shown in fig. s and predicted change in mobility in fig. s ). we find that the tendency to reduce going out during the weekends compared to weekdays increases significantly with the levels of risk-tolerance for all nonresidential and work locations, particularly in the post-declaration period (retail recreation: these results are highly robust to our checks (see fig. s and table s in si appendix). the six panels show the difference in average marginal effects of weekends on visits to locations classified as retail and recreation, grocery and pharmacy, parks, transit stations, workplaces, and residential pre-and post-pandemic declaration periods, over risk-tolerance levels. estimates are obtained from table s ; for illustration, predicted changes are calculated over five points of the risk-taking variable (at the st , th , th , th , and th percentiles of the distribution), which we categorized into five levels of willingness to take risks: very low, low, neutral, high, and very high, respectively. actual risk. next, we examine the relationship between mobility changes, risk attitude, and proportion of elderly in the population to test if the relationship between mobility and risk is moderated by the share of population at higher risk of dying from covid- . we thus regressed change in mobility on willingness to take risk and share of population over and the interaction between the two (see fig. ). we found that areas with a larger population at table s ). moreover, we found a significant interaction effects on mobility of retail and the six panels show the predicted change in visits to locations classified as retail and recreation, grocery and pharmacy, parks, transit stations, workplaces, and residential, over risk-tolerance levels and the proportion of over s in the population. estimates are obtained from table s . as with plato's cave, there are stark differences between how we perceive risk and the reality or the calculated level of risk, which can result in totally different behavioral outcomes. risk attitudes clearly shape behavioral responses to pandemics. the actual health risks of the covid- pandemic are (most likely) low for most groups apart from the elderly ( , ) . in terms of mortality, the overall health consequences of covid- could be similar to a pandemic influenza ( ) . nevertheless, risk attituderather than actual riskinfluence real behavioral activity. our results demonstrate the sharp shifts in the relation between behavioral activity and risk attitudes before and after declaration of covid- as a pandemic, as well as shifts before and after the first related death was recorded. the first thing that becomes apparent is that behavior and our willingness to take on risks have both shifted dramatically since the baseline period in mid-february. at this stage, only three deaths were recorded outside mainland china (one in hong kong, japan, and the philippines) and life was proceeding as normal. there was no imminent perception of a threat of the worldwide pandemic to come, reflected in the baseline reporting of behavior and the willingness to take risks. however, when we compare this to the first and second sample period, we observe mostly negative shifts in behavior (excluding residential) but a mixed set of reactions to risk. several categories saw a substantial negative shift in visits, including retail & recreation, transit stations, and workplaces; compared to the baseline, visiting behaviors had already started to drop off before the pandemic announcement but dropped off again afterward. during this first period, we can see that social distancing and work from home was starting to make an impact, as people stopped travelling to and from work (especially through crowded transit stations) and also stopped engaging in non-essential retail shopping (therapy). after the pandemic was officially announced, we see a second wave of behavioral shifts as more people reduce their travel, shopping and more either lose their jobs or are in shutdown mode. however, we do observe an interesting shift in risk attitudes across these three categories as they all exhibit a slightly positive trend in the period before the announcement, but they all shift to a much stronger negative risk trend after the announcement. given that 'flattening the curve' was the strategic focus for most governments, the social distancing message appears to have been received even prior to most lockdown measures. conversely, grocery & pharmacy, parks, and residential had much smaller shifts both before and after the announcements when compared to the baseline. however, the shifts in grocery & pharmacy and parkswhile much smaller than the other categoriesappear to undergo a large risk preference-mobility shift; that is, the first set of behavioral changes results in a positive sloping risk function that flipped into a negative sloped function after the pandemic announcement. while seemingly at odds with expectations, one may want to consider what the announcement of the pandemic would have meant to most individuals. with a looming threat of lockdown and isolation, at this point individuals would have ramped up shopping to stock up for likely upcoming government lockdown. in addition, those with an affinity for the outdoors may have wanted to enjoy their parks and outdoor lifestyle as much as possible before it was banned. this is in line with the reported shifts in the number of visits, which while still negative overall, indicate that the change to number of visits is less negative than prior to the announcement. the odd one out is the residential visits category; while small, we can still observe double increases in visitation numbers both pre and post the official pandemic announcement, and there is no change in the function representing the willingness to take risks. when interpreting these statistics, we need to bear in mind the 'normal' weekly habits of people; that is, work during the week and undertake other activities/pastimes on the weekends. in order to ensure we capture the shift in behavior, we compare the weekday behaviors and risk attitudes to that of the weekends. our result demonstrates that there are a few differences between weekdays and weekends, as one would expect that on weekends there are slightly more activities taking place other than work. furthermore, we see little variance in the slopes of weekdays and weekends risk attitudes. the large negative shifts across all categories except workplaces after the official declaration, but much smaller variations between weekdays and weekends before the declaration, further supports the discussion above: that the behavior had already started to change well before the declaration of a pandemic, with many individuals starting to increase their weekend activities. however, after the pandemic was announced, a raft of measures that tried to limit the spread of the virus resulted in a very large change in most economies due to closure of businesses and job losses. this fundamental change in economic activities and loss of work left very little to differentiate weekends from weekdays for a large number of people, which is reflected in the large negative changes in the comparisons. prior to the announcement, we see that the function on willingness to take risk is fairly flat or slightly downward sloping, but risk perceptions change significantly for all categories after the announcement. the most interesting changes are in workplace and residential, exhibiting a relatively large increase in the willingness to take high risks: this could be explained through people wanting to visit family and friends or the increased willingness to work despite the risk of infection. in general, throughout our analysis we observe that less risk-tolerating regions more actively adjust their behavioral patterns in response to the pandemic. risk seeking regions are less responsive to protective measures. thus, the tendency towards being more careless or more cautious carries substantial behavioral implications that is also affected by different levels of opportunity costs, as evidenced by the weekend effect. regional differences seem to matter, offering support for a "regional personality factor" in risk taking. as with individuals who allocate themselves to more risky professions there are regions that are likely more likely acting as "stunt persons", "fire-fighter", or "race-car driver regions". risk takers therefore seem to demonstrate a lower preference for their own and communal safety, as demonstrated that risk averse regions with higher percentages of + people are more actively to increase social isolation by staying at home. such behavioral differences due to risk preferences may indicate different levels of homeostatic responses. risk aversion seems to promote a stronger fluctuation around a target level. for example, if you are driving on a motorway and it starts to rain or snow, what do you do? our result would imply that risk averse individuals may be more likely to slow down to reduce the likelihood of having an accident. risk averse individuals have a higher need for risk compensation. thus, the level of risk at which a person feels best is maintained homeostatically in relation to factors such as emotional or physiological experiences ( ) . overall, the lack of adjustment among risk taking regions is interesting, as many settings that explore risk taking behavior are connected to the possibility of attracting social fame and praise, financial gains, or other potential positive outcomes. in our setting, the risks are strongly attached to the loss of their own and other's health or life without achieving major gains, although positive utility gains also arise from not restricting one's usual activities. it seems like the risk takers are more "pathologically" stable during such environmentally challenging circumstances. it is almost as if risk taking regions are more determined to maintain settings as activity-oriented, while risk averse regions are more goaloriented in achieving social distancing. the current analysis is interesting, as a large number of studies exploring the implications of risk are based on cross-sectional samples or between-subject designs in laboratory settings. in this case, the danger is more prolonged, lasting over several weeks or months, compared with other risk situations such as driving a car. automatic or response "scripts" become less relevant as individuals have the chance to think about their actions and adjust their behavior accordingly. strategic, tactical, or operational factors become more dominant while perceptual, emotional, and motivational factors remain active. in addition, individuals do not face a single "either-or" decision but are required to constantly evaluate their choices to go out or stay at home. thus, cognitive reevaluation is a core feature in our setting, and is based on dynamic feedback loops. risk loving regions are also less likely to adjust their behavior based on external stimulus such as the who announcement of classifying covid- as a pandemic. a core limitation is that we are only able to explore human behavior at the regional and not individual level. studies that use individual data could focus in more detail on individual differences such as age or gender or differences in affective reactions or perceived locus of control and could try to disentangle perceptions (risk preferences) partly from actual risk as statistics provide detailed information on the actual age risk profile. such a study would provide a better understanding of habit changes, as well as potentially reveal motivational reasons for behavioral changes or behavioral stickiness. to reduce levels of uncertainty or ambiguity, individuals will try to gain control over a situation or they will change their preferences to better the fit the situation, and thus try to gain control in a secondary way ( ) . other psychological factors such as overconfidence may also matter. in addition, we do not have information about the actual level of social mobility in the baseline time period. if that information were available, one could argue that those who had the highest levels of mobility prior to the lockdown have had the largest relative loss; we should therefore observe this group exhibiting the most risk seeking behavior and breaking the lockdown rules. on the other hand, those who previously had the least amount of social mobility have in relative terms only suffered a small lossand should be much less likely to break the lockdown rules. however, this may adjust over time, as individuals habituate to the changes and reset their reference points. this fits nicely into the suggestion that "a person who has not made peace with his losses is likely to accept gambles that would be unacceptable to him otherwise" ( , p. ), which is consistent with risk preference changes in a disaster situation ( ). risk is a fascinating topic as we have two forces in place. based on evolutionary theory, people are risk-inclined but also control-inclined. risk taking is necessary to cope with environmental changes and the constant level of uncertainty and danger. on other hand, control of the environment is required to reduce risks that go beyond the desired levels or that may pose danger to one's survival ( ) . the pandemic declaration caused a fundamental shift in behavior, independently of government lockdown measures. future studies could explore in more detail how information dissemination and media reporting are connected to behavioral responses and the level of risk taking within regions. removal of the lockdown policies is likely to be undertaken cautiously and slowly rather than via one large change. it is unclear at this stage how changesparticularly among the risk averse regionshave already led to new habit formation that will not readjust to previously normal settings. future studies will provide more insights into such a question. mobility. we obtained the mobility measures on country and regional level from the covid- community mobility reports ( ) table s to s in si appendix). we obtain the measure of risk preference from the globally representative global preferences survey collected in using the gallup world poll ( , ) , which is aggregated into the country (n= ) and regional (n= , ) level. risk preferences of the respondents were elicited through a qualitative question (self-rated perceived risk preference on a -point scale) and a set of quantitative questions using the staircase method, where respondents were asked to choose between varying sure payments and a fixed lottery, in which the individual could win x with some probability p or zero. the responses from the two questions were combined (with roughly equal weights) to produce the overall individual risk preference measure ( ) . for subnational regions where both mobility measures and risk preference measures are available at the region levels, we employed the regional aggregated combining datasets. to join datasets together for our analysis, we use regions defined in the google mobility dataset as our point of reference. in general, for regions with mobility measures but not from another dataset (i.e., risk attitude or average daily temperature is unavailable for that region), we employ its country values. the resulting number of countries in our final sample is , after merging all variables used in this study, with a total of subnational regions from countries (see table s in si appendix). the total number of region-day observations ranges from , to , , depending on the availability of mobility measures. to examine the main question of how mobility patterns during the covid- outbreak change according to risk attitude, we analyzed the data using random-effects linear model. standard errors are clustered on the smallest geographic unit in each regression. data and codes used in this study can be found on open science framework (https://osf.io/ bxqp/). this section presents the checks for robustness of our results, which are shown in table s to s for the six sets of regressions conducted in the main text, respectively. the first two checks concern including regions with censored mobility value in the sample of the analysis. for the overall risk-mobility relationship (comparing estimates from table s to . this suggests that the tendency to further reduce mobility on the weekends than during the week for low risk-tolerance regions (as compared to high risk-tolerance regions) is evident before pandemic declaration. moreover, we see that the results with triple interactions between risk preference, weekend, and pandemic declaration resembles to that in the main text, albeit for regions with very high risk preference, the preand post-declaration difference in the weekend reduction in mobility is less precisely estimated in the second sample restriction, in particular for retail and recreation, grocery and pharmacy, and parks. lastly, we found some of the estimates of the risk preference-risk pool interaction terms is similar to that in the main analysis. for retail & recreation, the first exclusion rule figure in the main text. random-effects gls regression estimates. standard errors (clustered at regional level) in parentheses. † p < . ; * p < . ; ** p < . ; *** p < . . reference categories are: before who declares covid- as pandemic, weekdays and no measures taken for all government response indicators. figure in the main text. random-effects gls regression estimates. standard errors (clustered at regional level) in parentheses. † p < . ; * p < . ; ** p < . ; *** p < . . reference categories are: before who declares covid- as pandemic, weekdays and no measures taken for all government response indicators. figure in the main text. random-effects gls regression estimates. standard errors (clustered at regional level) in parentheses. † p < . ; * p < . ; ** p < . ; *** p < . . reference categories are: before who declares covid- as pandemic, weekdays and no measures taken for all government response indicators. figure in the main text and supplementary figures s and s . random-effects gls regression estimates. standard errors (clustered at regional level) in parentheses. † p < . ; * p < . ; ** p < . ; *** p < . . reference categories are: before who declares covid- as pandemic, weekdays and no measures taken for all government response indicators. figure in the main text. random-effects gls regression estimates. standard errors (clustered at regional level) in parentheses. † p < . ; * p < . ; ** p < . ; *** p < . . reference categories are: before who declares covid- as pandemic, weekdays and no measures taken for all government response indicators. with at least one censored values on the outcome mobility measures excluded. robust = regions with at least one censored values on any mobility measures excluded. robust = government response indicators recoded as no measures taken if policy is not applied countrywide. random-effects gls regression estimates. standard errors (clustered at regional level) in parentheses. † p < . ; * p < . ; ** p < . ; *** p < . . we controlled for the day since first confirmed death, share of population over , number of confirmed cases (in logs), population density, and the set of government response indicators in each regression. reference categories are: before who declares covid- as pandemic, weekdays and no measures taken. notes: robust = regions with at least one censored values on the outcome mobility measures excluded. robust = regions with at least one censored values on any mobility measures excluded. robust = government response indicators recoded as no measures taken if policy is not applied countrywide. random-effects gls regression estimates. standard errors (clustered at regional level) in parentheses. † p < . ; * p < . ; ** p < . ; *** p < . . we controlled for weekend dummy, pandemic declaration dummy, days since first confirmed death, number of confirmed cases (in logs), population density, and the set of government response indicators in each regression. reference categories are: before who declares covid- as pandemic, weekdays and no measures taken. epidemics and society: from the black death to the present certified coronavirus immunity as a resource and strategy to cope with pandemic costs using social and behavioral science to support covid- pandemic response risk theory in epidemic times: sex, drugs and the social organisation of 'risk behavior social and behavioral aspects of the hiv epidemic-a review risk perception in epidemic modeling risk perception and behavioral change during epidemics: comparing models of individual and collective learning risk loving after the storm: a bayesian-network study of hurricane katrina evacuees risk-taking behavior in the wake of natural disasters variation in risk seeking behavior following large losses: a natural experiment personality and individual characteristics as indicators of lifetime climbing success among everest mountaineers risk preferences around the world experimental methods: eliciting risk preferences advances in prospect theory: cumulative representation of uncertainty risk aversion in the small and in the large risk aversion and expected-utility theory: a calibration theorem prospect theory: for risk and ambiguity the psychology of risk taking behavior the feeling of risk: new perspectives on risk perception life history variables and risk-taking propensity bounded rationality and organizational learning reason in human affairs emotions, risk perceptions and precautionary behavior under the threat of terror attacks: a field study among israeli college students risk-taking behavior" in wiley series in human performance and cognition the presence of an attractive woman elevates testosterone and physical risk taking in young men the ambiguities of experience perceived risk, trust, and democracy are risk preferences stable prospect theory: an analysis of decision under risk an experimental examination of the house money effect in a multi-period setting deal or no deal? decision making under risk in a large-payoff game show gambling with the house money and trying to break even: the effects of prior outcomes on risky choice affect, risk perception and future optimism after the tsunami disaster risk perceptions and behavior: towards pandemic control of emerging infectious diseases global evidence on economic preferences the preference survey module: a validated instrument for measuring risk, time, and social preferences heading into the unknown: everyday strategies for managing risk and uncertainty oxford covid- government response tracker, blavatnik school of government coronavirus disease : the harms of exaggerated information and nonevidence-based measures contopoulos-ioannidis, population-level covid- mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters covid- -navigating the uncharted a global dataset of human mobility for united nations, department of economic and social affairs, population division. database on household size and composition the free encyclopedia. workweek and weekend global historical climatology network -daily (ghcn-daily), version . noaa national climatic data center an overview of the global historical climatology network-daily database we received no specific funding for this work. we thank d. johnston for helpful feedback. the authors declare no competing interests. key: cord- - if qquj authors: nan title: perspectives on the economics of the environment in the shadow of coronavirus date: - - journal: environ resour econ (dordr) doi: . /s - - - sha: doc_id: cord_uid: if qquj nan the environmental and resource economics special issue "economics of the environment in the shadow of coronavirus" comes at a hugely critical time for environmental economists and policy makers alike. we are in a situation of significant social change, a change that could potentially lay the foundation for mankind's future in the years to come. as part of this special issue, ere is trialling a novel, experimental form of article, drawing together short, focussed pieces from a wide group of authors addressing the plethora of issues which such a fundamental challenge as the coronavirus pandemic generates. these provide critical and reflective perspectives on the environmental, socio-economic and policy paths that may be taken in the near and further future-strategies that could lead mankind either on roads to a much more sustainable development, or along paths that could bring about more instability, inequality and further environmental pressures. this innovative article combines short, policy-relevant and less technical papers that deal with specific aspects and provide clear recommendations for policy makers and suggestions for future research alike. the target audiences are policy makers and companies, but also researchers who want quick yet sufficiently detailed knowledge about particular analyses relating to covid- and issues in environmental economics. we hope that the articles contained within this perspectives collection provide the necessary information for policy makers to take wise decisions for our future, and for researchers the knowledge to help guide policy makers in their decisions. humankind has been very fortunate to have lived through a period of sustained economic growth pretty much since the agricultural revolution, with especially high rates of growth starting from the second half of the twentieth century. this economic progress has allowed us to make unprecedented improvements in consumption, in health, in education and in addressing inequality. many of us have been fortunate enough to have lived without a war for the past years, which is widely believed to be due to the development of international institutions and a deepening of international trade that led to widespread cooperation and, with it, it brought a new era of global stability. at the same time, the rapid increases in humankind's population, from around billion in to . billion in , coupled with an increase in real-world gdp by a factor of roughly during the same period, have led mankind to progressively push closer to the boundaries of planet earth. to provide additional food for the surge in population, agricultural land use has increased by %; to provide goods and services for the surge in demand, the material footprint of our production increased by an estimated factor of ; and to provide energy for our lifestyles, our use of non-renewable and polluting resources (coal, oil, gas) increased by a factor of . this increase in consumption coupled with a similar increase in input use has transformed the face of the planet earth and has given rise to unwanted side effects and new challenges. some of these challenges are well known, such as local and global pollution, problems of waste and certainly climate change. another, often neglected challenge, has been a consistent pressure on biodiversity due to our increase in land use. a mixture of burgeoning population and increasing resource use that carved deeply in nature's pristine areas has led to species conflict manifested not only in the rapid loss of other species, but also in a much ignored yet increasingly visible negative feedback in the form of viral crossovers (smith et al. ). the linkages between economic development, viral crossovers in the form of communicable diseases and environmental issues in particular have, up to now, seen little attention from environmental economists. as we have now seen, it was worryingly neglectful on our part to not consider these feedbacks more seriously. the greater interconnectedness via global trade and international migration, air travel for both tourism and business purposes, as well as the ongoing growth of large city hubs, have made it easy for communicable diseases to transcend local spaces and quickly make their appearance in even remote corners of the world. while the black death and the spanish flu have been among the worst communicable disease outbreaks in recent history, in late a new virus was detected in wuhan, china. identified as a new member of the coronavirus family and subsequently called covid- , within the course of half a year this virus has spread out from the huanan wet market in wuhan across the whole world. even inhabitants from otherwise remote places such as villages in timbuktu, the korubo and yanomami tribes of the amazon, the navajo nation of north america and the arctic inuit have already tested positive for due to initial uncertainty surrounding both the impact of covid- and its spread through society, many policy makers quickly decided to shut down interactions among individuals by restricting local, national and international mobility. these "lockdowns" had pervasive impacts on economic activity across the globe, with significant reductions in production, increases in unemployment, falls in international migration, diminished levels of international trade, significant increases in bankruptcy filings and large ripple effects down supply chains. relative impacts between developed and developing countries are still very much developing. globally, herd immunity is expected to take some time to develop if indeed it ever does. a vaccine that has the potential to be potent and widely available may need at least another or years for development and broad deployment. some countries are already close to a second wave-this pandemic is here to stay for a while. the question is as to how we shall deal with it. while reducing physical contacts to "flatten the curve" of disease and death has been the preferred policy to slow down the spread of the were advocating for. it is at this point where the contributions selected for this special issue provide first thoughts, first answers and first suggestions for policy makers from the cuttingedge research of environmental economists. in particular, the arguments forwarded support a strengthened focus on economic recovery that, first and foremost, should not undermine the green transition, while also, if possible, provide measures to advance the green transition. the articles then discuss the approaches and potential difficulties that policy makers will be faced with when being confronted with the precise means to implement these green recoveries. as a first step, due to unprecedented levels of unemployment in places such as the usa and significant contractions to economic growth in most countries of the world, an important consideration is that the focus of the stimuli packages should be the economic recovery, i.e. to predominantly deal with the direct impact of the lockdowns on economic activity. once the virus is contained and the short-run recoveries are under way, then it is, however, important to quickly integrate longer-term factors into policy making (borghesi and co-authors). here, it is vital that, in contrast to the stimuli in the aftermath of the financial crisis, policy makers also address inequality (koundouri and co-authors). a more specific focus on furthering a green transition should only be placed once a certain level of economic recovery has been achieved. this is especially vital as the disruptions to supply chains can have fundamental and unpredictable consequences, as often even companies themselves are not fully aware of their complete supply chains. cazcarro and co-authors estimate some of the impacts of these trade-related supply chains and, for example, show that the european demand changes due to covid- have, in total, larger impacts on the rest of the world than on europe itself. requirements for successful green stimuli are that these policies are implemented in a clear and transparent manner (rickels and peterson). in this regard, ing and nicolai argue that companies are likely to prefer stimuli packages that are tight to some environmental efforts rather than to new environmental regulations. on the converse, linking stimuli with environmental efforts is more costly for policy makers and likely to be less efficient. several of the articles in this special issue draw particular attention to the fact that the green stimuli are not enough to successfully further a green transition. what is also necessary is to couple this with a price on carbon and a restructuring of the subsidies paying attention to both the green and fossil industry (gawel and lehmann). a stronger social contract with a higher degree of citizen involvement will furthermore help gain public support but also strengthen social norms and thus decentralized internalization of externalities. lopez-feldman and co-authors discuss the policy responses to covid- with a focus on latin america and argue that, to minimize the likely rebound effect, policies need to be much better coordinated. we have seen that international cooperation quickly breaks down when a crisis looms, so that it would make sense to design international institutions with binding laws and penalties in case of non-compliance. what we have seen so far is that covid- has the potential to become a game changer when it comes to combining stimulus packages with the green transition. that this is a sensible strategy derives from the observation that restricting global warming to . °c requires efforts that go beyond what countries were willing to do so far, and that the stimuli provide the needed opportunity. while the articles contained in this special issue already provide many reasons for policy makers to push for green stimuli, they also clearly point out the difficulties associated with implementing these well. some articles in this special issue also show limitations of current policies or research approaches. for example, borghesi and co-authors discuss that during the covid- crisis the market stability reserve helped to stabilize the eu ets price, but imperfectly. it is, therefore, important to consider ways in which these imperfections can be redesigned. on a different topic, laude explains how the covid- crisis has brought to light both advantages and problems with having local, short supply chains for food, and that there is a substantial lack of research directed towards the impact of crises on the agricultural sector. another example is a more cautionary tale and deals with the covid- cases data. here, cohen and co-authors show very clearly that researchers must be careful with simply using these data as there are many problems in the data collection processes, which differ across countries and also time. as a final remark, we would like to observe that this special issue not only comes at a very turbulent time for mankind in general, but it also comes at a special time for environmental economists in particular. the covid- crisis gives the opportunity to invest significant amounts of money towards aiding the green transition, and the widespread public support is there. we need to now be able to advise policy makers on efficient, reasonable and relevant policies that they may implement as part of the green stimuli packages. however, these policies also need to be well structured and grounded in good research. the peer-reviewed articles in this special issue provide suggestions and articles with these features and will thus, hopefully, serve as a first benchmark in this endeavour. in this paper, we use a multisectoral and multiregional model of the world economy to evaluate the short-term effects that the covid- crisis may have on environmental pressures and resource consumption (measured in terms of water, air emissions and materials extraction). specifically, we focus on the relationship between current and forecast changes in demand and mobility patterns in the eu + uk for and its effect on global resources through global supply chains. this integrated analysis could answer urgent research questions: what are the short-term impacts on emissions and resource consumption of the current and predicted declines in final demand? do the impacts differ among environmental pressures? how elastic are environmental responses to demand drops? on the basis of these short-term responses, what is the relationship between economic growth and environmental pressure? do these effects go beyond european countries through global supply chains? in order to evaluate the short-term effects of changes in aggregated sectoral consumption and demand on environmental pressures, and their diffusion through global supply chains, we develop an environmentally extended multiregional input-output model (see miller and blair , or recently hubacek et al. ; guan et al. ), using the exiobase . database (stadler et al. ) . we focus on water consumption (blue and green), mineral extraction and emissions (co eq , sox, nox, nh and co). we rely on the estimates from the eurostat spring forecast (ec a) which estimate for the eu + uk a change of − % in consumer expenditure, . % in government expenditure and − . % in investment for . sectoral changes in private consumption are estimated based on ec ( b) and oecd ( ), assuming different sectoral sensitivities to the covid- crisis. specific details and the complete matching process can be found in online appendix. our results are as follows: figure shows the eu + uk (light blue bars) and global (dark blue bars) change in different environmental pressures associated with the shock to final demand and household mobility in eu + uk, as a consequence of the covid- lockdown. the expected percentage impacts are much larger in the eu + uk, as the simulation of final demand and mobility directly affects these countries, given the high level of intra-eu dependence. however, the european lockdown also impacts foreign resources due to the interlinkages throughout the production chain. in general, the largest decline happens to gas emissions, both in eu + uk and worldwide. the average . % fall in the aggregate of the three cited components of european final demand (households, government expenditure and investment, representing a . % fall in total final demand) that globally represents a . % decline, would involve a . % decline in global water consumption and . % in mineral extraction. the global fall in emissions from the slowdown in economic activity and european mobility restrictions would be around . % (co eq ). comparing the effect in eu + uk with the global impact, the percentage change runs from four times larger in europe, in the case of water, to times greater for co eq emissions. we find a drop of more than % for mineral extraction and emissions in eu + uk. emissions are reduced, and by more than water and minerals. also, even when no direct electricity demand change is assumed, given the reduction in sector activity, indirect energy demand diminishes and so do emissions. specifically, our model indicates that the production and supply of electricity explain approximately % of the greenhouse emissions fall worldwide and % in the eu + uk. in line with the results of le quéré et al. ( ) , our estimates confirm that the reduction of emissions associated with private mobility restrictions would account for % of the total fall in emissions in europe, whereas the reduction linked to air travel reaches . %. worldwide, these drops would be % and %, respectively. the european lockdown affects the iron and steel industries globally, representing % of the global fall in greenhouse emissions. several other resources are less dependent on the most-affected sectors. the supply chain of food clearly depends on the supply of water. it is difficult to estimate the reductions in the horeca sector based on the available data. that sector, as well as many others that indirectly require these natural factors throughout their supply chains, exhibits significant reductions in resource use. our data show that the largest decline in water consumption (both blue and green) is associated with the primary sectors, which, as expected, experience slight negative growth rates around − . %, given the relatively stable and anticyclical nature of food demand. analysing the changes induced by the different components of final demand, the decrease in household consumption and investment drives environmental impacts to a lesser extent. worldwide, the fall in investment mainly affects environmental impacts (except for water consumption). reductions in investment have a larger role in reducing emissions in small countries like croatia and malta, and also in eastern europe, such as in hungary, latvia, and slovenia. in the eu + uk, household consumption is the most significant element of final demand driving the changes in environmental pressures (with the exception of mineral extraction), explaining % of the european greenhouse gas emissions fall. as for minerals, their strong dependency on gross capital formation destinations, such as construction, manufacture of machinery and equipment, computer and related activities, explains that the . % fall in investment worldwide (- . % in eu + uk) triggers a . % drop in their global extraction (− . % in europe). these changes are distinct by country, with implications for different areas of the world. the intra-eu trade is revealed to be highly important, showing that the main changes occur within the eu + uk countries (even if the individual shock of a given country is not so significant). figure displays the percentage falls in co eq , so x , no x and nh emissions by eu + uk country. according to the projected changes, the greatest cuts are expected in co eq emissions. almost a quarter of the estimated reduction in co eq emissions occur in germany (figure si ) . the reductions in co eq emissions in smaller economies, such as ireland, austria, greece, and cyprus exhibit the largest percentage falls. reductions in mediterranean and eastern countries are high, mainly in large countries like france, romania, portugal, and spain. we note the potential reduction in no x emissions as a consequence of the production shutdown in france and germany (as it occurs with nh emissions), but the largest percentage drops occur in smaller economies, like austria, ireland, and greece. france also shows the highest reductions in so x emissions, together with poland and germany, ireland and smaller countries. our model also allows us to evaluate how the reduction in the eu + uk demand modifies the pressures on environmental resources outside europe, by considering transmission effects through global supply chains. the largest percentage reduction in domestic impacts arising from the lockdown and subsequent situations in europe occurs in non-european developed countries, with smaller effects in developing economies (fig. ) . we find considerable indirect declines in mineral extraction (larger than %) and gas emissions (between − . and − . %) in the usa and japan. these are mostly associated with linkages with italy, germany, uk and france. in countries such as china, brazil and india, none of the falls in environmental pressure exceeds . % (with the exception of a % fall in mineral extraction in india). again, we find important declines related to the commercial linkages of developing countries with european powers, such as france, germany and the uk, and with other european countries severely affected by the pandemic (and thus their final demand), such as italy and spain. these results support the statements of baldwin and mauro ( ) on the existence of a "supply-chain contagion" related to the covid- lockdown (in europe in this study). however, the "environmental supply-chain contagion" is modest outside the eu + uk. one of the main implications of our work is that the changes occurring in in the eu + uk are not, in and of themselves, able to sufficiently reduce global environmental pressures. these changes have entailed reductions in domestic activities, which have also affected other eu partners, given the high level of intra-eu trade. although some of those changes do not have strong impacts on domestic environmental pressures, transport restrictions within the eu have notably reduced co eq emissions and, even more positively, reduced other pollution-induced health damage. changes outside europe occur due to spillover effects, being relatively more notable for minerals. however, the demand for goods, which ultimately depends on resource use and pressures external to the eu + uk, has not fallen so clearly, and the lion's share of the pressures has not been reduced as much as final demand. in short, we have shown the importance of intersectoral relationships and multipliers to understand demand changes, which are uncertain along , and which we anastasios xepapadeas on december , the european commission presented the european green deal (egd )-a roadmap for making the eu's economy sustainable by turning climate and environmental challenges into opportunities across all policy areas, and making the transition just and inclusive for all. the central objective of the egd is to attain a climate neutral eu by , which means that the eu will aim to reach net-zero greenhouse gas emissions by that year. the actions required to reach this target include decarbonizing the energy sector, which accounts for more than % of the eu's greenhouse gas emissions; renovating buildings to help reduce energy use which currently accounts for % of the eu's energy consumption; supporting industry so it can innovate and become a global leader in the green economy; and promoting cleaner transport, which constitutes an important source of the eu's emissions. in terms of resources needed, at least € trillion (european commission ) are projected to be necessary over the next decade according to the european commission, with sources including the eu budget, national budgets and the private sector. furthermore, the egd encompasses the so-called just transition mechanism whose objective is to help reduce the negative impacts on coal mines or steel factories associated with decarbonization. the roadmap for the egd includes actions related to climate ambition, clean energy, circular economy, smart mobility, greening the common agricultural policy, preserving and protecting biodiversity, and attaining a toxic-free environment and was planned to commence during the spring of . the covid- pandemic which appeared in europe in early , and the containment measures taken in order to control the pandemic and reduce the transmissibility of the virusthe r -below , have had a profound impact on the economy. in terms of macroeconomics, the covid- shock on the economy can be regarded as a keynesian supply shock in a multi-sector economy which triggers shortages in aggregate demand larger than the shocks themselves (guerrieri et al. ) . policies to deal with immediate impacts of covid- are aimed at a fast recovery from the recession, so that the policies are designed and implemented in a short-run context. the question which this note seeks to explore is whether the policies undertaken as a response to covid- could have long-run implications-positive or negative-in terms of sustainability and the objective of carbon neutrality. arrow et al. ( ) state that economic development is sustained at a given point in time if intergenerational well-being is non-declining at this point in time. intergenerational well-being is non-declining if the comprehensive wealth of the economy is non-declining. comprehensive wealth is the value of the assets of an economy, with the asset base or productive base consisting of reproducible capital, natural capital, human capital and health capital. social capital can also be included in the productive base. thus, the issue of sustainability can be analysed in terms of non-declining comprehensive wealth or productive base. the implications of the covid- shock on sustainability should therefore be examined in the context of its impacts on the productive base of an economy. the impact of covid- on the productive base is realized directly through morbidity and mortality and indirectly through the recession that is induced by policies implemented to contain the pandemic and the positive effects of public spending aimed at recovery. r is the basic reproduction number which is defined as the average number of secondary infections produced when one infected individual is introduced into a host population where everyone is susceptible. in a fully susceptible population, an infection can get started if and only if r > . if r < , a typical infective replaces itself with less than one infective, and the number of infectives tends to zero with the passage of time (e.g. hethcote ) . see, for example, the world economic outlook (imf, ) in which the projection for the percentage change in output in the euro area in is − . % with a rebound to + . % in . it should be noted, however, that in the current world of deep uncertainty, these predictions could be inaccurate. greenstone and nigam ( ) indicate that moderate distancing policies have substantial economic benefits in terms of mortality benefits and avoided hospital intensive care unit costs. the valuation is performed in shadow prices, with the shadow price for an asset being the present value of the contribution to well-being from one additional unit of the given asset. sustainability can also be defined in a similar way in terms of comprehensive investment. thus, the virus does not destroy reproducible capital per se, but it reduces its utilization through containment policies. however, the pandemic could affect capital accumulation if the recession slows down investment in reproducible capital. covid- seems to be beneficial for natural capital, at least in the short run. coal use fell by % at china's six largest power plants between the last quarter of and march , while in europe satellite images showed nitrogen dioxide (no ) emissions fading away over northern italy, with a similar picture in spain and the uk (henriques ) . according to a recent international energy agency ( ) report, global co emissions are expected to decline during to . gtco , which is . % lower than in ( . gtco ) (global carbon project ). this would be the lowest level since , and six times larger than the previous record reduction of . gt in due to the financial crisis. however, the international energy agency ( ) report also indicates that if efforts to contain the virus and restart economies are more successful, the decrease in energy demand could be limited to less than %. since the international energy agency's ( ) april report, data show signs of a recovery in carbon emissions. a very recent reportin june -states that new data show a v-shaped recovery in carbon emissions, with carbon emissions declining from february , reaching a minimum in april and then recovering slowly towards the february levels (domjan ) . regarding human capital, defined in terms of changes in the work force and education level, the pandemic is having a short-term negative effect on work force, but in the long term it might change educational patterns and the geographical structure of the supply of education if extensive on-line teaching is established. health capital is, of course, negatively affected through the value of statistical life. the above discussion suggests that the pandemic has a profound impact on the factors characterizing sustainability. thus, policies to start up the economy after appropriate containment of the pandemic and return to long-term desired growth paths will be beneficial for productive-based sustainability components such as health, human and social capital and reproducible capital through the increase in its utilization. the issue of primary interest is the impact of recovery-related policies on natural capital and climate change. this issue relates to the way in which the egd might be adjusted during the start-up period and whether the current beneficial impact of the virus-induced recession on emissions signals a long-term impact. recent results in climate science have established an approximately proportional relationship between the change in the global average surface temperature relative to the preindustrial period (the temperature anomaly) and cumulative co emissions relative to the same base period (e.g. matthews et al. ). with cumulative emissions since being approximately ± gtco (friedlingtein et al. ) , the expected reduction of approximately . gtco relative to due to the covid-related recession will have negligible effects on the temperature anomaly. furthermore, if the recovery projections in are realized, then it is reasonable to expect that the pre-pandemic situation will reemerge with regard to greenhouse gas emissions, unless the pandemic continues in strong recurring waves which make extended and persistent lockdowns necessary. this situation, however, cannot be regarded as the most likely scenario. if emissions recover in the short or even medium term, the projected time period for crossing the . °c threshold-according to the business-as-usual or alternative emissions paths-will not be affected in a significant way (ipcc ) . in this context, the covid- event is expected to have a negative impact on the global productive base (health, human, social and reproducible capital) and therefore on the global sustainability conditions, while the seemingly beneficial impact on natural capital, and especially climate, will be temporary and a return to pre-pandemic paths is most likely. this means that in the post-pandemic world, risks related to climate change damages, including risks from tipping elements and crossing of climate thresholds, are not expected to change. how does this picture fit with the european response to covid- in the context of the egd? the eu is currently developing and implementing a number of policies and stimulus packages to address the recession. the purpose of this note is not to analyse these measures, but rather to explore induced adjustments to the egd. it has been reported that there will be some reprioritization of edg initiatives as a result of the eu response to the pandemic (involved in europe ). some of the initiatives such as the renewed sustainable financial strategy, which aims to increase private investment in sustainable projects, or the "renovation wave", will remain since they are expected to stimulate economic activity; others such as "offshore renewable energy" or "the biodiversity strategy for " might be delayed, but initiatives such as the new eu strategy on adaptation to climate change and the new eu forest strategy will be delayed to . it is clear that the covid- shock and the need to start up the economy will make substantial policy changes necessary. looking at sustainability in terms of natural capital and the environment, it should be clear that any short-run improvement is transient, while looking at sustainability in terms of climate change, it is most likely that there will be no change in the long-term trends. what is important is that, after the shock, the start-up will be based on environmentally friendly policies. thus, maintaining initiatives such as the renovation wave, or promoting the pillar of cleaner transport, is important. on the other hand, delaying initiatives like the strategy on adaptation to climate change may need to be reconsidered. this is because the rationale behind delaying such strategies seems to be that recovery from the recession is expected to be rapid and therefore the delays will be of short duration and no significant time will be lost. however, recovery might be impeded or delayed by issues such as new, possibly weaker waves of the pandemic or more technical issues such as fiscal multipliers. fiscal multipliers during a recession when shocks are concentrated in certain sectors are not expected to be operational, with the multiplier for government spending being around one and the multiplier for transfers likely less than one. these factors might result in the delays-initially projected to be of short duration-extending for a much longer period. the important point here is that the covid- shock will have a negligible effect on the evolution of the temperature anomaly. thus, if adaptation activities and decarbonization do not proceed rapidly, the risks of a climate shock will not be sufficiently mitigated. the need for strong action now is exemplified by the fact that the emissions gap in between current policies and the emissions necessary to keep the temperature anomaly below . °c in is approximately - gtco (unep ). the covid impact on emissions in is expected to reduce the gap by approximately gtco , which falls very far short of the gap that needs to be closed. the important aspect of a climate shock is that in addition to the negative impacts on the productive base of the economy-human, health and social capital-it will have a much more serious negative impact on the reproducible capital relative to the pandemic. this is because the climate shock will not just reduce the utilization of this type of capital, it will destroy part of the capital stock, since it will affect infrastructure, equipment, buildings and so on. recovery in such a case will clearly be slower and more difficult. this creates a serious argument against delaying adaptation programmes which could provide substantial benefits in the presence of climate shocks. typical adaptation projects (e.g. early warning systems, water resource and flood-risk management, sustainable agriculture, strengthening the resilience of existing infrastructure making new infrastructure resilient) are characterized by high benefit-cost ratios (fankhauser ; gca ) . under the resource constraints imposed by pandemic containment policies and the deep structural uncertainty characterizing the situation, the prioritization of these adaptation policies could necessitate the use of max-min expected utility criteria in decision making. as second-round benefits, adaptation programmes which involve investment could stimulate the economy and provide new jobs. to summarize, three important points should be taken into account: (i) that the indications thus far suggest that the benefits associated with the reduction of greenhouse gas emissions because of the covid- are transient, which means that the long-term trends associated with climate change are not expected to change, and therefore, mitigation and adaptation strategies should be strongly pursued in the post-covid- era ; (ii) that there is a need for an ambitious and comprehensive european economic recovery plan from the covid- crisis (european economic and social committee b); (iii) that climate-change-related investments, in particular in adaptation, are expected to deliver significant economic benefits. based on these points, it becomes clear that a green recovery plan with resources directed towards achieving the combined objective of both providing the necessary economic stimuli for recovery and also promoting the transition to a low-carbon economy and adaptation to climate change along with investment in natural capital and increase in comprehensive savings could be a feasible and efficient plan. the egd is an important strategy for securing the sustained development of the eu and protecting climate as a global public good. at the same time, it is clear that addressing the pandemic requires action now in the form of new policies and changes in priorities. however, although covid- is of necessity in the spotlight at present as a major global threat, it should not displace action aimed at an equal or greater global threatthat of climate change-under the misconception that the temporary drop in emissions during the pandemic allows us to delay climate change action now. a green recovery plan could realistically provide the double dividend of helping the eu economies to recover from the covid- crisis and, at the same time, promote the attainment of a climate-neutral eu. according to the gca ( ) study, adaptation investment of $ . trillion in the areas mentioned will provide total net benefits of $ . trillion by , with benefit-cost ratios ranging between and . see, for example, the recent eu european economic and social committee ( a) opinion about the transition to a low-carbon eu and the financing of adaptation to climate change. involved in europe ( ), leaked: full list of delayed european green deal initiatives-euractiv.com. available at https ://europ e.vivia nedeb eaufo rt.fr/leake d-full-list-ofdelay ed-europ ean-green -deal-initi ative s-eurac tiv-com/. ipcc ( ), global warming of . °c. an ipcc special report on the impacts of global warming of . °c above pre-industrial levels and related global greenhouse gas emission pathways, in the context of strengthening the global response to the threat of climate change, sustainable development, and efforts to eradicate poverty. masson-delmotte, v., zhai, p. rebound effect studies have been generally focused on energy use (sorrell ) , although some studies for other natural resources have recently emerged (freire-gonzález and font vivanco ). rebound effect occurs when the use of resources is not reduced as expected after a resource efficiency policy or a specific behaviour. empirical rebound studies aim at capturing the secondary effects of policies and behaviours in order to obtain more adjusted assessments of policies and actions. it is well known in the rebound literature that, counterintuitively, resource efficiency may not reduce the use of these resources, but the contrary. this extreme case is known as backfire, khazzoom-brookes postulate, or jevons' paradox. rebound effects are not usually observed by policy-makers, as it requires different perspectives and approaches coming from social, behavioural and environmental sciences. environmental and social sciences show us that human-environment systems are deeply interconnected. this way of thinking has, however, still not fully permeated in mainstream policy decision circles, which are largely rooted in old intellectual paradigms and other short-term interests. the pandemic has caused many abrupt changes in production and consumption, transport patterns, working conditions, social interaction and many other aspects. most of these changes have been triggered by the policies implemented to contain the pandemic. overall, they have translated into improvements in most environmental indicators, such as carbon emissions, air quality and biodiversity loss (saadat et al. ) . while some authors claim that such changes will not have a lasting impact when the epidemic subsides (mccloskey and heymann ), others argue that aspects related to urban planning, micro-mobility, sharing economy, public transportation, teleworking, tourism, etc., may change for good (honey-rosés et al. ). an important question is, thus, whether covid- will reduce environmental impacts in the future, when economic activity returns to "normality" (in terms of pre-covid conditions). rebound literature shows the importance of considering behavioural and systemic responses to answer this question. beyond other considerations, the pandemic has accelerated some already observed trends, like the pace of implementation and use of digital technologies. one of the most remarkable changes are those related to the impulse of information and communications technologies (ict), due to imposed social distancing rules. there already was a tendency towards an increased use of ict, but its use has been dramatically accelerated due to the pandemic. this acceleration can be observed in many areas, such as teleworking, e-commerce, remote social relationships, virtual sightseeing, surveillance technologies, and other online areas and events (cultural, academic, leisure, educational, etc.) . for instance, in many countries, nonessential workers have been legally obliged to be confined during the pandemic to stop the contagion of the virus, thus promoting telework. despite the potential advantages of teleworking in increasing labour productivity in many industries (harker martin and mcdonnell ) , rigidities in corporate culture and other legal and cultural restraints were hindering and adjourning its consolidation. the use of ict is thought to be environmentally beneficial, largely due to decreased transport, but this premise has been challenged by rebound effect studies. gossart ( ) shows that existing evidence suggests that ict are subject to important rebound effects, mainly because it is a general-purpose technology, and so prone to backfire (sorrell ) . takahashi et al. ( ) calculated the rebound effect of ict services in a case study on videoconferences and found that rebound can reduce up to % of carbon savings. joyce et al. ( ) recently found for sweden strong environmental rebound effects associated with ict use, in most cases far above % (more resources use than before). this backfire effect is strongest for energy use and total material footprint, both close to %. another change may take place in land use and the housing sector, as initial evidence suggests that attributes such as floor space and outdoor space will have elevated importance (mikolai et al. ) . the potential re-distribution of time and expenditures towards resource-intensive sectors, such as construction, water and energy services, will likely cause material, water and energy rebounds. however, the expansion of teleworking can, at the same time, reallocate space and incomes in office rental market. city centres will not need to concentrate workspaces, changing mobility patterns and urban structures in the long term (elldér ). public transport may also be negatively impacted in the short and mid-term, leading to increased private transport (honey-rosés et al. ), another resource-intensive activity. other structural changes may also take place, such as changes in sufficiency measures and broader productivity, leading to macro-economic rebound effects (lemoine ). the pandemic may increase the social acceptance of sufficiency measures such as working less time, spending more time with family and friends, or connecting with nature. these measures have long been proposed to reduce consumption and associated environmental impacts (hayden and shandra ). these measures have, however, been associated with macro-economic price rebound effects as the decreased demand for some products can lower their price and induce additional demand (sorrell et al. ) . moreover, the postpandemic society may likely be a more productive one in labour and capital terms. for example, teleworking (harker martin and macdonnell ) and increased spending in research and development have been associated with productivity growth, which boosts economic growth and resource use. the covid- pandemic will likely cause a range of changes in society, but their permanence and effect on the environment are unclear, especially if we contemplate the secondary effects of behaviour, measures and policies. a key question is whether they will acquire a certain level of permanence, even modifying the mindsets of agents. given the high uncertainty around this aspect, its real dimension could only be assessed ex-post. however, due to confinements, the pandemic has greatly accelerated the expansion and use of general-purpose technologies, like ict. as this has been a long-observed trend, before the irruption of the virus, they have probably come to stay to a large degree. the pandemic offers a great potential to improving (and consolidating) environmental conditions. but beyond what conventional environmental indicators show, additional measures would be needed to counteract hidden rebound effects and, therefore, take full advantage of potential improvements. recent literature shows that different economic instruments like environmental taxation, resource pricing or setting limits to resource use, can be effective for this purpose. this is particularly necessary in this case, given the high risk of backfire due to the high expansion of general-purpose technologies observed. the global financial and commodity markets are facing economic distortions caused by the coronavirus (covid- ) pandemic (fernandes ; irwin ). covid- acts as a negative shock to overall demand of goods and services, resulting in aggravated shortrun volatility in prices (albulescu ). among these products, oil has been dramatically affected due to community lockdown regulations, shutdown of car factories, decline in energy use and increase in unemployment (reed a; the associated press ). however, a decrease in oil consumption may lead to reductions in carbon dioxide emissions (peña-lévano et al. ). data recorded by epa ( ) during march-april show an improvement in overall air quality, especially in high-density populated cities (regan ). air pollution is considered by many scientists as a negative contributor in the coronavirus situation by worsening the susceptibility of infection. a decline in emissions somehow may help prevent mortality temporarily, especially among more vulnerable individuals with underlying health conditions, such as heart and respiratory diseases (conticini et al. ; dutheil et al. ; mooney ; ogen ). thus, in this short article, we discuss the interaction between fossil fuels, air pollution and health risk under the coronavirus pandemic and the lockdown regulations during the period of march-may . the oil market has been dramatically affected by several exogenous factors during the pandemic period: ( ) "shelter in place" mandates aimed at curbing the spread of the coronavirus have decreased people's social mobility and transportation activities. households leave their houses just for short travels for some essential errands, such as shopping groceries and/ or medicine. only essential personnel are required to be physically present at their jobs, whereas the majority are working from home (reed a); ( ) commercial flight demand plummeted globally (reuters ). in the usa, the passenger volume dropped % from a year ago (compared to april ) as estimated by airlines for america, with an overall reduced accommodation of passengers per carrier (rappeport and chokshi ); ( ) tourism activity slumped as many governments banned international travel, heightened border and immigration controls and barred the entrance of foreign visitors to decrease risk of infection. these policies further decreased the demand for taxis and cruise services. for regions such as the caribbean islands (where tourism is a primary economic staple good), this also represents a significant decline in their gross domestic products (semple ); ( ) unemployment has pervaded among the national economies (mazzei and tavernise ). more than million people have filed for unemployment in the usa in a -week period (u.s. department of labor ). this condition is mirrored in other countries. worsening unemployment conditions have substantially reduced consumers' purchasing power. among its consequences is an overall decline in car sales (reuters ; the associated press ); ( ) many industries, restaurants and buildings have been shut down during the lockdown. these closures reduced energy consumption, especially petroleum use, which is a large energy input in the usa and other countries (eia ). meanwhile, global oil supply responded slowly to the decline in demand as refineries cannot abruptly halt production (caldara et al. ; peña-lévano ). the russia-saudi arabia oil price war in march worsened the situation by oversupplying the market and consequently dropping oil prices (irwin ; reed a). in april, the major petroleum exporting countries agreed to decrease the world oil output by % during may-july, which is equivalent to . million barrels a day (krauss ; reed b). two recent studies published in geophysical research letters validate the realized reduction in nitrogen dioxide (no ) pollution in several regions. bauwens et al. ( ) compared no levels in the atmosphere recorded in january to april and for the same period in . notably, no , which is produced by emissions from vehicles and industrial operations, can cause serious lung ailments. their estimates indicate a significant reduction of % in china and - % drop in the usa and western europe. shi and brasseur ( ) estimate a % reduction in no pollution in northern china in january and february . in the same period, they also found a % reduction in particulate matter pollution (particles smaller than . µm). while such cleaner air conditions may persist only temporarily, these trends indicate that the desired environmental gains are feasible and realizable if stringent emission regulations, perhaps mirroring to some extent the pandemic's enforced limits on social mobility and industrial activities, are enforced in the future. several studies relate ambient air quality to mortality and morbidity conditions caused by covid- . this contention echoes an earlier correlation applied to the sars virus outbreak in china in the early s. researchers from ucla's school of public health analysed air pollution levels and sars fatality rates among chinese residents. their results indicate that sars patients' probability of dying would be doubled among residents in areas with high air pollution indexes (cui et al. ) . as applied to the current pandemic, the center for disease control and prevention (cdc) explains that covid- causes a respiratory illness with a heightened risk among people who are years and older as well as those with certain underlying health conditions. latest cdc statistics on the pandemic's severity and fatality indicate that persons with heart ailment, diabetes and chronic respiratory diseases could be at a higher risk of being severely infected by the virus (vogel ). wu et al. ( ) further clarify that pre-existing health conditions identified as relatively more susceptible to contracting covid- are similar to those normally affected by air pollution in the usa. their study estimates that an increase of g m − in long-term exposure to particular matter (pm . ) increases the coronavirus mortality rate by %. isaifan ( ) presents corroborating evidence indicating that % of covid- -related deaths were cases with pre-existing illnesses, with majority of the victims over years of age. conticini et al. ( ) , however, warn that even young and healthy individuals could also be at risk as prolonged exposure to dangerous air pollutants causing chronic respiratory issues could be an additional co-factor that helps increase their vulnerability to being infected by the virus. ogen ( ) establishes that exposure to no may be an important instigator of covid- fatalities according to his research involving four european union countries. these findings are supported by the findings of a study published by the italian society of environmental medicine (setti et al. ) on virus infections in northern italy associated with air pollutants tagged as carriers and boosters. poor air quality has been cited as an aggravating factor in virus transmission. using data from italian province capitals, coccia ( ) notes an accelerated transmission dynamics of covid- leading to his conclusion that the spread of this virus can be considered more as following an "air pollution-to-human transmission" mechanism instead of an interpersonal transmission mode. moreover, fattorini and regoli ( ) analyse long-term air quality data in northern italy and suggest that chronic exposure to a contaminated atmosphere may have created conducive conditions for the spread of the virus. several studies relate the time frame of exposure to toxic air pollutants to mortality and morbidity conditions. lim et al. ( ) establish a significant association between longterm ozone (o ) exposure and elevated mortality risk of certain respiratory diseases. given limited data on the current pandemic, hoang and jones ( ) present emerging evidence on the severity of covid- infection attributed to persistent air pollution conditions, thus suggesting that longer exposure to a polluted atmosphere could aggravate virus infection. zhu et al. ( ) , however, provide concrete evidence suggesting that even short-term exposure to air pollution could increase probability of virus infection. their study analysed daily confirmed cases in cities in china recorded from january to february and found significant relationships between the levels of certain air pollutants and the number of newly identified covid- -infected cases. specifically, their results indicate that a -μg/m increase in the air pollutants' levels was associated with about . % to . % increases in daily new covid- cases. conversely, the health benefits of cleaner air resulting from reduced emissions from fossil fuel during the pandemic's lockdown period deserve attention. several studies recognize that improved air quality during the pandemic temporarily mitigated health risks associated with respiratory illnesses. cole et al. ( ) employed a two-step analytical approach using machine learning techniques and the augmented synthetic control method to estimate possible reductions in death rates in certain regions in china and for the whole country that may be attributed to actual reductions in no concentrations during the lockdown period. isaifan ( ) analyse air quality conditions prior to and during the lockdown period. his results indicate that lives may have been saved due to diminished ambient pollution levels, although eluding possible virus infection still is not necessarily guaranteed. this contention is corroborated by another china-based study conducted by dutheil et al. ( ) . these studies' assertions imply that air quality improvements realized even in such a shorter period of time (spanning less than half of a year) already could have some health benefit potentials, especially in relation to respiratory ailments. the health benefits of the current pandemic's notable environmental gain in air quality, however, will be optimized only if such favourable conditions are sustained over the longer term. the recent lockdown has been short-lived as some communities nowadays have started to revert to normal social routines and regular users of fossil fuels among industries have resumed operations. a brief respite from a usual contaminated atmosphere does not ensure an effective permanent eradication of chronic health conditions. the pandemic experience, however, demonstrates that better health is maintained and ensured not only through medical remedies and but also through more favourable environmental conditions, if sustained over a much longer period. current restrictions on social mobility and economic flexibility under covid- pandemic conditions have actually produced important economic and environmental repercussions that are interestingly contrasting. a general economic slowdown overtly reflected in, among others, reduced consumer demand, spiralling unemployment figures and significant drop in oil consumption causes heightened fears of an imminent economic recession. however, in spite of all the negativity surrounding the pandemic, its environmental consequence of improved air quality is a highly positive note. interestingly, the global community has been trying to accomplish such feat of attaining better air quality over many years of discussions, policy making and policing each other. unexpectedly, it took a serious pandemic to realize such feat. this article traces the interplay of reduced oil consumption with economic issues as well as environmental consequences under pandemic conditions. the more imperative issues now lie on the severity of a looming recession and the global economy's resiliency in transcending the difficult challenges it may bring. should that happen, will the economic cost burdens be outweighed by the realized environmental gains? experts may be quick to assert that improved environmental conditions actually may be short-lived as expected resurgence of resumed economic activities may only quickly bring back pre-covid air conditions. however, proponents of a cleaner world can always draw some inspiration from recent successes in air quality control, especially with the assurance that cleaner air is not necessarily a lofty goal. the challenge in the future lies in achieving such environmental benefit without the need to sacrifice the economic health of the global community. on february , , the brazilian ministry of health confirmed that a -year-old man was positive for sars-cov- : covid- had arrived to latin america. as of july , there have been . million confirmed cases in latin america, compared to . million in the european union and . million in the usa (jh-csse ). furthermore, so far there have been more than , deaths in the region and the trends show that the first wave of the pandemic is far from over (ibid.). there is of course no suitable time for a pandemic to arrive, but these are especially complicated times for latin america. the region is in the midst of a difficult economic situation accompanied by rising social discontent (eclac ; oecd ). moreover, it is characterized by high rates of informality, health systems with limited and unequal capacity, and most of the countries have high levels of debt (oecd ). under these circumstances, covid- is having major short-run socio-economic effects with possible serious long-run consequences, including several potential implications for the environment and the management of natural resources. restrictions of free movement and circulation within and across urban areas of latin america have reduced economic activity as well as the use of motorized vehicles. as a result, many latin american megacities have experienced a short-run decrease in air pollution. concentrations of no have decreased considerably in cities all over the region compared to the levels observed prior to the lockdown measures (iadb ). levels of pm , pm . and co have decreased in bogota, buenos aires and quito (bogota's district secretary of environment, personal communication, june ; roa ; rocha ). nevertheless, the pandemia has not had the same effect on air quality in all the major cities in the region. in mexico city, the reductions in so , pm . and pm concentrations have been modest, and there has been no reduction in ozone. in rio de janeiro, ozone concentrations have increased (dantas et al. ) . furthermore, as the virus and its negative consequences spread across rural areas and make its way through the southernmost part of the region, outdoor and indoor pollution might actually increase. in mexico, as well as in other countries in the region, the use of firewood is likely to rise as rural households try to deal with income reductions (masera et al. ). meanwhile, as winter hits central and southern chile, urban households might increase their use of firewood for heating given that, due to the lockdowns, they have to spend more time inside dwellings (encinas et al. ) . this rise in air pollution could arguably increase the risks associated with covid- . it is too soon to do a formal evaluation of the effects of the pandemic on deforestation and land use change in the region. nevertheless, the available information suggests that covid- is likely to have negative effects on forest cover across the region. early deforestation warnings from peru show that, although deforestation decreased between march and april , since then it has increased surpassing the levels observed during the same period in . according to data from the brazilian national institute for space research (inpe), the first quarter of already evidenced a rise of % in deforested hectares compared to last year's figures. the figures for april reinforce this pattern, with a % increase with respect to april (manzano ). from january to april , deforestation alerts in indigenous territory increased % when compared to the same period of the previous year (greenpeace brasil ). although at this point it cannot be claimed that the pandemic caused the observed increase in deforestation, it certainly does not seem to have provided incentives to halt it. in colombia, contrary to other countries in the amazon region, the trend in showed a reduction in deforestation compared to . however, started with an increasing tendency and the quarantine seems to have worsened the situation (fcds ). the absence of environmental monitoring during the pandemic seems to have encouraged illegal armed groups and regional mafias to take advantage of the situation, exacerbating deforestation with the possible intensification of illegal activities from which these actors derive income, such as illegal mining, land grabbing and illicit crops (bbc ). according to the pan american health organization, in may there were already , covid- -confirmed cases in the amazon basin (martín ). the impact of the pandemic in forest-based indigenous communities is an important source of concern. the spread of the virus in these communities could imply a tragedy that, in addition to the human losses, could affect the traditional knowledge, having negative impacts on the governance of natural resources in the region. this could lead to even more deforestation processes in the future. covid- has caused a disruption in the national and international trade of nature-based goods and services. tourism has come to a halt, affecting the economy of almost all of the countries in the region (mooney and zegarra ). in countries like costa rica, where the touristic industry is intertwined with nature, the shock to the sector could have negative effects for biodiversity and forests. without income from tourism, and given that as a slow recovery process is anticipated, the incentives to protect forests are expected to decrease in the short and medium run. fishing and aquaculture are other industries that have been negatively affected. information for the case of the chilean salmon aquaculture industry suggests that there has been a reduction in demand from international markets (chávez et al. ) . the effect of the shock is being transmitted through the value chain, affecting processing plants and farming facilities. the economic crisis can end up having long-run negative consequences for the environment if, as a result, regulations and environmental policies are relaxed or if institutions are weakened. although at this point there is no evidence of any country in the region purposefully relaxing environmental regulations to promote growth, it is certainly a possibility. what has been observed is that, in order to fund measures to reduce the economic and social impacts of the pandemic, some countries have decided to reallocate funds across the public administration. ecuador, for example, announced cuts affecting the ministry responsible for enforcing environmental regulations (bbc news ). something similar is happening in mexico, where the plan announced by the president is to reduce the operational budget of almost all government entities by % (d.o.f. ). even if countries have a relatively strong environmental legal framework, without a budget to monitor and enforce the regulations, this framework is worthless. countries in the region will very likely incur fiscal deficits and increase their debts in order to fight the crisis. it remains to be seen how the service of the increased debt will impact economic growth and the environment. in the meantime, it seems that the short-run legitimate demands to recover employment levels and improve the health systems might very well push aside the necessary investments to successfully tackle climate change and biodiversity loss. if this indeed happens, it could be the most serious effect of the covid- pandemic in both environmental and social terms. the economic projections suggest that the region will experience a crisis whose magnitude has no precedent in modern history (eclac ). in order to overcome this apparently insurmountable challenge, latin american countries will need well-designed policies that should reconcile economic objectives with social and environmental goals. the social unrest manifested recently in the social mobilizations in the region, should make clear that the apparent trade-off between economic, social and environmental objectives is the result of a false dichotomy between shortand long-run objectives. if environmental objectives are put aside, as has so often happened with social objectives, the economy might recover in the short run but at a very high price. the lockdown measures seem to be having a temporal positive effect on reducing urban pollution in some latin american cities. the challenge now is how to intervene to prevent a return to the same or even higher pre-quarantine emission levels. this is an opportunity to rethink the urban environmental policies while trying to recover from an unprecedented social crisis. at the same time, the observed increase in deforestation reopens political and academic debates about the role of national parks, indigenous reserves and other protection categories in a context of deteriorated livelihoods, illegal economies and a lack of state presence. latin american countries could see this moment as an opportunity to improve regional cooperation in order to design and implement coordinated policy responses not only to the economic crisis but also to the challenges of mitigation and adaptation to climate change. furthermore, countries should coordinate efforts to increase monitoring and presence in the region to effectively reduce deforestation. we have presented an account of some of the most evident environmental effects that the covid- pandemic is having in latin america at this point. considering that we are in the midst of the health crisis and in the beginning of an economic one, it is natural to expect that the trends that we see now will change in the near future and that other environmental impacts will become evident. research that contributes to a better understanding of the environmental impacts and the effectiveness of different policy responses to the pandemic in latin america will be invaluable. there are many potential paths for future research; here, we mention just a few. the consequences of the interactions between poor air quality and covid- on human health are clearly worth studying. this is particularly relevant for the latin american context, characterized by health systems with very limited capacity and high numbers of population without formal employment. results from studies in this area could help us provide better guides to set environmental quality goals, as well as to implement policy interventions that can reduce pollution in the region's context of income inequality and spatial segregation. the short-run environmental effects of covid- show early warnings of an increase in the pressure on forest and other ecosystems across latin america. understanding the impacts of the pandemic on terrestrial and marine ecosystems, as well as on livelihood opportunities for local communities, has the potential to contribute to the design of policies which can improve management and conservation. the pandemic is opening new research questions regarding the impacts of global shocks on natural resource-based industries that participate in international markets. furthermore, the paths that different countries take to get out of the economic crisis might have profound impacts on international trade. if, for example, the world transitions to more reliance upon local production, or if emissions-related tariffs are imposed, large exporters of commodities in the region will be highly affected. the impacts that these potential trade changes could have on the environment are unknown. furthermore, if developed countries implement recovery plans that include provisions to reduce emissions in significant ways, as has been discussed in the european union, will latin american countries be able to respond in the same way? in any case, latin american countries are highly vulnerable to the effects of climate change and some of these effects (e.g. migration) could result in future health crises. a better understanding of the ways in which individuals might adapt to a changing climate, as well as of the barriers that they face to adopt adaptation measures, will be a valuable tool for the design of adaptation policies that prevent future health crises in the region and elsewhere. the distributional and gender-differentiated impacts of the pandemic, and the related environmental policy responses, is another area that deserves attention, especially because early evidence shows that the more vulnerable segments of the population in the region are the ones that are being hit hardest. finally, as has been recently pointed out by , the experience of the pandemic might lead to changes in behaviour and personal choices. it remains to be seen if this is in fact the case, and if so, how are these changes in behaviour modulated by the local context. an even more important issue to consider is what would these changes imply for the design of behaviour-based policy instruments aiming to change consumption and production patterns, as well as transport and land use decisions in latin america. bbc ( ) the place where nature isn´t healing. https ://www.bbc.com/reel/video / p bd wfc/the-forgo tten-peopl e-of-the-globa l-pande mic accessed june bbc news ( ) coronavirus en ecuador: las multitudinarias protestas por las drásticas medidas económicas y recortes de lenín moreno. https ://www.bbc.com/mundo / notic ias-ameri ca-latin a- accessed june chávez c, salazar c, simon j ( ) efectos socioeconómicos y respuestas públicoprivadas de corto plazo ante la crisis del covid- en el sector salmonicultor, una fotografía de la experiencia internacional. interdisciplinary center for aquaculture research-incar, fondap-anid, center, chile. https ://www.incar .cl/wp-conte nt/ uploa ds/ / /pb .pdf accessed june dantas g, siciliano b, frança b. b, da silva c. m, arbilla g ( ) the impact of covid- partial lockdown on the air quality of the city of rio de janeiro, brazil. sci total environ . https ://doi.org/ . /j.scito tenv. . . d.o.f. ( ) decreto por el que se establecen las medidas de austeridad que deberán observar las dependencias y entidades de la administración pública federal bajo los criterios que en el mismo se indican. de abril de . presidencia de la república de méxico. eclac ( ) report on the economic impact of coronavirus disease (covid- ) on latin america and the caribbean: study prepared by the eclac, santiago, p encinas f, truffello r, urquiza a, valdés m ( ) covid- , pobreza energética y contaminación: redefiniendo la vulnerabilidad en el centro-sur de chile. centro de investigación e información periodística. https ://ciper chile .cl/ / / /covid - pobre za-energ etica -y-conta minac ion-redefi nien do-la-vulne rabil idad-en-el-centr o-surde-chile /. accessed june fcds. ( ). cifras deforestación en el bioma amazónico, enero-abril .https :// fcds.org.co/site/wp-conte nt/uploa ds/ / /defor estac ion_ .pdf accessed june greenpeace brasil ( ). desmatamento em terras indígenas aumenta % em . https ://www.green peace .org/brasi l/press /desma tamen to-em-terra s-indig enas-aumen ta- -duran te-a-pande mia-da-covid - / accessed june helm d ( ) . contributing to a global effort. oecd. roa s ( ) medidas para enfrentar al covid- mejoran calidad del aire en dos ciudades ecuatorianas. mongabay-latam.https ://es.monga bay.com/ / /menor -conta minac ion-del-aire-por-coron aviru s-en-quito -y-cuenc a-ecuad or/ accessed jun rocha l ( ) por la cuarentena, la contaminación del aire bajó a la mitad en la ciudad de buenos aires. infobae. https ://www.infob ae.com/socie dad/ / / /por-lacuare ntena -la-conta minac ion-del-aire-bajo-a-la-mitad -en-la-ciuda d-de-bueno s-aires / accessed june resource exporters are now facing new urgent economic policy challenges due to covid- . these challenges are aggravated due to their dependence on finite commodities with volatile prices and demand. in response to the pandemic, resource exporters (such as botswana and saudi arabia) announced cuts in expenditures along with large fiscal (tax relief) and consumption-focused macroeconomic stimulus packages. critically, the novel issues raised by the coronavirus pandemic bring new trade-offs of energy policy between shortterm gains and long-term sustainability, creating an urgent need for critical, quantitative, policy-focused research in the resource exporters-energy policy nexus. a few novel issues emerged in resource exporters during the pandemic that give rise to short-term economic challenges. first, price shocks of unprecedented magnitude for commodities (deutsche bank ; world bank ), from coffee (hernandez et al. ) to hydrocarbons (iea b), causing a large drop in energy investment (iea a). for oil, prices dropped initially due to travel bans and economic activities hiatus, and further with oil price wars following the collapse of opec + agreement. by april , with oversupply, the rise of stockpiles, and the saturation of available oil storage, oil prices reached the lowest level in more than years, and west texas intermediate (wti) reached negative levels for the first time. prices have subsequently partially recovered but are expected to remain low with continuous fears of new covid- waves and uncertain demand. second, unprecedented economic contraction, because the pandemic-triggered decline in economic activity was significantly exacerbated by declines in export revenue. third, unprecedented fiscal pressure, resulting from costs of fiscal and economic stimulus packages plus a simultaneous rise in domestic expenses (especially healthcare and unemployment benefits) and sharp declines in resource export revenue. the effects have been so colossal that states like kuwait are considering halting legally-mandated contributions to the future generations sovereign wealth fund (swf) to ease fiscal pressures (al-zo'bi ). fourth, record and continuous withdrawals from swfs to fund post-pandemic recovery along with reallocation of funds and increased government debt (examples in arabian business ; holter and bloomberg ). even states with the largest swfs such as norway and kuwait have been affected, with the latter expecting depletion of its fiscal stabilization swf (al-zo'bi ). fifth, in oil-exporting gulf states, the unusual stay of millions of citizens and guest workers in the upcoming scorching summer in lieu of usual tourism travel or home-country visits, pressuring existing energy capacity. critically, in oil exporters, these novel issues and policy responses to them further expose existing economic fragilities and challenges, threatening long-term economic and environmental sustainability. for distorted oil economies in urgent need for economic diversification, said diversification and reverse dutch disease are impeded by their existing high distortions in labour, fiscal, industrial and energy markets (shehabi ) . oil exporters suffer from economic inefficiencies resulting from pervasive oligopolies (shehabi ) and market failure in long-run contracts for exploration and development of natural resources (ruta and venables ). fossil fuels are the primary source of energy in most oil exporters. in developing oil exporters, the dominant political economy undergirding policy making is a welfare rentier state, in which maintaining a political equilibrium is central. balancing spending-saving decisions for sustainable resource rents management depends on the sustainability of windfall expectations (gelb and grassmann ). reforming energy policy-which drives fiscal, industrial and environmental policies-is critical for these states' long-term development. yet the novel issues create new trade-offs of post-pandemic energy policy: achieving short-term gains will be at the expense of longterm gains in resource economies. thus, it is critical for fast policy-focused research to address the resource exporters-energy policy nexus, especially in the following two areas. although investments in renewables have been more resilient than in fossil fuels, and while we have seen an increased share of global energy spending on clean energy technologies in (iea a), the reality in hydrocarbon-exporting developing states is different. global oil market supply and demand dynamics have raised their opportunity cost for transitioning away from fossil fuels and for investing in green technology. accordingly, post-pandemic economic stimuli might achieve short-term recovery but harm long-term energy transition. first, the rise in opportunity costs of energy transition will facilitate the reallocation of funds away from renewables projects towards post-pandemic economic stimuli (similar to "green tape" cuts in australia and canada). second, recovering lost investments in energy transition projects is unlikely because the resource rents that fund them are likely to continue to be low in the future, given low resource prices and demand pressures of climate change mitigation. third, continuous withdrawals of diminishing swfs will entail limited resources for future energy transition projects. this is especially so as recovering swfs' withdrawals is unlikely in the light of expected low resource export revenue and the collapse in financial and commodity markets accompanying the unprecedented global recession. finally, economic stimuli expand consumption and welfare redistributive measures, which increase greenhouse gas (ghg) emissions ) and exacerbate existing distortions that have been shown to prevent economic and energy diversification (shehabi ) . new research should investigate the design and implementation of new economic solutions that have at their forefront long-term energy transition goals along with short-term economic recovery. three policy solutions are suggested at the consumer, the energy industry and economy-wide levels. a policy solution to target consumers is technological advancements (both private and public funded) in energy efficiency coupled with economic incentives to rationalize energy consumption. this policy combination can achieve energy transition goals despite expected delays in renewables and without requiring large multiyear investments. it is especially important in gulf oil states where skyrocketing cooling and desalination needs in the summer will be met using fossil fuels (renewables contribute less than % of power generation). a policy suggestion at the sectoral level is investing in clean energy technologies to decarbonize the energy sector itself, namely through carbon capture and storage as well as hydrogen. beyond short-term economic and environmental benefits, these investments can keep oil exporters relevant in a future with a diminishing role of hydrocarbons and collapsing commodity prices. the final policy suggestion is microeconomic and energy policy reform that can moderate effects of export price declines on the economy without the need for additional cuts in renewables investments or further withdrawals from swfs. examples include microeconomic reforms of labour and human capital to increase long-term productive capacity and oligopoly regulation in non-tradables and energy sectors which can increase efficiency and welfare gains that translate economywide (shehabi ) . consequently, resource rents could be salvaged for swfs resources or investments necessary for future development. in the light of the aforementioned novel issues in resource exporters, the postpandemic energy policy and economic stimulus packages are likely to have negative long-term effects on the environment. the reasons are as follows. first, while lockdown measures that minimized transportation and human activity reduced short-term emissions, they also increased power demand which in resource exporters is met mostly through fossil fuels, especially as international demand and prices remain low. second, short-term improvements will be negated upon the resumption of human activity, absent changes in energy policy regimes. importantly, as domestic energy prices remain low and highly subsidized in developing resource exporters, the extent to which covid- restrictions would shift energy consumption habits and behaviours of agents (households and institutions) remains very doubtful. third, there will be limited resources in the future to dedicate towards environmental regulation and ghg emissions reduction. the reason is that funding the post-pandemic recovery will reallocate funds away from environmental projects and savings in swfs. fourth, ghg emissions will increase due to consumption-focused economic stimulus packages and expanded use of fossil fuels to meet rising energy demand. this is particularly problematic because even prior to the advent of the pandemic, resource exporters were among the highest energy consumers and carbon emitters globally. indeed, the ten highest per capita carbon emitters are all resource exporters, with emissions ranging from tonnes (t) per capita (qatar) to . t per capita (kazakhstan), more than . times the global average of . t per capita (ritchie and roser ) . finally, and most importantly, the implementation of policy instruments-namely energy subsidy reform and carbon taxes-to achieve resource exporters' intended nationally determined contributions (indcs), is rendered significantly more difficult post-pandemic. it is a consequence of the magnitude of novel economic contraction and fiscal pressures in welfare-based states. these additional political constraints exacerbate environmental laws' enforcement, for which there already was a widespread failure in resource exporters (unep ). therefore, new research must quantify effects of proposed economic stimuli and of rising use of fossil fuels on resource exporters' environment and economy and accordingly evaluate and design new alternative policies that can achieve short-term recovery and national climate target goals. to that end, four policy suggestions are offered. first, reducing emissions in ways other than the politically difficult tax instruments, mainly through enhancing energy efficiency that reduces emissions at a given consumption level coupled with economic incentives that reduce energy consumption. second, implementing carbon tax instruments in ways that do not harm the most vulnerable of populations and reduce resource exporters' fiscal distortions, thus achieving a "double dividend". third, in the light of the novel issues, a key policy solution is adopting "green welfare expansion": including green options in the typical post-pandemic welfare packages at lower governmental budgetary requirements. examples include expanding subsidies for green technologies (such as solar panels, public transportation or electric cars), as well as excluding from subsidies non-essential high-carbon-emitting products for households above a certain income level. fourth, increasing the political viability of green recovery packages (such as clean physical infrastructure and natural capital investments), including engaging the private sector in initiatives that are typically public-led-such as climate finance, renewables expansion and resource mobilization. this policy is critical because, although green recovery packages may boost economic growth while helping climate change , they are politically contentious in resource exporters where they compete with welfare distribution. critically, applicable to the aforesaid two research areas, the pandemic offers resource exporters an opportunity to engage in a comprehensive reform agenda that addresses short-term pandemic effects while advancing long-term energy transition, economic and resource sustainability. the challenge for policy makers is to avoid implementing policies in haste. properly coordinated policy reforms offer an avenue to address inefficiencies and underlying structural distortions in a way to realize mutual gains and multiple policy objectives at the lowest cost. in designing these reforms and addressing the two areas above, the most suitable research methods are economy-wide general equilibrium models that can quantify effects of shocks and policy solutions in a "second-best" environment. this feature is necessary given the large existing economic distortions in resource economies. these models represent economic linkages and agents and include a wide range of policies (energy, carbon, fiscal, labour or industrial). as such, they can inform evidence-based policy making that accounts for political economic considerations. this research will be critical for filling gaps in the literature on long-term economic and resource sustainability in resource exporters. the current global greenhouse gas (ghg) emissions trajectory indicates that the world is likely to experience catastrophic consequences due to climate change, unless swift action is taken towards funding green solutions and the defunding of fossil fuel activities ( given the ambition of the european union to become a net zero-carbon economy by and the numerous calls to avoid the bailout and stimulus packages towards fossil fuel companies , we examine whether the features of the european central bank's (ecb) € billion pandemic emergency purchase programme (pepp) encourages the resilience of the incumbent fossil fuel sector, or whether it promotes the growth of the emerging low-carbon energy sector during the covid- pandemic and beyond. we draw on a novel dataset of corporate bonds issued in the european energy sector between january and june in combination with the european central bank's (ecb) purchases under the pandemic emergency purchase programme in response to covid- . we show that the likelihood of an energy company bond to be bought as part of the ecb's programme increases with the ghg intensity of the bond issuing firm. we also find weaker evidence that the ecb's pepp portfolio during the pandemic is likely to become tilted towards companies with anti-climate lobbying activities and companies with less transparent ghg emissions disclosure in the event of increased euro-denominated bond issuances in the following months, or re-denominations of non-euro bonds already issued by european energy companies. kainen et al. ). that does not mean, however, that the aim of central banks to remain sector neutral is achievable in practice, as the implementation of ecb's post- quantitative easing shows that assets purchased by central banks to stimulate overall economic growth are benefitting more from the policy than assets which are not purchased by the bank (haldane et al. ; matikainen et al. ) . this means that the choice of asset class through which asset purchasing programs are implemented matters. this is particularly important in the low-carbon economy context, as the fossil fuel energy sector is largely financed through bonds and syndicated bank loans (cojoianu et al. ) , whereas much of the emerging clean technology companies are financed through private equity, equity issuances and asset financing (cojoianu et al. ; gaddy et al. ) . given that the ecb has chosen to enact its asset purchasing program post- crisis predominantly through bonds, this has been shown to favour the incumbent fossil fuel industry (battiston and monasterolo ; matikainen et al. ) , as % of ecb's corporate bond purchases (out of a total of € billion) are in ghg intensive sectorsthough they make up only % of the eurozone area economy and produce % of ghg emissions. the criteria for the corporate bonds bought under the pepp are that: (i) the company must be incorporated in the eurozone and its bond issuance denominated in euro, (ii) the firm cannot be a financial corporation (or a credit institution supervised by the ecb), (iii) it cannot be a public entity, (iv) the bond issuance has to be endorsed by one positive credit rating by an external credit assessment institution accepted within the eurosystem credit assessment framework and (v) they have a maximum maturity of up to years and a minimum maturity of months. in order to understand whether the ecb's bond buying activity during the covid- pandemic has been tilted towards less transparent, more fossil fuel intensive as well as anticlimate lobbying european energy companies, we undertake the following steps. first, we collect all the bonds issued by european energy companies during the period january to june from bloomberg. these span the following energy subsectors as classified by bloomberg industry classification system (bics): power generation, renewable energy, integrated oil and gas companies, oil and gas exploration and production, oil and gas services and utilities. this results in bonds. we then match each bond with ecb's bondholding portfolio, the borrower's record on pro/anti-climate lobbying from influencemap, the ghg intensity of the borrower (collected from bloomberg and measured as thousands tco -e/million eur revenue) and the ghg reporting completeness of the borrower (which is assessed by bloomberg and quantified as if the company is transparent about the organisational boundary it chooses to quantify its ghg emissions and otherwise, bloomberg terminal code es ). we further collect the borrower's revenue (million eur), bond amount issued (million eur) and coupon rate for each bond, also from bloomberg. our resulting dataset with complete data across all variables of interest is comprised of a cross-section of bonds issued across several currencies, and eurodenominated bonds. our dependent variable quantifies the likelihood that the bond of a european energy company is bought by the ecb during the first months of and coded as if it has been bought by the ecb, and if it has not. for our model, we employ a binary logistic regression model with robust standard errors. the full model specification is the following, where ε i is the stochastic error: we show that after controlling for the revenue of the issuer, the bond amount raised and the rate of the coupon, the ecb is statistically significantly more likely to buy the bonds of more ghg intensive european energy companies (models - , table ). on average, a one standard deviation increase in the ghg intensity of an energy company results in a % increase in the likelihood that its bonds are bought by the ecb (β = . , p < . , odds ratio: . , model ). when we consider only euro-denominated bonds (models and ), which are directly under the remit of the ecb, ghg disclosure completeness and pro-climate lobbying are statistically insignificant, yet negative, which suggests that the ecb may be likely to tilt its portfolio towards companies with poorer ghg emission disclosures and less responsible climate lobbying activities. subsequently, we include the bonds issued by european energy companies in denominations other than euro, to account for potential sample selection bias due to the choice of energy companies to abstain from issuing euro-denominated bonds as they may have received discouraging signals from the ecb. in other words, analysing the bond issuance of european energy companies in all currencies considers signals that the ecb may have given to the energy companies prior to issuance, while analysing only euro-denominated bonds only considers the observable decision of the ecb to purchase the bonds of specific energy companies post-issuance. when we do so (model ), it emerges that considering the entire universe of bonds issued by european energy companies, the ecb's portfolio is tilted not only to those energy companies that are more ghg intensive, but also to companies which are less transparent on their ghg performance as well as those companies who are more likely to oppose progressive climate action. having established statistical significance, we investigate the economic and statistical relevance (brooks et al. ) . inspecting the economic relevance of the ghg intensity variable in model , we find ghg intensity to have the largest marginal effects. in terms of statistical relevance, we find ghg intensity to have by far the largest shapley r-squared value, contributing more than % to the overall explanatory power of model . in conclusion, the importance of ghg intensity is underlined by its marginal economic effects and its statistical relevance, as it explains more variation in the dependent variable on its own than all other variables taken together. we also conduct further robustness tests controlling for ecb bond i = + * pro-climate lobbying activities score i + * ghg emissions intensity i + * ghg reporting completeness i + * borrower revenue i + * bond issuance amount i + * bond coupon rate i + i . bond maturity, bond rating and interactions of key variables and find our results to remain statistically significant. in conclusion, drawing on a novel dataset of corporate bonds issued in the european energy sector since january and the database of ecb's purchases under the pepp in response to covid- , we find evidence that the likelihood for a bond to be bought by the ecb increases with the ghg intensity of the bond issuing firm. we also find weaker evidence that the ecb's pepp portfolio during the pandemic is likely to become tilted towards companies with anti-climate lobbying activities and companies with less transparent ghg emissions disclosure. our findings imply that, at later stages of the covid- recovery, an in-depth analysis may be necessary to understand if, and if yes, why the ecb fuelled the climate crisis. even if one accepts that fossil fuel companies were eligible for pepp, then our preliminary evidence still raises the significant question, why the ecb was more likely to directly finance those fossil fuel firms that are likely more harmful to the planet (i.e. have a higher ghg intensity)? the coronavirus covid- pandemic is the defining global health crisis of our time, causing over half a million deaths to date ( july ). but covid- is much more than a health crisis, it has tremendous socioeconomic impact, the scale of which is still hard to assess. measures to address the health crisis generate economic impacts (and vice versa). social isolation measures to "flatten the curve of the pandemic" buy time to increase capacity in the healthcare sector but inevitably deepen the macroeconomic recession. the world bank expect the global economy contract by . % in , approximately three times the size of the - great financial crisis (gfc) and far more widespread. emerging markets and developing economies (emdes) have been severely hit by massive capital outflows, reducing debt servicing abilities (especially for dollardenominated debt) and generating long-term challenges; "with more than % of emdes expected to experience contractions in per capita incomes this year, many millions are likely to fall back into poverty" (world bank ). the economic consequences of the adverse coronavirus shock are: (i) an elevation of uncertainty, which increases precautionary savings, thus reducing consumption and also curtails the appetite for productive investments; (ii) a rise in unemployment, part of which is likely to be permanent; (iii) a decline in the volume of international trade and disruptions in global supply chains; (iv) falls in commodity prices (especially the price of oil), making current account financing of traditional commodity exports challenging; (v) a sharp increase in the required risk premia for holding risky assets. this initially resulted in a plunge in prices of risky assets (e.g. stocks or high-yield bonds) and a sharp increase in financial volatility. however, central bank interventions (especially by the federal reserve of the united states of america-us fed) have seen recoveries from march . extraordinary macroeconomic policy response, on both the fiscal and monetary fronts, has slowed the rates of economic decline. in many countries, fiscal measures have replaced a proportion of lost incomes and mitigated default risk, loan guarantees have helped keep businesses afloat, and liquidity provision by central banks have kept the financial system functional. fiscal authorities in european and the usa took measures that can be classified within three broad categories: immediate fiscal measures and direct transfers to households; tax deferrals and liquidity measures; and loan guarantees. the scale of intervention is truly unprecedented reaching almost % of gdp in germany and % of gdp in the usa. on the monetary front, the fed cut interest rates to zero, announced unlimited purchases of treasuries and mortgage backed securities and started buying corporate debt. moreover, the fed opened debt swap lines with foreign central banks to provide dollar liquidity to the international financial system. the value of fed measures to date exceeds . trillion dollars. the european central bank ecb "has offered low-interest loans to banks, significantly boosted asset purchases, and allayed fears of member-country defaults by lifting distributional restrictions on its bond-buying program" (world bank ). moreover, the eu's recovery plan (proposed may ) mobilizes investments through a recovery instrument of € bn for the period - and a reinforced a long-term budget of € . trillion for the period - . despite these unprecedented measures, the course of the pandemic and its developing economic impact remains uncertain. how can long-term economic dislocation be avoided? a first priority should be to ensure that the work force remains employed. second, governments should channel financial support to public and private institutions that support vulnerable citizen groups. third, small medium enterprises (smes) should be safeguarded against bankruptcy. (the need for taxpayer money to support large nonfinancial corporations is much less obvious.) fourth, policies will be needed to support the financial system as nonperforming loans mount. fifth, fiscal packages, comparable to the loss of gdp, will have to be financed by national debt. while this should be structured to avoid another debt crisis, finance should be directed to investments with positive social, economic and environmentally sustainable profiles, as discussed in the following. there is widespread scientific speculation that economic growth has pushed humanity into new ecological niches wherein humans and animals exchange novel, infectious viruses of which covid- is just the latest in a considerable list of examples. furthermore, the intergovernmental panel on climate change (ipcc) has warned that global warming will likely accelerate the emergence of new viruses. overall, climate change has the potential to end up killing more people than covid- , although this is obtusely referred to as an "increased frequency and severity of natural disasters". such language, the delayed, cumulative nature of the threat and the necessity of coordinated international response, all mitigate against the urgent action that is required. timing is also important. as ipcc ( ) reports, the level and speed of change needed to successfully tackle the climate crisis, is unprecedented; incremental changes will not be enough. that said, there are aspects of the climate change crisis which are less challenging than the covid- pandemic. as sterner ( ) notes, the climate crisis requires policy changes that are less disruptive, economically, socially and culturally, than the measures being taken right now to tackle covid- . for the climate, we do not need to close down the economy. on the contrary, we need a transition to a low-carbon economy that supports public and private investments in renewables, energy efficient and circular, technologies and infrastructure. these technologies exist (wind, solar, etc.) and are becoming consistently cheaper than fossil fuels, while energy storage installations are increasing exponentially. there is growing evidence that green stimulus policies have advantages over traditional fiscal stimulus and that climate-positive policies also offer superior economic characteristics. for example, hepburn et al. run a global survey to assess stimulatory fiscal recovery policies implemented in response to gfc. the economists from countries were asked to ascertain their perspectives on covid- fiscal recovery packages according to: "speed of implementation", "long-run economic multiplier", "climate impact potential" and "overall desirability" according to social, political and personal factors. the responses indicate that green stimulus policies deliver higher multiples due to reduced long-term energy costs and flow-on effects to the wider economy. "relaunching the economy does not mean going back to the status quo before the crisis but bouncing forward. we must repair the short-term damage from the covid- crisis in a intergovernmental panel on climate change, . way that also invests in our long-term future". this code explains the strategy of the eu recovery plan based on three axis: the european green deal, adaptation to the digital age, and a fair and inclusive recovery for all. we must start investing in what makes our socio-economic system resilient to crisis. now is the time to usher in systemic economic change and the good news is that we have our blueprint: it is the combination of un agenda ( sdg) and european commission's european green deal. the european green deal (egd) announced december is the new growth strategy of the european union and is based on four principles: (a) climate neutrality by , (b) protection of human life and biodiversity by cutting pollution, (c) world leadership in clean technology, (d) leave no one behind. the egd investment plan amounts to eur billion per year by . the egd just transition mechanism will help mobilize at least € billion over the period - in the most affected regions. the - multiannual financial framework (mff) allocates an overall target of % for climate mainstreaming across all eu programs. the proposed european climate law aims to turn the egd's political commitment of climate neutrality, into a legal obligation. based in un environment program (unep) emissions gap report , global emissions need to be reduced by % by . unfortunately, the proposed law does not include an ambitious goal with regards emissions, nor does it address the legislative interventions required to achieve climate neutrality by . together with the egd, the sustainable development goals (sdgs) and the paris agreement call for deep transformations. while significant progress is being made on some goals, no country is currently on track towards achieving all sdgs. sachs et al. ( ) identify the major interventions needed to achieve each sdg and group them in six sdg transformations, which operationalize the sdgs at government level and can prove instrumental for egd implementation. the success of the join implementation of the sdgs, the egd and the eu recovery plan will depend on the eu's capacity to engage with its citizens in codesigning the pathways that will allow them to reach the vision, hence the introduction of the european commission climate pact. https ://ec.europ a.eu/info/live-work-trave l-eu/healt h/coron aviru s-respo nse/recov ery-plan-europ e_en. european parliament, committee on environment, public health and food safety draft report on the proposal for a regulation of the european parliament and of the council establishing the framework for achieving climate neutrality and amending regulation (eu) / (european climate law), / (cod). the review of the climate law summarizes the review of the climate change committee of the greek ministry of energy and the environment, the first author of this paper is a member of this committee and co-author of this greek review. united nations environment programme ( ). emissions gap report . unep, nairobi. the proposed climate law does not allow the european commission to impose sanctions on member states (ms), while there is lack of reference to the financial mechanisms that will be required to achieve the goal of climate neutrality. moreover, the law does not consider (a) the well-documented heterogeneity in area-specific climate vulnerability among ms, (b) an eu wide carbon tax and (c) strengthening the european ets. sachs et al. ( ) : the sustainable development goals and covid- . sustainable development report . cambridge: cambridge university press. ( ) education, gender and inequality; ( ) health, well-being and demography; ( ) energy decarbonization and sustainable industry; ( ) sustainable food, land, water and oceans; ( ) sustainable cities and communities; and ( ) digital revolution for sustainable development. https ://ec.europ a.eu/clima /polic ies/eu-clima te-actio n/pact_en. recent generations, including the present, have experienced at least three global crises: the financial crisis - , the ongoing covid- pandemic and the developing climate crisis. if we continue attempting to address the latter two with the same socio-economic model that gave rise to the former crisis, we will fail to find a sustainable and resilient socio-economic-environmental pathway. we believe that we can even do better than just react to crises by adapting to the new crisis-born reality. we can use the integration of scientific, economic and socio-political knowledge to design policies which not only address the immediate impacts of the covid- pandemic, but mitigate the existential threats of future pandemics and the ongoing and unfolding disasters of climate change, biodiversity loss and planetary boundary exceedance. what is needed now is a fundamental transformation of economic, social and financial systems that will trigger exponential change in strengthening social, economic, health and environmental resilience. we need big thinking and big changes. system innovation and transitions thinking can help but calls for intense public participation. now is the time, in addition to directing funds to the control of the epidemic and relevant biomedical research, as well as investing in border security, safe travel and safe trade, now is the time for financial institutions and governments to embrace eu taxonomy for sustainable investments ( ) to phase out fossil fuels by deploying existing renewable energy technologies, eliminate fossil fuel subsidies and redirect them to green and smart climate mitigation and adaptation infrastructural projects, invest in circular and low-carbon economies, shift from industrial to regenerative agriculture and invest in food security, promote european supply chains, reduce transportation needs and exploit the limits of the digital revolution, while ensuring secure information and communication technology networks. a decisive march along this sustainable pathway will enhance economic and environmental resilience, create jobs, and improve health and well-being. the transition should be inclusive and "leave no one behind", hence the need of transforming citizens into codesigners and co-owners of the sustainability transition pathways. kiel institute for the world economy, kiellinie , kiel, germany. wilfried. committing to rigid shutdown measures to contain the spreading of the corona virus has been undertaken on the tacit assumption that these measures will be temporary and can be loosened when the covid- infection rates decrease and discontinued altogether once vaccines are available. mitigating climate change and achieving ambitious temperature targets as set out in the paris agreement require a long-term structural change taking us away from our current carbon-intensive economy to a zero-carbon and then net-negative carbon economy. as current research holds out little hope that a "perfect" vaccine in the form of solar climate engineering will be available in the future, the measures and efforts required must translate into a permanent, ongoing form of commitment. while progressive climate change and the spread of the coronavirus operate on very different timescales, impatience about the duration of corona lockdown has indicated once more a fundamental problem for (long-term) environmental concerns. clearly, the economic and social costs associated with the emergence of the virus and the shutdown are significant , oecd . but any serious cost-benefit analysis would need to take into account not only the fact that different degrees of lockdown are available but also that the overall cost is affected by the expectations of agents regarding possible future re-lockdowns due to insufficient containment of the virus. seen thus, it is anything but clear at which point in time the actual cost of lockdown would have exceeded the economic cost of the virus spreading in an unmitigated (or insufficiently mitigated) way. during the course of lockdown measures, voices calling for a "green" recovery stimulus package centring around low-carbon investments in the aftermath of the corona crisis have make themselves heard. by contrast, advocates of postponing climate mitigation-related taxes, levies, and regulations have also entered the fray, claiming that timely recovery should not be jeopardized by any additional economic burdens. the debate on the relation between (economic) recovery and climate policies has been conducted from three major perspectives. the first of these is largely notable for general statements of intent recommending that the recovery should be "green" and sustainable, that eu climate targets should be supported, and that other environmental targets (maintaining biodiversity, etc.) need to be taken into account when designing recovery measures. such well-meant counsels as the statement issued by the german national academy of sciences leopoldina ( ) are useful in reminding us that recovery from the corona crisis should not come at the expense of neglecting other objectives and that climate policy should not be backburnered, as was the case after the financial crisis in . otherwise, they are of little practical value. the second approach has involved rather detailed proposals calling either for a "greening" of recovery by foregrounding measures to support renewable energies, public transport, energy efficiency, etc. or for a "blackening" of recovery by postponing and/or abandoning climate measures and environmental regulations. predominantly, these proposals are representing the positions of the various interest groups involved. for example, representatives of the aviation industry try to prevent the harmonization of carbon prices on fuels with respect to kerosene and argue against the introduction of kerosene taxes. this idea resurfaces in the discussion on recovery measures by, say, the austrian aviation association ( ). on the other hand, in its comprehensive list of (recovery) demands, the ngo german environment action ( ) urges for example for the abandonment of blue hydrogen projects (though not explaining why this is likely to stimulate economic recovery). various other interest groups are in favour of postponing, suspending or even abandoning existing environmental and climate regulations. for example, janusz kowlaski, the polish deputy minister of state assets urges "…[that] the ets [european emissions trading scheme] should be removed from january , or at least poland should be excluded from the system". clearly, there is no point in discussing nonsensical ideas of this kind. but some of these proposals also make sensible suggestions like adjusting the german cap on renewable energy installations or abandoning the eu average fleet-consumption regulation because the former contradicts german renewable energy targets and the latter is an inefficient instrument for regulating vehicle emissions. however, these suggestions do nothing to provide stimulus for a quick recovery. while specific processes and regulation timelines for regulations may need to be adjusted in the context of the corona crisis, sensible measures of this kind should be discussed and decided upon in the regular political process. confining potential stimulus and recovery measures to their proper purpose does not mean imposing a ban on meaningful (climate or environmental) policies that are not associated with the corona crisis. the third and most sensible perspective replaces specific proposals with (sustainability) assessment guidelines like those suggested by the world bank ( ). while hardly any possible recovery measure would perform well against the comprehensive list of criteria provided by the world bank, such guidelines are helpful in arguing against interest group driven proposals. the world bank has suggested that potential measures up for consideration as part of a recovery strategy need to be assessed against both, short-and long-term criteria, an example for the former being the expected economic multiplier associated with certain measures. bayer et al. ( ) suggest that income transfers (as planned under the us cares package) perform well against this specific short-term criteria: they could help to stabilize private-sector spending and the multiplier could increase to in the case of transfers being conditional-but not related to emissions but to the propensity to consume, i.e. conditional on being unemployed. however, privatesector spending like this should not imply any unintended adverse effects on essential long-term structural change that might arise from such things as (temporarily) adjusted risk preferences. once postponed or stimulated demand and investment take place during the recovery process, carbon-price signals are vital in providing technology-neutral incentives for low-co purchasing and production decisions. overloading stimulus or recovery packages with too many (emission-related) conditions performs poorly against the short-term criteria with respect to a timely recovery. even worse, the inclusion in recovery packages of various detailed suggestions from the various interest groups usually results in a non-transparent, rent-seeking, and political bargaining process in which it remains unclear whether (sensible) individual emissionrelated decisions are being prioritized at the expense of a more challenging long-term climate policy. accordingly, accounting for the long-term criteria requires that existing or planned climate policies providing incentives for emission reductions and technological innovation should remain in place and not be postponed, let alone weakened. otherwise, uncertain (short-term) recovery impulses most likely come at the cost of less efficient emission-reduction paths in the long term. the coronavirus pandemic is having a serious impact on the economy. eurostat estimates that seasonally adjusted gdp decreased by . % in the eu during the first quarter of , compared with the previous quarter. in certain sectors, the covid- crisis has led to the temporary or even permanent closure of sites, a collapse in demand and an increase in production costs linked to the fight against the spread of the virus. this decline in activity can trigger bankruptcies, which result in unemployment and the destruction of physical and human capital, leading in turn to a loss of specific knowledge and skills and to market concentration and the partial relocation of production activities. from an environmental point of view, bankruptcies and relocation may generate higher emissions by increasing production in more polluting sites abroad and by increasing the transportation of goods. in addition, the decline in economic activity may have a negative effect on research and development spending, which is crucial for future growth and the development of more environmentally friendly technologies. many measures have been put in place to limit the economic effects of the covid- crisis. at the european union level, a number of measures such as direct subsidies, selective tax benefits, advance payments, state guarantees for loans and subsidized public loans to companies have been implemented. in addition, many large companies are being bailed out and there is a debate on whether conditions should be attached to this state aid. these conditions could relate to various commitments such as relocating activities, paying taxes, safeguarding employment, and protecting the environment. on may , the eu confirmed that large companies receiving emergency cash during the covid- crisis will not be obliged to devote funds to "greening" their operations. rescued firms will only have to report on their use of the aid and in some cases the aid could be attached to conditions such as a ban on dividends and management bonus payments. nevertheless, member states are free to design national measures in line with additional policy objectives, such as further enabling the green transformation of their economies. many stakeholders are still pushing for conditions to be attached to the bailouts. for instance, the eg think tank proposes making the rescue of airlines conditional on the use of less polluting fuels and tying aid to car manufacturers to the development of electric vehicles. a group of german companies has also requested that state aid be linked to climate actions. this article examines the merits of making aid conditional on environmental efforts. we focus on the rescue plans for companies rather than on recovery plans or the european green deal, which was launched before the covid- crisis. we show that tying aid to environmental efforts is difficult to implement and requires both controls and sanctions, as well as a large amount of information. we also discuss the merits of tying bailouts to environmental efforts compared with implementing more stringent environmental policies (presuming that companies will be bailed out in any case). since environmental efforts can lead to higher product prices and lower profits, two dimensions of acceptability must be taken into account: acceptability from the point of view of companies and social acceptability. acceptability of environmental policies by companies is a necessary condition for their implementation. in the midst of the current crisis, many polluting industries are lobbying to weaken and delay environmental regulations. for instance, the environmental protection agency issued a sweeping suspension of its enforcement of environmental laws, allowing companies to breach environmental standards during the coronavirus outbreak. in indonesia, the trade ministry revoked rules requiring basic certification that wood exports were legally produced, in response to lobbying from the furniture and logging industries. lobbyists may also encourage legislators to compensate companies for losses related to environmental regulation. the implementation of rescue plans, by providing aid and guarantees, could be a tool to make environmental efforts more acceptable for firms. acceptability by society is also central. it depends on the redistributive effects of environmental policies, especially since they are often regressive. in france, the "red caps" and "yellow vests" movements illustrate the difficulty of implementing such policies. both of these movements led to the cancellation and delay of environmental policies (eco-tax applied to heavy vehicles and carbon tax, respectively). the covid- crisis may affect societies' support for more ambitious environmental policies. several observations can be made. first, it appears that there is a confirmation bias, as countries and ngos that had already committed to fight against global warming want to intensify efforts, while countries that were already recalcitrant are calling for a decrease in efforts in the light of the economic crisis. second, the covid- crisis makes the risk of disaster more salient and vivid and may therefore increase the demand for stronger environmental protection. as explained by sunstein ( ) , if a particular risk is cognitively "available" then people will have an increased fear of the risk in question. finally, the crisis has revealed that populations will accept drastic measures (lockdown, wearing face masks) and a rapid change in social norms (social-distancing, for instance), which shows the ease with which individuals could adapt to more ambitious environmental policies. see oates and portney ( ) for a literature review of interest groups and environmental regulation. "polluter bailouts and lobbying during covid- pandemic", the guardian, april , . burkey and durden ( ) and joskow and schmalensee ( ) have detailed how firms can influence the regulator's decisions in the context of pollution rights markets, while bovenberg and goulder ( ) , hepburn et al. ( ) and nicolaï ( ) have shown that few permits are sufficient to neutralize the losses in profits and make the implementation of pollution permits acceptable. on march , the czech prime minister, andrej babis said that the european green deal should be put to one side. during the same period, the green coalition of environmental organizations organized an appeal urging lawmakers to design a green, healthy and just recovery. we study two possible ways of increasing environmental efforts: making aid to companies conditional on environmental efforts or making existing environmental policy more stringent. making aid conditional on efforts to protect the environment can take different forms. commitments may relate, for example, to reducing pollutant emissions, using less polluting production processes, increasing expenditure on research and development, and producing less polluting products. for instance, in france, renault's bailout requires it to increase the share of electric vehicles, while the billion euro air france bailout imposes the use of at least % of alternative jet fuel by , a target of % emissions cuts by , and a % decrease in domestic flights by , especially those that compete with high-speed trains. conditional aid as currently envisaged is equivalent to negotiating and implementing individualized standards on technology, final products, research and development efforts, emissions and performance for each company. the first question that arises is how to determine the conditions. conditional bailouts allow the regulator to individualize the standards applied to a particular firm, making it possible to set the most appropriate instrument and the optimal level of severity for each firm. when making its decisions, the regulator should consider the possibility of a rebound effect as explained by saunders ( ) . an emissions standard may avoid such an effect, but a standard on technology may increase emissions. furthermore, the regulator should take into account its access to information. if the firm commits to finance research and development in green technology in exchange for being bailed out, it will be hard for the government to determine whether the state aid was actually allocated to research. for example, since the results of research are uncertain, a lack of innovation may be explained either by the firm's characteristics (anti-selection problem) or by the misallocation of public funds (moral hazard problem). finally, the regulator should take into account competition, since firms receiving bailouts usually have market power. a government will mainly intervene to save a firm if its bankruptcy would have a significant effect on the economy. the government should hence ensure that the conditions do not further distort competition. a firm with a competitive advantage, for example with cleaner technology, may have an interest in advocating more ambitious environmental efforts for itself but also for its competitors in order to increase its market share by preventing the entry or inducing the exit of such competitors. the effectiveness of conditions will therefore depend on the type of commitment, competition in the market, and the demand elasticity of the final good. another question relates to the duration of the contract. some actions are reversible and after a certain period of time companies can cancel or amend them. for example, the use of cleaner but more expensive inputs is an easily reversible strategy, while a shift in production, for example from internal combustion vehicles to electric vehicles, is a more expensive choice to change. in addition, research and development efforts produce long-term effects with the creation of innovations and possible technological spillovers. the duration must therefore be individualized in function of the company's characteristics. it should also be noted that conditional aid can lead to windfall gains. some companies had already planned emission reductions and changes in strategy. these decisions were aligned with the companies' interests. if the company benefits from the environmental efforts put in place, these can no longer be considered as a counterpart to the company's bailout and the company should then make greater efforts. it seems clear that the success of such schemes lies in companies' compliance with the commitments. companies may nonetheless have an interest in not complying with them. it is therefore necessary to monitor companies' implementation of the commitments and to sanction those that fail to honour them. supervision costs will thus be incurred. one possibility for alleviating control costs is to publicly announce the commitments, which facilitates the monitoring of companies' commitments by society (e.g. by journalists, politicians and non-governmental organizations). this also gives the firm a further incentive to respect the agreement in order to maintain its reputation and to retain its customer base (heyes et al. ( ) and heyes and kapur ( ) ). we now focus on the sanctions to be applied in the event of non-compliance with the commitments. various penalties could be considered, such as financial penalties, a ban on applying for the attribution of public contracts and the state's participation in the company. the sanctions must be explicit, credible and sufficiently significant to discourage companies from breaking their contracts. however, given the current economic situation and the fragility of companies, governments should be cautious when using financial penalties or bans from participating in public contracts since, if effective, they could be fatal to companies. an alternative could be for the state to take a share in the company in the event of non-compliance with commitments. such shareholdings would make it possible to influence companies' strategic choices, but they raise efficiency problems. cavaliere and scabrosetti ( ) , schmidt ( ) and de fraja ( ) , for instance, highlight two effects: production is more efficient in privatized firms because better incentives can be given to managers and employees (productive efficiency), while public firms are more socially efficient because the government cares about social welfare and internalizes externalities associated with firm liquidations (allocative efficiency). existing environmental policies inevitably generate monitoring costs; however, these costs will be borne in any case. increasing the stringency of environmental policy involves determining new levels for existing instruments, which generates costs, but there will be no additional monitoring costs. moreover, opting for a more stringent environmental policy means that market-based instruments can be employed, which is not feasible in the first strategy. due to the principle of non-discrimination, it is unlikely that individualized taxes could be introduced under the negotiated bailout conditions. environmental economists agree that these instruments are more effective than command-and-control instruments since they have the potential to generate revenue and allow for a double dividend, provide incentives to invest in clean technology and require less information to be designed. nevertheless, making aid conditional on environmental efforts makes it possible to individualize the regulatory instruments for each firm, which is not possible in the context of marketbased instruments. the positive effect of the instrumental individualization induced by conditionality only materializes if the existing environmental policy is based on commandand-control instruments. with market-based instruments, individualization is not required to achieve an efficient outcome, whereas it is necessary in the case of command-and-control instruments. companies' negotiation power is an additional argument for increasing the severity of environmental policies rather than conditioning bailouts on environmental efforts. regardless of the policy, firms may use their bargaining power to mitigate the stringency of the regulation or the effort they commit to make. it is clearly easier for a firm to influence its specific negotiated conditions, which are one-on-one relationships, than to influence environmental policies, which would require coordination and a common interest among firms. furthermore, making environmental policy more stringent will affect all companies and not only those receiving bailouts, which increases the attractiveness of this strategy. since they apply to a larger number of companies, these more restrictive policies will have a greater effect on the environment. to conclude, this note analyses the advantages and disadvantages of making bailouts conditional on environmental efforts. we show that such a system could be beneficial for the environment and would be a counterpart to bailing out companies. however, it is costly, requires a large amount of information, and is less efficient than increasing the stringency of existing environmental policies. on the other hand, making aid conditional on environmental effort is more acceptable from the companies' point of view than increasing the severity of environmental policies. companies would rather commit themselves to environmental efforts than pay taxes or buy permits in order to minimize compliance costs. to succeed in making environmental policy more ambitious, the regulator needs the support of society to compensate for companies' reluctance. if there is strong public support, governments should not negotiate conditional aid but should increase the severity of environmental policies. they can integrate such actions into recovery plans or, in the case of the european union, into the revision of the green deal. it is therefore particularly important to study how the covid- crisis has changed society's perception of the need for more stringent environmental policies. for instance, a recent survey by ipsos shows that three out of four people in major countries expect their government to make protection of the environment a priority when planning a recovery from the coronavirus pandemic, although there is considerable heterogeneity across countries. the post-covid- reality is changing the context of most policies, including those in the fields of energy and the environment. the eu green deal objectives should be maintained but concrete policies may have to be adjusted to this new reality. a major energy transition is under way, shaped by political will to tackle climate change. policies have been defined under the paris agreement and geared to a number of targets. the eu has decided to reduce its greenhouse gas emissions by by at least % compared to and has agreed to continue the path towards climate neutrality by . the immediate recession following the covid- crisis drastically reduced energy consumption and greenhouse gas emissions (le quéré et al. ) . the sudden decline in greenhouse gas emissions is the opposite of what a meaningful response to climate change should be, in terms of both quality of life and economic efficiency. the challenge is to structurally decouple economic growth from emissions, not to have them both going down. the lockdown may have some lasting effect in changing some of our habits ), e.g. a generalized familiarity with telework. one can also expect a more general reflection on whether all business and leisure travel, not least by air, is necessary. nevertheless, many changes may not be as extensive and lasting as some would wish. for this reason, it is important to integrate a climate check into the stimulus packages that governments and european institutions are currently designing. the current health crisis and the likely economic downturn could be seen as an unsolicited-and much regrettableopportunity towards a carbon-neutral future koundouri ) . the agreements reached in the context of the eurogroup, the latest turn in the european budgetary discussions, as well as the statements by the commission president all point into this promising direction. the eu green deal has confirmed the eu emissions trading system (ets) as a key element and the price of eu allowances serves as a key indicator worldwide. as could and should be expected, carbon prices have fallen during the lockdown reflecting reduced demand for allowances in line with the drop in power and industrial production. this temporary drop from the € to a € - range, acts as an important automatic stabilizer for businesses in distress. a repetition of the experience of a sharp fall in the see on this issue the important draft report prepared by the european parliament committee on the environment, public health and food safety (european parliament, ). https ://lifed icetp rojec t.eui.eu/ / / /covid - -clima te-polic y-and-carbo n-marke ts/. https ://www.consi lium.europ a.eu/en/press /press -relea ses/ / / /repor t-on-the-compr ehens iveecono mic-polic y-respo nse-to-the-covid - -pande mic/-point : "work is ongoing on a broader roadmap and an action plan to support the recovery of the european economy through high quality job creation and reforms to strengthen resilience and competitiveness, in line with a sustainable growth strategy". https ://ember -clima te.org/carbo n-price -viewe r/. price of eu ets allowances after the recession and a long period of very lowcarbon price levels should be avoided. there are two reasons to believe that this could happen: (i) the eu ets now has a market stability reserve (msr) operating in the short-medium term and (ii) long-term market expectations could be shaped by the carbon neutrality objective. the msr started to operate last year and absorbs a potential oversupply in the market in the short and medium term. if the allowances market is "long" beyond a threshold set in legislation ( million tons, which is approximately % of ets emissions in ), the msr intervenes by withdrawing allowances equal to a percentage ( % up to , % thereafter) of the excess. at the end of , the allowance market was . billion tons "long" and, therefore, the supply of allowances for the period september to august has been reduced by million tons (these allowances are placed in the msr). some question whether the msr, with its delayed adjustment mechanism, will be sufficient to avoid a sharp fall in the allowance price (cf. flachsland et al. ) . in fact, any reduction in the supply of allowances through the msr for the period september -august will still be based on the excess supply of allowances in , i.e. before the current crisis started. in case the msr is unable to absorb the surplus, the eu commission should propose changes in the planned review of the ets in . long-term expectations might overtake this short-term risk. in its european green deal, the commission already indicated its intention to tighten the greenhouse gas emission reduction target from % to %, or even % (with respect to levels). today, the ets sectors face a mandatory emission reduction of % by compared to , and revised targets will likely increase that obligation by at least another or %. such a reduction in the supply of allowances would likely push their prices up, or at least reduce the extent of their decline, in the face of lower demand due to the economic downturn. therefore, carbon market participants as well as those developing innovative clean technologies and products of the future are likely to expect significantly higher carbon prices in the future. this raises the question about a possible loss of competitiveness in europe's traditional industries vis-à-vis competitors located in countries where no similar burden is imposed. some proposed a border adjustment, which would imply both a levy on imports and possibly a rebate on exports. however, such mechanisms are not easy to implement and are subject to criticism on both analytical and political grounds. therefore, it is of crucial importance to realize that a wto-compatible border adjustment mechanism will take some time before it can be implemented. meanwhile, at least equal attention needs to go to domestic policy reinforcement, such as support for innovation and a less rigid interpretation of the state aid rules. governments and european institutions are currently developing a major investment stimulus package. the commission's impact assessments on climate and energy policy serve as useful guidance on where a major surge in investments is needed. we know that energy efficiency requires a major push in the construction sector, both for new buildings and renovations in social housing, hospitals and schools. we know that the energy transition requires more investments in renewable energy, digitised grid infrastructure and energy storage. the significantly reduced electricity demand of today indicates that much more attention should go towards managing flexibility in real time instead of increasing baseload capacity. in transport, electrification is on its way, but investment in charging facilities, traffic management, clean public transport and long-distance rail needs to be ramped up. in industry, not least in power generation and carbon intensive industrial sectors, major efforts are being undertaken to develop new technologies based on hydrogen and carbon capture, use and storage, for example. such investments can create the jobs we need in the post-covid- era and allow to realise the eu green deal objectives at the same time. apart from carbon prices and investment support schemes, it remains of equal importance to maintain a consistent energy price signal throughout the economy. however, the recent fall in the prices of fossil fuels is upsetting the incentives that should support a transition towards sustainability. a reference criterion for economic decisions has been lost and the consequence may be a paralysis, or even a "comeback" of fossil fuels, mothballing or abandonment of investment in renewables. consequently, the business case of the green transition may appear to be weakened in the near term, but a clear policy response may be politically more acceptable because of the price drop in fossil fuels. this raises the question about the other half of europe's emissions, namely those not covered by the ets, in particular the sectors of transport and buildings. the pricing of these emissions can be much improved through the planned review of the eu's energy tax directive. this offers a major opportunity to remove the all too generous exemptions, such as on maritime and aviation fuels, or by adding a co element to the harmonized minimum tax rates. in such a manner, prices of fossil fuels could be stabilized at the pre-covid levels via temporary taxes, whose revenue could help finance the various income-support policies adopted and/ or an acceleration of investment projects for sustainability. in this way the eu should better prepare for a long period of low oil and gas prices and seize the opportunities these can offer. public measures to combat the covid- pandemic have led to a severe economic crisis. in order to cope with this crisis, comprehensive government aid is being requested. accordingly, governments across the world have pledged billions of euros for extensive recovery programs. one of the main questions debated in this context at the moment is how "green" these recovery programs should be ). the expectation of huge amounts of public money being distributed at short notice brings interest groups of every shade to the scene-preferably with old wish lists on hand. consequently, there is a big risk that recovery programs will be captured by interest groups (for an overview of the literature on regulatory capture, see dal bo ). on the one hand, climate change mitigation is put under pressure as being an "extra burden" for industries. for example, european car manufacturers have called for postponing the upcoming tightening of eu emission standards for car fleets (topham and harvey ) . some eu member states call for stalling the eu commission's plan of a european green deal (simon ). on the other hand, many recommend spending the public money mainly on measures that also help mitigating climate change-among them frans timmermans, executive vice-president of the european commission (schulz ), or fatih birol, head of the international energy agency (birol ) . there is one thing that must not be overlooked in this politico-economic competition: public funds are still short and must be used reasonably. otherwise ill-designed (green) subsidies can quickly turn into a part of the problem instead of being the solution. previous "cash for clunkers" programs warn as an example of a misguided recovery measure. these programs were introduced in many countries after the financial crisis and provided financial incentives to trade old, less fuel-efficient cars for new, more efficient ones. empirical analyses have shown very mixed results regarding both the economic and the environmental stimulus effects of these measures (grigolon et al. ; li et al. ; mian and sufi ) . at the beginning of every discussion about (green) recovery programmes, it is therefore important to develop transparent and sensible criteria based on which public aid should be allocated. after the initial bail-out programmes, public recovery programmes to stabilize the economy are now debated politically. certainly, this generates an unprecedented window of opportunity for structural transformation. moreover, the distribution of public aid may also justify committing beneficiaries to public interests to a certain extent. consequently, the currently available political degrees of freedom should be used to promote the transition of society towards sustainability. subsidies to branches like tourism, aviation and agriculture-which are particularly hit by the crisis and are lagging behind in terms of sustainability-should be paid conditional on meeting minimum environmental standards. new investments into long-lived, fossil-fuelled assets must be avoided. a recovery program cannot only be about re-establishing the status quo ante by assigning large public funds, possibly creating new barriers for sustainability transitions. in this respect, it makes sense to implement recovery programs that are in line with the objective of mitigating climate change-as called for by many at the moment. however, such green recovery programmes must not be arbitrary. green recovery programmes must go beyond green subsidies. first of all, it is also important to reduce unnecessary barriers for green investments, for example by revising legal constraints to the expansion of renewable energies like solar photovoltaics of wind power. moreover, any green recovery program can only effectively and efficiently spur decarbonization if it combines with a carbon price and the abolition of environmentally harmful subsidies. the direction of recovery must be crystal clear. otherwise green subsidies risk being ineffective and costly approaches to mitigating climate change (kalkuhl et al. ; palmer and burtraw ) , while imposing additional burdens on public budgets and reducing political degrees of freedom in the future. for subsidies to be economically justified, they need to meet clear criteria. for green recovery programs to succeed in the competition for public funds with other important policy fields (such as health or digitalization), they must help stabilize the economy. moreover, policy makers need to be aware that some of the currently observed economic problems might even resolve without any government aid. it can expected, for example, that global supply chains will resume and that people will catch up on purchasing durable goods like cars, at least partly. it is exactly (the maintenance of) environmental regulation that may help steer this consumption towards more sustainable modes. government interventions must take effect where permanent disruptions are looming. one example: innovative green business models may particularly be at risk if banks limit loans in the presence of the current uncertainties (lehmann and söderholm ) . in this case, government loans may provide direct assistance. in contrast, attempts to lower prices for goods and services-e.g. for cars (vat reduction, purchase premiums) or electricity (reduction of energy levies)-are rather inappropriate means to stabilize the economy. such measures fail to address the actual sources of insufficient investments or reduced purchasing power, and are therefore inefficient ways of spending public budgets. furthermore, it is unclear whether and to what extent such discounts will be passed through to final consumers by market prices (peltzman ) . green recovery programs should focus on government interventions that would also have been economically reasonable without the covid- crisis-for example, to correct market failures next to the co externality (bennear and stavins ; fischer and newell ; lehmann )-and that have the highest priority for climate policy. moreover, those measures should be implemented for which rational concepts have been drafted already and that can be realized promptly. positive examples of such "no-regret measures" can be found in the transport sector, for instance. this sector is severely lagging behind in terms of climate change mitigation, and economic rationales for public expenditures exist at least partly (briggs et al. ; low and astle ). in addition to that, numerous actors have already developed elaborated programmes of measures. those measures that can be implemented quickly, should now be launched-for instance to electrify the transport sector or to strengthen public transport. (green) recovery programmes must not only address the expenditure side. a currently still disregarded issue is the question how the required billions of euro could be raised. public expenditures for a green recovery program should at least partly be funded by polluters by implementing a carbon price and abandoning ecological harmful subsidies. such policies internalizing environmental costs would not be an extra sacrifice-but rather part of the solution both for revenue problems and for the redirection towards sustainability (for a review of the double-dividend hypothesis, see goulder ). the coronavirus crisis has opened up a window of opportunity for transformation. this should be used without getting off the regulatory track. green recovery programs must not be reduced to a mere competition for green subsidies. abandoning barriers to green investments and imposing a carbon price are equally important. where economically sensible, green subsidies should contribute to both stabilizing the economy and mitigating climate change. moreover, smart green recovery programs may contribute to raising revenues for the additionally necessary public expenditures. the world is currently facing the largest pandemic since spanish flu in . this has led to a lockdown policy on an unprecedented scale and measures of social distancing that are expected to continue. in france, as elsewhere, the "great lockdown" has disrupted food production chains through simultaneous shocks to demand and supply. populations have seen their food consumption habits be severely modified (e.g. closure of restaurants and markets). fearing food shortages, consumers have often stockpiled basic necessities, which has led them to actually provoke shortages, albeit temporarily. food production has also been disturbed, most notably by the reduction in the available workforce, whether domestic (due to the lockdown, illness or childcare) or foreign (temporary closure of borders). the issues at stakes are numerous, including deglobalization and environmental impacts, in both the long and short terms . the pandemic will lead to unprecedented uncertainties in food supply chains. in addition to the health crisis, a dramatic drop in worldwide gdp is anticipatedapproximately %-with a partial catch-up in , according to the international monetary fund (imf ). the reduction in income will soon impact food consumption. some authors are already pointing to an increase in social inequalities. the most fragile populations could slide into severe food insecurity, including in developed countries, as shown by deaton and deaton ( ) for canada and power et al. ( ) for the uk. however, the fao is rather reassuring about the total volume of food (cereal) at the global level. it also notes that the world price index has fallen in recent months. this does not necessarily mean that this decline is effective regardless of the type of agricultural production. in particular, fruits and vegetables could become more expensive. agriculture is by nature a risky activity, and the adoption of eco-environmental practices can only increase this risk. as a consequence, organic farmers, for instance, could be particularly affected by the combination of health and economic crises. the cost of organic production is therefore structurally higher, which could pose a problem in the event of an income shock. to add value to their production, many small farmers combine organic farming with short food supply chains. this makes it possible to regain a more comfortable margin than that allowed by mass distribution. however, here again, the health crisis has profoundly changed marketing channels. while supermarkets were stormed with shoppers at the beginning of the crisis, some short channels were closed, such as markets and restaurants, to preserve social distancing. this article therefore considers the consequences of covid- for sustainable agricultural practices, particularly for farmers who have chosen organic farming in short supply chains. to do so, we use the multi-level perspective (geels ) approach to conceptualize socio-economic transitions. the multi-level perspective (mlp) approach analyses transitions as mutation processes from one socio-technical regime to another under the pressure of macrolevel forces and the emergence of market niches that could provide the basis for a new regime (geels ) . we show here why local food supply chains are perceived by some farmers-especially the smallest-as a way to enhance the economic value of eco-friendly agricultural practices, such as organic farming. in france, the current dominant socio-technical regime based on conventional agriculture emerged gradually in the s. conventional agriculture diffuses slowly at first because of the high investment costs. however, the french state and farmers' unions support it as a means of increasing production and improving living and working conditions. farmers are then inclined to take on more debt and become dependent on their suppliers (phytosanitary products, seeds, tools, etc.), the food industry and supermarkets. as a result, this modernization of agriculture has been controversial from the outset, at least with regard to farmer autonomy and the country's food sovereignty (levidow et al. ). the early development of organic farming in france began in the s due to the effects of three negative effects of conventional agriculture, namely pollution, soil impoverishment and the lack of autonomy mentioned above. the organic label has become a marketing argument that is profitable for large farms, since they achieve significant scale effects on these standardized products. large scale organic farming is therefore less demanding and, by its nature, allows to benefit from the effects of scale. this is new competition for small farmers struggling to differentiate themselves. the organic label itself does not allow farmers to free themselves from the pressures upstream and downstream in the production chain. to differentiate themselves from large organic farms, some farmers are starting to sell in open-air markets again. at the same time, the idea that fair trade can concern north-north relations and not only north-south relations is beginning to emerge, which favours the development of community-supported agriculture. a new initiative is gradually emerging: collective farmers' shops. these initiatives began, for example, in the south of france in the mid- s and represent a more important restructuring of the farmers' market. in the medium term, the drop in income could increase the consumption of basic necessities (giffen goods) to the detriment of organic products. everything will depend on the elasticity of the demand for these products. until now, organic products have been extremely popular. it is possible that "industrial organic" will take market share from a "more artisanal organic" if consumers still want to consume organic products but cannot afford to spend a large part of their budget on them. farmers in short supply chains often have several distribution channels simultaneously, especially market gardening farmers. this allows them to be more responsive to demand. thus, the closure of farmers' markets and restaurants can be compensated for by farm shops, community-supported agriculture (csa), fixed point or home delivery, or collective farmers' shops. regarding hygiene measures, farmers are faced with two main types of strategies: receiving customers in the original locations or digitizing the process, including the more marginal case of automatic food dispensers (e.g. for eggs). selling in physical places must respect social distancing, which discourages consumption. however, conserving this method makes it possible to maintain the relational proximity between farmers and consumers. initially, this relational proximity is one of the main arguments in favour of short supply chains, as it is supposed to allow better traceability of products and to fight against social isolation (especially of the elderly). the other strategy, therefore, is to limit direct contact between human beings by means of computer tools. internet platforms already existed before the crisis and are expected to develop. some were public, such as those set up to supply school canteens. the pandemic has accelerated this process, and some regions have launched their own platforms. this solution is very time-consuming and seems difficult to sustain, unlike the others, which should have an impact in the long term. another practice has been reinforced: farm shops. during the lockdown, some consumers presumably had more time to cook and go to farms. others fled from supermarkets, considering that the products were handled by a large number of people and that there was too much traffic. it is difficult to predict whether these changes in behaviour will have a long-term impact. in addition, the pandemic has raised concerns about the reliability of international distribution channels. it is therefore possible that some policies may be sensitive to the has been growing at a very fast pace (see an indicative list of references in supplementary material ). however, little attention has been paid to the reliability of this type of epidemiological data to make statistical inferences. our initial aim was to produce a detailed statistical analysis of the relationship between weather conditions and the spread of covid- . this question has attracted significant attention from the media (e.g. ravilious ; clive cookson ) and the research community (e.g. araujo and naimi ; carleton et al. ; see a wider list in supplementary material ) due to the possibility that summer weather might slow the spread of the virus. after going through all the steps of such an analysis, we reached the unexpected conclusion that the limitations of the available covid- data are so severe that we would not be able to make any reliable statistical inference. this applies, for example, to the data provided by the john hopkins university (dong et al. ) and the data collated by xu et al. ( ) . this is a concerning and very important finding considering that such data are being widely used to make crucial policy decisions on a wide range of topics. since invalid causal inferences could be made with the publicly available covid- data, and then enter policy-making discourse, there is an urgent need to raise awareness among the scientific community and decision makers regarding the limitations of the information at their disposal. the elements discussed in this paper are also likely to be applicable to other epidemiological datasets obtained with insufficient testing and monitoring, either during exceptional epidemics or seasonal outbreaks. several challenges could undermine any causal statistical analysis of the influence of a potential determinant, such as the weather, on the spread of covid- . to start, confounding variables are likely to pose a significant problem: many factors (e.g. changes in policy or social interactions) are simultaneously influencing how the disease spreads. in addition, significant challenges come from the limitations of the covid- case count data itself. firstly, testing capacity has been a major issue in most countries. before march , very few countries had sufficient testing capacity. by april , highincome countries had significantly increased their testing capacity, but testing remained critically infrequent in most low-and middle-income countries. figure , panel a, illustrates the effect that insufficient testing capacity has on the number of confirmed cases. it distinguishes between three phases of limited (i), intermediate (ii) and widespread (iii) testing. in phases i and ii, there is a risk that the number of confirmed cases depends more on the number of tests available than on the actual number of people who have covid- , questioning the validity of any analysis relying too heavily on these data. moreover, there have been numerous concerns regarding the accuracy of the covid- tests performed so far (ai et al. ; apostolopoulos and tzani ; hu ; hall et al. ) . figure , panel b , illustrates the effects of both false-negative and false-positive test results on the number of confirmed cases. false-negative results would imply that the number of confirmed covid- cases is underestimated. false-positive results would imply that people who do not have covid- are included in the number of confirmed covid- cases. concerns regarding test accuracy create an additional problem of measurement that might affect statistical analyses. the two above-mentioned challenges are inherent in all current datasets of covid- confirmed case count and mortality. in addition, specific datasets may have imperfect geographical or time coverage. to look at the impact of the weather on the spread of covid- , we initially used a well-established approach, similar to the ones used previously to look at the impact of the weather on other diseases (e.g. deschenes and enrico ; gasparrini et al. ) (see details in supplementary material ). however, the fundamental measurement issues associated with the covid- case count data cannot be corrected by statistical techniques, as we outline in the following. the main problem is that the weather could be influencing the number of tests carried out and the segment of the population tested. for example, other respiratory diseases are often similar to covid- in their symptoms (e.g. who ) and are more common during cold weather (e.g. deschenes and enrico ; gasparrini et al. ) , which could influence the number of tests performed on people displaying symptoms of respiratory infection. therefore, even if the model correctly identified the impact of the weather on covid- case counts, it cannot distinguish between the impact of the weather on the spread of the disease and its impact on testing. table provides a non-exhaustive list of elements that could undermine any analysis of the impact of the weather on the spread of covid- using data on confirmed cases. the evidence suggests that the weather may correlate with the number of tests conducted and who gets tested. we have not been able to find any specific covid- -related evidence that the weather could impact test accuracy (e.g. the weather affecting the nasopharyngeal or oropharyngeal swabs used in the pcr analysis), even though this could be possible. other points of concern include: the fact that there may be indirect effects of weather conditions on other factors that could have an impact on the spread of covid- (such as social interactions or air pollution); the heterogeneity of impacts across populations and subgroups within a population; and the fact that some people may have travelled and therefore been infected in a different place from where the cases are reported. we ran our model (as detailed in supplementary material ) and provide results and robustness checks in supplementary material . the model would technically suggest a negative correlation (e.g. colder days would be associated with more confirmed covid- cases, and hotter days with fewer cases). yet, these results could be highly misleading since these estimates are likely to be substantially biased because of the aforementioned reasons. figure , panel a, provides an illustration of how we could have obtained a negative correlation even if temperature had no impact or a positive impact on the spread of covid- in our sample. the total number of estimated cases is given by the size of the circles as a function of temperature (x-axis). the circles in green correspond to the effects we are interested in-those that explain the influence of temperature on the spread of covid- . if temperature has no effect on the spread of covid- , then the green circles should be the same size at low and high temperatures. the pink circles represent the possible effect of temperature on testing (as reported in table ) under the illustrative assumption that high temperatures reduce testing frequency. in this case, the overall result is a negative correlation between temperature and confirmed covid- cases, even if temperature has no effect on the spread of the disease. in practice, we naturally do not know the direction of the bias caused by the effect of temperature on testing when using standard statistical methods. there is also no way for us to evaluate the contribution of each of these effects (green table non-exhaustive list of reasons why weather conditions could affect the number of covid- tests carried out and who gets tested potential reason potential implication unrelated respiratory diseases are weather sensitive (e.g. deschenes and enrico ; gasparrini et al. ) and can be confused with covid- (e.g. ai et al. ; chen et al. ) more patients with symptoms of unrelated respiratory diseases could be tested during cold weather the prevalence of other weather-sensitive respiratory diseases might make false-positive results more likely, especially if only radiographic imaging is used, since it is possible to confuse these diseases for covid- (e.g. ai et al. ; chen et al. ) the incidence of other pathologies (e.g. cardiovascular diseases) is influenced by the weather (e.g. deschenes and enrico ; gasparrini et al. ) hospital capacity and the workload of medical staff and testing structures are affected by weather conditions, with potential implications on the number of tests conducted at-risk individuals suffering from unrelated conditions are more likely to be tested for covid- , even if they only have mild symptoms for covid- people may be more inclined to seek medical attention depending on the weather (e.g. norris et al. ) due to weather conditions, people may or may not decide to seek medical attention, affecting the number of patients going to the hospital with covid- , and the workload of medical staff or pink) in our estimate. we arrive at the final size of the circles and cannot be sure if the association that we are interested in is either negative, null or positive. figure , panel b, focuses on the risk that effects could be different across different samples. the circles in blue capture other underlying factors that are influenced by temperature (such as acclimatization or the level of social interactions in the population), as well as other socioeconomic factors (such as the demographic characteristics of a population). these factors could be radically different in different regions but may also evolve over time (e.g. between winter and summer seasons). there are strong reasons to be concerned with the scenario illustrated in figure , panel b. in our sample, for example, we only have data from the start of the pandemic until end of april ; some countries (e.g. china) may be over-represented in the dataset; and the average daily temperature is relatively low at . °c. furthermore, many countries have implemented a stringent containment policy during the period covered by the sample. containment policies may have heightened (or lowered) the sensitivity of the spread of the disease to the weather because social interactions are limited. we are not able to observe how for example, sars-cov- is more infecƟous; the weather affects people's immune systems; people-to-people transmission is higher. for example, changes in the number of people with respiratory diseases other than covid- , affecƟng the number of tests performed. for example, social interacƟons evolve; or samples are for different countries. example temperature (a) esƟmates are likely to be biased because the weather influences data collecƟon (b) esƟmates could vary between samples fig. effects potentially captured by our estimate. the size of the circles represents the estimated number of cases at different temperatures. these are examples that do not correspond to actual data. in these examples, we assume no correlation between temperature and the effects in green (see legend), a negative correlation with the effects in pink (example ) and a positive correlation with those in blue. (color figure online) the impact of the weather on covid- might change at different gradients of social interaction. finally, our estimate is based on small, observed changes in temperatures, and not on radical increases or reductions in temperatures. the spread of covid- may respond differently to large variations in temperature, e.g. by °c or °c across seasons, making seasonal predictions even more unreliable. strong precautions need to be taken before using covid- case count datasets for inference. the results of our model using existing covid- data would seemingly imply a negative association between temperature and confirmed covid- cases. any projection of covid- cases with such estimates could conclude that, during the upcoming months of june to september , southern hemisphere countries would be exposed to higher risks of covid- spread and northern hemisphere countries to lower risks. these types of unsubstantiated results could be used as a misinformed justification for an early relaxation of effective social distancing measures in the northern hemisphere. these findings have equally strong implications for statistical analyses focusing on other questions that rely on covid- confirmed case count and/or mortality count data. even though the exact nature of the effects may change, such studies are also at risk of capturing the effect that their parameters of interest have on tests and test results. for example, studies interested in the effect of containment policies may have to consider that these policies substantially affect testing because they change the awareness of the disease in the population, political demands for more testing or the risk of contracting other respiratory diseases. other studies may also produce estimates that are very specific to the current circumstances in the development of the pandemic and are, therefore, not suitable to use for forecasts of what could happen in the coming months. in the medium term, more reliable data need to be gathered, for example through experimental studies that randomly test a sample of the population for covid- . in the short term, we are in a situation of fundamental uncertainty about how different factors affect or are affected by the widespread societal changes we see with the covid- pandemic. therefore, scientists, policy makers, journalists and the general public need to be very cautious when discussing how the spread of covid- correlates with the weather or any other factor. in the long term, this paper suggests that more attention should be given to how epidemiological data is recorded and used during exceptional epidemics and seasonal outbreaks, since insufficient testing and monitoring can undermine essential statistical analyses. this article calls for the complementary use of different methods for data collection, such as random testing in samples of the population. sars to novel coronavirus-old lessons and new lessons global rise in human infectious disease outbreaks carbon emissions come roaring back: will the economy, too? tellimer the european green deal sets out how to make europe the first climate-neutral continent by , boosting the economy, improving people's health and quality of life, caring for nature, and leaving no one behind. european neighbourhood policy and enlargement negotiations the eu's response to the covid- outbreak and the need for unprecedented solidarity amongst member states adaptation to climate change global carbon budget adapt now: a global call for leadership on climate resilience. the global commission on adaptation does social distancing matter? wp - macroeconomic implications of covid- : can negative supply shocks cause demand shortages? wp - will covid- have a lasting impact on the environment? bbc global energy and co emissions in does telework weaken urban structure-travel relationships? the influence of energy efficiency on other natural resources use: an input-output perspective rebound effects and ict: a review of the literature energy efficiency and consumptionthe rebound effect-a survey is telework effective for organizations? a meta-analysis of empirical research on perceptions of telework and organizational outcomes hours of work and the ecological footprint of nations: an exploratory analysis the impact of covid- on public space: a review of the emerging questions al-hukoma al-kuwaitiyya tuhathir min nafath al-ihtiyati khilal ash'hur [the kuwaiti government warns of depletion of the reserves gulf sovereign wealth funds could shed $ bn amid covid- chaos will covid- fiscal recovery packages accelerate or retard progress on climate change? oxford review of economic policy volatile coffee prices: covid- and market fundamentals (ico coffee break series no. ; ed.). international food policy research institute (ifpri) and international coffee organization (ico) oil-rich norway will withdraw a record $ billion from wealth fund as covid- batters economy world energy investment international trade in natural resources: practice and policy commodity markets outlook: implications of covid- for commodities path dependency and directed technical change: evidence from the auto industry the porter hypothesis at : can environmental regulation enhance innovation and competitiveness? how could the ecb's monetary policy support the sustainable finance transition? mimeo financial data science: the birth of a new financial research paradigm complementing econometrics? does the fossil fuel divestment movement impact new oil & gas fundraising? available at ssrn entrepreneurs for a low carbon world: how environmental knowledge and policy shape the creation and financing of green start-ups venture capital and cleantech: the wrong model for energy innovation ita-per-un-esper iment o-di-massa -never -waste -a-good-crisi s/ european economic and social committee (eesc, dg regio) opinion on "financing the transition to a low-carbon economy and the challenges in financing climate change adaptation letter: let's not waste this chance to transition to an environmentally sustainable future. financial times °c above pre-industrial levels and related global greenhouse gas emission pathways, in the context of strengthening the global response to the threat of climate change, sustainable development and efforts to eradicate poverty report prepared by the world in initiative. international institute for applied systems analysis (iiasa), laxenburg, austria. www.twi .org sachs the ages of globalization: geography, technology, and institutions the sustainable development goals and covid- . sustainable development report six transformations to achieve the sustainable development goals e-confe rence -the-epide miolo gy-and-econo mics-of-coron aviru s visual toolbox for system innovation the coronavirus stimulus package: how large is the transfer multiplier? centre for economic policy research discussion paper dp mit klimafreundlichen investitionen raus aus der wirtschaftskrise the environmental impacts of the coronavirus world bank group ( ) proposed sustainability checklist for assessing economic recovery interventions the survey is published on the ipsos website and covers , people from may to . behavioral and distributional effects of environmental policy the political economy of clean air act legislation: an analysis of voting in the us senate on amendments to the privatization and efficiency: from principals and agents to political economy multiple receptor ambient monitoring and firm compliance with environmental taxes under budget and target driven regulatory missions productive efficiency in public and private firms emissions trading with profit-neutral permit allocations salience games: private politics when public attention is limited community pressure for green behavior is environmental regulation bad for competition? a survey the political economy of market-based environmental policy: the u.s. acid rain program regulating pollution with endogenous monitoring emission reduction and profit-neutral allowances the strategic use of innovation to influence regulatory standards the khazzoom-brookes postulate and neoclassical growth incomplete contracts and privatization the availability heuristic, intuitive cost-benefit analysis, and climate change draft report on the proposal for a regulation of the european parliament and of the council establishing the framework for achieving climate neutrality and amending regulation (eu) / (european climate law will covid- fiscal recovery packages accelerate or retard progress on climate change? never waste a good crisis: for a sustainable recovery from covid- , sustainable development solutions network the use of multiple policy instruments for environmental protection: an economic perspective automotive modal lock-in: the role of path dependence and large socio-economic regimes in market failure regulatory capture: a environmental and technology policies for climate change mitigation climate change policy's interactions with the tax system scrapping subsidies during the financial crisis -evidence from europe the environmental impacts of the coronavirus will covid- fiscal recovery packages accelerate or retard progress on climate change? renewable energy subsidies: secondbest policy or fatal aberration for mitigation? resour justifying a policy mix for pollution control: a review of economic literature can technology-specific deployment policies be cost-effective? the case of renewable energy support schemes evaluating "cash-for-clunkers": program effects on auto sales and the environment path dependence in urban transport: an institutional analysis of urban passenger transport in the effects of fiscal stimulus: evidence from the cash for clunkers program cost-effectiveness of renewable electricity policies prices rise faster than they fall timmermans promises green recovery to eu lawmakers green deal facing delays due to coronavirus, eu admits issue of food sovereignty and seek to reinforce the relocation of part of the food supply chains. of course, it is not a question of valuing protectionist policies at all costs. in contrast, in addition to raising prices (french labour is expensive), this would make the national food system more vulnerable in the event of poor harvests (droughts, floods, etc.). however, to be truly effective, relocation would require profound changes to the french food system, for example, reducing the production of meat and cheese, which are heavily dependent on soybeans. both environmental (greenhouse gases and biodiversity) and social (food sovereignty, profitability of small farms) objectives are compatible here. finally, the short food supply chains therefore represent a radical change to consumption that food security and canada's agricultural system challenged by covid- technological transitions as evolutionary reconfiguration processes: a multi-level perspective and a case-study international monetary fund's ( ) world economic outlook agroecological research: conforming or transforming the dominant agro-food regime? how covid- has exposed inequalities in the uk food system: the case of uk food and poverty the challenge of using epidemiological case count data: the example of confirmed covid- cases and the weather university of oxford; and institute for new economic thinking at the oxford martin school the publicly available datasets on confirmed covid- cases and deaths provide a key opportunity to better understand the drivers of the pandemic will spring slow spread of coronavirus in northern hemisphere? the guardian scientists hopeful warmer weather can slow spread of coronavirus. the financial times spread of sars-cov- coronavirus likely to be constrained by climate ultraviolet radiation decreases covid- growth rates: global causal estimates and seasonal implications an interactive web-based dashboard to track covid- in real time epidemiological data from the covid- outbreak, real-time case information correlation of chest ct and rt-pcr testing in coronavirus disease (covid- ) in china: a report of cases covid- : automatic detection from x-ray images utilizing transfer learning with convolutional neural networks covid- testing: challenges, limitations and suggestions for improvement finding covid- from chest x-rays using deep learning on a small dataset extreme weather events, mortality, and migration mortality risk attributable to high and low ambient temperature: a multicountry observational study q&a: similarities and differences-covid- and influenza". ( ) consulted on th april use of radiographic features in covid- diagnosis: challenges and perspectives an empirical investigation into factors affecting patient cancellations and no-shows at outpatient clinics cohen is the first author. he had the original idea, wrote most of the paper and the code to produce the econometric analysis. he also coordinated the team. jani ensured the material was consistent with the epidemiological evidence. li produced the required climate data for the statistical analysis. lu helped on literature review, on coding the econometric analysis and on producing the tables. schwarz helped on data coding and matching and created the projections. all authors contributed to the text. data and materials availability all data and software are publicly available at https :// githu b.com/morit zpsch warz/covid - -weath er-oxfor d. key: cord- -pue mv authors: shamshiripour, ali; rahimi, ehsan; shabanpour, ramin; mohammadian, abolfazl title: how is covid- reshaping activity-travel behavior? evidence from a comprehensive survey in chicago date: - - journal: nan doi: . /j.trip. . sha: doc_id: cord_uid: pue mv the novel covid- pandemic has caused upheaval around the world and has led to drastic changes in our daily routines. long-established routines such as commuting to workplace and in-store shopping are being replaced by telecommuting and online shopping. many of these shifts were already underway for a long time, but the pandemic has accelerated them remarkably. this research is an effort to investigate how and to what extent people's mobility-styles and habitual travel behaviors have changed during the covid- pandemic and to explore whether these changes will persist afterward or will bounce back to the pre-pandemic situation. to do so, a stated preference-revealed preference (sp-rp) survey is designed and implemented in the chicago metropolitan area. the survey incorporates a comprehensive set of questions associated with individuals' travel behaviors, habits, and perceptions before and during the pandemic, as well as their expectations about the future. analysis of the collected data reveals significant changes in various aspects of people's travel behavior. we also provide several insights for policymakers to be able to proactively plan for more equitable, sustainable, and resilient cities. the rp portion of the survey mostly collects retrospective information from the respondents about their travel attitudes, habits, and behaviors prior to and during the covid- pandemic. the sp portion further asks the respondents about how they perceive the future. the survey puts this information together with socio-demographic details and health-related indicators such as indicators of whether the respondents have been tested positive for covid- or they have pre-existing medical conditions. the remainder of this article is structured as follows: in section we review the underlying literature on people's activity-travel behavior during the pandemic situations. afterwards in section , we present comprehensive information about the survey design and implementation, as well as general descriptions on the collected data. expanding the discussions, then, the study findings will be discussed in sections and . after that in section , we put the results into perspective for planning towards a more sustainable, resilient, and equitable future. in the end, the article concludes with a summary of the findings and potential avenues for future research. reviewing the underlying literature, a limited number of studies can be found on the impacts of outbreaks on the transportation sector. focusing on leisure travels, wen et al. ( ) analyzed the impacts of the sars outbreak on the travel behavior of chinese domestic tourists. the authors observed that the outbreak had greatly affected people's life, work, and travel behavior. besides, the decrease in travel was found to be associated with a combination of internal motivations (e.g., perceived risks) and external enforced measures (e.g., travel bans, stay-at-home orders). this research, however, did not explicitly explore the effects of the outbreak on the post-outbreak world. focusing on the international air travel, liu et al. ( ) studied the effects of the same outbreak on air travel between the u.s. and three destinations: china, hong kong, and taiwan. highlighting the influence of lifestyles on travel behavior during an outbreak, the authors found that although the frequency of these international trips reduced for all countries, the level of risk was perceived differently among those countries. in another study, fenichel et al. ( ) examined more than . million detailed flight records to analyze air travelers' behavioral responses to the h n pandemic that occurred in . the authors estimated that the overall concerns over the h n influenza (as measured by google trends) accounted for . % of missed flights during the pandemic. according to this study, people respond to epidemiological risks with behavioral changes. focusing on public transit trips, kim et al. ( ) analyzed the smart card data in seoul before and after the mers outbreak in south korea. the authors observed that individuals living in neighborhoods with higher land prices decreased their transit trips more than others. besides, the fear of exposure was significantly associated with changes in travel behavior. focusing on the relationship between the changes in travel behavior and built environment settings, they found that land price, location of mers hotspots, number of businesses, seniors population, and number of restaurants might significantly influence transit ridership during the outbreak. more recently, hotle et al. ( ) investigated risk perception and risk mitigation of travelrelated decisions concerning influenza to characterize: ) the risk perceptions, ) the risk mitigation decisions when one is infected and wants to prevent spreading it, and ) risk mitigation decisions when one is not infected and wants to minimize the exposure. the risk perception analyses showed that personal experience of having influenza-like symptoms as well as being female significantly increased risk perception at the places that one performs mandatory and medical-related activities. moreover, the risk mitigation analyses highlighted that individuals are less likely to travel to places where they perceive a medium or high risk of exposure to the influenza virus. the authors also found that high perceived risks do not lead people to travel to their workplaces less frequently. there are also a limited, but growing, number of studies focusing on the impact of recent covid- pandemic on the transportation sector (e.g., de vos, ; ito et al., ; lee and lee, ; molloy et al., ; sobieralski, ) . in particular, there exists a dearth of research on the changes in travel patterns caused by the current covid- pandemic. in a short but informative study, de vos ( ) discussed the potential implications of social distancing on daily travel patterns and, accordingly, provided some suggestions for policymakers. the authors highlighted that stay-at-home might be a threat to individuals' subjective well-being, causing limited physical activities and social isolation. according to this study, promoting active travel behavior is a potential solution for policymakers to encourage individuals to maintain a satisfactory level of well-being. focusing on the airline industry in the u.s., sobieralski ( ) studied the interactions among economic and industry variables in the covid- pandemic in which reductions in capacity of airlines are growing, and the post-stimulus employment requirements expire. the author found that the estimated job loss in the airline industry is around % of the airline workforce, with an upper bound of over %. moreover, the author highlighted the high vulnerability of the airline industry during such uncertain periods as the current pandemic and showed that the adverse effects of the current uncertainty shocks might last for more than four years. in another study, molloy et al. ( ) investigated the changes in travel behavior due to the spread of the covid- pandemic in switzerland. focusing on different income groups as well as various accessibility states, they suggested a few first insights into how the spread of the disease can be limited in the study context. . , as well as sections and . the focus of the present subsection is on higher-level discussions around the survey, including its structure and temporal coverage. combining stated preference (sp) and revealed preference (rp) methods, the survey was structured to collect information in three major categories: ) socio-demographic details such as residential location, age, gender, race, as well as the economic factors including individual job categories and annual household income; ) health-related factors such as weight and height, and physical exercise habits, as well as covid- exposure risk factors such as having pre-existing medical conditions and being in close contact with a confirmed case; and ) an extensive set of questions about people's attitudes and perceptions, habits, and daily activity-travel behavior. in terms of the various aspects of activity-travel behavior, the survey covered online and in-store shopping, teleworking, physical exercise, mode choice, and air travel. the survey questionnaire was distributed from april , , to june , , through the online platform of qualtrics (uic irb protocol number: # - ). we also implemented google map api to collect respondents' approximate residential locations in the online questionnaire ( fig. ). as shown in fig. , our collected sample is decently distributed all over the study area and covers neighborhoods with different levels of covid- positive cases. the survey was distributed among individuals older than . to ensure the quality of the collected data, we included multiple screening questions throughout the survey. for instance, in order to be able to flag those who responded to the questions without paying enough attention, we embedded a few questions and asked the respondents to choose a specific option. also, we monitored the response time for each section to ensure that the respondents spent enough time on answering the questions. as another quality control measure, we also monitored the duration of the time that each respondent spent on the entire survey to exclude overly fast responses (with a -minute cut off point). furthermore, the critical socio-demographic questions were designed in a similar way to the national household travel survey to facilitate validation and weighting. besides, we asked qualtrics to control for the distribution of respondents concerning the age, gender, and education to be aligned with the u.s. census data for the region. after excluding those respondents who failed to meet the screening criteria mentioned above, valid responses remained for the analysis. fig. and fig. summarize frequency distributions of our collected data in terms of basic socio-demographics, including gender, age, education, individual job categories, and household income. also asked people if they felt they had symptoms of the covid- disease in the past days (see fig. (a)). around percent of the respondents (i.e., five times as high as the proportion of the confirmed cases) reported having the symptoms, indicating the high importance of providing enough testing instruments and facilities to the responsible organizations to facilitate the screening process. also, we asked the respondents to indicate if they had close contact with a person who was confirmed to have the virus (see fig. (b) ). the designated question had three choice alternatives to distinguish between those who had the contact within the past days (~ %) and before the past days (also ~ %). furthermore, we asked the respondents if they had preexisting conditions that can elevate the severity of the disease in case of infection. fig. is set out to summarize the responses while breaking down by two primary age groups: the seniors older than and the younger individuals. as can be seen, around % of seniors and % of younger individuals believed that they had a pre-existing condition. this section is devoted to uncovering the most economically vulnerable groups of society. towards this, we focused on two main areas: ) the burden imposed on people due to losing their jobs either temporarily or permanently, and ) the changes that people made in their expenditures on shopping for errands. identifying the most economically vulnerable groups of the society provides essential insights into the priorities while planning for a more equitable future. moreover, it also provides essential insights to enrich our understanding of the dynamics of activity-travel behavior in the future. a prerequisite to an unbiased analysis of who will change his/her travel behavior and how is an accurate recognition of how much the expenditure power of each person has been affected. looking into the changes of unemployment status, our results show a considerably concerning gap between the unemployment rates among the former full-time and part-time workers. fig. (a) shows how the covid- pandemic has affected full-time workers. around % of such workers indicated that they were temporarily laid off. it is worthy to note that, although the unemployment of such individuals is temporary, the side effects of losing their source of income for months might easily expand to the future for them even after starting to get paid. the economic complexities would be even harsher for around % of the full-time workers who lost their jobs permanently. fig. . (b) shows similar information for the formerly part-time workers. as can be seen, % of part-time workers lost their jobs permanently (around . times as high as the full-time workers), and an additional % were temporarily laid off (around . times as high as the full-time workers). put differently, more than half of part-time workers and % of full-time workers have lived the past few months without having been paid, which shows a % gap between the two groups. moving forward to the job categories, fig. depicts the unemployment-status changes observed for the various job categories discussed in section . . as can be seen in fig. , the j o u r n a l p r e -p r o o f situation with workers in restaurants, food services, and bars as well as workers in the arts, entertainment, or recreation industries is considerably more alarming as compared to the rest of the workers. according to the results, more than % of such workers have been living without being paid during the covid- pandemic. the highest rate of permanent loss of jobs also belongs to the same groupsmore than % for both groups. depicts the unemployment-status changes for different household-income groups. as an alarming first insight, the results reveal that around % (i.e., % plus %) of those who live in very low-income households (i.e., an annual income of less than $ k) have been dealing with at least one discontinued source of income. this number, according to fig. is four times as high as the corresponding number for those households who earn $ k or higher (i.e., %, which is the sum of % and %). this shows how severely the economic impacts hit the lowincome groups of the society. fig. adds more details on the economic effects of covid- on low-income families. the following elaborates on this figure. as part of the survey, we also collected the individual expenditures on three errandshopping categories: groceries, prepared meals, and other errands. fig. shows the average expenditures on each category for different income groups. as can be seen, all income groups have been expending more on groceries and meals, and less on other errands. this is understandable given that, these days, people have been less sensitive about how expensive an option is and more concerned about how safe and accessible it is. focusing on low-income households, an average member of such families has been spending % more on their groceries. this makes sense, given that the more expensive stores have been adopting more safety measures to ensure the safety of their customers. therefore, a low-income person who wants to minimize the risk of catching the virus may have to switch to more expensive alternatives. similarly, grocery online shopping alternatives (which are safer in terms of exposure to covid- ) are also usually more expensive than their in-store shopping counterparts. putting this observation on the low-income households (less than $ k) together with the last observation that such people have also been more prone to losing their job, brings us to the conclusion that they have been probably experiencing notably tough situations. in section , we focused on identifying the economically vulnerable groups of the society and discussed the economic impacts in terms of average expenditures and losing jobs. in this section, we focus on the dynamics of working from home. the various aspects discussed in this section include: ) the dynamics of working from home before and during the pandemic, and ) the dynamics of work productivity before and during the pandemic. fig. shows the frequency of working from home before and during the pandemic in our sample. as can be seen, around % of our respondents had not experienced working from home before the covid- pandemic, while % were already working from home for at least days a week. with the pandemic wave hitting the state of illinois and the corresponding stay-at-home order, however, this pattern changed drastically, as shown by the red bars in this fig. as can be seen, % of the respondents reported that they had not worked from home -even for a single day-during the endemic. scrutinizing this category, we realized that around % out of the % are healthcare personnel, and the rest are those who work in retail stores, in the transportation industry, or have other service jobs. these are essential jobs that cannot be forced to stay home, and this fact highlights that there is a limit to how effective policies such as the stay-at-home order and the closure of non-essential businesses could enforce social distancing. the discussions in section will expand on this subject. figure . frequency of working from home, before and during the covid- pandemic as part of the survey, we also asked those workers who have been working from home about how they evaluate their productivity as compared to the before covid- situations. summarizes the answers provided to us while distinguishing between two major groups of: ) those who had not experienced working from home before the stay-at-home order but were doing so days a week during it (named as "new telecommuters"), and ) those who were working from home days a week before and continued doing so during the stay-at-home order (named as "continuing telecommuters"). as can be seen, % (i.e., % + % + %) of new telecommuters believe that their productivity has been the same or higher. notably, however, the rest % of the new telecommuters did not have a productive experience. the fact that both of these two groups constitute significant portions of the society sheds light on the importance of taking a closer look at the underlying heterogeneities. this importance becomes more evident given the concrete evidence from the literature suggesting that working from home can significantly alleviate traffic congestion and air pollution if adopted by a large portion of workers (shabanpour et al., ) . to better understand the subject, we also asked the respondents about the factors that have been negatively and positively affecting their productivity at home. they could choose multiple items. fig. (a) and fig. (b) summarize the frequency of the factors that have been negatively and positively affecting the productivity of working from home, respectively. the more frequent distractions at home (i.e., %) and lack of comfortable workspace (i.e., %) were the most frequently chosen reasons for not having a productive experience. on the other hand, no commuting time to work (i.e., %) and a more casual environment at home (i.e., %) were among the factors of productivity improvement for those who could cope with working from home well. the overall dynamics of shopping expenditures during the covid- pandemic was discussed in section . as people have embraced social distancing to slow down the spread of the coronavirus, we expect to observe a considerable drop-off in the habits of in-store shopping. due to the importance of this matter, we dedicated a significant part of our analysis to exploring how and to what extent people's shopping behavior has been changingboth the grocery shopping as well as ordering food from restaurants. this section is dedicated to discussing the findings. the first critical element is to understand what portion of the society had already experienced online shopping, and more importantly, what portion turned to online shopping during the pandemic. towards this, we asked our respondents to indicate the first time they had such an experience. they had three-time options, which were defined relative to january (i.e., the date that the first confirmed case in illinois was announced) and march (i.e., the date that the illinois governor issued the stay-at-home order). thus, they had three options of ) before january , ) between january and march , and ) after march , . fig. summarizes the results. as can be seen, about % of our respondents never experienced online shopping for groceries before taking our survey. the rest ( %), however, indicated that they had done online shopping for groceries, at least once, before responding to our survey. with regards to online shopping from restaurants, however, we observed that % had the experience of using such services before taking the survey. getting into more details, % (i.e., % plus %) of those who had experienced online grocery shopping before, indicated that their very first-time online grocery shopping was after january , which can be reasonably assumed that it was because of the pandemic restrictions. moreover, among that %, about % had experienced online shopping before the pandemic started (i.e., equal to about % of the total sample). therefore, we can conclude that the percentage of those who tried online grocery shopping has increased from % to % during the past few months of the pandemicindicating a % growth. a more or less similar increasing pattern was observed for those who used online platforms to order food from restaurants. we observed that the percentage of those who ordered food online has increased from % (i.e., the product of % and %) to %indicating a % growth. ordering food online from restaurants the discussions so far focused only on the experience of online shopping for groceries and from restaurants and left the habitual aspect unclear. we also asked two specific questions with regards to the habits of online shopping, one question for grocery shopping and one for ordering food from restaurants. fig. summarizes the results of these questions. putting the results of fig. (a) and fig. (a) together, we conclude that among the % who experienced online grocery shopping at least once, % (i.e., % plus %) identified it as their primary way of meeting their grocery needs during the pandemic. this % constitute around % of the whole sample (i.e., % times %), which shows a % growth in the proportion of the habitual online grocery shoppers (the corresponding statistics was around % before the pandemic, i.e., % times %, which itself is equal to % plus %). this is while performing the same math to combine the results of fig. (b) and fig. (b) indicates a % growth in the proportion of habitual users of online delivery platforms for ordering food from a restaurant (e.g., uber eats and grubhub). comparing the two online shopping categories, therefore, yields the impressive statistics that the growth in habitual behavior of online shopping for groceries has been almost . times as high as the growth in habits of online shopping for food from restaurants. furthermore, the results indicate that a significant portion of the society (i.e., % of the % who experienced online grocery shopping plus the rest %, or equivalently %) have been still relying mostly (or solely) on in-store shopping for meeting their grocery needs. another interesting observation was based on two questions that focused on people's expectations about their future online shopping behavioreach for the short-term and the long run. we asked our respondents to indicate if it is likely that they will engage in online shopping for groceries and from restaurants more frequently in the future as compared to the beforepandemic time. the results are depicted in fig. . it is very interesting to see that around % of our respondents (i.e., % plus % plus %) indicated that they would rely more on online grocery shopping in the first few months after the pandemic compared to the before-pandemic routines. even more interestingly, around % indicated that they would do online grocery shopping more frequently even far after the pandemic. thus, we conclude that while there will be a slight bounce-back in the long run, people still would be more engaged in online grocery shopping. a similar pattern has been observed for ordering food from restaurants where % of respondents said they would do so more frequently in the short-term future, and % said they would do so long after the pandemic. in summary, we can expect that a considerable portion of this notable increase in online shopping for both groceries and meals during the pandemic will sustain in the future. understanding the most influential factors on people's preferences towards opting for online shopping over in-store shopping or vice-versa would help the investment and marketing agencies as well as the urban policymakers to better plan for the post-pandemic future. towards this, we designed a set of questions in which respondents were presented with a list of potential advantages of and concerns about online shopping, and they were asked to indicate how appealing or concerning each item was for them. to better understand the impact of the pandemic restrictions, these items were asked for both before the pandemic and during the pandemic. fig. summarizes the results of the pandemic situation and tables . . and . . outline the percentage change in the positive and negative perceptions towards each item from before-pandemic to the during-pandemic situations. among the potentially-positive aspects of online shopping ( fig. (a) ), we found that the following factors are the most appealing aspects during the pandemic: avoiding crowds and going to public places such as stores, as well as the ability to find high-demand items more easily. another observation was regarding the changes in perceptions towards appealing reasons (table ). our results showed that, as compared to before the pandemic, people have been putting considerably more emphasis on avoiding crowds, avoiding to go to public places such as stores, and shopping / during the pandemic, as they have the highest increase in table . on the other hand, with respect to the negative aspects ( fig. (b) ), we found that people are more concerned about the possible inaccurate information about the product, the shipping costs, and not being able to try or examine the product before purchasing it. with respect to shifts in concerns (table ), we found that the possibilities of inaccurate information and not having instant access to the item are associated with the most significant increases in being considered as highly concerning. note: *** , ** , and * indicate significance level of %, %, and % j o u r n a l p r e -p r o o f the return process . - . - . note : *** , ** , and * indicate significance level of %, %, and % another important aspect of travel behavior that might change in the future constitutes the higher-level orientations, preferences, and attitudes towards long-distance travels. airplane travels have long served as the primary mode for long-distance travel that could not be alternatively performed by personal vehicles in a reasonably short period. the recent evidence on the covid- exposure risk factor, however, has made many to re-evaluate their routines to either eliminate some travels -for example, by teleworking-or switch to alternative modes of travel, including personal vehicles. for instance, (sobieralski, ) suggested that airline industries have faced a rapid and severe threats posed by the spread of the novel coronavirus, resulting in a significant job loss. in this sense, how people perceive airplane travels could be considered as a critical predictor of the emerging changes in their long-distance travel behavior. having this in mind, we designed two questions in our survey to better understand the dynamics of airplane travels in the future. first, we asked our respondents about how they expect their airplane travels for leisure or personal business to change in the future after the pandemic is over, as compared to their beforepandemic routines. fig. outlines the results. as can be seen, a considerable portion of the society (i.e., around %, which is the sum of % and %) is expected to travel with airplanes less frequently in the future. similarly, (de haas et al., ) also reported that dutch people are expected to significantly reduce their flight frequencies in the future after the pandemic. in addition, we asked those who expected more (or less) airplane travels than before about the reason(s) behind their expectation (multiple choices were allowed). fig. summarizes the results. it was interesting to see that a significant portion (around %) indicated not feeling safe or comfortable with sharing space with others. the next highest portion ( %) corresponded to shifting towards personal vehicles. among the other reasons that negatively affect airplane j o u r n a l p r e -p r o o f travels, we can also refer to the financial and affordability issues ( %). figure . expected change in airplane travels once the covid- is no longer a threat as compared to the before-pandemic situations figure . factors underlying the expected change in airplane travels once the covid- is no longer a threat as compared to the before-pandemic situations in previous sections, we discussed the dynamics of travel behavior in terms of a variety of aspects, including working from home, online shopping, mode choice, and airplane travels. a factor that underlies many of these aspects is how people perceive the risk of exposure to the virus. this section is dedicated to exploring the perception of people towards the exposure risk given a variety of travel choices. fig. summarizes the perceived risk of using various travel modes. according to the results, personal vehicles turned out to be associated with the lowest perceived risk of exposure. ranked after personal vehicles, biking with private bicycles and walking are found to have the second-and third-lowest perceived risks of exposurerespectively, % and % categorized as medium to high risk of exposure. this shows the notable role of active transportation and micro-j o u r n a l p r e -p r o o f mobility during the pandemics in preventing the users of transit, taxi, and ride-hailing services from switching to personal vehicles. similarly, (teixeira and lopes, ) found evidence on a possible modal shift from the subway to the bike sharing system in new york, u.s. furthermore, transit, taxi and ride-hailing services (e.g., uberx), as well as pooled ridehailing (e.g., uberpool) are the first three highest risky modes in people's view. around % of the respondents indicated that they associate transit with medium to extremely high risk of exposure to the novel coronavirus. this finding is in line with (bucsky, ) who observed that usage of public transit decreased dramatically by %, while the overall mobility was reduced maximally by %. however, out of this % portion, more than % either reported that their household owns no personal vehicles or someone else in their household is the main driver of the vehicles owned. moreover, around % were found to be senior citizens older than (who probably have difficulty substituting transit with active modes), over % are from lower income households (i.e., annual income of $ k or less) who neither own a bike nor have a bike-sharing membership. as mentioned in section , we collected the nearest intersection to the home address of the respondents via google maps api. linking this information to the smart locations database (cite), we also noticed that over % out of the % portion of the observations belong to those who live in low pedestrian-oriented neighborhoods (i.e., where the density of pedestrian-oriented facilities is lower than the th percentile). these results, collectively, shed light on the importance of pro-actively planning for a more "equitable" future transportation system to minimize the disparities in accessibility among various socio-demographic groups and residents of various urban settings. explaining the sensitivity of the demand for using transit, taxis and, ride-hailing services to the pandemics, the results also highlight the need to expand the concept of "resiliency" beyond its current domain of service disruptions rahimi et al., ) . the recent pandemic experiences showed us that there should also be a longer-term aspect to "resiliency of the transportation systems" to focus on the resiliency during the prolonged pandemics. fig. . the results indicated that the risk of indoor activities is generally considered to be more than outdoor activities. interestingly, also, going to gyms or fitness centers are found to be almost as risky as going to the hospitals in people's view-around % of the respondents associated medium to extremely high risk of exposure to these activities. in-store shopping and restaurants stand at the second and third ranks, respectively, with % and % categorizing as a medium to extremely high-risk activity. the previous sections discussed the dynamics of various aspects of activity-travel behavior and perceptions impacted by the covid- pandemic, and this section seeks to put the results into perspective for transportation planning and offer insights for future research. the first theme that emerged from our results pertains to the productivity of working from home and its association to individuals' perceptions towards their home environment. the results suggest that working from home carries high potential for moving towards a more sustainable future. the underlying literature supports the significant influence of policies to promote telecommuting on alleviate traffic congestion and improving air quality (shabanpour et al., ) . as a practical way of influencing the workers' preferences, the results of this study point to the significant role of their productivity while working from home. according to results described in section . , although the "new telecommuters" in our sample evaluate their productivity in various ways, the "workability of their home environment" is a common theme in their evaluations. the two most reported reasons for a negative productivity were distractions in the home environment, and lack of a comfortable working environment at home. at the same time, two of the first three most common reasons behind positive work productivity levels at home are also related to the home environment. that is, those who work from home are significantly more productive if their home-office provides comfortable and energetic workspaces, with opportunities for restful breaks and minimal disruptions. these results suggest that "home workability" is a critical factor for consideration in future research regarding work productivity levels in the home environment. from a different perspective, the results also suggest potential shifts in peoples' perceptions towards residential location choice given that several businesses and companies have been allowing employees to work from home-even permanently in some cases. therefore, our results also point towards "home workability" as a critical factor to be considered in future research that pertains to residential location preferences. the second theme that emerged from the results pertains to shared mobility and active transportation. they suggest a potential shift from usage of shared mobility options such as pooled ridesharing and transit services to modes that avoid contact-such as walking, biking, using scooters, and personal vehicles. the results in section . show that a notable portion of the society associates transit and pooled ride-sharing services with medium to extremely high exposure risks, and thus opt to use other modes as safer alternatives. an important implication that can be made from this observation is that active transportation and micro-mobility modes can play substantial roles in planning towards more sustainable and resilient cities. promoting mobility-styles and habitual travel behaviors centered around active transportation and micromobility options not only paves the way towards a more sustainable future but also improves the resiliency of our cities in limiting person-to-person contact during infectious disease outbreaks such as the covid- pandemic. the third theme emerging from the results relates to the concept of "equity". per the results, while a significant portion of respondents associated a high risk of exposure to the virus while using public transit, not all of them have access to alternative modes of transportation. they may not have access to a personal vehicle or live in areas with sufficient pedestrianoriented facilities or biking infrastructure. this finding highlights the importance of equity when designing multi-modal transportation systems, and how this importance becomes even more apparent during crises like the covid- pandemic. an equitable transportation system can reduce disparities in accessibility among residents of a region across various socio-economic backgrounds, helping to promote safe and convenient access to opportunities such as jobs and healthcare. the importance of equitable transportation systems that maximizes distribution levels and access across the whole service area is especially important when considering the context of chicago. the chicago metropolitan area displays a sizable level of economic and demographic diversity, as well as persisting issues in racial segregation, posing challenges in ensuring transportation equity across the region. these results also point towards an ever more car-reliant society in the post-pandemic era, given the personal sense of safety and non-contact nature that comes with personal vehicles. nonetheless, the overall lesson to be gleaned from these results is the need for proactive transportation planning in a way that promotes an active and equitable transportation system. additionally, the current covid- experience showed us how inequitable certain policies such as the as the stay-at-home order could be for various member of society based on their job categories-especially for low-income households, and part-time workers. in section , j o u r n a l p r e -p r o o f we observed that the percentage of workers with an annual household income of less than $ k that became unemployed due to the pandemic for the first few months was four times as high as the corresponding statistics for high-income households (annual income of $ k or more). indeed, our analyses highlight the need for more equitable approaches to implementing work restriction guidelines in future pandemic situations. the fourth theme of the policy implications relates to the efficacy of such policies as the stay-at-home order and the closure of non-essential businesses in moving towards the social distancing goals. we observed a considerably high proportion of workers in essential business (i.e., around percent) which potentially puts a cap on the efficacy of governmental orders to close non-essential businesses. our observations also yielded a more or less similar finding with regards to the shopping trips for groceries and meals, which put a cap on the efficacy of the stayat-home order. as shown in section . , despite the notable growth in online shopping for groceries, a significant portion of the society still relies on in-store shopping as their primary choice in meeting grocery needs. these observations along with the equity issues related to such policies (as discussed above), shed light on the importance of pro-actively planning for the future pandemics, by designing comprehensive decision support systems which can guide the future policies towards being more equitable and efficient. to improve the efficacy and equitability of such policies, they could be designed based on complex combinations of a range of strategies including proper adjustments of the operating hours of various essential businesses. as a comprehensive decision support system, we suggest agent-based models c, due to the highly complex and dynamic nature of the policy evaluation needs. the dynamic and modular design of the algorithmic core of adapts (auld and mohammadian, ; shamshiripour et al., ) makes it a flexible tool that can be proficiently adjusted to incorporate changes in people's activity-travel behavior during the pandemic situations. the last, but not the least, key takeaway in the aftermath of covid- pertains to the future autonomous vehicles (avs). as discussed in section . , another notable shift in travel behavior is from airplanes as a mode for travel for leisure or personal business trips to car road trips. as a result of this shift, people may be more apt to adopt avs in the future since such vehicles are geared towards facilitating long-distance travel by eliminating the need to continually pay attention to the task of driving, and enables riders to make better use of their travel time. as with the expected shift away from transit and ride-hailing services (i.e., due to avoidance of crowds), we also expect that promoting shared avs (savs) and pooled savs (psavs) over privately-owned avs will become more challenging in the future lavieri and bhat, ; , which could potentially pose serious sustainability challenges for our av-dominated future cities. as suggested by (levin et al., ) , domination of privately-owned avs over psavs could result in heightened traffic congestion levels. furthermore, we can expect an increase in the adoption rate of larger body sizes (e.g., avs in the form of recreational vehicles or vans), since they provide a more comfortable road trip experience. j o u r n a l p r e -p r o o f the covid- pandemic has caused many to re-examine their habits and priorities, and thereby, brought considerable changes to how people perform their everyday tasks. the present research has set out to shed light on the dynamics of people's mobility-styles-including habits, predispositions, and higher-level orientations toward tele-activities (i.e., online shopping, online business meetings and working from home, etc.) and travels (i.e., long-distance commutes and urban travel mode choice) during and after the covid- pandemic. this research's framework is designed as a longitudinal analysis with multiple survey waves to monitor the activity-travel dynamics continually. the present article reports on the preliminary results of the first wave (i.e., conducted from april , , to june , ) which was dedicated to the chicago metropolitan area. focusing on the overall behavioral trends caused by the covid- pandemic, the discussions in this article provide essential insights for planners and policymakers to better prepare for the post-pandemic era. the details of the survey and the results of our analyses are discussed in sections to . furthermore, a detailed description of the insights into the future of our cities and suggested directions for future research is discussed in section . the future insights provided in section includes suggestions that consider various aspects of planning towards the resident-centric smart cities, including the work-related productivity of the agents, equitable and smart governance, as well as sustainability and resiliency of the transportation system. the suggested research directions includes: ) conceptualization of a "home workability" index and inclusion in the future modeling efforts concentrating on residential location analyses, as well as multitasking and work-related productivity; ) expansion of the current domain of the concept of "transportation system resiliency" to include longer-term aspects such as resiliency in pandemic situations; and ) researching potential avenues to promote sustainable and safe modes of travel to prevent further car-dependency. as a limitation of the discussions in this article, the presented analyses are mostly geared towards identifying the overall behavioral trends, while relying on the future research for more detailed, individual-level analyses. as such, we call for future research to go beyond the aggregate-level trends presented in this article and focus more on the individual-level behaviors. this necessity becomes apparent specially with respect to the need for updating the current activity-travel agent-based simulation frameworks like adapts to serve as flexible decision support systems. the future research should pay especial attention on identification of the underlying temporal and spatial variations, among other confounding factors. j o u r n a l p r e -p r o o f the authors confirm contribution to the paper as follows: study conception and design all authors reviewed the results and approved the final version of the manuscript. the authors do not have any conflicts of framework for the development of the agent-based dynamic activity planning and travel scheduling (adapts) model role of attitudes in transit and auto users' mode choice of ridesourcing travel-based multitasking: modeling the propensity to conduct activities while commuting modal share changes due to covid- : the case of budapest how covid- and the dutch 'intelligent lockdown' change activities, work and travel behaviour: evidence from longitudinal data in the netherlands the effect of covid- and subsequent social distancing on travel behavior skip the trip: air travelers' behavioral responses to pandemic influenza making time count: traveler activity engagement on urban transit introduction: habitual travel choice mobilitätsstile-ein sozialökologischer untersuchungsansatz influenza risk perception and travel-related health protection behavior in the us: insights for the aftermath of the covid- outbreak covid- statistics in illinois the cruise industry and the covid- outbreak exposure to fear: changes in travel behavior during mers outbreak in seoul modeling individuals' willingness to share trips with strangers in an autonomous vehicle future testing on the move: south korea's rapid response to the covid- pandemic a general framework for modeling shared autonomous vehicles with dynamic network-loading and dynamic ride-sharing application the life cycle of a pandemic crisis tracing the sars-cov- impact: the first month in switzerland examining human attitudes toward shared mobility options and autonomous vehicles analysis of transit users' response behavior in case of unplanned service disruptions analysis of transit users' waiting tolerance in response to unplanned service disruptions urban rhythms and travel behaviour: spatial and temporal phenomena of daily travel analysis of telecommuting behavior and impacts on travel demand and the environment kouros), . dynamics of travelers' modality style in the presence of mobility-on-demand services a flexible activity scheduling conflict resolution framework, in: mapping the travel behavior genome covid- and airline employment: insights from historical uncertainty shocks to the industry the link between bike sharing and subway use during the covid- pandemic: the case-study of new york's citi bike incorporating the influence of latent modal preferences on travel mode choice behavior the impacts of sars on the consumer behaviour of chinese domestic tourists modes of transmission of virus causing covid- : implications for ipc precaution recommendations the research team greatly appreciates the valuable comments on our survey questionnaire received from dr. ram pendyala and dr. deborah salon from arizona state university. we would also like to thank dr. sybil derrible from university of illinois at chicago and monique stinson from argonne national laboratory for their constructive suggestions on the survey instruments.j o u r n a l p r e -p r o o f journal pre-proof key: cord- -wdnnjlcw authors: jandrić, petar title: postdigital research in the time of covid- date: - - journal: nan doi: . /s - - - sha: doc_id: cord_uid: wdnnjlcw nan patents' (crowe ) . worldwide closures of schools and universities have pushed millions of students and teachers online, bringing decades of experience in the field under the public eye (bates ) . commentators compare chinese and western responses to the crisis, often under bombastic titles such as 'coronavirus and the clash of civilizations' (maçães ) . political scientists discuss whether the pandemic is an argument for total dismissal of capitalism or just a passing aberration in its functioning (roberts ) . economists advise us to prepare the new recession (elliott ) . sociologists see worldwide border closures as an anti-globalization experiment (peters et al. ) , and philosophers go back to questions pertaining to human nature. worldwide governments are responding in radically different ways-the government of montenegro has closed down the whole country before it registered the first patient within its borders (world health organization b), while the uk has opted for a laissez faire approach which is hoped to result in herd immunity (dunn and kahn ) . from official news to social networks, everyone and anyone has something to contribute to these debates, creating an infodemic which will be analysed long after covid- is gone. as i write these words on march from self-isolation in my flat in zagreb, croatia, the future of the pandemic is unclear. we have no idea what percentage of the global population will be affected by the virus, whether the virus will mutate, how many people the virus might kill, and what might happen with our politics and economy after the pandemic is gone. at this point, we need to develop immediate measures to protect ourselves individually and collectively-weed out reliable information, self-isolate, reduce panic, develop educated guesses and emergency plans. however, these urgent measures cannot arrive from thin air, and it is just as important to step back and take a birds-eye, longue durée view at the pandemic. while doctors, nurses, politicians, food suppliers, and many other brave people self-sacrifice to support our daily survival, this editorial argues that academics have a unique opportunity, and a moral duty, to immediately start conducting in-depth studies of current events. viruses are nanoscale infectious agents (one nanometre is a billionth of one meter). viruses do not have their own cellular structure and cannot naturally reproduce without a host cell. yet viruses do have genes, which evolve by natural selection, and when they enter the host cell, viruses reproduce through self-assembly. looking at different aspects of their existence, viruses can be understood both as an inanimate matter and as a form of life, and 'the question about the origin of viruses and life itself remains for the most part a philosophical debate and largely dealt with theoretical arguments rather than molecular data, especially because viral genomic repertoires are limited and patchy' (nasir et al. : - ) . according to antonio Šiber ( ) , the border between non-life and life lies somewhere at the point when inanimate organic matter becomes soaked with information which enables self-replication and evolution. while it is easy to agree with Šiber's definition, this point is hard to determine and far from agreed upon. viruses are within our bodies and in our environment. over the centuries, viral pandemics such as the spanish flu have been major biological, social, and cultural events. viral behaviour (and some would say viruses) can also be found beyond the organic world. recent examples include viral internet memes and videos, viral marketing, and computer viruses (computer programs which enter host programs, modify them, and replicate themselves). while computer viruses are clearly even further from life than biological viruses, 'some scientists have begun to ask if computer viruses are not a form of artificial life-a self-replicating organism. simply because computer viruses do not exist as organic molecules may not be sufficient reason to dismiss the classification of this form of "vandalware" as a form of life.' (spafford : ) . this argument sits well with a growing number of posthumanist critiques, which suggest that what we should accept as life is largely 'a normative not a descriptive category' (fuller and jandrić : ) . covid- is an organic virus which has caused various sorts of organic and nonorganic viral behaviours in all spheres of (human) biology, culture, and society. the interplay of these behaviours can be approached through the lens of michael peters' viral modernity, which is 'a concept that is based upon the nature of viruses, the ancient and critical role they play in evolution and culture, and the basic application to understanding the role of information and forms of bioinformation in the social world' (peters et al. ). viral diseases have always been intrinsic to human existence. every age has its own viral modernity, and the covid- pandemic is merely the first global exercise of viral modernity in our 'hard to define; messy; unpredictable; digital and analog; technological and non-technological; biological and informational' postdigital reality (jandrić et al. : ) . these days, we can speak of viral education (exemplified in a current global switch to online education), viral post-truth (exemplified in a global covid- infodemic), viral open science (exemplified in exponential growth of open science and associated publications) (see peters et al. ) , and so on. writing these words from home isolation in the midst of the covid- pandemic, it is hard not to overstate the viral nature of, and viral perspective to, our postdigital reality. while the exact relationships between viral modernity and postdigital reality will need to be soberly examined after the heat of the moment is gone, there is no doubt that the covid- pandemic is an extreme postdigital 'rupture and continuation event' (jandrić et al. : ) , and that this event will significantly influence the way we see and experience the world in the foreseeable future. writing these words at the beginning of the global community outbreak phase of the covid- pandemic, i am painfully aware of their ephemeral nature. hopefully, the pandemic could soon wind down; yet it is just as possible that we might be heading towards a large-scale disaster or towards anything in the between. and yet, most of us cannot do much at this stage. being in self-isolation, my 'research' of covid- consists of cooking nice meals, cleaning my flat, endless consummation of the infodemic, frantic exchange of emails with friends all over the globe, and feeble attempts to make sense of what happens. unsurprisingly, that involves a lot of trivia and a bit of humour. reading semi-serious, semi-bitter, semi-hopeful 'predictions' of a possible baby-boom nine months after introduction of a curfew in italy, austria, and spain, my first instinct was to think of all those academics now sitting at home. those of us who teach are now dealing with the complexities of online education, and many of us will also try and catch up with writing that one paper that has always hovered at the bottom of our to-do lists. in the sea of covid- -related speculations, the only prediction i would put my money on is an increased number of paper submissions to academic journals in the months to come. researchers in some areas of medical sciences, biology, economy, logistics, and others, can help people directly affected by the pandemic through the development of diagnostic tools, medicines, and vaccinations; analysing counter-recession measures; increasing efficiency of shipping food and medicine; and the like. however, what happens to people who have not been infected by covid- but have lost their jobs, cannot pay their mortgages, or have become homeless due to economic slowdown? what happens to the most vulnerable members of the society -children, elderly, disabled, those with mental issues? how many indirect victims will the covid- pandemic create? in our context of advanced global capitalism, what should be done to spread the burden of the pandemic at least a bit more equally? and which consequences will the covid- pandemic have in regards to the environment, surveillance, worlwide rise of fascism, democracy? postdigital viral modernity is equally about biology, culture, and society; in the long run, humanity cannot defend itself from covid- and create a better future without engaging all strata of the society. therefore, it is crucial that academic researchers working in the humanities and social sciences immediately join the struggle against the pandemic. in the postdigital context of viral modernity, decades of training and experience in any academic field can contribute to making sense of the crisis. postdigital researchers should read, research, and write about all imaginable aspects of covid- !-even if that research, at present, does not seem to offer much help in getting us through and over the pandemic. the covid- pandemic has brought a huge social experiment into our homes, streets, cities, countries, and globally. outcomes of this social experiment will follow the whole humankind, probably fairly unequally, far into the future. as i write these words, nurses and doctors undertake huge health risks to support our wellbeing. supermarket tellers undertake similar health risks, but receive much less praise, to bring supplies to people who are not (or will not be) allowed to leave their houses. teachers work nights and weekends to develop learning materials and support their online students. people working in many other occupations, pensioners, children, and many others, need to stay at home, watch the news, and follow instructions. none of these roles is less important than the other. while we obviously need food, healthcare, and education, the virus can be contained only through discipline and solidarity of all strata of the society. the humanities and social sciences are already making significant contributions in areas such as informing citizens, prevention of panic, big data analysis, open science, and others. for instance, uk's wellcome trust statement, 'sharing research data and findings relevant to the novel coronavirus (covid- ) outbreak' (wellcome trust ) has enabled unprecedented levels of sharing covid- -related information which have already significantly contributed to development of diagnostic tools, medical procedures, and vaccines (see peters et al. ). while we struggle against immediate threats, however, we should also keep in mind the broader picture. other areas of the humanities and social sciences, which may now seem unrelated to our immediate struggle against the pandemic, are not less crucial for long-term flourishing of the human race. we, postdigital scholars working in the humanities and social sciences, should not take our home isolations and quarantines as unexpected vacations or opportunties to catch up with old projects. instead, we should look into the strengths of our disciplinary knowledges and research methods to try and create opportunities to contribute to humanity's collective struggle against the covid- pandemic and point towards more sustainable futures. some of our current insights will be hasted, and will serve as mere first-hand testimonies for later (and more balanced) research. some of our insights will be picked up only in the next pandemic. some of our insights will be plainly wrong, and consequently retracted. in our current infodemic, the most of our current produce will probably simply remain overlooked and unread. yet some of our insights may raise awareness of important issues, add more nuance to our thinking, and perhaps even influence the course of the pandemic. it is impossible to know which piece of research will end up in the garbage bin of history, which piece of research will make a difference, and when that difference may surface. anne frank's diary did absolutely nothing to stop the second world war, and poor anne had not lived long enough to even see it published. yet seventy years later, anne frank's diary still makes a huge service to humanity by providing a constant reminder of the perils of fascism. wearing my academic researcher hat, i am not ashamed of naivety of this paper-it honestly represents my current thoughts and feelings about the covid- pandemic on march . these thoughts are likely to be overridden by new developments, but they will nevertheless serve as a testimony of this historical moment. wearing my academic editor hat, i am not afraid of publishing papers that might be proven wrong or even retracted-messy and unpredictable postdigital challenges pertaining to viral modernity require messy and unpredictable attempts at answering. wearing my daddy hat, i am admittedly a bit ashamed of withdrawing into the world of research while my son lives through some of the most challenging times in his -year-old life. yet beneath all these hats, there is a head; in this head, there is a mind; and in this mind, there is a tiny, persistent voice that whispers: knowledge and solidarity are the key to long-term survival and flourishing of the human race. i invite all postdigital scholars to take this voice seriously, get out of our comfort zones, and explore all imaginable aspects of this large social experiment that the covid- pandemic has lain down in front of us. in the midst of the pandemic, many of these efforts may seem useless. yet paraphrasing john fitzgerald kennedy ( ) , those who dare to fail miserably are also those who might change the course of history. advice to those about to teach online because of the corona-virus coronavirus epicenter has shifted from china to europe we're opening everything': scientists share coronavirus data in unprecedented way to contain, treat disease. cbc news world health organization declares covid- a 'pandemic even while canceling mass gatherings, the u.k. is still aiming for deliberate 'herd immunity'. fortune, march prepare for the coronavirus global recession. the guardian, march the postdigital human: making the history of the future the chinese doctor who tried to warn others about coronavirus postdigital science and education day of affirmation address coronavirus and the clash of civilizations viral evolution: primordial cellular origins and late adaptation to parasitism viral modernity? epidemics, infodemics, and the 'bioinformational' paradigm. educational philosophy and theory it was the virus that did it mass quarantine effective against coronavirus in china. statista treći element computer viruses as artificial life press release: sharing research data and findings relevant to the novel coronavirus coronavirus disease (covid- ) outbreak key: cord- - r dnse authors: van wijhe, maarten; ingholt, mathias mølbak; andreasen, viggo; simonsen, lone title: loose ends in the epidemiology of the pandemic: explaining the extreme mortality risk in young adults date: - - journal: am j epidemiol doi: . /aje/kwy sha: doc_id: cord_uid: r dnse in the century since the influenza pandemic, insights have been sought to explain the pandemic’s signature pattern of high death rates in young adults and low death rates in the elderly and infants. our understanding of the origin and evolution of the pandemic has shifted considerably. we review evidence of the characteristic age-related pattern of death during the pandemic relative to the “original antigenic sin” hypothesis. we analyze age-stratified mortality data from copenhagen around to identify break points associated with unusual death risk. whereas infants had no meaningful risk elevation, death risk gradually increased, peaking for young adults – years of age before dropping sharply for adults ages – years, suggesting break points for birth cohorts around and . taken together with data from previous studies, there is strong evidence that those born before or after were not at increased risk of dying of pandemic influenza. although the peak death risk coincided with the – pandemic, the and break points do not correspond with known pandemics. an increasing number of interdisciplinary studies covering fields such as virology, phylogenetics, death, and serology offer exciting insights into patterns and reasons for the unusual extreme pandemic mortality risk in young adults. initially submitted april , ; accepted for publication july , . in the century since the influenza pandemic, insights have been sought to explain the pandemic's signature pattern of high death rates in young adults and low death rates in the elderly and infants. our understanding of the origin and evolution of the pandemic has shifted considerably. we review evidence of the characteristic agerelated pattern of death during the pandemic relative to the "original antigenic sin" hypothesis. we analyze age-stratified mortality data from copenhagen around to identify break points associated with unusual death risk. whereas infants had no meaningful risk elevation, death risk gradually increased, peaking for young adults - years of age before dropping sharply for adults ages - years, suggesting break points for birth cohorts around and . taken together with data from previous studies, there is strong evidence that those born before or after were not at increased risk of dying of pandemic influenza. although the peak death risk coincided with the - pandemic, the and break points do not correspond with known pandemics. an increasing number of interdisciplinary studies covering fields such as virology, phylogenetics, death, and serology offer exciting insights into patterns and reasons for the unusual extreme pandemic mortality risk in young adults. spanish flu; age patterns; antigenic sin; excess mortality; pandemic influenza abbreviation: wwi, world war i. this year marks the th anniversary of the iconic influenza pandemic. over the years, the impact of the pandemic on death, demography, society, and its general characteristic features have been studied in depth. although many questions have already been resolved, answers to some key questions continue to elude us, such as the origin of the virus, the role of world war i (wwi), the economic and societal impacts, and, most importantly, the unusual death-rate pattern in young adults. in this article, we review some of these outstanding questions, focusing on the origin of the pandemic as well as its "signature" age pattern of an extremely high death rate among young adults, whereas the elderly tended to be spared. we address the hypothesis of "original antigenic sin" ( )-that early childhood exposure may determine death risk during influenza pandemics encountered later in life-which may explain why some age cohorts fared differently in this pandemic. this hypothesis has brewed for some time ( ) , and detailed analyses of data from kentucky ( ) as well as analysis of the dramatically different age patterns among victims of avian h n and h n influenza who were born before and after the pandemic ( - ) have brought new steam to this old question. to further investigate the age-related patterns of death rates and risk change points in , we analyzed monthly all-cause and age-stratified mortality data from copenhagen to address the antigenic sin hypothesis. specifically, we reviewed data on age groups from the pandemic and sought to pinpoint change points in relative risk elevation. we also sought to link these change points to particular years when the so-called original sin would have occurred. for this purpose, we used weekly surveillance for outpatient influenzalike illness in copenhagen and looked for unusual influenza activity. it has been argued that the h n virus originated in the context of wwi efforts in the trenches and army camps in england and france in ; affected persons received a diagnosis of "purulent bronchitis." the reports of an unusual clinical picture of young men with respiratory febrile illness, heliotrope cyanosis, and bloody coughing are strong support for this hypothesis ( ) ( ) ( ) . others have argued that it all started in a military camp in kansas in early march ; again, military doctors saw a similar unusual picture of hemorrhage and edematous lungs on autopsy among enlisted men who had clinical symptoms of influenza ( , ) . according to a third theory, the pandemic originated in inner northern china, where in - , an epidemic of "pneumonic plague" ( ) may have been pandemic influenza that then spread to europe via chinese migrant workers ( ) . although we cannot resolve these different views, the evidence of unusual cyanotic respiratory illness in young men that was later a signature clinical feature in the severe autumn pandemic supports the idea that the emerging h n pandemic virus had festered in immunesuppressed wwi army populations for some time before it gained effective transmissibility. indeed, it may have been wwi troop movements that brought the emerging virus to the united states and it was there that the first documented epidemics took place. the central role of wwi troop movements has previously been documented in a study of brazilian naval ships whose personnel became infected with pandemic influenza after an encounter with the british fleet along the african coast in the early summer of ( ) . meanwhile, the genetic origins of the h n pandemic virus have been studied through phylogenetic analysis of fully sequenced viral rna isolated from lung specimens of victims of the pandemic. taubenberger et al. ( ) concluded that the pandemic virus emerged as an all-avian virus crossing over to human populations in . however, evidence from smith et al. ( ) suggests the virus arose through multiple reassortment events among circulating swine, avian, and human strains in the decade before the pandemic. in , contradictory evidence was brought forth by worobey et al. ( ) , who argued that the h n virus was not all avian but rather was assembled by reassortment of a human h hemagglutinin and avian viral segments shortly before . they concluded that the hemagglutinin segment had already emerged in human strains around and that about a decade later, the h n pandemic virus fully formed in a single event when the human h strain reassorted with an avian source. taken together with clinical evidence, it is not easy to reconstruct the actual reassortment timeline. it is possible that the unusual occurrence of cyanotic respiratory illness in wwi army camps was, in fact, a manifestation of the h reassortant circulating in the years before the pandemic virus had fully formed and gained the ability to spread effectively. epidemiologists have long analyzed death time series to study the signature age patterns of the pandemic influenza, characterized by extreme death rates in young adults while seniors were spared ( ) ( ) ( ) . using unique influenza outpatient and death time-series data from copenhagen, we demonstrated the existence and the mild nature of the first pandemic wave in the summer of ( , ) and we recently reviewed all evidence of herald waves in ( ) . why this first summer wave was milder than the following fall and winter waves remains unclear. it is possible that the virus had not yet acquired the virulence mutations before autumn, or that important bacterial cofactors were not present during the summer wave. the devastating impact of deaths resulting from the pandemic was due to a combination of high attack rates ( %- %), high case-fatality rates ( %- %), and the unusual age distribution: an estimated % of pandemic deaths occurred in young adults ( ) . the unique pandemic age pattern holds important clues about the meeting of the pandemic virus with the immune landscape of the human population that was shaped by decades of experience with influenza. so far, the observation that adults older than years suffered no excess mortality in cities like new york city and in copenhagen has been interpreted as evidence of "recycling" of the h antigen that age group had encountered during their childhood some years earlier ( , ) . meanwhile, the extreme death rate in young adults suggests that having been born between the (pseudo) pandemic and the russian pandemic resulted in that age group's "antigenic sin" ( ) . the exact break points on the age-risk pattern have been elegantly studied using individual-level death records from kentucky ( ). viboud et al. ( ) found several change points in age-specific excess death rates: a minimum at approximately years of age, followed by a steep increase that peaked at ages - years and another minimum at ages - years. viboud et al. hypothesized that these peaks and valleys in the corresponding birth years (cohorts born during - , - , and - ) should correspond with known dates of historic pandemics. however, they found that this was not the case. the large geographical discrepancies in age patterns provide additional clues. it was found in studies of death patterns in south american populations that elderly people were not spared from pandemic influenza; in fact, all age groups seemed to be at highly elevated risk ( , ) . similarly, observations of high pandemic impact in remote populations such as inuits in newfoundland and the maoris in new zealand can be interpreted in the same way ( , ) . for example, the maoris were -fold more likely to die during the influenza pandemic than were the new zealand population who were of european descent. although far higher death risk in ethnic populations could also be interpreted as a consequence of genetic risk factors, we think a more parsimonious explanation is the remoteness of these ethnic populations in their childhood some - years earlier. these findings of high risk for death associated with pandemic influenza in elderly adults living in remote settings would then support the recycling hypothesis. gostic et al. ( ) brought new evidence to this immunity agesignature puzzle. they demonstrated that victims of h n and h n avian influenza had very different age distributions, such that birth cohorts born before and after the pandemic had completely opposite risk profiles for these zoonotic viruses ( ) . their findings expand on the fascinating possibility proposed earlier by worobey et al. ( ) that it is the phylogenetic group of influenza a hemagglutinin segment (group or group ) that may determine death risk of a novel influenza infection. members of these groups may elicit crossimmunity because their subtypes (h , h and h , belonging to group , and h and h belonging to group ) are from the same major hemagglutinin phylogenetic clade. thus, the recycling hypotheses can be relaxed to having experienced an original sin of group versus group influenza a hemagglutinin in childhood, rather than requiring that the original exposure had to be the exact same hemagglutinin subtype. the high young adult death rate during the pandemic may be due to different imprinting between age groups. all-cause, age-specific death patterns can help us determine which age groups were more affected by the pandemic and thus help uncover clues about the evolutionary history of the virus. therefore, we looked at the death patterns of different age cohorts in copenhagen in and sought to place these patterns in the context of long time series of outpatient records of influenza-like illness. we used detailed, long time series of age-stratified monthly death records from copenhagen along with population census statistics (see andreasen et al. ( ) for more information on the data sources) to look for break points in the age profile of cases during the various seasons of the pandemic ( figure ) . we took the same general approach as viboud et al. ( ) , but rather than look at excess death rates, we studied the relative death risk over the baseline level for each age group. all-cause death data with a -to -year age resolution were available from through through annual reports from the medical officers of copenhagen. as a baseline for and data, we interpolated the death rates for each month between and and calculated incidence rates (the baseline) during each of the pandemic waves. all rates were expressed as all-cause deaths per , individuals (linearly interpolating between successive census data). we then computed the incidence ratio as the ratio of incidence rates for each wave over the baseline. there were pandemic waves in copenhagen during - : a milder first (herald) wave in july to august , followed by the main wave peaking in october to november. this was followed by a winter wave peaking in january to february , and a fourth recrudescent wave in january to february . already in june , the danish national newspapers began reporting on the "spanish sickness" ( ) ( ) ( ) . in the second week of july, the pandemic broke out in both copenhagen and the town of roskilde, km to the west of copenhagen. although the source of the outbreak in copenhagen is impossible to track, in roskilde, it was likely introduced by a circus artist arriving from oslo, norway, where the first wave had already reached epidemic levels a week earlier (table ) . interestingly, before the outbreak in copenhagen and roskilde, an outbreak occurred in the town of christiansfeld just south of the danish border in jutland, apparently introduced by a postal clerk returning from germany ( , ) . it was widely accepted among physicians in copenhagen at the time that the outbreak was a novel, atypical form of influenza and they likened it to the influenza that had caused substantial impact in madrid, spain, in june ( , ) . also, they commented on the outbreak's mildness and suggested that people should not worry-unfortunate advice, in hindsight, because the subsequent autumn wave killed . % of the danish population and %- % of the entire world population ( , ) . across the study period, the pandemic death rate in young adults stood out dramatically in the severe autumn wave (the second wave) and the recrudescent (fourth) wave during winter - . in contrast, young children as well as older adults did not have unusual excess death in the - period (figure ; web figure , available at https:// academic.oup.com/aje). during the severe autumn pandemic wave, the risk ratio was highest for persons in age groups between approximately and years, reiterating earlier findings in other studies (figure ). the risk ratio steadily increased to more than -fold of baseline for the - -years age group during the autumn of . the incidence ratio then dropped sharply for the - -years age group and reached a risk ratio of approximately for older age groups, consistent with no risk elevation during the pandemic. the exact risk break point is likely approximately years of age, judging by the steep decline in this group compared with the surrounding age groups. a similar risk-ratio pattern was seen in all pandemic waves, in particular in the second and fourth waves. we next looked for evidence of pandemic-level activity in the decade before in long time series of weekly influenza outpatient morbidity data available since when influenza was added to the list of notifications (figure ). we could not identify any standout epidemics between the pandemics of and . unfortunately, these morbidity data did not allow us to go back further to check for epidemics around . we next perused annual medical reports for denmark and found that influenza, in fact, was noted and discussed during - but without mention of pandemic or severe activity before . one physician commented that there had been no notable influenza in the years between the pandemic in the s and ( ) . reviewing the evidence that has accumulated from various disciplines, including medical history, quantitative epidemiological analyses, seroepidemiology, virology, and phylogenetics, answers to key questions about the pandemic still elude us. however, we are moving closer, in particular regarding the unusual age pattern of deaths. the recycling hypothesis was first put forward to explain the patterns and has since been investigated for more recent pandemics. age-specific excess death rates were used in a study to review age-groups data to identify points at which pandemic protection begins. such change points have been found for persons older than years during the pandemic, corresponding to those born before the pandemic in ( ) . for the recent pandemic, middle-aged and older adults born before the pandemic were nearly completely spared and showed evidence of preexisting cross-reactive antibodies ( , ) . thus, there is good reason to believe that adult protection relates to exposure to pandemics in childhood. for the pandemic, such an inquiry can only be done with epidemiologic excess death data, because of the absence of seroepidemiology from blood sampled before that pandemic and the absence of virologic evidence from the th century. - , - , - , - , - , - , - , - , - , - , - , and or earlier. in our analysis of copenhagen data, we managed to pinpoint the break point from high to low death risk at approximately years of age (in the middle of the - -years age group). this corresponds to having been born around (range, - ), which is curiously a pandemic-free period in humans as far as we know (there was a severe pandemic in horses ( ) ). in denmark, certainly, there is no mention in the medical literature of a human pandemic event in that period. however, our finding that the maximum death risk occurred in the - -years age group (probably at approximately years of age) is consistent with having been born around the time of the - pandemic, as if exposure to the emerging pandemic virus led to enhanced risk later in life. unfortunately, we could not pinpoint with accuracy a particular break point in terms of risk among the pediatric age groups; rather, we found a gradual increase in the incidence ratios, starting with the - -years age group. explanations for the lack of a steep cutoff could be the limited total number of deaths in the toddler and schoolchildren age groups, or the resolution of the age groups. infants were at no particular year no. of influenza cases increased risk relative to the baseline level. this is not to say that there were no infant deaths due to the pandemic-rather, those would be few compared with the overall background number of deaths. our results are remarkably similar to those of viboud et al. ( ) , given the lower resolution of our data (table ) . whereas in kentucky it was clear that those approximately years of age were at the lowest risk for death associated with the pandemic, our analysis points to children under being at lower risk than those in other pediatric age groups. however, it is also clear that those - years of age were at a relatively low risk compared with those - years old. the highest risk in kentucky was in people between and years old-similar to data from copenhagen. in kentucky, the excess death declined steadily after years; in copenhagen, this decline was sharper and mainly evident in the age groups older than years. these results suggest diverging antigenic sins between birth cohorts. birth cohorts born before may have been exposed predominantly to group influenza a hemagglutinin, whereas those born between and may be been exposed to group influenza a hemagglutinin, and those born after may have an antigenic sin related to reemerging group influenza a hemagglutinin, very likely of the h subtype. it is possible that h was also circulating around , which would explain the low risk among the elderly. seroepidemiology, epidemiologic, and phylogenetic evidence seem to point to the same time period around (table ) ( , , ). the possibility of a -step assembly raised by worobey et al. ( ) in a newer phylogenetic analysis is in disagreement with earlier phylogenetic analyses by taubenberger et al. ( ) and reid et al. ( ) , who concluded that the pandemic was an all-avian zoonosis. although these hypotheses disagree on the origin of the pandemic and its reassortment history, they are consistent with the idea that h (of avian or human origin) was already circulating well before the pandemic arose and was likely introduced in humans between and . it is possible that the pandemic virus was assembled in multiple steps: around , the virus acquired h by recombination ( ). this precursor virus may have been circulating for a decade or more before the pandemic, along with the previous group influenza virus, thereby explaining the intermediate risk profile for those born between and (some would have experienced a group infection and others a group infection as their first influenza illness). certainly, a consolidating view on this issue, and of the possible contribution of other segments, like neuraminidase, would be most helpful to elucidate the likely human immunity landscape at the time. the nature, origin, and timing of a future pandemic may be unknown; however, it is clear from historical accounts that one will occur again. pandemic preparedness relies on our understanding of what might happen given our pandemic experiences; in particular, our understanding of patterns of severity and highrisk age groups. studying historical influenza pandemics is only natural, therefore, and may resolve important conundrums about the interaction between population immunity and pathogen evolution. although some aspects of events such as the h n outbreak and other pandemics of the th and th centuries still elude us, they provide invaluable insights for informing pandemic planning whatever the next threat may be. a serological recapitulation of human infection with different strains of influenza virus the virtues of antigenic sin: consequences of pandemic recycling on influenzaassociated mortality age-and sex-specific mortality associated with the - influenza pandemic in kentucky potent protection against h n and h n influenza via childhood hemagglutinin imprinting first flu is forever genesis and pathogenesis of the pandemic h n influenza a virus the so-called great spanish influenza pandemic of may have originated in france in early herald wave outbreaks of influenza in prior to the pandemic of a hypothesis: the conjunction of soldiers, gas, pigs, ducks, geese and horses in northern france during the great war provided the conditions for the emergence of the "spanish" influenza pandemic of - america's forgotten pandemic: the influenza of the great influenza: the epic story of the deadliest plague in history paths of infection: the first world war and the origins of the influenza pandemic did the - influenza pandemic originate in china? exceptionally high mortality rate of the influenza pandemic in the brazilian naval fleet. influenza other respir viruses characterization of the influenza virus polymerase genes dating the emergence of pandemic influenza viruses further elucidating h n mortality patterns pandemic versus epidemic influenza mortality: a pattern of changing age distribution epidemiological evidence of an early wave of the influenza pandemic in new york city death patterns during the influenza pandemic in chile epidemiologic characterization of the influenza pandemic summer wave in copenhagen: implications for pandemic control strategies a review of the herald pandemic wave: importance for contemporary pandemic response strategies estimation of potential global pandemic influenza mortality on the basis of vital registry data from the - pandemic: a quantitative analysis mortality patterns associated with the influenza pandemic in mexico: evidence for a spring herald wave and lack of preexisting immunity in older populations the - influenza pandemic in boyacá, colombia. emerg infect dis regional patterns of mortality during the influenza pandemic in newfoundland black flu -the story of new zealand's worst public health disaster det drejer sig om influenza, ledsaget af staerk feber kliniske og aetiologiske bemaerkninger om influenzaepidemien den spanske syge i sønderjylland. nationaltidende bidrag til oplysning om influenza, med hensyn til dens forhold til denguefeber cross-reactive antibody responses to the pandemic h n influenza virus incidence of pandemic influenza a h n infection in england: a crosssectional serological study an avian outbreak associated with panzootic equine influenza in : an early example of highly pathogenic avian influenza? influenza other respir viruses recycling of h n influenza a virus in man-a haemagglutinin antibody study a synchronized global sweep of the internal genes of modern avian influenza virus origin and evolution of the "spanish" influenza virus hemagglutinin gene kommer farsoten hertil? -en lille samtale med stadslaegen. nationaltidende en influenzaepidemi i roskilde? roskilde avis den spanske syge i flaaden? mariner indlagt paa epidemihospitalet. politiken den spanske syge i taarbaek. politiken the next influenza pandemic: can it be predicted? conflict of interest: none declared. key: cord- - ufwlw authors: nan title: covid- and social distancing date: - - journal: can j addict doi: . /cxa. sha: doc_id: cord_uid: ufwlw nan these days, drafting an editorial which will be of relevance months hence is a daunting task. a planning meeting with our editorial team and publisher inspired us to chronicle our current pandemic anticipating with some trepidation to compare the accuracy of our perceptions with the realities in june. this vision may also be an important archive for future similar events. on april th, the recorded global number of cases was . million with , deaths ( . %), the united states cases were , with , deaths ( %) and canada was at , cases and deaths ( . %). on march st, canada had no recorded deaths. we also learned that these numbers very much depended on the extent of population screening performed. in north america, the "apex" of the epidemic curve is still nowhere in sight but people draw solace from the fact that drastic public health measures in china and south korea appear to have abated the escalation of number of cases and eventually signifi cantly reduced the incidence of new ones. social distancing in a compliant population has been credited for controlling the epidemic. drones were even used to monitor behaviour. that experience was contrasted with rapidly escalating european statistics overwhelming the health care system and resulting in a higher rate of mortality, including among health care providers. the diff erence again was attributed to a culturally freer society with a higher rate of interconnectedness and perhaps diff erences in vulnerable age groups. spurred by these experiences, canada, like other countries, adopted social distancing as its most visible public health measure. travelling back from the united states, i completed a day period of isolation which i am sure contributed to my choice of topic. socialisolation as a public health measure highlighted some unintended challenges for our addiction services. this pandemic demonstrated once more that an essential target of our practices is to rebuild our patients' positive social connectedness with peer groups, families, worksites, and communities in general. our detailed assessments aim to establish a rapport with our patients along with motivational interviews to encourage initiation and compliance with treatment programs. these programs largely provide a mix of individual, group, and family activities where interactive professional and peer support is promoted. the frequency of the administration of medication in harm reduction programs aim to encourage regular treatment contact in addition to monitoring. residential programs emphasize group identifi cation and mutual help fellowship is a pillar of the maintenance of recovery. it is fully realized that measures to control a lethal viral pandemic aim to keep people alive. in most cases, the epidemic will hopefully resolve in a matter of months and distancing is temporary. gratitude is due to our colleagues and other fi rst responders who risk their lives by willingly exposing themselves and their loved ones to potentially lethal infection in our midst. can we however learn from this fresh experience to refi ne our strategies? as a consumer of north american media, a recipient of a fl ood of daily emails and listening to experts (ccsa, who), i cannot help but draw the following perceptions: ( ) public health preparedness-pandemics are a recurrent phenomenon. in the last years, the world has experienced sars, h n , ebola, zika, mers, and now covid- . they are salient by their lethality but also occur on top of other more endemic epidemics, such as viral hepatitis, hiv, or west nile encephalitis among others. this frequent occurrence should dictate education and training in disaster strategies in our curricula. we may have short memories, but we were caught fl at footed with very limited inventories in screening tests, pipettes, and protective gear all the way up to icu beds and ventilators. social distancing to ensure new cases did not overwhelm limited inventories became the major dilemma. covid chronicles volume no. www.canadianjournalofaddiction.org editorial ( ) isolation and testing-every pandemic has its own characteristics and predictions can be diffi cult at the onset. in a few short weeks, we experienced a number of changes in the criteria for entering or leaving isolation, but the relative absence of screening tests and results awaiting to days led to a loss of valuable healthcare resources. uniformly isolating for weeks, people, many untested, led to the loss of valuable workforce. the risks associated with asymptomatic contacts remain a mystery, as we have so far no reliable prevalence data. ( ) recognition of addiction and mental health issues as part of an infectious disease pandemic -perhaps as an indication of stigma reduction, addiction, and mental health challenges are receiving better scrutiny. social distancing is required but social isolation should be prevented. of note, the concept of social distancing evolved into physical distancing. are countless webinars enough? local epicentres of the disease occurred in nursing homes, shelters, prisons, and the homeless all sharing degrees of isolation. the reaction to the pandemic has been compared to a mass grief reaction, with phases starting with denial, followed by anger, bargaining, and fi nally acceptance. ( ) technology as an alternative to personal contact-predictably, we have been reminded how electronic communication could supplement or replace face to face contact and the empirical evidence for the eff ectiveness of some of these interventions is rising. i must betray a generational bias by confessing a preference for direct connection between a patient with addiction and a therapist, particularly in the initial stages of the involvement. not everybody has access to or is just comfortable using a computer, and this certainly applies to some of our most vulnerable populations. younger generations weaned on computers as their preferred means of communication may be more comfortable with reduced human contact, but a third of our population at least is estimated not to be there yet. meanwhile, virtual care will get a boost and governments will recognize variations of this modality as a billable service. ( ) impetus for research-this pandemic raises so many questions on every front! how valid were the assumptions of epidemiological models resulting in a wide range of conclusions and fear of the unknown? will we get secondary epidemics? what are the determinants of interprovincial diff erences? the spectrum of addiction and mental health implications of public health measures remain a fi eld in its infancy. is the knowledge borrowed from natural and war time disasters valid against an "invisible enemy" mutating at regular intervals? will we need to "fl atten the curve" once or several times? a plethora of guidelines from various sources made their integration somewhat diffi cult. top of the list was the need for reliable, readily available testing. the uncomfortable interaction of public health policies and politics were on full display. politics played a major role in denying the recognition of a pandemic in most countries. on the other hand, once recognized, it also played a major role in marshalling resources. promises of a -min test, trials of hydroxychloroquine accepted by fda in a week, the building of fi eld hospitals in days in several countries were unheard of so far. closer to home, should liquor and cannabis stores be considered "essential services" to prevent panic buying? never to miss an opportunity, the internet gaming industry marketed #playaparttogether with a pretense of who support. ( ) social resilience and ingenuity-i should conclude by reminding ourselves that pandemics can also bring out the best in us. heartwarming displays of resilience will be remembered, such as the singing from balconies, the banging of pots and pans to recognize fi rst responders at the end of their shifts as well as the parades of cars in front of the nursing home to celebrate a grandparent's birthday. industrial ingenuity in retooling mobile hospitals and trials of vaccines, antibodies, and other therapeutics will have longstanding benefi cial implications. www.canadianjournalofaddiction.org editorial let's review these perceptions in june. the cja welcomes more empirically based chronicling of the pandemic. we are all in this together. nady el-guebaly, c.m., md, frcpc editor-in-chief, cja-jca canadian centre on substance use and addiction. the impact of covid- on people who use drugs collision of the covid- and addiction epidemics on grief and grieving: finding the meaning of grief through the five stages of loss world health organization. mental health and psychosocial considerations during the covid- outbreak key: cord- -as yhroz authors: crespo-facorro, benedicto title: mental health and the sars-cov- pandemic date: - - journal: rev psiquiatr salud ment doi: . /j.rpsm. . . sha: doc_id: cord_uid: as yhroz nan less than one month. that is how long the sars-cov- pandemic gave us to adapt individually, socially and professionally to a context never before experienced or even imagined, a scenario of high stress that has already changed our way of life and that of future generations. the uniqueness of the covid- pandemic is that we must adapt to those changes quickly, in a scenario of great uncertainty, and almost with no time to reflect or assimilate it. maximum interest has been awakened in knowing and analyzing the impact of the pandemic on the mental health of the general population, patients, caregivers and healthcare professionals directly involved in treatment on the front line of covid- patients. ibañez-vizoso et al. describe, with historic and international vision of this and other pandemics, the experiences and action plans related to mental health services involved in responding to the diversity of needs generated. this knowledge is of maximum interest to be able to design strategies and measures preserving the maximum integrity of mental health in countries where the pandemic is fully developed or still to develop. in recent weeks, there has been continual discussion in all areas of stress (physiological and psychological) coping, adaptation, etc. this volume of analysis, foresight and prediction in itself is surely another source of stress. the term stress was first used to describe situations in which aggressive external factors trigger a physiological response and behavior to prepare the individual to cope with these e-mail address: benedicto.crespo.sspa@juntadeandalucia.es stimuli . valdes-florido et al. describe a series of four clinical cases of brief reactive psychosis coinciding with the stressful situation we have been experiencing for the last four weeks, and in which an important emotional instability component and impulsive/suicidal behavior are evident. but only exceptional human and social situations, such as the one we are now living in, which endanger the most basic human needs, are those which unanimously and directly make us question established functional schemes. these are the behavioral and cognitive routines which allow our brain to live ''relaxed''. if they are broken, our brain can be overcome by the number of decisions and emotions that have to be faced in a menacing and negative affective reality. on a personal level, we need to create new heuristic models to achieve that new cerebral homeostasis. we have to face this reality, and we will do so as individuals and as a society, as history has demonstrated . as individuals and society, we need to seek solutions to the external problem, but it is also fundamental to our mental health to be able to manage our distress and emotions in coping with this polyhedral stressor (even if we cannot do anything to change the situation) . the challenges for coping are many and diverse, and we know the stress of establishing new habits. what we do not know, although it is often conjectured, are the mid-to-long term consequences of this adaptive effort. in this issue, vieta et al. reflect on and provide their perspective, in an elegant and illustrative manner, of the reality that has built up in recent weeks and the possible repercussions of the covid- pandemic on different spheres of international mental health perspectives on the novel coronavirus sars-cov- pandemic a syndrome produced by diverse nocuous agents reactive psychoses in the context of the covid- pandemic: clinical perspectives from a cases series estrés y salud (valencia). hombrados mi (comp), promolibro estrés y procesos cognitivos psychiatry in the aftermath of covid- psychiatry, with a message implicit in the need to learn and identify the opportunities for improvement arising from this tragic situation. key: cord- -c skxte authors: méthot, pierre-olivier; alizon, samuel title: emerging disease and the evolution of virulence: the case of the – influenza pandemic date: - - journal: classification, disease and evidence doi: . / - - - - _ sha: doc_id: cord_uid: c skxte “why do parasites harm their host?” is a recurrent question in evolutionary biology and ecology, and has several implications for the biomedical sciences, particularly public health and epidemiology. contrasting the meaning(s) of the concept of “virulence” in molecular pathology and evolutionary ecology, we review different explanations proposed as to why, and under what conditions, parasites cause harm to their host: whereas the former uses molecular techniques and concepts to explain changes and the nature of virulence seen as a categorical trait, the latter conceptualizes virulence as a phenotypic quantitative trait (usually related to a reduction in the host’s fitness). after describing the biology of emerging influenza viruses we illustrate how the ecological and the molecular approaches provide distinct (but incomplete) explanations of the – influenza pandemic. we suggest that an evolutionary approach is necessary to understand the dynamics of disease transmission but that a broader understanding of virulence will ultimately benefit from articulating and integrating the ecological dynamics with cellular mechanisms of virulence. both ecological and functional perspectives on host-pathogens’ interactions are required to answer the opening question but also to devise appropriate health-care measures in order to prevent (and predict?) future influenza pandemics and other emerging threats. finally, the difficult co-existence of distinct explanatory frameworks reflects the fact that scientists can work on a same problem using various methodologies but it also highlights the enduring tension between two scientific styles of practice in biomedicine. the question "why do parasites harm their hosts?" is recurrent in evolutionary biology and ecology, and has several implications for the medical sciences, particularly public health and epidemiology. the question is perplexing because of its paradoxical aspect. indeed, one wonders why natural selection favours high virulence if this inevitably results in both the host and the pathogen's deaths. shouldn't host and pathogens peacefully coevolve, and thus maximize both their chances of survival, instead of engaging in a near-infi nite arms race? very much along these lines, the lives of a cell ( ) by american physician lewis thomas refl ected the conviction that "there is nothing to be gained, in an evolutionary sense, by the capacity to cause illness or death" (thomas , ) . thomas' views on the nature of disease were once widely accepted among medical scientists during the past century. the possibility of eradicating diseases like smallpox, combined with the belief that evolution was going to naturally wipe out infections, worked together in supporting the idea of the end of infectious diseases (levins ) . physician and epidemiologist aidan cockburn, for instance, stated confi dently: "it seems reasonable to anticipate that within some measurable time, such as years, all the major infections will have disappeared" (cockburn , ) . following the improved control over infections provided by vaccines, antibiotics, and chemotherapy, biomedical authorities in the s and s, particularly in the u.s., ceased to regard infectious diseases as one of the major causes of death and morbidity, and argued, furthermore, that fundamental research on microorganisms could be halted altogether (burnet in fantini . this perspective was also refl ected at the political and economic levels. after the "war" on cancer and cardio-vascular diseases was declared in the early s, for instance, the budget of the national institute of health (nih) doubled in years, while the funding for the national institute of allergy and infectious diseases (niaid) grew by only % (krause , ) . the belief in the power of medical technology to conquer infectious diseases with newly developed drugs resulted in the idea that given suffi cient time most of these diseases would naturally decline as a result of the evolutionary dynamics that govern host and pathogens' relation and lead to lower levels of virulence over time (méthot a ; snowden ) . the return of infectious diseases from the early s onwards turned this perspective on its head, however, as the responses of modern medicine seemed no longer adequate in the face of the steep rise of nosocomial infections and the evolution of drug resistance worldwide. particularly, the acute sense of control over infectious disease felt by many was thrown into disarray with the onset of the hiv pandemic and other emerging infections such as ebola fever, sars, and more recently with the return of h n infl uenza. partly because "many people fi nd it diffi cult to accommodate the reality that nature is far from benign" (lederberg , ) , the rationale of the "conventional wisdom" (as named by may and anderson ) -namely that hosts and pathogens should coevolve towards a state of harmlessness -was promoted far into the second half of the twentieth century (see ewald for a review). an additional reason for the success of this avirulence hypothesis, besides its intuitive soundness, was the fact that no serious alternatives to it were introduced before the late s (alizon et al. ), even though some like zoologist gordon ball ( ) did raise important objections to the conventional wisdom. the thesis of a natural decline in the virulence of infectious disease postulated by earlier evolution-led models has been challenged on both theoretical and experimental grounds in the last years. empirical evidence and advances in modelling in evolutionary ecology (e.g. the trade-off model) have shown, for instance, that the evolution of hosts and parasites into a commensal state is not the vanishing, obligate point it was once held to be, but is rather only one of the possible evolutionary outcomes (anderson and may ; levin and pimentel ; ewald ; reviewed in alizon et al. ). as biologist carl bergstrom recently stressed: "we cannot count on evolution to do our work for us" (bergstrom , ) . selective pressures, on the contrary, can drive the emergence of new diseases (antia et al. ) . and as some have argued, humans may well be the "world's greatest evolutionary force" (palumbi ) behind the increased virulence of pathogens. through new social and cultural practices we open-up new routes for "viral traffi c" (e.g. blood transfusions, organ transplants), foster behavioural changes facilitating pathogens' transmission (e.g. air travel, migrations, sexual practices, use of drugs, etc.), and introduce "new" pathogens from different parts of the world into immunologically naive populations (morse (morse , (morse , . this of course adds up to the continuing emergence of human pathogens through zoonotic reservoirs (wolfe et al. ) . infectious diseases continue to be a serious threat to human health, and some diseases once believed to be eradicated might return. between and , diseases have emerged in human populations, the majority of them appearing during the s after rapid increase in drug resistance was detected (jones et al. ) . despite the recent steep rise in chronic and degenerative illnesses, emerging infections are still a global challenge for twenty-fi rst century biomedicine and they continue to claim million lives annually (morens et al. ; fauci ) . following the resurgence of infectious diseases as a leading cause of death and morbidity, and the detection of previously unknown diseasecausing entities, the idea that newly emerged pathogens have thrown the natural world "out of balance" (garrett ) has garnered a signifi cant amount of scientifi c attention and has led to the adoption of new international health regulations in order to monitor, limit, and control the spread of communicable diseases (castillo-salgado ) . here, we explore how, and in what contexts (molecular, ecological, and evolutionary) , knowledge claims about disease emergence and changes in virulence are made and justifi ed in the case one specifi c example: the - infl uenza pandemic. emerging diseases are usually defi ned as diseases whose incidence has signifi cantly increased within a population over a defi nite period of time (morse ) . as weir and mykhalovski ( ) recently observed, two of the most infl uential books on emerging diseases in the early s (lederberg et al. ; morse ) have stressed the need to investigate factors driving disease emergence from both an ecological and a molecular-genetic point of view. both books argued that the biology of the host and the pathogen, in addition to their complex interactions in changing ecological and evolutionary contexts, must be carefully considered in order to devise appropriate public health measures. in practice, though, it remains a challenging task to integrate those perspectives. indeed, our starting point is the current gap -and lack of integration -in the literature between studies of virulence as applied to emerging disease in the biomedical sciences broadly understood and in molecular pathology and evolutionary ecology in particular. integration is a multi-faceted concept that is often promoted as a promising goal of scientifi c practice. as discussed by philosophers of science, integration in science is a complex process that encompasses several activities such as methodological integration, data integration, and explanatory integration (o'malley and soyer ; see also mitchell ), among others. more rarely is the possibility that integration will fail discussed, however (see o'malley ( ) for an example of such). as this chapter exemplifi es, ecological and molecular methodologies have yet to come together to provide a broader picture of changes in virulence in emerging diseases. here, we focus particularly on experimental and modelling practices in molecular biomedicine and evolutionary ecology and on their respective explanatory limitations. very often, explanations of the virulence of a pandemics are constructed as an alternative between knowing the biological nature of the pathogen or that of the environmental conditions that facilitate its transmission. while both consider the nature of the host as part of the disease process, most of the time one branch of the alternative alone is considered as the right (or at least suffi cient) explanation while attention to other explanatory schemes is scant. using the - infl uenza pandemic as a case study of a particularly virulent emerging disease, we illustrate the enduring persistence of two distinct scientifi c styles of practice in the recent history of virulence studies. beginning with a discussion of the evolution of virulence as seen through the lens of ecological and molecular perspectives in biology, we show how each of them conceptualizes both the nature of virulence and emergence in quite different ways. next, we describe the biology of infl uenza viruses with a focus on the - pandemics and we move on to the ecological-evolutionary explanations of its exceptional virulence, paying attention to the trade-off model, before turning to molecular on the history, epistemology, and social aspects of the concept of emerging disease see grmek ( ); farmer ( ) , king ( ) ; and weir and mykhalovski ( ) . see the recent special issue on integration in studies in history and philosophy of the biological and biomedical sciences ( ). pathology. we argue that an evolutionary approach is necessary to understand the dynamics of disease transmission and evolution but that a broader understanding of virulence will ultimately benefi t from articulating the ecological dynamics with cellular mechanisms of virulence. in sum, both ecological and functional perspectives on host-pathogens' interactions are required to answer the opening question of this essay but also to devise appropriate health-care measures in order to prevent (and predict?) future infl uenza pandemics and other emerging threats. the diffi cult co-existence of distinct explanatory frameworks refl ects the fact that scientists can work on a same problem using distinct methodologies (godfrey-smith ) , but it also highlights the enduring tension between two scientifi c styles of practice in biomedicine. evolutionary biologist ernst mayr has long suggested that functional (proximate) and evolutionary (ultimate) perspectives in biology lack unifi cation (mayr ; see morange ) . more recently, evolutionary ecologists have argued in the direction of a better integration of those perspectives ( frank and schmid-hempel ) . while mayr's point that proximate and ultimate explanations are not alternatives is sound, developmental biology advocates, among others, have persuasively argued that evolutionary questions are relevant to understanding developmental processes, and vice-versa (see laland et al. for a review). today, another, and perhaps equally signifi cant divide, seems to be that between ecological and functional (or proximate) approaches to biological systems and their evolution. as we show, what we call exogenous and endogenous approaches to virulence both make knowledge claims based (sometimes loosely) on evolutionary theory, although each of them invokes one particular aspect of the theory. whereas the ecological (or exogenous) style focuses on processes (e.g. selective pressures, population density, within and between host competition, and so on) acting on the hosts and the pathogen, the molecular (or endogenous) style traces the evolutionary pathway, or patterns, of the infl uenza virus from animal(s) to man, and, by constructing molecular phylogenies, identifi es particular genes for pathogenesis and mutation sites within lineages. in other words, the former analyses one of the main mechanisms of evolution (i.e. natural selection) and the latter describe the path of evolution (i.e. they construct phylogenies) (ruse ) . the construction of molecular phylogenetic trees by the use of the concept of "exogenous" and "endogenous" styles is inspired by the work of historian of science ton van helvoort ( ) . in turn, this approach is indebted to polish immunologist and epistemologist ludwik fleck ( ). patterns derive from processes. the former can be described as the "study of order in nature" while the second refers to "mechanisms generating and maintaining this order" (chapleau, johansen, and williamson , ) . molecular pathologists refl ects the recent "data-driven" trend itself supported by genomics, molecular biology, and the development of high throughput technologies. the use of "evolution" by molecular pathologists is, however, secondary to fi nding molecular mechanisms for pathogenesis and thus explaining changes in virulence mechanistically. each perspective also provides a different way of thinking about disease emergence. briefl y, the endogenous view describes how bacteria and viruses can be transformed into pathogenic, emerging diseases by gaining intracellular and genetic material such as, for instance, a polysaccharide capsule, a large plasmid, a set of virulence genes, or pathogenicity islands (friesen et al. ). these and similar fi ndings have led some to claim that pathogens can evolve in "quantum leap" (groisman and ochman ) . point mutations allowing the virus to bind to a host receptor also belong to this category. while the capacity to cause disease due to new sets of genes is a crucial aspect of how organisms become pathogenic, this capacity can also occasionally result from genomic deletion and gene loss (maurelli ) . in sum, acquisition of novel "virulence factors" (or deletion of other genetic elements) can rapidly lead to the emergence of new diseases or enhanced virulence in some pathogens. for molecular pathologists the concept of virulence is similar to the traditional defi nition of plant pathologists, i.e. the infectivity: a strain is virulent if it is able to infect a host. this defi nition could be traced back to the work of pasteur, for whom "virulent cultures killed, attenuated ones did not" (mendelsohn , - , p. ) . a more classical defi nition is the ability to generate symptoms. in both cases, virulence is an all or nothing trait; it is qualitative and not quantitative. note that these defi nitions have the advantage that they can be translated at different levels, for instance at the cellular level, where virulence can be the ability to infect cells. the ecological or exogenous style adopts another approach to disease emergence, virulence, and evolution. often described as a two-step process, disease emergence requires the introduction of a pathogen within a population followed by its successful dissemination (morse , - ) . the "rules of viral traffi c" (morse ) dictate that both steps usually result from one or several changes in the environment, not from a modifi cation in the biological characteristics of the pathogen. for instance, in a change in the air conditioning system in a hotel in philadelphia facilitated the spread of legionellosis, a bacterium usually commensal to humans, which caused an outbreak of fever and pneumonia now known as legionnaire's disease. however, there are cases supporting a biological explanation of emergence, for instance when a maladapted strain mutates into a well-adapted strain before going extinct (antia et al. ) . the trade-off model developed by robert may and roy anderson, and independently by paul ewald, in the early note that, for historical reasons, in the phytopathology literature the virulence used to refer to the ability of the pathogen to infect a plant (i.e. a qualitative trait). since the american phytopathological society has decided to use the term virulence to refer to the damage done to the host and the term pathogenicity for the ability to infect the plant but few researchers have adopted it. in a way, the debate between two fi elds (evolutionary ecology and molecular biology) has already happened within one of the fi elds (see shapiro-ilan et al. ; thomas and elkinton ; shaner et al. ). s currently underpins the bulk of the theoretical research on host-pathogen's interactions in evolutionary ecology. put simply, the model postulates the existence of ecological trade-offs between a number of epidemiological variables. as a consequence, the evolution of virulence becomes linked to several factors: host resistance and recovery rate, pathogen transmission rate, the timing of infection lifehistory events and population density, among others. the trade-off model permits the investigation of the role of environmental changes broadly conceived (including within and between hosts selection) and selective pressures acting on pathogen transmission, and thus on the level of virulence (alizon ) . while molecular geneticists quickly adopted the concepts of virulence genes and pathogenicity islands, evolutionary ecologists working with the trade-off model continued to regard them with suspicion (see poulin and combes ) . we think this suspicion is probably due to the way virulence is defi ned. for evolutionary biologists, virulence typically is a quantitative trait that can be measured. therefore, genes that are suffi cient to render a pathogen virulent and essentially act as a qualitative trait are diffi cult to fi t into the picture. furthermore, there is no such thing as pathogen virulence alone in ecology. virulence, typically, is a "shared trait" that results from the interaction between a host genotype, a parasite genotype and their environment. in other words, some parasite genotypes might only cause virulence when they infect some host genotypes or some parasites may only be virulent to hosts in certain contexts (e.g. starvation). for evolutionary biologists and ecologists, virulence is the harm a pathogen does to its host, i.e. the reduction in host fi tness due to the infection (read ). fitness is notoriously diffi cult to evaluate but arguably the two most common measures are lifespan and fecundity. one problem is that a pathogen strain described as being very virulent in vitro could turn out to be mild in vivo (and vice-versa) . furthermore, recent work shows that levels of virulence can actually be the result of the immune system's over-response itself (see graham et al. for a review). in the end, evolutionary ecologists focus on a combination of within-host processes when they refer to virulence. importantly, this does not mean that they disregard the molecular processes that lead to virulence. for instance, studies have shown that immune-pathology contributions to virulence lead to a different evolutionary outcome than "virulence factors" produced by pathogens ( alizon and van baalen ) . recent explanations advanced to account for the rapid changes in virulence during the - infl uenza pandemic refl ect the polarity between ecological and molecular explicative strategies. applying the trade-off model to the - pandemic, paul ewald has argued that the proximity of soldiers in the trenches, the hospitals, the transport, and the military camps during world war i greatly facilitated transmission of the virus from host to host. high viral replication rate by natural selection was therefore favoured, which resulted in exceptionally high virulence and the high level of mortality of the pandemic (ewald (ewald , (ewald , . but since the late s, molecular pathology has provided an alternative viewpoint on the evolution of virulence in the pandemic. the identifi cation of the viral rna from frozen bodies and wax blocks in the u.s. and its further sequencing has led to a renewed emphasis on genetic and molecular determinants of the virus as being the most important cause of this dramatic event (see holmes ) . according to molecular pathologist jeffrey taubenberger, one of the leading scientists involved in reviving the infl uenza strain, "it is possible that a mutation or reassortment occurred in the late summer of , resulting in signifi cantly enhanced virulence" ( , ) . taubenberger believes that this "unique feature" of the virus -its extreme virulence -"could be revealed in its [genetic] sequence" ( , ) . both approaches -the exogenous and the endogenous -evolved along parallel lines during most of the twentieth century, and though the concept of emerging infectious diseases brought them closer to one another in the s, we show how they remain in tension (méthot b ) . before describing in more details the potentials and limits of these two perspectives we fi rst describe significant aspects of the biology of infl uenza viruses. the natural history and ecology of infl uenza a virus has been extensively studied (webster (webster , webster et al. ; webster and rott ) . the virus' natural reservoir is the wild waterfowl, as supported by the fact that species of wild duck are not affected by the virus and remain "healthy". the virus replicates inside the host, mostly in the intestinal tract, and is then washed into the ponds where ducks live and breed (webster ) . the relative harmlessness of this relationship is similar to the way myxoma virus is adapted to its natural host, the south american rabbit (see fenner and fantini ) . the family tree of infl uenza viruses contains two genera: one that includes infl uenza a and b viruses and the other infl uenza c viruses. the two genera are distinct in terms of host range and virulence factors. type a is the most common of all, and can infect a wide range of hosts, including, pigs, horses, seals, whales and birds. this type of virus is also the most redoubtable as it has the potential to cause pandemics. type b is believed to infect only humans (especially young children) and type c (another genus) can infect both humans and swine. in this sense infl uenza can hardly be regarded as a "single disease" (johnson , ) . infl uenza viruses are enveloped negative strand rna viruses and belong to the genus orthomyxoviridae (taubenberger ) . the virus of the spanish fl u pandemic belongs to the type a infl uenza, known as h n . infl uenza a and b viruses contain eight discrete gene segments, coding for at least one protein. the surface of infl uenza a viruses is covered by three types of proteins hemmagglutinin (ha), neuraminidases (na) and matrix (m ). the structural confi guration of ha proteins is that of a triangular spike. these spikes allow the virus to bind to red blood cells by causing the latter to agglutinate (i.e. hemmagglutinin). they facilitate entrance into the host and they trigger the infective processes. once the infection is over, antibodies responding to hemmagglutinin spikes are formed, allowing the immune system to recognize the signature of the viral strain in case of another infection episode. in contrast, neuraminidases (na) also form spikes on the surface coat of the virus but their function is to cleave glycoproteins into two and to facilitate the propagation of the virus from cell to cell. na proteins open-up cells for infection, so to speak. antiviral drugs target na in order to block their exit, and antibodies to na are also produced after the infection. infl uenza a viruses are further subdivided into serological types, which is the genetic characterization of the surface glycoproteins ha and na. ha and na proteins have been described to date. these surface glycoproteins defi ne the virus' identity in terms of what the immune system detects and attacks. the different major families of fl u are combinations of the two, hence the designation "h n " for the recent threat. the virus was h n . the genes coding for these glycoproteins can reassort (i.e. reshuffl e) due to two processes known as antigenic drift and antigenic shift. the former consists in the accumulation of point mutations in the genome of the virus, modifying both the shape and the electric charge of viral surface antigens and preventing their recognition by the antibodies of the host that were developed in reaction to previous exposures to the virus. the need to update the infl uenza vaccines every year illustrates the evolutionary success of antigenic drift. in contrast, antigenic shifts refer to the introduction of whole or part of infl uenza genes into viruses that circulate among human populations. this form of genetic reassortment or reshuffl ing occurs especially in swine that act as "mixing vessels" for the viral strains and are considered the intermediate host between birds and humans (webster and kawaoka ) . the introduction of a new hemmagglutinin gene (ha) is often hailed as the responsible factor for increased virulence (bush ). the fast reassortment of nucleotides and the high rate of mutation in infl uenza viruses result in infl uenza posing a continual threat for human and animal health. as a result, infl uenza is regarded as being a continually "re-emerging" disease (webby and webster ; webster and kawaoka ) , and international efforts are made to understand why the - pandemic was so exceptionally virulent. the motivation behind these global efforts in gaining a better understanding of this pandemic is to draw lessons from the past in order to be better prepared for the rise of future infl uenza and other viral pandemics. recorded history suggests that the fi rst infl uenza pandemic occurred in . beginning in asia, it rapidly spread to africa, america and to europe. between the eighteenth and the nineteenth century, medical historians identifi ed (at least) pandemics out of epidemics of infl uenza a virus (beveridge ) . the most devastating pandemic, however, occurred in - ( fig. ) . the emergence of on the history of the infl uenza pandemic, see barry ( a ) , johnson and mueller ( ) , van helvoort ( ), crosby ( ) , and burnet and clark ( ) . for a short but informative "chronicle" of infl uenza pandemics, see beveridge ( ) , and for a detailed scientifi c account of the biology of infl uenza see stuart-harris ( ) . the (misnamed) "spanish" infl uenza pandemic of - is the fi rst of the three major infl uenza pandemics that occurred during the past century -and is regarded as one of the most devastating episodes in medical history (mcneill ) . once described as "the biggest unsolved problem of theoretical epidemiology and public health practice" (burnet and clark ) , its consequences rendered many wary about the emergence of respiratory disease pandemics in a near future (webby and webster ) . in addition to the - pandemic, two other major infl uenza pandemics occurred in - ("asian" infl uenza, h n ) and in ("hong kong" infl uenza, h n ). the death of david lewis, a soldier at the military camp of fort dix in the u.s., and the infection of a few hundreds of others in led public health authorities to believe they were facing a new infl uenza epidemic. amidst some scepticism, vaccines against h n fl u were quickly stockpiled as president ford gave the green light to mass vaccination. however, no epidemic occurred while a number of vaccinated individuals came down with guillain-barré syndrome, an autoimmune disease, a few weeks later (see krause ) . one year later, in , the h n virus, which had disappeared in , reappeared (the socalled "russian" infl uenza) in the soviet union and spread to taiwan, the philippines, singapore, and within months had reached south america and new zealand. the virus was similar to a virus isolated in the u.s. in at fort warren and had perhaps been accidentally released from a laboratory located in the former the reference to spain is due to the fact the publication of medical reports on infl uenza was authorized in spain during the war, in contrast to other countries at war. as a consequence, the disease became associated with spain that was subsequently blamed for it and considered responsible. one of the fi rst papers to appear in london times (june ) was titled "the spanish infl uenza -a sufferer's symptoms" (in johnson , ) . like syphilis, the spanish infl uenza received other names in other countries, however. for instance, it was called the "swiss fl u" in france. soviet union (berche , ) . affecting mostly individuals born after , this virus coexisted with the h n virus until , when a new variant of h n emerged (the "swine" fl u, which is the latest pandemic) that replaced the variant. in comparison to the spanish fl u pandemic of , the hong kong and the asian pandemics were more "benign", the former causing between . and million deaths, and the latter million. the recent h n pandemic caused a few deaths only between and (taubenberger , ) . despite the (crucial) facts that antibiotics were available during the second two pandemics, and that medical care had signifi cantly improved and was more effi cient after , this raises the question: why was the - pandemic so deadly to humans? a fi rst important aspect of the - infl uenza pandemic is its likely western origin. in part because of its extensive pig-duck farming industry, china was previously singled out as the possible origin of most infl uenza pandemics. however, whereas most pandemics to have befallen man have come from china (morse , ) the "spanish" fl u originated (likely) from france as early as causing acute respiratory symptoms closely resembling the phenotype of the disease during the - fl u pandemic (oxford et al. (oxford et al. , . some have recently argued that there was an early wave of infl uenza in new york between february and april (olson et al. ). the precise geographical origins of the pandemic are still a matter of debate, however. the world's deadliest fl u pandemic kicked off in october and in just a few months, the virus killed between and million people (philips and killingray ; johnson and mueller ; crosby ; some estimate deaths to number about million, see mcneil ) . according to the "three waves theory", infl uenza swept through all fi ve continents in three recurrences. the fi rst wave (or the "spring wave") of the fl u started in march in the u.s. (mid west) before moving to europe, then to asia and north africa before reaching australia in july . while morbidity was high, mortality was not higher than the habitual norm (reid et al. , ) . the second wave (or "fall wave"), however, was highly devastating and rapidly went extinct after causing millions of deaths worldwide, with peaks in october and november. it started in late august and within week reports of the virus came from distant cities, including boston (u.s.), freetown (africa), and brest (france). on many accounts, this second wave lasted until november. the speed at which the virus circulated makes it diffi cult to pinpoint one specifi c location as being "the" source of the pandemic but a western origin appears to be the most plausible hypothesis according to the available evidence. reports indicated a further third wave that hit in the fi rst months of but was much less severe (burnet and clark ; barry a ). however, the three waves pattern of the pandemic is not uniformly applicable to all countries; for instance australia experienced a single occurrence of the fl u pandemic (johnson and mueller ; ). in , during an attack of infl uenza most victims died of secondary infections as death often resulted from bacteria invading the lungs of immunocompromised individuals (burnet and clark ) . symptoms lasted generally between and days and could, more rarely, be extended up to weeks. the respiratory disease was characterized by fever, body pain, and severe headaches. without the possibility of treating patients with antibiotics, bacteria turned "those vital organs [lungs] into sacks of fl uids […] effectively drowning the patient" (philips and killingray , ). people therefore died within just a few days of hemorrhagic pulmonary oedema and other lung affl ictions (bush ; see also taubenberger et al. ) . related to this, the second striking aspect of the infl uenza pandemic is the young age of the victims, which was qualitatively distinctive: most of them were men, supposedly healthy, of between - years old (some say - ), irrespective of whether the country was involved in the war or not. instead of forming a u shaped mortality curve, the shape of the pandemic was w shaped. an additional peak (the central peak in the w) represents the male victims of the fl u. figure (above) shows the u shaped curve of and the w shaped one of . the distribution of deaths on this curve refl ects the virulence of the pandemic and underlines the pattern of mortality of a group usually not affected by seasonal fl u. finally, the third and most signifi cant feature of the pandemic was its lethality: the disease was of exceptional virulence and estimates suggest that the pandemic claimed more victims than the first world war (mcneil ) . this central aspect was almost universally recognized as being somewhat unusual and very specifi c to it although the estimates of fatalities during the twentieth century vary between and million deaths (johnson and mueller ) . infl uenza type a viruses are not at all uncommon, and strains had circulated in human populations for a few centuries before since a few centuries when the pandemic broke out. in the united states alone only, annual death tolls related to seasonal infl uenza are estimated to be about , individuals (thompson et al. ) . seasonal outbreaks of infl uenza normally last a few weeks and then disappear abruptly; they result from infl uenza viruses present in human populations that are able to infect individuals due to antigenic drift. on occasions, however, the virus can infect up to % of the world population. during these pandemic years, in contrast, the number of deaths rises way above the average, claiming millions of victims all around the globe. in the course of seasonal epidemics strains of infl uenza type a and b can sometimes coexist, if at different frequencies among populations. so why was the spanish infl uenza so devastating? recent work in molecular biology argues that the waves pattern, the group mortality, and the clinical course of the disease "may fi nd their explanation in genetic features of the virus" (reid et al. , ) . others, however, defend the view that the changes in virulence result from signifi cant changes in the wider ecological context in which the outbreak occurred (ewald ) . in the next sections, we review both ecologicalenvironmental and molecular-led approaches to this problem, we indicate some of the limitations of each and we suggest that a better integration of those perspectives would lead to positive outcomes regarding prediction, prevention, and preparedness in the face of other similar infl uenza and other bacterial or viral pandemics. from an ecological point of view, for a disease to emerge in a population the basic reproductive rate of the pathogen ( r ) must be higher than , where r is the average number of secondary infections that follow from one infected individual in a wholly susceptible population (anderson and may ) . in other words, a pathogen must cause at least one subsequent infection to persist in the host population. the classical formula used to capture the trade-off model is as follows: where r serves as a measure of darwinian fi tness of the pathogen at the epidemiological level. in the denominator are α , the host mortality due to the infection (i.e. the virulence), μ , the rate of microparasite independent-mortality and γ is the rate of recovery of the host. the inverse of μ + α + γ is the average duration of the infection. in the numerator, we have β , the transmission rate, and s , the host population size. importantly, one should not confuse β , which is a rate (number of infections per unit of time and per susceptible host in the population) and r , which is roughly the number of new hosts infected over the whole duration of the infection. overall, this expression indicates that parasite fi tness is the product between the number of secondary infections generated per unit of time and the duration of the infection. any animal that produces less than one offspring over its lifetime infections generating less than secondary infection will eventually become extinct and die out. this r > threshold is of course a simplifi cation. for instance, in the early stages of an outbreak, emerging pathogens infect very few hosts which means that they are particularly prone to extinction going extinct due to stochastic effects. in fact, it can be shown that in an ideal situation where all the hosts would be identical, the probability of emergence of a pathogen with an r strictly greater than unity is only of - / r , due to these stochastic effects (diekmann and heesterbeek ) . conversely, pathogens with r < can nevertheless be dangerous because they can persist in the population for a while stochastically, which leaves time for a variant with an r > to evolve (antia et al. ) . in other words, the transmission between hosts (in these cases humans) must be effective for disease emergence to occur. historically, the fi rst example of a trade-off came from the analysis of myxoma virus infecting rabbits (anderson and may ; fenner and fantini ) . however, since then, clearer examples have been worked out. fraser et al. ( ) , for instance, combined data on virulence from an amsterdam cohort and data on transmission rate in discordant hiv-infected couples from a rakai cohort to show that individuals with a higher set-point viral load (i.e. the viral load during the asymptomatic stage, which has the property to often remain constant over several years) have a shorter lifespan and a higher transmission rate. when they combined host lifespan and virulence together to obtain a measure of parasite fi tness (i.e. r ), they found that viruses with an intermediate virus load achieved the highest fi tness. they also show the observed abundance of virus loads in a human population follows the distribution virus fi tnesses. the classic trade-off model focuses primarily on pathogen populations and their evolution. it often ignores host evolution because generation times for hosts (here, humans) tend to be much longer and so evolution in the host population is likely to be slow. from a trade-off model perspective, pathogens' rate of replication within a host, which usually increases the probability of its being transmitted to a new host, is balanced with its negative effect on the duration of the infectious period (may and anderson ) . if the pathogen is not virulent, it is unlikely to reach a high transmission rate. conversely, a pathogen that replicates intensively in the host will have a higher transmission rate but over a shorter time because rapid host exploitation also means shorter host lifespan. similarly to achilles who, according to homer, had to choose between a short and glorious life or a long but dull one, the pathogen has to evolve a strategy between causing long and mild infections or short and virulent infections (alizon et al. ). if such a trade-off is at work, external factors can affect virulence evolution in a predictable way. for instance, the lower the baseline mortality of the host (independently of the disease), then the higher the pathogen virulence should be. this is so because the infectious period is reduced and the pathogen has to use up the host resources in a shorter time. there is also a growing interest in the host reaction to an infection, which can broadly be split into resistance (i.e. fi ghting the disease, which decreases both virulence and transmission) or tolerance phenomena (decreasing only the virulence, not the transmission rate) that affect parasite evolution (raberg et al. ; boots et al. ). the density of susceptible hosts can also affect short-term evolutionary dynamics of virulence, as clearly shown by a recent evolutionary epidemiology framework that combines epidemiology and population genetics (day and proulx ) . indeed, early on during the course of an epidemic, most of the hosts are susceptible to infection so natural selection acts to favour strains with a high transmission rate (which happen to be more virulent according to the trade-off hypothesis). once the disease has reached an endemic stage, the pool of susceptible hosts is smaller (hosts are either already infected, dead, or immunised) and natural selection then acts to favour strains that cause longer infections. in conclusion, virulence can thus be expected to vary over the course of an epidemic for rapidly evolving pathogens. another dimension of the model is that it does not concern itself with morbidity (at least not explicitly). thus, symptoms like pain or injuries are not taken into account by the trade-off model and are implicitly integrated with other variables like host recovery and parasite transmission (levin ) . this assumption impacts on the ways in which virulence will be measured and operationalized. whereas for doctors morbidity (illness) is a key feature of virulence, for evolutionary biologists or population biologists host's pathological factors do not need to be taken into account when measuring virulence; what matters are effects that modify the pathogen's fi tness (i.e. that appear in the expression of r ). in sum, the model rests on the idea that the pathogen transmission rate cannot increase beyond a certain point without at the same time infl icting damage to the host which would, in turn, be harmful to the pathogen by decreasing the duration of the infection. what matters for an evolutionary biologist is the fi tness of an individual where the fi tness of a parasite strain typically is given by the r , i.e. the number of secondary infections. in other words, for a given parasite species, natural selection favours strains with the highest r . this can explain why the highest possible level of virulence is not always the evolutionary stable ("optimal") strategy to increase parasite's fi tness: increased transmission will indeed increase one component of parasite fi tness r (the transmission rate) but it will also decrease another component of r that is the duration of the infection (through increased virulence) as the host is likely to die more rapidly from the infection. the balance between the two selective pressures (transmission favouring higher virulence and duration of infection favouring lower virulence) determines the evolutionary stable level of virulence. ewald's early work on pathogen's virulence and transmission developed a verbal theory for the trade-off model by comparing diseases with different transmission routes (ewald ) . his work was based on the concept of "cultural vectors" and on the assumption that parasites that do not rely on host mobility for transmission should evolve towards higher levels of virulence. in ewald's terminology, a cultural vector is "a set of characteristics that allow transmission from immobilized hosts to susceptible when at least one of the characteristics is some aspects of human cultures" ( ; ; see also ewald ) . in the case of waterborne transmission, cultural vectors include contaminated bed sheets in hospitals, sewage systems carrying the pathogens, medical staff disposing of the contaminated water to water supplies, and so on. waterborne diseases can become more virulent because they do not rely on host mobility for transmission (see ewald , ) , that is, the host can be isolated and still be highly contagious; a "healthy" host is not needed for transmission (in contrast with what was postulated by the conventional wisdom). note that implicit in his reasoning is the idea that more virulent pathogens have a higher transmission because they produce more spores. applying the trade-off model to the case of the pandemic, ewald argued that host proximity and population density were key elements in enhancing virulence. more precisely, he argued that the exceptionally high virulence resulted from rapid passages of the virus in soldiers, recruits and wounded people in hospitals during the war. though a similar explanation had already been heralded in the s- s, it had to be supplemented with an essential "evolutionary mechanism": the classical explanation is based on the analogy with rapid passages of a viral strain through a series of animals (i.e. guinea pigs) in a laboratory that can enhance virulence (as pasteur et al. ( pasteur et al. ( [ ) had experimentally demonstrated, see mendelsohn ( ) ). ewald's argument is that, just like biological vectors, cultural vectors enhance virulence by facilitating transmission. the central point about the serial passages is that it removes the "requirement that hosts be mobile to transmit their infections" (ewald , ) . once this obstacle is lifted nothing (a priori) stands in the way of a steep increase in virulence. in a laboratory context, experimenters inoculate different animals with artifi cially selected viral strains; in the fi eld, this selection process results from another cultural vector, namely the warfare conditions. in the trenches, during the great war, conditions were such that transmission was maximized and with it, the observed level of virulence. as postulated by the trade-off model, the density of the population ( s ) infl uences the level of observed virulence in a biological system (at least for short-term evolutionary dynamics). in this case, the high density resulted from the proximity of the soldiers in the trenches, in hospitals, on trains bringing soldiers to the front, and in military camps. in turn, this resulted in the unusual situation that immobilized individuals who normally should not be able to infect new people (because they would be isolated in a hospital) were now easily able to transmit the infections. similarly, removing wounded soldiers from the trenches and bringing them to war hospitals facilitated transmission. the constant arrival of new susceptible individuals into the population through transport networks resulted in maintaining a high density of infected people; and as a consequence, an equally high level of virulence. related to this is the idea that spatial structure in the host population affects virulence evolution. if hosts tend to have few contacts among them, e.g. because they live in isolation (the technical term to describe such a population is "viscous"), then a parasite has to keep its host alive suffi ciently long enough to be transmitted. on the other hand, if the population is "well mixed", host encounter rate is not an issue -as in the - example -and parasites can afford to be more virulent (boots and sasaki ) . despite its theoretical appeal, some detected a number of problems in the explanation advanced by ewald and with the trade-off model in general. for other evolutionary ecologists, ewald's cost-benefi t argument is too adaptationist -i.e. virulence is depicted as being always adaptive for the parasite. as a consequence, "alternatives such as virulence being non-adaptive, or virulence being a consequence of short-sighted, within-host evolution of the parasite are ignored" (bull and levin , ) . evolutionary theory states that virulence can be directly selected but it can also be coincidental with other infection or biological processes (levin and edén ) , and in some cases it can be potentially maladaptive. this point connects to one of the usual critiques levered against the trade-off hypothesis, namely that it is very verbal and lacks empirical support (levin and bull ; lipsitch and moxon ) . however, the lack of support largely comes from the diffi culty of fi nding an appropriate biological system; arguably, when people have looked for a trade-off in a host parasite system that satisfi es the assumptions of the theory they have found it (alizon et al. ). there is actually a tendency to challenge the trade-off hypothesis using host-parasite systems that do not fi t the underlying model (see alizon and michalakis ( ) for an illustration). a second problem stems from the low level of transmissibility in infl uenza viruses and rate of pathogens' reproduction. when taken into account, this concern weakens the claim that high transmission in the case of the pandemic has favoured high virulence because transmission was lower than with most infectious diseases. r are typically variable but given ewald's argument it would be expected to fi nd a high transmissibility rate between the virus and its hosts. in turn, this would support the claim that natural selection acted on transmission in ways that increased the overall level of virulence. moreover, the trade-off assumes a homogeneous population and was developed for diseases transmitted by contact like infl uenza. however, a comparison of r between the - pandemic with other major disease outbreaks in recent history, or with infl uenza pandemics in general, does not reveal a signifi cantly higher transmissibility in the case of the spanish infl uenza. calculations suggest that the basic reproductive rate of viruses during infl uenza pandemics ranges from and (mills et al. ) . in comparison, the reproductive rate during an outbreak of measles in england in - was between and secondary infections; a pertussis outbreak in maryland (u.s.) in yielded a reproductive rate between and ; and a mumps outbreak in the netherlands during the s produced between and secondary infections in a wholly susceptible populations (anderson and may , ) . in the case of the pandemic, more recent calculations suggest that r was perhaps equal to (morse , ) . finally, a recent article on the transmission of infl uenza in households during the pandemic (fraser et al. ) used historical data and mathematical models to study the rate of transmission. the authors found a relatively low level of transmission between individuals and suggest that prior immunity to the virus should be considered. though transmissibility may, theoretically, have been fostered so that the virus reached unprecedented virulence, the trade-off model alone does not fully explain why it was so deadly. a third issue is the lack of empirical details in ewald's explanation of the steep increase in virulence circa - . to make his argument more compelling, ewald needs additional data that accurately and empirically describe the environmental conditions in the trenches. for instance, how close were the troops? how many soldiers were there? and more importantly, what was the rate of transmission between hosts? if a similar study to fraser et al. ( ) could be conducted on viral transmission in the trenches it would perhaps yield interesting insights into the changes of virulence. to date, no epidemiological data exists that could serve as a basis to model the dynamic patterns, however. though ewald's account seems to suffer from a number of theoretical and empirical problems, it nevertheless supports the argument that properties other than those of the virus need to be taken into account and that without them we would are not able to fully understand the changes in virulence that occurred. as he remarked, progress towards the evolution of virulence "has largely been limited to improve understanding of the genetic mechanisms of antigenic changes and the infl uences of these changes and host immunity on the occurrence of epidemics" (ewald , ) . the recent work of microbiologist john oxford on what we could call the "war hypothesis" reinforces ewald's conclusion by feeding in some of the missing empirical and historical data. while many would agree that the great war is a variable that must be included, in one way or another, in the broader explanation of the steep evolution of virulence of the - pandemic, ewald is convinced that the infl uenza pandemic was "caused evolutionarily by the war rather than being just coincidental with the war" (ewald , ) . the "war hypothesis", as we may call it, received new support from oxford ( ; reid et al. ; oxford et al. ) who does not claim that the great war caused the disease, evolutionarily or otherwise, but instead that the war created the right environment for the virus to become extremely deadly. when the pandemic broke out air travel was minimal and this suggests, according to oxford, that "earlier 'seeding' has occurred" ( , ) . taking an environmentally oriented approach to the evolution of virulence, oxford and his colleagues argued that the - pandemic originated in france in before going global years later. they did not postulate the evolutionary emergence of a mutant strain but rather that the ecological conditions facilitated the spread of a pre-existing infl uenza strain. studying several epidemiological and medical reports of sporadic outbreaks of respiratory infections at the british base camp in the town of etaples in northern france in , oxford argued that the disease's clinical picture maps very precisely onto the description of the - infl uenza: not only were the respiratory diseases extremely deadly, but post-mortem examination revealed in most cases clear evidence of bronchopneumonia and histological analyses of lung tissues indicated "acute purulent bronchitis" (oxford (oxford , . in an article published a few years later (oxford et al. ), oxford and his colleagues took their examination of the situation one step further. rejecting the possibility that "a particular virulence gene of infl uenza" could help to identify future pandemics, they argued that surveillance and detection of emerging infl uenza pandemics would be best served by understanding the contexts that give rise to pandemics, rather than by an analysis of genetic factors alone. in particular, concerning the pandemic, they noted that so far "there is no clear genetic indication of why this virus [the strain] was so virulent". they also remarked that what is needed is a closer examination of the environmental and social conditions of the time such as population upheavals to explain the exceptional virulence. the authors asked specifi cally whether "the special circumstances engendered in the war itself have allowed or caused the emergence, evolution and spread of a pandemic virus" (oxford et al. , ) . for them, the "unprecedented circumstances" of the war in europe were critical. back in , the front was a landscape that was contaminated with respiratory irritants such as chlorine and phosgene, and characterized by stress and overcrowding, the partial starvation of its civilians, and the opportunity for rapid "passages" of infl uenza in young soldiers would have provided the opportunity for small mutational charges throughout the viral genome […] could have been important factors in the evolution of the virus into a particularly virulent form (oxford et al. , ) . the military camp of etaples in france was subject to high traffi c in - . in addition to soldiers moving up to the front and back, , sick and injured individuals were in the hospitals "at any given time", making them overcrowded and allowing the virus plenty of opportunities for "rapid passages". overall, it is estimated that the region of etaples hosted two million soldiers who camped there during the war, in addition to the six million others who occupied and fought in the trenches system that connected the english channel with switzerland (oxford et al. , ) . secondly, as the camp had an "extensive piggery", villagers could buy geese, ducks, and chickens, providing ideal conditions for the infl uenza virus to undergo antigenic shift. thirdly, the extensive use of gases during the war (estimated at one hundred tons), some of which were mutagenic rendered the soldiers immunocompromised and more susceptible to infl uenza infections. finally, demobilisation after the war sent the soldiers back home by boat or by train, and contributed to the spread of the disease by person-to-person contact all over the world (oxford et al. ) . taken together, all these factors (overcrowding, being immunocompromised, pig-duck farming, demobilisation) created exceptional conditions for the virus to go pandemic. ewald had noted that in the absence of a recreation of those circumstances it is unlikely that such a severe pandemic will happen again. what oxford and his colleagues emphasized in their turn is that the appropriate response to a future pandemic cannot rest of putative virulence genes alone; one has also to consider the context that will allow the virus to spread in a pandemic fashion. at the same time that this ecological perspective was developed, another view on the sources of virulence was well underway in the united states. in the mid-twentieth century, leading british bacteriologist wilson smith, co-discoverer of the viral nature of infl uenza in humans in , doubted that the exceptional virulence could be linked to a particular genetic or molecular structure of the virus alone: "if we had the chance of getting a - strain of the infl uenza virus now", he said, "it is at least conceivable that, on comparing with the asian strain, we might fi nd no difference in intrinsic virulence at all, but the conditions in the human population during the two epidemic periods might have affected the degree of heterogeneity displayed by viruses possessed of the same intrinsic virulence" ( , ) . his comments were intended to provide support to a paper delivered earlier by edwin kilbourne, an american virologist who specialised in infl uenza, who had argued that the greater virulence of the pandemic was due to a combination of "the emergence of a new antigenic type in a population with little specifi c immunity" and "the dislocation of and crowding of wartime which favoured not only dissemination and high dosage of virus but spread of bacterial pathogens to an unusual degree" (kilbourne , ) . kilbourne argued that the "study of the host and his environment are more crucial to the interpretation of virulence than laboratory study of the virus itself" ( , ) . attempts to locate the cause of virulence inside specifi c genes or to relate them to other mobile, structural elements (i.e. plasmids) were met with scepticism by people like wilson, kilbourne, until the late s and early s, and the work of olitsky and gates and richard shope, most bacteriologists believed that the causative organism of infl uenza was the gram negative pfeiffer bacillus ( haemophilius infl uenza ) isolated by german scientist richard pfeiffer in . however, the causal role of this organism in infl uenza aetiology was also disputed, particularly during the - pandemic (witte ) . the discover of the viral nature of infl uenza was made by smith, andrewes, and laidlaw in (smith et al. ). and burnet who were interested in large-scale ecological processes and in the formation of evolutionary equilibriums between hosts and parasites. ecologically minded biologists were also reacting against the growing place of molecular biology since the s and its reductionist vision of the life process and the life sciences. this is how we can interpret kilbourne who scornfully remarked that "ironically in this era of molecular biology, the control of no infectious disease has yet depended on understanding its molecular mechanisms" ( , ) . in the early s, scientifi c expeditions were organized to discover the remains of victims of the spanish fl u in the hope of fi nding traces of the virus. one of the expeditors was john hultin ( -), a pathologist from sweden who immigrated to iowa in to study medicine. as part of a project funded by the university of iowa, he travelled in to a small inuit village whose population was decimated by the pandemic, which had killed people in a week, a loss amounting to % of the inhabitants. hoping to fi nd preserved corpses buried in the permafrost hosting traces of the infectious organism, hultin travelled to the seward peninsular of alaska in a village known as teller mission (taubenberger ) . he extracted lung tissue from several bodies he exhumed from the village cemetery, but all attempts to culture remaining traces of the virus of infl uenza from these samples failed to give any result. forty years later, in the context of the human genome project, the idea of resurrecting the infl uenza virus surfaced again, this time powered by genomic technology. since the late s, a renewed emphasis has been placed on the molecular, internal constituents of virulence. newly developed technology and the availability of pathogenic viral and bacterial material have facilitated the development of this approach towards explaining infectiousness. this led, in , to the publication of the complete infl uenza virus' genomic map in both nature and science . though all samples of the strain were thought to be long extinct and lost, bits of rna of the virus were discovered and processed in order to generate the complete map of its genetic structure. after the discovery of frozen individuals killed by the - pandemic and preserved in permafrost, scientists worked on the pathogenic mechanisms that possibly enabled the infl uenza virus to achieve unprecedented levels of virulence. microbiologist jeffrey taubenberger of the national institute of allergies and infectious diseases in washington led this work together with terrence tumpey from the center for disease control in atlanta. we now turn to this recent technological success and the diffi culties of pinpointing any particular molecular feature of the fl u virus of that could account for its exceptional virulence. in a u.s. lab-group based at the armed forces institute of pathology in washington (d.c.), and led by molecular pathologist jeffrey taubenberger, published a piece in science titled "initial genetic characterization of the - ʻspanish' infl uenza virus" (taubenberger et al. ) . the article provided a fi rst and partial genetic map of the virus from "archival formalin-fi xed, paraffi nembedded autopsy tissues of fl u victims" (taubenberger , ) . the examined samples were kept at, and provided by, the national tissue repository of the armed forces institute of pathology. as several mutations in hemmagglutinin, especially on cleavage-sites, often contribute to the virulence (e.g. on infl uenza subtypes h and h ) by increasing the tissue tropism, it was hoped that the genetic make-up of the virus would provide insights into the virulence of the spanish infl uenza pandemic. the goal of the project was "fi rst, to discover where the infl uenza came from, and how it got into people, and second, whether there were any genetic features of the sequence that would give insight into the exceptional virulence of the strain" (taubenberger , ) . this fi rst publication of the team describes the technique used to obtain, amplify (pcr), and sequence the genetic material. the main fi nding of the paper, based on molecular phylogenetic analyses of gene segments, was that the pandemic was caused by a strain of h n infl uenza virus, and that it was of avian origin ( , ) . in their fi rst article, taubenberger et al. randomly selected cases of paraffi n-embedded tissues collected from army servicemen who died during the pandemic for pathological review, searching for symptoms indicative of death by infl uenza. most of the individuals examined died of secondary pulmonary infection, which was a common feature of victims of the pandemic. in effect, bacterial infection very often works together with the infl uenza virus in delineating the clinical picture of the disease. one case, indeed ( case ), could be linked to viral pneumonia and exhibited symptoms of acute pneumonia in the left lung combined with an acute form of bronchiolitis in the right lung, a pathological characteristic typical of a "primary viral pneumonia". focusing on case , researchers performed control amplifi cation of reversetranscribed genetics of the nine gene fragments of the virus using the technique of polymerase chain reaction (pcr). they then carried out phylogenetic analyses based on the gene sequences to reconstruct the genealogical relationships between these elements. it was concluded that the genetic sequence of this strain was different from every other infl uenza strain, and that it was more closely related to strains found in birds than in mammals (taubenberger et al. ) . this partial analysis of the genetic map of human infl uenza was soon followed by a complete sequencing of the hemmagglutinin gene (ha) -a gene long believed to be "pivotal" in the pathogenicity of infl uenza a viruses (webster and rott ; see also cox and bender ) . this gene codes for a protein located on the surface of the virus that plays a crucial role in allowing the virus to bind to host cells. if the virus is able to spread to another species this means it has somehow (through antigenic drift) acquired a new protein that enables it to bind on a different receptor. however, the team did not identify a mutation of the cleave site of the hemmagglutinin gene taubenberger et al. ) . two years later, the team published another article on the "origin and evolution of the 'spanish' infl uenza virus hemmagglutinin gene" (reid, fanning, hultin, and taubenberger ) . johan hultin, the pathologist who attempted to fi nd traces of the infl uenza virus in alaska in the early s, was among the authors of the study. after reading the science paper, hultin wrote a letter to taubenberger offering to return to brevig mission to look for samples of people who had died of the fl u (taubenberger , ) . against all odds, hultin was successful. after he received the approval of taubenberger he set out to alaska for a second time and in august he found in situ frozen lung biopsies. once in the village, he was granted permission from the council to dig the graveyard again; with the help of a few villagers and after days work, he unearthed the body of a year-old woman whom he called "lucy". opening up her chest he found two frozen lungs that he immediately sent to taubenberger's laboratory in washington, along with some tissues taken from three other frozen corpses (berche ) . reid et al. ( ) reported on the full sequence of the hemmagglutinin gene using rna fragments from case discussed in the fi rst article. they investigated three case histories to fi nd evidence of infl uenza rna. the fi rst one was a year-old man who died at fort jackson in south carolina. pathological records indicate he had pneumonia and infl uenza symptoms; he was admitted to the camp hospital on september th and died within days. the autopsy records also show that his left lung suffered from an acute and fatal attack of pneumonia, whereas his right one showed acute bronchiolitis and alveolitis -a clear sign of infl uenza infection. no rna was found in the left lung. however, the team performed a minute microscopic analysis on the paraffi n-embedded tissue of the right lung and tissues tested positive for infl uenza rna. the fragments of fi ve genes were sequenced, amplifi ed through pcr technique and then determined. the second case was also a male soldier, this one years old and based at camp upton in the state of new york. he was admitted to hospital with pneumonia and died within days on the rd of september . microscopic examination of his lungs by taubenberger and his team revealed acute pulmonary oedema and acute bronchopneumonia. formalin-fi xed, paraffi n-embedded samples of lung tissues tested positive for infl uenza rna, the sequence of which was no longer than nucleotides. the third case history was the one found by hultin in brevig mission, alaska. using the sequences of these three case histories, the washington-based team worked out the genealogical relationships between them. their analysis reasserted that the virus that caused the pandemic was avian in nature and that it entered human populations between and , following the modifi cation of the binding site on the ha protein. in , taubenberger and tumpey published two separate articles in nature and science : the fi rst provided the complete genomic sequence of the infl uenza virus and the second revealed the methods used to artifi cially reconstruct it. yet, even before the complete genomic map of the virus was made available, it became unclear whether the genes of the infl uenza virus had indeed disclosed the causes of its exceptional virulence (see taubenberger et al. ). moreover, their argument of a likely avian origin of the virus was criticized. efforts to sequence the virus that caused the - infl uenza pandemic were motivated by the possibility of understanding the genetic origin and virulence of such an organism. while this work allowed for a more precise characterization of the hemagglutinin, neuraminidase, matrix, and nucleoprotein gene segments from a functional point of view, it is less clear, however, whether the fi rst goal was achieved. in effect, the washington team reported that a cleavage-site mutation on the hemmagglutinin gene that played a crucial role in the virulence of the hong kong pandemic in was not found in the strain obtained from the south carolina case. sequencing the specifi c cleavage site in the rna of the virus obtained from the brevig mission case and new york case also confi rmed that this mutation was absent. inquiring into this mutation site (hemmagglutinin) -understood as a key determinant of virulence -was a central motivation of taubenberger's work as it would have "offered an appealing explanation of the 's fl u virulence" (taubenberger , ). yet taubenberger was forced to recognize that "the strain (as confi rmed by all three cases) does not possess a mutation at this site" (ibid.; see also reid et al. ; stevens et al. ). in the light of this conclusion, virologist and infl uenza expert robert webster wrote that the secret of the spanish infl uenza will "remain elusive". webster commented that such "biological properties" [i.e. virulence] may "not be resolved" and suggested that the results of the sequencing project could only provide a partial explanation of this phenomenon. indeed, for him "the entire gene sequence is unlikely to reveal the secret of the high pathogenicity of the spanish virus" (webster (webster , . while taubenberger's paper ends with some remarks about the complex, likely polygenic, nature of virulence determinants in a particular strain, it also concludes -contra webster -with the hope that more sequencing would "shed additional light on the nature of the infl uenza virus" (reid et al. (reid et al. , . another molecular explanation of the - fl u pandemic emerged in from another research team. virologists hideo goto and yoshihiro kawaoka published a paper in the proceedings of the national academy of science on a novel mechanism for the acquisition of virulence by human infl uenza a viruses. there, they argued that a change in another major protein -neuraminidase -able to increase the cleavage of ha could bring about higher levels of virulence. in fact, goto and kawaoka even suggested that a change in a single amino-acid sequestering plasminogen might facilitate the cleavage of na. the authors were cautious, however, stating they "do not conclude that single mutation will convert nonplasminogen-binding nas to effi cient plasminogen binders, thus rendering the virus highly virulent" ( , ). yet, they acknowledged at the same time that it is "tempting to speculate that the pandemic strain […] may have acquired its unprecedented virulence from the mechanism we describe" (ibid). but such a change in amino-acid was also absent (or at least not observed) in the neuraminidase sequence (taubenberger , ; ; see also reid et al. ; kawaoka and watanabe ) . also, similar to taubenberger, goto and kawaoka concluded with a plea for "further sequencing", in order "to address the issue of its [the - pandemic] unprecedented virulence" (goto and kawaoka , ) . in , both taubenberger and tumpey acknowledged the lack of evidence provided by the molecular structure of the virus to explain its virulence: sequence analysis of the infl uenza virus from fi xed and frozen lung tissue has provided molecular characterization and phylogenetic analysis of this strain. the complete coding sequence of the nonstructural (ns), hemagglutinin (ha), neuraminidase (na), and matrix (m) genes have been determined; however, the sequences of these genes did not reveal features that could account for its high virulence" (tumpey et al. ; emphasis added) . and yet, despite evidence for an absence, there seems to be something particular about the structure of the ha protein that contributes to an enhanced level of virulence (morange ) . indeed, using a mouse model, another team of molecular pathologists (kobasa et al. ) showed that when the ha protein taken from the viral strain is inserted into mice it confers high pathogenicity and facilitates lung infections. for instance, infected mice show , times more virus particles after infection with the strain than with other viral strains like the texas virus, and infected mice died after days following infection with the strain, while all survived when infected with the texas virus (von bubnoff , ) . the particular structure of the protein responsible for such pathological effect remains to be found, however, and it is unclear whether similar effects could hold true in humans as well. as we have described, taubenberger's team provided the fi rst molecular characterisation of the spanish infl uenza organism based on the construction of phylogenetic trees of of the rna-polymerase genes of the - virus (taubenberger ) . the authors of this research project that spanned several years concluded that the virus did not originate from gene reshuffl ing (or reassortment) but rather that it jumped from birds to humans shortly before the onset of the pandemic. the virus was thus of avian origin. however, their interpretation of the similarity by descent, and thus of the genealogical relationships between the virus and today's avian viruses was disputed (gibbs and gibbs ; antonovics et al. ) . as the current head of the viral pathogenesis and evolution section at the national institute for allergy and infectious diseases, taubenberger's work is underpinned by evolutionary considerations. but what aspects of his work exactly are evolutionary or darwinian? philosopher michael ruse has long pointed out that the term "darwinism" carries two broad meanings. it can be used fi rstly in a metaphysical sense to characterize change, development and transformation in the natural world. in this sense, the concept of darwinism is older than darwin himself. another sense of darwinism is important to acknowledge. in this second sense, darwinism is a scientifi c notion that emerges in the work of naturalist charles darwin and refers to the fact of evolution, the paths (phylogenies) of evolution, and the mechanism (natural selection) of evolution (ruse , ) . this distinction between path and mechanism maps on the more traditional distinction between patterns and processes in evolutionary biology mentioned above. the research of taubenberger and ewald -and more generally molecular pathology and evolutionary ecology -displays these two aspects of darwinian theory. arguably, both accept evolution as a "fact". however, the former is more interested in the "patterns" of evolution and uses evolutionary thinking to unravel the biological (including genetic) and adaptive processes that led to an increase in virulence. in contrast, ewald focuses on the "process" of evolution -natural selection -as it occurred in various environments and populations of hosts and pathogens. as described above, taubenberger's research focuses on precise and minute description of the small steps that allow viruses to infect more than one species; this work painstakingly tracks changes in nucleotides and charts the genealogical relationships between several strains of infl uenza. ewald and oxford, in contrast, take a broader view and ask why those mutations were selected, what were the selective pressures that drove them to be passed on and conserved in the gene pool, and especially, what is the role of the milieu, largely understood, in shaping virulence. though the centrality of the concept of natural selection is not really in dispute here, the ways in which taubenberger and ewald (and other evolutionary ecologists) understand these processes differs signifi cantly on one important point: whereas the former describes the small incremental steps leading to the high, observable level of virulence, the latter looks for a plausible, eventually testable evolutionary scenario leading to the accumulation and conservation of these small, gradual changes. in other words, the second approach, the ecological one, seeks not only to describe organic changes leading to the formation of new viral strains, for example, but also attempts to give an account of the adaptive value of these transformations in the particular milieu in which the microorganisms lived, reproduced and eventually died. these two components of evolutionary theory -patterns and processes -are well known in the history of biology. evolutionary ecologists nowadays might want to argue that taubenberger is primarily interested in constructing and comparing distinct phylogenetic trees, no matter what the signifi cance of their (evolutionary) relationship may be. we think that the two aspects of evolutionary theory discussed here, however, refl ect more broadly the existence of two distinct styles of scientifi c practices in biomedicine. the diffi culty in addressing both aspects of the theory at the same time is indicative of a genuine tension between distinct explanatory strategies where knowledge claims are made according to different assumptions as to what counts as explanatory. confronted with the lack of evidence supporting a molecular explanation, and in the light of the limitations of the environmental-ecological account, one could have expected researchers to seek support in each other's work in order to complement their researches, and to move beyond the limitations of their own methodologies and research paradigms. yet it is striking to note that reid, taubenberger et al. ( ) , on the one hand, and goto and kawaoka ( ) , on the other, reached a conclusion diametrically opposed to that of webster and also ewald: for the former, in order to explain better the infl uenza pandemic, more genomic sequencing is needed. instead of considering other possible explanations of the exceptional virulence (i.e. ecological explanations) they persist in their attempt to provide a complete and satisfying explanation within a single explanatory framework. at this point, a few remarks are in order. firstly, and from a broad sociological point of view, this may just be a sign of our times: sequencing genetic material is an effective, and now rather inexpensive, way of obtaining prestigious research grants. proposals in genomics, synthetic biology, and other cognate fi elds with a strong engineering approach to biology can highlight potential fi ndings and even future applications, some of which are likely to be patentable and thus rapidly rentable from a fi nancial point of view. in brief, promoting more sequencing is likely to provide additional research money. while this may be a reason why taubenberger's team value more genetic sequencing other reasons of a more epistemological and historical nature must also be envisaged. a second reason to consider has to do with what historians and philosophers of science have called a scientifi c "style of practice" (keating and cambrosio ) . derivative of ian hacking's concept of "styles of reasoning" -itself inspired by alistair crombie's "style of scientifi c thinking in the european tradition"-(hacking ; crombie ), the notion of "style" typically refers to the historical formation of distinctive practices and methodologies in science. styles frame what counts as evidence, relevant questions to ask, truth-value, and sound explanation in distinct research and/or cultural contexts. alongside the development of individual styles of practice one fi nds the emergence of new standards for measurements, objectivity, proof, and so on (hacking ). though styles are fl exible they are not loose or relativist categories; they admit rules, systems of norms, stabilization techniques, and methods of justifi cation. as they progressively become stabilised over time and entrenched within scientifi c activities, however, the very existence of styles of reasoning and their historical development become taken for granted. while the notion of style is often employed to analyse scientifi c controversies (amsterdamska ; fujimura and chou ) , it is interesting to note here that the two styles at play in the present case study have grown in relative ignorance of each other. going back to the missing mutations, we can see that even though taubenberger's programme did not provide the answers it sought it could not be halted hastily, especially after gathering immense publicity and funding. on the contrary, it is expected that these scientists, working within their style of practice, continue to do so until all possibilities of fi nding the key to the exceptional virulence have been looked at and examined in detail. from this point of view, their persistence in seeking a complete molecular explanation makes sense -even if, from a public health and biosecurity point of view, their research raises ethical concerns about the development of dual-use technologies (rappert ) . moreover, the results obtained on the biology of infl uenza a viruses and the methods developed by taubenberger and his team now enable worldwide researchers to better understand the molecular differences between various infl uenza strains. what appears as a sign of determination in pursuing a research objective can also refl ect a lack of communication between distinct scientifi c communities, the problems of interdisciplinary work, the self-containment of styles of scientifi c practice, and/or the resistance offered by epistemological obstacles. the current gap between ecological and molecular explanations, as it emerged in the present case, may be due to the fact that functional explanations such as those constructed in molecular biology tend to appear "self-suffi cient", as historian and biologist michel morange recently put it ( ). this sort of epistemological obstacle means that, for many, there is no (obvious) need to complement molecular explanations with ecological considerations. to say that integration between mathematical modelling and molecular microbiological approaches has failed in this case would be going too far, however. indeed, integration of ecological and molecular approaches of virulence evolution has not even been seriously attempted so far. also, it would be misleading to suggest that molecular pathologists wholly ignore the environmental perspectives on virulence evolution and emerging diseases. yet when they do take them into account, the result does not necessarily amount to a better integration of data, theories, or methods but reveals, instead, the heights of disciplinary boundaries and the valuing of one style of practice over another. for example, in one of the last publications of taubenberger and his colleagues at the national institute of health, the authors concluded that the diminution of severity of infl uenza pandemics over time "is surely due in part to advances in medicine and public health, but it may also refl ect viral evolutionary choices that favor optimal transmissibility with minimal pathogenicitya virus that kills its host too fast or sends them to bed is not optimally transmissible " (morens et al. , ; emphasis added) . in other words, the biological interests of the virus will best be served by evolving lower virulence over time in order to facilitate transmission to new hosts, an explanation that rests on the conventional wisdom rejected by most evolutionary ecologists who advocate the theoretical trade-off model but that is still defended by some microbiologists. this may come as a surprise given that anthony fauci, on of the authors of the paper, and current head of the national institute for allergy and infectious diseases, has long criticized this view (see fauci ) . it shows, however, that branches of sciences in which the same problem is addressed, through distinct methodologies, can be surprisingly disconnected and separated by epistemic gaps, professional or institutional barriers. in other words, integration is no easy goal to achieve. problems within the molecular style of practice, however, are not only epistemological but also ethical and social. the publication of the whole sequence of the - strain in sparked lively debates among scientists and the public as it raised concerns as to whether it was safe to publish the methodology used to resurrect the pathogen (rappert ; selgelid ) . what if someone with nefarious intentions reconstructs the virus? how likely is it that this genetic information be used for harmful purposes? what if, by accident or not, the virus escapes into the environment? for some, like biologist richard h. ebright from rutgers university, "there is a risk, verging on inevitability, of accidental release of the virus" but "there is also a risk of deliberate release of the virus". yet others argued that the work of taubenberger and tumpey was entirely legitimate and could be applied to other areas and problems in virology such as the h n pandemic and "could have an immediate impact by helping scientists focus on detecting changes in the evolving h n virus that might make widespread transmission among humans more likely". the case of the spanish infl uenza pandemic is today a classical example of a technology that has the potential for "dual-use" research (i.e. it could help to understand the disease and fi ght it, but it also could be used to disseminate it further in a population). a recent case of potential dual-use consequences in infl uenza research involving a group of researchers led by ron fouchier in the netherlands and by yoshihiro kawaoka, from madison, in the u.s, led in january to a day suspension of research on infl uenza and virulent diseases, following consensus to delay publication. both teams had submitted a paper, to science and nature respectively, describing the methodology employed to artifi cially render an h n infl uenza strain transmissible between ferrets (which is, arguably, a reliable indicator of possible transmission to humans) due to a mutation on the hemmagglutinin protein. both studies have now been published (imai et al. ; herfst et al. ) . as an aside, it is interesting to see that these two studies, although undoubtedly driven by molecular biology questions, were based on classical approaches in evolutionary ecology known as serial passage experiments (ebert ). in the early s, the institute of medicine's report on microbial threats (lederberg, shope, and oaks ) and stephen morse's emerging viruses (morse ) have emphasized how emerging infectious diseases are posing a renewed threat to public health that needs to be addressed on a global scale, from the combined perspective of ecological and molecular approaches. the concept of emerging diseases has helped focus international efforts to contain infectious diseases within well-defi ned geographical and temporal limitations. with the (re)creation of the - infl uenza strain and others (e.g. yersinia pestis , polio virus, h n ), a different form of biological threat arises and it requires different political, institutional, and legal response mechanisms. indeed, while the threat of emerging infections was mostly perceived as coming from outside northern-hemisphere countries, it now appears to be growing from within the heartland of western countries itself. instead of stressing possible disease invasions in previously unexposed countries (or with only low incidence of a particular disease), recently developed technologies in synthetic biology and genomics have opened-up the possibility to artifi cially create new diseases, or to resurrect old ones such as the plague, the infl uenza strain responsible for the pandemic, and the polio virus (bos et al. ; taubenberger ; tumpey et al. ; celo et al. ; rosengard et al. ) . on the other hand, it might be argued that new variants appear constantly and the risk of a laboratory accident might be comparable to what happens naturally in the fi eld. moreover, while dual-use is a characteristic of most life sciences nowadays (atlas ), only a small number of experiments and experimental practices are, overall, seen as posing real threats to public health and global security (for a recent analysis see aucouturier ; morens et al. ) . finally, it is worth noting that dual-use technologies -like scientifi c research more generally -are often characterized by unexpected fi ndings such as, for instance, the accidental discovery that a modifi ed virus injected into mice was lethal to otherwise vaccinated animals (jackson et al. ) . as is often the case in science, the experimental system designed to answer certain questions opens-up theoretical and practical possibilities that could sometimes not be envisaged at the outset (rheinberger ) . if unpredictability and unforeseen results are truly the essence of scientifi c research, dual-use technologies are then an unavoidable tradeoff to deal with, a point that reinforces the need to develop appropriate governance responses to biomedical research programmes on pathogens and potentially pathogenic organisms (méthot ) . more generally, those new research avenues underline the need for the development of a "culture of responsibility" (nsabb ) in the life sciences, that is, a new ethos to address and balance questions of biosecurity and risk with scientifi c autonomy and progress, among others. the two most important glycoproteins allowing infl uenza viruses to invade host tissues -hemmagglutinin (ha) and neuraminidase (na) -were signifi cant molecular determinants of the virulence of infl uenza pandemics in and , and can yield potentially pathogenic effects when inserted into some animal models. considerable explanatory power was placed on these special proteins that seemed to provide a fi rst-hand, adequate, simple and certainly elegant mechanism to account for the exceptional virulence of the pandemic. indeed, the "most popular theory" was that the virus had "unique pathogenic properties, most likely encoded within the hemagglutinin protein" (holmes ) . identifying a molecular and genetic basis of virulence could not only provide a window into the most devastating epidemic of modern times, but could also help to prevent and predict those to come. overall, the remarkable technological success -i.e. the retrieving and sequencing of the avian virus -promised nothing less than to unlock one of the oldest and well-kept secrets in the whole of medical history. however, after sequencing the genome of the viral strain that killed perhaps up to million people according to the who estimates, both factors were found to be lacking in the killer strain. one might wonder about the extent to which it is possible to generalize from the example of the spanish infl uenza pandemic to other cases. researchers on ancient pathogens using high throughput technologies have recently claimed to identify the causal organism of the black death ( yersinia pestis ) in the fourteenth century and the sources of its virulence in the form of a single plasmid (schuenemann et al. ). however, determining why an organism is pathogenic or what makes it a pathogen is not straightforward and is rarely based on a specifi c structural characteristic alone (méthot c ) . as microbiologist charles nicolle once said ( ) , virulence is the expression of a "mosaic of powers" resulting from a constellation of factors that are irreducible to any particular structure and must be understood against a broad biological and even historical background. it is interesting to note, therefore, that the same team went on to revise its position in a subsequent article by pointing out the inherent limitations of molecular-oriented explanation and, furthermore, emphasized the need to widen the explanation and integrate ecological factors as well. they write: regardless, although no extant y. pestis strain possesses the same genetic profi le as our ancient organism, our data suggest that few changes in known virulence-associated genes have accrued in the organism's years of evolution as a human pathogen, further suggesting that its perceived increased virulence in history may not be due to novel fi xed point mutations detectable via the analytical approach described here. at our current resolution, we posit that molecular changes in pathogens are but one component of a constellation of factors contributing to changing infectious disease prevalence and severity, where genetics of the host population, climate, vector dynamics, social conditions and synergistic interactions with concurrent diseases should be foremost in discussions of population susceptibility to infectious disease and host-pathogen relationships with reference to y. pestis infections (bos et al. ; emphasis added) . in sum, the study of bos et al. ( ) did not reveal any signifi cant genetic or evolutionary change in years that could explain the virulence of plague in the fourteenth century. as a consequence, they argue that a molecular approach only provides an incomplete picture when applied in isolation, and that a complementary ecological perspective is needed. more precisely, the more recent study emphasizes that a full understanding of the evolution of virulence requires a multi-dimensional framework that encompasses host resistance, ecological factors, and the interactions between the different diseases occuring in a well-defi ned geographical area over a specifi c time period. to go beyond the limitations of analytical approaches that investigate one disease at a time, a synthetic and global approach is necessary in order to understand more broadly the evolution of emerging diseases that compose the past, present, and future of any "pathocenosis" (grmek ) . to conclude, our analyses of the case of the spanish infl uenza pandemic show that there is an irreducible tension in studying the phenomenon of virulence comparatively across the sciences: one can either look for determinants of pathogenic power analytically, that is from within microorganisms, or synthetically at the level of host-pathogen interactions in a given ecological environment. both approaches face limitations and neither appears to be suffi cient to account for a complex phenomenon like the - infl uenza pandemic. besides, each level of analysis has its own ways of characterizing the nature and causes of virulence (and pathogenicity), and both lead to the development of different measures to prevent or to treat emerging infectious diseases. while ecological approaches contribute to the establishment of national and international programmes intended to increase detection and surveillance in emerging infections on a global scale, monitoring changes in virulence to prevent pandemics worldwide, molecular approaches facilitate the development of biomedical tools, such as vaccines or antibiotics, to fi ght infectious diseases either by reducing their pathogenic power, and/or by enhancing individual and group (or herd) immunity. yet both perspectives can also work together: molecular phylogenies can provide evidence regarding the likely origins of future pandemics and help to channel the attention of a detection network onto particularly sensitive sites (see morens et al. ) . a better integration of ecological and molecular approaches would thus benefi t public health medicine by providing stronger theoretical approaches and empirical mechanistic models to understand, manage and perhaps even predict future infl uenza pandemics. evolution of disease virulence the transmission-virulence trade-off and superinfection: a comment to smith emergence of a convex trade-off between transmission and virulence virulence model and the trade-off hypothesis: history, current state of affairs and the future achieving disbelief: thought styles, microbial variation, and american and british epidemiology, - coevolution of hosts and parasites infectious diseases of humans: dynamics and control the role of evolution in the emergence of infectious diseases responsible conduct by life scientists in an age of terrorism la guerre biologique: perspective historique et critique ball gh ( ) parasitism and evolution the great infl uenza: the epic story of the deadliest plague in history the site of the origin of the infl uenza pandemic and its public health implications an evolutionary biologist considers the virulence of emerging infectious diseases the chronicle of infl uenza pandemics the role of ecological feedbacks in the evolution of host defence: what does theory tell us small worlds' and the evolution of virulence: infection occurs locally not at a distance a draft genome of yersinia pestis from victims of the black death evolution, fi tness, and the struggle for persistence parasites on the move virus as organism. evolutionary and ecological aspects of some human virus diseases the future of medical research. the lancet i chairman's opening remarks infl uenza, monographs from the walter and eliza hall institute of research in pathology and medicine trends and directions of global public health surveillance chemical synthesis of poliovirus cdna: generation of infectious virus in the absence of a natural template. science express the distinction between pattern and process in evolutionary biology: the use and abuse of the term 'strategy the evolution and eradication of infectious diseases the molecular epidemiology of infl uenza viruses styles of scientifi c thinking in the european tradition: the history of argumentation and explanation especially in the mathematical and biomedical sciences and arts america's forgotten pandemic. the infl uenza of a general theory for evolutionary dynamics of virulence mathematical epidemiology of infectious diseases. model building, analysis, and interpretation host-parasite relations, vectors and the evolution of disease severity cultural vectors, virulence, and the emergence of evolutionary epidemiology transmission modes and the evolution of virulence, with special reference to cholera, infl uenza, and aids guarding against the most dangerous emerging pathogens: insights from evolutionary biology les organisations sanitaires internationales face à l'émergence des maladies infectieuses nouvelles social inequalities and emerging diseases infectious diseases: consideration for st century emerging and re-emerging infectious diseases: the perpetual challenge, robert h. ebert memorial lecture biological control of vertebrate pests. the history of myxomatosis. an experiment in evolution. cabi, new york fleck l ( ) genesis and development of a scientifi c fact mechanisms of pathogenesis and the evolution of parasite virulence variation in hiv- set-point viral load: epidemiological analysis and an evolutionary hypothesis infl uenza transmission in households during the pandemic emergence of a new disease as a result of interspecifi c virulence gene transfer dissent in science: styles of scientifi c practice and the controversy over the cause of the coming plague: newly emerging diseases in a world out of balance. farrar, straus and giroux a novel mechanism for the acquisition of virulence by a human infl uenza a virus evolutionary causes and consequences of immunopathology préliminaires d'une étude historique des maladies le concept de maladie émergente pathogenicity islands: bacterial evolution in quantum leaps hacking i ( ) styles for historians and philosophers airborne transmission of infl uenza a/h n virus between ferrets and all that history of the great infl uenza pandemic. death, panic, and hysteria - . i.b. tauris academic experimental adaptation of an infl uenza h ha confers respiratory droplet transmission to a reassortant h ha/h n virus in ferrets expression of mouse interleukin- by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox updating the account: global mortality of the - « spanish » infl uenza pandemic global trends in emerging infectious diseases pathogenesis of the pandemic infl uenza virus cancer clinical trials: the emergence and development of a new style of practice the severity of infl uenza as a reciprocal of host susceptibility the scale politics of emerging diseases enhanced virulence of infl uenza a viruses with the haemagglutinin of the pandemic virus ?pagewanted=all krause rm ( ) introduction. in: krause rm (ed) emerging infections. biomedical research report cause and effect in biology revisited: is mayr's proximate-ultimate dichotomy still useful? did the - infl uenza pandemic originate in china? viruses and humankind: intracellular symbiosis and evolutionary competition emerging infections: microbial threats to health in the united states the evolution and maintenance of virulence in microparasites selection and evolution of virulence in bacteria: an ecumenical excursion and modest suggestion selection for intermediate rates of increase in parasite-host systems disease in evolution. global changes and emergence of infectious diseases virulence and transmissibility of pathogens: what is the relationship? black holes, antivirulence genes, and gene inactivation in the evolution of bacterial pathogens parasite host coevolution cause and effect in biology: kinds of causes, predictability, and teleology are viewed by a practicing biologist plagues and people like all that lives': biology, medicine and bacteria in the age of pasteur and koch why do parasites harm their hosts? on the origin and legacy of theobald smith's 'law of declining virulence' - - historical epistemology of the concept of virulence: molecular, ecological, and evolutionary aspects of emerging infectious diseases in the th and th century understanding pathogens in the era of next-generation sequencing science and science policy: regulating 'select agents' in the age of synthetic biology alizon s (forthcoming) what is a pathogen? towards a process view of host-parasite interactions transmissibility of the pandemic infl uenza unsimple truths: science, complexity, and policy contre la pensée unique en biologie. la découverte, paris morange m ( ) what will result from the interaction between functional and evolutionary biology understanding infl uenza backward the challenge of emerging and re-emerging infectious diseases the persistent legacy of the infl uenza virus engineering h n avian infl uenza viruses to study human adaptation emerging viruses: defi ning the rules for viral traffi c examining the origins of emerging viruses factors in the emergence of infectious diseases pandemic infl uenza: studying the lessons of history guidance for enhancing personal reliability and strengthening the culture of responsibility epidemics and time. infl uenza and tuberculosis during and after the - pandemic the roles of integration in molecular systems biology epidemiological evidence of an early wave of the infl uenza pandemic in new york city the so-called great spanish infl uenza pandemic of may have originated in france in world war i may have allowed the emergence of "spanish" infl uenza a hypothesis: the conjunction of soldiers, gas, pigs, ducks, geese and horses in northern france during the great war provided the conditions for the emergence of the "spanish human as the world's greatest evolutionary force de l'atténuation des virus et de leur retour à la virulence the spanish infl uenza pandemic of - . new perspectives, studies in the social history of medicine decomposing health: tolerance and resistance to parasites in animals biotechnology, security and the search for limits the origin of the pandemic infl uenza virus: a continuing enigma origin and evolution of the "spanish" infl uenza virus hemagglutinin gene characterisation of the "spanish" infl uenza virus neuraminidase gene infl uenza pandemic caused by highly conserved viruses with two receptor-binding variants the spanish infl uenza: integrating history and biology variola virus immune evasion design: expression of a highly effi cient inhibitor of human complement keywords in evolutionary biology targeted enrichment of ancient pathogens yielding the ppcp plasmid of yersinia pestis from victims of the black death ethics and infectious disease nomenclature and concepts of pathogenicity and virulence defi nitions of pathogenicity and virulence in invertebrate pathology a virus obtained from infl uenza patients emerging and reemerging diseases: a historical perspective structure of the uncleaved human h hemagglutinin from the extinct infl uenza virus chasing the elusive virus: preparing for the future by examining the past. in: the threat of pandemic infl uenza: are we ready? workshop summary the origin and virulence of the "spanish" infl uenza virus the spanish infl uenza pandemic of - . new perspectives. . studies in the social history of medicine infl uenza: the once and future pandemic initial genetic characterisation of the "spanish" infl uenza virus the infl uenza virus: a killer comes into view integrating historical, clinical and molecular genetic data in order to explain the origin and virulence of the spanish infl uenza virus elkinton js ( ) pathogenicity and virulence mortality associated with infl uenza and respiratory syncytial virus in the united states pathogenicity and immunogenicity of infl uenza viruses with genes from the pandemic virus characterization of the reconstructed spanish infl uenza pandemic virus a bacteriological paradigm in infl uenza research in the fi rst half of the twentieth century the construction of bacteriophage as bacterial virus: linking endogenous and exogenous thought styles the fl u virus resurrected are we ready for pandemic infl uenza infl uenza spanish infl uenza: the secrets remain elusive infl uenza -an emerging and re-emerging disease infl uenza virus a pathogenicity: the pivotal role of hemagglutinin evolution and ecology of infl uenza a viruses global public health vigilance. creating a world on alert the spanish infl uenza pandemic of - . new perspectives. . studies in the social history of medicine origins of major human infectious diseases key: cord- -gs j fxo authors: yamin, mohammad title: counting the cost of covid- date: - - journal: int j inf technol doi: . /s - - - sha: doc_id: cord_uid: gs j fxo coronavirus disease (covid- ) is the name given by the world health organization (who) to the highly contagious and infectious disease caused by the novel corona virus or sars-cov- , which was first reported on december in wuhan city of the capital of china's hubei province. due to the rapid increase in the number of infections worldwide, the who in march , declared covid- as a pandemic. historically, first coronavirus had surfaced in with symptoms of common cold. since then five different strands of this virus have emerged, most lethal of them was the severe acute respiratory syndrome (sars), which infected about eight thousand people, killing ten percent of them. the covid- is not the most deadly pandemic world has ever witnessed as the spanish influenza pandemic, during – , killed more than fifty million people. indeed covid- has turned out to be the most lethal of all coronaviruses as it has infected at least three million people killing more than two hundred thousands of them in the first months of its spread. many politicians and social scientists have dubbed the depression, being caused by covid- , worse than that caused by the second world war. in this article, we shall analyze economic, social, cultural, educational and political impact of the covid- . we are witnessing the spread of the most deadly and devastating virus attack of the last one hundred years. this virus is known as the novel corona virus or sars-cov- and the disease resulting from this virus has been named by as covid- by [ ] , where a historical background of the corona virus can also be found. figure shows a visual of a virus. covid- was first detected in december in wuhan city of the peoples republic of china. as the virus spread, the world health organization (who) [ ] declared it to be a pandemic on th march [ ] , signaling the significance of its global spread. during the first months of spread, this deadly disease has infected about three million people resulting in about two hundred thousand deaths in more than countries. these figures are mostly of the hospital admissions of a handful countries as reported by the media. real numbers would never be known. the united states of america has the maximum number of casualties as well as infections, followed by italy, spain, france and the united kingdom. these figures are largely reported by a handful of developed countries. however, there is limited information of fatalities reported from developing countries, many of which do not have adequate testing facilities and/or hospital beds to treat all the patients. therefore, the extent of actual damage by covid- would be limited in its accuracy. undoubtedly covid- is causing the most severe economic crisis after the great depression of s. as the virus continues to cause havoc, the extent of the global damage resulting from it cannot be counted until it subsides. in this article we shall discuss damage which it has already caused to different walks of life and speculate further damage it could inflict. in recent years we have witnessed an increased growth and spread of communicable and highly contagious viruses and diseases like ebola [ ] , hiv aids [ ] , swine influenza (h n , h n ) [ ] , various strands of flu [ ] , severe acute respiratory syndrome (sars) [ ] and middle eastern respiratory syndrome (mers) [ ] in africa, the middle east and several other parts of the world. wiping, cleaning and treatment of some of these viruses is a very challenging job [ ] , and so it is very difficult to assess the spread of some of these viruses (e.g. ebola) which could create havoc in the society. in this article we shall analyze issues associated with and impact of covid- in different walks of life. in particular we shall describe the devastation and damage it has caused to economic, social, cultural, and political fabric of the society globally, particularly in different regions. indeed some industries have benefited from the crisis caused by covid- , which we shall also analyze. the coronavirus disease covid- is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus (sars-cov- ) ( fig. ) , which is resulting in a heavy toll on people's lives and colossal economic damage. some reports (e.g. [ ] .) suggest that covid- would ''cause the worst recession since the great depression (of s). it is said the pandemic had plunged the world into a ''crisis like no other''. although covid- is being dubbed to be very destructive to the human lives and economies, it is currently not as lethal as many other pandemics have been. there have been more destructive epidemics in the past. the most deadly of all pandemics occurred in - , which is known as the ''spanish'' influenza pandemic causing acute illness in about thirty percent of the world's population and claiming the lives of at least million people [ ] . according to [ ] , it caused up to one hundred million deaths. but the best estimates seem to be fifty million [ ] . let us glance at some of the earlier pandemics and diseases. the archaeological sites called ''hamin mangha'' and miaozigou, in north-eastern china suggest that it was an epidemic which devastated the entire region. around b.c., an epidemic in athens went on for about years killing an estimated one hundred thousand people [ ] . during - a.d., the antonine plague, is thought have killed more than five million people in the roman empire. during - the bubonic plague, named as justinian (after the name of the emperor) killed up to one tenth of the world's population [ ] . the black death during - killed more than half of the population of europe [ ] . during - , the cocoliztli epidemic took the lives of fifteen million people of mexico and central america. the great plague of london during - killed about one hundred thousand people, and the great plague of marseille during - wiped out thirty percent of the population of the area [ ] . the russian plague during - took the lives of about one hundred thousand people in and around moscow, and flu pandemic during - took the lives of about one million people globally [ ] . the swine flu pandemic was caused by a new strain of h n that originated in mexico in the spring of before spreading to the rest of the world. in one year, the virus infected as many as . billion people across the globe and killed between , and , people, according to the centre for disease control and prevention (cdc). a vaccine for the h n virus that caused the swine flu is now included in the annual flu vaccine. ebola ravaged west africa between and , with , reported cases and , deaths. there are other pandemics and diseases including the philadelphia yellow fever of , american polio epidemic of , for which a vaccine was developed in , and the middle east respiratory syndrome coronavirus (mers-cov) of which has accounted for thousands of lives. covid- appears to cause dry cough, high fever and ultimately chest congestion and pain resulting in breathlessness if not controlled. the source and causes of sars-cov- are not known as a certainty. however [ ] asserts that the virus is found in bats but what causes its transfer to humans is not known. another study [ ] claims that the virus has jumped from snakes to humans. to date there is no vaccine or medicine to prevent or treat covid- . however, many health centres are treating patients with some antibiotics (erythromycin), and chloroquine or hydroxychloroquine. these drugs neither provide a definitive treatment nor are approved by who or any credible organization. nevertheless [ ] claims, based on clinical trials in china, chloroquine phosphate is apparently shown to be effective with acceptable safety level to cure pneumonia in covid- patients. according to [ ] , combination of the chinese medicine, interferon, lopinavir, ritonavir and corticosteroids was helpful in the recovery of out of patients. according to [ ] , administration of moxifloxacin, lopinavir, interferon, and methylprednisolone to non-icu patients was successful in treating icu patients- patients were discharged from the intensive care unit (icu) and sixteen were relived from the hospital. there are some unconfirmed success stories of treatment of covid- with herbal ingredients like black seeds, ginger, and honey, etc. these ingredients are indeed recognised as good for health in general. pain relieving medicines like panadol are of course used to bring down the body temperature caused by virus. in severe cases, when patients cannot breathe by themselves, ventilators have to be used. there are many myths surrounding the treatment of covid- , which we shall look at next. the world health organization has framed some guidelines and measures to check or slow the spread of covid- to the community. some of these measures are also summed up in [ ] . here we provide a summary of these measures. first and foremost, it is highly recommended to wash hands properly and regularly. whenever the hands are exposed to any surface, the hands should be washed with soap for at least s. use of hand gloves is helpful in preventing exposure of hands to contaminated surfaces and places. protective gears for medicos are a necessity but the case of medical and medical workers will be dealt elsewhere. frequent and regular use of sanitizers (creams, gels, sprays) is also recommended. there seems to be some controversy about the effectiveness of face masks. various outlets have frequently reported the shortage of medical grade masks (n ) due to high demand for medical professionals and general public globally. the centers for diseases and prevention (cdc) has also advised people to use face masks, and even use cloth masks if proper ones are not available. studies have revealed that even the best face masks cannot prevent some unfiltered air getting through. in order to make them highly effective, social distancing is recommended to reduce the risk of contaminated droplets being spread from an infected person to other people through coughing or sneezing. self-isolation is also a very useful technique to prevent the spread of covid- . unfortunately, there are many myths about curing covid- patients, some of them are astonishing. the world health organization [ ] has refuted many of them. we provide a summary. the following acts or practices do not prevent covid- . • g mobile network • exposure to temperatures more than the following are also clarified in [ ] . if one is exposed to coronavirus, the virus would not stay in the body for the rest of life. holding the breath for s or more without coughing or feeling discomfort does not mean that the body is free from covid- . mosquito bites cannot transmit coronavirus. there is no evidence that eating garlic prevents coronavirus although garlic is considered very healthy for the body. people of all ages can be infected by the new coronavirus ( -ncov). but those at greatest risk of infection include the elderly, people with compromised immune systems and people with chronic health conditions (e.g. asthma, diabetes and heart disease). thermal scanners are only effective in detecting people with fever but cannot detect people with coronavirus. one should not use uv lamps to sterilize hands or other areas of skin because uv radiation can cause skin irritation. some people have claimed that cow urine can prevent coronavirus. there is no evidence to support their claim. on the contrary [ ] and [ ] have categorically stated that the cow urine doesn't help prevent the virus. in [ ] it is stated that ''experts have repeatedly asserted that cow urine does not cure illnesses like cancer and there is no evidence that it can prevent coronavirus''. the covid- pandemic is although a health crisis but it is damaging the world economy. if the pandemic was prolonged, it could even threaten the monitory systems of some countries. civil aviation industry is one of the hardest hit and many airlines have slashed their staff by up to %. int. j. inf. tecnol. hospitality and tourism is another sector which is facing the brunt of covid- . revenue generating historical monuments and places have shut their doors due to social distancing measures such as mandatory lockdown, impacting the economy of several nations. these and other setbacks have soared unemployment in most of the countries threatening even the governance of some of the countries. the pandemic is in its full fury even after the first months of its emergence. the full scale damage can only be assessed when the pandemic subsides. let us look at some of the damage to various aspects of the society so far. the covid- is causing the most severe losses to the economies of many nations. recently we have witnessed the oil prices to hit the subzero territory for the first time during the history of the mankind. we are already witnessing some very serious impact in china, where the virus first emerged in december , seems to be coming out of the pandemic. according to [ ] , china has suffered loss of . % in its industrial production, % in retail sales, % in car sales, and % in restaurants. according to [ ], world's working class, estimated to be more than three and a quarter billion strong is being severely impacted by the sudden and unimaginable slowdown in the world economy causing unprecedented loss in employment in all countries. one of the reasons cited for the heavy toll lies in the fact that more than four-fifth of the workforce lives in countries which are under severe restrictions of distancing and lockdown due to curfews and other mandatory closures. according to [ ] , decline in working hours by st aril is estimated to be equivalent to two hundred million fulltime job loss. many developed countries are facing a two digit unemployment rate forcing people to seek unemployment benefits, severely impacting the economies of those countries. if the pandemic is prolonged, the loss of jobs could be many folds. goldman sachs has predicted that the us economy in the april-june quarter of could shrink to about three fourth, more than twice worse of any previous setbacks [ ] . the pandemic has the potential to cause the worst recession ever. politicians in many countries have responded to salvage their economies. the us has come up with a stimulus package of more than us $ trillion. one of the hardest hit economic sectors is civil aviation. most of the air travel has been suspended for weeks now, forcing many airlines to slash their staff by up to % and asking their government to salvage the industry. preliminary estimates according to [ ] for the period of january to june of suggest the loss of over five hundred million passengers, amounting to about fifty percent of the seats available, causing loss of revenue of more than one hundred billion dollars. if the pandemic was prolonged, we should expect even more severe economic losses to the economy in general and civil aviation in particular. the oil producers are reeling on the face of the current pandemic. due to lockdowns and severe restrictions on all modes of transportations, the demand for oil has drastically depleted. despite the reduction in oil production, the price of crude oil has gone to under twenty dollars a barrel. this will severely impact the economies of the oil exporting countries like saudi arabia and other countries of the arabian peninsula and africa, as well other oil producers like russia, brazil, venezuela, mexico, and kazakhstan. on the face of covid- , many countries had debated whether closing down educational institution was in their interest. many countries like australia delayed their action plan but in eventually they had rightly decided to close down or limit attendance to all educational institutions to prevent the spread of covid- . due to these closures, millions of children and adults in many countries have suffered not only the loss of education but also the mental health. educational institutions, mostly in the developed countries, with the help of online tools have managed to impart education in this situation but mostly in the higher education sector. some developing countries like saudi arabia have also done a remarkable job to provide education through learning management systems or open access internet tools like teams, skype etc. but in many other developing countries there has been a virtual wash out of educational activities at all level since march . the pandemic has forced many countries to invest more in the online teaching delivery. however the online teaching would not be very helpful at the school level. many other activities like conferences, symposia have adopted online mode. due to uncertainties surrounding the pandemic and the disrupted educational sector, the admissions to the academic year in the northern hemisphere face a difficult task to manage. authors in [ ] and [ ] have assessed the impact, which covid- has caused so during the first months of its spread. sadly, social and religious setbacks arising from covid- have been heart-breaking. most death have occurred to the elderly, disabled and indigenous people. the highly contagious virus has not only killed tens of thousands people but have also prevented their loved ones to be with them in their last moments. an account of social carnage is presented by the un [ ] . the daily loss of lives in some cities have caused severe difficulties in in their last rites. mass graves, like one in new york (fig. ) , are very sad realities of our lives. the pandemic has caused severe setback to religious practices, which has no parallels in the history. many religious institutions, including mosques were closed in march in efforts to limit the spread of virus. this closure also included the grand mosque in makkah which houses kaaba (fig. ) , the most sacred site for muslims. kaaba is center of hajj and umrah pilgrimages [ , ] , which attracts millions of pilgrims. its closure, especially during the upcoming fasting month of ramadan, is very unfortunate. the grand mosque closure causes losses of billions of dollars to the government of saudi arabia. if the pandemic caused the cancellation of the annual pilgrimages of hajj in late july , the saudi economy would incur the loss of several billion dollars. there have also been setbacks to other religious communities of the world. the pope john paul had to address an empty hall at vatican on the occasion of easter. also the devotees were denied the entry to bethlehem, the birth place of jesus the son of marry. the pandemic also severely impacted the religious observation of passover. while more than half of the world population locked down to contain the spread of covid- , accusations and counter accusations have surfaced in different parts of the world. some of these accusations are aimed against certain ethnicities and religious minorities, which are divisive in a time when unified approach is required. many of the accusations are centered on the action plans of different countries and the origins of the virus itself. it is a general belief that many governments did not take the threat of covid- serious enough. reported by the guardian, leader of the democratic party in the us, where more than , people have died in the first months, nancy pelosi on th march accused the president of the usa, mr. donald trump, of denials and delays in action plane to limit the spread of covid- to save costing human lives. on the other hand, mr. trump claims to have saved hundreds of thousands of american lives. as reported by the international media, he also called sars-cov- to be a chinese virus. many accusations have also surfaced in australia, england and other developed countries. in some countries, hatful behavior and even physical assaults have also been witnessed against certain communities. many doctors and nurses have been attacked by the patients or public mobs. there are many economic and social sectors which are indirectly affected by the covid- . full extent of the damage to these sectors will be known after sometime. some of the business sectors, which have severely been impacted by the pandemic, include general transport, investment banking, traditional retail, professional sports and entertainment, cinemas, general (home and car) insurance, manufacturing, some form of healthcare. although the losses from covid- are staggering, there are some winners as well. environment is the greatest winner from the covid- . pollution levels globally are so low that none of us expected them to go down so much, especially in china, india and other developing countries. businesswise, super markets and grocery stores have witnessed increase in sales without relying on any discounts and promotions. initially, the supermarkets in australia and elsewhere were unable to meet the demand of essential food and other items. the online businesses in general and digital content providers in particular have also witnessed bumper sales. indeed price of many items have doubled and tripled. there have been complains of some stores charging excessive prices for the sought after items like face masks and hand sanitizers. the pharmaceutical companies have also benefited from the pandemic. demand for certain drugs (antibiotics, chloroquine, and sedatives) have created shortage. face masks, gloves, sanitization gels and creams have also disappeared from the shelves of the pharmaceuticals. other sectors which have benefited from the pandemics are logistics/delivery, entertainment streaming and gaming, and video conferencing. covid- is causing human, economic, social, and cultural setbacks of our lives. we already witnessed colossal economic losses in the first months of the emergence of coronavirus in china. during the first months of the battle with covid- , people, including many health workers, have lost their lives. we know that many countries lack resources for testing and treating the epidemic, therefore the real loss of lives caused by it will never be known. indeed the pandemic is causing severe depression across the board. with no cure or vaccine in sight, we cannot the end of this crises caused by this pandemic. evidence based warning of the medical experts on the reoccurrence of covid- attacks on already treated people, are heartbreaking. one wonders if the worst is yet to come. when we come out this crisis, only then we shall be able to assess the actual damage it caused. many of us would be left without our loved ones. a sizable section of the society would have lost their jobs. all these add to the ingredients of a depression of a magnitude unimaginable to many of us. unfortunately, some politicians are perusing their political agenda in disregard to the suffering of the society reeling under covid- . although the end of this pandemic is currently unknown, historically mankind has managed to recover from similar events in the past. this suggests that we will eventually be able to recover from this crisis. world health organization (who) rolling updates on coronavirus disease (covid- ) world health organization (who) regional office for europe. who announces covid- outbreak a pandemic ebola virus: a global public health menace: a narrative review current scenario of hiv/ aids, treatment options, and major challenges with compliance to antiretroviral therapy from where did the 'swine-origin' influenza a virus (h n ) emerge? low, severe acute respiratory syndrome middle east respiratory syndrome coronavirus (mers-cov): a review strategy and technology to prevent hospital-acquired infections: lessons from sars, ebola, and mers in asia and west africa bbc news, coronavirus: 'world faces worst recession since great depression the origin and virulence of the ''spanish'' influenza virus of the worst epidemics and pandemics in history. live science updating the accounts: global mortality of the - ''spanish'' influenza pandemic covid- infection: origin, transmission, and characteristics of human coronaviruses new coronavirus may have 'jumped' to humans from snakes, live science breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of covid- associated pneumonia in clinical studies clinical characteristics of patients discharged from hospital with covid- in chongqing clinical characteristics of covid- -infected cancer patients: a retrospective case study in three hospitals within wuhan public health measures to slow community spread of coronavirus disease coronavirus disease (covid- ) advice for the public: myth busters world newsmarch , / : pm if the world fails to protect the economy, covid- will damage health not just now but also in the future effects of novel coronavirus (covid- ) on civil aviation: economic impact analysis covid , school closures, and child poverty: a social crisis in the making closure of universities due to coronavirus disease (covid- ): impact on education and mental health of students and academic staff united nations (department of economic and social affairs) managing crowds with technology: cases of hajj and kumbh mela health management in crowded events: hajj and kumbh. bijit-bvicam's key: cord- - uvb qsk authors: tanveer, faouzia; khalil, ali talha; ali, muhammad; shinwari, zabta khan title: ethics, pandemic and environment; looking at the future of low middle income countries date: - - journal: int j equity health doi: . /s - - -z sha: doc_id: cord_uid: uvb qsk covid- which started in wuhan, china and swiftly expanded geographically worldwide, including to low to middle income countries (lmics). this in turn raised numerous ethical concerns in preparedness, knowledge sharing, intellectual property rights, environmental health together with the serious constraints regarding readiness of health care systems in lmics to respond to this enormous public health crisis. from the restrictions on public freedom and burgeoning socio-economic impacts to the rationing of scarce medical resources, the spread of covid- is an extraordinary ethical dilemma for resource constrained nations with less developed health and research systems. in the current crisis, scientific knowledge and technology has an important role to play in effective response. emergency preparedness is a shared responsibility of all countries with a moral obligation to support each other. this review discusses the ethical concerns regarding the national capacities and response strategies in lmics to deal with the covid- pandemic as well as the deep link between the environment and the increasing risk of pandemics. like the previous outbreaks of coronaviruses i.e. severe acute respiratory syndrome (sars) and middle east respiratory syndrome (mers), the ongoing pandemic covid- has characterized that the infectious diseases represent a problem that does not recognize borders, race, ethnicity, religion, caste or any other status quo. now known as "covid- ", "sars-cov- ", " -ncov", the virus has already made a huge impact on a global scale [ ] and changed human ways of thinking and characterizing the problem. covid- is an issue beyond borders, thus necessitates a globally coherent, combined, inclusive and holistic approach which can help in the reduction of transmission and overall risk mitigation, which otherwise, is predicted to impact entire human race. according to the who situational report on th april, , the total number of global cases surged up to , , [ ] , with almost every country affected or threatened by the geographical expansion of sars-cov- . the grand total of the total infections as of th sept, , is , , with death toll of , [ ] . a summary of the statistics taken from the who showing the data of th april and th september is indicated in inset fig. revealing the regional distribution of the sars-cov- cases and rate of mortalities. international regimes are on high alert to stop its spread, however, as far as the global scenario is concerned, countries and governments are clueless in stopping the expanding pandemic as not much is known about sars-cov- , while left only with implementing nationwide lock downs and curfews which opened new economic fronts and social challenges. one of the major challenges is the intermittent psychological burden on segments of the society who have not been well versed with the scientific knowledge. rumors and false information through social media brings enormous mental distress and singles out the need for responsible information sharing. similarly, the deepened cultural norms that people find difficult to abandon in lmics has created situations more favorable for transmission of sars-cov- , with the religious fundamentalists also playing their part. zoonotic origins of the coronaviruses and their circulation in the intermediate animal hosts presents another challenge of sustaining biodiversity and human-animal relationships. the primary reservoir of the sars-cov were bats while the intermediate source was civet cats that expanded across countries in - . mers-cov jumped to humans from camels and possessed an exceptional fatality rate of % in . now, sars-cov- has been proposed to jump to human beings from bats and pangolins [ , ] . the ongoing pandemic has resulted in a situation in which the scale of emergency is similar to world war ii (ww-ii), requiring decisiveness and commitment [ ] . in the developing and under developed regions, the risk management is extremely challenging because of the resource limitation as well as lack of basic health necessities and poor sanitation etc. [ , ] . it is now established that the oral-fecal route of transmission of sars-cov- is also possible beside respiratory droplets and person to person contact which further multiply the complexities of sars-cov- for less advanced regions [ , ] . apart from the lack of resources and technology, negligence due to the lack of awareness presents a grim picture. covid- has unleashed an enormous psychological burden that may have long term detrimental consequences. covid- has presented itself as a test case for the humanity in terms of global fraternity, decision making, technology and expertise sharing, rapid pandemic response mechanisms, stability, crises management and policy making. it is of paramount importance that the decisions regarding covid- pandemic should be strictly governed by ethical and moral principles. a shared threat cannot be defeated without a combined response. keeping in view the significance of the current situation, we have attempted to discuss various issues from the lens of ethics with special reference to the developing and under developing regions. covid- pandemic is an unprecedented situation facing the world in current times, with large, unimaginable socio-economic impacts. in such a situation, pandemic preparedness and response efforts require careful analysis of core ethical values and principles with an informed and evidence-based decision making. the ethical aspects that require special consideration include the greater need for public engagement, disease surveillance, clinical research and novel experimental interventions. the moral obligations in relation to "duty to treat" and "duty to plan" must consider the rights of health care workers and affected communities. moreover, necessary measures should be taken with respect to allocation of scarce resources, priority setting and social distancing [ ] . the decision making process for outbreak preparedness planning involves a number of stakeholders including governments, ngos, the military, commercial businesses, research funders, academic institutes, public health officials, researchers, ethicists, health care workers, volunteers, communities and families. all of them have different moral or legal obligations to fulfil [ ] . in a public health emergency, it becomes difficult to keep a balance between competing ethical principles i.e. need for necessary interventions in the interest of public health without compromising the public liberty. measures that limit individual rights must be reasonable, proportionate, least-restrictive, impartial, non-discriminatory, and in accordance with national and international regulations [ ] . when thoroughly implemented, home quarantine orders by government are legal and effective, as long as individual freedom and privacy is respected [ ] . the principal of equal respect must be implied by decision makers when a lock down or quarantine is imposed on the public. hereby restricting the public right to freedom is to be reciprocated by readily providing their basic needs, by ensuring effective risk communication through ethical and logical backing of this decision and giving easy access to latest information about the uncertain, ever changing risks [ ] . resource allocation should be ethical, transparent and based on scientific evidence. in this regard, the primary obligation is to protect front line health care workers as the entire health care systems depends on these individuals. furthermore, public health measures should focus on prioritizing the provision of resources when and where required e.g. to the public in confined settings which are prone to rapid spread of disease (such as homeless shelters, prisons, and slum areas), to areas with localized outbreaks to control community transmission and to high-risk groups such as older people, people with co-morbidities and weekend immune systems [ ] . health equity i.e. equal health opportunities for all should be the focus of all health policies planned by the state actors to better prepare a country's health system in the face of current pandemic or any health crisis that may come in future [ ] . during a pandemic, issues of resource scarcity can be mitigated to a large extent if early public health interventions are introduced e.g. through social distancing which is crucial in reducing pressure on the health system. this is particularly important with regard to resource constrained settings such as those in low to middle income countries (lmics). the failure to contain the spread at an early stage can severely constrain the health system's capacity in these countries. access to scarce resources which is considered reasonable in one country may be different in another such as in the case of developed and developing countries. particularly in developing countries, the public should be well informed about decisions regarding allocation of limited resources with clear communication of proper justification to gain trust and avoid chaos [ ] . resource scarcity may also be encountered at the global level. lower-income countries may face more scarcity than developed countries in countering covid- spread. hoarding of important medical supplies such as personal protective equipment and inaccessibility of vaccines and treatments when made available, should be discouraged by developed countries or the countries where they happen to be produced [ ] . ethical aspects must also be considered in covid- pandemic research policy and practice. it is an ethical obligation to conduct research in infectious disease outbreaks needed to address pertinent research questions that arise during such a health crisis [ ] . according to nuffield council on bioethics, the core values of ethical research include helping reduce suffering, demonstrating equal moral respect for the communities involved and fairness in terms of benefit sharing. the ethical principle of helping reduce suffering provides the basis for prioritization of more valuable and much needed research during a public health emergency such as covid- [ ] . for example, conducting rapid review of research proposals becomes all the more important during a pandemic. however the decision of ethics review committees (ercs) should not be too hasty so as to avoid approval of mediocre or non-pertinent research at the same time ensuring a speedy review to facilitate important research. in these circumstances, standard operating procedures (sops) could be introduced to form a multi-disciplinary sub-committee composed of members from erc who could be immediately called in times of emergency to conduct rapid reviews [ ] . to make the process more rapid, technological interventions should be encouraged. an erc in a chinese hospital used the video conference to review batches of research proposals. moreover, these conferences were held more frequently during the corona virus pandemic than they normally did. the mean time between receiving the application and initial review decision was . days [ ] . ethical principle of fairness entails the equitable sharing of benefits and the burdens of research between different actors involved in research i.e. the participating community as well as the collaborating partners from low and high resourced settings. similarly, the principle of equal respect emphasizes respectful relationships between researchers and the affected communities going through the emergency for meaningful community engagement. with respect to health care workers and researchers, the employers and the funders are responsible to make sure their needs are met as an equal moral obligation in exchange for their services [ ] . science and technology should be at the forefront of the outbreak research ranging from health sciences including risk assessment, risk management, vaccine development and modelling studies for improved data analysis to social sciences fighting discrimination/violence and promoting human rights [ ] . in contrast to research and development (r&d) focused on medical care and treatment, less attention is given to the improvement of coordination in assessment and modelling studies on data generated during an outbreak. integration of data analysis generated across disciplines is critical to provide support to decision makers during a pandemic in order to understand the course of the outbreak, the risk of its spread, and the potential effects of infection control measures [ ] . this should be given due share in research practice during a pandemic. ethical standards also advocate the notion of "duty to care" and "duty to treat" by health care professionals during pandemics. supporting arguments in relation to professional duty in the face of uncertainty and risk to life are guided by ethical principles of virtue, generosity and social utility [ , ] . besides, in dealing with this covid- crisis, health care workers may have to take difficult decisions based on a utilitarian approach when faced with ethical dilemma of managing critical care resource allocation. keeping in view the uncertainty surrounding this novel outbreak, rationing of resources might be required for a much longer time period and a far larger number of people. the response decision may require shifting from providing all the patients the maximum number of available resources to allocating minimal resources necessary for an individual's survival. so that the additional resources are left out for others who may have an equal chance of a good outcome [ ] . this is where governments and health care departments are obliged to guide and provide training to health care workers to handle difficult situations. furthermore, ethical practice emphasizes the duty to plan where proactive planning by the public health leaders and health professionals to prepare beforehand can help reduce morbidity and mortality in a worst case scenario. the aim is to have a system in place across all levels of health care to maximize benefits to the community in the time of need [ ] . besides being an expanding pandemic, sars-cov- is accompanied by huge chunk of information floating through the social, electronic and print media making it the surge for authentic information and news much harder, as iterated by the who and unicef [ ] . while people must rely on authentic data, the news spread through social media platforms often masks the original news/statistics. the tsunami of in-correct information and rumors has appeared as a major concern. the focus should be on awareness regarding sars-cov- and not on overburdening people with psychological distress which may lead our way to a psychological pandemic. one of the key steps to reduce the spread of misinformation is to automatically direct the users seeking information to who when keywords like coronavirus, covid- , pandemic etc. are searched on the online platforms. the only way in which traditional media will be helpful in fighting the expansion of the sars-cov- pandemic is through responsible reporting and sharing so that the information trickles down to common people. in pandemic of this global scale, media can be used as a source to mobilize communities to help the underprivileged segments of the society by keeping with the general safety protocols. team of social media experts linked to the official sources can be helpful in diffusing correct information across the social media platforms. evidence based information can be sought through the country specific official advisories and who. limiting ones information resources can be helpful. media giants must be adhered to strict norms of not to create panic but spread awareness. environmental ethics, climate crises and covid- : preparing for the worst covid- pandemic is an example of complex threat to humanity from emerging and re-emerging pathogens and signifies the need for a holistic and integrated one health approach for reducing their risk [ ] . one health approach is characterized by the inter dependence of human, animal and environmental health [ ] . both the animals and environment have a significant role in the emergence of infections with zoonotic origin in human population. several factors like climate crises, increased travelling, population explosion, urbanization, deforestation, animal trade and rapidly evolving pathogens have further amplified the threat of emerging zoonosis. due to evolutionary pressures and acquiring mutations, previously an animal pathogen, now gains the ability to cross the specie barrier, jumping and adapting to a new host i.e. human, which happened in case of sars, mers and now covid- [ , ] . circumstantial evidence suggest that the pandemic started in the seafood market which was a hotspot for buying and selling animals like bats, snakes, poultry etc. and provided sufficient humananimal interaction leading to spillover. initial studies on the genome of sars-cov- reveals . % similarity with bat coronaviruses leading to the conclusion that these viruses emerged from horseshoe bats [ ] . studies also revealed pangolins as one of the possible intermediate host [ ] . these converging evidences signify the need for one health approach. increasing demand for urbanization has led to human encroachment of more and more natural habitats, thereby, increasing exposure to novel exotic pathogens from the wild. a rapid consensus is building among the scientific community which infer the transition from holocene era to anthropocene era on the geologic time scale, in which human species are involved in changing the geology of the planet through anthropogenic activities [ ] . as a consequence of plastic pollution, distribution of radioactive material across the planet, co emissions, mining, deforestation and the sea level rise, the global ecosystem is becoming destabilized with time and threatens the animal species in the wild which may otherwise serve as a buffer between human and animals for harboring deadly infections. extinction of megaflora and megafauna signifies the need of exclusive one health strategies to combat this ever expanding threat. the emerging diseases and climate crises cannot be separated and requires extensive research, funding and attention of the international leaders. climate action cannot be shelved even in the pandemic as it is one of the tools for mankind to fight the emerging and re-emerging pathogens. figure indicates a holistic perspective of the sars-cov- pandemic while fig. illustrates the one health concept. adding more to the role of the environment, it is pertinent to mention that the developed countries are the major contributors towards the greenhouse gas emissions leading to global warming and climate change. this raises an ethical dilemma as most of the countries affected as a result of these changes are contributing negligible amount of green house gases (ghgs) but often become the adversely affected. the burden of responsibility regarding contributions to the climate change in relation to the pandemic needs significant discussions and dialogues. ethical issues concerning covid- outbreak: situational analysis in low to middle income countries (lmics) pandemic response should be guided by the ethical principles of fairness, respect and transparency. however, outbreaks are more often confronted with fear, discrimination, and interventions lacking evidence which raises public health concerns [ ] . in this section, we discuss the ethical challenges faced by low to middle income countries as they struggle to respond to the escalating spread of covid- . based on the idea that no "one size fits all", it is important to consider how the cultural and economic values in these countries impact approaches to address the corresponding ethical issues [ ] . figure indicates the issues in the lmics regarding global health emergencies using an ice berg analogy. various ethical dilemmas arising from the current situation are indicated in fig. . rapidly growing contagion in less developed countries mainly in africa, asia and certain parts of the americas is a global health emergency. different countries require a context-specific response depending upon their current situation whether there are no cases, infrequent cases, clusters or local transmission. overall, decisive actions necessitate effective social distancing, quarantines and if required even lock downs as well as massive testing and systematic contact tracing to stop further spread. developing and least developed countries are the most vulnerable to this crisis, many of which are affected due to war conflicts, are overly populated with urban areas and slums, lack access to basic health services and are thus at high risk of covid- spread [ ] . in lmics, the greatest challenge is how fast the gaps in early response to covid- outbreak are filled before the infection control goes out of hand. the best chance is to have the systematic containment measures in place and massive testing done before the virus overwhelms the weaker health care systems. a well-organized response should also incorporate scientific knowledge generation e.g. studies on changing disease epidemiology such as duration of incubation period between infection and appearance of first symptoms so the people are retained in quarantine no longer than it is necessary in order to keep the costs down [ ] . moreover, rapid and actionable research conducted at local level should be encouraged in lmics so as to deal with the pandemic more effectively. data generated from response activities can be utilized for research purposes to make foreseeable predictions in the local context [ ] and change the ongoing response strategies as and when required in order to minimize socio-economic impacts. response preparedness is weak in many low income countries as evident by preparedness assessments of countries, none of which were evaluated as ready to respond, making them predominantly susceptible to epidemics. it is due to the poor health and nutrition conditions, aggravated by co-morbidities and low average annual health spending of only $ per person in these countries. according to who, the regional readiness level is assessed to be only % with serious gaps in the response capacities for these countries to investigate disease spread alerts, treatment of patients in quarantine facilities and transmission control in both the health facilities and the public [ ] . south asia which holds a quarter of the world's population with currently covid- affected countries including afghanistan, pakistan, india, nepal, bangladesh, sri lanka are likely to face severe constraints in the management of the outbreak if it spreads uncontrollably. the current low number of reported cases may be due to less testing with limited resources in these countries. for example, india's testing rate is exceptionally low given its large number of population with an average of just over tests per million persons which is way less than advanced countries like south korea with more than and italy more than tests per million persons, as of march , [ ] . total cumulative corona cases in india were reported to be , , while the death toll has risen to , , as of th september [ ] . pakistan reported its first coronavirus case on february , . there were confirmed cases and deaths, as of april , . the weekly report of th to th september by who reveals a total of , cumulative cases of sars-cov- in pakistan, with cumulative deaths [ ] . initially, the country's response was appropriate and timely just when the virus was already spreading from china to its neighboring countries due to travel. the containment measures proved effective in preventing the import of virus from china. later, when a considerable number of people travelled back from neighboring iran which was badly affected by the virus, the whole dynamics changed for pakistan. partial or complete lockdowns were imposed throughout the country, and all businesses apart from those providing essential goods were closed [ ] . the government estimated that the number of cases were expected to rise up to , by april , in a national action plan report submitted to the supreme court [ , ] . however, the lockdown situation was gradually eased with implementation of "smart lockdowns" and reopening of the economy in stages. afghanistan, a war-torn nation started to feel the brunt of covid- just like its neighbors. controlling its spread in afghanistan is governed by a number of social and political complexities, including the incursion of afghan refugees from neighboring iran. less public awareness of the virus and lower health literacy is a major issue illustrated by an individual who was confirmed to have the virus, and people who were the potential suspects, left the quarantine facility, risking the virus transmission in the communities [ ] . the cumulative deaths in afghanistan have risen to while the total reported cases are , as of th sept. [ ] . iran faced the worst situation among lmics and was the epicenter of corona virus in asia with over , confirmed cases and over deaths as of april , . as of th sept. , the total number of reported cases are , and cumulative deaths are reported to be , in iran [ ] . the iranian government was criticized for failure to respond early which resulted in shear increase in the number of cases, affecting both citizens and several top officials [ ] . also, insufficient public awareness regarding risk of the virus, and poor public attitude in observing self-quarantine were attributed as reasons for higher rate of spread [ ] . in addition to resource limitations, us sanctions on iran even increased the difficulty in procurement of medical supplies from companies abroad. it is due to the stricter sanctions imposed by us since may, with severe penalties for non-us firms doing business with iran. this is a humanitarian crises and the global community must look at the impacts of such sanctions on humanitarian aid during a pandemic so that the sufferings of the public could be reduced [ ] . some countries also faced challenges in implementation of ongoing lockdowns due to religious or cultural values such as religious congregations [ ] . congregations in pakistan, malaysia and india were considered responsible for transmission of the virus. pakistan reported hundreds of cases directly linked with the congregation which was held in march at raiwind, lahore [ ] . developing and less developed countries also face several challenges in self-quarantine which might not be very effective where large families live together often in congested settings, sometimes three or more people sharing the sleeping quarters. households in sierra leone, tajikistan, guinea, pakistan, afghanistan, and senegal are the largest, with six or more members on average [ ] . in africa, the first case was confirmed in egypt on feb , . according to the recent data of who available on th sept. , the total number of cases has risen to , , with the death toll rising to , in african continent, with south africa affected the most [ ] . the covid- outbreak continues to spread across africa with a number of countries in the continent where community transmission is becoming established such as south africa. african countries are more vulnerable to faster spread of covid- due to weak health care systems, high occurrence of hiv and malnourishment among other factors such as scarcity of medical supplies for personnel and the patients [ ] . resource constrained countries in africa, should take steps for prepardeness and development of basic technological interventions for responding to health emergency [ ] . the who african regional office along with cdc immediately started taking measures to prepare african countries for covid- outbreak. the previous experiences from ebola preparedness came handy as coordination response mechanisms were already in place. over the past few years, the who has helped develop a national network of surveillance laboratories and health facilities in the african region amidst the previous outbreaks which could prove really helpful in current crisis [ ] . the rapid response measures taken in china and other countries like taiwan, hong kong, singapore and south korea ranged from strict quarantine measures, to detailed contact tracing, augmented with use of big data analytics. these measures helped the countries in keeping down the number of growing cases by breaking the chain of transmission. taiwan leveraged all the technological resources, integrating national health insurance and immigration and customs databases to generate big data for tracing potential cases or areas [ ] . the impacts of these early interventions for effective response towards covid is encouraging for the countries where covid- is spreading fast. effective public engagement should be made meaningful through gaining public trust and seeking cooperation instead of using the coercive measures especially in resource constrained settings with low level of literacy and social, religious and cultural complexities. only this way, the lockdowns or quarantine measures will be more effective [ ] . effective risk communication is mandatory in public health response measures taken in lmics ensuring the public's right of access to information. poor populations without access to information channels are the most vulnerable during health crisis and are most likely to ignore the government's warnings regarding the precautionary measures such as social distancing [ ] . a larger population of lmics is living without access to mass media in rural areas or some poor countries such as madagascar, nigeria, zambia etc. [ ] . awareness about the risk can be spread through simple health messaging and regular briefings by the government on television and radio; through public officials at the district level; or any other means deemed appropriate so as to provide access even to the poorer communities living without internet or communications channels. it is the government's obligation to keep the public well informed about the risk of covid- . it also means that governments may have to take difficult decisions given the uncertainty and time constraints surrounding this pandemic. therefore, it is important that information must be communicated in a transparent, honest and timely manner [ , ] . scarcity of resources including trained personnel, health centers, and protective gears is a major problem in lmics. even under normal circumstances, the poorest countries have acute shortage of icu beds in comparison to high income countries e.g. roughly us has icu beds per million people whereas countries such as india, pakistan and bangladesh have only beds per million people. the situation is worse in sub-saharan africa where zambia has . icu beds per million, gambia has . and uganda has . beds per million. so the fatality rate in these countries is estimated to be much higher in these countries than wealthier nations [ ] . during a pandemic, standard crises care protocols should be developed by public health institutions to establish a systematic and evidence based procedure which ensures fair distribution of health care resources. thus shifting the focus from prioritizing individual patient benefits to maximizing benefits to the community as a whole [ ] . priority decisions regarding resource allocation should not be discriminatory i.e. based on sex, race, religion, disability, wealth, citizenship, social status or connections [ ] . moreover, the ethical debate regarding allocation of resources in lmics must take into consideration a wider context where critical care resources may already be scarce or non-existent even in a normal situation as compared to developed countries. in such conditions, ethical justification encompasses social justice governed with locally adapted global approaches [ ] . ethical standards support the idea that state is responsible for compensating the public losses incurred upon them due to public health interventions such as the containment measures including social distancing, quarantine and isolation. this is particularly important for people residing in resource constrained regions. the state ought to make social policies with the aim to share some of their burdens and costs e.g. by protecting the employment rights of citizens [ ] , providing financial support to the poor and needy such as daily wagers who might suffer due to shutting down of several industries as a result of lock down orders. however, lack of resources could seriously defeat this argument of compensation in these countries which cannot even provide for the basic health care needs of the people [ ] . in pakistan, it was estimated that between . million to . million workers in various industries were at risk of losing their jobs. according to human rights watch, the government must tend to the poorer workers who might be further pushed into poverty and it may dissuade them from voluntary quarantine necessary to contain the spread of the virus [ ] . a multi-lateral response by international community has been previously seen against similar threats posed in by severe acute respiratory syndrome (sars), in by swine flu (h n ), in by middle east respiratory syndrome (mers) and in - by ebola. all these crises were contained well via multilateralism and current crises of covid- is yet to be further materialized by this strategy. the current covid- crisis presents challenges that are beyond and above the earlier outbreaks, hence it deserves a well-established multilateral response. any pandemic requires the weak links to be strengthened on individual basis i.e. at the hospital level as well as community basis, country basis and even globally. therefore, it is the urgent need to shore up the health care systems in order to handle the current flood of cases as well as the future waves of the same or other related viruses. efforts for developing and supplying medical devices, diagnostic tools, vaccines, therapeutics, and other medical technologies for covid- pandemic can be seen globally. even though medical and scientific urgency are building, the medical technologies need to be tested efficiently, ethically and urgently with equitable availability to everyone around the globe. therefore, a multi-lateral response strategy which can accelerate scientific discovery and technology development with ensured safety, efficacy and quality is essential. further, there is need to coordinate the world health organization (who) for operational implementations. technology pooling and benefit sharing as previously witnessed during influenza [ ] and sars epidemic [ ] will not only save lives of millions of individuals by response acceleration to pandemics but will also encourage powerful administration of the global solidarity for the future epidemics. to protect people against deadly infectious disease outbreaks, it is critical that scientists and governments rapidly share information about the pathogens that cause them. the genetic information of sars-cov- was shared immediately and openly [ ] that accelerated the initial stages of diagnostic tests development and novel therapeutic compounds exploration. likewise, many researchers immediately shared their research information via open source publication [ ] . scientist from different countries are sharing medical course and epidemiological data and collaborating for medical guidelines development in response to the current pandemic [ ] . such examples of sharing information and open science need be incorporated throughout research and development of covid- medical technologies. moreover, the scientific community need to share every progress, every success and even the negative data so the research can be continued with uppermost speed to obtain the best results. some of the current and early research by pharmaceuticals, universities and medical device companies are funded by charities and governments. it is therefore imperative that such funding agreements mandate full data sharing, open source publishing and open collaboration following ethical guidelines regarding identity of subjects. a data-sharing system needs to allow collaboration between stakeholders in the absence of pre-existing relationships and all collaborators must adhere to fundamental ethical principles of data use. above all, it must ensure that people in all affected countries benefit from timely access to evidence-based interventions in emergencies. the multi-lateral response needs to be opened to the wide range of intellectual property rights, technology blueprints, technology specification, copyrights, patent rights, cell lines, research and regulation rights, data rights and clinical trial rights. in simple words, no exclusive right has to stand in the way of response to covid- pandemic by global research community in order to prioritize public health. similarly, all the rights such as confidential business information rights and trade secret rights required for bio similars, vaccine development and medical technology need to be accumulated and distributed hence to accelerate access to the market. it is therefore important to enable fast track registration along with emergency access to new medical technologies and medicines around the globe. some of the regulatory barriers can be eliminated by access to regulatory data and fast-track registration, however, countries should ensure that producers can bring medical technologies quickly into the market with equitable access. competition between producers has always resulted in increased supply with lower prices. in response to current pandemic, facilitating competitive supply source can present more advantages. as coronavirus infection is exponentially increasing with life threating outcomes, there is need of utilizing every possible option to mobilize supply capacity with respect to diagnostics tests, therapeutics, protective equipment, vaccines and other medical devices as soon as possible. with expanding supply, necessary actions should be taken to limit the export of needed ingredients, medical technologies and hoarding of medical supply to other countries [ , ] . compulsory licensing is a useful tool to be used during public health emergencies such as the covid- crisis when a treatment becomes available. international organizations and pharmaceutical companies should encourage the developing countries to pursue this option in the time of a pandemic [ ] . it would be difficult to minimize the socio economic impacts of covid- in due time. it is the prime responsibility of the international community to take public health measures in best interest of the public with providing access to basic health care facilities, information and resources without discrimination, embodying the values of respectfulness and cultural appropriateness. in the long run, governments in developing countries should strive to achieve self-sufficiency through policy interventions by mobilizing local industries to manufacture medical care resources such as personal protective equipment, ventilators for capacity building and facilitate the propagation of scientific research and technological innovations. once a vaccine is made available, it will be important to increase collaboration across the regions to ensure that the world's poorest countries have an equal access to adequate vaccine supply. through anthropogenic activities animal species are constantly under a severe threat of extinction amplified by the loss of biodiversity, global warming and animal trade. global communities must unite for the climate action if we are to prevent any further global scale pandemics. from sars to covid- : a previously unknown sars-cov- virus of pandemic potential infecting humans-call for a one health approach who. coronavirus disease (covid- ) situation report - edition: world health organisation zoonotic origins of human coronaviruses severe acute respiratory syndrome: historical, epidemiologic, and clinical features securing justice, health, and democracy against the covid- threat emerging viral infections in pakistan: issues, concerns, and future prospects natural or deliberate outbreak in pakistan: how to prevent or detect and trace its origin: biosecurity, surveillance, forensics high expression of ace receptor of -ncov on the epithelial cells of oral mucosa molecular and serological investigation of -ncov infected patients: implication of multiple shedding routes guidance for managing ethical issues in infectious disease outbreaks research in global health emergencies: ethical issues ethical considerations in developing a public health response to pandemic influenza. geneva: world health organization us emergency legal responses to novel coronavirus: balancing public health and civil liberties responding to covid- : how to navigate a public health emergency legally and ethically combating covid- : health equity matters ethical standards for research during public health emergencies: distilling existing guidance to support covid- r&d: world health organization ethics preparedness: facilitating ethics review during outbreaks-recommendations from an expert panel ethics committee reviews of applications for research studies at hospital in china during the novel coronavirus epidemic building resilience against biological hazards and pandemics: covid- and its implications for the sendai framework using "outbreak science" to strengthen the use of models during epidemics ready and willing? physicians' sense of preparedness for bioterrorism declaration of professional responsibility covid- -legal and ethical implications for your practice duty to plan: health care, crisis standards of care, and novel coronavirus sars-cov- . nam perspect how to fight an infodemic revisiting the one health approach in the context of covid- : a look into the ecology of this emerging disease zoonotic spillover and emerging viral diseases-time to intensify zoonoses surveillance in brazil one world, one health: the novel coronavirus covid- epidemic the sars-cov- outbreak from a one health perspective identification of -ncov related coronaviruses in malayan pangolins in southern china the anthropocene epoch: scientists declare dawn of humaninfluenced age ethics guidance for the public health containment of serious infectious disease outbreaks in lowincome settings: lessons from ebola key ethical issues discussed at cdc-sponsored international, regional meetings to explore cultural perspectives and contexts on pandemic influenza preparedness and response responding to the socio-economic impacts of covid- scientists are sprinting to outpace the novel coronavirus the need for covid- research in low-and middle-income countries covid- : a fast evolving pandemic can india keep up with covid- policy responses to covid- virus cases may top , by april end, sc told. dawn. th the news internatonal: govt tells sc number of coronavirus cases expected to rise to , by covid- : the current situation in afghanistan the coronavirus has caused a full breakdown in iran, with an unknown death toll, infected leaders, and massive burial pits visible from space covid- battle during the toughest sanctions against iran covid- and religious congregations: implications for spread of novel pathogens covid- & other fears. the dawn dhs. data should drive covid- mitigation strategies in lower-and middle-income countries covid- pandemic-an african perspective covid- threatens health systems in sub-saharan africa: the eye of the crocodile response to covid- in taiwan: big data analytics, new technology, and proactive testing human rights dimensions of covid- response why inequality could spread covid- hospital capacity and operations in the coronavirus disease (covid- ) pandemic-planning for the nth patient when the pandemic hits the most vulnerable. foreign affairs the ethics of creating a resource allocation strategy during the covid- pandemic allocation of scarce resources in africa during covid- : utility and justice for the bottom of the pyramid. developing world bioethics a general approach to compensation for losses incurred due to public health interventions in the infectious disease context pakistan: workers face health, economic risks the race to patent the sars virus: the trips agreement and access to essential medicines pandemic influenza preparedness framework whole genome of novel coronavirus, -ncov, sequenced. science daily data sharing for novel coronavirus (covid- ) who launches global megatrial of the four most promising coronavirus treatment germany confirms that trump tried to buy firm working on coronavirus vaccine eu limits on medical gear exports put poor countries and europeans at risk. peterson institute for international economics the case for compulsory licensing during covid- publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we are thankful to the fellows of qau for providing valuable inputs. we are also thankful to ms. xanthine muller, from the radiobiology department of ithemba labs, cape town, south africa, for checking the manuscript for consistency and english language corrections. all authors contributed equally. the author(s) read and approved the final manuscript. this work is not funded. available on request.ethics approval and consent to participate not required. all authors agreed on publishing. authors declare no conflict of interest. key: cord- -fq urilg authors: elderfield, ruth; barclay, wendy title: influenza pandemics date: - - journal: hot topics in infection and immunity in children viii doi: . / - - - - _ sha: doc_id: cord_uid: fq urilg the recent h n pandemic that emerged in has illustrated how swiftly a new influenza virus can circulate the globe. here we explain the origins of the pandemic virus, and other twentieth century pandemics. we also consider the impact of the pandemic in the human population and the use of vaccines and antiviral drugs. thankfully this outbreak was much less severe than that associated with spanish flu in . we describe the viral factors that affect virulence of influenza and speculate on the future course of this virus in humans and animals. influenza is a seasonal respiratory illness associated with more serious consequence and even death in the very young, old and immunocompromised. annual epidemics are predictable and affect a relatively small percentage of the global population at any one time. pandemics differ from epidemics in that they are a global phenomenon, affecting large numbers of people in multiple countries simultaneously. pandemics tend to arise swiftly often out of the normal season, and affect a wider age group and spectrum of individuals than seasonal influenza. the first recorded influenza pandemic was in [ ] . since then human populations have been subjected to at least pandemics, most notably in when estimates of the human deaths that resulted vary between and million [ , ] . the influenza virus, the etiologic agent, is a member of the family orthomyxoviridae. there are three categories of influenza known as types a, b and c. only type a causes pandemics and thus is the most widely studied. influenza b viruses cause typical seasonal infections restricted to humans. influenza c viruses also infect humans and have been isolated from clusters of children, but are often not recognised and may be dismissed as an untyped influenza like illness, due to the lack of diagnostic tests [ ] . the virus particle is enveloped, whereby the genome is protected by a lipid bilayer derived from the host cell membrane. the appropriated membrane is studded with viral glycoproteins: the attachment spike protein haemagglutinin (ha) which binds to sialic acid (sa) receptors on the cell surface; the integral m protein, an ion channel involved in the uncoating of the virus inside the infected cell, and the neuraminidase protein (na) which cleaves the cell membrane sas that would otherwise tether the budding nascent virus particle to the infected cell. lining the inside of the virion membrane is the abundant matrix protein (m ), surrounding the eight genomic negative-sense rna segments which are intertwined with nucleoprotein (np) and each associated with one set of the three viral polymerase subunit proteins (pb , pb and pa) (fig. ). the viral ribonucleoproteins (vrnps) are the replicative units that are transported into the nucleus of the host cell after virus entry. there, the virus co-opts a number of host factors to assist the polymerase in transcribing viral mrna, and replicating new genomes via crna intermediates. finally the newly synthesized viral proteins and genomes are transported to the host cell's external membrane where the progeny virions assemble and bud. the pandemic dealt a devastating impact on a global population. several features of the era, in addition to the extraordinary virulence of the virus itself that will be discussed below, contributed to the impact of the pandemic. at that time, although influenza was known as an infectious disease in terms of symptoms, the virus itself had not yet been identified. indeed for a good proportion of the pandemic, hemophilius influenzae (known as bacillus influenzae at the time) was suggested as the causative agent. the influenza virus was eventually isolated from pigs by richard shope in [ , ] , then from humans by andrewes, laidlaw and wilson smith in [ , ] . at the start of the influenza pandemic in , the world was at war. the situation in america is absorbingly described in john m. barry's "the great influenza" (penguin, ) complied from military records, personal papers, oral history and newspapers of the period. there is some epidemiological and historical evidence that the outbreak may have begun in army camps either in the usa or in europe where large numbers of young susceptible hosts were living in very crowded conditions. there is also evidence of at least two waves of disease, and indications that the second wave was more virulent than the first. for example, by the second wave historical accounts by the medical and scientific staff at the time describe symptoms such as: cyanosis which started as mahogany spots over the cheek bones, and could expand until the patient turned black, caused by the lack of oxygen transfer in the lungs, leading to blue unoxygenated blood; extreme chills and fever, severe joint pains, vomiting and abdominal pains; earaches, headaches often localised around the eyes; and disturbing blood loss from nose, stomach, intestine and eyes. at post mortem the lungs were often filled with the debris of destroyed cells and blood, which today would be diagnosed as acute respiratory distress syndrome (ards). in philadelphia, where the virus had been introduced from the local port, health workers and scientists were requesting widespread restrictions on gatherings and provision of information to the media. unheeding, the governor and the senior health official sanctioned a large city wide liberty loan parade in order to gather funds for the war effort. within h of the parade every bed in the city's hospitals was filled. the daily death rates for the city rose at an alarming rate, days after the parade died in one day, on day more than people died. the second and third waves of the pandemic resulted in a cumulative case fatality rate (expressed as a ratio of the number of people infected to the number of people who died) of > . %. later pandemics of the twentieth and twenty-first century only reached case fatality rates of less than . % [ ] . remarkably, although it has not been possible to isolate infectious virus directly from stored samples of that era, we do today have access to the causative agent of this pandemic following the elegant application of modern science. in , jeffrey taubenberger and colleagues used the polymerase chain reaction to amplify small fragments of viral rna isolated from formalin-treated post-mortem pathological slides and also from frozen lung tissue obtained from a person who died in alaska and was buried in the permafrost, from this material the nucleotide sequence of the virus was deduced [ , ] . taubenberger joined forces with terence tumpey and colleagues at the cdc. they used the virus sequence information to generate plasmids containing the viral cdna which when transfected into suitable mammalian cells, allowed the recovery of infectious virus [ , [ ] [ ] [ ] [ ] [ ] [ ] . the reconstituted virus was more virulent in animal models than any other influenza virus strains studied previously [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . thus although there is strong evidence that secondary bacterial infection contributed significantly to deaths from virus in humans [ , ] , the virus itself, in the absence of bacteria, is remarkably pathogenic to animals. studies have been carried out to map the genetic determinants of this virus in the hope that this will help us to predict the virulence of future influenza strains as they emerge. the polymerase genes and the virus ha gene have been implicated in the extreme virulence of this virus, but work continues to understand the mechanisms by which this particular influenza strain is so deadly [ ] [ ] [ ] [ ] . phylogenetic studies suggest that the genome of the virus is most similar to viruses found in birds. however there are a number of key amino acid changes that indicate that, although it originated in an avian host, the virus underwent adaptation in order to replicate and transmit within human and swine hosts [ ] . interestingly the virus exhibits low pathogenicity in experimentally infected swine [ ] . the pandemic virus has been called the 'mother of all pandemic viruses' [ ] as all of the twentieth century pandemics are derived from virus lineages descended from the virus. after , viruses derived from that outbreak continued to circulate in humans causing annual epidemics of moderate or mild severity [ ] . however, because of their segmented genomes, influenza viruses are particularly prone to a special form of recombination known as reassortment that occurs if one host is coinfected by two different viruses. such mixing events allow the introduction of genetic material from viruses that usually circulate in birds with the human adapted viruses, and new viruses thereby created may be able to cause a novel outbreak. we know that the two major pandemics in the second half of the twentieth century were formed in this way: the 'asian' pandemic of was caused by the emergence of an h n sub-type virus that retained the m, np, pb , pa and the nonetheless, perhaps because antibiotics were available by that time or perhaps the h virus itself had a milder phenotype, the death toll of this pandemic was much lower at only ~two million people. the h n 'hong kong' pandemic that followed just years later resulted in between one and two million deaths. this virus was a recombinant between the circulating human h n virus and an avian strain with h ha. the reassortant virus still retained five segments originally derived from the strain, but acquired the ha and pb from the avian virus. each of the h and h pandemic events were so universal that the virus displaced the previously circulating strains [ , ] . in , the h n strain re-emerged as a circulating human strain (not to be confused with the swine h n outbreak at fort dix). the colourfully named 'red' or 'russian' flu appeared initially in china in may of with isolates found in russia soon after [ ] . this strain produced a relatively mild disease mainly in young children. however, subsequent genetic analysis indicated a year gap in the evolutionary history of this virus. in fact it was genetically similar to virus isolated in . the eventual conclusion drawn was that this virus had been deep frozen in a laboratory and its release was accidental. the h n and h n subtypes have continued to co-circulate and to cause human seasonal influenza outbreaks into the twenty-first century (fig. ) [ ] [ ] [ ] [ ] [ ] . the influenza a virus naturally circulates in aquatic birds, where it replicates in the gut [ ] [ ] [ ] . all of the ha and na subtypes have been isolated from either or both of the anseriformes (an order which includes ducks and geese) and from the charadriiformes (the order to which shore birds and gulls belong). no other species has been infected by all the influenza types. different subtypes predominate in the different orders of birds; h and h for example, are found mainly in anseriformes, whereas in charadriiformes h , h , h and h are the predominant ha subtype. the virus is excreted in high titres into the water bodies that are home to domestic and migratory birds [ , ] . the virus can then be picked up by migratory birds and spread along the migratory routes. however, the relative geographic isolation of some flocks has been proposed as one cause of genetic divergence within the ha and na subtypes [ ] . whilst the disease caused by influenza is mainly asymptomatic in aquatic birds, some isolates are capable of developing from low pathogenic avian influenza (lpai) into a highly pathogenic influenza (hpai) capable of killing domestic poultry. the two subtypes that are prone to change pathogenicity are h and h , as seen in eurasia with the hpai h n viruses and the netherlands with the h n virus. economically, the now widely-distributed h n virus has been responsible for the death of over a billion head of poultry either directly through the disease or indirectly through preventative culling measures [ ] other subtypes h , h , h , h and h , whilst still appearing mild in aquatic birds, can be fatal in domesticated flocks [ ] . only viruses of the h , h or h subtypes are known to have circulated among humans or pigs. the drastic recombination events that result in novel pandemic viruses described above are called antigenic shift. after the introduction of the new subtype and its wide circulation in humans, the increasing prevalence of specific immunity among human hosts exerts selection pressure that drives evolutionary change in the ha protein via the accumulation of point mutations that block the antibody recognition through conformational changes or glycosylation events on the antigenic epitopes. this process is called antigenic drift. as the virus continues to circulate in humans in the interpandemic periods, mutations accumulate that confer antigenic drift as well as other adaptive mutations that alter the nature of the virus and may be associated with loss of virulence. this, along with increased wide vaccination campaigns for the elderly and immuno-compromised populations, could explain the gradual decrease in influenza-like illness since the hong kong pandemic of , particularly in recent years ( fig. ) [ , ] . the ability of influenza a viruses to recombine so readily has worried virologists and public health planners alike, because of the risk that a seasonal strain of influenza with human adapted components might recombine with one of the highly pathogenic avian influenza (hpai) viruses such as the notorious h or h subtypes. these two subtypes are lethal in poultry because of an extended tropism conferred by mutation in the ha gene that allows them to infect and propagate in many organs and tissues, rather than being restricted to areas where the appropriate host cell proteases exist. consequently infection with these viruses carries a high mortality in humans of more than %. h n virus has been responsible for over cases of human infection and deaths (as of st august according to the world health organisation avian influenza surveillance system) but thankfully has not yet reassorted with a human-adapted influenza virus, nor given rise to a pandemic outbreak [ ] . because the research community was so focused on surveillance of and strategies to control h and h infections, the outbreak of the 'swine' influenza was a surprise. we had largely overlooked the idea that the next pandemic would originate in pigs even though an outbreak in fort dix, new jersey in associated with the death of a soldier from infection with an h n swine flu had led to mass vaccination campaigns at that time. the fort dix incident did not give rise to a pandemic, the virus remained contained within the military and transmission of the virus had fizzled out by the time the now-infamous vaccination campaign began [ , ] . most text books propose that swine are the mixing vessel in which influenza viruses of avian and human origin reassort. it has been evident that pigs can be infected with influenza since the early days of virus isolation. indeed, shope initially isolated influenza from a pig [ , ] and kida et al. showed that pigs could be infected by many different subtypes of avian influenza [ ] . the pandemic virus illustrates just how good a mixing pot the swine host can be. the origins of its eight gene segments come from at least four different sources and three different hosts. the pb and pa segments appear to have originated in an avian reservoir and transmitted to the swine host around . the pb segment derives from a human virus but was transferred to swine in . the ha, np and ns segments once again can trace their lineage back to the pandemic influenza, when the virus infected pigs and subsequently circulated through the years to become a classical swine virus. the na and m segments are from circulating swine viruses, of the eurasian lineage, believed to have transferred from birds in ( fig. ) [ , ] . why do swine make such good mixing vessels? ito et al. showed in that the pig respiratory tract displayed sa receptors that are bound by viruses isolated from birds as well as those used by human-adapted viruses, implying that the pig was capable of being infected by an avian and a human-adapted virus at the same time [ ] . in addition, the co-expression of the avian-like and human-like receptors in swine potentially allows for the selection of avian viruses with small mutations that adapt them to bind to and replicate in mammalian cells, a process known as 'receptor switching.' for avian influenza viruses to adapt to and transmit between humans, it is now apparent that in addition to the reassortment events that occur during antigenic shift, their ha proteins must also undergo modifications that alter their fine receptor binding specificity. the influenza ha protein binds to sa residues on the host cell surface as a prelude to cell entry. in the avian gut, these are predominantly a- , linked receptors but in the human upper respiratory tract a- , linked receptors predominate. avian influenza viruses would therefore preferentially bind a- , linked receptors and human-adapted influenza viruses have changed key residues at the receptor binding site allowing greater affinity for a- , linked receptors (fig. ) [ ] . in h ha proteins, receptor switching occurs if there is a change from glutamine (q) at position to leucine (l) (h numbering) and is enhanced by glycine (g) at to serine (s) [ , ] . for other subtypes the changes required for human adaptation are not exactly the same. some h viruses still bind to a- , human-like receptors even when the q is present, a trait shared by avian h and h proteins. the h subtype tends to show changes at residues (aspartate [d] to g) and (d to glutamic acid [e]) rather than and but they achieve the same end [ , , [ ] [ ] [ ] . fortunately, in the case of h ha, none of the changes found in other subtypes have completely mediated a receptor binding switch, suggesting that the barrier to human adaptation may be particularly high for this subtype [ , ] . one important difficulty in understanding these adaptive events is that the nature of the influenza virus receptor is not completely clear, but it is certainly more complex than a single sugar moiety [ ] . the nature of carbohydrate to which influenza virus might attach has been recently studied using glycan arrays. glycan arrays present hundreds of different carbohydrates. different viruses or expressed ha proteins are then given the opportunity to bind to a favourite residue [ ] [ ] [ ] [ ] [ ] . this type of experimental procedure was used recently to elucidate the receptor binding preferences of the novel pandemic h n virus. interestingly, this virus along with two other swine viruses tested, was able to bind both a- , and a- , sa, whereas seasonal h n influenza virus had a strong preference to bind carbohydrates with a- , linkages and showed no binding to those with a- , [ ] there multiple recombination events of classical swine influenza (black) resulted in a triple reassortant (trig), when recombined with eurasian swine influenza (grey) generated the ph n virus [ ] the emergence of swine origin influenza (ph n ) the swine origin pandemic influenza virus appears to have emerged from san luis potosi, mexico in late february [ ] , though it has been suggested that the virus was circulating at low levels in humans for some months prior to this. indeed the most common ancestor may have emerged between august and january [ , , ] . the pandemic threat of the new virus was realised as the first wave peaked in mexico in late april . the virus quickly spread across the globe. who moved to pandemic phase after confirming human to human transmission on the th april, and just two days later, phase was declared as the outbreak was found in two or more countries within one who region. finally passage of the virus into a second who region triggered escalation to phase on the th june. the h n virus responsible for the pandemic is not the same h n virus that had been circulating in humans in recent years causing seasonal h n outbreaks. both viruses have ha proteins originating from the pandemic virus. however the ha of the seasonal h had been under antigenic and other selective pressure as it circulated in the human population over a total of seven decades. on the other hand, since pigs are short lived, they exert little antigenic pressure to drive evolution of ha because the likelihood that a pig will be re-infected by the same influenza virus during its brief life time is very low. the rather genetically static -derived pig virus became known as 'classical' swine influenza virus and it was the predominant influenza virus of swine on the north american continent throughout the twentieth century. at the time this classical swine h ha recombined into what was to become the pandemic virus, it still retained % amino acid sequence identity to its progenitor. however, the human seasonal virus had changed so dramatically that it shared only % amino acids with the ha protein, and this did not allow for any antigenic cross protection for humans who had been infected with seasonal h in recent years against the novel pandemic strain. in the uk, the first reported case was on the th april , brought back by those returning from holidays in mexico. by may th there were uk cases, of whom were returning travellers, were direct contacts of those travellers and were people who had links to the secondary cases. already at this early stage there were eight sporadic cases which were not linked to travel. on st june, the influenza-like-illness (ili) incidence baseline was crossed and the first wave in the uk was clearly underway. this wave peaked in july and then fell well below baseline by mid-august, after schools closed for the summer holidays. nevertheless % of the deaths in the uk occurred during this wave. the second wave was far shallower, but endured for a longer period from september until february , and was responsible for the remaining % of fatal cases [ , ] . the height of the peak of ili cases in the second wave was much lower than had been predicted. several factors contribute to the explanation for this: a proportion of the population (> %) most vulnerable to seasonal influenza infection, the elderly, were already immune. in blood samples of those over years old, collected in before the pandemic virus emerged, it was possible to detect antibodies that cross react with pandemic virus' ha in > % of the samples (haemagglutination titre / ). in those aged - years, the seropositive frequency drops to ~ %, whereas in the - year old age bracket, the proportion with significant hai was just ~ % [ ] . these neutralising antibodies in sera collected from the elderly exist because many people in older age groups were infected in early life by closer derivatives of the h n virus. the second factor was the surprisingly mild nature of the pandemic virus in most people. serology conducted retrospectively detected neutralising antibodies in a far larger percentage of the population than could be expected from the reports of ili. one in three of the children in london and birmingham were seropositive for the virus by september [ ] suggesting that many people who had the infection did not report it. this could be because the symptoms were sufficiently mild that they did not feel they needed the flu service that was on offer at the time, or they did not even realise they had the infection. in this respect, the population was fortunate; this virus spread effectively but did not produce overtly pathogenic effects in most people. the case fatality rate was . %, far lower than the . % of the pandemic or the . % of the and pandemics. despite that, there were over , hospitalizations due to influenza like illnesses in the uk and deaths [ ] . globally mortality far exceeds , deaths [ ]. in the event of a pandemic, such as in , difficult decisions need to be made by health authorities to prioritise limited supplies of drugs and vaccines. pharmaceutical companies may generate millions of doses of vaccine ( million for the pandemic) [ ] to protect the population, but this is still only enough to immunize a small proportion of the globe, so provision of vaccine to those most vulnerable to this virus needed to be prioritized. usually vaccine is given primarily to those most susceptible to poor outcome from infection by seasonal influenza, namely the elderly. in the uk, from to , % of those who died from seasonal influenza were > years old. however, with the pandemic virus only % of deaths were in the > demographic. true to form, those elderly individuals who did succumb to the pandemic influenza suffered a severe illness, with a case fatality rate of . %, indicating the virus was able to cause serious morbidity in those who were immunologically susceptible [ ] . the first infection with an influenza virus in children can often be quite severe. johnson et al. showed that the high incidence of unexpected paediatric fatalities from the fujian h n seasonal drift variant in was linked with a higher than usual infection rate for seasonal influenza in the young in that year, possibly explained by a more drastic antigenic drift than in immediately previous years [ ] . similarly when a novel pandemic virus circulates widely, the incidence rate in the very young is particularly high and their clinical course in the face of lack of any relevant immunological experience is often severe. indeed during the pandemic, the highest mortality rates were observed in those under year of age [ ] . in addition since school age children are major transmitters of influenza, there is good logic in targeting them in pandemic and seasonal immunization campaigns because overall community incidence may be curtailed in this way [ ] [ ] [ ] [ ] . the pandemic virus was certainly able to infect and transmit well within the paediatric cohort. in the uk one in three children and in hong kong half of the children had been infected after the first wave [ , ] , supporting the global observations that school aged children and young adults were most likely to contract influenza [ ] . generally seasonal influenza causes two paediatric deaths per million people, while ph n , by mid- , had been responsible for - deaths per million in the netherlands and the uk respectively and per million in argentina in the paediatric cohort [ , [ ] [ ] [ ] . in their study of paediatric mortality from pandemic influenza in the uk, sachedina and donaldson identified deaths in the - year old age group directly attributable to infection with the virus. as in similar studies across the world, they described common symptoms including fever, cough and shortness of breath [ , , [ ] [ ] [ ] [ ] . the uk study observed that a combination of neurological, gastrointestinal and respiratory disease was present in more than half the deaths, an observation again echoed in other countries. indeed pre-existing neurological disorders have frequently been listed as a co-morbidity [ , , [ ] [ ] [ ] [ ] [ ] [ ] . half of those of school age who died in the uk attended schools for those with special needs [ ] . as with adults, bacterial coinfections were often observed; in the us % of paediatric deaths were associated with secondary bacterial infections and in the uk % were associated with laboratory confirmed cases [ , ] . pregnant women appear to be especially at risk from complications of influenza of either a seasonal or pandemic nature, especially during the second and third trimesters [ ] . this increased susceptibility has been ascribed to mechanical changes within the body, which act to increase the pressure on the cardiovascular system, including an increased heart rate, stroke volume and oxygen consumption set against a decreased lung capacity [ , ] . this may also account for increased risk in obesity. in addition, hormonal changes in pregnancy cause what might be broadly termed a swing away from cell mediated immunity and a bias towards the humoral system that may affect the ability to clear the virus [ , ] . on the other hand humoral immunity is also not complete in pregnancy and depletion in the levels of igg were observed in pregnant women who died in the ph n pandemic [ ] . there is evidence from previous pandemics that the mortality rate was high amongst pregnant women: in the pandemic between % and % of those pregnant who contracted influenza died. in the percentage of deaths was lower, but still considerable at % [ ] . there is also evidence of complications; of those pregnant women who developed pneumonia but survived during the pandemic, more than % did not carry the foetus to full term [ ] . in the pandemic it was very evident that other co-morbidities increased susceptibility to severe influenza infection. these included obesity, asthma and chronic obstructive pulmonary disease (copd), diabetes, immunosuppression, heart conditions and neurological complications. whilst only a third of those who were admitted to intensive care had co-morbidities, over three quarters of those who died did [ ] . in the uk, the flucin database collected data from all those admitted to hospital with influenza during the pandemic first wave. co-morbidities were described for around % cases, leaving a significant number of young healthy adults that suffered severe disease and even death despite no obvious prior predisposition for bad outcome [ ] . in the us, a study of the first fatal cases caused by ph n found that % of them had bacterial coinfections, with staphylococcus aureus and streptococcus pneumoniae being the most common pathogens [ ] . other fatal case studies have put the incidence of bacterial coinfections between % and % and also included streptococcus pyogenes in the list of common bacterial coinfections [ , , ] . in argentina, coinfection with streptococci increased the likelihood of severe outcome with an odds ratio of [ ] . however in the uk, high incidence of bacterial coinfection was less evident [ ] . the effect of bacterial superinfection on the outcome of infection with pandemic h n is likely to have been affected by differences in the bacterial strains circulating in communities around the world at the time and this may, in part, account for the widely different case fatality rates seen in different areas. there is a well-established system in place for the generation of seasonal influenza vaccines; the dominant circulating strains are carefully monitored and predictions are made annually about which viruses are likely to predominate in the forth-coming 'flu season. the chosen seasonal viruses are recombined with the internal segments of the high growth a/puerto rico/ / (pr ) vaccine backbone strain, to create viruses with ha and na antigens from seasonal strains that can be readily amplified in eggs. similarly for the pandemic vaccine, a reassortant virus bearing the h ha and n na genes of the pandemic strain a/california/ / on a high growth body was used to generate high yield virus in eggs. however, vaccine production problems became apparent early during production phase when manufacturers realized that the growth of the cal/ / reassortant was only - % of that seen for the seasonal strains. eventually a higher growth variant was obtained. in all about versions of h n / pandemic vaccine were generated in multiple countries by different manufacturers, with either wild type or reassortant viruses grown traditionally in eggs or in cell based systems and vaccines produced as spilt (just the ha and na genes) preparations, whole inactivated virion preparations or, in one case, a live attenuated virus. using a strategy based on development of h n pandemic vaccines, the most widely used pandemic vaccine in the uk was an inactivated vaccine generated by gsk that was administered combined with as adjuvant (composed of a-tocopherol, squalene and polysorbate emulsion) a chemical mix added to enhance and prolong the immunogenic response and reduce the amount of ha protein required per dose to achieve immunity (antigen sparing). the immunogenicity of the pandemic vaccine was in fact much higher than expected based on experience of clinical trials with the h n equivalent. in the end, a single dose of adjuvanted vaccine was sufficient to achieve seroconversion in adults. although it was expected that two doses would be needed in children, who usually require a prime boost regimen for effective levels of antibody to be achieved, a single dose was eventually used as it turned out to be adequately immunogenic and significantly less reactogenic after the first dose than the second [ ] . this vaccine was recorded as having a % effectiveness despite the relatively small doses of . mg of ha protein (unadjuvanted vaccines typically contain - mg). other adjuvants were also trialled globally including alum (aluminium hydroxide) in china and russia and another oil-in-water adjuvant broadly similar to aso called mf in korea and italy. clinical trials were run using the proprietary sanofi-pasteur af adjuvant in the usa, europe and asia [ ] . live attenuated vaccine (laiv) for pandemic was widely administered in the us. other vaccine strategies that were not yet licensed have been researched using the h n virus as antigen. these include: the use of virosomes (lipid vesicles) that have the ha and na proteins scattered through the bilayer, live recombinant adenovirus vaccines that express the ha protein, virus like particles in which the ha, na and m are expressed in insect cells which are infected with a recombinant baculovirus, these are purified and self assembled into immunogenic particles, finally plants infected with a transformed agrobacterum vector that generate ha proteins [ ] . although the outcome of infection in most people infected with pandemic virus was mild, in animal models this virus causes more severe disease than recent seasonal h n viruses. itoh et al., compared seasonal h n (a/kawasaki/utk- / ) and pandemic h n (a/california/ / ) viruses in a number of animal models. interestingly, infected mini-pigs remained relatively asymptomatic. in contrast, ph n virus caused severe lung pathology in mice, ferrets and macaques including lung lesions and damage caused by the infiltration of inflammatory mediators to a greater extent than was observed with infection with the seasonal viruses [ , , ] . van de brand et al., infected ferrets intratracheally with very high doses of seasonal h n , ph n or hpai h n virus and found that infection with ph n caused pathology intermediate between seasonal influenza and h n and could lead to severe pneumonia and death in this model [ ] . infection of alveolar pneumocytes, not observed with the seasonal virus [ , ] may correlate with the more profound binding of the ph n ha to a- , linked sa [ ] which tends to be located deeper into the lung [ ] . the difference between the animal models and the epidemiology in humans suggests that a basal level of existing immunity in the human population has protected against the moderately severe disease this virus can cause in immunologically naive experimental animals. there are two antiviral drug classes currently available to treat influenza. adamantanes (amantadine and rimantadine) are directed against the ion channel m protein and prevent the uncoating of the virus genome early in infection. the second class of drugs, the neuraminidase inhibitors (oseltamivir -tamiflu ® and zanamivir-relenza ® ) were rationally designed to block the active site of the neuraminidase of the influenza virus. na acts to cleave the sa receptors on the surface of the host cell, allowing the release of newly formed virions which can then infect uninfected cells. unfortunately, influenza viruses readily developed resistance to the adamantanes through point mutations at residues , , , or in the m protein, with no compromise in viral fitness [ , ] . % of the seasonal h n isolated in the us and asia contain a resistant phenotype and the s n mutation was already present in the ph n at the time it crossed into humans [ , ] . the nai drug class has therefore become a favourite for stockpiling anti-influenza therapies. the first of these drugs to reach the clinic was zanamivir (relenza) but use of this drug is hindered by the necessity to inhale it because it is not orally bioavailable. the second nai oseltamivir (tamiflu ® ) benefits from a convenient oral formulation, good bioavailability and is suitable for use in paediatric and adult populations. data have not yet emerged fully for its effects in those > years of age or the immunocompromised [ ] . according to the cochrane review of efficacy in , if zanamivir or oseltamivir are used to treat an infection h after onset of symptoms, there is a 'modest' reduction in influenza symptoms within . days in adults and day in children for zanamivir and . days in adults and . days in children for oseltamivir [ , ] . as prophylactics, both drugs fare well, in control groups taking the medications during seasonal influenza, there was a reduction in incidence of % and % for zanamivir and oseltamivir respectively. for post-exposure prophylaxis there were % and % relative reductions in infection after zanamivir and oseltamivir administration respectively [ , ] . resistance to oseltamivir can emerge, but early experiments indicated that mutations such as h y (n numbering, h y in n ), would confer a fitness cost to the virus by reducing na affinity for the sa substrate [ , ] . thus, it was assumed that the resistance mutation would not persist in the community. however, by , ~ % of seasonal h n viruses had acquired the h y mutation that was associated with the resistant phenotype without fitness cost [ , ] . the lack of fitness cost can be ascribed to compensating mutations in the na protein [ , ] . the obvious fear was that the ph n virus would develop oseltamivir resistance given the widespread use of the drug in the early waves of the pandemic. ph n viruses with the h y mutation have been isolated, however these were predominantly in those undergoing prolonged treatment regimens (often in immunocompromised patients) or through the use of low dose prophylaxis [ , ] . at the time of writing, there had not been widespread transmission spread of the resistant strain. indeed the fitness cost to this strain of virus is still under debate, with different labs publishing conflicting results [ ] [ ] [ ] . there is historical evidence that implies that during the pandemic, the second and third waves were more severe than the first. it has been suggested that the virus acquired mutations as it circulated in its new human host and these 'hotted up' its virulence. thus it is important to identify any mutations that may similarly increase virulence of the ph n strain. in particular it was possible that critically ill or deceased patients had been infected with a virus variant that had more pathogenic potential than the viruses that predominated in the community. the sequence of viruses from such cases has been analysed in a number of studies [ ] [ ] [ ] [ ] [ ] [ ] . one of the interesting mutations observed is a d g (h numbering, d g in h ) mutation in the ha protein. % of critical cases in norway and . % of the critically ill in hong kong had this mutation [ ] . in scotland this mutation was only found in patients who were critically ill ( . %) [ ] . however it is not clear that this mutation alone is responsible for poor outcome: the d g mutation was found in the virus from a nasopharyngeal swab and tracheal aspirate from a year old man admitted to intensive care with pneumonia and ards. however the same virus transmitted to a contact case, but did not lead to severe illness despite the latter individual having two hallmark co-morbidities, namely obesity and diabetes [ ] . although d g was detected predominately in viruses from critical cases in greece, it was also isolated in two mild cases of the disease [ ] . it has been suggested that some of the reported isolates with this change are the results of egg adaptation during the culture period [ ] . in addition, the prevalence of this mutation in the critically ill has been ascribed to factors such as sampling bias, the critically ill being more likely to be genotyped than the mild cases. the presence of this mutation enhances binding of h ha to a , linked sa receptors [ ] . the proposed mechanism by which such a mutation may enhance virulence is that the ability to bind more efficiently to a , sa receptors extends the lung tropism of the virus to bind ciliated cells that may then be unable to clear virus efficiently via the mucociliary escalator [ ] . additionally, increased binding to type ii pneumocytes and macrophages in the alveoli and to submucosal glands in the trachea and bronchi may enhance lung damage [ ] . however using reverse genetics to engineer this point mutation into an otherwise isogenic background, it was shown that the d g change was not associated with an increase in virulence in the ferret or guinea pig models and remains easily transmitted between guinea pigs [ ] . the mutation did result in a lower infectious dose for infection of mice who predominately express the a , , linked form of sa receptor [ ] . the pb segment has a second reading frame (+ ) which encodes a small protein ( - amino acids), pb -f [ ] . this protein has been assigned two functions, induction of apoptosis through its mitochondrial targeting c terminal domain and a role in lung inflammation [ ] [ ] [ ] [ ] [ ] . a proposed third function, relating to polymerase function and reflected by the retention of the pb protein in the nucleus appears to be strain specific [ , ] . viruses with intact pb -f genes cause increased pathology in the mouse model [ ] and also predispose the host to secondary bacterial infections and subsequent pneumonia. mice infected with a pr virus containing the full length pb -f suffered greater weight loss and increased mortality when subjected to a secondary bacterial infection than mice infected with a pr with a truncated form of pb -f [ ] . however in natural isolates, particularly those from swine, the pb -f gene is not always full length. zell et al. analysed the influenza a sequences available in genbank in [ ] . they found that % avian strains possessed the full length pb -f , but in contrast only % of swine viruses and % of human viruses had the full length gene. classical swine influenza strains have truncated forms of pb -f with premature stop codons after , and residues [ ] . truncation of the pb -f gene to just amino acids also occurred in seasonal h n viruses in the s. loss of the c terminus of pb -f removes the mitochondrial targeting sequence of the protein, abrogating its interaction with host proteins ant and vdac and reducing its ability to trigger apoptosis in immune cells [ , ] . in addition this region of the protein appears to harbour pro-inflammatory properties. indeed, peptides generated to contain amino acid sequence from the c-terminal region of pb -f generated an inflammatory response when administered to mouse lung. two days post exposure mice lost up to % body weight. interestingly the same peptide derived from recent h n seasonal virus contains amino acid differences from early h n homologues that appear to abrogate the pro-inflammatory function. inflammation triggered by pb -f peptides from highly virulent strains such as influenza may predispose to secondary bacterial pneumonia [ ] . indeed, some highly virulent viruses such as h n and h n viruses possess a point mutation in this region of pb -f , n s, that is partly responsible for their enhanced morbidity and mortality in mice [ ] . the ph n influenza virus has a pb -f gene truncated to just amino acids in length which is inactive. using reverse genetics to engineer viruses in which full length protein was restored, hai et al. noted no increase in virulence in mice or ferrets [ ] . even the introduction of the notorious like n s point mutation did not affect the outcome of infection in these models. thus acquisition of virulence by restoration of this gene to the pandemic virus seems unlikely [ ] . the tropism of influenza virus is not only determined by its receptor use. sa is a widely distributed cell surface sugar but influenza in humans is largely restricted to the respiratory tract. the reliance on host cell proteases to cleave and thus activate the fusogenic properties of the ha protein determines the organs in which the virus can undergo productive infection. in humans the abundance of clara tryptase in respiratory secretions allows the virus efficient replication in the lung [ ] . in highly pathogenic avian influenza viruses such as h and h strains, the insertion of a polybasic motif allows the ha to be cleaved by ubiquitous proteases such as furin, facilitating systemic infection [ ] . despite the high mortality rates of those afflicted with the virus, it does not contain the polybasic cleavage site found in the highly pathogenic h n viruses. the acquisition of this virulence motif in h and h subtypes of ha occurs during amplification in poultry [ , ] . this motif has not been seen in any ph n isolates in or , and ph n viruses remain dependent on the addition of trypsin to growth media for their propagation in cell culture. the influenza virus counteracts the otherwise suppressive effect of the interferon response using a nonstructural protein ns , reviewed in detail by hale et al., [ ] . ns works in at least two ways to prevent induction of interferon. firstly in the cytoplasm ns binds dsrna and other rnas that are the likely triggers of innate immunity as well as forming a complex with the host cell pattern recognition receptor rig-i and its controlling protein trim . secondly in the nucleus some ns proteins can bind to the host cell factor cpsf and in doing so they suppress the processing of newly synthesized mrnas and prevent their export to the cytoplasm. this latter function is strain specific. it has been suggested that viruses that have enhanced ability to perform both these functions may induce a more severe disease because they can evade the innate immune response more efficiently. indeed introduction of cpsf binding ability to the lab adapted pr vaccine strain that usually lack this function enhanced its virulence in mice [ ] . the ph n virus lacks cpsf binding capacity. however hale et al. have shown that reintroduction of this phenotype did not affect virulence of ph n in ferrets or mice [ ] . despite lacking cpsf binding capacity, the ph n virus induces very low levels of interferon in infected cells [ ] . the and pandemic viruses both displaced the previously circulating subtypes. in contrast the re-emergence of h n in humans in was not associated with subtype displacement likely because a large cohort of the older population was not susceptible to the virus and therefore remained viable hosts for the contemporary h n viruses. similarly due to residual immunity in the elderly, ph n has not displaced the h n subtype. initially it was believed that the seasonal h n subtype may have gone extinct after ph n emerged, as there was a period of many months where this virus was not isolated, however recently seasonal h n isolates have been detected in texas [ ] . the trivalent vaccine administered in contains ph n , h n and influenza b virus antigens but no seasonal h n component. influenza is a seasonal disease. infections peak once a year in the cold, dry season in the northern or southern hemispheres, although in the tropics the seasons are less clearly separated and it may be that virus continually circulates [ ] . the royal college of general practitioners (rcgp) scheme in the uk has monitored the incidence of ili since the emergence of the h n subtype in the pandemic (fig. ) , the re-emergence of related h n and seasonal h n strains has been observed year on year and is due to the capacity of the virus to accumulate small point mutations in ha and na antigens, the process called antigenic drift. these mutations occur at antigenic sites and allow the circulating virus to evade immune suppression by throwing off antibody binding through confirmation changes or glycosylation events. accumulated drift mutations may ultimately change the phenotype of the virus. the virus may alter its affinity or specificity for the receptors on the host cell surface in its efforts to avoid the immune response [ ] . indeed it is clear that, as it has evolved over four decades in humans, the h n virus has changed its receptor binding affinities with phenotypic consequence [ , ] . as herd immunity increases against the newly emerged ph n virus, it is not in doubt that antigenic drift will occur. however, the resulting phenotypic changes are unknown and currently unpredictable. moreover since the virus has re-infected swine, a species in which frequent reassortments occur [ ] , the evolution of this h n virus and the consequence of reassortment events in animals for human disease remain to be observed in the coming years. the influenza pandemic: lessons for and the future updating the accounts: global mortality of the - "spanish" influenza pandemic. bulletin of the history of medicine study of influenza c virus infection in france swine influenza : i. experimental transmission and pathology the etiology of swine influenza the susceptibility of mice to the viruses of human and swine influenza virus obtained from influenza patients influenza: the mother of all pandemics. emerging infectious diseases origin and evolution of the "spanish" influenza virus hemagglutinin gene initial genetic characterization of the "spanish" influenza virus science characterization of the reconstructed spanish influenza pandemic virus characterization of the "spanish" influenza virus neuraminidase gene sequence of the pandemic influenza virus nonstructural gene (ns) segment and characterization of recombinant viruses bearing the ns genes characterization of the "spanish" influenza virus matrix gene segment novel origin of the pandemic influenza virus nucleoprotein gene characterization of the influenza virus polymerase genes severity of pneumonia due to new h n influenza virus in ferrets is intermediate between that due to seasonal h n virus and highly pathogenic avian influenza h n virus. the journal of infectious diseases an early "classical" swine h n influenza virus shows similar pathogenicity to the pandemic virus in ferrets and mice pathogenicity and immunogenicity of influenza viruses with genes from the pandemic virus experimental infection of pigs with the human pandemic influenza virus influenza pathogenesis: lessons learned from animal studies with h n , h n spanish, and pandemic h n influenza viral rna polymerase complex promotes optimal growth of virus in the lower respiratory tract of ferrets pathogenesis of pandemic influenza a (h n ) and triple-reassortant swine influenza a (h ) viruses in mice infl uenza and pneumococcal pneumonia clinical infectious diseases : an official publication of the infectious diseases society of america predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. the journal of infectious diseases macaque proteome response to highly pathogenic avian influenza and reassortant influenza virus infections the ns protein of the pandemic influenza virus blocks host interferon and lipid metabolism pathways global host immune response: pathogenesis and transcriptional profiling of type a influenza viruses expressing the hemagglutinin and neuraminidase genes from the pandemic virus aberrant innate immune response in lethal infection of macaques with the influenza virus multiple reassortment events in the evolutionary history of h n influenza a virus since influenza epidemiology-past, present, and future. critical care medicine global epidemiology of influenza: past and present the re-emergence of h n influenza virus in : a cautionary tale for estimating divergence times using biologically unrealistic sampling dates historical perspective-emergence of influenza a (h n ) viruses genetic relatedness between the new epidemic strains (h n ) of influenza and human influenza strains isolated between and (h n ) recent human influenza a (h n ) viruses are closely related genetically to strains isolated in pathogenicity of h influenza viruses for ducks. archives of virology avian influenza virus infections. iv. response of pheasants, ducks, and geese to influenza a-turkey-wisconsin- virus avian influenza virus surveillance and wild birds: past and present effects of ph, temperature, and salinity on persistence of avian influenza viruses in water persistence of avian influenza viruses in water distinct lineages of influenza virus h hemagglutinin genes in different regions of the world infection of human airway epithelium by human and avian strains of influenza a virus changes in in vitro susceptibility of influenza a h n viruses to a neuraminidase inhibitor drug during evolution in the human host who | cumulative number of confirmed human cases of avian influenza a/(h n ) reported to who surveillance of influenza-like illness in england and wales during - transmissibility of swine flu at fort dix swine influenza a outbreak potential for transmission of avian influenza viruses to pigs antigenic and genetic characteristics of swine-origin a(h n ) influenza viruses circulating in humans origins and evolutionary genomics of the swine-origin h n influenza a epidemic molecular basis for the generation in pigs of influenza a viruses with pandemic potential mutations in the hemagglutinin receptor-binding site can change the biological properties of an influenza virus early alterations of the receptor-binding properties of h , h , and h avian influenza virus hemagglutinins after their introduction into mammals receptor specificity and transmission of h n subtype viruses isolated from the pandemic of mutations in h n influenza virus hemagglutinin that confer binding to human tracheal airway epithelium in vitro assessment of attachment pattern and replication efficiency of h n influenza a viruses with altered receptor specificity evolving complexities of influenza virus and its receptors glycan microarray analysis of the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities recent avian h n viruses exhibit increased propensity for acquiring human receptor specificity printed covalent glycan array for ligand profiling of diverse glycan binding proteins differential receptor binding affinities of influenza hemagglutinins on glycan arrays receptor-binding specificity of pandemic influenza a (h n ) virus determined by carbohydrate microarray influenza a (h n ) virus. emerging infectious diseases pandemic influenza a (h n ) and mortality in the united kingdom: risk factors for death the role of the health protection agency in the "containment" phase during the first wave of pandemic influenza in england in incidence of pandemic influenza a h n infection in england: a cross-sectional serological study. the lancet h n ) -update world health organisation, global alert response report of the th meeting on the evaluation of pandemic influenza vaccines in clinical trials world health organization fatal cases of influenza a in childhood paediatric mortality related to pandemic influenza a h n infection in england: an observational population-based study. the lancet complications of seasonal and pandemic influenza strategies for mitigating an influenza pandemic emerging infectious diseases school closure and mitigation of pandemic (h n ) , hong kong. emerging infectious diseases incidence of pandemic influenza a h n infection in england: a cross-sectional serological study the infection attack rate and severity of pandemic h n influenza in hong kong population-based surveillance for pandemic influenza a (h n ) virus in guatemala pediatric hospitalizations associated with pandemic influenza a (h n ) in argentina surveillance of hospitalisations for pandemic influenza a(h n ) in the netherlands assessing the burden of influenza and other respiratory infections in england and wales. the journal of infection radiographic study of severe influenza-a (h n ) disease in children hospitalized children with influenza a (h n ) infection in shenzhen update on the pandemic influenza a h n in children. current opinion in pediatrics pandemic influenza a (h n ) outbreak among school-aged hiv- -infected children. clinical infectious diseases: an official publication of the infectious diseases society of america pandemic a(h n ) influenza: review of the southern hemisphere experience influenza a (ph n ) infection in children admitted to a pediatric intensive care unit: differences with other respiratory viruses. pediatric critical care medicine: a journal of the society of critical care medicine and the world federation of pediatric intensive and critical care societies clinical aspects of pandemic influenza a (h n ) virus infection pandemic influenza a(h n ) virus illness among pregnant women in the united states pneumonia in pregnancy pandemic influenza and pregnant women emerging infections and pregnancy. emerging infectious diseases association between severe pandemic influenza a (h n ) virus infection and immunoglobulin g( ) subclass deficiency. clinical infectious diseases: an official publication of the infectious diseases society of america risk factors for hospitalisation and poor outcome with pandemic a/h n influenza: united kingdom first wave pandemic influenza a (h n ): pathology and pathogenesis of fatal cases in the united states pulmonary pathologic findings of fatal pandemic influenza a/h n viral infections lung pathology in fatal novel human influenza a (h n ) infection. american journal of respiratory and critical care medicine streptococcus pneumoniae coinfection is correlated with the severity of h n pandemic influenza safety and immunogenicity of as b adjuvanted split virion versus non-adjuvanted whole virion h n influenza vaccine in uk children aged months- years: open label, randomised, parallel group, multicentre study pathogenesis and transmission of swine-origin a(h n ) influenza virus in ferrets in vitro and in vivo characterization of new swine-origin h n influenza viruses avian flu: influenza virus receptors in the human airway incidence of adamantane resistance among influenza a (h n ) viruses isolated worldwide from to : a cause for concern. the lancet virulence of rimantadine-resistant human influenza a (h n ) viruses in ferrets. the journal of infectious diseases the origin and global emergence of adamantane resistant a/h n influenza viruses susceptibility of antiviral drugs against influenza a (h n ) virus. biochemical and biophysical research communications targeting pandemic influenza: a primer on influenza antivirals and drug resistance neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis bmj influenza virus carrying neuraminidase with reduced sensitivity to oseltamivir carboxylate has altered properties in vitro and is compromised for infectivity and replicative ability in vivo the h y mutation in the influenza a/ h n neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo oseltamivir-resistant influenza virus a (h n ), europe, - season. emerging infectious diseases structural basis for oseltamivir resistance of influenza viruses enzymatic properties of the neuraminidase of seasonal h n influenza viruses provide insights for the emergence of natural resistance to oseltamivir oseltamivir-resistant influenza a pandemic (h n ) virus, hong kong, china emerging infectious diseases emergence of oseltamivir-resistant pandemic h n virus during prophylaxis oseltamivir-resistant pandemic h n / influenza virus possesses lower transmissibility and fitness in ferrets oseltamivir-resistant variants of the pandemic h n influenza a virus are not attenuated in the guinea pig and ferret transmission models oseltamivir-resistant pandemic a/ h n virus is as virulent as its wild-type counterpart in mice and ferrets occurrence of haemagglutinin mutation d g in pandemic influenza a(h n ) infected patients in the west of scotland transmission of hemagglutinin d g mutant strain of pandemic (h n ) virus. emerging infectious diseases molecular and phylogenetic analysis of the haemagglutinin gene of pandemic influenza h n viruses associated with severe and fatal infections quasispecies of the d g substitution in the hemagglutinin of pandemic influenza a(h n ) virus from patients with severe disease in hong kong, china. the journal of infectious diseases altered receptor specificity and cell tropism of d g haemagglutinin mutants from fatal cases of pandemic a(h n ) influenza d g mutation in the hemagglutinin protein found in severe cases of pandemic influenza a (h n ) in spain. diagnostic microbiology and infectious disease preliminary review of d g amino acid substitution in the haemagglutinin of pandemic influenza a (h n ) viruses. relevé épidémiologique hebdomadaire/section d'hygiène du secrétariat de la société des nations = weekly epidemiological record/health section of the secretariat of the league of nations virulence-associated substitution d g in hemagglutinin of pandemic influenza a(h n ) virus affects receptor binding detection of expression of influenza virus receptors in tissues of balb/c mice by histochemistry. veterinary research communications a novel influenza a virus mitochondrial protein that induces cell death influenza virus pb -f protein induces cell death through mitochondrial ant and vdac influenza a virus pb -f protein contributes to viral pathogenesis in mice the influenza a virus pb -f protein targets the inner mitochondrial membrane via a predicted basic amphipathic helix that disrupts mitochondrial function expression of the influenza a virus pb -f enhances the pathogenesis of viral and secondary bacterial pneumonia the effects of influenza a virus pb -f protein on polymerase activity are strain specific and do not impact pathogenesis the proapoptotic influenza a virus protein pb -f regulates viral polymerase activity by interaction with the pb protein prevalence of pb -f of influenza a viruses. the journal of general virology the proapoptotic influenza a virus protein pb -f forms a nonselective ion channel improving therapeutic strategies for secondary bacterial pneumonia following influenza. future microbiology a single mutation in the pb -f of h n (hk/ ) and influenza a viruses contributes to increased virulence pb -f expression by the pandemic h n influenza virus has minimal impact on virulence in animal models the multifunctional ns protein of influenza a viruses. the journal of general virology glycine in the non-structural protein ns determines virulence of influenza a virus strain pr without affecting the host interferon response inefficient control of host gene expression by the pandemic h n influenza a virus ns protein pandemic h n influenza a virus induces weak cytokine responses in human macrophages and dendritic cells and is highly sensitive to the antiviral actions of interferons texas state health services the global circulation of seasonal influenza a (h n ) viruses hemagglutinin receptor binding avidity drives influenza a virus antigenic drift changes in in vitro susceptibility of influenza a h n viruses to a neuraminidase inhibitor drug during evolution in the human host reassortment of pandemic h n / influenza a virus in swine isolation and characterization of a novel trypsin-like protease found in rat bronchiolar epithelial clara cells. a possible activator of the viral fusion glycoprotein influenza virus hemagglutinin with multibasic cleavage site is activated by furin, a subtilisin-like endoprotease molecular analyses of the hemagglutinin genes of h influenza viruses: origin of a virulent turkey strain the overall evolution of the h influenza virus haemagglutinins is different from the evolution of the proteolytic cleavage site key: cord- - l le authors: yang, honglin; pang, xiaoping; zheng, bo; wang, linxian; wang, yadong; du, shuai; lu, xinyi title: a strategy study on risk communication of pandemic influenza: a mental model study of college students in beijing date: - - journal: risk manag healthc policy doi: . /rmhp.s sha: doc_id: cord_uid: l le purpose: to understand the characteristics of risk perception of influenza pandemic in college students with prominent frequency and the differences between these risk perceptions and professionals. then, offering a proposal for the government to improve the efficiency of risk communication and health education. methods: according to the mental model theory, researchers first draw a framework of key risk factors, and then they ask these students about the understanding of the framework with questionnaire and then making concept statistics and content analysis on the respondents’ answers. results: researchers find some students’ misunderstanding of pandemic including excessive optimism to the consequences of a pandemic, a lack of detailed understanding of mitigation measures, and negative attitudes towards health education and vaccination. most students showed incomplete and incorrect views about concepts related to the development and exposure factors, impact and mitigation measures. once threatened, it may lead to the failure of decision-making. the majority of students we interviewed had positive attitudes towards personal emergency preparedness for a pandemic influenza and specialized health education in the future. conclusion: researchers suggest that the government should make a specific pandemic guidance plan by referring to the risk cognitive characteristics of college students shown in the research results, and update the methods of health education to college students. influenza, which is a highly variable infectious disease that can quickly evolve into a pandemic, can pose a significant threat to people's health. the corresponding emergency response measures require the active cooperation of the public to work effectively. because of its wide range of impact and potential mortality, effective risk communication will help the public understand information related to influenza. compared to risk communication in other fields, when public health events occur, the government often turns to experts to ask them what the public should know. so, it is a challenge that how to effectively transform scientific knowledge into useful structures and non-professional backgrounds. our researchers use influence diagrams from mental model interview to analyze the critical risk factors of flu, which can improve student`s ability of decision-making to maintain their physical health. [ ] [ ] [ ] [ ] [ ] morgan et als monograph on mental model theory argues that everyone relies on their mental models to understand information. it grows into a unique and intrinsic pattern as individuals grow, similar to a workflow chart. splitting the outside world into multiple components to help us understand may not be perfect; however, it affects our way of thinking and behavior choice. , , a person's mental model is influenced by various factors, including personal experience, acquired learning, and living environment, and these factors are changeable and also important in affecting our health-related behaviors. , [ ] [ ] [ ] [ ] [ ] therefore, targeted education can help an individual correct misunderstanding in their mental models and then improve their risk management. in china, there is no application of mental model theory in the field of health education and no special pandemic preparedness guideline for the general public. however, in western countries, particularly the united states, many scholars have conducted substantial research in this area. lazrus et al have studied the public mountain flood communication framework in boulder county, colorado state. casman et al used the influence map to establish a dynamic risk model for waterborne cryptosporidiosis, which defines "key awareness variables" in risk communication and assigns scores for evaluation. our researchers hope to use the mental model theory to analyze the most critical risk factors of influenza pandemic from a broader perspective and find out college students` risk perception of these factors. the understanding and cognitive characteristics help improve the communication work of the government, which is the aim of this article. this study refers to the impact map formed by morss et al in the flood risk communication of boulder county and draws the risk factor framework of the influenza pandemic. the entire frame is an analysis of disaster events from a macro perspective, including "causes," "development," "response," "event impact" and "risk information dissemination." then, through literature research and expert consultation, the researchers summarized the concept of the communication framework and initially formed its content suitable for the influenza epidemic. the content of the whole frame consists of the causes of influenza epidemics, the impact of pandemics, emergency preparedness and strategies of different groups, risk information, and emergency response decisions, as shown in figure . the researchers subsequently searched for the corresponding supporting documents according to the content of the framework and conducted expert seminars. combined with the materials of the literature and expert opinions, the authors initially wrote identical concept items under each part of the frame. finally, we used the delphi method to invite experts from the related fields to judge the structure, importance and scientific nature of these items. the purpose of mental model interviews is to determine which concepts or beliefs are "out there" with sufficient frequency such that in smaller samples, these concepts or beliefs become reasonable. there is no standard method for determining sample size in relevant theories and research practice. according to professor morgan's monograph and related research examples, the sample size for a mental model interview should be ~ , at which point new information has reached saturation. based on these research facts, combined with the research design of lazrus and morss, , we recruited the first respondents from randomly selected non-medical college by telephone and posters. to avoid confounding bias, these students are also from non-medical majors (including russian, finance, urban planning and marketing) and have not studied medical related professional courses. after all the investigations have been completed, we discussed the results and deleted two poor interview results, and then drew a line chart of information saturation according to the number of concepts mentioned by the respondents in figure . we found that after the nd interviewee, information saturation began to show a downward trend, and subsequent respondents did not propose new concepts. we believe that the information provided by these respondents can meet the sample size required for the analysis of this study, because the purpose of mental model study is not to use statistical methods to analyze the distribution of some risk cognition in the population, but to find out which concepts or beliefs, are "out there" with some reasonable frequency, so as to help government departments identify what should be focused on when developing guidance programs and health education materials for this population. the interview began with an open question, such as "please tell us about the pandemic." our investigators guided the respondents to elaborate on their main concepts, then details of the outbreak, as well as the mitigation measures that should be employed. if the interviewer had experienced emergencies, then they were encouraged to talk about the decision or idea at that time. the interview results were subsequently transcribed, encoded and classified using the coding software atlas.ti. we also conducted a quantitative analysis of the results of the compilation, then created a statistical chart, observed the degree of attention of the respondents, and compared these results with the risk perception of experts to determine the interviewee's understanding of the related concepts and other features. the questions used in this interview refer to a questionnaire in the study of skarlatidou et al. the interview covers the content in figure . two researchers simultaneously coded the results of the interviews. the classification consistency index (holsti reliability) of the coder was subsequently calculated, which fluctuated between . and . , and the average reliability statistic was . . according to the study of boyatzis and burrus, the coding reliability of trained different coders ranges from . to . ; therefore, the reliability of the coder was within the normal range and displayed adequate consistency. information saturation trend provided by respondents. for each of the respondents' answers to the number of concepts noted, the researchers first mapped the scatter plots. then, to better show the increase and decrease in the information provided by the respondents, polylines were used to connect the points. the content of the concept is derived from the framework of figure and is described by the responses of all respondents. here is the result of two rounds of delphi expert consultation. the value of the authority coefficient is . (> . ), which indicates that the study has a good expert score. , , as shown in table , in the first round of expert consultation, the coordination coefficient of each item was . (p< . ), and in the second round of expert consultation, the coordination coefficient was . (p< . ), which was better than the first round and indicates that the opinions of the experts are consistent from the perspective of significance test. finally, we created a communication framework for an influenza pandemic, as shown in figure . it serves as the basis for our investigation of the problem content of college students and can also be regarded as a kind of "standardized communication content". the respondent may have a higher probability of taking the correct protective measures if he has a good understanding of the entire framework. communication framework of pandemic influenza. the frame is composed of six main conceptual dimensions; the central concept is the bold label, and the ndlevel concept in the box is the part. more complicated concepts in the framework are omitted; refer to the coding manual in the appendix. the whole frame contains concepts, and the arrowhead represents the influence relationship of each part. the analogy part is listed separately to describe the events associated with the respondents. note: table shows the statistical coefficient calculation results of the two delphi studies, and the p values of the two coefficients all meet the requirements. the researchers counted the percentage of respondents that mentioned a concept item. also, this study used a stacked bar chart to show the number of concepts mentioned by the respondents ( figure ). as shown in the graph, we distinguish the concept of different attributes in terms of dimensions (risk factors). the richness of the color can visually distinguish the depth of the mental model of each interviewee [the number of concepts mentioned by an interviewee], and we can determine which dimensions of the expert`s risk perception the public is highly aware of and in which areas the public lacks awareness. furthermore, the length of the bar graph reflects the number of concepts mentioned in the dimension: a taller bar graph reflects more relevant concept items indicated by the respondents and a deeper degree of understanding of the related content. for example, respondents , and knew more about the emergency response decisions during the pandemic, whereas interviewee # was less aware in this regard. figure shows the differences in thinking about the risk of and coping with the influenza pandemic among different groups. even with a higher education level, each college student interviewee displayed a significant difference in the depth and detail of their mental model. some of the respondents' mental models appear particularly "scarce" (such as respondents # and ). nearly all respondents discussed less information than the risk perception of experts. only one interviewee (interviewee # ) cited concepts that reflected almost all the parts of the communication framework in figure . the other students did not suggest many more new concepts in the interview. their conceptual descriptions reflect the concern for specific content and common cognitive deficiencies and misunderstandings. the following sections discuss these best features of the interview answers. the interactions between multiple factors may affect the formation and development of pandemic influenza. several factors mentioned by our respondents are shown in table ; % of the respondents believed that influenza virus variation was an essential cause of the pandemic. they used statements such as "new virus," "virus mutation," and "an unknown virus." additionally, % of the respondents referred to disease surveillance, which included "poor supervision of the source of infection" and "unchecked work", and they were more inclined to use terms to express their views (for example, "gene mutation", "isolation treatment", "infrared surveillance", and "take the body temperature"). forty-six percent of the respondents cited characteristics related to the international spread of the pandemic. interviewee # indicated "foreign virus carriers from foreign places into beijing." however, some respondents believed that climate factors could lead to flu cases because they confused pandemic influenza with seasonal flu, such as interviewee # , who answered "when the seasons change, people may catch a cold easily. if they do not pay attention, a pandemic will happen if they don`t do that." many respondents ( %) also cited the impact of population density, including densely populated places and more floating cities with higher risk areas for influenza. other factors were less frequently cited by less than % of interviewee, including virus resistance, viral power, avian influenza immunity, and a human lack of immunity to new viruses. compared to the experts, the mental models of many of the students interviewed contained only part of the communication framework. although some key factors were cited by most of the respondents, other essential factors were rarely cited or were misunderstood by the respondents. for example, interviewee # believed that the flu was a "foodborne disease" and "caused by drugs." for individuals infected with influenza, no respondents discussed the impact of vulnerable groups on the development of the pandemic, and there was no further detailed description of the virus variation. a full understanding of these information can help people to evaluate the risk level in the environment, including which situations may have a higher risk of infectious diseases. another neglected concept is the lethality of the virus. no respondents mentioned this concept or discuss the content related to us. in fact, the lethal rate is also an important indicator of a new infectious virus. from the perspective of scientific disease control, the lethal rate affects whether the virus has the characteristics of limited regional transmission (for example, ebola virus, its lethal rate is - %, making the virus only intermittently epidemic in individual countries and regions, with certain limitations in time and space.) from the perspective of promoting public participation in disease response, highrisk events can promote individual polar to make protective decisions. knowing the virulence of the virus can avoid the negative attitude to personal disease prevention caused by fluke psychology. as shown in table , approximately % of the respondents discussed the fatality of the flu, while only % of the respondents described the severe symptoms that could occur after the infection, such as interviewee # : " . . . if there goes a pandemic, it would be more than a common cold. runny nose and sneezing or, maybe, pneumonia?" none of the respondents cited complications related to influenza infection. even if a real pandemic is only composed of common symptoms of fever and fatigue, complications such as pneumonia, myocarditis, and bronchitis are the real causes of death in some vulnerable patients. , therefore, although most of the respondents understood that the flu could have serious health threats, they did not understand how people die as a result of the flu. these misunderstandings may be related to some respondents' personal and onesided understanding of the pandemic and the lack of targeted health education. for example, interviewee # stated "that is, people usually do not pay attention to clothes, then they catch a cold. it is quite a normal situation every year." most respondents also discussed the social and economic impacts of the pandemic, and % of the respondents referred to negative effects on schools, shops, public transport, and other infrastructure during the pandemic, such as interviewee # : "schools may shut down . . . the shops outside may be closed because of this disease, and the economy may be seriously affected because everyone will hide at home." most of the types of infrastructure, of which transportation was the most frequently cited, were generally quoted as examples of people during the sars or bird flu period, such as interviewee # who stated, "everyone is not going out at the time of the outbreak . . . wearing a mask if you have to go outside." thirty-two percent of the respondents were worried about overburdened hospital patients during the pandemic. some of the respondents ( %) also imagined disastrous consequences, including the impact of the pandemic on the community. according to interviewee # , for a long time . . . our life may be threatened, many people steal food and drugs and will be locked inside their house . . . not just the direct impact, it will bring other serious problems. although the respondents mentioned the relevant concepts in the communication framework, they fail to understand the severe damage that pandemic influenza could cause to individual health; moreover, they are not fully aware of panic actions during the outbreak. the most common panic behavior is to escape from the epidemic area. to avoid disaster is people's instinctive behavior, especially in the outbreak of infectious diseases. in fact, during the outbreak of the novel coronavirus (covid- ) in china, people in some areas fled the outbreak area. and it happened to be the chinese new year's holiday. lots of college students returned home to celebrate festival, which strongly increased the risk of virus transmission. although these situations have not caused irreparable serious consequences, they have also brought great interference to the case investigation and disease monitoring in all provinces of the country. surprisingly, there are % of the respondents believed that a negative impact of a flu pandemic would be minimal or more positive, and nearly all of them stated that it "feels like the pandemic is far away from me." according to interviewee # , it "is a kind of epidemic disease, but speaking of cold and flu, what is generally not a major disease, easier to treat the feeling, plus the pandemic, it is only a larger scope of infection, right?" the content reflects that some students do not pay substantial attention to public health and their health. more people choose to passively wait and accept the strategies and measures employed by the school or the state government; they lack the initiative to understand the relevant information and take preventive actions. the coping strategies in table are essential to pandemic emergency work and a necessary part of the communication framework in figure . twenty-nine percent of the respondents cited the importance of personal hygiene habits, such as wearing masks and isolating patients; however, there are not many people who provided detail regarding these aspects. a few respondents described these strategies on the government, organization, and individual levels. most of them referred to "masks" and "be far away from the cough" in the relevant description and noted details of whether to use a special mask or separate the patient from the family. for example, interviewee # stated: "if it is a more serious situation, we will wear a mask, and then the hospital will be more nervous about the flu . . . " another % of the respondents believed that there was no need to isolate the suspected patients, such as interviewee # : "you cannot go to the hospital first because most of the cases are not true flu, to the hospital may be isolated, so look first." for the government's decision-making, % of the respondents cited health education and counseling. most of them were willing to accept the necessary emergency response; over / of the respondents referred to influenza surveillance, public disinfection, and hospital treatment. these answers demonstrate these students still make mistakes and lack of understanding of the most effective protection decisions, although they have better educational backgrounds and a high degree of potential coordination. moreover, although vaccination is the most effective way to prevent the flu, only two of the respondents said they were willing to receive the flu vaccine, and the other respondents said they would not vaccinate themselves if it were not compulsory. "there is no need for voluntary vaccination" (respondents and ), "some vaccines may have side effects . . . it will hurt me" (interviewee ). notably, interviewee # , who originated from hong kong, was able to describe all the individual and government contingency strategies and discussed his own experience of avian influenza in hong kong in addition to elaborating on the entire process of emergency work. this fully embodies the maturity and perfection of the hong kong government in the risk communication of emergencies and the higher risk awareness. thus, the related communication and publicity strategies are worth referencing. the risk of pandemic influenza can be reduced by timely warning, access to correct information, and attitudes towards communication and interest in the face of threats. as shown in table , % of the respondents had a specific information identification ability; % of the respondents chose to obtain their information on pandemic risk from the official channels. all respondents were willing to take several methods to search for risk information, including using the internet. however, although knowing first-hand influenza warning and decision support information originates from the cdc, very few of the respondents ( %) were able to clarify what types of communicators can provide help and detailed descriptions on this topic, including the specific types of early warning information that is available, where the information is, and how it is transmitted. individuals have only mastered the general concept, such as interviewee # : " . . . go to the official website or wechat (to) find how to prevent." for health education and publicity, most of the respondents indicated that they would not take the initiative to participate in similar activities. the reasons were "traditional lectures are boring," "the publicity manual was not attractive". moreover, as interviewee # indicated, "i think all of them are theoretical knowledge which can be seen on the internet. if they can tell us something that you need to deal with when an event comes, it would be better." regarding suggestions for future risk communication. most of the respondents were satisfied with the current government's work and had a positive attitude towards the emergency plan of the official guide form; they were more focused on "the details of the emergency work" (cited by % of the respondents) and "hope to get official plan" (cited by % of the respondents). for example, interviewee indicated that " . . . the way must be change, not as before, because the flu is not like a common cold, people will not pay much attention to it. communication, whether it is a family or school, it is best to have some specific suggestions, such as how to wash hands and disinfection, everyone can refer to themselves to do it." in general, there was a clear difference in the breadth and depth of the overall understanding of the pandemic-related information and communication framework among each student interviewed. as expected, in the context of the communication framework, most of the students' mental models were not as rich as those of the experts. they were more concerned with the critical information necessary to make individual decisions in the interpretation of risk information, for example, interviewee # says: "now, i want to know what type of impact will it cause, and what type of protection measures can protect me?" most respondents only referred to the critical concepts in the communication framework, without a detailed description or in an inaccurate or unclear manner; therefore, these gaps may reduce the ability of people to manage their behavior and their compliance with expert opinions. compared to the communication framework in figure , the respondents used personal experience and analogies to produce more related concepts to establish the information base they needed to make decisions. table the discussion of related items complete negation of self-media % dialectical view of self-media % willing to participate in publicity % refusing to participate in publicity % access to information from the authority % access to information from other mass media % obtaining information from other trusted sources % differences between pandemic and seasonal influenza % the influence of rumors % note: table shows the concept of risk information mentioned by respondents and their suggestions on current government risk communication. the infection of flu often brings many complications, in the heart and lung systems, to those who have low immunity, such as infants and young children, and these are also the significant causes of virus' potential lethality. , the interview results show that some students do not pay sufficient attention to the impact of pandemic influenza and remain optimistic, particularly the lethality of virus, serious complications, and identification of vulnerable populations. our respondents trust in the country's sound epidemic prevention system. however, because we still have a lot of unknown information to explore about the virus, the outbreak of a new virus often brings challenges to the health system of a region. for example, virus identification, targeted program formulation, and information release all need time. for the existence of these time lags between case generation and interventions, if we want to carry out successful disease control actions, it is more important for the public to actively carry out personal protection rather than passively wait for the intervention of government departments. moreover, the desalination of the history of the epidemic, and the lack of targeted health education may also be reasons for the over-optimism of the pandemic. consequently, those who have inaccurate risk perception will estimate themselves as "the strongest young people" or "a person who having enough understanding about the flu." once a new virus outbreaks, these people may also bring misleading information to other individuals in their social circle, which will affect others' emergency decisions. in particular, for those who have experienced influenza pandemic without being negatively affected, luck may cause them to have a more positive response to future pandemics. , furthermore, although the h n , h n , and other influenza outbreaks have been derived from new viruses following mutation, the repetition of the old virus and the prevention of the flu season risk becoming a pandemic. being able to distinguish the key differences between the pandemic and common flu can effectively improve the level of personal risk cognition. among the respondents, we found that some students remained confusion: they believed that a pandemic is the mass spread of seasonal influenza or a pandemic is an almost impossible "super calamity". moreover, a pandemic is often unpredictable and generally involves international outbreak. therefore, it is important for the public to understand that the pandemic is not far away from us. we need to pay attention to our own prevention during the flu season, and at the same time, we need to be alert to unusual cold symptoms, especially when we go abroad. otherwise, patients may mistakenly think that they are suffering from common influenza, choose to place or take medicine, thus delaying the diagnosis and treatment time, infecting others and causing serious consequences. finally, concerning vaccination, our respondents have negative views regarding this issue. only of the respondents cited the importance of the vaccine and had a history of active vaccination, and the reasons mainly focused on the conventional "i feel good and don`t need vaccination" and "doubts about the safety of vaccines." therefore, our risk communication at present seems inadequate in promoting the necessity of vaccination. the public is not aware of the importance of the vaccine for influenza prevention or the misperceptions caused by its one-sided understanding of the pandemic, as discussed in "the countermeasures of the pandemic". in an investigation of the willingness of the elderly to be vaccinated, shaoliang geng found that the primary sources of influenza and related knowledge in elderly adults were family, relatives, friends, and television, and the most trusted means of knowledge were doctors. there are cracks in clinical and public health knowledge, and patients lack knowledge about the importance of vaccination. the correction of this misunderstanding is vital for college students and because it can promote the dissemination of inoculation knowledge of young students in the family, thus improving the injection of the recommended groups (old people and young children). as discussed in the acquisition of risk information and public suggestion, in the absence of relevant knowledge and information, the respondents applied personal experiences and analogies to compose the foundation of their mental model and help themselves understand the risk of the pandemic. understanding differences in causality between risk factors can also lead to substantial differences in risk perception and coping between individuals. many students only know a few general concepts and have not formed a complete emergency preparedness mode of thinking in a communication framework, knowing what one can do during the pandemic but not much about what to do and what is truly meaningful. for example, although nearly all respondents cited wearing masks and bringing in patients in time for medical treatment, the most basic measures can be limited in the presence of a real pandemic, which is only a result of a personal experience analogy (compared to a cold or related disease). what ` s more, for those in the outbreak area, especially those with suspected symptoms, it is the right and effective decision to stay at home and seek the help of local medical institutions to protect personal health than to conceal facts and escaping from outbreak area in panic. but none of our respondents know that. also, most respondents have only basic concepts (the government and the health department) regarding the types of communicators who provide the relevant risk information. these overly broad understandings may limit their ability to rapidly identify critical information or influence their knowledge of specific report under the threat of severe flu, mainly when their typical sources of information or communication channels are not available, or the necessary information is not provided. if the government is unable to offer exact messages or be out of protection from the spread of information. public trust in official authority may be reduced. students always prefer health education with new styles and systematic content. the appeal of traditional lectures and guideline books full of academic words is far less attractive, and it is hoped that the government will "reduce the over the generality of the description" and "release relevant data to increase persuasion" in future communication work. foltz's research confirms that it is necessary to use various mechanisms in the risk communication of emergencies. individuals with nonprofessional backgrounds tend to think in more specific terms, their vocabulary is less expansive, and subtle expressions cannot be well understood. bright colors and charts easily attract them. complex text information transmission will make people feel tired and irritable. if possible, two student respondents also suggested organizing practical exercises, which they think is more helpful to deepen the impression and understand self-protection measures used to cope with the pandemic. information consistency is the decisive factor in understanding and perceiving personal risk. in terms of communication effectiveness, multiple sources of consistent messages are typically more effective than messages from a single source or with different contents. the earlier the warning people receive and the higher the threat of information is, the higher the possibility that people take active preventive measures. therefore, the government department should incorporate the outbreak situational information and the proposed measures into influenza warnings, while maintaining the consistency of multiple communication messages. first, the results of this research reflect some misunderstanding in the respondents with a more prominent frequency: ) influenza virus mutation and seasonal influenza have the potential to evolve into a pandemic, and the prevention of common influenza cannot be ignored. ) the impact of an influenza pandemic is often unprecedented, and influenza virus infection can be lethal; in addition to severe cold symptoms, it also results in severe complications in patients. ) influenza vaccination plays an active role in pandemic prevention and should be actively vaccinated, particularly children with low immunity and elderly adults, a vulnerable group. ) for suspected patients in the family, the first choice is a social isolate, and it is very dangerous for family members to remain in close contact with their protection work. it is imperative for individuals to have common knowledge regarding influenza, the correct personal response and the degree of risk in our area for making the right decisions. therefore, we suggest that the government should put the above content as the focus of communication when communicating the risks related to the pandemic, or formulating the corresponding health education materials, so as to improve the compliance of the audience. on the other hand, the content of government risk communication should not be limited to medical advice. the public health department should develop a response plan for individuals and organizations. in terms of organization, a pandemic does not directly damage related facilities in contrast to many other catastrophic events. however, the regular work of employees within the organization will be affected. the absence of ill employees in central positions will have a severe impact on the regular operation of the organization. therefore, we need to develop a "continuous work plan" for these particular circumstances. the government should release relevant risk information on an influenza pandemic in the form of a preparation plan, or, use the network for distance health education or guiding emergency response work through local radio or television stations. finally, we should update the channels and methods of risk communication and health education. the government should strengthen the application of new media to adapt to young people's information acquisition preferences. in the form of communication, it can be gradually changed from traditional lectures to novel approaches, such as public welfare videos, songs, and scene construction experiences. moreover, scene effects can play an essential role in enhancing the personal experience because analogies are encountered in the event of a risk event to facilitate their correct risk assessment and response behavior. risk communication for public health emergencies the perception of risk risk communicaiton: a mental models approach rational choice and the framing of decisions a warning shot: influenza and the flu vaccine shortage the determinants of trust and credibility in environmental risk communication: an empirical study news influence on our pictures of the world health information on the internet: accessibility, quality, and readability in english and spanish? best practices in public health risk and crisis communication? risk perception and communication unplugged: twenty years of progress risk society. ho po wen translation acceptable risk the nature of explanation rating the risk know what to do if you encounter a flash flood": mental models analysis for improving flash flood risk communication and public decision making an integrated risk model of a drinking-water -borne cryptosporidiosis outbreak flash flood risks and warning decisions: a mental models' study of forecasters, public officials, and media broadcasters in application of delphi method in screening self-rated health evaluation index system what do lay people want to know about the disposal of nuclear waste? a mental model approach to the design and development of an online risk communication validity in the qualitative research interview the competent manager: a model for effective performance delphi method and its application in medical research and decision making research on the structure of public risk communication ability of influenza pandemic in health sector coordination coefficient w test and its spss implementation influenza century: review and enlightenment of influenza pandemic in the th century discrete logistic dynamic model and its parameter identification for the ebola epidemic modern epidemiology methods and applications beijing: beijing medical university peking union medical college joint publishing house research on monitoring and evaluation index system of national essential medicine system in primary health care institutions. hubei: hua zhong university of science and technology analysis of the clinical characteristics of influenza a (h n ) how does the general public evaluate risk information? the impact of associations with other risks prevalence and characteristics of children at increased risk for complications from influenza analysis of the information demand characteristics of public health emergencies of infectious diseases investigation on knowledge and willingness of influenza vaccination among the elderly over years old in xuchang city social and hydrological responses to extreme precipitations: an interdisciplinary strategy for post-flood investigation the authors would like to acknowledge linxian wang for helping compiling interview questionnaires, making suggestions on interview skills and finding supporting documents. we also express the sincere gratitude to students involved in the interviews of this research. this research did not involve any experiments or investigation which need ethical approval, and did not receive any specific funding too. the authors report no conflicts of interest for this work. risk management and healthcare policy is an international, peerreviewed, open access journal focusing on all aspects of public health, policy, and preventative measures to promote good health and improve morbidity and mortality in the population. the journal welcomes submitted papers covering original research, basic science, clinical & epidemiological studies, reviews and evaluations, guidelines, expert opinion and commentary, case reports and extended reports. the manuscript management system is completely online and includes a very quick and fair peer-review system, which is all easy to use. visit http://www.dovepress.com/testimonials.php to read real quotes from published authors. key: cord- -w bl fer authors: kvasnovsky, charlotte title: reply to letter to the editor date: - - journal: j pediatr surg doi: . /j.jpedsurg. . . sha: doc_id: cord_uid: w bl fer nan to the editor, we thank dr. ayesha saleem and associates for sharing their experience. unlike your findings, we and other researchers did not find an increase in patients presenting with complicated appendicitis during the height of the pandemic, although these are admittedly all small studies. we agree that this pandemic has forced us all to be flexible and re-think our previous workflows. the long-term impact of the covid- pandemic on patient care and research remains to be seen. pre-existing disparities in access to quality care are being amplified by this pandemic. the resilience of our social safety nets will be tested in the months and years to come. the decreasing incidence of acute appendicitis during covid- : a retrospective multi-centre study key: cord- - yrh ab authors: susskind, daniel; vines, david title: the economics of the covid- pandemic: an assessment date: - - journal: nan doi: . /oxrep/graa sha: doc_id: cord_uid: yrh ab the covid- pandemic has created both a medical crisis and an economic crisis. as others have noted, we face challenges just as big as those in the spanish flu pandemic and the great depression—all at once. the tasks facing policy-makers are extraordinary. many new kinds of intervention are urgently required. this issue of the oxford review of economic policy has two objectives. the first is to explore these new interventions: evaluating their use, suggesting how they might be improved, and proposing alternatives. the second is to show that the challenges facing us are global and will require international cooperation if they are to be dealt with effectively. this short introductory essay positions the papers in the issue within an overall conceptual framework, with the aim of telling an overarching story about the pandemic. the covid- pandemic has created both a medical crisis and an economic crisis. as others have noted, we face challenges just as big as those in the spanish flu pandemic and the great depression-all at once. the tasks facing policy-makers are extraordinary. many new kinds of intervention are urgently required. this issue of the oxford review of economic policy has two objectives. the first is to explore these new interventions: evaluating their use, suggesting how they might be improved, and proposing alternatives. the second is to show that the challenges facing us are global and will require international cooperation if they are to be dealt with effectively. just months ago we all knew very little about any of this. aspects of the story have emerged with greater clarity as more information has been revealed, and as the results where to begin? only months ago few economists knew anything about sir models. now we all know that the central framework for studying the spread of any infectious disease is the sir model. and we know that the only way to control a pandemic is to keep the reproduction number, r, the expected number of cases directly generated by an infectious case, below . when that happens, each infected person will infect less than one new person on average and the epidemic will come to an end (cleevely et al., , this issue) . but despite the central nature of the sir model in the epidemiological literature, until recently most versions of that model did not adequately capture the economic costs associated with the interventions that are being made to control the disease. there are now any number of papers available which begin to do this (see, for instance, acemoglu et al., and eichenbaum et al., ) . rowthorn and maciejowski ( , this issue ) make another welcome contribution to this set of ideas. at the core of these papers is the challenge of how to understand the trade-off between the cost of, on the one hand, the likely illness and deaths-however valued-and, on the other hand, the costs of the policies being adopted to reduce such illness and death. this trade-off is not simple to understand because it is an intertemporal one. policies adopted now, with immediate costs, have implications for future infections and future deaths, and these implications work themselves out in highly non-linear ways. clearly how one thinks about this depends on the value which one places on human life. the particular attraction of rowthorn and maciejowski ( ) 's paper is that it provides a mapping from the value attached to human life to the severity of lockdown that is justified, after allowing clearly for the intertemporal nature of the problem. and it does this in an intuitively clear and elegant manner. (see figure of rowthorn and maciejowski ( ) . ) the paper argues that that the optimal response to covid- would have been to lock down the economy very swiftly, to bring r down below , before the infection had taken hold; just one week of delay makes a huge difference. but when saying this we need to be clear how little was known at the beginning. would it have been optimal to lock down so swiftly, knowing what we knew at the time and given the enormous uncertainty around the parameter estimates? this is difficult to judge, as experience of previous epidemics has shown. for instance, neil ferguson and his modelling team at imperial college, who have played a critical role in influencing the uk's response to covid- , were also responsible for shaping the decision to cull several million uk cattle to bring the foot-and-mouth disease outbreak to an end: but a more recent study, which found the disease had a shorter infectious period, suggested that such an aggressive approach may not always be optimal (cressey, ; charleston et al., ) . lockdowns can only eliminate the transmission of disease if they remain in place more or less for ever, i.e. until a vaccine is available. that is because many people will go on being susceptible to infection so that, if lockdown is abandoned, the unstable spread of the disease will again become likely. but because of the enormous economic cost associated with lockdowns, they cannot be allowed to continue more or less for ever. rowthorn and maciejowski ( ) argue that how long lockdown should be made to last depends fundamentally on the valuation attached to life: a lower value implies that a shorter lockdown is desirable. the study is based on a standard but simple epidemiological model, and should be regarded as presenting a methodological framework rather than giving actual policy prescriptions. they argue that a full lockdown of even as little as weeks would only be optimal if the value of life for covid- victims exceeded £ m (rowthorn and maciejowski, , figure ). this number is much larger than the figure implied by official guidelines for drug evaluation, which is £ , to £ , . a robustness check, performed by changing the parameter values in the social welfare function used in the policy optimization algorithm, reduces this number to £ m. but that is still a larger number than the numbers used in the official guidelines. the paper also suggests that it would be optimal to dispense with lockdown altogether if the value of life were to drop below £ . m (see figure ). it is clear that this troubling trade-off between reducing the number of lives lost and rising economic costs raises significant questions about how exactly life should be valued. colmer ( , this issue) discusses just how hard these questions are. he argues that efforts to engage with this issue have lacked clarity. he argues that the choice of numbers used to represent the 'value of lives saved' from covid- interventions, more than likely, substantially understate the social benefits. in light of what are very large uncertainties over how much larger the social benefits could be, this raises concerns about how useful traditional benefit-cost analyses can be in contexts such as the current crisis. if a full lockdown cannot continue indefinitely, it is obvious that alternative interventions will be required to keep r below . the ultimate goal must be to discover, manufacture, and distribute a vaccine so as to eliminate the threat of covid- altogether. and as brown and susskind ( , this issue) argue, countries must cooperate much more actively than at present in their pursuit of this common objective. but before a vaccine or an effective treatment is available for widespread use, another strategy will be necessary to control the spread of the disease in the meantime. in part, this strategy must involve bottom-up measures adopted by individuals: social distancing, decisions by the most vulnerable to shield themselves, wearing masks, and washing hands. but it must also involve additional top-down interventions imposed by governments. the two are closely related: it is becoming clear that the use of compulsory lockdowns-by the end of march , over countries had one in place-had an important signalling effect at the start of the pandemic, making clear how critical it was for individuals to change their behaviour. this puts to one side the possibility that herd immunity, or something close to herd immunity, is achieved by allowing the disease to run rampant throughout the community. the national institute for health and care excellence (nice) assumes £ , -£ , per qualityadjusted year of life. office for national statistics life tables and statistics on the age, sex, and underlying health condition of covid- fatalities suggest that the average person dying from the disease loses about ten years of life. if the authors impose the condition that peak infection must not exceed what the health service can handle, they show that it would be optimal to dispense with lockdown if the value of life were to be below £ . million. indeed, these behaviour changes may explain why fears at the start of the pandemic about prolonged draconian intervention might have been misplaced (rowthorn and maciejowski, ) . alongside a full lockdown, though, there are other important interventions available to governments. to begin with, it is clear that targeted lockdowns, as per acemoglu et al. ( ) , will need to become part of the strategy: rather than lock everyone down, the lockdown is instead stratified by, for instance, location, age group, or other risk factor. another important intervention is an effective testing strategy: testing individuals for the infection and isolating those who test positive. however, such a strategy must also be workable: countries have finite testing resources and testing capacity can be difficult or impossible to ramp up (kasy and teytelboym, , this issue) . in cleevely et al. ( ) , the authors question the viability of universal random testing, a strategy in which a random fraction of the entire population would be selected each day for testing. they show that, on reasonable assumptions, this would not be a feasible strategy; it would require testing about per cent of the population every day (or everyone, every days). instead, the authors argue for stratified period testing: stratified because it is focused on at-risk groups, and periodic because tests would be conducted on each person at regular intervals. the authors show that this approach dramatically reduces the required testing resources. following on from this, kasy and teytelboym ( ) examine the tradeoffs involved in allocating testing resources to some individuals but not others; the so-called 'shadow cost' of a test. they explore the difficult dynamic balancing that policy-makers face, between using tests to protect people today, versus using tests to identify the prevalence of the disease in the population to benefit people in the future. if the number of infections in a population is sufficiently low, or is brought down to a sufficiently low level, then a test-and-trace strategy can be used as an important part of a strategy. with such a policy, infectious individuals and their contacts are identified and isolated so they cannot infect others. the effect of such a policy will enable lockdown to be abandoned much earlier, even although the threat of unstable spread of the disease remains present. such a policy becomes possible because an effective test-andtrace operation will quickly remove from public circulation anyone who is shown to be infectious. such an individualized (and very costly) form of intervention enables r to be kept well below , even though, without it, and without lockdown, r still remains well above . the model in the paper by rowthorn and maciejowski ( ) illuminates this process very clearly. it now appears from both theory and repeated experience that the two best investments a country could have made in the run-up to the covid- pandemic are the production and distribution of 'personal protective equipment' (ppe), including face masks, and an effective test-and-trace regime. looking ahead, there are important concerns about the consequences of existing safety regulations for such a regime: it appears that some businesses, for instance, are not testing their employees with sufficient frequency for fear of being shut down (this explains large but localized outbreaks at, for example, german abattoirs, at the time of writing). more of these outbreaks should be anticipated and can be dealt with, providing that businesses are encouraged to test and isolate their employees, rather than being encouraged not to do this by the threat of being punished (galeotti et al., ) . what we have just said explains why the economic impact of covid- has been so enormous. the deaths, and the reduction in the work which can be done by those who fall ill, are costly enough. but that is true of any infectious disease, like the flu. what is special about covid- is that it is both very infectious and very deadly. that is why the policies adopted to deal with it-which we have been discussing-have needed to be so radical. at the start of the pandemic, del rio-chanona et al. ( , this issue) estimated that, in the us, the first-order effect of the virus would threaten per cent of gdp, per cent of employment, and reduce wage income by per cent. these figures initially looked almost fantastical. but their predictions have turned out to be surprisingly close to the mark-not only in the us but around the world. but the details of how these costs have played themselves out have varied enormously from country to country. evidence from pakistan, for instance, suggests that microfinance in low-income communities now faces a drastic crisis (malik et al., , this issue) . rapid-response surveys suggest that on average, week-on-week sales among microenterprise owners and household income both fell by about per cent, households' primary immediate concern in early april became how to secure food, and about per cent of the sample of current microfinance borrowers reported that they could not repay their loans. significantly, the economic impact of covid- has also been extremely unequal. again, rio-chanona et al. ( ) correctly predicted that certain sectors would be hit by demand shocks (transport, for instance), others by supply shocks (manufacturing and mining, for instance), and others by both (entertainment, restaurants, and tourism), while some-and in particular, high-wage occupations-were relatively immune. but there are further very significant inequalities too. for instance, there are substantial gender inequalities associated with the pandemic: the requirement to stay at home, for instance, created a major shock to the demand and supply of home childcare (sevilla and smith, , this issue) . couples with young children in the uk, for example, now find themselves performing a working week's worth of additional childcare. the pre-covid- characteristic-that women do the majority of such childcare (on average, about per cent)-has continued, and women have been more likely than men to lose employment due to the pandemic (sevilla and smith, ) . in turn, there appear to be important age inequalities, too: the international labour office (ilo), for instance, argues that young people have been 'disproportionately affected' by the pandemic, which has disrupted their education and training, and forced them out of work; one in six young people surveyed by the ilo, for example, had stopped working since the start of the covid- crisis (ilo, ). and finally, there is growing evidence that the health impacts of covid- are particularly harmful for black, asian, and minority ethnic (bame) communities; the uk government, for example, is launching a review to better understand this very troubling feature of the pandemic (kirby, ). alongside the dramatic actions taken to mitigate the medical crisis are the extraordinary interventions that have been taken to tackle the economic crisis. unprecedented discretionary fiscal policies have been adopted around the world. governments have put forward swift and significant emergency lifelines to protect workers and businesses. the international monetary fund (imf) first measured these interventions in april , but as countries have stepped up their efforts it has updated its calculations: in may, the total was about us$ trillion (imf, ). this is a staggering sum: what has been spent or promised amounts to about per cent of world gdp. the breakdown looks like this: direct budget support is currently estimated at $ . trillion globally, and additional public-sector loans and equity injections, guarantees, and other quasi-fiscal operations (such as non-commercial activity of public corporations) amount to another $ . trillion (imf, ). these interventions have had an important impact in mitigating the economic crisis. in the uk again, for instance, on some measures it appears that the fall in household incomes is more evenly spread across the income distribution than the loss of jobs is distributed across the earnings distribution (brewer and gardiner, , this issue) . in turn, unlike during the financial crisis of - , the financial system has remained strong and stable during the pandemic. as giese and haldane ( , this issue) explain, this was not the case a decade ago, when both bank balance sheets and the prudential regulatory standards that banks had to follow were very different from what they are now. furthermore, monetary and financial policy have been able to support fiscal policy; the bank of england, for instance, has expanded its balance sheets by almost a third in months during the crisis (hauser, ) . in the uk, the policy centrepiece has been the job retention scheme (jrs) or 'furlough' scheme, where employers receive per cent (up to a limit £ , per month) of the wages of employees who are temporarily asked to stop working (mayhew and anand, , this issue) . this intervention not only reflects the scale of those seen in other countries, but also their imperfections. by early may, . m workers had been furloughed, and it was expected it would rise further to m, about a quarter of the uk workforce. yet as mayhew and anand ( ) explain, this bold policy still leaves large gaps and has significant flaws: the scheme, for instance, failed to cover per cent of the uk's workforce; the data were not available to judge if per cent was the right figure; and it is unsustainable in the longer run. this final point is key: around the world, many of these remarkable economic interventions were intended to be temporary emergency measures. there was a moment at the start of the pandemic when some commentators appeared to think the crisis might be relatively swift: lockdown would be imposed, but once the peak in infections had passed in a matter of weeks, extraordinary but temporary measures could be relaxed, economies would go through a swift v-shaped recovery, and economic life as it was before the pandemic would return. historians would look back at the 'great panic' of . this now seems extremely unlikely without an effective vaccine. a reasonable base case is that the virus and its consequences will be with us for some time. and so, the coming months are likely to be dominated by continued responses to both the medical and economic crises. however, if the pandemic is to be more long-lasting, interventions designed for a short-lived crisis must be revisited. with respect to the medical crisis, as noted before, as lockdowns are relaxed, other interventions to keep r below will need to be intensified. also see fiscal monitor. world gdp is somewhere between $ and $ trillion, depending on how it is measured. but in a similar way, our economic interventions must change. as devereux et al. ( , this issue) argue, as we move out of lockdown and into a tentative period of recovery, it will be necessary to consider a new set of policy options: extension of short-time work and possible temporary subsidy for re-employment; corporation tax incentives; vat reductions; and a holiday from taxes on business property. more generally, as noted before, radical fiscal measures that were designed to temporarily keep workers attached to their existing employers must be replaced with alternative, and more sustainable, measures (mayhew and anand, ) . for instance, with respect to the jrs in the uk, from the beginning of july, the scheme becomes more targeted and is due to finish at the end of october: mayhew and anand ( ) argue that, rather than go cold turkey at this point and remove employment subsidies, there is a case for the introduction of a variant of the germanstyle working time accounts scheme. nevertheless, there are difficulties ahead here. the structure of the economy which re-emerges may well be somewhat different from what it was in the past. to take one small example, it is likely that much more office work will be done remotely, setting up pressures for change in both the commercial property market and the residential property market. to take another example, some jobs are likely to just disappear, for example in retail. although cold turkey seems like a bad idea, a generous furlough scheme which keeps workers in place where they have no future is also not a good idea. what is required, mayhew and anand, ( ) argue, is a comprehensive active manpower policy in its place to efficiently match job-seekers to available jobs. other substantial challenges also lie ahead. some of the new-found economic interventions have created new risks for the corporate sector. for instance, another key policy in the uk has been the variety of covid- loans which have been made available to firms. it is not clear how these are working: many firms appear to be unable to access them, and time will tell what the default rate on these loans will be-it seems likely that default rates will be high, and the systemic consequences are likely to be large. as johnstone-louis et al. ( , this issue) argue, massive bailouts of companies may end up being needed. these will impose substantial obligations on the corporate sector to respond and to lead the economy out of the crisis. when similar bailouts were provided for commercial banks after the financial crisis of - , the banks ended up imposing significant costs on the rest of the society in that they prioritized the rebuilding of their balance sheets ahead of looking after their customers. this is something which needs to be avoided. and there is a more general point: to offset the large debt overhang problem that has emerged and avoid the wave of bankruptcies that threaten economies, financial institutions will be expected to provide substantial amounts of new equity funding as well as accepting dividend cuts. the covid- pandemic has also led to more fundamental calls to reform business and finance. the last crisis-the financial crisis of - -was clearly the fault of business, and the financial sector in particular. this time round, business cannot be blamed for causing the pandemic. but it can be blamed for leaving economies so vulnerable to its consequences. with many companies having less than months of reserves to cover their operating costs, they have been forced to cut costs draconianly, be bailed out by governments, and slash their workforces. there is a case for arguing that stress testing should be extended beyond the financial sector as a whole to business more generally, and relate to a broader range of events than the macroeconomic ones on which they have been focused to date, for example pandemics, weather, and technology-related risks (giese and haldane, ) . to some, the pandemic has exposed a failed system of corporate governance. as economies begin to recover, many are appealing to the idea of 'building back better'. but this requires a clearer conception of what exactly it is they want to build-and it is unlikely to be a corporate sector that generates profits on the back of environmental degradation, rising inequality, or social exclusion. fixing this needs a recognition that business's reason for being is to serve others than itself, its investors, or executives, and that their interests are derivative of, not the determinant of, its success in so doing (mayer, , , morris and vines, . good business can drive profits; profits do not necessarily drive good business, and good regulation does not solve the problem without good business. but business cannot do this on its own. the pandemic has shown that business needs government, as well as government needs business. mazzucato and kattel ( , this issue) argue that we should forge new relations between government and the private sector. the innovation and experimentation that will be required to recover must come from the private sector, but this must take place in the context of governance arrangements that address social concerns and avoid the types of problems that have arisen in relation to, for example, data usage. neither privatization nor public ownership have proven adequate to the task; 'government actively shaping markets rather than simply fixing failures' is how mazzucato and kattel describe an alternative approach. and as collier and mayer ( , this issue) note, public-sector funding will be needed alongside private finance, in particular in relation to the small and medium-sized enterprises (smes) that are most at risk of failure, especially in the most depressed and disadvantaged areas of a country. channelling public funding to smes in these areas may involve more than the existing banking system can provide. the authors describe why this is the case in the uk and put forward suggestions for the development of new funding institutions to cope with it. milton friedman was prescient when he said that 'only a crisis, actual or perceived produces real change. when that change occurs, the actions that are taken depend on the ideas that are lying around'. 'that', he said, 'is our basic function: to develop alternatives to existing policies, to keep them alive and available until the politically impossible becomes the politically inevitable.' the only question is how many crises will it take until we realize that he was quite wrong when he said that 'there is one and only one social responsibility of business . . . to increase profits so long as it stays within the rules of the game'? at the time of writing, covid- had already begun to reach low-income and middleincome countries. such countries face an enormous challenge in dealing with this crisis, because the institutions of government and of public administration are much less well developed in these countries than in advanced countries. this issue of the oxford review of economic policy contains only one paper which discusses this challenge, by gerard et al. ( , this issue) , but that paper provides an eye-opening account of tasks that policy-makers will face in these countries. it seems that these countries may need to use a much broader patchwork of interventions than high-income countries. and the authors provide a view of what this patchwork might need to look like. job retention programmes already exist in some countries; some governments have leveraged id-linked bank accounts opened for financial inclusion purposes to provide direct support to the poor; and even populations that live at the margins of social protection systems-like migrant workers-are being reached through associations that work with them. yet, as the authors show, any government response will be imperfectly targeted, with important inclusion and exclusion errors: government responses based on social insurance programmes will miss the informal sector; social assistance programmes are always specific to a particular dimension of poverty, and their delivery is often plagued with leakages; and involving local governments or non-state actors runs the risk of resources being diverted by local elites or used for clientelism. nevertheless, the authors conclude that fewer even imperfectly targeted transfers will reach some 'left-behind' households through family, informal, or formal sharing structures. the paper provides important examples of how, and in what way, this might happen and is already happening. the authors conclude that the challenge of mitigating the economic effects of the pandemic is enormous in low-income and middle-income countries. any solution will be flawed in many ways because speed is of the essence. but, they say, governments, donors, and civil societies have made major gains in the last years in building infrastructure to reach the poorest. if internal and external financing can be found-and this is a big if-then developing countries might be able to use this to create the economic space for an effective public health response. but the challenge really will be enormous. the covid- pandemic has created a global medical crisis, not just a national one. in brown and susskind ( ) , the authors show that the international response to the pandemic has fallen short, primarily because of a lack of effective global cooperation. many of the tasks involved in controlling an infectious disease like covid- are global public goods-a public good that spills across national borders with far-reaching consequences as a result-that can only be delivered through global cooperation. the paper discusses the discovery of vaccines as an example of the kind of cooperation that is needed: only one success, if shared with others, is needed to bring the pandemic to an end. but cooperation would also have to be strengthened because it is not enough just to discover a vaccine: it has to be mass manufactured and, if the disease is to be eradicated in every country to avoid further waves of the disease emerging in the future, distributed equitably. brown and susskind ( ) discuss just why many activities like this have been underfunded and under-provided until now, and they discuss how this might be remedied. the pandemic has also created a global economic crisis. indeed, it has caused the greatest collapse in global economic activity since the collapse of the south sea bubble in . as noted before, some advanced countries have mounted a massive fiscal response, both to pay for disease-fighting action and to preserve the incomes of firms and workers until the economic recovery is under way. but there are many emerging market economies that have been prevented from doing what is needed by their high existing levels of public debt and-especially-by the external financial constraints which they face. mckibbin and vines ( , this issue) argue that there is a need for international cooperation to allow such countries to undertake the kind of massive fiscal response that all countries now need, and that many advanced countries have been able to carry out. they show what such cooperation would involve and they use a global macroeconomic model to explore how extraordinarily beneficial such cooperation would be. their simulations of the model suggest that gdp in the countries in which the extra fiscal support takes place would be something like two and a half per cent higher in the first year, and that gdp in other countries in the world be more than per cent higher. and the percentage increase in employment in the countries in which there is extra fiscal support would be very much larger than the percentage increase in gdp. so far, such cooperation has been notably lacking, in striking contrast with what happened in the wake of the global financial crisis of - . the necessary cooperation needs to be led by the group of twenty (g ), just as happened in that crisis, since the g brings together the leaders of the world's largest economies. but this cooperation must also necessarily involve a promise of international financial support from the imf, otherwise international financial markets might take fright at the large budget deficits and current account deficits which will emerge, creating fiscal crises and currency crises and so causing such expansionary policies which we advocate to be brought to an end. mckibbin and vines ( ) do not discuss the case of the poorest countries in the world. but the problem just described has created huge problems for countries in sub-saharan africa. these are discussed in detail by adam et al. ( , this issue) . the authors capture quite what a catastrophic external position these countries are now in, something which is likely to require them to embark on massive fiscal austerity at just the wrong time. they show very clearly just how much of an increase in overseas development assistance (oda) would be required to help these countries deal with the medical and fiscal problems which the covid- pandemic has thrust upon them. in particular, they show that merely keeping the degree of domestic fiscal adjustment within reasonable bounds-i.e. ones which seem politically feasible-would require about an extra $ billion of oda. that would, in effect, mean a doubling of the aid which these countries receive. they would need three times as much aid if the aim was to fully isolate them from the covid- shock. the pandemic is also likely to have dramatic consequences for global progress on mitigating climate change. as hepburn et al. ( , this issue) note, in the short term the policy response has curtailed economic activity and thus also slashed greenhouse gas emissions. but once restrictions are relaxed, emissions will be likely to soar once again. in the medium term, then, there is an opportunity, when designing discretionary fiscal policy, to consider interventions that are likely both to promote economic recovery and displace the current fossil-fuel intensive economic system: hepburn et al. ( ) identify possible policies that score highly on both economic multiplier and climate impact metrics. in the longer term, covid- could also result in changes to human habits and behaviours, business, and global institutions, which will have impacts-positive and negative-on the likelihood of reaching net zero emissions before temperatures rise to catastrophic levels. the pandemic raises many other significant international issues. for instance, as fernández-reino et al. ( , this issue) note, the pandemic has increased public awareness of the extent to which the economy relies on a low-wage workforce. but given that many of these occupations are also heavily dependent on migrant workers, this is likely to have substantial implications for immigration policy: now, and in the future, not just in the uk but elsewhere, too. in turn, there are the enormous problems the pandemic has created for the international trading system. it has had a dramatic impact on international trade between countries: a drop by about per cent in france, and per cent in turkey and germany, for instance, relative to historical averages (demir and javorcik, this issue). and already protectionist pressures have reared their head, as brown and susskind ( ) also describe. there is a need to ensure that global cooperation in trade policy goes hand in hand with global cooperation on health and macroeconomic policy. the last time the world faced challenges as serious as those which we now face was at the end of the second world war. at that time there was an extraordinary burst of institutional creativity. the bretton woods conference in led to the creation of the imf, in order to ensure international financial stability. it also led to the establishment of the world bank as an institution which would lend money to what were then the emerging market economies of europe and asia. soon afterwards the marshall plan also started to provide money for countries in need. the next year, in , saw the foundation of the united nations (un); the world health organization became part of the un in . a conference in san francisco led to the establishment of the general agreement on tariffs and trade, which, nearly years later became the world trade organization. after the first world war things were very different. although the league of nations was established in , it never really gained the necessary authority. first the world slid into the great depression of s. then the world lurched into the second world war. the post-second world war institutions have served the world remarkably well. now, following the covid- pandemic, they need strengthening and reinvigorating. but they still provide a framework within which international cooperation can take place. because the pandemic is such a very large event we need to realize that the world faces a very large choice. we can do what the world did in the late s, when the institutional choices which were made helped to support the golden age of global growth during the s and s. or we can instead allow what happened in the s to happen all over again. that is the decision which we now face. optimal targeted lockdowns in a multi-group sir model after the lockdown: macroeconomic adjustment to the covid- pandemic in sub-saharan africa the initial impact of covid- and policy responses on household incomes international cooperation during the covid- pandemic relationship between clinical signs and transmission of an infectious disease and the implications for control a workable strategy for covid- testing: stratified periodic testing rather than universal random testing reforming the uk financial system to promote regional development in post-covid britain what is the meaning of (statistical) life? benefit-cost analysis in the time of covid- foot-and-mouth culls could be cut supply and demand shocks in the covid- pandemic: an industry and occupation perspective trade finance matters: evidence from the covid- crisis discretionary fiscal responses to the covid- pandemic the macroeconomics of epidemics from low-skilled to key workers: the implications of emergencies for immigration policy capitalism and freedom how should we allocate limited capacity for coronavirus testing? social protection response to the covid- crisis: options for developing countries covid- and the financial system: a tale of two crises seven moments in spring: covid- , financial markets and the bank of england's balance sheet operations', speech delivered at bloomberg fiscal recovery packages accelerate or retard progress on climate change? ilo monitor: covid- and the world of work, fourth edition', international labour organization tracking the $ trillion global fiscal support to fight covid- ', imf blog business in times of crisis adaptive targeted infectious disease testing evidence mounts on the disproportionate effect of covid- on ethnic minorities global macroeconomic cooperation in response to the covid- pandemic: a roadmap for the g and the imf covid- and the future of microfinance: evidence and insights from pakistan firm commitment: why business has failed us and how to restore trust in it prosperity: better business makes the greater good covid- and the uk labour market covid- and public-sector capacity capital failure: rebuilding trust in financial services a cost-benefit analysis of the covid- disease baby steps: the gender division of childcare during the covid- pandemic key: cord- -gduhterq authors: spitzer, ernest; ren, ben; brugts, jasper j; daemen, joost; mcfadden, eugene; tijssen, jan gp; van mieghem, nicolas m title: cardiovascular clinical trials in a pandemic: immediate implications of coronavirus disease date: - - journal: card fail rev doi: . /cfr. . sha: doc_id: cord_uid: gduhterq the coronavirus disease (covid- ) pandemic started in wuhan, hubei province, china, in december , and by april , it had affected > . million people in countries and caused > , deaths. despite diverse societal measures to reduce transmission of the severe acute respiratory syndrome coronavirus , such as implementing social distancing, quarantine, curfews and total lockdowns, its control remains challenging. healthcare practitioners are at the frontline of defence against the virus, with increasing institutional and governmental supports. nevertheless, new or ongoing clinical trials, not related to the disease itself, remain important for the development of new therapies, and require interactions among patients, clinicians and research personnel, which is challenging, given isolation measures. in this article, the authors summarise the acute effects and consequences of the covid- pandemic on current cardiovascular trials. trials may not be able to attend hospitals for follow-up visits or to collect study medications. a careful and periodic risk assessment by sponsors and investigators is required to preserve the safety of trial participants (and employees) and the integrity of trials. in this article, we summarise the immediate implications of the covid- pandemic on ongoing cardiovascular trials. this review incorporates recent recommendations from the us food and drug administration (fda), the european medicines agency, the uk's medicines and healthcare products regulatory agency and australia's therapeutic goods administration, as well as personal views. [ ] [ ] [ ] [ ] [ ] [ ] planning, executing and reporting clinical trials designed for the approval of (or to extend indications for) drugs, biological products, devices and combinations thereof, are highly regulated activities. clinical trialists must observe national regulations, as well as international standards, such as those proposed by the international conference of harmonization, the international organization for standardization and the international medical device regulators forum. two general principles governing the execution of clinical trials are ensuring patient safety and clinical trial integrity. according to the who, patient safety is "the absence of preventable harm to a patient during the process of health care and reduction of risk of unnecessary harm associated with health care to an acceptable minimum." as defined by the fda, data integrity refers to "the completeness, consistency, and accuracy of data. complete, consistent and accurate data should be attributable, legible, contemporaneously recorded, original or a true copy and accurate (alcoa)." data are to be recorded exactly as intended, and when retrieved at a later time, should be the same as originally recorded. while patient safety is paramount, both should be prioritised for the successful execution of clinical trials. if data integrity is compromised, study results may no longer be interpretable, reliable or usable. a pandemic has the potential to directly impact all individuals and organisations involved in clinical research (figure ) . highly contagious and rapidly spreading viruses, such as sars-cov- , require comprehensive measures to avoid human-to-human spread. with the ongoing pandemic, the world has progressively witnessed a reduction of airline activity to almost zero with widespread travel bans, and limitation of private and public transportation, temporary closure of retail businesses, banning of public gatherings and the requirement to work from home. all these measures are designed to limit exposure to potential carriers of the virus. individual measures, such as meticulous hand hygiene, self-isolation and social distancing, are encouraged. public measures, such as quarantines, curfews or lockdowns, have been implemented. however, sectors, such as healthcare, food supply chains, law enforcement, governmental agencies and regulatory bodies, remain indispensable, with an increased workload challenging the capacity of local and national systems, as well as risking (if not sufficiently protected) the well-being of individuals. overall, the majority of people stay at home, work remotely and limit use of healthcare systems as much as possible. the clinical trial life cycle can be divided into trial design and registration, trial start-up, enrolment, follow-up, reporting and regulatory submission. changes in trial conduct should be documented and, if substantial, incorporated as protocol amendments (although not in an expedited manner unless impacting on patient safety); lesser changes may be captured as protocol deviations related to the pandemic. regulatory agencies offer a diverse range of flexibility in such procedures, and applicable guidance documents should be consulted to establish the most appropriate approach for a particular trial. [ ] [ ] [ ] , trial enrolment should be put on hold or stopped if there is significantly reduced feasibility (e.g. drug trials with infusions), when participants require intensive care post-treatment (e.g. surgical trials) or when the investigator is unavailable. when inclusion is delayed by the pandemic, it should be dealt with in a similar manner to other circumstances that lead to a low recruitment rate. if appropriate, and especially if foreseen by the protocol, a data and safety monitoring board may assess futility due to severe impact on data collection or outcomes. however, if stopping or putting on hold a trial puts participants at increased risk, efforts should be taken to continue with trial-related activities. enrolment in cardiovascular trials generally takes place at outpatient visits or during hospitalisation. trials in patient populations with acute presentations (e.g. st-elevation mi [stemi]) may identify potentially suitable trial candidates; however, the capacity to comply with study procedures needs to be assessed, as well as considerations related to patient safety during follow-up. it is also pertinent to consider that covid- may mimic some classical presentations, such as stemi; ecg changes are shown to reflect myocarditis, after angiography demonstrates non-obstructive disease. it is problematic when the trial design mandates a protocol-related treatment before angiography. furthermore, the analysis of outcomes may be rendered more difficult, and parallel analyses of the intention-to-treat and per protocol populations will be pertinent. participants in the follow-up phase (when they are generally at home) constitute a higher-risk population in the reduced capacity at investigational sites will impact on availability to perform study visits (or phone calls) to assess and confirm eligibility, enter data in electronic case report forms (ecrfs), to report (serious) adverse events and to follow the protocol in general. all protocol deviations should be noted, with those that are pandemic related clearly participants should be given the option to continue, suspend or withdraw participation. reporting of sever adverse events is expected to continue according to standard procedures and regulation. dsmbs may be appointed to determine feasibility of continuing trials based on overall conduct, patient safety and date integrity. all meetings should be remote, by means of teleconference/ video conferencing. steering committee calls, investigator meetings, endpoint adjudication committees and dsmbs should meet remotely with appropriate technology in place. consideration should be given to changes that limit the exposure of participants, investigators and staff to sars-cov ; changes in enrolment and testing. reporting should differentiate between pre-pandemic, peri-pandemic and post-pandemic, as well as covid- positivity/negativity. novel trial approaches that reduce physical contact remote site management and monitoring could be considered, if feasible (i.e. privacy issues and site workload are considered). consider virtual visits, telemedicine, electronic consent or teletrials. change site location outside the hospital. deliver medication to homes. clinical research organisations need to swiftly transition into home-based organisations and increase level of oversight to deliver urgent and ongoing responsibilities. remote systems need to be upgraded to allow adequate online execution and oversight. ongoing core laboratory activities during a pandemic core laboratories continue operations utilising virtual environments to analyse and review materials. remote analysts and supervisors utilise secure platforms with access to required validated analysis software and study datasets. continued ict support is pivotal. perform risk-bene t assessment. decide to continue with or without changes, to put on hold or stop trials. evaluate feasibility of protocol adherence or need for modi cation. evaluate capacity to continue trials based on human resources, logistics and drug distribution. limit enrolment. prioritise pandemic-related research, as evidence-based treatments are lacking. incorporate measures that limit physical contact between researchers and participants. consider novel approaches that allow remote data capture and remote monitoring. identified. most importantly, principal investigators must ensure that enrolled subjects fully comply with eligibility criteria and that all measures are taken to report adverse events in a timely fashion, given that these two are of paramount importance for patient safety. coordinating centres may require an increased level of monitoring of ecrfs and a degree of flexibility in terms of timing for data cleaning. , , , large, multicentre collaborative trials require the participation of a coordinating centre, either a contract or an academic research organisation. coordinating centres execute the study, or activities within, on behalf of the sponsor or manufacturer. a study team is composed of a project manager, clinical research associates and study monitors, data managers, biostatistician, quality assurance manager and safety reporting units, with or without a medical monitor. a pandemic prompts the need to work from home and cancel face-toface visits. where systems are upgraded to allow remote work and staff remain available for reception of materials, coordinating centres can continue to operate during a pandemic. site initiation and monitoring visits are cancelled, postponed or performed remotely using webbased technology (although source data verification can be postponed). remote monitoring is possible, but might not be feasible at all participating sites in a trial and increases the workload at the site. moreover, technical requirements, confidentiality issues, updated consents and the increased burden to site personnel could make it impractical. in line with this, quality assurance measures, such as site audits, are postponed unless serious non-compliance is identified. the participation of several committees in clinical trials ensures proper scientific and operational oversight, data integrity and quality, as well as patient safety. typically, the steering committee is composed of established investigators or key opinion leaders, and representatives from parties involved (e.g. coordinating centres, sponsor, grant givers). during the pandemic, office-based professionals work from home, and participation may be limited. nevertheless, given the oversight duties of the steering committee and data and safety monitoring boards, the frequency of meetings might need to be increased to address immediate pandemic-related needs. at the beginning of the pandemic, cardiovascular clinicians saw a reduction in patient load, as the population was advised to stay at home. unfortunately, this has resulted in late presentations of severe conditions (e.g. non-stemi or decompensated heart failure). however, as hospital resources are depleted, not only in materials but also in personnel, cardiovascular clinicians are required to perform pandemic-related tasks and to self-isolate, potentially limiting their availability for participation in committees. the same applies to members of clinical event committees and data and safety monitoring boards. potential exceptions are data managers and biostatisticians. in theory, this could reduce the availability of clinicians to participate in committee calls; however, in practice, this might not be the case. committed investigators tend to stretch time when required, as shown by chinese investigators who managed to report initial cohorts despite being at the centre of the pandemic. , all meetings are planned as teleconferences. cardiovascular trials, particularly interventional trials, rely heavily on imaging. for the purpose of an unbiased and consistent analysis, central laboratories are utilised. imaging modalities, such as echocardiography, ecg, cardiac mri, angiography assessments, intracoronary imaging and cardiac ct, are frequently used. thus, for a core laboratory to ensure timely delivery during a pandemic, conditions should allow analysts and supervisors to work remotely. data should reach core laboratories electronically, with secure and certified datatransfer providers. time windows for imaging follow-up might need to be adjusted and uploading activities may also be interrupted. analysing cardiovascular images might not be as efficient at home when compared with a well-equipped work environment. however, remote access through a secure connection to software and datasets, as well as databases, will allow continuity of activities. information and communication technology departments play a pivotal role in setting up and maintaining reliable infrastructure. a lack of remote access could force activities to stop during a pandemic. safety reporting should continue in line with national regulations and following standard procedures. [ ] [ ] [ ] , investigators should ensure timely capture of serious adverse events, a process that might involve extended use of telehealth. moreover, serious adverse events should be identified, where possible, as pandemic or non-pandemic related. the inability to deliver investigational drugs could pose additional risks to participants and warrants an increased level of safety monitoring. , ongoing trials lacking data and safety monitoring boards might need to revisit that decision on a per-case basis. data and safety monitoring boards may independently assess an ongoing trial that has been severely affected by the pandemic (e.g. incomplete data, incomplete follow-up) to help investigators and sponsors elucidate, without compromising the integrity of the trial, whether continuing the trial will yield interpretable data. a pandemic has a significant impact on the ability to adhere to protocol requirements (e.g. missed follow-up visits or tests). importantly, protocol deviations should be documented with an indication that they are pandemic-related following standard procedures. , - data collection could be challenging, but should not stop. when reporting the results of a trial, cohorts might need to be divided as pre-pandemic, peri-pandemic and post-pandemic. statistical analysis plans might need adaptions when considering the influence of the pandemic in the interpretability of results, especially when endpoints share characteristics with covid- related events. guidance on the interpretability of results when analysing data with missing values, unbalanced completeness or out-of-window assessments (e.g. echocardiograms, control angiograms, laboratory values) might also be required, depending on the duration of the pandemic. for multicentre trials, a per-site assessment might be required for outbreak areas versus non-outbreak areas. the interpretability of the overall evidence generated should be discussed with regulatory authorities. , - the use of vaccines, once available, might also require adequate documentation in study databases to avoid unbalanced usage. ethics committees (ecs; or institutional review boards [irbs]) and regulatory agencies experience a significant increase in activity during a pandemic. ecs/irbs face the burden of protocol amendments for ongoing trials, and prioritise activities related to the pandemic, including the review of covid- trial submissions. , - regulatory agencies play a critical role in protecting citizens from threats, including emerging infectious diseases, thus the importance of providing timely guidance, such as the regulatory documents that form the basis of this article. [ ] [ ] [ ] [ ] [ ] [ ] based on accumulating experience, the advice of ecs/irbs and regulatory agencies to sponsors and investigators could be critical to determine the continuation, modification or pause of trial activities. such recommendations are complex, given the uncertainties related to the pandemic duration. a pandemic has a significant impact on every component of cardiovascular clinical research. when facing a rapidly spreading disease with no effective treatment or vaccine, efforts should be focused on facilitating the day-to-day work of healthcare professionals with required personal protective equipment. pandemic-related investigations should be prioritised. nevertheless, sponsors and investigators should take all necessary actions to ensure patient (and employee) safety and to maintain trial integrity in ongoing, nonpandemic-related clinical trials, and capture pandemic-induced trial adjustments in focused amendments so that meaningful conclusions can be achieved when reporting results. a novel coronavirus from patients with pneumonia in china the novel chinese coronavirus ( -ncov) infections: challenges for fighting the storm clinical characteristics of coronavirus disease in china the reproductive number of covid- is higher compared to sars coronavirus severe acute respiratory syndrome -retrospect and lessons of outbreak in china emerging threats from zoonotic coronaviruses -from sars and mers to -ncov high contagiousness and rapid spread of severe acute respiratory syndrome coronavirus . emerg infect dis fda guidance on conduct of clinical trials of medical products during covid- public health emergency postmarketing adverse event reporting for medical products and dietary supplements during a pandemic guidance on the management of clinical trials during the covid- (coronavirus) pandemic. brussels: european medicines agency points to consider on implications of coronavirus disease (covid- ) on methodological aspects of ongoing clinical trials medicines and healthcare products regulatory agency. managing clinical trials during coronavirus (covid- ) covid- : guidance on clinical trials for institutions, hrecs, researchers and sponsors. canberra: doh data-integrity-and-compliance-with-current-good-manufacturing-practice-guidance-for-industry key: cord- -nj ub in authors: woods, eric taylor; schertzer, robert; greenfeld, liah; hughes, chris; miller‐idriss, cynthia title: covid‐ , nationalism, and the politics of crisis: a scholarly exchange date: - - journal: nations natl doi: . /nana. sha: doc_id: cord_uid: nj ub in in this article, several scholars of nationalism discuss the potential for the covid‐ pandemic to impact the development of nationalism and world politics. to structure the discussion, the contributors respond to three questions: ( ) how should we understand the relationship between nationalism and covid‐ ; ( ) will covid‐ fuel ethnic and nationalist conflict; and ( ) will covid‐ reinforce or erode the nation‐state in the long run? the contributors formulated their responses to these questions near to the outset of the pandemic, amid intense uncertainty. this made it acutely difficult, if not impossible, to make predictions. nevertheless, it was felt that a historically and theoretically informed discussion would shed light on the types of political processes that could be triggered by the covid‐ pandemic. in doing so, the aim is to help orient researchers and policy‐makers as they grapple with what has rapidly become the most urgent issue of our times. covid- reinforce or erode the nation-state in the long run? together, these questions allow the contributors to reflect on how covid- may affect nationalism and the nation-state and how these core aspects of politics will in turn shape the response to covid- . the first question asks contributors to explain how they understand nationalism, how it may shape the response to covid- and whether covid- will in turn impact on nationalism. in their replies, greenfeld, hughes and miller-idriss discuss the ways in which nationalism is shaping the response to the pandemic. greenfeld argues that ethnic nationalism is a key variable shaping the responses of many states to covid- when compared with previous pandemics such as h n . miller-idriss strongly agrees and points out that states led by populist nationalists are faring much worse than others. hughes picks up on these themes by arguing that the medical and health care response is being 'weaponized' to support nationalist aims. on the other hand, the contributors argue that covid- will also shape nationalism. on this point, woods and schertzer put forward a typology for analysing how the pandemic could affect the development of nationalism, arguing that it could be constitutive, amplifying or transformative. ultimately, among these three possible trajectories, they argue that the most likely impact of the pandemic will be to amplify existing ethnic and national cleavages. miller-idriss joins woods and schertzer in highlighting this amplifying effect by pointing to rising anti-immigrant, xenophobic and conspiratorial anti-state sentiments in many states in the wake of covid- . hughes takes a slightly different view here by drawing attention to the potential for covid- to act as a transformative moment in chinese nationalism that revolves around pride for containing the virus. the second question asks contributors to reflect upon one of the most pressing issues on people's minds today-the potential for covid- to trigger and enflame ethnic and national conflict. several commentators have already raised the possibility of large-scale global warfare, given parallels to the decades following the spanish flu in and the economic ruin of the interwar period. however, there are many different types and levels of conflict: ethnic and national conflict has external (interstate) and internal (intrastate) dimensions, and it runs the gamut from largely peaceful political conflict to outright violence and warfare (schertzer & woods, ) . in their responses, the contributors consider these differing dimensions of conflict. focusing on the potential for covid- to exacerbate conflict between china, hong kong and taiwan, hughes notes how the pandemic has already provided the chinese government with a pretext for accomplishing its nationalist aims of integrating the territories with the mainland. on the other hand, hughes observes that taiwan has also used covid- to secure greater visibility in the international arena. this, in turn, risks drawing in more state actors, to become a larger interstate conflict between china and the west, particularly with the united states. on this score, greenfeld agrees that covid- risks amplifying conflict between china and the united states. greenfeld also comments on the possibility of the pandemic amplifying ethnic nationalism leading to the persecution of ethnic minorities. miller-idriss similarly focuses on the potential for covid- to increase persecution of minorities, noting the rise in anti-asian racism in the united states. however, for miller-idriss, it is in the fragile states of the global south where the risks of nationalist and ethnic conflict are greatest. for their part, woods and schertzer discuss many of these same themes, highlighting the specific risks that occur when a "politics of blame" is combined with nationalism. they argue that this combination can increase the risks of conflict with individuals and communities who are perceived as 'others.' finally, the third question asks contributors to project forward and reflect on whether the pandemic will have a lasting impact on the building block of our international order-the nation-state. as noted above, covid- arrived in a world where nationalism, trade protectionism and migration controls were on the ascent. it is possible that the pandemic will amplify these forces, leading nation-states to turn further inward. at the same time, the global nature of the virus may force international collaboration to mount an effective response. among these possible futures, no matter how much upheaval that may be caused by covid- , greenfeld doubts that it will shake the ideal of the nation-state as a vehicle for securing the identity and dignity of its citizens. quite the opposite, greenfeld suggests that the pandemic will work to erode global institutions. here, hughes broadly agrees with greenfeld, while also highlighting the ways in which the response to the pandemic could be used as a cover to strengthen the nation-state. hughes also warns that even the scientific community may not be immune to a process of nationalization. miller-idriss parts ways from greenfeld and hughes by suggesting that while the powerful nation-states may be strengthened by covid- , it is likely that the pandemic will erode the more fragile states of the global south. woods and schertzer pick up on this theme, while also pointing to a range of potential threats that covid- may throw at the nation-state, whether "from above" by neo-imperialisms or "from below" by new nationalist movements. however, while these threats may undermine some individual nation-states, they argue, like greenfeld, that this will not necessarily erode the potency of the nation-state as an idea. to answer these questions, as any question regarding the relationship between nationalism and other phenomena, it is necessary, first, to have a clear understanding of how cultures and societies function and evolve, in general, and of the nature of the cultural and social phenomenon of nationalism, specifically. to address these issues in , or so words fully is impossible, so i shall only state the empirical conclusions of my investigations and proceed on this basis. even these introductory remarks, however, must be introduced with a methodological consideration. when i am talking about a clear understanding, i do not mean to say "my understanding"; this would be tantamount to a chemist, for instance, saying "my understanding of gas is such and such," presuming that someone else's understanding is expected to be different. rather, assuming that cultures, societies and nationalism, just like gases, are empirical phenomena, i am approaching social and historical facts, following classical methodological recommendations, as things, without any prejudgement (bloch, ; durkheim, ) . the cultural (social, political, economic, etc.) process occurs simultaneously on the level of the individual mind and the collective level of the surrounding culture and consists of the constant give and take between these two levels. every collective trend begins with a new individual experience, to which the mind will react using existing cultural resources, but the reaction may be creative, that is, unpredictable. if the experience is sufficiently provocative and common, a new interest may transform this creative individual reaction into a shared ideal, eventually resulting in a new way of thinking and acting, that is, give rise to a new social institution, adding to the cultural resources and changing the institutional structure-the nature-of a society (greenfeld, (greenfeld, , (greenfeld, , . this, in most basic terms, is how societies change and evolve, in general, and how nationalism evolved, in particular. in regard to nationalism, specifically, one must keep in mind the following. (a) it is a historical, modern phenomenon: before the th century, there were no nations. (b) it is essentially a way of thinking, the basis of any institutional structure-thinking that the social world is naturally divided into sovereign communities of fundamentally equal members (communities called nations) and that a just society, consistent with the human nature, therefore, is an egalitarian society based on the principles of popular sovereignty. (c) as a result, nationalism implies democracy, every nation being a democratic society by definition. (d) the democratic/national principles of fundamental equality of membership and popular sovereignty can be interpreted and implemented differently, producing several types of nationalism: not every nationalism is ethnic. in the monotheistic civilization alone, in which ethnic nationalism is indeed the most common type, there exist two other types of nationalism: individualistic nationalism (such as the original english one) and collectivistic-civic nationalism (such as the french). (e) the broad appeal of nationalism is due to the fact that fundamental equality of membership in the nation and the consciousness of popular sovereignty dignify personal identities of members of the nation (greenfeld, ) . in this framework, we can examine the relationship between nationalism and covid- . let us begin with the possible effects of nationalism on the course of the pandemic. the course of the pandemic was certainly affected by the ways it was handled in different countries, and the way it was handled, i would argue, was a direct function of nationalism, specifically, of the national conflict between china and the united states. what leads me to say this? the comparison between coronavirus and previous pandemics: be it h n , sars, mers, ebola, hiv-aids of the recent decades, or such historically remote lethal attacks of infectious disease as the spanish flu of the last century or the plague (black death) in the middle ages. none of the previous pandemics involved worldwide lockdowns, cessation of normal activities and massive statesponsored and state-controlled mitigation. both the black death, which, incidentally, also came from china, and the spanish flu were incomparably more lethal than coronavirus: the plague would kill one in two people, %, in settlements it reached; if one contacted it, the fatality rate was between % and %. yet, only a few governments, such as that of the city of milan, ruled by a most brutal dictator, attempted to mitigate (benedictow, ) . of course, one can argue, no government at the time but a brutal dictatorship in a small city-state had the means to control its population (and the spread of the disease) to the extent that nationstates of today have. but this cannot be said of the influenza of and even less of recent pandemics (sars, h n , etc.), when the means of disease control at the disposal of governments were identical to what they are now. sars and h n , for instance, were at least as frightening as coronavirus (snowden, ) . but no worldwide panic ensued. neither the world economy nor that of any separate nation came to a standstill. one may argue that all of the recent pandemics proved far less devastating than was originally expected. but mitigation of coronavirus on a massive, coordinated scale began before it was known how devastating it might be (which is still not really known): reports that china was investigating a respiratory illness in wuhan appeared only on december , . the chinese government imposed a lockdown on the -million-large city of wuhan on january , . on january , when only one case of infection on the american soil was identified, the coronavirus task force was created in the united states, and on january , a ban on travel from china was imposed. closure of inessential businesses and schools, stay-at-home orders and construction of new medical coronavirus-ready facilities in record-breaking times followed. although the response of some other countries (japan, south korea and taiwan in the immediate vicinity of china, but also italy) was independent, most of the world was directly influenced by the reaction of china and the united states. within the first two months of the pandemic, economies contracted around the world, registering negative growth, unemployment skyrocketed, lives were universally disrupted, leaders interpreting this as they would results of a war on domestic soil and publics taking this in stride as they would indeed a war effort. what was different in the cases of h n , for instance, and coronavirus in the first two months of the declared pandemic? nothing. the difference in the reaction was not a function of the known difference in the nature or threat of the virus; it was a function of a difference in the political configuration of the world at the two points in time when the virus appeared. in april , when h n was first reported, the united states was still the one uncontested (though resented and attacked) superpower in the world. no nation yet took the place of the soviet union vis-à-vis it, challenging its position as the world's leader and arbiter. the superiority, the dignity and authority of the united states were beyond competition, if not beyond idle question. in , this was definitely not so. china, which only announced its nationalism in at its coming out party during the beijing olympics, has been steadily and at an increasing speed gaining on the united states in this competition in the past years, and the chief american national interest-the interest in superiority, dignity and authority-was now at stake. chinese leadership used coronavirus (whether intentionally or not) to challenge the united states to a single combat, so to speak. could you match us, president xi essentially offered, in containing a pandemic? the united states could no more disregard this challenge than it could disregard the sputnik in . and so, the public health race started: who could build a larger hospital in a shorter period of time, produce more ppe, administer more tests, stop outbreaks sooner and ensure more cooperation from the population? what could the rest of the world do, but follow the example of the two giants, disputing who would preside over it past ? now let us address the question of the possible effects of the pandemic on nationalism. would it, for instance, strengthen nationalist and especially ethnic-nationalist conflicts? given the news reaching us from washington and beijing, it seems clear that it has strengthened the nationalist conflict between the united states and china, which is as momentous as a nationalist conflict for the world today, as the nationalist conflict between the united states and russia (ruling over the soviet union) was at the time of the cold war. it is also quite clear that the pandemic had brought to the surface the nationalist conflicts within the eu, undermining the confidence in globalization in the one region which has been seen by experts as its empirical proof-the proof that human society was becoming transnational, transcending its national stage and moving towards a global community-and even among its staunchest erstwhile supporters. the universal reversion to nationalist policies and defence of particularistic national interests at the expense of transnational solidarity during the pandemic, however, only proved that rumours of nationalism's demise in the core western european nations have been grossly exaggerated. widespread manifestations of euroscepticism, such as strong national feeling in france, italy, the netherlands and so on, or even brexit, have not been regarded by theorists of globalization as an empirical contradiction of their theoretical position, but as proof of reactionary, right-wing or even extreme right political agenda of populist leaders and benighted, false consciousness among their uneducated followers. now it is obvious to all that the theorists were wrong (though how long this would remain obvious is another question): thanks to the pandemic, globalization today no longer seems the obvious current stage of human development, and nationalism no longer appears as the stage obviously transcended. nationalism in western europe (in distinction to central and eastern europe, for instance) has traditionally not been ethnic however, but rather individualistic, as in britain, or collectivistic-civic, as in france, italy and spain. would the pandemic fuel ethnic nationalist conflicts? the psychological foundation of ethnic nationalism is ressentiment, that is, existential envy, which is most efficiently assuaged by the humiliation to the point of elimination of the envied other; therefore, ethnic nationalism is inherently aggressive (greenfeld, ; greenfeld & chirot, ) . where it exists, anything can serve as fuel for ethnic aggression. the pandemic has already added to anti-semitic conspiracy theories (very much in line with medieval poisoning of the wells narrative born during the black death) in palestine and among certain publics in europe (adl, ). anti-semitism, of course, is the most deeply embedded institution (established way of thinking and acting) in the monotheistic world, predating nationalism by many centuries-and for this reason offering a particularly virulent and reliable channel of expression to ethnic nationalism-but one can imagine temporary flare-ups of less widespread ethnonational hostilities, in which a group identifies the object of ethnic national antagonism as the carrier of the virus. and, finally, will covid- reinforce or erode nation-state-that is, nationalism, nationalist institutions-in the long run? leaving aside the question of what can be said about the long run, in general, we should consider this in the wider framework of processes involved in social change, briefly sketched above. to use the most striking example of the social disruption caused by a sudden assault of infectious disease, the black death, the plague might have disrupted the medieval society of orders and shaken this social structure. land became cheap and labour dear, which allowed people from the lower classes to behave as if they belonged to the upper ones and encouraged intermarriage between poor noblemen and daughters of rich commoners. however, as with a dilapidating building, the unravelling of society did not in itself provide any orientation for reconstruction. the thinking remained the same, and for several centuries after the plague years of - , the reconstruction took the form of piecemeal patch-ups: sumptuary laws characterized the period, reflecting both that the old order was unravelling and that the only way society was imagined was exactly as it had been before the pandemic (cantor, ; cohn, ; herlihy, ) . only when reality was reimagined and new (national, as it happened) consciousness appeared did the direction of reconstruction became clear and set. institutions, which, as already durkheim emphasized, are just established ways of thinking and acting, are never stable-they are always in the process of waxing and waning, strengthening, weakening and modifying. conceptualization-ways of thinking, that is, to use weber's terminology, ideals, especially if encoded in laws, sacred texts, whether religious or secular, such as the american declaration of independence, popular and high culture, and so on-is always their strongest feature, but can rapidly be abandoned, if the interests supporting these ideals disappear. the interest behind nationalism and its institutions (e.g., nation-state)-dignity of personal identityis alive and well. covid- also ranged behind it the essential material interests (health, life and livelihood), pointing at the same time to the inability of transnational institutions-globalization-to serve these interests. it is transnational institutions, rather than nation-state, that are likely to fall victim to the pandemic. i would like to interpret the three questions as addressing national identity, policy-making and state-building, respectively. greenfeld is right to highlight how covid- has been politicized by growing tensions between the united states and china over a range of issues. this can be explored further by looking at the way in which covid- is being used in a process of mutual identity construction, which makes it impossible for medicine and science to be politically neutral. a good starting point is the naming of the virus. who has been aware that identifying the geographical origin of a virus can provoke a backlash against members of a particular religious or ethnic community since , at least, when it produced guidelines that call on governments to avoid this (who, ) . the convention was breached when the trump administration saw political mileage in using labels such as "wuhan virus" and "china virus" instead of the neutral name "covid- ," leading the chinese government to castigate it as suffering from an "ideological virus" (people's daily, ; wang, ) . this is despite the fact that the chinese government had already used the name "wuhan virus" to imply that the epidemic was a localized outbreak. it may be true, as greenfeld points out, that there has been an unprecedented scale of international coordination to contain covid- , but the history of pandemics shows that measures to control movement can be used to form national identity. this actually goes back to the age of empire, when thousands of muslim pilgrims were detained under sanitary controls imposed on the red sea area. in contrast, few people called for the quarantine of lawrence of arabia or other allied soldiers returning from the middle east in world war i (chase-levenson, ). a similar dynamic can be seen when various countries responded to covid- by imposing bans on travel from china in february , motivating the chinese government and commentators to make accusations of racial prejudice. beijing's ambassador to israel even went so far as to liken the closure of borders to the turning away of jewish refugees during the holocaust, which the embassy had to quickly retract (the guardian, ). this is typical of the process by which governing elites use the spectre of the external enemy, or the "other," to build national identity, that woods and schertzer draw attention to. at present, china and the united states are clearly using covid- in this way. this is illustrated by the controversy that blew up when the wall street journal published an article titled "china is the real sick man of asia" in february (mead, ) . china reacted by expelling three of the newspaper's reporters, while its foreign ministry warned that it "must be held responsible for what it has said and done," to which us secretary of state mike pompeo responded that "mature, responsible countries understand that a free press reports facts and expresses opinions." it is also important acknowledge that the pandemic is being used for a more positive construction of identity. this is quite clear in the way that the chinese government is using its apparently successful containment of the pandemic to propagate the superiority of the "china model" of politics, after the legitimacy of the chinese communist party (ccp) was badly dented by the early mismanagement of the crisis. by describing the campaign in terms of a "people's war," it can also be linked with the narrative of the ccp's "salvation of the nation" from japanese aggression and misrule by the nationalists in the s and s. one of the most disturbing aspects of the covid- crisis is the way in which it is used to weaponize medicine in ethnic and nationalist conflicts. this is most evident in the ccp's attempts to exert control over territories that are central to its nationalist mission. it could already be seen in the summer of . during that time, medics were subjected to police intimidation, arrest and surveillance as they came to the aid of citizens who were injured in demonstrations against the introduction of a law to extradite residents to mainland china, according to dr darren mann's eyewitness testimony before the house of lords on december , . such behaviour is in breach of the principle that access to treatment is a universal right without distinction of race, religion, political belief and economic or social condition, as enshrined in the who charter. this was already a strong deterrent to demonstrators when beijing took advantage of a ban on mass gatherings in the territory to impose a national security law in may , which will criminalize criticism of the ccp as unpatriotic and secessionist. when demonstrators defied the ban, they were condemned as a "political virus" (scmp, ). the use of covid- to fuel a nationalist conflict can also be observed in china's insistence that taiwan should be excluded from who, on the grounds that it is a part of china, despite its excellent record in containing the pandemic. it is too early to know how covid- will shape taiwan's identity politics, but the same situation during the sars epidemic of - allowed its incumbent president to use the "chinese plague" to galvanize flagging support in the polls by holding a referendum on demanding representation in international organizations, which helped him to win re-election in . given that an opinion poll conducted before the virus hit taiwan shows that the proportion of the population who self-identify as taiwanese has already risen to a new high of %, while % identify as both taiwanese and chinese (pew, ), taiwan's current president can gain substantial political capital by ramping up the campaign for who representation. the potential for covid- to fuel a nationalist conflict is further heightened when such issues become part of global and regional geopolitics. this is deepening as taiwan gains substantial support from other democratic states, while china appears to be taking advantage of the health crisis to step up its naval and air force intrusions into the waters around the island and into the south china sea. this growing linkage of the pandemic with the national security of the united states and china creates a context within which individuals in both countries are likely to be harassed as carriers of covid- , especially in the context of the rising populism that is highlighted by miller-idriss. this can be seen in the united states, where anybody deemed to be "chinese" due to their east asian features has become more liable to be harassed and assaulted. in china, where popular nationalism has long been used by the ccp as a source of legitimacy, xenophobia been fed by the narrative that the party is fighting and winning a "war" against a virus that was sent by the united states and is being spread by foreigners. there have been particularly serious cases of racism towards africans, due to the erroneous belief that they are unhygienic carriers. while miller-idriss is right to point to the ways in which covid- has been used to fuel anti-government extremism and conspiratorial sedition, it is also possible to find examples where civil society actors have criticized its use for nationalistic purposes: some reporters and editors at the wall street journal signed a letter calling for the "sick man" headline to be changed and for an apology to be made; chinese commentators have pointed out that it was their own intellectuals who began to refer to their country as a "sick man," going as far back as the defeat of the qing empire by japan in . such voices will remain marginal compared with the advocates of nationalism, however, unless covid- gives medical science sufficient authority to force the kind of cooperation between states that will weaken national sovereignty. history provides little evidence to support this prospect, however. from the coordination of quarantine procedures between the italian city-states down to today's who, contagious diseases have allowed governments to steadily accrue power over their citizens. china's use of information and communications technology to surveil its citizens as it manages covid- marks a new stage in this process. the dangers posed to civil liberties in democratic systems are also shown by cases such as the use of mobile telephones to identify and trace a disproportionate number of south korea's lgbt community, who face serious discrimination as a result. the state will become even more powerful if covid- justifies the introduction of new barriers to migration and the targeting of border health checks according to the national origins of travellers. the current crisis also shows how disease can be used not only to undermine the authority of scientists and medics, as miller-idriss points out, but also to turn them into political actors and national symbols. most controversial is the casting of dr li wenliang, as a "martyr" after he died from the virus, despite having been detained and disciplined by the authorities for trying to warn his colleagues at the early stage of the outbreak in wuhan. he the harnessing of scientists and medics to the nation-state can even be traced back to the china's first international conference, a meeting of epidemiologists in to discuss a pneumonic plague that had killed some , people in manchuria. to be sure that a "chinese" scientist should play a leading role, the qing empire appointed dr wu lien-teh ( - as its representative, despite the fact that he was born in malaysia and was thus a subject of the british empire. having been on the receiving end of the racism of european scientists and diplomats, wu was happy to lead a project that was partly seen as a way to prevent japan and russia from using the plague to assert their growing control over manchuria (wu, ) . he would go on to become an authority in the emerging international health system, challenge british interests in malaya by establishing an anti-opium society, campaign to remove racial discrimination in the provision of public services, and co-author a history of chinese medicine (wu & wong, ) . members of the scientific community can thus be agents of nationalism as much as they can be a force for cooperation. the latter becomes less likely as the decoupling of the united states and china requires them to prove their loyalty or face accusations of subterfuge or even espionage. the need for states to ensure self-sufficiency and reliable partnerships for the supply of essential medicines and protective equipment is also leading to the securitization of health, which will accelerate the deglobalization of trade and the movement of people. the recent decision of the united states to withdraw from who due to its handling of the pandemic thus looks more like a throwback to the years when sovereignty trumped international cooperation and brought down the league of nations than a world in which the nation-state is in decline. i thus agree with greenfeld that transnational institutions are more likely than the nation-state to be damaged by the pandemic. there are several dimensions to the relationship between nationalism and covid- that ought to be disentangled, but first, let me be clear about how i understand the concept of nationalism itself and the version of it i analyse here. nationalism is an exclusionary political project to make the state congruent with the nation (fox and miller-idriss ) . this can take many forms, from fully secessionist and independence movements to xenophobic and antiimmigrant expressions within an existing state. the current form of nationalist governance that we have seen emerge in several global states is what i call populist nationalism. populism is both a schema (way of thinking) and a rhetorical strategy that pits the ordinary, pure people against the corrupt elites (bonikowski, ; canovan, ; brubaker, ; miller-idriss ; mudde, ; müller, ) . populist nationalism, in turn, extends this pure people-nefarious elite dichotomy to a framing in which all "others" pose an essential threat to the pure nation and its ordinary people. only a stronger state, so the argument goes, can protect the nation from the growing danger posed by immigrants, ethnic others, non-christian religions and more. this is what jan kubik ( ) calls a "thick" form of populism, in contrast to mudde's ( ) description of populism as having a thin ideology. others have described "thick" populism using slightly different terms, such as rogers brubaker's classification of vertical and horizontal dimensions of populism, where the vertical dimension positions the people against the elite and the horizontal dimension creates intense polarization and fixed boundaries between groups of people (brubaker, ; berezin, ; kubik, ; miller-idriss, ) . populist nationalism is the form and expression of nationalism that i refer to in this essay, although i will also use the shorthand "nationalism" to refer to it. with this understanding of nationalism, i return to the relationship between nationalism and covid- . i suggest that there are at least three major impacts to explore. first, early indicators suggest that there is a direct impact of populist nationalism on the public health, infection rates and mortality rates of covid- . as i write this, several of the countries in the world with the highest covid- infection rates are led by populist nationalist leaders-including the united states, brazil and the united kingdom. the united states alone is responsible for over a quarter each of covid- infections and deaths globally, although the us population represents only . % of the global population (see world health organization, , online; united states census bureau, , online). why would populist nationalism itself be detrimental to a public health crisis? one reason is that populist nationalists' attacks on the "corrupt elite" have gone well beyond critiques of political leaders and opponents to include other "elite" experts, academics and scientists, as evidenced by a rejection of climate science and global environmental agreements, for example. undermining and delegitimizing scientific expertise and global cooperation and information sharing makes it significantly more difficult to convince the public of the benefits of shelter in place orders or practices to reduce the spread of the disease. in the case of covid- , populist nationalist leaders are thus more likely than other national leaders to reject scientists' advice, attack global organizations like who, promote scientifically unproven and potentially harmful treatments for covid- and reject scientifically proven practices like wearing masks in public. populist nationalist anti-elite and antiscience sentiments have undoubtedly led to higher covid- infection and mortality rates as a result. populist nationalists do not only attack and undermine scientific expertise, of course. the purity of the people, within populist nationalist frames, rests both in contrast to corrupt elites and to racial, ethnic, religious and immigrant "others." this is where the second impact of nationalism on covid- outcomes becomes clear. across europe and north america, there has already been a documented rise in xenophobic, anti-immigrant, anti-asian and anti-semitic hate during the global pandemic. the us administration's insistence on using the term "wuhan virus" or "chinese virus" is one of "many strategies of apportioning the blame for the (spread of the) virus to a specific place/country and to construct the disease as a foreign-grown threat to the nation" (nossem : ). in the united states alone, over , anti-asian hate incidents were reported within the first weeks of a new website established by asian american and pacific islander civil rights groups (lee & yadav, ) , to name just one example (see stop aapi hate reporting center, n.d. online) . such xenophobic expressions of nationalism are part of a clearly documented, pre-covid- rise in far right and extremist hate and the legitimation of white supremacist extremism (ebner, ; miller-idriss, mudde ) . white identity and the need for its protection and defence is a common thread across white supremacist and white nationalist beliefs and practices (belew, ) . during the covid- pandemic, these expressions have found a home in the circulation of memes and social media commentary that scapegoat entire populations as being responsible for the virus and its spread (see anti-defamation league, ) . dehumanizing language about "dirty" immigrants carrying disease has accompanied immigration bans along with border closures, asylum application denials, deportations and more, even while the practices of local "native" populations that rapidly spread the virus in local churches, parties, funerals, ski lodges and more have continued in more or less unchecked ways. at the extreme fringe, moreover, there are clear risks that the covid- era will help reinforce white supremacist extremists' sense of white victimhood and concomitant emotional appeals to protect, defend and take heroic action to restore sacred national space, territory and homelands (miller-idriss, ) . the third impact that has emerged as a result of the relationship between nationalism and covid- is the rise in anti-government extremism and conspirational sedition (finkelstein et al., ) . anti-government and apocalyptic far right extremists have rapidly grown in online and offline presence across the united states and europe, in part through organized protests against state and national shelter in place orders. calls for violent uprising against the state, political opponents and law enforcement-resulting in part from widely circulating misinformation and disinformation about governments' responses to covid- -have already inspired several violent attacks on law enforcement and at least two planned or enacted plots against hospitals. the growing popularity of conspiracies about a "deep state" and an apparent new convergence among anti-government groups across the political spectrumincluding anti-vaxxers and flat earthers, qanon conspiracy theorists, guns' rights advocates, patriot militias and white supremacist extremists-have created a combustive mix that brings a high risk of serious violence, particularly as we head into a likely second wave of spiking infections and shut downs in the fall of . conspiracy theories about governments' and corporations' plans to use a vaccine to microchip, neuter or control citizens are also circulating widely in extremist circles, which suggests that nation-states have a significant implementation challenge ahead of them even after a vaccine is successfully produced. covid- is likely to fuel ethnic and nationalist conflict in several ways. in the global north, as discussed above, rising xenophobia, conspiracy-fueled anti-asian and anti-semitic violence and anti-immigrant hate are already prevalent during the covid- pandemic. the potential short-and long-term impacts of school and university closures on youth radicalization are also significant. in the united states alone, over million youth in the primary, secondary and postsecondary systems are currently affected by school and college closures. this has led to massive increases in online engagement in ways that create incalculable risks of engagement with extremist material and recruiters. shortly after the pandemic began, us federal law enforcement issued warnings about the increased risk of child exploitation as a result of highly online youth presence, combined with reduced parental/caregiver supervision and lessoned interactions with other trusted adult networks, including teachers, coaches, youth group leaders and adult relatives outside the home (federal bureau of investigation, , online). similar risks exist for online radicalization (e.g., see state of new jersey office of homeland security and preparedness, ). the impact of extraordinary amounts of time spent online during the covid- pandemic-along with a risk in the drivers and grievances that create susceptibility to radicalization, such as anxiety, uncertainty, isolation and lack of purpose-will be clearer as time passes, but should be understood for now as a high-risk situation related to potential future violent extremism and terror. in the global south, covid- will potentially exacerbate ethnic tensions or fuel new ones in already-fragile states. a heightened lack of trust between local communities and governments or international organizations is part of the problem-in some cases, caused by very real abuses and instances of violence perpetrated by some frontline police and military responders during covid- curfew enforcement. in places where trust in governments is already low, or where there are existing grievances about inequitable distribution of resources, uneven responses in health care provision or distribution of resources can fuel ethnic conflict. these vertical tensions (between communities and authorities) are matched by deeper horizontal tensions between ethnic groups as shelter-in-place orders have reversed gains that had been made through promising communal engagement programmes that brought people together across dividing lines. as families retreat into ethnic communities, the fragile bonds from emerging crossethnic forms of engagement and cooperation are at risk. finally, both kinds of tensions-vertical and horizontal-are further heightened through the actions of bad actors who have circulated unreliable sources of information, disinformation, misinformation and conspiracy theories about the virus. some campaigns have targeted ethnic minorities through labels like the "rohinga virus," the "muslim virus" or the "refugee virus," aiming to produce fear and uncertainty and incite conflict (see search for common ground, n.d.). i would expect to see splintering on this question, for several reasons. one has to do with the issues of trust in government discussed above. in countries where the national response has strengthened public trust in the government-such as germany and new zealand-the nation-state will likely be strengthened. but in places where trust is weakened as a result of the government's response to covid- , including in the united states but also in more fragile states in the global south, the nation-state will likely be further eroded. the widespread circulation of misinformation, disinformation and conspiracy theories related to the virus and a covid- vaccine will also exacerbate declines in the nation-state's power, particularly in states where elected officials have failed to counter or have actively supported some conspiracy theories, even prior to covid- (see rosenblum & muirhead, ) . the same is likely true for the ways that covid- has illuminated existing disparities in health care provision across ethnic and racial groups. the drastically different infection and mortality rates for minorities compared with whites in the united states, for example, make it clearer than ever that the nation-state does not serve all its people equally. the uneven loss of life for black americans and communities of colour should be a wake-up call to nationstates and their citizens about the need for systematic change in social services and health care provision, as well as the need to address ongoing legacies of structural racism and discrimination. i would argue that the extent to which nation-states respond to these grievances will play a big part in whether the pandemic ultimately is a strengthening or a weakening force for the nation-state more generally. finally, increases in ethnic group conflict and political or ethnic group polarization and hate in the wake of covid- continue will also likely have differential impacts, depending on how states react. countries whose local, regional and national leadership firmly and unequivocally condemns hate and scapegoating related to the virus may be able to come out of the pandemic with stronger and more resilient communities and nation-states. but in places where political leaders ignore or exacerbate these tensions and contribute to further polarization, it is hard to see how covid- will not contribute to the further decline of the nation-state and the people's identification with it. we approach all three questions through a lens that conceives of the covid- pandemic as a crisis. this enables us to construct a typology of the differing ways that crises can impact the development of nationalism. we then use this typology to frame our discussion of how the pandemic could shape nationalism and how nationalism in turn could shape the response to the pandemic. covid- constitutes a severe global threat. it has significant potential to trigger multiple, cascading crises in nearly every aspect of our lives. in addition to the presence of a threat, crises typically involve systemic disruption, uncertainty and stress (brecher, ; quarantelli & dynes, ; rosenthal et al., ) . as a result of this widespread upheaval, crises have a high potential for triggering change (falleti & lynch, : . the concept of crisis has not been a specific focus in the field of nationalism studies. that being said, events that could readily be defined as crises, such as warfare, revolution or economic catastrophe, have been central to research on nationalism. this literature suggests that crises can impact the development of nationalism in three distinct ways: they can be ( ) constitutive, ( ) amplifying, or ( ) transformative crises as constitutive events. crises, particularly those that are associated with revolution, can be constitutive events in the formation of new nationalisms. indeed, the french revolution of is often depicted as the formative event for the worldwide spread of nationalism. during a revolution, the struggle against perceived illegitimate rule can provide a catalyst for the emergence of nationalist sentiment-the idea that "we" constitute our own nation and therefore ought to have political autonomy (see hobsbawm, ; bell, ) . similarly, warfare can be a powerful catalyst for the emergence of nationalist sentiment through conflict with a common threat (hutchinson, , pp. - ) . crises as amplifying events. crises can also have an amplifying effect on existing nationalisms. as such, they can reinforce both solidarity and division within and between national communities. solidarity is often expressed through a "rally around the flag effect," in which people unite under national leaders during the crisis (brody & shapiro, ; mueller, ; oneal, lian, & joyner, ) . nationalism can also provide a collective cipher for succour and inspiration during a crisis, whereby myths, symbols and practices associated with past crises are "rediscovered" and applied to the new crisis (hutchinson, ) . the crisis might also give rise to new cultural content and practices, which can further reinforce solidarity (hutchinson, ) . however, the inevitable search for responsibility that accompanies a crisis can also amplify divisions with perceived malevolent "others," both within and outside the national community. thus, during a crisis, it has been widely observed that attacks against internal minorities tend to surge, while the potential for conflict with external adversaries is heightened. crises as transformative events. as much as crises can amplify existing nationalisms, they can also be transformative. for example, crises can lead to new configurations of cultural boundaries between who is perceived to belong and who does not. previously excluded minorities might be incorporated into the national "we" as they make common cause against the threat. for example, the war against a genocidal germany was an important catalyst for the increased social inclusion of jews in america (alexander, : chapter ) . however, by the same token, minorities that were once included, or at least tolerated, might now be excluded if they become associated with the new threat. thus, after the terrorist attacks of september , muslims in the west became the new significant "others" (byng, ; poynting & mason, ) . in the international sphere, perceptions of who is the "friend" and "foe" can also undergo reconfiguration during a crisis. this occurred, for example, in the dramatic reversal of how the west perceived the soviet union following the world war ii. so, which of these potential pathways might nationalism take in the wake of covid- ? it is too early to tell whether this pandemic will be a constitutive event for the rise of new nationalisms. the same goes for whether it will have a transformative impact. there are signs of a potential "hamiltonian" moment in europe with the agreement between germany and france to pursue a € bn aid package for the eu, but there are no guarantees that all member states will agree to the proposal, nor whether this will persuade the citizens of those states to relinquish their national identities in favour of a pan-european identity. nevertheless, in some instances, there are early signals that covid- could move the boundary of who belongs and who does not. in the united kingdom, the importance of ethnic minorities to the nation has been made salient through their increased visibility in the professions on the frontlines of the struggle against the pandemic (hirsch, ) . this is also happening in canada, where leaders are considering making asylum seekers permanent residents to recognize their work in long-term care facilities (seidle, ) . but these are only two examples and it is still early days; in many other cases, we are seeing the opposite happen where migrants are being targeted. we therefore think that among the three pathways we described, the most likely impact of covid- will be to amplify existing nationalisms. there are already indications that covid- is amplifying nationalism across numerous contexts. most national leaders are enjoying a surge of support. myths and symbols related to how nations endured past crises, such as warfare, have been rediscovered and repurposed by national leaders in order to inspire their constituents as they confront the pandemic. new collective rituals have also emerged, such as weekly national "clapping" for key workers in the united kingdom, or the newly founded national days of mourning in spain. but this amplifying effect has not been entirely solidary. for example, in the united states, there has been a surge in racist attacks against asian americans (tavernise & oppel, ) . meanwhile, as we discuss in our response to question , it is fuelling division in the international sphere. the divisive othering and attribution of responsibility that stem from a crisis can increase the likelihood of intrastate political conflict, but not necessarily lead towards interstate violence. the splitting of populations into categories of "us" and "them" is central to nationalism. as fredrik barth ( ) points out in relation to ethnic identity, it is through contact with "others" that we construct a sense of "our" group. this othering tends to also entail a moralizing process that glorifies "us" and vilifies "them" (schertzer & woods, a) . and therein lies the rub: at times of crisis, this tendency can propel ethnic and national conflict because it creates logics that rationalize violent or discriminatory practices against perceived malign or corrupted "others." this is because nationalism provides a cultural roadmap for attributing responsibility for a crisis, in the sense that it is typically the vilified "others" that shoulder the blame. with covid- , attributing responsibility to an "other" is somewhat indirect, because ultimately, the responsibility lies with a virus rather than human actors. covid- is an "invisible enemy," as donald trump likes to quip. in this regard, the pandemic is akin to a natural disaster. but even natural disasters typically provoke efforts to attribute responsibility to human actors-to lay blame at the feet of an individual, group or institution for failing to act appropriately (bucher, ; yates, ) . this process of attributing blame can be highly conflictual. as the conflict takes shape, it tends to align with and amplify existing cleavages (tilley & hobolt, ) . for example, after hurricane katrina, an emotive struggle over responsibility ensued that ultimately enflamed a longer running conflict over the place of african americans in america (eyerman, ) . similar processes are emerging in relation to covid- . the pandemic is amplifying nationalist sentiment (see legrain, ) , which is precipitating a "politics of blame." this is particularly visible in relations between the united states and china. as hughes discusses in this exchange, a relationship that was already strained is now rapidly worsening, as the two countries blame one another for the pandemic. there is a fear that these political disputes may lead towards violent conflict. the vastly simplified argument here is that covid- creates a series of economic, social and political crises that increases incentives and opportunities for interstate conflict. and when rising nationalism is added to the mix, it increases the probability that leaders will opt for war (see hutchinson, ) . in our view, this account gives too much power to nationalism as the key driver of conflict. we know many of the conditions and logics that drive interstate warfare, and covid- does not necessarily lead us down these pathways. as others have argued, the pandemic has created significant logistical issues for mass troop mobilization, it has shaken the confidence of states and leaders and there is no necessary link between economic downturns and warfare-recessions are a bad predictor of interstate conflict (posen, ; walt, ) . while nationalism can shape decisions and introduce irrationality, it does not necessarily have the structuring power to overcome the current barriers to interstate warfare. the view that increasing nationalist sentiment will inevitably lead to violent conflict also oversimplifies nationalism. this logic assumes that nationalism is always dangerous and illiberal, which in our view is an outmoded that builds on a normative distinction between bad (ethnic) and good (civic) forms of identity. what is more likely is that covid- will amplify internal ethnic divisions within states. the process of othering, the search for blame and the calls to protect our "own" are driving a dynamic whereby foreigners and migrants are being targeted in many states. as miller-idriss details in her contribution, asians in western countries are suffering racist and violent attacks as perceived stand-ins, carriers and collaborators of the "silent enemy." migrants are facing hostility as potentially dangerous vectors of the virus and threats to the host society. asylum seekers are being denied entry into many countries or held in dangerous camps where they are at greater risk of contracting covid- . in short, some ethnic divisions within states are becoming increasingly salient. this type of internal ethnic conflict is not directly attributable to the pandemic. rather, it reflects how the internal dynamics of a national community are shaping the response of leaders and the public at a time of crisis. political culture matters in how covid- is shaping nationalism: it is the nation's cultural and political characteristics that are driving the emergent dynamics of conflict. these dynamics are not necessarily marching us down a path towards interstate violence, but they are making existing ethnic divisions within and between nations more salient. the nation-state has a privileged position in our political order. the international system is based upon the idea that political communities, called nation-states, deserve autonomy. the logic of nationalism provides legitimacy to this order: it is because states protect and represent a nation that they have sovereignty (mayall, ) . at first blush, we might expect that a global pandemic would erode the status and autonomy of nation-states: international collaboration and a pooling of resources are necessary to combat the virus. and yet, nation-states are leading the response to covid- , while the legitimacy of international organizations like the who is being questioned. given these early trends, and what we know about the endurance of nation-states, in our view, covid- will likely reinforce the nation-state. the early signals point towards a trend of nation-states greatly increasing their power in the face of covid- . they are reinforcing borders, curtailing migration, limiting internal population movements, spending vast amounts of money on economic stimulus and increasing surveillance of citizens. many of these moves have come at the cost of individual liberty and privacy (economist, ) . some of these measures will be relatively short lived, and others will likely be difficult to roll back. regardless, these patterns recentre the state in our lives. they bring the state back into view as a powerful actor (skocpol, ) . but these developments are about more than simply expanding the administrative capacity of states-they also reinforce the nationalist idea that they represent "nations." leaders and publics alike have embraced the rationale that increased state authority and power is necessary to protect the safety and way of life of the nation. this rationale is evident in the competition over medical supplies, which is increasingly nationalist in tone (goodman, thomas, wee, & gettleman, ) . european union states have worked against one another by limiting the export of protective equipment to other members in need. the united states has taken actions to limit the export of protective equipment to canada. conflicts over the production and distribution of an eventual vaccine are already taking shape. rather than concerted international collaboration and coordination, we are seeing increasingly protectionist approaches driven by the logic of the nation-state. at the same time, the nation-state is facing threats-from below and from above. there is an argument that substate national movements may use covid- to push for greater autonomy. this could trigger renewed instability, particularly in multinational states. but the evidence so far suggests the contrary. many multinational states are seeing a remarkable degree of pan-national solidarity. both dynamics are playing out now in the united kingdom: an early surge in solidarity across the union is increasingly diverging along national lines, with scotland, wales and northern ireland adopting different approaches to the pandemic. however, even if covid- does destabilize multinational states through national minority mobilization, this does not completely threaten the idea of the nation-state. national minorities seeking independence are not working to undermine the international society of nation-states; they are working to join it (williams & schertzer, , p. ). covid- may also threaten the nation-state from above. the economic and political crises that it will inevitably trigger can create opportunities for powerful nation-states to extend their influence over less powerful ones. in this regard, the pandemic may enable new forms of imperialism, undermining the status and sovereignty of nationstates. there are clear parallels supporting this argument: "foreign aid" provided by powerful states and institutions during past crises often belied thinly veiled forms of neo-colonialism (see charbonneau, ; fieldhouse, ; langan, ) . but even a resurgent imperialism may not undermine the idea of the nation-state system. history can serve as a guide. during the "cold war," the idea of the sovereign nation-state was strengthened. despite the widespread influence of the united states and soviet union, the idea that the world was fundamentally composed of sovereign nation-states did not diminish. therefore, we tend to agree with greenfeld that the covid- pandemic will not diminish the nation-state system in the long run. if we are right-if covid- reinforces the nation-state-then there are some potential perils. the amplification of power and autonomy of nation-states, paired with limited checks and accountability, may have long-lasting effects for privacy, security and democracy. people are rightly fearful that newly emboldened nation-states may hinder the necessary international collaboration to manage the pandemic. but this fear rests on a false dichotomy: a strengthened nation-state is not irreconcilable with strong international collaboration-quite the opposite (schertzer & woods, b) . the security and autonomy afforded by the nation-state can allow actors to engage in meaningful international collaboration. the establishment and growth of our key international institutions and related norms principally stem from actions taken by states, often following major crises. if this collaboration can be undertaken while being mindful of existing power imbalances-listening to the better angels of our nature-it could both assist in the immediate response to the pandemic and improve international institutions and norms over the longer-term. the civil sphere how the world will look after the coronavirus pandemic international scapegoating of israel and jews for spreading covid- ethnic groups and boundaries: the social organization of culture difference bring the war home: the white power movement and paramilitary america for the good of humanity: ludwig rajchman medical statesman the cult of the nation in france: inventing nationalism the black death - : the complete history populism and fascism: are they useful categories for comparative sociological analysis? is nationalism on the rise? assessing global trends ethno-nationalist populism and the mobilization of collective resentment crisis and change in world politics a reconsideration of the rally phenomenon in public opinion why populism? theory and society blame and hostility in disaster complex inequalities: the case of muslim americans after / trust the people!': populism and the two faces of democracy in the wake of the plague: the black death and the world it made the study of critical junctures: theory, narrative, and counterfactuals in historical institutionalism dreams of empire: france, europe, and the new interventionism in africa. modern and contemporary france the yellow flag: quarantine and the british mediterranean world - . cambridge: cambridge university press black death, social and economic impact of the the rules of sociological method going dark: the secret social lives of extremists. bloomsbury. economist. . the state in the time of covid- is this america?: katrina as cultural trauma context and causal mechanisms in political analysis online. 'fbi urges vigilance during covid- pandemic the west and the third world: trade, colonialism, dependence, and development covid- , conspiracy and contagious sedition: a case-study on the militia sphere a new front for nationalism: the global battle against a virus nationalism and aggression greenfeld mind, modernity, madness: the impact of culture on human experience advanced introduction to nationalism nationalism: a short history what is new and what is nationalist about europe's new nationalism? explaining the rise of the far right in europe the black death and the transformation of the west after coronavirus, black and brown people must be at the heart of britain's story, the guardian age of revolution hot and banal nationalism: the nationalization of the masses nationalism and war keynote remarks at the london school of economics workshop on the politics of emotions neo-colonialism and donor interventions: western aid mechanisms the rise of anti-asian hate in the wake of covid- . items, social science research council the coronavirus is killing globalization as we know it foreign policy the legacies of liberalism: path dependence and political regimes in central america nationalism and international society china is the real sick man of asia the extreme gone mainstream: commercialization and far right youth culture in germany the global dimensions of nationalist populism hate in the homeland: the new global far right the populist zeitgeist. government and opposition presidential popularity from truman to johnson what is populism? philadelphia: university of pennsylvania press are the american people 'pretty prudent'? public responses to u.s. uses of force, - people's daily (renmin ribao) pew. . most in taiwan identify as taiwanese do pandemics promote peace? why sickness slows the march to war. foreign affairs tolerance, freedom, justice and peace response to social crisis and disaster a lot of people are saying: the new conspiracism and the assault on democracy coping with crises: the management of disasters, riots, and terrorism beyond multinational canada nationalism: the ethno-nationalist populism of donald trump's twitter communication how nationalism can be a force for good in the struggle against covid- . usapp-american politics and policy blog hong kong anti-government protests: keep 'political virus' of unrest off streets, beijing urges as covid- eases should canada regularize the immigration status of asylum seekers helping fight covid- ? policy for pandemics bringing the state back in epidemics and society: from the black death to the present online extremists exploit covid- to inspire supporters spit on, yelled at, attacked: chinese-americans fear for their safety the guardian. . chinese ambassador to israel likens coronavirus bans to holocaust is the government to blame online. 'u.s. and world population clock will a global depression trigger another world war? foreign policy speech of is indigeneity like ethnicity? theorizing and assessing models of indigenous political representation who issues best practices for naming new human infectious diseases online. who coronavirus disease (covid- ) dashboard plague fighter: the autobiography of a modern chinese physician history of chinese medicine: being a chronicle of medical happenings in china from ancient times to the present period attributions about the causes and consequences of cataclysmic events covid- , nationalism, and the politics of crisis: a scholarly exchange key: cord- -oy e cpx authors: krishnan, lakshmi; ogunwole, s. michelle; cooper, lisa a. title: historical insights on coronavirus disease (covid- ), the influenza pandemic, and racial disparities: illuminating a path forward date: - - journal: ann intern med doi: . /m - sha: doc_id: cord_uid: oy e cpx the coronavirus disease (covid- ) pandemic is exacting a disproportionate toll on ethnic minority communities and magnifying existing disparities in health care access and treatment. to understand this crisis, physicians and public health researchers have searched history for insights, especially from a great outbreak approximately a century ago: the influenza pandemic. however, of the accounts examining the influenza pandemic and covid- , only a notable few discuss race. yet, a rich, broader scholarship on race and epidemic disease as a “sampling device for social analysis” exists. this commentary examines the historical arc of the influenza pandemic, focusing on black americans and showing the complex and sometimes surprising ways it operated, triggering particular responses both within a minority community and in wider racial, sociopolitical, and public health structures. this analysis reveals that critical structural inequities and health care gaps have historically contributed to and continue to compound disparate health outcomes among communities of color. shifting from this context to the present, this article frames a discussion of racial health disparities through a resilience approach rather than a deficit approach and offers a blueprint for approaching the covid- crisis and its afterlives through the lens of health equity. the coronavirus disease (covid- ) pandemic is exacting a disproportionate toll on ethnic minority communities and magnifying existing disparities in health care access and treatment. to understand this crisis, physicians and public health researchers have searched history for insights, especially from a great outbreak approximately a century ago: the influenza pandemic. however, of the accounts examining the influenza pandemic and covid- , only a notable few discuss race. yet, a rich, broader scholarship on race and epidemic disease as a "sampling device for social analysis" exists. this commentary examines the historical arc of the influenza pandemic, focusing on black americans and showing the complex and sometimes surprising ways it operated, triggering particular re-sponses both within a minority community and in wider racial, sociopolitical, and public health structures. this analysis reveals that critical structural inequities and health care gaps have historically contributed to and continue to compound disparate health outcomes among communities of color. shifting from this context to the present, this article frames a discussion of racial health disparities through a resilience approach rather than a deficit approach and offers a blueprint for approaching the covid- crisis and its afterlives through the lens of health equity. ann intern med. doi: . /m - annals.org for author, article, and disclosure information, see end of text. this article was published at annals.org on june . * drs. krishnan and ogunwole contributed equally to this work. t he coronavirus disease (covid- ) pandemic has killed more than persons in the united states ( ) . nationwide data indicate that ethnic minority communities, particularly black, latinx, and native or indigenous communities, suffer disproportionately ( ) ( ) ( ) ( ) ( ) ( ) . this has significant historical antecedents; as evelynn hammonds recently argued, epidemic diseases "lay bare and make visible inequalities in a society" ( ) . yet, at the onset of the crisis, few reported its effect on minorities ( ) . even now, we may not know the full scope and details. many states have published limited statistics, and race-stratified data, once fully released, will need to be carefully interpreted to address the causes of inequity rather than to perpetuate stigma and discrimination ( ) . unfortunately, this comes as no surprise to health equity researchers and historians of medicine and public health. the united states has a long history of racial and socioeconomic disparities, with the current pandemic further revealing the rifts created by historical injustice, structural racism, and interpersonal bias ( - ). although some have touted covid- as a "great equalizer" that strikes across age, sex, race/ethnicity, and geography, we contend that it has magnified the many "unequalizers" in our society ( , ) . to understand the current crisis, physicians and public health researchers have mined history for insights ( ) . most have focused on a century-old outbreak, the influenza pandemic (misleadingly called the "spanish flu"), because covid- most closely approximates it in scope and effect ( ) ( ) ( ) . of the accounts comparing the influenza pandemic and covid- , only a notable few discuss race ( , , ). yet, a rich, broader scholarship on race and epidemic disease as a "sampling device for social analysis" exists ( ) ( ) ( ) ( ) ( ) ( ) . given the excessive mortality due to covid- in minority communities, reexamination of such historical antecedents is fruitful. although this scholarship hesitates to offer predictions, this kind of analysis can provide orienting frameworks, reveal nuance, and modulate our approach to the current crisiswhich has been called "unprecedented," reflecting a lack of historical context. we examine the historical arc of the influenza pandemic, focusing on black americans and showing the complex, sometimes surprising ways it triggered particular responses both within a minority community and in wider racial, sociopolitical, and public health structures. shifting to the present, we frame a discussion of racial health disparities through a resilience approach versus a deficit approach and offer a blueprint (table) for approaching the covid- crisis and its afterlives through the lens of health equity. elected leaders should exercise an abundance of precaution when facing potential public health threats. providing accurate information, overpreparing, and not underreacting are key. leaders (whether community based or elected) are role models. communities of color may look to these persons to guide their own behaviors. persons in positions of power or influence should be held to high standards and model the importance of strict adherence to strategies aimed at controlling and reducing infectious disease spread. transparency and communication are key to timely adoption of mitigation strategies by the general public; when these are absent, erosion of trust ensues. early transparency and communication are key to timely adoption of mitigation strategies by the general public. however, even with these strategies, historical precedence may make it difficult for communities of color to trust information from the government. in this scenario, it is especially important to engage trusted messengers, such as community leaders and faith-based organizations, to help deliver critical information. for communities of color, each conversation and transfer of information is an opportunity to either rebuild trust or further substantiate mistrust. elected leaders should thus be held accountable for misinformation, and the public should be aware of credible sources of information. counting and reporting are critical for measuring disparities in health and planning equitable interventions. technology should be leveraged to support data collection for public health surveillance and social service needs. data collected on disease incidence should be stratified by key demographic factors. blaming specific groups for infectious disease spread is counterproductive and can be dangerous for the groups indicted. disinformation based on racism and stigma is unacceptable; leaders in all sectors should rely on scientific facts to guide conversations on infectious disease spread. they should maintain neutral positions and should not place blame on specific groups. social determinants of health are key drivers of health disparities and also affect the ability to participate in infectious disease mitigation strategies. policy initiatives must address social determinants of health before pandemics arise. support for social services must be better integrated into the health care system. health systems should anticipate increased need for social support during pandemics and have strategies in place to deliver services to the most vulnerable populations. this includes enhanced access to technology to support telecommunication for vulnerable populations. chronic medical conditions are significant contributors to morbidity and mortality during the pandemic. health care policy changes are needed to enable access to primary care and preventative services throughout the life course. there will be long-term sequelae related to covid- (both directly because of virus-related morbidity and indirectly as a result of reduced access to care during social distancing periods). the health care system should plan for and anticipate a surge in the need for primary and specialty care services. institutional and structural forces keep communities of color from achieving their full potential. a restorative justice approach that includes the following strategies, among others, should be used: • investments in early education • financial assistance for higher education or trade schools; forgiveness for previously accumulated education debt • investment in public housing; fair and equitable access to home loans • fair and equitable access to business loans; incentives for minority-owned businesses • investment in neighborhood environments: resources for community-led neighborhood violence prevention strategies, increases in green space, walking trails, reduction in food deserts • universal access to health care, including mental health care • integration of faith-based organizations into the health care system • restructuring of the criminal justice system; employment opportunities after incarceration communities of color lead, persevere, and innovate. they play an essential role in building bridges toward trust in the health care system and improving health outcomes within their communities. their contributions help to advance science and medicine and deserve recognition. communities of color should be given opportunities to actively participate in agenda setting, research, and policy initiatives aimed at improving their communities so they can be recognized and acknowledged for their contributions. building and restoring trust is an ongoing process that is necessary to advance medicine, science, and health care. this can be aided through some of the following measures: • support for strategies aimed at improving and maintaining a diverse health care workforce • community-based participatory research throughout all phases of the research process (design, implementation, dissemination, and evaluation) • utilization of trusted community partners and community health workers to aid in community education; improvement in recruitment and participation in research, including clinical trials; gathering of quantitative and qualitative data in the field throughout all phases of pandemic response covid- = coronavirus disease . * all phases should be responsive to the possibility of future waves of disease. historical insights on covid- , influenza, and racial disparities on black americans, who, for example, accounted for an overwhelming number of the deaths in the - smallpox epidemic ( ) . contagion also augmented biologically deterministic beliefs, including that blacks were innately immune to certain diseases. during the - yellow fever epidemic in philadelphia, white physicians, such as benjamin rush, asked black community leaders absalom jones and william gray to "furnish nurses to attend the afflicted" because of the erroneous assumption that blacks could not contract the disease ( , ) . however, in the context of these preceding epidemics, the influenza pandemic forms a unique case study. although all-cause morbidity and mortality in the early th century was higher for black americans than white americans, the few studies examining racial differences in the pandemic found that the black population had lower influenza incidence and morbidity but higher case fatality ( , ) . black physicians shared this view, as evidenced in the journal of the national medical association and local newspaper articles ( , ). meanwhile, white public health figures, like chicago commissioner of public health john dill robertson, used these findings to justify biological determinism, concluding that "the colored race was more immune than the white to influenza" ( ) . rebuttals to these innate immunity theories circulated in the black print media. respected and widely read periodicals, such as baltimore's afro-american, the chicago defender, and the philadelphia tribune, carefully documented influenza's effect, with personal columns, church registers, and town updates listing the many community members who had the "flu," shaming those not taking it seriously, or mourning others, such as a promising young teacher and morgan college graduate ( - ). other articles warned black americans to take adequate precautions and discounted theoretical immunity: "while the death rate from the epidemic of influenza is not as high as the white death rate, colored people are far from being immune of the disease" ( ) . in december , african american columnist william pickens debunked the claim of a white west virginian who claimed the "influenza germ had shown that god was partial in favor of black people." pickens countered that for whites, "when negroes die faster, it is often escribed [sic] to their inferiority," but if spared, "well, that proves they are not human like the rest of us" ( ) . these critiques highlight differences between pandemic coverage and explanatory models in the "mainstream" versus black press-the latter was community-centered, focused on trusted sources and internal solutions, and skeptical about the veracity and benevolence of white responses. how do we account for black americans' lower influenza infection rates and all-cause mortality but higher case-fatality rate during the influenza pandemic? alfred crosby hypothesizes that higher exposure to the less virulent early wave may have made black americans less susceptible to the fall/winter wave ( , ) . this assumes many interlinked circumstances, including higher likelihood of blacks living in over-crowded environments and therefore greater exposure during the spring/summer wave; poorer access to sanitation, potable water, and hygiene than white counterparts; and early exposure conferring immunity against the deadlier autumn wave. segregation may also have functioned as an unintentional cordon sanitaire, quarantining blacks from whites. finally, recall that supporting data are limited by likely underreporting ( ) . nonetheless, it is worth noting the higher case-fatality rate, which could be attributed to several factors still present today: higher risk for pulmonary disease, malnutrition, poor housing conditions, social and economic disparities, and inadequate access to care. in sum, if a black person caught influenza in , they were more likely to die-an outcome which, despite lower infection and all-cause mortality rates, has significant repercussions. aggregate influenza data before and after the - season reflect a more familiar pattern: significantly higher morbidity and mortality among nonwhites compared with whites ( ) . that the outcomes of black americans did not improve in the interim suggests that the influenza pandemic did little to mobilize national responses for improving their health status, a precedent that we hope is not replicated in the current crisis. the broader context of the pandemic is critical for understanding the historical, as well as contemporaneous, landscape of health disparities. a confluence of factors, including social policies of racial exclusion and discrimination, unequal provision of health care, housing inequality, malnutrition, chronic respiratory disease, and increased epidemiologic burden of infectious diseases (such as tuberculosis, typhoid fever, whooping cough, and infant diarrheal illnesses), contributed to lower life expectancy for black americans ( ) . new academic disciplines, such as anthropology, evolutionary biology, genetics, and eugenics, helped promote theories of biological determinism, which compounded older views attributing poor health outcomes to the inferior qualities of black americans ( ) . the jim crow laws boosted white supremacy with these ideologies to enforce racial segregation, and between and , in the thick of the influenza pandemic, approximately half a million blacks fled the punitive south for midwestern and northern cities in the now-famous great migration. however, those cities often greeted them with prejudice, stigma, segregationist policies, and violence, allegedly aimed at improving public health. a march chicago daily tribune headline proclaimed, "rush of negroes to city starts health inquiry"; during the pandemic, the headline "half a million darkies from dixie swarm to the north to better themselves" appeared. reporter henry m. hyde named southern black migrants as disease vectors: "compelled to live crowded in dark and insanitary rooms; they are surrounded by constant temptations" ( , ) . these views provided justification for draconian public health ordinances and restrictive housing covenants that maintained housing color lines and prevented black chicagoans from leaving overcrowded conditions ("the black ( ) . residential segregation also played a role in the outbreak in baltimore, the first large american city to pass drastic housing legislation in . consequently, many black baltimoreans lived in "alley districts" or high-occupancy "tenant houses" with poor sanitation and ventilation and higher rates of epidemic disease ( , ) . influenza overwhelmed medical resources straining under the burden of urban density, unequal living conditions, and a high concentration of military training camps ( , ) . downplaying by authorities like health commissioner dr. john d. blake, who called it the "same old influenza" physicians have long treated, exacerbated the problem ( ). blake eventually reversed course, imposing citywide restrictions and "social distancing," but not in time to stanch the tide. segregation and structural racism extended to medical education and health care delivery, but community mobilization, well under way before the pandemic, was a counterbalance. by the early th century, black activists and professionals led many health institutions and flagship organizations: howard university college of medicine (founded in ), tuskegee institute hospital and nurse training school (founded in ), meharry medical college (founded in ), the national medical association (founded in ), and the national association of colored graduate nurses (founded in ). at the same time, the flexner report (published in ) disadvantaged minority health education-only of the initial black medical schools survived its reforms, and they struggled financially during the influenza pandemic ( ) . black nurses, excluded from world war i service by the u.s. army medical corps and the red cross and battling for inclusion in the u.s. armed forces nurses corps, nevertheless served on influenza frontlines. in october , afro-american declared that these essential workers were "at a premium," noting that the self-same "red cross leaders are appreciative of the response colored women have made . . ." ( ) . yet, black patients were often disbarred from care, leading to local and decentralized efforts to provide care within the community. black professionals took great pride in their role fighting influenza. as dr. john p. turner wrote ( ): the negro physician played a most prominent part in treating and relieving victims of every race . . . [yet] will possibly never be cited in the history to be written of the epidemic. however we want to call to the attention of the medical profession of america the unselfish devotion to duty that impelled three thousand legal practitioners of medicine of african de-scent to work night and day to aid in checking the monster scourge. although most black health professionals did not receive due praise or recognition, disruptions in the wake of world war i and the pandemic did shift the u.s. medical landscape. it was partly because of the "scarcity of white medical men" as well as ardent community efforts and activism that places like the harlem hospital desegregated ( - ) ; louis t. wright, later a prominent surgeon and civil rights activist, became the first black physician to join its staff in ( ) . historians remark that, unlike other cataclysmic events, the pandemic left minimal traces in public memory and culture; its neglect has led to its being called the "forgotten pandemic" ( ). however, this assertion overlooks its multivariate effect on the african american community. although the influenza pandemic does not reveal ready associations between deleterious social, cultural, and economic conditions and poor outcomes (aside from higher case-fatality rate) for black americans, the gaps in historical documentation may reflect inherent disparities and consequences of limited racial/ethnic data collection. this absent archive may indeed have been a setback for public health and health equity-a missed opportunity to intervene on the basis of the specific contexts and unique vulnerabilities of different groups. in this way, the influenza pandemic is an illuminating case study for understanding the role of pandemics in the history of health disparities and the broader health equity movement. for black americans, surviving and fighting the pandemic was a catalyzing step up the social ladder, a cause for communal effort and activism, and a justification for profound engagement with health, which was seen as bound to the greater social condition. it concretized the spirit of community resilience and helped contribute to desegregation and the nascent civil rights movement. however, because of minimal national mobilization to improve the health of communities of color, it also compounded mounting distrust in the u.s. government to intervene and help improve the health and lives of its nonwhite citizens, a wariness that we see replayed in the covid- pandemic. reflecting on the influenza pandemic in the setting of covid- , we note important parallels while recognizing many differences in context. despite the past century's therapeutic evolution, we find ourselves in a situation similar to , without a vaccine or proven treatments for a deadly disease. furthermore, structural inequities have historically contributed and continue to compound disparate health outcomes in communities of color. evaluating historical trends is critical for health equity work, and through attending to the complexities of the pandemic, we have the opportunity to ground our current and future strategies in this historical context, deliver a more equitable pan- historical insights on covid- , influenza, and racial disparities demic strategy, and reduce disparities in marginalized communities. as physicians who also serve other roles (health equity researchers, historians of medicine, educators, and advocates), we propose several areas for intervention and mobilization throughout the various phases of pandemic response. delaying swift public health measures significantly affected the pandemic curve trajectory in the influenza pandemic. cities that enacted swift and sustained nonpharmaceutical interventions had lower excess mortality rates than their counterparts ( - ) . similarly, initial failure to acknowledge severe acute respiratory syndrome coronavirus as a credible threat hampered containment and mitigation efforts ( ). several months later, as much of the nation strategizes reopening, we must maintain vigilant mitigation strategies while aligning recommendations with emerging epidemiologic data. failure to do so could result in new waves of disease, as was the case in . within the african american community, specific communication barriers, augmented by a lack of covid- -related demographic data, contributed to underestimating the pandemic's effect. misinformation and recycled, erroneous narratives about black immunity circulated through social media ( ) . historical distrust of biomedicine amplified these effects ( ) . however, as available data emerged outlining covid- 's devastating disparities, black organizations, leaders, and media outlets aggressively campaigned to dispel myths, implored citizens to heed sanitation and containment advice, and advocated for community resources. this kind of community-led strategy has repeatedly been critical in counteracting national failures to protect minorities. furthermore, such interventions bridge divides forged by historical mistrust-they are central to dissemination of information and community activation ( ) . however, misinformation, oversight, and delayed mitigation strategies alone do not fully explain differential covid- incidence. many have deeply analyzed the effect of social determinants on covid- disparities ( , , ) . this historical inheritance, of which the influenza pandemic forms just episode, shapes how social conditions obstruct minority participation in public health mitigation and containment measures. it also extends to risk factors for chronic disease development, making african americans more susceptible to covid- -related morbidity and mortality ( ) . as a result of redlining, for instance, minority residential environments bear substantial barriers to health optimization, such as reduced green space access, disproportionate tobacco and alcohol marketing, low perceived neighborhood safety, and food deserts ( ) . health equity researchers have proposed reforms, including interventions by local governments to provide food, housing, education, employment, and technological support, but this approach is necessarily reactive rather than reparative and preventive ( , ) . an advantage of the current era compared with is our ability to collect robust data that can inform a more proactive strategy. structural, environmental, and economic data on essential goods and services can enhance epidemiologic data. when stratified at the level of key social determinants of health, this information can be used to identify which communities are most vulnerable and ensure prudent and equitable dissemination of resources. in addition to the relief response, we must examine the nature of blame and stigma during pandemics, paying particular attention to dangerous narratives of personal responsibility as a key driver of health outcomes ( ) . these accounts place the burden of differential outcomes on minorities rather than acknowledging the lasting legacy of structural racism. they also detach minority health from that of the majority rather than viewing it as part of the nation's collective mission. the trajectory of the covid- pandemic remains uncertain; it may abate, or we may face resurgent waves during reopening, as seen during the influenza pandemic. if the latter, we must acknowledge the history of public health response, correcting prior mistakes and attempting to duplicate applicable practices. if the former, we must still consider our path toward equity in recovery. challenges for communities of color will include long-term covid- sequelae, exacerbation of underlying chronic conditions, and mistrust in the health care system, perhaps reinforced by the current crisis. creating antidotes to this mistrust will be critical; components should include collaboration with trusted community and media partners, a diverse health care workforce to offer racially concordant care teams, and community-based participatory research. this will in turn support the actions needed to reduce disparities, including recruiting a representative population into future covid- -related clinical trials and epidemiologic studies, ensuring adequate uptake during vaccination campaigns, enhancing engagement with primary care for improved chronic disease prevention and management, and seeking the narrative and lived experience of minorities to guide future public health communication and strategy ( , ) . however, there is reason to be hopeful. perhaps the most important conclusion drawn from an analysis of the influenza pandemic is that minority communities are resilient, are resourceful, and find restoration in community. the most successful strategies to advance health equity would be to ) examine the historical arc contextualizing current disparities in vulnerable communities; ) recognize the inherent strengths in these communities, empowering them to participate in research and generate solutions alongside those who traditionally hold power; ) acknowledge the contributions of frontline workers in communities of color; ) prepare for future public health emergencies by enhancing minority civic participation; and ) use a restorative justice framework to acknowledge and make amends for the structures contributing to disadvantages in these communities ( , ) . taken together, these strategies provide the opportunity to use this challenging moment to transform clinical and public health practice by grounding it in social justice. although the covid- pandemic will eventually abate, its aftershocks will be perceptible for generations. there is no doubt that it will change public health practice and clinical delivery, which are intimately intertwined. yet, it will also shift the political and social landscapes. as arundhati roy recently wrote in "the pandemic is a portal": "we can choose to walk through it, dragging the carcasses of our prejudice and hatred, our avarice, our data banks and dead ideas . . . or we can walk through lightly, with little luggage, ready to imagine another world. and ready to fight for it" ( ) . when the dust settles in the wake of covid- , let us not allow ourselves to fall into a great amnesia, another forgotten pandemic. let us remember whom this disproportionately affected and why. taking this as impetus for mobilization, let us begin to rewrite the story of health disparities in america. in this new chapter, we will be better prepared to offer all citizens a fair and just opportunity to attain their highest level of health. current author addresses and author contributions are available at annals.org. covid- dashboard covid- fatalities covid- infection rates based on education and race. abc news chicago's coronavirus disparity: black chicagoans are dying at nearly six times the rate of white residents, data show hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease -covid-net, states, march - arizona: percent of covid- deaths are native americans. indian country today early data shows african americans have contracted and died of coronavirus at an alarming rate. propublica accessed at www.propublica.org/article/early-data -shows-african-americans-have-contracted-and-died-of-coronavirus -at-an-alarming-rate on how racism is shaping the coronavirus pandemic minority groups at risk as states withhold, provide partial covid- racial data institute of medicine. unequal treatment: confronting racial and ethnic disparities in health care. national academies pr; . . washington ha. medical apartheid: the dark history of medical experimentation on black americans from colonial times to the present you are a sweet, beautiful guy and my best friend. if anyone is #newyorktough it's you covid- and african americans this time must be different: disparities during the covid- pandemic historian draws parallels between the spanish flu and today's coronavirus pandemic the spanish flu killed more than million people. these lessons could help avoid a repeat with coronavirus the influenza pandemic and covid- . pbs race colors america's response to epidemics: a look at how jim crow affected the treatment of african americans fighting the spanish flu. the undefeated history in a crisis-lessons for covid- african americans, public health, and the influenza epidemic. public health rep childhood's deadly scourge: the campaign to control diphtheria infectious fear: politics, disease, and the health effects of segregation sick from freedom: african-american illness and suffering during the civil war and reconstruction immunities of empire: race, disease, and the new tropical medicine, - the health and physique of the negro american the geography and mortality of the influenza pandemic influenza: the mother of all pandemics the influenza epidemic and jim crow public health policies and practices in chicago an account of the bilious remitting yellow fever, as it appeared in the city of philadelphia, in the year . thomas dobson the myth of innate racial differences between white and black people's bodies: lessons from the yellow fever epidemic in race and influenza pandemic in the united states: a review of the literature american pandemic: the lost worlds of the influenza epidemic report and handbook of the department of health of the city of chicago for years to inclusive. department of health of the city of chicago; . . personal. afro-american ( - ) whole families in lewes have flu. afro-american proquest historical newspapers: the baltimore afro-american proquest historical newspapers: the baltimore afro-american closed on last sunday: one pastor boasted that services would be held at his church as usual. the board of health acts. philadelphia tribune baltimore afro-american baltimore afro-american. december greenwood pr; . . crosby aw. america's forgotten pandemic: the influenza of protection of racial/ethnic minority populations during an influenza pandemic germs and jim crow: the impact of microbiology on public health policies in progressive era american south half a million darkies from dixie swarm to the north to better themselves. chicago daily tribune black metropolis: a study of negro life in a northern city germs know no color: racial segregation in baltimore during the influenza pandemic of - apartheid baltimore style: the residential segregation ordinances of - / /archives/baltimore-tries-drastic-plan-of-race-segregation-strange -situation the flexner report and black medical schools black nurses in the great war: fighting for and with the american military in the struggle for civil rights epidemic influenza and the negro physician desegregating harlem hospital: a centennial. the new york academy of medicine nonpharmaceutical interventions implemented by us cities during the - influenza pandemic public health interventions and epidemic intensity during the influenza pandemic baltimore city plans coronavirus ad campaign to combat myth that african american residents are immune. baltimore sun coronavirus fight shifts to baltimore's poor neighborhoods as city leaders battle mistrust. baltimore sun public communications and its role in reducing and eliminating health disparities. in: institute of medicine (us) committee on the review and assessment of the nih's strategic research plan and budget to reduce and ultimately eliminate health disparities examining the health disparities research plan of the national institutes of health: unfinished business failing another national stress test on health disparities covid- and health equity-a new kind of "herd immunity hospitalization and mortality among black patients and white patients with covid- social sources of racial disparities in health a game plan to help the most vulnerable data and policy solutions to address racial and ethnic disparities in the covid- pandemic what the surgeon general gets wrong about african americans and covid- . cnn. reducing racial inequities in health: using what we already know to take action restorative justice & other public health approaches for healing: transforming conflict into resiliency. lorenn walker blog accessed at www.ft.com/content/ d f e - eb- ea- fe-fcd e ca on history of medicine historical insights on covid- , influenza, and racial disparities current author addresses: dr. krishnan: johns hopkins university school of medicine suite # - a critical revision of the article for important intellectual content historical insights on covid- , influenza, and racial disparities key: cord- -rg gcc authors: aoyagi, yumiko; beck, charles r; dingwall, robert; nguyen-van-tam, jonathan s title: healthcare workers' willingness to work during an influenza pandemic: a systematic review and meta-analysis date: - - journal: influenza other respir viruses doi: . /irv. sha: doc_id: cord_uid: rg gcc to estimate the proportion of healthcare workers (hcws) willing to work during an influenza pandemic and identify associated risk factors, we undertook a systematic review and meta-analysis compliant with prisma guidance. databases and grey literature were searched to april , and records were screened against protocol eligibility criteria. data extraction and risk of bias assessments were undertaken using a piloted form. random-effects meta-analyses estimated (i) pooled proportion of hcws willing to work and (ii) pooled odds ratios of risk factors associated with willingness to work. heterogeneity was quantified using the i( ) statistic, and publication bias was assessed using funnel plots and egger's test. data were synthesized narratively where meta-analyses were not possible. forty-three studies met our inclusion criteria. meta-analysis of the proportion of hcws willing to work was abandoned due to excessive heterogeneity (i( ) = · %). narrative synthesis showed study estimates ranged from · % to · % willingness to work, depending on context. meta-analyses of specific factors showed that male hcws, physicians and nurses, full-time employment, perceived personal safety, awareness of pandemic risk and clinical knowledge of influenza pandemics, role-specific knowledge, pandemic response training, and confidence in personal skills were statistically significantly associated with increased willingness. childcare obligations were significantly associated with decreased willingness. hcws' willingness to work during an influenza pandemic was moderately high, albeit highly variable. numerous risk factors showed a statistically significant association with willingness to work despite significant heterogeneity between studies. none of the included studies were based on appropriate theoretical constructs of population behaviour. although variable in severity, , one consistent feature of pandemic influenza is a surge in demand for health care. , hospitalization due to influenza a(h n )pdm in the usa was estimated at approximately cases between april and april contrasting with annual influenza-associated primary hospitalizations from to . in - , the availability of intensive care unit beds came under pressure in most national health systems. , healthcare workers (hcws) play key roles during an influenza pandemic, but a serious shortage of personnel may occur at peak times or in severe pandemics because of absenteeism due to illness, caring for family members who are ill, or refusal to work. effective preparation for the next pandemic requires estimates of hcws' willingness to work and an understanding of influencing factors. the available data are highly variable. one nigerian study found only one quarter of hcws stating they would be willing to work in a unit treating patients with influenza a(h n )pdm , whilst an australian qualitative study of family physicians found % of participants willing to work. chaffee first reviewed willingness to work during disasters and reported that the following factors would be influential: type of disaster, concern for close family, friends and pets, responsibility for dependants, the perceived value of one's response, belief in a duty of care, access to personal protective equipment (ppe), provision of basic needs (water, food, rest, shelter and communication tools) and prolonged working hours. three published reviews reported that similar factors would be associated with willingness to work during an influenza pandemic, [ ] [ ] [ ] but the data were not summarized quantitatively. we addressed this evidence gap by conducting a systematic review and meta-analysis in accordance with the preferred reporting items for systematic review and meta-analyses (prisma) statement. the review questions sought to elucidate the proportion of hcws willing to work during an influenza pandemic, and to identify risk factors associated with willingness to work. our findings are interpreted with reference to sociological understandings of population behaviour, which have to date largely been absent from the peer-reviewed literature, but are highly relevant to the development of appropriate interventions to minimize refusal to work. the study protocol was registered with the national institute for health research international prospective register of scientific reviews (prospero; #crd ) prior to executing the literature search strategy. the prisma checklist is available as supporting information. we sought to analyse data collected exclusively from hcws including doctors, nurses, hospital workers, emergency healthcare service workers, public health workers, medical and nursing students, non-clinical support staff and retirees. the outcome measures of interest were the proportion of hcws reporting willingness to work during an influenza pandemic, and odds ratios or case counts allowing the derivation of odds ratios pertaining to factors associated with willingness to work. we included study manuscripts written in english reporting original quantitative research derived from a cross-sectional design, studies pertaining to a prior or hypothetical influenza pandemic, and studies reporting data pertaining to the aforementioned outcome measures, with no limitations on the time and place of publication. the following databases were searched from their inception to april : medline, embase, web of knowledge, scopus, amed, assia, bioethicsweb, cinahl, cochrane library and psycinfo. google scholar and opengrey were also searched. search terms were 'pandemic + influenza + willingness to work/report to work' to avoid including studies on willingness to accept vaccination. these terms were used in both keyword and mesh searches as appropriate for each database as follows: # . pandemics (mesh); # . influenza, human (mesh); # . 'attitude of health personnel' (mesh) or willingness (keyword); # . hospital administration (mesh) or report to work (keyword); # . willing* adj work (keyword); # . respon* adj work (keyword); # . would come (keyword); # . # or # or # or # or # ; # . # and # and # (see also table s ). reference lists in eligible articles were also searched. all identified records were imported to endnote software x (thomson reuters, toronto, ca, usa) and duplicate entries removed. the remaining records were screened by a single researcher (ya) against the protocol eligibility criteria following a sequential assessment of the study title, abstract and full-text article. where this was unclear, agreement on eligibility of each study was achieved through discussion with a second researcher (rd or jsn-v-t). data extraction was performed by a single researcher (ya) using a piloted form collecting details of study characteristics {title, author, publication year, place, study period, study design, participants, subject [pandemic of avian influenza origin/influenza a(h n )pdm /non-specified, hypothetical influenza pandemic]}; definition of outcome measures; questionnaire type; validation; statistical analysis and any stated limitations; percentage of willingness to work; and risk factors association with willingness. odds ratios (ors) of factors both unadjusted and adjusted were extracted to estimate the association with willingness to work. crude case counts and the percentage of people in each risk factor stratum were extracted where available. risk of bias was assessed for each study using a newcastle-ottawa assessment scale modified for crosssectional studies by herzog et al. descriptive statistics were calculated using microsoft â office excel â (microsoft corporation, richmond, va, usa). random-effects meta-analysis estimated the proportion of hcws (including % confidence intervals [cis]) who reported willingness to work during an influenza pandemic. random-effect meta-analysis of pooled odds ratios (including % cis) estimated the association of factors with willingness to work. heterogeneity between studies was assessed using the i statistic. we considered it statistically inappropriate to perform meta-analysis where i exceeded %. to explore sources of heterogeneity, we planned to conduct subgroup analyses according to the type of influenza pandemic; geographical region; survey time period; type of questionnaire; type of participants; sex of participants; and newcastle-ottawa assessment scale score. we used galbraith plots to detect those studies that contributed substantial heterogeneity and conducted sensitivity analyses excluding them from our pooled estimates. for each meta-analysis, publication bias was assessed graphically using a funnel plot of effect size versus standard error and statistically using egger's regression test. meta-analysis of pooled proportions was conducted using statsdirect version . . (statsdirect ltd., cheshire, uk), and meta-analysis of pooled odds ratios was conducted using we identified a total of unique records of which studies met protocol eligibility criteria (see figure ). two the included studies comprised entirely of cross-sectional surveys including two pre-/post-intervention studies and are summarized in table . the participant population sizes ranged from to with a median of (interquartile range [iqr] - ). the earliest publication was in , and the majority of articles were published in ( ; Á %) and ( ; Á %). of ( Á %) studies used a hypothetical influenza pandemic as the subject, ( Á %) were conducted in the usa, and ( Á %) investigated both clinical and non-clinical staff within hospital settings. assessments using the modified newcastle-ottawa scale showed that of studies were at moderate risk of bias ( - of five stars) for the selection domain, whilst studies were at low risk ( - stars) and ten studies were at high risk ( - stars); many studies used convenience sampling and few justified the study sample size, appropriately considered nonresponders and used a validated measurement tool. for the comparability domain, were at high risk ( of two stars), eight at moderate risk (one star) and at low risk of bias (two stars). many studies did not clarify how statistical adjustment for confounding variables was carried out, or reported unadjusted estimates only. for the outcome domain, studies were at moderate risk of bias (two of three stars) and four were at high risk (one star). willingness to work was self-reported in all studies although the statistical test used was clearly described in only studies (see figure s ). the percentage of participants who expressed a willingness to work ranged from Á % (community nurses during the influenza a(h n )pdm pandemic in hong kong in ) to Á % (a study of us medical students targeting a hypothetical influenza pandemic). we abandoned metaanalysis to estimate a pooled mean proportion of hcws willing to work due to very high statistical heterogeneity between studies (i = Á %). our planned subgroup analyses were unable to adequately explain the sources of heterogeneity between studies as this remained above our threshold of % in each analysis. the percentage of willingness to work seemed to depend on the particular context of the study. studies of hypothetical influenza pandemics, which did not include detailed conditions such as virulence of the strain and availability of protective equipment, tended to show a high level of willingness to work. however, studies of precise scenarios or those which investigated willingness during the relatively mild influenza a (h n )pdm pandemic tended to present relatively low levels of willingness. this finding may correspond with earlier work by syrett et al. which showed that willingness factors associated with willingness to work data were extracted from studies. pooled estimates from meta-analyses of individual factors associated with willingness to work are summarized in table . overall, females were one-third less likely to be willing to work compared with males. by occupational group, physicians were most likely to be willing to work, followed by nurses, then other health workers. urban or metropolitan area workers were less likely to be willing to work than rural area workers. full-time workers were more likely to be willing to work than parttime employees. respondents living with children or having childcare obligations were one-third less likely to be willing to work compared with those without these obligations. one study identified that pregnancy in a family member reduced willingness to work. marital status (not meta-analysed) did not influence willingness to work. perceived personal safety at work and perception of pandemic risk (aware that a pandemic was likely) were both associated with increased willingness to work. likewise, the provision of protective measures (mainly personal protective equipment) increased willingness to work, although metaanalysis was abandoned due to high heterogeneity (i = Á %). training in pandemic preparedness, general and specific role knowledge, confidence in personal skills, good communication skills and perception of role importance all had positive effects on willingness to work. confidence in employers as judged by 'belief that the employer can provide timely information' also positively influenced willingness to work, although meta-analysis was abandoned due to high heterogeneity. the funnel plot of the percentage of hcws willing to work did not present a clear funnel shape, appeared to scatter widely without any detectable association with the standard error and overflowed the false % ci range. egger's regression test reached statistical significance and showed that studies reporting a lower percentage were more likely to be published (p = Á ). funnel plots and egger's regressions tests pertaining to meta-analyses of factors associated with willingness to work revealed no evidence of publication bias except for previous training and comparison of physicians and nurses (see table ), which suggested possible underreporting of studies with an adverse result. this study advances knowledge from previous reviews on willingness to work during influenza pandemics by adding further new studies and subjecting the findings to statistical evaluation where possible. the search was conducted comprehensively and yielded studies from countries. however, quality of the included studies was not uniformly high and excessive statistical heterogeneity prevented metaanalysis of the primary outcome measure. whilst it was not possible to identify a single clear source of the heterogeneity encountered, almost certainly the wide variation in settings, scenarios and respondents contributed significantly. metaanalysis suggested that sex and job category would affect willingness to work although studies varied greatly in the composition of their samples. hypothetical scenarios varied in virulence, stage and the amount of information provided to respondents. studies of influenza a(h n )pdm were conducted at different junctures during the evolution of the - pandemic. there was no consistency in terms of how respondents were asked about their willingness to work, and the design of questionnaires used to collect outcome data from respondents varied between studies. remarkably, despite such high heterogeneity, some factors emerged showing a consistent association with willingness to work. whilst previous reviews suggested these from a narrative approach, this study has confirmed them statistically. being male, a physician or nurse (especially the former), and a full-time worker were all positively associated with willingness to work. these factors are essentially nonmodifiable; without access to the raw data, we could not disentangle any potential confounding between being male and the likelihood of being a physician or full-time worker in studies providing only unadjusted ors. nevertheless these were consistent findings across most studies and firm knowledge that these are reliable and statistically proven influencers of willingness to work is important information for both policy makers and healthcare service managers, even though they are difficult factors to influence. childcare obligation was a consistent barrier to hcws' willingness to work. the importance of this factor may be an artefact of the high participation of women in the hcw workforce in most countries, combined with traditional cultural expectations that they will take primary responsibility for childcare. it is, nevertheless, an important finding for managers. it is not clear whether this is driven mainly by practicality, that is the need to provide childcare at home, or by concerns about whether the safety of children might be compromised by infection brought in from the parental workplace. paradoxically, the evidence that hcws are at increased risk of influenza infection is rather mixed and somewhat inconsistent, whereas the evidence that children (rather than adults) are usually the introducers of influenza infection into households is firmly established. this question should be further investigated because it has implications for appropriate organizational responses. if it is simply a practical matter, then managers need to consider what help could be given in emergencies through the expansion of onsite or community childcare provision. if it is a concern about cross-infection, then appropriate education and information programmes may resolve the problem. in either case, it is unlikely that simple disciplinary sanctions will be effective, because of the social force of parental obligations. indeed, these may well be counterproductive, if other workers perceive them to have been unreasonably applied by managers unsympathetic to real personal dilemmas. confidence in safety, risk perception, prior training, general and role knowledge and confidence in skills were statistically proven facilitators for willingness to work. these are all addressable by detailed pandemic preparedness educational activities at healthcare unit level. importantly, one message arising from assessments of pandemic planning activities prior to the - pandemic was that whilst national level pandemic planning was generally successful, the level of planning at local level was insufficient, including training on pandemic influenza for hcws. a particular feature of pandemics is the level of anxiety provoked by the disruption of 'business as usual' and the destabilization of usually stable organizational environments. whilst it is not necessary to retrain hcws frequently, this is a topic that should be addressed in their basic education and managers should ensure that updating materials are readily available, and regularly revised, so that programmes can rapidly be rolled out when a pandemic is identified. evidence of organizational preparedness will contribute to the confidence of hcws that they will not be placed at undue risk by being asked to work in different ways or in different environments from those that they are accustomed to. a number of limitations with the present study warrant discussion. our literature search was limited to records published in english. therefore, we cannot exclude the possibility of having omitted outcome data published in other languages. many of the included studies were at moderate or high risk of bias. moreover, only a small number were available for analysis in relation to some risk factors; these results should be interpreted cautiously. the possibility of publication bias might also be a limitation. however, considering that the percentage of willingness was relatively high in most studies, this suggests that unpublished data may not have found statistically significantly higher percentages of willingness to work. whilst some studies used questionnaires based on recognized psychological theories, these were commonly 'fear-appeal' theories. unfortunately, this may not be appropriate as the preferable behaviour (working during an influenza pandemic) would not result in release from personal fear. we did not identify any studies that investigated the interaction between individual and organizational responses, which biased the findings towards individual fears rather than the social conditions that might provoke or alleviate these. as important as our specific results themselves, is the fact that we identified a multiplicity of approaches to studying the issue of hcw willingness to work during a pandemic; mainly small, ad hoc enquiries, not based on any consistent scenarios or theoretical approaches. to solve this, a consistent methodological framework is needed before any further studies are undertaken. the outbreaks of ebola virus disease in west africa and mers-cov in the middle east offer two very different settings in which to improve study designs and understanding of hcws' willingness to work where infectious disease creates appreciable personal risk. in the meantime, policy makers should recognize that hcw willingness to work during an influenza pandemic is likely to be improved by practical measures to support childcare responsibilities and by the timely provision of relevant and high-quality training and information as a pandemic develops. whilst the above would hold true for influenza, the actual risks and perceptions are not consistent across all novel respiratory viruses. for example, % of nurses in ontario refused to work during the sars crisis when the risk to hcws was almost exclusively nosocomial (compared with pandemic influenza where the risk is community-wide). similarly, in the ongoing mers-cov epidemic, the risk of nosocomial infection is presently greater than in wider community settings. , conclusions hcws' willingness to work during an influenza pandemic is moderately high although highly variable, and substantial statistical heterogeneity precluded formal meta-analysis. numerous risk factors are associated with willingness of hcws to work during an influenza pandemic, revealing potential points of intervention to increase willingness to work. we identified a wide variety of approaches to the study of willingness to work. for improved future understanding, we advocate a coordinated global approach with standardized protocols and based on appropriate theoretical constructs; and the evaluation of packages of intervention through controlled studies. additional supporting information may be found in the online version of this article: table s . full electronic search strategy (medline). figure s . summary of risk of bias of included studies using the modified newcastle-ottawa scale (n = ). data s . prisma checklist. pandemic influenza preliminary estimates of mortality and years of life lost associated with the a/h n pandemic in the us and comparison with past influenza seasons world health organization. pandemic influenza preparedness and response: a who guidance document. geneva: world health organization america's forgotten pandemic estimating the burden of pandemic influenza a (h n ) in the united states influenza-associated hospitalizations in the united states complications among adults hospitalized with influenza: a comparison of seasonal influenza and the h n pandemic pandemic influenza and hospital resources pandemic ): how prepared are healthcare providers in calabar, nigeria? the gp's response to pandemic influenza: a qualitative study willingness of health care personnel to work in a disaster: an integrative review of the literature healthcare workers willingness to work during a pandemic factors associated with the willingness of health care personnel to work during an influenza public health emergency: an integrative review healthcare workers' willingness to report to work during an influenza pandemic: a systematic literature review an international registry of systematic-review protocols are healthcare workers' intentions to vaccinate related to their knowledge, beliefs and attitudes? a systematic review meta-analysis in clinical trials measuring inconsistency in meta-analyses influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective graphical display of estimates having differing standard errors bias in meta-analysis detected by a simple, graphical test will the community nurse continue to function during h n influenza pandemic: a cross-sectional study of hong kong community nurses? perspectives of future physicians on disaster medicine and public health preparedness: challenges of building a capable and sustainable auxiliary medical workforce will emergency health care providers respond to mass casualty incidents? how would australian hospital staff react to an avian influenza admission, or an influenza pandemic incidence of influenza in healthy adults and healthcare workers: a systematic review and metaanalysis estimating household and community transmission parameters for influenza who regional office for europe. recommendations for good practice in pandemic preparedness: identified through evaluation of the response to pandemic (h n ) . copenhagen: who regional office for europe introduction: why a sociology of pandemics? putting the fear back into fear appeals: the extended parallel process model spring of fear, chapter : the nurses' survey hospital-associated outbreak of middle east respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description hospital outbreak of middle east respiratory syndrome coronavirus gauging us emergency medical services workers' willingness to respond to pandemic influenza using a threat-and efficacy-based assessment framework assessment of local public health workers' willingness to respond to pandemic influenza through application of the extended parallel process model assessment of medical reserve corps volunteers' emergency response willingness using a threat-and efficacy-based model determinants of emergency response willingness in the local public health workforce by jurisdictional and scenario patterns: a cross-sectional survey nurses' ability and willingness to work during pandemic flu health care workers' ability and willingness to report to work during public health emergencies hospital health care workers' understanding of and attitudes toward pandemic influenza in beijing who will show up? estimating ability and willingness of essential hospital personnel to report to work in response to a disaster will they just pack up and leave?"-attitudes and intended behaviour of hospital health care workers during an influenza pandemic characterizing hospital workers' willingness to report to duty in an influenza pandemic through threat-and efficacy-based assessment ethical planning for an influenza pandemic survey study of the knowledge, attitudes, and expected behaviors of critical care clinicians regarding an influenza pandemic hospital disaster staffing: if you call, will they come? survey of alberta family physicians' reactions to the spring and summer phase of ph n (pandemic swine flu) outbreak willingness of university nursing students to volunteer during a pandemic preparing for an influenza pandemic: healthcare workers' opinions on working during a pandemic willingness of frontline health care workers to work during a public health emergency factors associated with the ability and willingness of essential workers to report to duty during a pandemic will the nhs continue to function in an influenza pandemic? a survey of healthcare workers in the west midlands healthcare workers' perceptions of the duty to work during an influenza pandemic evaluation of a pandemic preparedness training intervention of emergency medical services personnel pre-pandemic planning survey of healthcare workers at a tertiary care children's hospital: ethical and workforce issues anticipated behaviors of emergency prehospital medical care providers during an influenza pandemic assessing public health department employees' willingness to report to work during an influenza pandemic local public health workers' perceptions toward responding to an influenza pandemic senior clinical nurses effectively contribute to the pandemic influenza public health response pandemic-related ability and willingness in home healthcare workers mitigating absenteeism in hospital workers during a pandemic knowledge and anticipated behavior of health care workers in response to an outbreak of pandemic influenza in georgia a national survey of emergency nurses and avian influenza threat are belgian senior medical students ready to deliver basic medical care in case of a h n pandemic ensuring adequate human medical resources during an avian influenza a/h n pandemic nurses' fears and professional obligations concerning possible human-to-human avian flu survey of hospital healthcare personnel response during a potential avian influenza pandemic: will they come to work knowledge and attitudes of healthcare workers in chinese intensive care units regarding h n influenza pandemic perception, attitudes and knowledge regarding the swine-origin influenza a (h n ) virus pandemic among health-care workers in australia influenza vaccination and intention to receive the pandemic h n influenza vaccine among healthcare workers of british columbia, canada: a cross-sectional study nurses' perspectives and concerns towards an infectious disease epidemic in egypt influenza a h ni (pandemic ): how prepared are healthcare providers in calabar, nigeria? factors associated with motivation and hesitation to work among health professionals during a public crisis: a cross sectional study of hospital workers in japan during the pandemic (h n ) we thank the authors of the articles cited in this paper. we also thank nicola darlington (university of nottingham) for assistance with developing the search terms and john mair jenkins (health education east midlands) and roshni joshi (university of nottingham) for help with manuscript preparation. this research was supported by the university of nottingham as a master of public health dissertation project. jsn-v-t and crb are respectively editor-in-chief and associate editor for influenza and other respiratory viruses; however they played no role whatsoever in the editorial process for this paper, including decisions to send the manuscript for independent peer-review or about final acceptance of a revised version. all of the above functions were handled alone by dr john wood, senior editor (reviews). key: cord- -w sk m authors: caduff, carlo title: what went wrong: corona and the world after the full stop date: - - journal: med anthropol q doi: . /maq. sha: doc_id: cord_uid: w sk m this article examines the global response to the covid‐ pandemic. it argues that we urgently need to look beyond the virus if we want to understand the real seriousness of what is happening today. how did we end up in a space of thinking, acting, and feeling that has normalized extremes and is based on the assumption that biological life is an absolute value separate from politics? the author suggests that today's fear is fueled by mathematical disease modeling, neoliberal health policies, nervous media reporting, and authoritarian longings. it is as though mankind had divided itself between those who believe in human omnipotence (who think that everything is possible if one knows how to organize masses for it) and those for whom powerlessness has become the major experience of their lives. ---hannah arendt the measures that governments across the world have taken to contain the spread of coronavirus disease are massive and unprecedented. as a result of these measures, life has come to an almost complete standstill, with many countries under lockdown. never in the history of humanity have such drastic interventions into the lives of populations occurred in the name of health on such a scale and in such a short period of time. as a result of the world's largest and perhaps most stringent lockdown, millions of daily wage laborers have lost their source of income in india. health care workers have been attacked and evicted from their homes because they are seen as potential spreaders of contagious disease (kalra and ghoshal ) . neighborhoods have been scared into panic when an ambulance appears on the street. due to the sudden ban on any form of transportation, migrant workers have been stranded between the cities where they used to work and the villages where their families are living (daniyal et al. ) . cancer patients have been unable to receive essential medical care because they cannot reach the hospital. it is the poor, the marginalized, and the vulnerable who are most affected by drastic measures, exacerbating already existing inequalities. in kenya, the police enforced a coronavirus curfew using teargas and excessive force against presumable violators of lockdown law (namwaya ) . in bangladesh, the government created a special unit to monitor social media and arrest people for spreading "misinformation" about the virus (hrw ). in hungary, parliament passed a law allowing prime minister orbán to limit freedom of speech, defer elections, and suspend rules and regulations by decree (gebrekidan ) . in india, state governments released companies from the purview of labor laws, including occupational health laws, to stimulate the economy (sharma ) . in lebanon, the currency collapsed, leaving % of the population in need of food aid (chulov ) . in the united states, over million people have filed for unemployment benefits (rushe and aratani ) . unfortunately, as of the writing of this article, many things remain completely unknown in this pandemic despite intensive investigation. for example, we don't know what helped contain the outbreak in china, and particularly whether government interventions reduced the spread of the virus or if the virus burned out there before moving on to other susceptible populations. the fact is: we simply don't know. nevertheless, many actors and institutions have proceeded as if they did know, imposing extreme measures that have affected billions of people and that have pushed societies to the edge of collapse by creating poverty, hunger, misery, debt, and unemployment. today, many wonder how we ended up where we are. how was it possible for a virus to trigger such a massive response that continues to threaten society and the economy, with so little discussion about the costs and consequences of extreme measures? why is there widespread agreement that aggressive interventions to "flatten the curve" were necessary and justified? it seems that this unprecedented public health experiment occurred without sufficient consideration of the social, political, and economic consequences. the failure to consider the impact of extreme measures that have become the norm in many places in the covid- pandemic has been stunning. the destruction of lives and livelihoods in the name of survival will haunt us for decades. the coronavirus disease outbreak seems to have started in the chinese city of wuhan in december . in january, the chinese government put wuhan and other major cities in the province under lockdown. a lockdown of million people "is unprecedented in public health history, so it is certainly not a recommendation the who has made," dr. gauden galea, the world health organization's (who) representative in beijing, emphasized at the time (reuters ). in other provinces, the chinese government implemented tailored measures, including factory shutdowns and school closures, but not a lockdown or restriction of movement to limit the spread of disease. major media outlets in the united states called china's locked-city strategy deployed in and around wuhan "harsh," "extreme," "severe," and "controversial," emphasizing that it offered "no guarantee of success" (qin et al. ) . a new york times article noted that "china is trying to halt a coronavirus outbreak using a tactic … with a long and complicated history fraught with social, political and ethical concerns" (levenson ) . experts quoted in the article called the lockdown of cities "an unbelievable undertaking" that would be "patently unconstitutional in the united states." "that type of thing," said james hodge, a professor of law, "is obviously an excessive response." another expert cited in the article, historian howard markel, pointed to the "darker side of quarantine-its use as a social tool rather than its scientific use as a medical tool." in the united kingdom, newspaper articles suggested that the chinese government would not be able to keep the city of wuhan "closed for business indefinitely" (graham-harrison ). in february, the virus continued to circulate and soon appeared in other countries. in march, the who declared the covid- outbreak a global pandemic. despite the criticism of china's approach, a crude and extreme version of lockdown became the international norm promoted by experts, officials, and the media across the world. concerns with the dark side of quarantine faded rapidly. a few countries like south korea veered from this norm and chose instead a classic infectious disease intervention: test-trace-isolate, with a highly centralized approach to public health intelligence gathering. emphasizing mass testing and meticulous contact tracing to interrupt the chain of transmission, south korean health officials closed schools and managed the crisis successfully without any lockdowns or roadblocks, and few restrictions of movement. significantly, south korea learned from earlier outbreaks of infectious disease (sars in particular), and imposed central control, used digital technologies, and enforced quarantines, and it witnessed one of the lowest covid- mortality rates. by the end of april , around , cases of infection had been detected there, but only people had died. germany developed its own testing protocol, which was published on january by the who (beaumont ) . when the first case was detected on january , germany launched mass testing, systematic contact tracing, and early hospitalization, keeping the mortality rate low and hospitals functional even when cases of infection increased (mohr and datan-grajewski ) . health officials relied on an extensive network of laboratories and were able to conduct over , sars-cov- (covid- ) tests per week (buck ) . along with south korea, germany put testing and contact tracing at the heart of the response. despite the who's emphasis on testing and south korea's and germany's early success in reducing the spread of the virus, most countries considered testing at scale as a low priority and relied on an extreme version of the chinese approach of lockdown. however, in china, the approach was tailored and regionalized; as a who report noted, "specific containment measures were adjusted to the provincial, county and even community context, the capacity of the setting and the nature of novel coronavirus transmission there" (who ). the lockdown focused on the major cities in the most affected province, constraining the life of million people in a country of . billion. in other words, it was a limited lockdown affecting % of china's total population. in contrast to the tailored and regionally differentiated intervention that sought to minimize the socio-economic impact of the response, many other governments across the world imposed nationwide lockdowns that went far beyond china's locked-city approach. in practice, these lockdowns amounted to curfews (often legalized after the fact by emergency laws). italy was the world's first country with a nationwide lockdown/curfew. many countries followed suit, partly motivated by shocking images of overwhelmed hospitals in italy's north and partly driven by a disease model report released in the united kingdom a few days after italy's surprising national lockdown announcement . this moment of shock and surprise triggered a chain reaction in the pandemic response. the horizon shifted, the inconceivable became possible, and life suddenly felt surreal. the u.k.'s disease model garnered a lot of attention, creating a sense of urgency that amplified the political pressure because the numbers were alarming . published by a group of experts without peer review on an institutional website, the report compared covid- with the great pandemic of , which killed over million people worldwide and suggested, without any evidence, that sars-cov- was "a virus with comparable lethality to h n influenza in ." most frightening in all this was not so much the lethality of the sars-cov- virus but the license to rush forward with predictions, abandon basic standards of science, and make dramatic claims to scare people. for covid- , the report predicted , deaths in the united kingdom and . million deaths in the united states. it presented possible strategies to reduce the impact of the pandemic, but the focus was exclusively on "non-pharmaceutical interventions." there was no discussion of testing and contact tracing. a proven public health strategy known to be effective was systematically sidelined in one of the most influential reports to emerge in the covid- pandemic. significantly, the report claimed to focus on "feasibility" of measures and promoted the idea that systematic suppression of transmission would work best-in other words, lockdowns. however, it excluded from any consideration the social, political, and economic implications of lockdowns, noting that "no public health intervention with such disruptive effects on society has been previously attempted for such a long duration of time." in addition to ignoring testing and contact tracing as a possible strategy, disregarding the social, political, and economic implications of lockdowns, and conceding that there is no "easy policy decision to be made," the authors of the report felt confident enough to claim that "suppression" was the "preferred policy option" and the "only viable strategy" that countries across the world needed to implement "imminently." the lockdowns that were required for suppression would need to be maintained "until a vaccine becomes available" (which they predicted to be "potentially months or more"). a crude, extreme, and ultimately unsustainable version of the chinese approach became the international norm. shutting down society and the economy until a preventive medical treatment becomes available was advanced as an appropriate response and the only possible way of dealing with the crisis, despite the costs and consequences. italy figured as an important but fundamentally ambivalent model, shifting the locked-city into a locked-country approach. the italian scenario was sobering and frightening but also inspiring and motivating. to avoid italy's disaster, governments appropriated the italian approach of mass confinement and rigid restriction of movement as a one-size-fits-all intervention. in many places throughout the world, including italy and france, the locked-country approach took a militarized form with massive deployment of the police to enforce lockdown restrictions. the locked-country approach seemed to obviate the necessity of justifying a differentiated strategy that might have looked unequal and unfair and that might have intensified social and political conflicts along multiple internal fractures and fault lines. to avoid the political fallout of a differentiated strategy, which would have required systematic testing, government officials in europe and elsewhere invoked the politically expedient image of a total threat and suggested that "we are all in the same boat" and that "we are all in this together." the idea that regional lockdowns would not be possible and that it was best to treat the virus as a global threat that would uniformly impact all people involved conjuring an image of a united nation confronting a total threat that required everyone's sacrifice. this image relied on a false assumption of equality. solidarity came to mean not mutual support in a situation of uneven risk, but rather generalization of a sense of danger across a national population perceived as a homogeneous body under attack. the ideology of national pandemic solidarity-putting everybody under confinement and treating everyone the same-obscured the reality that lockdowns mean different things to different people, and that not everyone is equally exposed or equally vulnerable. both the virus and the lockdown disproportionately affected those who were already vulnerable along lines of age, class, and race. dramatic references to the magnitude of the threat served as justification for nationwide lockdown policies. this extreme and unprecedented blanket approach systematically imposed on entire populations was driven by a number of factors that variously prevailed in different countries across the world: a growing sense of panic, constant media sensationalism, deep authoritarian longings, increasing political pressure to contain the spread of the virus, disturbing accounts of overwhelmed hospitals unable to cope with the surge of patients, misleading mortality calculations, and, most importantly, a trust in the power of mathematical disease modeling. throughout the covid- pandemic, there has been an abiding assumption among observers and the public that it is clear what is happening; that everyone knows what is going on because everyone can see it on television. however, what an endless stream of media reports from around the world have continued to obscure is the fact that it is impossible to know what is happening in a population when there is no systematic testing. the lack of testing created a void that was filled by the flexible evidence of disease modeling. in the absence of robust data, disease modeling emerged as the presumably best and only available science to inform policy. media hyperbole focused on absolute numbers independent of context and made covid- deaths politically visible. flexible disease modeling (often based on data derived from viruses such as influenza) took the place of accurate epidemiological surveillance. scientific papers published online without peer review made scary projections and painted a grim picture. widely reported simulation models created shock effects that shaped government policies. a narrow focus on numbers played an important role in understandings of the magnitude of the threat, fueling fear and panic in the absence of actual evidence. a distinct imaginary took hold, "the imaginary of an unprecedented event," which seemed to require an unprecedented response (kelly ). there was a widespread sense, among experts and the media, that the sars-cov- virus was much more lethal than influenza. that this pandemic was different from influenza and thus necessitated a different approach was typically claimed on the basis of the case-fatality rate, the number of deaths as a subset of those infected with sars-cov- . the casefatality rate played a crucial role in the justification of the public health experiment now unfolding before our eyes. estimates of the case-fatality rate initially varied hugely from . % to %. in an article published in the lancet, scientists claimed the case-fatality rate could even be as high as % (baud et al. ). in early march , the who directorgeneral stated that the case-fatality rate for sars-cov- was . %. he added: "by comparison, seasonal flu generally kills far fewer than % among those infected." whatever the estimates, the fact remains that it is impossible to calculate the case-fatality rate in the absence of systematic testing. given the lack of evidence, the only scientifically valid statement at the time would have been to say that we simply don't know how lethal the virus is. early on in this pandemic, it became clear that over % of infected people were experiencing no symptoms at all at the time of testing (gudbjartsson et al. ) . this means that a surveillance regime where only people with symptoms were tested will automatically exclude a large number of infections. additionally, patients with symptoms are much more likely to die than asymptomatic people. the result is an exaggerated case-fatality rate. testing strategies differed across countries and changed within countries over time. for example, on february , , the italian ministry of health published a revised policy for testing, prioritizing patients with severe clinical symptoms (and thus higher chances of dying). this change in policy resulted in an apparent increase in the case-fatality rate of . % on february to . % on march (onder et al. ) . suddenly, the virus seemed to have become much more deadly. however, this increase was a numerical illusion-a statistical artifact. there was no change in the lethality of the virus. changes in testing policy occurred in many countries and even across regions where different tactics for counting deaths were used. in china, test-positive asymptomatic patients were excluded from being counted as cases of infection (wu et al. ) . in belgium, deaths were counted independent of any testing (schultz ) . of % of all deaths, only . % turned out to be confirmed by laboratory test as covid- positive. almost half of all victims were merely suspected to be linked with the virus but had never actually been tested. there was and remains no agreement among experts and officials on what counts as a death caused by the virus. in italy, covid- -related deaths were defined as those occurring in test-positive patients, "independently from preexisting diseases that may have caused death" (onder et al. ) . this is particularly concerning in terms of data quality because the vast majority of deaths occur in patients who are older than with one or more comorbidity. test-positive patients who die because of heart disease or terminal cancer are not necessarily dying because of sars-cov- infection. yet they appear in the statistics of some countries. this confusion between patients who die with the virus and those who die from it has had an impact on the data and their quality, making comparisons between countries impossible. further, almost all tests that are done use rna tests, which can detect an infection only as long as the virus is present in the body. these tests, however, cannot tell whether a person had the virus in the past. only serological tests for antibodies against the virus can provide an accurate picture of how many people have been infected in a given population. and yet, such systematic serological studies were and are missing. given the lack of testing and taking into account the role of selection bias, the large number of asymptomatic cases, the confusions in case definitions, the changes in testing policies, and the difficulty of knowing who is dying with versus dying from the disease, the denominator for calculating actual death rates cannot be reliably determined. without a denominator, it is mathematically impossible to calculate the case-fatality rate. nevertheless, despite the lack of data, experts, officials, and the media have remained transfixed by the assumption of clarity and reliability of numbers, and they continued to circulate wild estimates, unleashing a pandemic of scary charts with exponential curves. over the last weeks of march, more and more testing was done globally, and more testing continues as of the time of this publication. not surprisingly, estimates of the case-fatality rate have come down significantly, because the denominator has gone up due to the increase of testing. in iceland, % of the population has been tested using rt-pcr-based tests independent of symptoms, suggesting a case-fatality rate of . %. this figure is six times lower than who's official estimate for covid- . the center for evidence-based medicine at the university of oxford noted that if one assumes that % of iceland's population is infected, then the corresponding infection-fatality rate would be . %. a study using both rt-pcr-based and serological tests conducted in one of germany's most affected regions indicated a case-fatality rate of . % and an infection-fatality rate of . % (streeck et al. ) . we know from epidemics and pandemics of the past that the case-fatality rate is often massively overestimated at the beginning of an outbreak because case detection is limited, largely based on hospital patients and typically biased toward the severest cases of disease. when the h n swine flu pandemic occurred in , the estimated case-fatality rate varied between . % to . % in the first weeks of the outbreak. in , a decade after the pandemic, the who reported that the swine flu pandemic turned out to have a case-fatality rate of . %. this means that the actual casefatality rate was five times lower than the lowest estimate. social science scholarship has shown how numbers can deceive. numbers have the ability to reveal as well as conceal. therein lies their magic. they appear as seemingly neutral bearers of truth. they offer a sense of mathematical precision, making things seem more certain than they actually are and displacing attention away from the conditions under which they were produced. abstracting from limitations on the conditions of their production and treating numbers as absolute is dangerous because it makes things comparable that are not comparable, because it suggests scientific knowledge where there is lack of evidence, and because it creates the sense of a major threat obscuring the differential nature of risk. what using numbers this way fails to account for is the fact that not everyone is at risk in the same way. among the more interesting figures of the sars-cov- pandemic is the number of deaths per million inhabitants per country. this number is probably more reliable than the case-fatality rate because deaths are less likely to be missed (ignoring for now the case of belgium and the difficulty of defining deaths caused by sars-cov- ) and because the denominator, a country's population, is known. here are the current numbers of deaths per million inhabitants for five countries as of may , : spain: italy: france: germany: south korea: the staggering differences between countries cannot solely be explained by demography or rates of infection (some countries seem to have more infected people per million inhabitants than others and so might be overwhelmed, though this is also a question of time-how many cases per week per region). what the differences might reveal (and it is important to note that they may well change) is that some health care systems are able to deal with the crisis in a better way than others. the structural fragilities of an underfunded, understaffed, overstretched, and increasingly privatized and fractured health care system contribute to higher mortality rates (adams ) . in a sense, each society has the mortality it deserves (canguilhem : ) . where medical care is easily accessible, with sufficient and well-trained staff, and with capacity flexibility, patients are more likely to receive better care and survive. in this sense, it matters that spain turns out to have beds per , inhabitants, italy . , france , germany , and south korea . . although beds per inhabitants is a crude indicator, it is noteworthy that germany can rely on over , staffed intensive care beds, out of which only , were occupied in early april (see mohr and datan-grajewski ) . this at a time when there were more cases in germany than in france and the united kingdom and slightly less than in spain and italy. germany's was clearly not a health care system overwhelmed by a sudden surge of patients. ironically, organizations such as the oecd frequently scolded germany's health care system in the past for "oversupply" of hospital beds and its "inability" to "rationalize hospital capacity" (kumar and schoenstein ) . this means that the case-fatality rate is not just dependent on the biological nature of the virus and the age and health profile of the population (people most at risk of death are older than with one or more comorbidity). the case-fatality rate also depends on systematic testing, meticulous contact tracing, well-trained health care workers, nursing homes with adequate resources, and the ability of the health care system to cope with the crisis (excess as well as surge capacity) and provide high-quality medical care, particularly keeping medical workers safe and healthy. in this sense, the pandemic has and will continue to brutally expose policy failures and structural health care system deficits. the situation in many hospitals in italy, spain, and france is troubling, especially in densely populated areas. but it is important to understand why some of these highly visible institutions of care were overwhelmed. lombardy, italy's most affected region, has long been an experimental site for health care privatization: community-centered care "has been all but wiped out" (bagnato ) . the lack of general practitioners and the defunding and low emphasis on community care have increased the pressure on hospitals in urban centers. these hospitals have neither excess nor surge capacity to cope with a sudden rise in demand. over the past five years, hospitals across europe held numerous strike actions "with doctors and health workers complaining of funding cuts, a government reduction in the number of beds and a serious lack of medical staff leading to dire working conditions for emergency room staff" (chrisafis ). hospital systems in italy, spain, and france were on the brink of collapse even before the virus arrived. the most telling demonstration of the structural contradictions of pandemic preparedness under neoliberalism occurred, not surprisingly, in the united states. as american newspaper articles reported, hospitals across the country deferred regular medical services to free up space, equipment, and staff for the pandemic response. when patients started to avoid hospitals due to fear of infection, a main source of income was drastically cut off, "causing huge losses that have forced some hospitals to let go of health care workers as they struggle to treat infected patients" (harris and schneider ). facing a "financial nightmare," hospitals filled their intensive care units with patients who did not really need intensive care so that they could charge more and make up for the financial loss. additionally, administrators cut salaries, laid off hundreds of staff, and sent others on unpaid leave, weakening the health care system further in the midst of the pandemic response. when a new virus appears, things start to fall apart. once everyone gets scared, extreme measures are implemented, in a more or less improvised manner, and trillions of dollars, euros, and pounds are pumped into the economy to make up for the loss. once the worst is over, however, the normal crisis continues, and the structural fragilities remain (caduff ) . this pandemic will haunt us all for decades in ways that we can barely imagine at this point. the nature and sheer scale of the interventions that we have witnessed are staggering, and the consequences-social, political, and economic-remain unforeseeable. there are no systematic accounts of the implications and repercussions seen so far, nor do we have any idea about the number of indirect deaths due to the lockdowns/curfews, the social distancing and the self-isolation. we have yet to see a realistic plan that would outline how we might learn to live with a virus that is unlikely to disappear any time soon (sullivan and chalkidou ) . in the meantime, i suggest that we reframe the corona conversation to cut through the confusion and dimness that is pervading this pandemic in the following ways: the emergence of new viruses in human populations is normal. it has happened before; it will happen again. coronaviruses are common and circulate widely in humans. they have infected people and killed thousands year after year, especially in winter. worldwide, between , to , people die from influenza viruses every year. the sars-cov- virus has killed , people so far. there is no doubt, sars-cov- is causing a serious infectious disease, but so far it is still in the range of what we observe in terms of mortality during a severe influenza season. the main difference is the speed of infection, the clinical picture of the disease, and the impact on demographically older populations causing massive compression of morbidity and mortality that is overwhelming weak health care systems with no excess and little surge capacity. the influenza pandemic killed between and million people worldwide, and the influenza pandemic killed between and million people. as of the writing of this article, covid- has killed , people, according to the official numbers. clearly, the world has witnessed worse pandemics, including . million deaths due to tb each year, , deaths due to hiv infections each year, and , deaths due to malaria, all preventable and treatable conditions. this observation does not mean that influenza and covid- are clinically similar or that nothing should be done to contain the spread of sars-cov- and mitigate the consequences. however, it raises the question of why fear and panic are spreading like wildfire, provoking such extreme measures, and why experts and government officials are willing to mount an unprecedented effort for sars-cov- but have never considered similar interventions for the , - , people who die every year due to influenza. influenza is a relatively well-known virus. to say that sars-cov- is an unknown virus doesn't automatically justify the most extreme measures that the world has ever seen. what makes this pandemic unprecedented is not the virus but the response to it. extreme measures to contain the spread of the virus have resulted in extreme fallouts. it is difficult to overestimate what we are witnessing today. the pandemic response has pushed the world into a space of fragility and uncertainty. there hovers a "perhaps" over everything now (caduff ) . blinded by the urgency of the immediate moment, the response has created an opening for actors and institutions to push agendas and reorder the world. we will grapple for years to come with the changes that are happening today. the response to the disease is driven by a fantasy of control that overestimates and overreacts. this fantasy has caused and is causing enormous harm. it is unrealistic, misleading, and bound to fail. a pandemic like this cannot be controlled; it can only be managed. if we keep using words such as control, we are only setting ourselves up for disappointment. this pandemic is far from having found a language that is adequate to the problems it is posing. we urgently need new concepts but seem to have little imagination. the urgency of the crisis has displaced reliance on basic standards for quality and control of quality of scientific research. papers are published without peer review. claims are made without evidence. perhaps not surprisingly, given the fragile health care infrastructures in some countries, speed appears to be more important than quality, rigor, and integrity. underscrutinized science, lack of data, speculative evidence, strong opinions, deliberate misinformation, exaggerated mortality rates, the / news media attention, and the rapid spread of dramatic stories on social media have led to poor political choices and major public anxiety. we are afraid of covid- . we are not afraid of influenza. we see one thing as a public health emergency and another as a fact of life. today, we are learning an old insight the hard way: not every life and not every death are equal. some deaths are more important than others, drawing more attention, triggering a bigger response and mobilizing more resources. in the covid- pandemic, the belief seems to have taken root that health is an absolute value and that every life needs to be saved by all means. meanwhile, millions of people are dying of influenza, tb, hiv, malaria, and diarrhea, not to mention chronic diseases and accidents. there seems to be less political urgency for these preventable deaths. some health care systems were overwhelmed in this pandemic. others were not. for decades, governments have underfunded, understaffed, and privatized health care systems across the world, and these trends have exacerbated the impact of the pandemic. the response to sars-cov- took a particular shape, converging in extreme measures that have become the norm in many countries. questions that remain include: was it the only possible way of managing the crisis? why has a crude version of china's approach become the dominant model? at the heart of this pandemic was and is the widespread assumption that there were and are no alternatives to extreme measures implemented on entire populations with little consideration of cost and consequences. this is not true. as some countries have shown, adequate testing and less drastic policies of social distancing work well to manage the pandemic. it seems that some officials saw covid- as a disease that could be contained. as the who director-general suggested in early march , "we don't even talk about containment for seasonal flu-it's just not possible. but it is possible for covid- ." this perception may have contributed to the radically different approach seen across many countries. the idea of "flattening the curve" is often seen as the optimal solution, but there is no guarantee that the effort to do this will actually impact the total number of deaths over the long run of the disease's presence in any community. it may ultimately simply spread the same number of deaths over a longer period of time and thus perhaps reduce the pressure on hospitals but not overall mortality. nationwide lockdowns are not a solution. they prevent infection as long as they are in place, but they also keep people susceptible. this is particularly concerning in a pandemic where the virus has become endemic. once lockdowns are lifted, the number of infected people may well rise again later. this is why it has been so hard for countries who adopted this strategy to return to normal life-the strategy is not sustainable over the long run. as andrea bagnato noted about the stay-at-home strategy: "it is not in the harshness of its lockdown, but in the effectivity of separating the infected from the non-infected, that china's response has excelled: a centralized system of dedicated structures (called fangcang) was built in no time, where all patients and their contacts were treated and divided in four groups according to severity. instead, lombardy simply closed everything down. and it becomes clearer by the day that the main landscapes of infection were not public spaces, but hospitals, retirement homes, workplaces, and indeed private homes" (bagnato ). in germany, % of the people who died due to covid- are years or older (mohr and datan-grajewski ) . a majority of the patients who died have one or more underlying health condition such as hypertension, diabetes, cardiovascular disease, chronic respiratory disease, or cancer. this means that the pandemic is killing predominantly people with an already reduced life expectancy. the key question then becomes excess deaths-the difference between the statistically expected number of deaths and actually occurring deaths over a period of time. there is no doubt that there will be excess deaths due to covid- , but it is unclear how large that number will be. the pandemic response has produced a substantial rise in the number of people who now live with untreated illness. prohibition of public transport has made it difficult for patients and staff to reach hospitals. patients with conditions other than covid- avoid doctors because they are afraid of getting infected. emergency room attendance dropped substantively the world over. cancer referrals decreased and cancer screening services stopped entirely. rural health services in countries such as india crashed. essential public health programs have been paused; many resources have been reallocated. this means that patients are neglected, receiving no or less medical care, leading to untreated illness and a rise in mortality. a virus causes disease, not hunger. it is not the pandemic, but the response to it that threatens the livelihood of millions of people. in many countries, both rich and poor, the trends are shocking. in india, children die of starvation. farmers commit suicide because they are unable to harvest crops. stranded daily wage laborers drop dead after walking hundreds of miles. the poor, marginalized, and vulnerable bear the brunt of the pandemic response. the lockdown is a political mechanism not simply for the prevention but for the redistribution of negative effects. lockdowns shift negative effects away from hotspots of public attention to places where they are less visible and presumably less serious. in this way, they are part and parcel of a politics of inequality. this pandemic is not just about health, it is about fear, and the objects that are singled out and then made the ground and motivation of systematic thought and action. to be afraid has become an obligation, a responsibility, a duty. people are afraid not just because of what they experience but because they are told to be afraid and encouraged to inhabit the world with fear of "foreign bodies" and "invisible enemies." public discourse is highly moralized. looking for someone to blame, individuals are exposed as "super-spreaders" responsible for the rising number of cases. on social media, "lockdown warriors" accuse citizens of lack of patriotism and failure to "do their duty" in the face of danger. in this highly moralized public discourse, life is considered an absolute value that can justify almost every form of disciplinary intervention in the name of health. public health needs to be front and center in any infectious disease intervention. investing in strong public health infrastructures should happen even when there is no pandemic. mathematical disease modeling cannot replace systematic epidemiological surveillance on the ground. the most effective way to manage an infectious disease outbreak is to test, trace, and isolate. interventions need to be phased over time; they need to be dynamic, regionally targeted and risk based. all interventions must take into account the social, political, and economic impact, as well as the indirect impact on other health conditions. interventions that do this will create management strategies that work to minimize collateral damage. absolute numbers cannot be used for policy, they only fuel fear and panic. national lockdowns are not a solution. they protect people temporarily, but they also leave them susceptible. once restrictions are lifted, cases of infection are likely to increase again. there is no exit from the pandemic; there is only an exit from the response to it. we are still at an early stage of understanding how best to clinically manage covid- both as a disease and as a risk factor to potentially vulnerable populations. it is vital to find better ways of sharing quality data and effective practice to ensure health systems learn and adapt quickly. what this pandemic shows is a lack of preparedness. this will come as a surprise, given the billions of dollars, euros, and pounds that were spent over the last years on pandemic preparedness, including experience with past epidemics and pandemics such as ebola and swine flu. how can it be that hospitals ran out of n masks in week one? where did all the billions spent on preparedness go? outsourced production capacity and insufficient stockpiles of personal protective equipment put nursing home residents, community health care workers, and hospital staff at risk, weakening health care systems further. key preparedness concepts need to be at the heart of the response. fifteen years of pandemic preparedness seem to have evaporated into thin air in this pandemic. instead of activating existing plans and drawing on concepts such as the pandemic severity assessment framework, countries imposed a massive, untested, and unproven generic lockdown with unforeseeable social, political, and economic repercussions. sars-cov- is less lethal than every single scenario exercise that has been conducted for preparedness planning by governments and non-governmental organizations in europe and america. it will be important to understand why key preparedness concepts were sidelined in this pandemic, despite the attention that preparedness received and the substantial resources it consumed for over a decade. the fear of death is powerful in societies eager to repress the inescapable reality of death. in such a context, it is important to flatten the curve of extreme speaking, feeling, and acting. what was and will always be urgently needed is moderation and perspective. to continue to engage in today's competition for ever more extreme predictions is dangerous. it will only support those who ignored the virus initially and who are more than willing to blame it now for the mess. equally dangerous is a public health populism of clapping hands that leaves out any consideration of the social, political, and economic costs and consequences of sweeping interventions. attempts to obscure political failures are growing rapidly. those who contribute to extreme predictions and apocalyptic readings of the current situation are only contributing to the obfuscation of the policy failures and underlying structural issues that are responsible for many of today's problems. there are already attempts in countries such as the united kingdom and the united states to rewrite failure as success. not surprisingly, governments are calling on citizens to participate in public performances, demonstrate national unity in the face of danger, and celebrate collective strength and resolve. fighter jets soaring through the sky and helicopters showering rose petals on "frontline warriors" are militarized state spectacles. but health care workers deserve more than patriotic feelings and symbolic gestures; they deserve better health care policies. to challenge and critique now is essential. the story of how the chinese approach became a model for generic lockdowns in the global north and then exported to countries in the global south is important to note, particularly considering the dramatic consequences for millions of people struggling to survive without any source of income. ironically, these extremely restrictive lockdowns were sometimes demanded by people eager to criticize the authoritarianism of the chinese state. across the world, the pandemic unleashed authoritarian longings in democratic societies, allowing governments to seize the opportunity, create states of exception and push political agendas. commentators have presented the pandemic as a chance for the west to learn authoritarianism from the east. this pandemic risks teaching people to love power and call for its meticulous application. pandemic time is an auspicious time for all kinds of political projects. as a result of the unforeseeable social, political, and economic consequences of today's sweeping measures, governments across the world have launched record stimulus bills costing trillions of dollars, pounds, pesos, rand, and rupees. earmarked predominantly for individuals and businesses, these historic emergency relief bills are pumping staggering amounts of money into the economy, but, ironically, they are not intended to strengthen the public health infrastructure or improve medical care. the trillions that governments are spending now as stimulus packages surpass even those of the financial crisis and will need to be paid for somehow. today, there is a massive global recession in the making. if austerity policies of the past are at the root of the current crisis with overwhelmed health care systems in some countries, the rapidly rising public debt is creating the perfect conditions for more austerity in the future. the pandemic response will have major implications for the public funding of education, welfare, social security, environment, and health in the future. if you think something good will come out of this crisis, you should think again. today we are just driving faster and with a much bigger car, but it is the same road with the same destination. wolf bukowski notes that the political discussion in italy is now dominated by an "uncritical 'responsibility'" that cannot find a place outside the imperative to contain the virus. "the right intuition that 'we should not question the reality of the epidemic' shifts all too easily into 'we should not question the government's response to the epidemic'" (bukowski ). in such a context, any control intervention imposed by the state is perceived as lawful, and no democratic discussion and debate appears necessary ("let the experts speak!"). in other places, critique has become difficult for other reasons. the tragedy of today's political moment in the united states, the united kingdom, and brazil is that right-wing politicians pushed many into embracing measures that one thought were only possible in authoritarian regimes. here, an engagement in critical analysis has become almost impossible because it is seen as playing into the hands of trump, johnson, and bolsonaro, political figures who seem unconcerned with public health and the staggering inequalities that afflict our world and whose public statements have reached an unmatched level of ignorance and incompetence. however, it is important to understand that the strategic combination of confusion, contradiction, and the play of extreme opposites is foundational for authoritarian rule. everything that instills a sense of disorder and that intensifies the crisis magnifies the desire for decisive action. in this article, i have tried to carve a path through the morass of fear, panic, and desire for control to see how one can sustain a critical analysis of the pandemic response. as scholars and citizens, we have the obligation to think beyond the crisis, create openings in the world, and consider, critically and democratically, how we want to govern ourselves. as veena das underscores, it is important that we do not let our "love for the subtle and nuanced understanding of issues disappear on the grounds of needs for the rough and the ready in an emergency" (das ) . the pandemic and the response to it will require us to reimagine lives, rebuild conditions of existence, and find better ways of doing science and politics. like every engagement in a serious pedagogical project, it will entail a reconsideration of the objects we desire. today's fear is fueled by four main forces: mathematical disease modeling-a flexible and highly adaptable tool for prediction, mixing calculations with speculations, often based on codes that are kept secret and assumptions that are difficult to scrutinize from the outside. neoliberal policies-systematic disinvestments in public health and medical care that have created fragile systems unable to cope with the crisis. nervous media reporting-an endless stream of information, obsessed with absolute numbers, exploiting the lack of trust in the health care infrastructure and magnifying the fear of collapsing systems. authoritarian longings-a deep desire for sovereign rule, which derives pleasure from destruction and tries to push the world to the edge of collapse so that it can be rebuilt from scratch. this set of forces inspires thought, action, and passion in powerful ways. energized by the thrilling experience of witnessing "history in the making," actors and institutions have seized the opportunity to reorder the world, push political agendas in the name of survival, and shape life for years to come. the pandemic has become an auspicious moment to change the rules of engagement and expand the scope of scientific, medical, and political authority over bodies and populations. it is an occasion to publish papers and make dramatic statements, to feel relevant and important to the world, and enjoy the moment in the limelight. in the midst of death and destruction, the pandemic creates opportunities for innovation, domination, and profit-making. this unexpected opening connects elites in science, politics, and the media, releasing shocks of information, instruction, and command that are pushing hard against our confined, anxious, restless bodies. mathematical disease modeling, neoliberal policies, nervous media, and authoritarian longings fuel a fatal spiral centered around the fear of collapse. this fear is now literally in the air; it moves in and out of us with every breath; it operates as animating medium of our intense isolation and immobility. pandemic fear is unnerving and mentally exhausting. yet for those who embrace the feeling, it has the power of sustaining a state of excitement-excitement derived from the secret pleasure of spoiling a precious thing, wasting enormous resources, and engaging in an all-consuming project with total dedication. what we might call the provocation of the crisis-its intensification, expansion, and totalization beyond any notion of utility-seems so excessive and extreme that it borders on sheer madness. what could be more dangerous, more daring, more exciting than a walk on the wild side, an excursion to the other side of reason? melodramatic phrases such as "beating the virus," "winning the war," and "defeating the darkness" are rhetorically powerful and contagious. equally popular notions like "corona heroes" and "lockdown warriors" are symptoms of overidentification in a hegemonic discourse of power. all these terms reveal how this pandemic is "fabulously textual, through and through," and, at the same time, is lacking a source of symbolization strong, creative, and disturbing enough to move our engagement with the world beyond the most conventional of tropes (derrida ) . the language that we are asked to adopt today, in the midst of this outbreak, is contaminated with words that are stiff, stale, and corrupt like putrid air. given that so much of today's response is based on and driven by mathematical disease modeling and that millions of lives and livelihoods are being destroyed before our eyes, it is not an option anymore to exclude the "externalities" of a pandemic response that lacks imagination and that has resorted to the crudest interventions of all: the full stop. for those with permanent jobs, a comfortable couch, and no daycare duties, this unforeseen interruption may feel like a gift, a welcome relief from the non-stop world of global capitalism. but for millions of people living in less privileged parts of the planet, the pause button spells unemployment and hunger, not breaktime and downtime. without income, food, and access to basic health care, people are not making the most of the confinement outside in the garden; they are desperate and dying. we urgently need to look beyond the virus if we want to understand the real seriousness of what is happening today. how did we end up in this strange space of thinking, acting, and feeling that has normalized extremes and that is based on the assumption that biological life is an absolute value separate from politics? never has it been more important to insist that another politics of life is possible. the latest imperial college disease model report summarizes the staggering blindness that has prevailed in this pandemic: "we do not consider the wider social and economic costs of suppression, which will be high" (walker et al. ) . the time to suppress the costs of suppression and cast the consequences of interventions as an externality to model-based policy is over. these claims are utterly misleading, ignoring the influenza pandemics of and , including the hiv/aids pandemic, ebola, and many other infectious disease outbreaks that have killed millions of people worldwide with no vaccine available. last but not least, the toll of covid- is not even close to the toll of the influenza pandemic. . the report distinguishes between two strategies these days i sometimes catch myself wishing to get the virus-in this way, at least the debilitating uncertainty would be over… a clear sign of how my anxiety is growing is how i relate to sleep. till around a week ago i was eagerly awaiting the evening: finally, i can escape into sleep and forget about the fears of my daily life… now it's almost the opposite: i am afraid to fall asleep since nightmares haunt me in my dreams and awaken me in panic-nightmares about the reality that awaits me disasters and capitalism … and covid- . somatosphere website staying at home. e-flux real estimates of mortality following covid- infection. the lancet coronavirus testing: how some countries got ahead of the rest. the guardian website germany's coronavirus anomaly controllo e autocontrollo sociale ai tempi del covid- the pandemic perhaps: dramatic events in a public culture of danger the normal and the pathological french medics warn health service is on the brink of collapse. the guardian website anger and poverty grip lebanese city. the guardian as covid- pandemic hits india's daily-wage earners hard, some leave city for their home towns. scroll.in website facing covid- : my land of neither hope nor despair no apocalypse, not now impact of non-pharmaceutical interventions (npis) to reduce covid- mortality and health care demand. imperial college website for autocrats and others corona virus is a chance to grab even more power. the new york times website wartime conditions" as global coronavirus deaths reach . the guardian website spread of sars-cov- in the icelandic population cash-starved hospitals and doctor groups cut staff amid pandemic. the washington post bangladesh: end wave of covid- "rumor" arrests. human rights watch website indian doctors evicted over coronavirus transmission fears, says medical body. the wire website, march ebola vaccines, evidentiary charisma and the rise of global health emergency research managing hospital volumes germany and experiences from oecd countries scale of china's wuhan shutdown is believed to be without precedent. the new york times so stark ist die krankenhaus-auslastung mit corona-patienten. mdr website kenya police abuses could undermine coronavirus fight. human rights watch website . case-fatality rate and characteristics of patients dying in relation to covid- in italy china tightens wuhan lockdown in "wartime" battle with coronavirus. the new york times website shows commitment to contain virus: who representation in china. reuters website us unemployment rises another m, bringing total to m since pandemic began. the guardian website india moves big labour law changes to limit coronavirus impact others make these changes. financial express website why belgium's death rate is so high: it counts lots of suspected covid- cases. npr website vorläufiges ergebnis und schlussfolgerungen der covid- case-cluster-study urgent call for an exit plan: the economic and social consequences of response to covid- pandemic. centre for global development website the global impact of covid- and strategies for mitigation and suppression who. . report of the who-china joint mission on coronavirus disease (covid- estimating clinical severity of covid- from the transmission dynamics in wuhan, china is barbarism with a human face our fate? critical inquiry blog stavrianakis, nancy tamini, and laurence tessier. i am particularly grateful for conversations with richard sullivan. maria josé de abreu insisted i start writing and put thoughts on paper. for suggestions, i would like to thank the editor of medical anthropology quarterly, vincanne adams, and the two anonymous reviewers. none of these colleagues and friends are responsible for the arguments in this article. key: cord- -syirijql authors: adiga, aniruddha; chen, jiangzhuo; marathe, madhav; mortveit, henning; venkatramanan, srinivasan; vullikanti, anil title: data-driven modeling for different stages of pandemic response date: - - journal: arxiv doi: nan sha: doc_id: cord_uid: syirijql some of the key questions of interest during the covid- pandemic (and all outbreaks) include: where did the disease start, how is it spreading, who is at risk, and how to control the spread. there are a large number of complex factors driving the spread of pandemics, and, as a result, multiple modeling techniques play an increasingly important role in shaping public policy and decision making. as different countries and regions go through phases of the pandemic, the questions and data availability also changes. especially of interest is aligning model development and data collection to support response efforts at each stage of the pandemic. the covid- pandemic has been unprecedented in terms of real-time collection and dissemination of a number of diverse datasets, ranging from disease outcomes, to mobility, behaviors, and socio-economic factors. the data sets have been critical from the perspective of disease modeling and analytics to support policymakers in real-time. in this overview article, we survey the data landscape around covid- , with a focus on how such datasets have aided modeling and response through different stages so far in the pandemic. we also discuss some of the current challenges and the needs that will arise as we plan our way out of the pandemic. as the sars-cov- pandemic has demonstrated, the spread of a highly infectious disease is a complex dynamical process. a large number of factors are at play as infectious diseases spread, including variable individual susceptibility to the pathogen (e.g., by age and health conditions), variable individual behaviors (e.g., compliance with social distancing and the use of masks), differing response strategies implemented by governments (e.g., school and workplace closure policies and criteria for testing), and potential availability of pharmaceutical interventions. governments have been forced to respond to the rapidly changing dynamics of the pandemic, and are becoming increasingly reliant on different modeling and analytical techniques to understand, forecast, plan and respond; this includes statistical methods and decision support methods using multi-agent models, such as: (i) forecasting epidemic outcomes (e.g., case counts, mortality and hospital demands), using a diverse set of data-driven methods e.g., arima type time series forecasting, bayesian techniques and deep learning, e.g., [ ] [ ] [ ] [ ] [ ] , (ii) disease surveillance, e.g., [ , ] , and (iii) counter-factual analysis of epidemics using multi-agent models, e.g., [ ] [ ] [ ] [ ] [ ] [ ] ; indeed, the results of [ , ] were very influential in the early decisions for lockdowns in a number of countries. the specific questions of interest change with the stage of the pandemic. in the pre-pandemic stage, the focus was on understanding how the outbreak started, epidemic parameters, and the risk of importation to different regions. once outbreaks started-the acceleration stage, the focus is on determining the growth rates, the differences in spatio-temporal characteristics, and testing bias. in the mitigation stage, the questions are focused on non-prophylactic interventions, such as school and work place closures and other social-distancing strategies, determining the demand for healthcare resources, and testing and tracing. in the suppression stage, the focus shifts to using prophylactic interventions, combined with better tracing. these phases are not linear, and overlap with each other. for instance, the acceleration and mitigation stages of the pandemic might overlap spatially, temporally as well as within certain social groups. different kinds of models are appropriate at different stages, and for addressing different kinds of questions. for instance, statistical and machine learning models are very useful in forecasting and short term projections. however, they are not very effective for longer-term projections, understanding the effects of different kinds of interventions, and counter-factual analysis. mechanistic models are very useful for such questions. simple compartmental type models, and their extensions, namely, structured metapopulation models are useful for several population level questions. however, once the outbreak has spread, and complex individual and community level behaviors are at play, multi-agent models are most effective, since they allow for a more systematic representation of complex social interactions, individual and collective behavioral adaptation and public policies. as with any mathematical modeling effort, data plays a big role in the utility of such models. till recently, data on infectious diseases was very hard to obtain due to various issues, such as privacy and sensitivity of the data (since it is information about individual health), and logistics of collecting such data. the data landscape during the sars-cov- pandemic has been very different: a large number of datasets are becoming available, ranging from disease outcomes (e.g., time series of the number of confirmed cases, deaths, and hospitalizations), some characteristics of their locations and demographics, healthcare infrastructure capacity (e.g., number of icu beds, number of healthcare personnel, and ventilators), and various kinds of behaviors (e.g., level of social distancing, usage of ppes); see [ ] [ ] [ ] for comprehensive surveys on available datasets. however, using these datasets for developing good models, and addressing important public health questions remains challenging. the goal of this article is to use the widely accepted stages of a pandemic as a guiding framework to highlight a few important problems that require attention in each of these stages. we will aim to provide a succinct model-agnostic formulation while identifying the key datasets needed, how they can be used, and the challenges arising in that process. we will also use sars-cov- as a case study unfolding in real-time, and highlight some interesting peer-reviewed and preprint literature that pertains to each of these problems. an important point to note is the necessity of randomly sampled data, e.g. data needed to assess the number of active cases and various demographics of individuals that were affected. census provides an excellent rationale. it is the only way one can develop rigorous estimates of various epidemiologically relevant quantities. there have been numerous surveys on the different types of datasets available for sars-cov- , e.g., [ ] [ ] [ ] [ ] , as well as different kinds of modeling approaches. however, they do not describe how these models become relevant through the phases of pandemic response. an earlier similar attempt to summarize such responsedriven modeling efforts can be found in [ ] , based on the -h n experience, this paper builds on their work and discusses these phases in the present context and the sars-cov- pandemic. although the paper touches upon different aspects of model-based decision making, we refer the readers to a companion article in the same special issue [ ] for a focused review of models used for projection and forecasting. multiple organizations including cdc and who have their frameworks for preparing and planning response to a pandemic. for instance, the pandemic intervals framework from cdc describes the stages in the context of an influenza pandemic; these are illustrated in figure . these six stages span investigation, recognition and initiation in the early phase, followed by most of the disease spread occurring during the acceleration and deceleration stages. they also provide indicators for identifying when the pandemic has progressed from one stage to the next [ ] . as envisioned, risk evaluation (i.e., using tools like influenza risk assessment tool (irat) and pandemic severity assessment framework (psaf)) and early case identification characterize the first three stages, while non-pharmaceutical interventions (npis) and available figure : cdc pandemic intervals framework and who phases for influenza pandemic therapeutics become central to the acceleration stage. the deceleration is facilitated by mass vaccination programs, exhaustion of susceptible population, or unsuitability of environmental conditions (such as weather). a similar framework is laid out in who's pandemic continuum and phases of pandemic alert . while such frameworks aid in streamlining the response efforts of these organizations, they also enable effective messaging. to the best of our knowledge, there has not been a similar characterization of mathematical modeling efforts that go hand in hand with supporting the response. for summarizing the key models, we consider four of the stages of pandemic response mentioned in section : pre-pandemic, acceleration, mitigation and suppression. here we provide the key problems in each stage, the datasets needed, the main tools and techniques used, and pertinent challenges. we structure our discussion based on our experience with modeling the spread of covid- in the us, done in collaboration with local and federal agencies. • acceleration (section ): this stage is relevant once the epidemic takes root within a country. there is usually a big lag in surveillance and response efforts, and the key questions are to model spread patterns at different spatio-temporal scales, and to derive short-term forecasts and projections. a broad class of datasets is used for developing models, including mobility, populations, land-use, and activities. these are combined with various kinds of time series data and covariates such as weather for forecasting. • mitigation (section ): in this stage, different interventions, which are mostly non-pharmaceutical in the case of a novel pathogen, are implemented by government agencies, once the outbreak has taken hold within the population. this stage involves understanding the impact of interventions on case counts and health infrastructure demands, taking individual behaviors into account. the additional datasets needed in this stage include those on behavioral changes and hospital capacities. • suppression (section ): this stage involves designing methods to control the outbreak by contact tracing & isolation and vaccination. data on contact tracing, associated biases, vaccine production schedules, and compliance & hesitancy are needed in this stage. figure gives an overview of this framework and summarizes the data needs in these stages. these stages also align well with the focus of the various modeling working groups organized by cdc which include epidemic parameter estimation, international spread risk, sub-national spread forecasting, impact of interventions, healthcare systems, and university modeling. in reality, one should note that these stages may overlap, and may vary based on geographical factors and response efforts. moreover, specific problems can be approached prospectively in earlier stages, or retrospectively during later stages. this framework is thus meant to be more conceptual than interpreted along a linear timeline. results from such stages are very useful for policymakers to guide real-time response. consider a novel pathogen emerging in human populations that is detected through early cases involving unusual symptoms or unknown etiology. such outbreaks are characterized by some kind of spillover event, mostly through zoonotic means, like in the case of covid- or past influenza pandemics (e.g., swine flu and avian flu). a similar scenario can occur when an incidence of a well-documented disease with no known vaccine or therapeutics emerges in some part of the world, causing severe outcomes or fatalities (e.g., ebola and zika.) regardless of the development status of the country where the pathogen emerged, such outbreaks now contains the risk of causing a worldwide pandemic due to the global connectivity induced by human travel. two questions become relevant at this stage: what are the epidemiological attributes of this disease, and what are the risks of importation to a different country? while the first question involves biological and clinical investigations, the latter is more related with societal and environmental factors. one of the crucial tasks during early disease investigation is to ascertain the transmission and severity of the disease. these are important dimensions along which the pandemic potential is characterized because together they determine the overall disease burden, as demonstrated within the pandemic severity assessment framework [ ] . in addition to risk assessment for right-sizing response, they are integral to developing meaningful disease models. formulation let Θ = {θ t , θ s } represent the transmission and severity parameters of interest. they can be further subdivided into sojourn time parameters θ δ · and transition probability parameters θ p · . here Θ corresponds to a continuous time markov chain (ctmc) on the disease states. the problem formulation can be represented as follows: given Π(Θ), the prior distribution on the disease parameters and a dataset d, estimate the posterior distribution p(Θ|d) over all possible values of Θ. in a model-specific form, this can be expressed as p(Θ|d, m) where m is a statistical, compartmental or agent-based disease model. in order to estimate the disease parameters sufficiently, line lists for individual confirmed cases is ideal. such datasets contain, for each record, the date of confirmation, possible date of onset, severity (hospitalization/icu) status, and date of recovery/discharge/death. furthermore, age-and demographic/comorbidity information allow development of models that are age-and risk group stratified. one such crowdsourced line list was compiled during the early stages of covid- [ ] and later released by cdc for us cases [ ] . data from detailed clinical investigations from other countries such as china, south korea, and singapore was also used to parameterize these models [ ] . in the absence of such datasets, past parameter estimates of similar diseases (e.g., sars, mers) were used for early analyses. modeling approaches for a model agnostic approach, the delays and probabilities are obtained by various techniques, including bayesian and ordinary least squares fitting to various delay distributions. for a particular disease model, these are estimated through model calibration techniques such as mcmc and particle filtering approaches. a summary of community estimates of various disease parameters is provided at https://github.com/midas-network/covid- . further such estimates allow the design of pandemic planning scenarios varying in levels of impact, as seen in the cdc scenarios page . see [ ] [ ] [ ] for methods and results related to estimating covid- disease parameters from real data. current models use a large set of disease parameters for modeling covid- dynamics; they can be broadly classified as transmission parameters and hospital resource parameters. for instance in our work, we currently use parameters (with explanations) shown in table . challenges often these parameters are model specific, and hence one needs to be careful when reusing parameter estimates from literature. they are related but not identifiable with respect to population level measures such as basic reproductive number r (or effective reproductive number r eff ) and doubling time which allow tracking the rate of epidemic growth. also the estimation is hindered by inherent biases in case ascertainment rate, reporting delays and other gaps in the surveillance system. aligning different data streams (e.g., outpatient surveillance, hospitalization rates, mortality records) is in itself challenging. when a disease outbreak occurs in some part of the world, it is imperative for most countries to estimate their risk of importation through spatial proximity or international travel. such measures are incredibly valuable in setting a timeline for preparation efforts, and initiating health checks at the borders. over centuries, pandemics have spread faster and faster across the globe, making it all the more important to characterize this risk as early as possible. formulation let c be the set of countries, and g = {c, e} an international network, where edges (often weighted and directed) in e represent some notion of connectivity. the importation risk problem can be formulated as below: given c o ∈ c the country of origin with an initial case at time , and c i the country of interest, using g, estimate the expected time taken t i for the first cases to arrive in country c i . in its probabilistic form, the same can be expressed as estimating the probability p i (t) of seeing the first case in country c i by time t. data needs assuming we have initial case reports from the origin country, the first data needed is a network that connects the countries of the world to represent human travel. the most common source of such information is the airline network datasets, from sources such as iata, oag, and openflights; [ ] provides a systematic review of how airline passenger data has been used for infectious disease modeling. these datasets could either capture static measures such as number of seats available or flight schedules, or a dynamic count of passengers per month along each itinerary. since the latter has intrinsic delays in collection and reporting, for an ongoing pandemic they may not be representative. during such times, data on ongoing travel restrictions [ ] become important to incorporate. multi-modal traffic will also be important to incorporate for countries that share land borders or have heavy maritime traffic. for diseases such as zika, where establishment risk is more relevant, data on vector abundance or prevailing weather conditions are appropriate. modeling approaches simple structural measures on networks (such as degree, pagerank) could provide static indicators of vulnerability of countries. by transforming the weighted, directed edges into probabilities, one can use simple contagion models (e.g., independent cascades) to simulate disease spread and empirically estimate expected time of arrival. global metapopulation models (gleam) that combine seir type dynamics with an airline network have also been used in the past for estimating importation risk. brockmann and helbing [ ] used a similar framework to quantify effective distance on the network which seemed to be well correlated with time of arrival for multiple pandemics in the past; this has been extended to covid- [ , ] . in [ ] , the authors employ air travel volume obtained through iata from ten major cities across china to rank various countries along with the idvi to convey their vulnerability. [ ] consider the task of forecasting international and domestic spread of covid- and employ official airline group (oag) data for determining air traffic to various countries, and [ ] fit a generalized linear model for observed number of cases in various countries as a function of air traffic volume obtained from oag data to determine countries with potential risk of under-detection. also, [ ] provide africa-specific case-study of vulnerability and preparedness using data from civil aviation administration of china. challenges note that arrival of an infected traveler will precede a local transmission event in a country. hence the former is more appropriate to quantify in early stages. also, the formulation is agnostic to whether it is the first infected arrival or first detected case. however, in real world, the former is difficult to observe, while the latter is influenced by security measures at ports of entry (land, sea, air) and the ease of identification for the pathogen. for instance, in the case of covid- , the long incubation period and the high likelihood of asymptomaticity could have resulted in many infected travelers being missed by health checks at poes. we also noticed potential administrative delays in reporting by multiple countries fearing travel restrictions. as the epidemic takes root within a country, it may enter the acceleration phase. depending on the testing infrastructure and agility of surveillance system, response efforts might lag or lead the rapid growth in case rate. under such a scenario, two crucial questions emerge that pertain to how the disease may spread spatially/socially and how the case rate may grow over time. within the country, there is need to model the spatial spread of the disease at different scales: state, county, and community levels. similar to the importation risk, such models may provide an estimate of when cases may emerge in different parts of the country. when coupled with vulnerability indicators (socioeconomic, demographic, co-morbidities) they provide a framework for assessing the heterogeneous impact the disease may have across the country. detailed agent-based models for urban centers may help identify hotspots and potential case clusters that may emerge (e.g., correctional facilities, nursing homes, food processing plants, etc. in the case of covid- ). formulation given a population representation p at appropriate scale and a disease model m per entity (individual or sub-region), model the disease spread under different assumptions of underlying connectivity c and disease parameters Θ. the result will be a spatio-temporal spread model that results in z s,t , the time series of disease states over time for region s. data needs some of the common datasets needed by most modeling approaches include: ( ) social and spatial representation, which includes census, and population data, which are available from census departments (see, e.g., [ ] ), and landscan [ ] , ( ) connectivity between regions (commuter, airline, road/rail/river), e.g., [ , ] , ( ) data on locations, including points of interest, e.g., openstreetmap [ ] , and ( ) activity data, e.g., the american time use survey [ ] . these datasets help capture where people reside and how they move around, and come in contact with each other. while some of these are static, more dynamic measures, such as from gps traces, become relevant as individuals change their behavior during a pandemic. modeling approaches different kinds of structured metapopulation models [ , [ ] [ ] [ ] [ ] , and agent based models [ ] [ ] [ ] [ ] [ ] have been used in the past to model the sub-national spread; we refer to [ , , ] for surveys on different modeling approaches. these models incorporate typical mixing patterns, which result from detailed activities and co-location (in the case of agent based models), and different modes of travel and commuting (in the case of metapopulation models). challenges while metapopulation models can be built relatively rapidly, agent based models are much harder-the datasets need to be assembled at a large scale, with detailed construction pipelines, see, e.g., [ ] [ ] [ ] [ ] [ ] . since detailed individual activities drive the dynamics in agent based models, schools and workplaces have to be modeled, in order to make predictions meaningful. such models will get reused at different stages of the outbreak, so they need to be generic enough to incorporate dynamically evolving disease information. finally, a common challenge across modeling paradigms is the ability to calibrate to the dynamically evolving spatio-temporal data from the outbreak-this is especially challenging in the presence of reporting biases and data insufficiency issues. given the early growth of cases within the country (or sub-region), there is need for quantifying the rate of increase in comparable terms across the duration of the outbreak (accounting for the exponential nature of such processes). these estimates also serve as references, when evaluating the impact of various interventions. as an extension, such methods and more sophisticated time series methods can be used to produce short-term forecasts for disease evolution. formulation given the disease time series data within the country z s,t until data horizon t , provide scale-independent growth rate measures g s (t ), and forecastsẐ s,u for u ∈ [t, t + ∆t ], where ∆t is the forecast horizon. data needs models at this stage require datasets such as ( ) time series data on different kinds of disease outcomes, including case counts, mortality, hospitalizations, along with attributes, such as age, gender and location, e.g., [ ] [ ] [ ] [ ] [ ] , ( ) any associated data for reporting bias (total tests, test positivity rate) [ ] , which need to be incorporated into the models, as these biases can have a significant impact on the dynamics, and ( ) exogenous regressors (mobility, weather), which have been shown to have a significant impact on other diseases, such as influenza, e.g., [ ] . modeling approaches even before building statistical or mechanistic time series forecasting methods, one can derive insights through analytical measures of the time series data. for instance, the effective reproductive number, estimated from the time series [ ] can serve as a scale-independent metric to compare the outbreaks across space and time. additionally multiple statistical methods ranging from autoregressive models to deep learning techniques can be applied to the time series data, with additional exogenous variables as input. while such methods perform reasonably for short-term targets, mechanistic approaches as described earlier can provide better long-term projections. various ensembling techniques have also been developed in the recent past to combine such multi-model forecasts to provide a single robust forecast with better uncertainty quantification. one such effort that combines more than methods for covid- can be found at the covid forecasting hub . we also point to the companion paper for more details on projection and forecasting models. challenges data on epidemic outcomes usually has a lot of uncertainties and errors, including missing data, collection bias, and backfill. for forecasting tasks, these time series data need to be near real-time, else one needs to do both nowcasting, as well as forecasting. other exogenous regressors can provide valuable lead time, due to inherent delays in disease dynamics from exposure to case identification. such frameworks need to be generalized to accommodate qualitative inputs on future policies (shutdowns, mask mandates, etc.), as well as behaviors, as we discuss in the next section. once the outbreak has taken hold within the population, local, state and national governments attempt to mitigate and control its spread by considering different kinds of interventions. unfortunately, as the covid- pandemic has shown, there is a significant delay in the time taken by governments to respond. as a result, this has caused a large number of cases, a fraction of which lead to hospitalizations. two key questions in this stage are: ( ) how to evaluate different kinds of interventions, and choose the most effective ones, and ( ) how to estimate the healthcare infrastructure demand, and how to mitigate it. the effectiveness of an intervention (e.g., social distancing) depends on how individuals respond to them, and the level of compliance. the health resource demand depends on the specific interventions which are implemented. as a result, both these questions are connected, and require models which incorporate appropriate behavioral responses. in the initial stages, only non-prophylactic interventions are available, such as: social distancing, school and workplace closures, and use of ppes, since no vaccinations and anti-virals are available. as mentioned above, such analyses are almost entirely model based, and the specific model depends on the nature of the intervention and the population being studied. formulation given a model, denoted abstractly as m, the general goals are ( ) to evaluate the impact of an intervention (e.g., school and workplace closure, and other social distancing strategies) on different epidemic outcomes (e.g., average outbreak size, peak size, and time to peak), and ( ) find the most effective intervention from a suite of interventions, with given resource constraints. the specific formulation depends crucially on the model and type of intervention. even for a single intervention, evaluating its impact is quite challenging, since there are a number of sources of uncertainty, and a number of parameters associated with the intervention (e.g., when to start school closure, how long, and how to restart). therefore, finding uncertainty bounds is a key part of the problem. data needs while all the data needs from the previous stages for developing a model are still there, representation of different kinds of behaviors is a crucial component of the models in this stage; this includes: use of ppes, compliance to social distancing measures, and level of mobility. statistics on such behaviors are available at a fairly detailed level (e.g., counties and daily) from multiple sources, such as ( ) the covid- impact analysis platform from the university of maryland [ ] , which gives metrics related to social distancing activities, including level of staying home, outside county trips, outside state trips, ( ) changes in mobility associated with different kinds of activities from google [ ] , and other sources, ( ) survey data on different kinds of behaviors, such as usage of masks [ ] . modeling approaches as mentioned above, such analyses are almost entirely model based, including structured metapopulation models [ , [ ] [ ] [ ] [ ] , and agent based models [ ] [ ] [ ] [ ] [ ] . different kinds of behaviors relevant to such interventions, including compliance with using ppes and compliance to social distancing guidelines, need to be incorporated into these models. since there is a great deal of heterogeneity in such behaviors, it is conceptually easiest to incorporate them into agent based models, since individual agents are represented. however, calibration, simulation and analysis of such models pose significant computational challenges. on the other hand, the simulation of metapopulation models is much easier, but such behaviors cannot be directly represented-instead, modelers have to estimate the effect of different behaviors on the disease model parameters, which can pose modeling challenges. challenges there are a number of challenges in using data on behaviors, which depends on the specific datasets. much of the data available for covid- is estimated through indirect sources, e.g., through cell phone and online activities, and crowd-sourced platforms. this can provide large spatio-temporal datasets, but have unknown biases and uncertainties. on the other hand, survey data is often more reliable, and provides several covariates, but is typically very sparse. handling such uncertainties, rigorous sensitivity analysis, and incorporating the uncertainties into the analysis of the simulation outputs are important steps for modelers. the covid- pandemic has led to a significant increase in hospitalizations. hospitals are typically optimized to run near capacity, so there have been fears that the hospital capacities would not be adequate, especially in several countries in asia, but also in some regions in the us. nosocomial transmission could further increase this burden. formulation the overall problem is to estimate the demand for hospital resources within a populationthis includes the number of hospitalizations, and more refined types of resources, such as icus, ccus, medical personnel and equipment, such as ventilators. an important issue is whether the capacity of hospitals within the region would be overrun by the demand, when this is expected to happen, and how to design strategies to meet the demand-this could be through augmenting the capacities at existing hospitals, or building new facilities. timing is of essence, and projections of when the demands exceed capacity are important for governments to plan. the demands for hospitalization and other health resources can be estimated from the epidemic models mentioned earlier, by incorporating suitable health states, e.g., [ , ] ; in addition to the inputs needed for setting up the models for case counts, datasets are needed for hospitalization rates and durations of hospital stay, icu care, and ventilation. the other important inputs for this component are hospital capacity, and the referral regions (which represent where patients travel for hospitalization). different public and commercial datasets provide such information, e.g., [ , ] . modeling approaches demand for health resources is typically incorporated into both metapopulation and agent based models, by having a fraction of the infectious individuals transition into a hospitalization state. an important issue to consider is what happens if there is a shortage of hospital capacity. studying this requires modeling the hospital infrastructure, i.e., different kinds of hospitals within the region, and which hospital a patient goes to. there is typically limited data on this, and data on hospital referral regions, or voronoi tesselation can be used. understanding the regimes in which hospital demand exceeds capacity is an important question to study. nosocomial transmission is typically much harder to study, since it requires more detailed modeling of processes within hospitals. challenges there is a lot of uncertainty and variability in all the datasets involved in this process, making its modeling difficult. for instance, forecasts of the number of cases and hospitalizations have huge uncertainty bounds for medium or long term horizon, which is the kind of input necessary for understanding hospital demands, and whether there would be any deficits. the suppression stage involves methods to control the outbreak, including reducing the incidence rate and potentially leading to the eradication of the disease in the end. eradication in case of covid- appears unlikely as of now, what is more likely is that this will become part of seasonal human coronaviruses that will mutate continuously much like the influenza virus. contact tracing problem refers to the ability to trace the neighbors of an infected individual. ideally, if one is successful, each neighbor of an infected neighbor would be identified and isolated from the larger population to reduce the growth of a pandemic. in some cases, each such neighbor could be tested to see if the individual has contracted the disease. contact tracing is the workhorse in epidemiology and has been immensely successful in controlling slow moving diseases. when combined with vaccination and other pharmaceutical interventions, it provides the best way to control and suppress an epidemic. formulation the basic contact tracing problem is stated as follows: given a social contact network g(v, e) and subset of nodes s ⊂ v that are infected and a subset s ⊂ s of nodes identified as infected, find all neighbors of s. here a neighbor means an individual who is likely to have a substantial contact with the infected person. one then tests them (if tests are available), and following that, isolates these neighbors, or vaccinates them or administers anti-viral. the measures of effectiveness for the problem include: (i) maximizing the size of s , (ii) maximizing the size of set n (s ) ⊆ n (s), i.e. the potential number of neighbors of set s , (iii) doing this within a short period of time so that these neighbors either do not become infectious, or they minimize the number of days that they are infectious, while they are still interacting in the community in a normal manner, (iv) the eventual goal is to try and reduce the incidence rate in the community-thus if all the neighbors of s cannot be identified, one aims to identify those individuals who when isolated/treated lead to a large impact; (v) and finally verifying that these individuals indeed came in contact with the infected individuals and thus can be asked to isolate or be treated. data needs data needed for the contact tracing problem includes: (i) a line list of individuals who are currently known to be infected (this is needed in case of human based contact tracing). in the real world, when carrying out human contact tracers based deployment, one interviews all the individuals who are known to be infectious and reaches out to their contacts. modeling approaches human contact tracing is routinely done in epidemiology. most states in the us have hired such contact tracers. they obtain the daily incidence report from the state health departments and then proceed to contact the individuals who are confirmed to be infected. earlier, human contact tracers used to go from house to house and identify the potential neighbors through a well defined interview process. although very effective it is very time consuming and labor intensive. phones were used extensively in the last - years as they allow the contact tracers to reach individuals. they are helpful but have the downside that it might be hard to reach all individuals. during covid- outbreak, for the first time, societies and governments have considered and deployed digital contact tracing tools [ ] [ ] [ ] [ ] [ ] . these can be quite effective but also have certain weaknesses, including, privacy, accuracy, and limited market penetration of the digital apps. challenges these include: (i) inability to identify everyone who is infectious (the set s) -this is virtually impossible for covid- like disease unless the incidence rate has come down drastically and for the reason that many individuals are infected but asymptomatic; (ii) identifying all contacts of s (or s ) -this is hard since individuals cannot recall everyone they met, certain folks that they were in close proximity might have been in stores or social events and thus not known to individuals in the set s. furthermore, even if a person is able to identify the contacts, it is often hard to reach all the individuals due to resource constraints (each human tracer can only contact a small number of individuals. the overall goal of the vaccine allocation problem is to allocate vaccine efficiently and in a timely manner to reduce the overall burden of the pandemic. formulation the basic version of the problem can be cast in a very simple manner (for networked models): given a graph g(v, e) and a budget b on the number of vaccines available, find a set s of size b to vaccinate so as to optimize certain measure of effectiveness. the measure of effectiveness can be (i) minimizing the total number of individuals infected (or maximizing the total number of uninfected individuals); (ii) minimizing the total number of deaths (or maximizing the total number of deaths averted); (iii) optimizing the above quantities but keeping in mind certain equity and fairness criteria (across socio-demographic groups, e.g. age, race, income); (iv) taking into account vaccine hesitancy of individuals; (v) taking into account the fact that all vaccines are not available at the start of the pandemic, and when they become available, one gets limited number of doses each month; (vi) deciding how to share the stockpile between countries, state, and other organizations; (vii) taking into account efficacy of the vaccine. data needs as in other problems, vaccine allocation problems need as input a good representation of the system; network based, meta-population based and compartmental mass action models can be used. one other key input is the vaccine budget, i.e., the production schedule and timeline, which serves as the constraint for the allocation problem. additional data on prevailing vaccine sentiment and past compliance to seasonal/neonatal vaccinations are useful to estimate coverage. modeling approaches the problem has been studied actively in the literature; network science community has focused on optimal allocation schemes, while public health community has focused on using meta-population models and assessing certain fixed allocation schemes based on socio-economic and demographic considerations. game theoretic approaches that try and understand strategic behavior of individuals and organization has also been studied. challenges the problem is computationally challenging and thus most of the time simulation based optimization techniques are used. challenge to the optimization approach comes from the fact that the optimal allocation scheme might be hard to compute or hard to implement. other challenges include fairness criteria (e.g. the optimal set might be a specific group) and also multiple objectives that one needs to balance. while the above sections provide an overview of salient modeling questions that arise during the key stages of a pandemic, mathematical and computational model development is equally if not more important as we approach the post-pandemic (or more appropriately inter-pandemic) phase. often referred to as peace time efforts, this phase allows modelers to retrospectively assess individual and collective models on how they performed during the pandemic. in order to encourage continued development and identifying data gaps, synthetic forecasting challenge exercises [ ] may be conducted where multiple modeling groups are invited to forecast synthetic scenarios with varying levels of data availability. another set of models that are quite relevant for policymakers during the winding down stages, are those that help assess overall health burden and economic costs of the pandemic. epideep: exploiting embeddings for epidemic forecasting an arima model to forecast the spread and the final size of covid- epidemic in italy (first version on ssrn march) real-time epidemic forecasting: challenges and opportunities accuracy of real-time multi-model ensemble forecasts for seasonal influenza in the u.s realtime forecasting of infectious disease dynamics with a stochastic semi-mechanistic model healthmap the use of social media in public health surveillance. western pacific surveillance and response journal : wpsar the effect of travel restrictions on the spread of the novel coronavirus (covid- ) outbreak basic prediction methodology for covid- : estimation and sensitivity considerations. medrxiv covid- outbreak on the diamond princess cruise ship: estimating the epidemic potential and effectiveness of public health countermeasures impact of non-pharmaceutical interventions (npis) to reduce covid mortality and healthcare demand. imperial college technical report modelling disease outbreaks in realistic urban social networks computational epidemiology forecasting covid- impact on hospital bed-days, icudays, ventilator-days and deaths by us state in the next months open data resources for fighting covid- data-driven methods to monitor, model, forecast and control covid- pandemic: leveraging data science, epidemiology and control theory covid- datasets: a survey and future challenges. medrxiv mathematical modeling of epidemic diseases the use of mathematical models to inform influenza pandemic preparedness and response mathematical models for covid- pandemic: a comparative analysis updated preparedness and response framework for influenza pandemics novel framework for assessing epidemiologic effects of influenza epidemics and pandemics covid- pandemic planning scenarios epidemiological data from the covid- outbreak, real-time case information covid- case surveillance public use data -data -centers for disease control and prevention covid- patients' clinical characteristics, discharge rate, and fatality rate of meta-analysis estimating the generation interval for coronavirus disease (covid- ) based on symptom onset data the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application estimating clinical severity of covid- from the transmission dynamics in wuhan, china the use and reporting of airline passenger data for infectious disease modelling: a systematic review flight cancellations related to -ncov (covid- ) the hidden geometry of complex, network-driven contagion phenomena potential for global spread of a novel coronavirus from china forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study. the lancet using predicted imports of -ncov cases to determine locations that may not be identifying all imported cases. medrxiv preparedness and vulnerability of african countries against introductions of -ncov. medrxiv creating synthetic baseline populations openstreetmap american time use survey multiscale mobility networks and the spatial spreading of infectious diseases optimizing spatial allocation of seasonal influenza vaccine under temporal constraints assessing the international spreading risk associated with the west african ebola outbreak spread of zika virus in the americas structure of social contact networks and their impact on epidemics generation and analysis of large synthetic social contact networks modelling disease outbreaks in realistic urban social networks containing pandemic influenza at the source report : impact of non-pharmaceutical interventions (npis) to reduce covid mortality and healthcare demand the structure and function of complex networks a public data lake for analysis of covid- data midas network. midas novel coronavirus repository covid- ) data in the united states covid- impact analysis platform covid- surveillance dashboard the covid tracking project absolute humidity and the seasonal onset of influenza in the continental united states epiestim: a package to estimate time varying reproduction numbers from epidemic curves. r package version google covid- community mobility reports mask-wearing survey data impact of social distancing measures on coronavirus disease healthcare demand, central texas, usa current hospital capacity estimates -snapshot total hospital bed occupancy quantifying the effects of contact tracing, testing, and containment covid- epidemic in switzerland: on the importance of testing, contact tracing and isolation quantifying sars-cov- transmission suggests epidemic control with digital contact tracing isolation and contact tracing can tip the scale to containment of covid- in populations with social distancing. available at ssrn privacy sensitive protocols and mechanisms for mobile contact tracing the rapidd ebola forecasting challenge: synthesis and lessons learnt acknowledgments. the authors would like to thank members of the biocomplexity covid- response team and network systems science and advanced computing (nssac) division for their thoughtful comments and suggestions related to epidemic modeling and response support. we thank members of the biocomplexity institute and initiative, university of virginia for useful discussion and suggestions. this key: cord- -y il hyb authors: nan title: pandemic flu: clinical management of patients with an influenza-like illness during an influenza pandemic date: - - journal: j infect doi: . /s - ( ) - sha: doc_id: cord_uid: y il hyb nan • this document is intended for use in the uk in the event that the world health organisation declares that an influenza pandemic has started , and the department of health in england (uk-wide lead agency on pandemic influenza, including the devolved administrations) has declared uk pandemic alert level (cases of pandemic influenza identified within the uk). • these guidelines are not relevant for the management of patients affected by seasonal/interpandemic influenza, lower respiratory tract infections, community-acquired pneumonia or exacerbations of chronic obstructive pulmonary disease (copd). • once an influenza pandemic is under way, users are strongly urged to ensure that they refer to the most up-todate version of these guidelines (from web-based access points). synopsis . clinical management of adults referred to hospitals s . . severity assessment in hospital • patients with uncomplicated influenza infection would be expected to make a full recovery and do not require hospital care. • in uncomplicated infection, the illness usually resolves in seven days although cough, malaise and lassitude may persist for weeks. • patients with worsening of pre-existing co-morbid medical conditions should be managed according to best practice for that condition with reference to published disease-specific guidelines, if available, for example, the national institute of clinical excellence's copd guideline. • in hospital, patients with influenza-related pneumonia and who have a curb- score of , or (see box a) are at high risk of death and should be managed as having severe pneumonia. • patients with bilateral lung infiltrates on chest radiography consistent with primary viral pneumonia should be managed as having severe pneumonia regardless of curb- score. • patients who have a curb- score of are at increased risk of death. they should be considered for short stay inpatient treatment or hospital supervised outpatient treatment. this decision is a matter of clinical judgment. • patients who have a curb- score of or are at low risk of death. they can be treated as having non-severe pneumonia and may be suitable for home treatment. • patients with primary viral pneumonia or a curb- score of or should be considered for hdu/icu transfer. • general indications for hdu/icu transfer include: ( ) persisting hypoxia with pao < kpa despite maximal oxygen administration ( ) progressive hypercapnia ( ) severe acidosis (ph < . ) ( ) septic shock • patients with influenza admitted to intensive care unit should be managed by specialists with appropriate training in intensive care, respiratory medicine and/or infectious diseases. pandemic flu. clinical management of patients with an influenza-like illness during an influenza pandemic s s . . general investigations • the following investigations are recommended in patients referred to hospital: who this applies to full blood count all patients urea and electrolytes all patients liver function tests all patients chest x-ray all patients pulse oximetry all patients. if < % on air, then arterial blood gases. patients with cardiac and respiratory complications or co-morbid illnesses. c-reactive protein if influenza-related pneumonia is suspected • in those patients who are subsequently followed up in a hospital outpatient clinic or by a general practitioner a repeat chest x-ray should be obtained at around six weeks if respiratory symptoms or signs persist or where there is a higher risk of underlying malignancy (especially smokers and those over years of age). • further investigations including a ct thoracic scan and bronchoscopy should be considered if the chest x-ray remains abnormal at follow up. s . . microbiological investigations s . . . early in a pandemic (uk alert levels , and ) • virology all patients ( ) nose and throat swabs in virus transport medium. ( ) if presentation is more than seven days after onset of illness, an 'acute' serum ( ml clotted blood) should be collected and a 'convalescent' sample ( ml clotted blood) obtained after an interval of not less than seven days. • bacteriology patients with influenza-related pneumonia ( ) blood culture (preferably before antibiotic treatment is commenced) ( ) pneumococcal urine antigen ( ml urine sample) ( ) legionella urine antigen ( ml urine sample) ( ) sputum gram stain, culture and antimicrobial susceptibility tests on samples obtained from patients who: (i) are able to expectorate purulent samples, and (ii) have not received prior antibiotic treatment. ( ) paired serological examination for influenza/other agents. acute serum should be collected and a 'convalescent' sample obtained after an interval not less than seven days (both ml clotted blood). • virology not routinely recommended • bacteriology patients with influenza-related pneumonia in accordance to the severity of illness. (a) non-severe pneumonia (curb- score , or ) no routine testing. in patients who do not respond to empirical antibiotic therapy, sputum samples should be sent for gram stain culture and antimicrobial susceptibility tests. b severe pneumonia (curb- score , or , or bilateral cxr changes) blood culture, preferably before antibiotic treatment is commenced pneumococcal urine antigen ( ml urine) sputum gram stain, culture and antimicrobial susceptibility tests on samples obtained from patients who are able to expectorate purulent samples, and have not received prior antibiotic treatment. paired serological examination for influenza/other agents. 'acute' serum should be collected and a 'convalescent' sample obtained after an interval not less than seven days (both ml clotted blood). tracheal or endotracheal aspirate samples, if available, should be sent for gram stain, culture and antimicrobial susceptibility testing. s . . general management s . • hypoxic patients should receive appropriate oxygen therapy with monitoring of oxygen saturations and inspired oxygen concentration with the aim to maintain pao kpa and sao ges; %. high concentrations of oxygen can safely be given in uncomplicated pneumonia. • oxygen therapy in patients with pre-existing chronic obstructive pulmonary disease complicated by ventilatory failure should be guided by repeated arterial blood gas measurements. non-invasive ventilation may be helpful. • in patients without pre-existing copd who develop respiratory failure, niv may be of value as a bridge to invasive ventilation in specific circumstances when level beds are in high demand. respiratory and/or critical care units experienced in the use of niv are best placed to ensure the appropriate infection control measures are adopted at all times. • patients should be assessed for cardiac complications and also volume depletion and their need for additional intravenous fluids. • nutritional support should be given in severe or prolonged illness. • temperature, respiratory rate, pulse, blood pressure, mental status, oxygen saturation and inspired oxygen concentration should be monitored and recorded initially at least twice daily and more frequently in those with severe illness or requiring regular oxygen therapy. an early warning score system is a convenient way to perform this. • in patients who are not progressing satisfactorily a full clinical reassessment and a repeat chest radiograph are recommended. • patients should be reviewed hours prior to discharge home. those with two or more of the following unstable clinical factors should consider remaining in hospital: ( ) temperature > . ºc ( ) heart rate > /min ( ) respiratory rate > /min ( ) systolic blood pressure < mmhg ( ) oxygen saturation < % ( ) inability to maintain oral intake ( ) abnormal mental status • follow up clinical review should be considered for all patients who suffered significant complications or who had significant worsening of their underlying disease, either with their general practitioner or in a hospital clinic. • at discharge or at follow up, patients should be offered access to information about their illness, take home medication and any follow up arrangements. • it is the responsibility of the hospital team to arrange the follow up plan with the patient and the general practitioner. • individuals should only be considered for treatment with antivirals (neuraminidase inhibitors) if they have all of the following: ( ) an acute influenza-like illness ( ) fever (> ºc) and ( ) been symptomatic for two days or less. • treatment schedule: adults oseltamivir mg every hours for five days. (dose to be reduced by % if creatinine clearance is less than ml/minute, i.e. mg od). • patients who are unable to mount an adequate febrile response, e.g. the immunocompromised or very elderly, may still be eligible for antiviral treatment despite lack of documented fever. • hospitalised patients who are severely ill, particularly if also immunocompromised, may benefit from antiviral treatment started more than hours from disease onset, although there is no evidence to demonstrate benefit, or lack of it, in such circumstances. s . . antibiotic management s . . . influenza • previously well adults with acute bronchitis complicating influenza, in the absence of pneumonia, do not routinely require antibiotics. • antibiotics should be considered in those previously well adults who develop worsening symptoms (recrudescent fever or increasing dyspnoea). • patients at high risk of complications or secondary infection (appendix ) should be considered for antibiotics in the presence of lower respiratory features. • most patients can be adequately treated with oral antibiotics. • the preferred choice includes co-amoxiclav or a tetracycline. • a macrolide such as clarithromycin (or erythromycin) or a fluoroquinolone active against streptococcus pneumoniae and staphylococcus aureus is an alternative choice in certain circumstances. • most patients can be adequately treated with oral antibiotics. • oral therapy with co-amoxiclav or a tetracycline is preferred. • when oral therapy is contra-indicated, recommended parenteral choices include intravenous co-amoxiclav, or a second or third generation cephalosporin (cefuroxime or cefotaxime). • a macrolide (erythromycin or clarithromycin) or a fluoroquinolone active against s. pneumoniae and staph. aureus is an alternative regimen where required eg. for those intolerant of penicillins. currently levofloxacin and moxifloxacin are the only recommended fluoroquinolones licensed in the uk. • antibiotics should be administered within four hours of admission. • patients with severe pneumonia should be treated immediately after diagnosis with parenteral antibiotics. • an intravenous combination of a broad spectrum b-lactamase stable antibiotic such as co-amoxiclav or a second (e.g. cefuroxime) or third (e.g. cefotaxime) generation cephalosporin together with a macrolide (e.g. clarithromycin or erythromycin) is preferred. • an alternative regimen includes a fluoroquinolone with enhanced activity against pneumococci together with a broad spectrum b-lactamase stable antibiotic or a macrolide. currently levofloxacin is the only fluoroquinolone with an intravenous formulation licensed in the uk. • patients treated initially with parenteral antibiotics should be transferred to an oral regimen as soon as clinical improvement occurs and the temperature has been normal for hours, providing there is no contra-indication to the oral route. • for most patients admitted to hospital with non severe and uncomplicated pneumonia, seven days of appropriate antibiotics is recommended. • for those with severe, microbiologically undefined pneumonia, ten days treatment is proposed. this should synopsis . clinical management of adults referred to hospitals synopsis of main recommendations pandemic flu. clinical management of patients with an influenza-like illness during an influenza pandemic s be extended to to days where staph aureus or gram negative enteric bacilli pneumonia is suspected or confirmed. • for those with non-severe pneumonia in hospital on combination therapy, changing to a fluoroquinolone with effective pneumococcal and staphylococcal cover is an option. • adding further antibiotics effective against mrsa is an option for those with severe pneumonia not responding to combination antibiotic therapy. • high fever (> . ºc) and cough or influenza-like symptoms. these children should seek advice from a community health professional. if there are no features that put them at high risk of complications they should be treated with oseltamivir, and given advice on antipyretics and fluids. children aged < year and those at risk of complications (appendix ) should be seen by a gp. • high fever (> . ºc) and cough or influenza-like symptoms, plus at risk group. these children should be seen by a gp or in a&e. children may be considered at increased risk of complications if they have cough and fever (or influenza-like illness) and temperature > . ºc, plus either chronic co-morbid disease or one of following features: breathing difficulties severe earache vomiting > hours drowsiness these patients should be offered an antibiotic as well as oseltamivir (in those > year of age) and advice on antipyretics and fluids. children aged < year with none of the above features should be treated with antipyretics and fluids with a low threshold for antibiotics if they become more unwell. • indicators for hospital admission are: ( ) signs of respiratory distress. markedly raised respiratory rate grunting intercostal recession breathlessness with chest signs ( ) cyanosis ( ) severe dehydration ( ) altered conscious level ( ) complicated or prolonged seizure ( ) signs of septicaemia extreme pallor, hypotension, floppy infant • most children admitted to hospital are likely to need oxygen therapy and/or intravenous support as well as antibiotics and oseltamivir. • indications for transfer to high dependency or intensive care are: ( ) failure to maintain sao > % in fio > % ( ) the child is shocked ( ) severe respiratory distress and a raised paco (> . kpa) ( ) rising respiratory rate and pulse rate with clinical evidence of severe respiratory distress with or without a raised paco ( ) recurrent apnoea or slow irregular breathing ( ) evidence of encephalopathy • when there are no picu beds available, children will have to be triaged on the basis of the severity of their acute and co-existing disease, and the likelihood of their achieving full recovery. • a full blood count with differential, urea, creatinine and electrolytes, liver enzymes and a blood culture should be done in all severely ill children. • a cxr should be performed in children who are hypoxic, have severe illness or who are deteriorating despite treatment. • pulse oximetry should be performed in every child being assessed for admission to hospital with pneumonia. • virology all children ( ) nasopharyngeal aspirate or nose and throat swabs ( ) if presentation is more than days after onset of illness, an 'acute' serum ( ml clotted blood) should be collected and a 'convalescent' sample ( ml clotted blood) obtained after an interval of not less than days. • bacteriology children with influenza-related pneumonia ( ) blood culture (before antibiotic treatment is commenced) ( ) sputum samples obtained from older children ( ) paired serological examination for influenza/other agents. • virology not routinely recommended • bacteriology children with influenza-related pneumonia ( ) blood culture (before antibiotic treatment is commenced) ( ) sputum samples obtained from older children • patients whose oxygen saturation is % or less while breathing air should be treated with oxygen given by nasal cannulae, head box, or face mask to maintain oxygen saturation above %. • when children are unable to maintain oral intake, supplementary fluids should, when possible, be given by the enteral route. intravenous fluids in those with severe pneumonia should be given at % basal levels. • children can be safely discharged from hospital when they: ( ) are clearly improving ( ) are physiologically stable ( ) can tolerate oral feeds ( ) have a respiratory rate < /min (< /min in infants) ( ) have an awake oxygen saturation of > % in air. • in the setting of a pandemic, children should only be considered for treatment with antivirals if they have all of the following: ( ) an acute influenza-like illness ( ) fever (> . ºc) and ( ) been symptomatic for two days or less • oseltamivir is the antiviral agent of choice. • in children who are severely ill in hospital oseltamivir may be used if the child has been symptomatic for < days (but there is no evidence to demonstrate benefit, or lack of it, in such circumstances). • children (a) who are at risk of complications of influenza or (b) with disease severe enough to merit hospital admission during an influenza pandemic should be treated with an antibiotic that will provide cover against s. pneumoniae, staph. aureus and h. influenzae. • for children under years co-amoxiclav is the drug of choice. clarithromycin or cefuroxime should be used in children allergic to penicillin. for children over years doxycycline is an alternative. • oral antibiotics should be given provided oral fluids are tolerated. • children who are severely ill with pneumonia complicating influenza should have a second agent added to the regime (e.g. clarithromycin or cefuroxime) and the drugs should be given intravenously to ensure high serum and tissue antibiotic levels. to facilitate preparedness planning, this document has been written in advance of the emergence of the next influenza pandemic, at a time when the identity of the causative virus remains unknown. these guidelines are based on the best evidence available from previous pandemic and interpandemic influenza periods. the guidance may evolve as clinicopathological information on the eventual pandemic virus emerges. once an influenza pandemic is under way, users are strongly urged to refer to the most up-todate version of these guidelines (from web-based access points). seasonal influenza is a familiar infection in the uk, especially during winter. every year strains of influenza (type a or b) circulate, giving rise to clinical consultations in primary care (age-specific impact varies by season), episodes of hospital treatment (mainly in older persons and young children, but occasionally in working age adults), and deaths (mainly in the elderly). treatment in primary care and hospital may be required due to the direct effects of influenza virus infection or its possible complications, most commonly secondary bacterial pneumonia. increases in gp consultations for influenza-like illness and winter bed pressures are frequently associated with periods of known community influenza activity . pandemic influenza occurs when a new influenza a virus subtype emerges which is markedly different from recently circulating subtypes and strains, and is able to: • infect humans; • spread efficiently from person to person; • cause significant clinical illness in a high proportion of those infected. because the virus is novel in humans, a high proportion of the population will have little or no immunity, producing a large pool of susceptible persons; accordingly the disease spreads widely and rapidly. influenza pandemics occur sporadically and unpredictably. in , a devastating and unusual pandemic caused by influenza a/h n ('spanish flu') killed between and million people worldwide. other pandemics that followed had a less devastating impact but were nevertheless severe. influenza a/h n ('asian flu') emerged in , and h n ('hong kong flu') in ; both produced roughly million excess deaths worldwide . the circumstances still exist for a new influenza virus with pandemic potential to emerge and spread, and the longest interval so far recorded between pandemics is years ( ) . the unpredictability of the timing of the next pandemic is underlined by the occurrence of several large outbreaks of highly pathogenic avian influenza associated with epizootic transmission to humans . by far the most serious has been the massive and unprecedented outbreak of highly pathogenic influenza (a/h n ) affecting poultry in east and south east asia in late , which is still continuing. this outbreak has so far been associated with a small number of human cases but a high proportion of deaths. recently, epidemiological and virological changes have been reported from northern vietnam which may indicate that the virus is beginning to adapt to humans . although the emergence of an a/h n strain with capacity to spread efficiently between humans is neither inevitable nor imminent, international concern has increased regarding the possibility that avian influenza a/h n may evolve to produce the next pandemic. other events and developments that inform the creation of this guidance are the development and licensing of a new class of drug (neuraminidase inhibitors) active against influenza, and uk government's announcement of plans to procure . million treatment courses of oseltamivir (tamiflu ® ) for use in the uk in the event of a pandemic. be involved in the management of patients with influenza. it is intended that these guidelines also be of value to health-care practitioners who do not usually manage patients with influenza but may be called upon to do so in a pandemic situation. modification of some recommendations at a local level may be necessary in specific instances. these guidelines are not relevant for the management of patients affected by seasonal influenza, sporadic acute exacerbations of chronic obstructive pulmonary disease (aecopd), lower respiratory tract infections (lrtis) or community-acquired pneumonia (cap). at the primary care level, a national operational plan including the following three broad areas is deemed important: (a) clinical management of patients with influenza (b) management of patient demand, including patients who do not have influenza (c) health service delivery plans these guidelines cover the first of these areas and will serve as the source document for the primary care operational plan. the primary care operational plan will incorporate all three areas within a single reference and is being developed by the dh in collaboration with the rcgp and the bma. even though it is impossible to predict with certainty the impact of the next pandemic, based upon the available epidemiological and modelling information, it is clear that it will generate demands for health care which may saturate or overwhelm normal nhs acute services for a period of time, perhaps several weeks or months. accordingly, it should be anticipated that the nhs (in common with all health systems around the world) will need to revert to emergency arrangements. these are laid out in further detail in operational guidance for health service planners , the uk operational framework for stockpiling, distributing and using antiviral drugs in the event of pandemic influenza and in the primary care operational plan. with regard to the delivery of medical care for patients with influenza this is normally achieved through: • gp treatment of community patients 'well' enough to be managed in the community • hospital care in acute medicine for persons considered too ill to be managed at home. in the event of a pandemic, the following additional care settings may have to be considered as the threshold for hospital admission rises: • treatment of patients in the community (who would normally receive care from a gp) by other health-care professionals (nurses, paramedics, pharmacists etc.) following treatment guidance laid out in this publication and using prescription-only medicines according to patient group directives (pgds). • treatment of patients in their own homes or in temporary intermediate care facilities by a gp, following treatment guidance laid out in this publication when, under normal circumstances, such patients would have been admitted for hospital care. • treatment of severely ill patients in hospital by medical and nursing teams who do not normally manage patients with influenza or community-acquired pneumonia, in areas of the hospital not normally used for providing medical care (for example, surgical teams and bed space diverted from routine elective work towards pandemic response). the recommendations offered in the current guidelines are based on a matrix of evidence centred mainly around seasonal influenza, expert opinion and group consensus. grading of these recommendations based on the strength of the evidence base was deemed inappropriate. section . epidemiology and health impact projections ( ) the scale and severity of illness (and hence consequences) caused by pandemic influenza generally exceed those of even the most severe winter epidemics. ( ) mortality in the uk is likely to exceed , deaths, possibly appreciably higher. ( ) besides the elderly, excess mortality is also likely in younger adults and children. ( ) modelling studies suggest that after a case occurs in hong kong, because of international travel, it will take less than one month for the virus to reach the uk. ( ) once cases begin to occur in the uk it will take only two to three weeks before activity is widespread and roughly a further three weeks (six weeks after initial cases in uk) until activity peaks. ( ) it is possible that there will be more than one epidemic wave (with an interval of several months) and, if a second wave occurs, it may be more severe than the first. ( ) cumulative clinical and serological attack rates across all waves together may be in the order of % and % respectively. ( ) increases in demand for health-care services are likely to be very substantial in both primary care and hospital settings. when an influenza pandemic occurs, a substantial proportion (possibly all) of the population is likely to be non-immune, producing a large pool of susceptible persons. in past pandemics, the scale and severity of illness (and hence consequences) have been variable but broadly of a § . epidemiology and health impact projections introductory observations higher order than even the most severe winter epidemics. it is reasonable to expect this to be the case with the next pandemic as well. excess mortality due to influenza occurs in most winter seasons but is especially marked during epidemics. the average annual excess mortality attributable to influenza in recent years is around , deaths per annum in england and wales , although there is considerable yearly variation and some years are notably much higher than the average (est. , in / epidemic). excess mortality in england and wales associated with the three pandemics of the twentieth century has also varied widely; this was estimated at , civilians in / , and , in / . in / and / (both seasons considered to be associated with the influenza a/h n pandemic), there were an estimated , and , deaths respectively . therefore the extent of mortality associated with the next pandemic cannot be reliably predicted although it is reasonable to plan for a scenario worse than a severe winter epidemic of normal influenza. typically, there are changes in the age-distribution of cases compared with seasonal influenza. mortality, which in typical seasonal influenza is usually confined to age groups over years, tends to be increased in younger age groups. the size of any increase in morbidity and mortality and the extent to which a shift in age distribution occurs depend on a variety of factors including the nature of the pandemic virus and pre-existing immunity but appears to be a consistent phenomenon . therefore, clinicians can expect to see relatively larger amounts of influenza-related illness in younger adults compared with normal winter activity. at least one third of all excess deaths may be expected in persons under years of age. virological and clinical surveillance of influenza have improved markedly since the last pandemic in . however, the extent of international travel has also grown. modelling studies using transmission characteristics based on the / pandemic and international air-traffic data from indicate that the approximate delay between a first case in hong kong and first introduction to uk will be less than one month . in terms of the spread within the uk, it will probably take only two to three weeks from the initial introduction(s) until activity is widespread and a further three weeks (six weeks from initial uk cases) until activity peaks. the temporal and spatial spread of a pandemic strain is important, particularly in terms of the demand placed on health-care services. pandemic activity taking the form of a brief but severe peak in cases will be more difficult for all services to cope with, compared with an identical number of cases distributed over a longer time course. for example, during the a/h n pandemic a long first wave occurred in the winter of / with morbidity and mortality approximately at the same level as the previous seasonal influenza; but in the following winter of / a short and more severe epidemic occurred with a threefold higher peak in general practice consultation rates and a four-fold higher peak in mortality attributed to influenza, bronchitis and pneumonia. the high peak in consultation rates is well illustrated in fig. . . in / , the a/h n pandemic occurred in three distinct epidemic waves: early spring , autumn introductory observations § . epidemiology and health impact projections s provisional guidelines from bis/bts/hpa in collaboration with the department of health, version ( october ) and late winter . the second wave was by far the largest and case-fatality rates were also higher than in the first wave. the a/h n pandemic caused an epidemic wave in the winter of / but a more severe one in / . in contrast, the second wave of the / pandemic in the uk was very small in comparison to the first . thus it should be considered a possibility that more than one wave of influenza will occur within a few months of the emergence of a pandemic virus and a subsequent wave could be worse than the first. it is impossible to predict reliably with precision the level of excess mortality that will be experienced in the next pandemic. however, table . illustrates the broad range of excess mortality that it is reasonable to consider, based on various realistic combinations of case fatality rate and clinical attack rates derived from previous pandemics and epidemics. a case fatality rate of . % corresponds to the aggregate rate observed in recent epidemic seasons ( / , / , / , / , / , / and / ) and the pandemic, although the overall case-fatality rate observed in the pandemic was in the region of %. a clinical attack rate of around % corresponds to the approximate clinical attack rate seen in all three previous pandemics of the twentieth century. thus, a figure of at least , excess deaths is likely. using mathematical projections, it is possible to illustrate the potential impact of the next pandemic, but these do not amount to accurate predictions. table . summarises the number of events that might be expected by a gp with patients on his/her list and by a pct serving a population of , persons. using the same assumptions, table . illustrates the number of events by week over an assumed -week (single wave) pandemic period in a typical pct population of , . most major acute trusts receive patients from a catchment area spanning several pcts and the figures below require pro-rata adjustment before applying to individual hospitals. section . clinical features in adults ( ) influenza is clinically defined as the presence of fever and new (or, in those with chronic lung disease, worsening) cough of acute onset in the context of influenza circulating in the community. this clinical definition may be modified once a pandemic occurs. ( ) the spectrum of clinical disease associated with a pandemic strain cannot be forecast. ( ) pneumonia, either primary viral or secondary bacterial, is the commonest complication of influenza in adults. ( ) neurological complications are rare in adults. the clinical manifestations of infection by influenza viruses are diverse, ranging from asymptomatic infection to fulminant respiratory distress leading to respiratory failure and death. furthermore, the presence of an influenza-like illness (ili) comprising of a combination of fever, cough, sore throat, myalgia and headache is not specific for influenza infection. other respiratory pathogens that may present with an ili include viruses such as respiratory syncytial virus (rsv), adenovirus, rhinovirus and parainfluenza virus, as well as bacterial pathogens such as chlamydia pneumoniae, legionella sp., mycoplasma pneumoniae and streptococcus pneumoniae [ ] [ ] [ ] . studies that have examined the value of a clinical definition of ili in the diagnosis of influenza infection have not always used the same clinical definition for an ili and have included different study populations, making comparison between studies complicated. a systematic review of the literature in this area identified the threefold combination of the presence of fever, cough and acute onset to be the most predictive clinical features. the accuracy of this clinical definition was higher in persons aged years and above compared to patient groups without age restrictions [positive likelihood ratio ( % ci) . ( . . ) vs . ( . . )] . the probability of influenza infection also increases with increasing level of fever , . importantly, the predictive value of clinical definitions based on an ili increases when influenza virus is known to be circulating in the community , , . in cohort studies, correlation of ili with laboratory-confirmed influenza infection ranges from % to % while in clinical trials, rates of % have been consistently reported , [ ] [ ] [ ] .. these findings relate to influenza infections during interpandemic periods. during a global influenza pandemic, when a pandemic strain is known to be circulating locally in an immunologically susceptible population, the presence of an ili would be expected to be highly predictive for influenza infection. (however, the extent to which a clinical diagnosis of ili becomes predictive during a pandemic will also be determined by the behaviour of the public. if many who would not normally present to a health professional are prompted to present, then the predictive value of a clinical diagnosis of ili will be reduced.) the following description will relate mainly to interpandemic influenza a infections. influenza b and c are not considered pandemic threats. different strains may be associated with different clinical presentations and disease severity. for instance, there is evidence to suggest that the h n subtype causes more severe disease than h n subtype . the spectrum of clinical disease associated with a new influenza a subtype (eg. a pandemic strain) cannot be determined currently and may differ from that described for interpandemic influenza. the incubation period prior to the onset of symptoms is commonly two to four days (range days). in adults, the illness typically presents as an abrupt onset of fever accompanied by a range of other symptoms as listed in box . [ ] [ ] [ ] [ ] [ ] . fever is the paramount symptom and may reach ºc although more usually it ranges between ºc and ºc. the peak occurs within hours of onset and lasts typically for three days (range days) [ ] [ ] [ ] [ ] [ ] . the cough is generally dry although in up to % of cases it may be productive. a productive cough together with chest tightness and substernal soreness is more common in patients with underlying chronic lung disease. myalgia affects mainly the back and limbs. gastrointestinal symptoms such as vomiting and diarrhoea are uncommon (< %) in adults. abdominal pain is rare. clinical findings include a toxic appearance in the initial stages, hot and moist skin, a flushed face, injected eyes and hyperaemic mucous membranes around the nose and pharynx. tender cervical lymphadenopathy is found in a minority (~ %) of cases. wheezing or lung crackles are recognised findings (~ %) more commonly noted in patients with coexisting chronic lung disease. although the overall clinical picture of uncomplicated influenza in any specific age group is similar for different influenza a subtypes, the frequency of certain symptoms may vary. for instance, during the 'asian' pandemic of (h n ), headache and sore throat were frequent initial symptoms . in uncomplicated infection, the illness usually resolves in seven days although cough, malaise and lassitude may persist for weeks. influenza virus infection has been associated with worsening in the clinical condition of patients with a range of existing medical conditions, such as, heart failure, diabetes, coronary heart disease, asthma and chronic obstructive airways disease (copd). in addition, specific complications associated with influenza infection regardless of co-existing medical conditions are recognised (table . ). based on data from interpandemic influenza, certain persons are identified as being at high risk from influenza-related complications. such patients are similar to the group currently recommended for influenza vaccination by the department of health. these include those of all ages with chronic respiratory disease including asthma, chronic heart disease, chronic renal disease, chronic liver disease, immunosuppression due to disease or treatment, or diabetes mellitus, and all those aged years or older, or those in long stay residential care (see appendix ). in the course of a pandemic, it may emerge that the patient group at high risk of complications differs from the group currently identified. in such circumstance, details of the 'high risk' patient group will be altered according to relevant clinico-epidemiological data. the incidence of pneumonia (defined as a combination of respiratory symptoms and signs supported by chest radiographic changes consistent with infection) complicating influenza infection varies widely, from % to %, and is dependent on viral and host factors [ ] [ ] [ ] . pneumonia generally occurs more frequently and with greater severity in patients with pre-existing chronic cardiac and respiratory conditions. patients who develop pneumonia may present with symptoms and signs indistinguishable from pneumonia related to other viral and bacterial pathogens. in the context of an influenza pandemic, the presence of an ili and new or worsening dyspnoea should prompt a careful examination for the presence of complicating pneumonia. two main types of influenza-related pneumonia are recognised: primary viral pneumonia and secondary bacterial pneumonia [ ] [ ] [ ] [ ] . patients with primary viral pneumonia typically become breathless within the first hours of onset of fever. an initially dry cough may become productive of blood-stained sputum. cyanosis, tachypnoea, bilateral crepitations and wheeze on chest examination and leucocytosis are usual. the commonest chest radiographic abnormality is of bilateral interstitial infiltrates predominantly in the mid-zones, although focal consolidation is also well recognised. rapid clinical deterioration with respiratory failure may ensue . the mortality in hospitalised patients is high (> %) despite maximum supportive treatment on intensive care [ ] [ ] [ ] [ ] . in the majority of fatal cases, death occurs within seven days of hospital admission. secondary bacterial pneumonia is more common (up to four times) than primary viral pneumonia. typically, symptoms and signs of pneumonia develop during the early convalescent period (four to five days from onset of initial symptoms). in others, symptoms of pneumonia blend in with the initial symptoms of influenza. chest radiography usually demonstrates a lobar pattern of consolidation. mortality rate ranges from % to % [ ] [ ] [ ] [ ] [ ] , although some small studies report higher mortality rates. the spectrum of pathogens implicated is similar to that observed in cap and includes streptococcus pneumoniae, staphylococcus aureus, haemophilus influenzae and groups a, c and g b-haemolytic streptococci , , [ ] [ ] [ ] . different pathogens have predominated at different times. for instance, in the pandemic, h. influenzae, b-haemolytic streptococci and s. pneumoniae were the predominant pathogens isolated. in , s. pneumoniae was the predominant pathogen ( %) followed by staph. aureus ( %) and non-typeable h. influenzae ( %) . notably, staph. aureus was identified two and a half times more frequently during the pandemic compared to pneumonia occurring in the interpandemic period , . secondary staphylococcal pneumonia is associated with a higher incidence of lung abscess formation ( % vs %) and carries a poorer prognosis compared to non-staphylococcal pneumonias (mortality % vs %) , , , . during the pandemic, staph. aureus was the predominant bacterial pathogen isolated in fatal cases of influenzarelated pneumonia (up to % of cases in some series) . bacterial and viral pneumonia can occur concurrently. in these instances, the chest radiograph may demonstrate lobar consolidation superimposed on bilateral diffuse lung infiltrates. the mortality rate in mixed viral bacterial pneumonia is high (> %), as for primary viral pneumonia [ ] [ ] [ ] [ ] . minor abnormalities on ecg such as st segment deviation, t wave changes and rhythm disturbances have been described in uncomplicated influenza illness. they have been reported in up to % of patients hospitalised with influenza . most do not have cardiac symptoms. myocarditis and pericarditis are occasionally encountered in severe illness , . post mortem evidence of necrotising myocarditis has been reported in patients without clinically significant myocarditis in the antemortem period. in contrast with myalgia affecting the back and limbs which is common on initial presentation, myositis generally develops after the subsidence of the acute upper respiratory tract symptoms. the gastrocnemius and soleus muscles are typically involved with pain and tenderness to palpation. complete recovery usually occurs in three days. elevation in serum creatine phosphokinase is recognised , . rarely, this is associated with myoglobinuria and renal failure , . myositis is more commonly described in children than in adults. central nervous system (cns) involvement in adults is uncommon. most reports originate from japan and occur in children , . the main clinical syndrome is an encephalitis or encephalopathy manifesting in the form of decreased consciousness and seizures about three days (range days) following the onset of upper respiratory tract symptoms. focal neurological signs such as paresis, aphasia, choreoathetosis and cranial nerve palsies are less common. cerebrospinal fluid (csf) examination may be normal or reveal an elevation in protein or white cell count. imaging by ct or mri may be normal and if so, is indicative of a good prognosis and full recovery may be anticipated . young age and abnormal ct/mri findings are associated with a poor outcome including death or recovery with severe neurological sequelae. [a fuller description is given in section . . .] acute necrotising encephalopathy is a rare fulminant syndrome associated with multifocal brain lesions that is described mainly in japan . other rare manifestations include transverse myelitis and guillain barré syndrome , . reye's syndrome, characterised by an encephalopathy, acute fatty liver, association with aspirin use and high mortality (~ %), is a special situation that is almost exclusively seen in children and adolescents . nevertheless, physicians managing adults are advised to be aware of this complication. [a fuller description is given in section . . . .] other complications rarely encountered in adults with influenza a infection include toxic shock syndrome in conjunction with secondary staph. aureus infection , and parotitis . otitis media is more commonly encountered in children than adults. human infections have been caused by different avian influenza a viruses in the past, including h n , h n , h n and h n . in recent years, outbreaks of human infections by a novel strain of avian influenza a (h n ) have raised particular concerns globally regarding the risk of a human pandemic . these concerns have been due in part to recognition that (a) avian influenza a (h n ) can pass directly from birds to humans and (b) once in humans, avian influenza a (h n ) causes severe disease with a high mortality. the full spectrum of human illness associated with avian influenza a (h n ) infection is not completely known. descriptions of the clinical features of influenza a (h n ) infection in humans are based largely on case series of hospitalised patients. subclinical infections, mild illnesses and atypical presentations of influenza a (h n ) infections in humans have been reported, but the frequency of such infections is difficult to determine [ ] [ ] [ ] . in hospitalised patients, an ili similar to that associated with seasonal influenza a (h n or h n ) infection is recognised. gastrointestinal symptoms are present in a relatively large proportion of both adult and paediatric cases, in contrast to the relatively low incidence of gastrointestinal symptoms in seasonal influenza. the majority of patients develop a severe primary viral pneumonia usually associated with lymphopenia, thrombocytopenia and deranged liver function tests. renal failure and multiorgan failure may develop subsequently. mortality is high. a more detailed description is given in appendix . should influenza a (h n ) acquire efficient humanto-human transmission capabilities, it may result in an influenza pandemic. in such an event, the clinical features of human h n disease may alter. ( ) the commonest presenting features of influenza during an epidemic are fever, cough and rhinorrhoea. in infants, fever with non-specific symptoms or diarrhoea and vomiting is common; in older children pharyngitis and headache are frequent. ( ) the clinical features of influenza in children during a pandemic cannot be forecast. ( ) children with underlying respiratory or cardiac disease, immune compromise or who are nonambulant are more likely to be severely affected. ( ) the younger the child the more likely hospital admission will be needed. the clinical features of influenza presenting in a pandemic cannot be predicted as they appear to be dependent on the strain of influenza and, in some respects, the host. a new strain of influenza a responsible for an epidemic or pandemic may result in a different spectrum of clinical features than previous strains , . common features during previous epidemics have been described and depend on the age of the child. the studies of clinical features are hospital based and are therefore likely to reflect more severe illness. these are nevertheless informative as one of the main issues in a pandemic is which patients require hospital admission. in young children presenting to primary care in a non-pandemic influenza season there are no specific clinical features that distinguish influenza from other winter viruses . neonates may present with non-specific signs of sepsis such as pallor, floppiness, (poor peripheral circulation, poor tone), lethargy, poor feeding, episodes of apnoea . fever may be the only presenting feature. a north american study identified influenza as the most common reason for children aged days being admitted to hospital during an epidemic with fever as the only clinical feature . fever may be the only presenting feature in this age group too. they may also be irritable and toxic and are more likely than older children to present with gastrointestinal symptoms such as diarrhoea and vomiting. febrile convulsions, particularly repeated convulsions, are positively associated with influenza a . otitis media is also a common complication in children . admission rates for under two year olds are times higher than for children aged years . the presentation does not differ significantly from adults. common features are sudden onset of high fever, chills ( %), cough, headache, sore throat, fatigue ( %), nasal stuffiness and conjunctivitis ( %) . fever tends to settle two to four days later though a dry cough and clear nasal discharge last for one to two weeks . a clinical prediction model from north america for influenza in children has shown that the triad of cough, headache and pharyngitis had a sensitivity of % and a specificity of % for a positive viral culture for influenza . the subjects, mean age six years, presented during an epidemic to a suburban emergency department with a febrile respiratory illness and one or more symptoms of influenza. a finnish retrospective study of children referred to hospital from to with influenza confirmed by antigen testing reported that the median age for those with influenza a was two years. the most common features were cough, fever and rhinorrhoea . these were also the commonest features reported in a chinese study where the mean age of the subjects with influenza a was four years . conditions these children (table . ) and those who are not ambulant experience substantial morbidity during influenza seasons, with a disproportionate number requiring inpatient care and ventilatory support. of the % of (table . ) as in adults, influenza can present with either primary viral pneumonia or bacterial pneumonia most commonly caused by s. pneumoniae or staph. aureus. there is much less published about pneumonia complicating influenza in children. an outbreak of severe pneumococcal pneumonia in children occurred in iowa in the winter of . this was coincident with an epidemic of influenza (h n ). compared with controls, patients were times more likely to have rare experienced a recent influenza-like illness. they were also more likely to have family members with the illness and to have positive serology in the convalescent period. many of these patients required chest drainage . another study in of children with proven influenza reported that who had chest radiographs had either radiographic evidence of viral pneumonia or normal radiographs. no child had lobar pneumonia reported . evidence from recent outbreaks of avian influenza (h n ) in hong kong and vietnam suggests that while some children had mild disease , others appeared to have multi-organ disease including acute respiratory distress syndrome (ards) . all children who developed progressive pneumonia with ards died. there were no reports of bacterial pneumonia. there is no reason to believe that, apart from ards, pneumonia complicating influenza presents differently from community-acquired pneumonia in children . the general clinical indicators for severity assessment of lower respiratory tract infection are summarised in the bts guidelines (appendix ). failure to improve following hours of antibiotics, or deterioration including a new, distinct spike of fever, should also be treated as severe and further complicating factors sought. the clinical course of croup caused by influenza appears to be more severe than croup caused by the more common parainfluenza virus . it is more likely to be complicated by bacterial tracheitis . influenza is a well recognised cause of otitis media . it is the commonest bacterial superinfection of influenza and is reported in approximately % of patients aged < years . influenza ranks second only to respiratory syncytial virus as a cause of bronchiolitis . the clinical features are the same . children with influenza may present with febrile convulsions. in a community study in the netherlands, recurrent febrile seizures were positively related to influenza a. it was recommended that children who have had a previous febrile convulsion should be immunised against influenza a . these complications are described in small case series. this is defined as depressed or altered level of consciousness including lethargy and/or extreme irritability in younger children or significant change in personality or behaviour persisting beyond hrs or confusion (older children). encephalopathy usually presents as seizures within several days of the onset of fever . seizures at this point are usually the first symptom of involvement of the central nervous system. febrile convulsions, which are more likely to be repeated with influenza than with other causes of fever, generally occur with the onset of fever. disturbances of behaviour and neurological deficit have been reported. a rapid and severe clinical course is usual with encephalopathy and is thought to be due to brain oedema mediated by cytokines rather than by direct invasion of the brain. steroids are therefore considered. children with encephalopathy were recognised in japan between and . death occurred in %, residual neurological deficit in % and full recovery in % . this is a rare childhood acute encephalopathy associated with liver dysfunction. the cause is unknown but it typically follows viral illness and there is a clear association with aspirin therapy: thus an innate susceptibility coupled with aspirin taken for relief of viral symptoms. influenza (particularly influenza b) is commonly implicated . there was a dramatic fall in incidence following warnings about aspirin use in children . it is possible that children on long term aspirin treatment for medical conditions may be at increased risk if they develop influenza infection. reye's syndrome is characterised by protracted vomiting and encephalopathy in afebrile patients with minimal or absent jaundice, and hepatomegaly in % of patients. it comprises: • acute non-inflammatory encephalopathy with an altered level of consciousness • elevation of ammonia levels hours after the onset of mental status changes (the most frequent laboratory abnormality) • hepatic dysfunction with a liver biopsy showing fatty metamorphosis or a more than three-fold increase in alanine aminotransferase (alt), aspartate aminotransferase (ast) neurological symptoms usually occur hours after the onset of vomiting. lethargy is usually the first neurological manifestation. diarrhoea and hyperventilation may be the first signs in children younger than two years. other investigations: head ct scanning may reveal cerebral oedema but results are usually normal. an electroencephalogram (eeg) may reveal slow wave activity in the early stages and flattened waves in advanced stages. cerebrospinal fluid may or may not have increased opening pressure with white blood cells (wbcs) fewer than /ml (usually lymphocytes). there is no specific treatment for reye's syndrome. key aspects of management are correction of metabolic imbalance and reduction of intracranial pressure. advice should be requested from a specialist in metabolic medicine. many children have an underlying inborn error of metabolism. mortality has fallen from % to less than % as a result of earlier diagnosis and more aggressive therapy. acute necrotising encephalopathy (ane): this occurs mainly in japan where it was first described in . an estimated deaths per annum are related to central nervous system complications of influenza in japan . this suggests either a genetic predisposition for this complication or a variation in the strains of influenza circulating in japan. ane is characterised by high fever, convulsions and coma in children aged one to five years. the onset is two to four days after the respiratory symptoms, and fewer than % of patients survive . there are no specific markers although some patients have raised liver transaminases. in many, the csf is normal. symmetrical multi-focal brain lesions are seen and bilateral thalamic involvement is characteristic and may be demonstrated on mri . this is defined as encephalopathy plus two of the following: fever of ºc or higher, seizures, focal neurological findings, wbc > cells/ml in csf, eeg findings consistent with encephalitis, abnormal neuro-imaging . these must be considered when a child presents with altered level of consciousness or irritability. there is good evidence of an increased risk of meningococcal disease following influenza infection . during a pandemic, the focus will be on diagnosing influenza-related illness. other neurological conditions or drug toxicity, for example, may be missed. a literature review of cases of myositis suggested that this was a complication mainly of schoolchildren. the calf muscles are predominantly affected. rhabdomyolysis and renal failure are rare. these are also rare complications but have been described in children with underlying medical conditions . section . general management and investigations in primary care with widespread concern during a pandemic, a significantly increased demand for advice and consultation should be anticipated. there are likely to be significantly higher consultation rates for all types of respiratory tract infections including those which are normally managed well at home using over-the-counter remedies (e.g. febrile colds, sore throat with temperatures). consequently, demand management in both the practice and the pct will be crucial to avoid the service's capacity to triage care being overwhelmed. guidance on demand management and health service delivery is given in the primary care operational plan (see section . ) . management decisions of patients with influenza should be based primarily on: • an assessment of illness severity • identification of whether the individual is in an 'at risk' group • current advice from doh/local public health officials based on the epidemiology of the pandemic patients who are not considered to be at high risk and who have no features suggesting severe disease or complications may not need to be seen in face to face consultations by a primary care clinician. all patients presenting in general practice with symptoms suggestive of influenza (except perhaps those in whom urgent admission is required) should be given general advice and advice on symptomatic treatment. it is important that clinicians identify and address individual concerns and expectations, provide information about the illness, and provide information about what patients can do to help themselves and when they should seek further help. some useful facts that can be provided to the patient are included in box . . there is little scientific evidence for most symptomatic and self-help treatment, but experience suggests that some of the following may help, and are unlikely to cause harm: • treat fever, myalgias and headache with paracetamol or ibuprofen • rest • drink plenty of fluids • avoid smoking • consider: short course of topical decongestants, throat lozenges, saline nose drops many infants and children will have coughs and mild fevers which may be due to other infections such as respiratory syncytial virus, especially over the winter months. these children should be managed in the usual way at home by parents with antipyretics and fluids. (note: aspirin should not be used in children.) management of these children is determined by disease severity (see appendix ). the principles of symptomatic management are similar to those for adults. box . . information about influenza to provide to patients • influenza is caused by a number different types of 'influenza' viruses. • the incubation period is typically one to four days and infected adults are usually contagious from the day of illness onset to five days after. children are typically contagious for seven days, although sometimes for longer. • fever usually declines after two to three days and normally disappears by the sixth day. • cough, weakness and fatigue can persist for one to two weeks and up to six weeks. • antibiotics do not benefit most people with influenza but are sometimes needed to treat secondary infections. (important note: this information may be modified once a pandemic occurs) • fever for four to five days and not starting to get better (or getting worse) • started to feel better then developing high fever and feeling unwell again • if taking antiviral drugs (eg. oseltamivir), symptoms should start to improve within two days. lack of any improvement after two days from starting antiviral drugs is an indication to re-consult. (important note: this information may be modified once a pandemic occurs) • children under one year of age year and those at high risk of complications (see appendix ) should be seen and assessed by a gp or at the a&e department. • children over one but under seven years of age may be seen by a nurse or a gp and those aged seven years and above may be seen by a member of the community health team (e.g. community pharmacist). • all children (and parents) should be given advice on antipyretics and fluids. • aspirin is contraindicated in children (aged under years). examples of what should prompt a patient to re-consult are given in box . . patients who are started on antiviral agents (see section for indications for antiviral use) would be expected to begin to improve within hours of starting treatment. failure to improve two days after starting an antiviral agent is an indication to re-consult. at the time of re-consultation, an alternative diagnosis should be considered as well as the occurrence of any influenzarelated complications. • any rapid deterioration following first consultation should prompt a patient to re-consult. • failure to improve two days after starting an antiviral agent is an indication to re-consult. • if the first consultation did not involve contact with a physician, re-consultation should preferably involve a physician, usually a gp. . . what general investigations should be done in the community? • general investigations, including a chest x-ray, are not necessary for the majority of patients managed in the community. the aim of microbiological investigations early in a pandemic (uk alert levels , and ) will be to confirm that influenza a is circulating in the local community. once a pandemic is established (uk alert level ), microbiological investigations are not recommended routinely or likely to be available readily. routine testing for bacterial pathogens is not recommended at any stage. • where possible, early in a pandemic (uk alert levels , and ), nose and throat swabs, or nasopharyngeal swabs (in children), in virus transport medium should be submitted to the local laboratory. • once a pandemic is established (uk alert level ), microbiological investigations are not recommended. section . criteria for hospital referral . . which adults require hospital referral? adults with uncomplicated influenza infection usually do not require hospital referral. patients who might require hospital admission fall into two main groups: those with worsening of a pre-existing medical condition and those with an influenza-related complication. patients who experience a worsening or clinical deterioration of pre-existing medical problems due to influenza infection should be managed according to recommended best practice for the medical condition in question. for instance, a patient with an acute exacerbation of copd triggered by influenza infection should be managed according to current nice guidelines for copd . those with a worsening of a pre-existing condition are likely to be in a group at 'high risk' of influenzarelated respiratory complications and consequently at risk § . criteria for hospital referral part . clinical management in primary care pandemic flu. clinical management of patients with an influenza-like illness during an influenza pandemic s . this group should be promptly reassessed if the illness is getting worse to consider hospital referral. pneumonia is the commonest influenza-related complication requiring hospital admission. patients complaining of new or worsening dyspnoea should be carefully assessed for signs of pneumonia. if pneumonia is diagnosed, disease severity assessment is recommended and hospital referral made accordingly. there is no validated severity assessment tool developed specifically for influenza-related pneumonia. the crb- score (table . ) is a well validated severity assessment tool developed for patients with community-acquired pneumonia (cap) , and recommended in the british thoracic society cap guidelines for use in the community setting . it is offered as an example of an assessment tool for influenza-related pneumonia. the use of any severity assessment tool does not replace clinical judgement. a patient's social circumstances should also always be taken into account. in view of the rapid and fulminant course of primary viral pneumonia, patients with pneumonia who have bilateral chest signs (crackles) should be considered for hospital referral. other influenza-related complications are uncommon. there are no specific recommendations relating to criteria for hospital admission or disease severity assessment in these cases. • patients with clinically defined uncomplicated influenza infection would be expected to make a full recovery. they require good symptomatic management, access to antiviral treatment, information about the natural history, and advice as to when to re-consult. • patients with new or worsening symptoms particularly shortness or breath or recrudescent fever not responding to treatment should be examined to assess the presence and severity of influenza-related pneumonia. • patients with worsening of pre-existing co-morbid medical conditions should be managed according to best practice for that condition with reference to published disease-specific guidelines, if available. • in patients with influenza-related pneumonia clinically, hospital referral and assessment should be considered for patients with a crb- score of or (particularly score ) and urgent admission for those with crb- score of or more. • patients with bilateral chest signs of pneumonia should be referred to hospital for further assessment regardless of crb- score. • the crb- score does not replace clinical judgment. • the antiviral treatment of choice is oseltamivir (tamiflu tm ). this is given as a five-day course of oral tablets; mg twice daily for adults. liquid suspension is available for children from the age of one year upwards. (see table . .) from clinical trial data accrued to date and based on seasonal, interpandemic influenza, the anticipated positive effect of antivirals in a pandemic will be: (a) a reduction of illness duration by hours, and therefore more rapid mobilisation of affected individuals including essential workers (b) a possible reduction in hospitalisation of infected individuals (c) a reduction of subsequent antibiotic use by infected individuals the evidence accrued to date does not suggest there will be a reduction of overall mortality, nor does it rule it out. . . who should receive antiviral drugs? • ideally, antiviral treatment should be offered to every patient who is over one year of age who (a) has an acute influenza-like illness (b) has fever ( ºc in adults, or . ºc in children) and (c) presents within hours of the onset of symptoms. • exceptions: (i) patients who are unable to mount an adequate febrile response, e.g. the immunocompromised or very elderly, may still be eligible for antiviral treatment despite the lack of documented fever. (ii) immunosuppressed patients, including those on long-term corticosteroid therapy, may suffer more prolonged viraemia, and could possibly benefit from antiviral therapy commenced later than hours after the onset of ili. (iii) patients who are severely ill, but who have not been hospitalised due to non-clinical reasons, may benefit from antiviral therapy commenced later than hours after the onset of ili. there is no strong evidence to support antiviral use in these exceptional situations. the commonest adverse effect of oseltamivir is nausea in about % of patients. this can be managed with mild anti-emetic medication. other side-effects are listed in appendix . national distribution arrangements are laid out in the uk operational framework for stockpiling, distributing and using antiviral drugs in the event of pandemic influenza and the primary care operational plan. the drug will be made available through these arrangements to pharmacies, pcts and/or gp surgeries. • pcts are encouraged to plan for the delivery of antivirals to the large numbers of previously healthy persons with an ili via community health professionals, including community pharmacists. • gps should focus their efforts on assessment and management of those persons at high risk of complications (see appendix ) and patients developing complications. section . antibiotic use in primary care the use of antibiotics in adults with influenza not complicated by pneumonia is determined by (a) the presence of any co-morbid illnesses and (b) the timing of first consultation with respect to the onset of symptoms. features of an acute bronchitis, with cough, retrosternal discomfort, wheeze and sputum production are an integral part of the influenzal illness. in previously well individuals who do not have pneumonia or new focal chest signs, antibiotics are not indicated. if the patient is seen later in the course of the illness and the illness is worsening, for instance with recrudescent fever or increasing breathlessness, a worsening bacterial bronchitis § . antibiotic use in primary care part . clinical management in primary care pandemic flu. clinical management of patients with an influenza-like illness during an influenza pandemic s or developing pneumonia is possible and the use of antibiotics should be considered. in selected patients, a delayed antibiotic prescription may be offered at first consultation. the antibiotic prescription should come with clear instructions that the antibiotics should be used if the illness is not starting to settle after two days or if there is worsening of symptoms. the potential advantage of this approach of delayed antibiotic prescription is to minimise rates of reconsultation . there are no robust data regarding the effect of such an approach on the incidence of influenzarelated complications. those at high risk of influenza-related complications because of (a) chronic obstructive pulmonary disease (copd) and/or (b) other severe co-morbid diseases should be strongly considered for antibiotics at first consultation. if, having started antibiotics, patients do not begin to improve over the next hours of antibiotic treatment (or if they get worse) they should be advised to re-contact their gp for assessment of pneumonia and its severity (see sections and ). antibiotics should cover the likely bacterial pathogens including s. pneumoniae, h. influenzae, m. catarrhalis and staph. aureus. the preferred first choice of antibiotic for nonpneumonic bronchial infections, including those patients with copd, should include an effective oral b-lactamase stable agent such as a tetracycline (e.g. doxycycline) or co-amoxiclav. a macrolide (e.g. erythromycin or clarithromycin) is an alternative for those intolerant of the preferred first choices, whilst remembering the possibility of antimicrobial resistance. clarithromycin has better activity against h. influenzae than azithromycin. further details regarding the principles of antibiotic use including antibiotic resistance patterns are given in section . • patients without severe pre-existing illnesses and who have uncomplicated influenza, or simple bronchitis, do not routinely require antibiotics. • patients without severe pre-existing illnesses who are seen later in the course of illness and who have developed significant worsening of symptoms (particularly recrudescent fever or increasing breathlessness) should be considered for antibiotics. • patients with copd and/or other severe pre-existing illnesses, and who are therefore at high risk of influenzarelated complications, should be strongly considered for antibiotics at first consultation. • most patients can be adequately treated with a week's course of oral antibiotics. • the preferred choice of antibiotic needs also to cover infection with staph. aureus for example either doxycycline or co-amoxiclav (see table . ). • a macrolide (e.g. erythromycin or clarithromycin) is an alternative choice in certain circumstances. the principles of antibiotic selection for patients with influenza-related pneumonia who can be managed in the community are similar to those for the management of sporadic community-acquired pneumonia in general except that adequate cover for staph. aureus, in addition to cover for s. pneumoniae, should be included in any empirical regimen. for this reason a tetracycline, such as doxycycline or oral co-amoxiclav, is the preferred regimen (table . ). a macrolide (e.g. erythromycin or clarithromycin) is an alternative for those intolerant of the preferred first choices. macrolide (erythromycin mg qds po or clarithromycin mg bd b po) a an alternative regimen is provided for those intolerant of or hypersensitive to the preferred regimen. b clarithromycin may be substituted for those with gastrointestinal intolerance to oral erythromycin and also has the benefit of twice daily dosage and better cover against h. influenzae. abbreviations: od, once daily; bd, twice; tds, times; qds, times. secondary bacterial infections particularly pneumonia and otitis media are common in children with influenza. s. pneumoniae, staph. aureus and h. influenzae are the most common pathogens encountered during influenza outbreaks. • children in any one of the following groups should be treated with an antibiotic that will provide cover against s. pneumoniae, staph. aureus and h. influenzae: ( ) those at risk of complications of influenza (see appendix ). ( ) those with one or more of the following adverse features: (a) breathing difficulties (b) severe earache (c) vomiting for more than hours (d) drowsiness. part . clinical management of adults referred to hospital section . severity assessment of adults referred to hospital . . what severity assessment strategy is recommended for patients referred to hospital with influenzarelated pneumonia? there is no validated severity assessment tool developed specifically for influenza-related pneumonia. the curb- severity assessment tool as described in the bts cap guidelines is recommended for the stratification of hospitalised patients with influenza-related pneumonia into disease severity groups (table . ). in addition, the presence of diffuse bilateral lung infiltrates on chest radiography consistent with primary viral pneumonia is an adverse prognostic feature. such patients should be treated as for severe pneumonia. in all instances, clinical judgement is essential when assessing disease severity. • patients with bilateral lung infiltrates on chest radiography consistent with primary viral pneumonia should be managed as having severe pneumonia regardless of curb- score. • in hospital, patients with influenza-related pneumonia who have a curb- score of or more are at high risk of death and should be managed as having severe pneumonia. • patients who have a curb- score of are at increased risk of death. they should be considered for short stay inpatient treatment or hospital-supervised outpatient treatment. this decision is a matter of clinical judgement. • patients who have a curb- score of or are at low risk of death. they can be treated as having non-severe pneumonia and may be suitable for home treatment. . . when should transfer to a high dependency unit (hdu) or intensive care unit (icu) be considered? the indications for transfer to hdu or icu are no different in patients with influenza infection compared to other patients. most patients who might require hdu/icu care will have influenza-related pneumonia or a severe exacerbation of underlying comorbid illness, e.g. exacerbation of copd. in a pandemic situation when hdu/icu beds may not be readily available, prioritisation of patients on an individual basis matched against available resources will be expected. • patients with primary viral pneumonia or a curb- score of or should be considered for hdu/icu transfer. • general indications for hdu/icu transfer include: ( ) persisting hypoxia with pao < kpa despite maximal oxygen administration ( ) progressive hypercapnia ( ) severe acidosis (ph < . ) ( ) septic shock • patients with influenza admitted to an intensive care unit should be managed by specialists with appropriate training in intensive care, respiratory medicine and/or infectious diseases. in acute uncomplicated influenza the chest x-ray is usually normal. when primary viral pneumonia occurs as a complication, particularly in elderly adults the chest x-ray often shows multiple infiltrates or consolidation. cavitations or pleural changes suggest bacterial superinfection. in combined viral-bacterial pneumonia, the clinical features typically appear later than primary viral pneumonia and the chest x-ray often shows cavitation or pleural effusions. secondary bacterial pneumonia usually occurs after apparent improvement from the viral infection; the chest x-ray may show consolidation. • a chest x-ray should be obtained during assessment of a suspected case of influenza seen in the hospital setting (accident and emergency department or acute admissions ward). • in those patients who are subsequently followed up in a hospital outpatient clinic or by a general practitioner a repeat chest x-ray should be obtained at around six weeks if respiratory symptoms or signs persist or where there is a higher risk of underlying malignancy (especially smokers and those over years of age). • further investigations including a ct thoracic scan, and bronchoscopy should be considered if the chest x-ray remains abnormal at follow up . in those patients with illness severe enough to present to secondary care the following tests may be useful: full blood count: a leucocytosis with left shift may occur in those with primary viral pneumonia, mixed viralbacterial pneumonia or secondary bacterial pneumonia. (lymphopenia has been noted in human cases of severe avian h n influenza.) urea and electrolytes may reveal evidence of hypo or hypernatraemia or renal impairment. liver function tests are usually normal. creatine kinase (ck) may be elevated in those with severe myalgia. c-reactive protein (crp) is unlikely to be helpful except where superimposed bacterial infection is suspected . however, the diagnostic value of crp in lower respiratory tract infections remains controversial . • the following blood tests should be obtained in patients admitted to hospital: ( ) full blood count; ( ) urea, creatinine and electrolytes; ( ) liver function tests; ( ) creatine kinase (if myositis is suspected). • in patients with suspected secondary bacterial infection, the c-reactive protein (crp) level may aid diagnosis. in acute uncomplicated influenza larger airway function remains normal. however, there is often an increase in bronchial reactivity which may persist for many weeks after resolution of the infection . lung function tests are unnecessary in most patients. section . microbiological investigations for adults in hospital . . introduction the guidelines provided below are based on the assumption that when cases are first occurring in the uk as part of a global pandemic, it will be possible to perform full microbiological investigations in all new cases of influenzalike illness and influenza-related pneumonia. as case numbers rise, possibly to pandemic levels, full or indeed any microbiological investigation will become increasingly difficult. thus, data on the relative frequency of different bacterial causes of influenza-related pneumonia and their antimicrobial susceptibilities amongst investigated cases gathered earlier in the pandemic should be available to guide and refine empirical antimicrobial therapy choices for cases occurring later in the pandemic. the most likely pathogens implicated in influenzarelated pneumonia are streptococcus pneumoniae, staphylococcus aureus, haemophilus influenzae and to a lesser extent b-haemolytic streptococci (see section . ). in the early phases (uk alert levels , and see appendix ) of a pandemic, microbiological diagnostic approaches should focus on confirming influenza as the primary illness, defining bacterial causes of influenza-related pneumonia, and optimizing both specific (for individual patients) and general (for populations) antimicrobial treatment recommendations. in later pandemic phases (uk alert level ) with the much higher caseloads anticipated, microbiological investigation should be focused on patients with severe influenza-related pneumonia unresponsive to empirical antimicrobial therapy. actual and practical local level transition to less intense microbiological investigation may occur at uk alert level in some regions as the number of local cases is likely to vary between regions. § . microbiological investigations for adults in hospital part . clinical management of adults referred to hospital pandemic flu. clinical management of patients with an influenza-like illness during an influenza pandemic s it will be necessary to perform full microbiological investigations on all hospitalised cases, including patients with severe and non-severe influenza-related pneumonia, in order to: confirm influenza as the primary infection, optimize treatment options for the patients investigated and define the most common bacterial causes of influenzarelated pneumonia and their antimicrobial susceptibility patterns. the latter data will help to inform empirical antimicrobial therapy of subsequent cases for which microbiological investigation may not be undertaken fully, or at all. in influenza, rapid virological tests, viral culture and pcr of respiratory samples will yield positive results between one and seven days after illness onset. however, if presentation is more than seven days after the onset of influenzalike illness then such sampling and testing is unhelpful. instead, serum samples for serological testing for evidence of recent influenza infection are recommended. specific detailed microbiological guidance for taking and handling specimens from individuals at risk of avian influenza prepared by prof maria zambon of health protection agency (hpa) centre for infections is available at: www.hpa.org.uk/infections/topics_az/avianinfluenza/ guidance/microbiological_guidance.htm bacteriological investigations are only recommended in patients with influenza-related pneumonia. legionella pneumophila infection is not normally associated with influenza-related pneumonia. despite this, legionella urine antigen tests should be performed on severe cap cases in the early stages of an outbreak/incident in order to confirm legionella infection is not the reason for a local increase in pneumonia admissions. these recommendations are modified from those contained in the british thoracic society community acquired pneumonia (bts cap) guidelines [thorax ; (suppl iv), see sections . , . and . (pp. iv iv )] and the update (see pages ), both available at: www.brit-thoracic.org.uk/ iqs/bts_#guidelines_pneumonia_html. sputum investigative efforts must be focused on quality samples (i.e. those from patients who are able to expectorate purulent samples, and have not received prior antibiotic treatment) and not dissipated on large numbers of poor quality samples. it is important to acknowledge that the criteria for quality samples may only be met for a minority of admissions. laboratories should offer a reliable sputum gram stain for appropriate samples, as on occasions this can give immediate indication of likely pathogens. the most likely influenzarelated pneumonia pathogens are s. pneumoniae, staph. aureus and h. influenzae, all of which may present a characteristic appearance on gram stain of purulent sputum. laboratories performing sputum gram stains should adhere to strict and locally agreed criteria for interpretation and reporting of results. a. virology all patients: • nose and throat swabs in virus transport medium should be collected from all patients and submitted to the local laboratory. the relevant laboratory should be notified of the suspected diagnosis and there should be close liaison over sample collection, handling and transport. • rapid testing by direct immunofluorescence or rapid eia test, virus culture and/or pcr should be undertaken according to local availability and/or referred to an appropriate laboratory • during uk alert level , when the uk is on high alert for the first cases of pandemic influenza, suspected cases are likely to be investigated by local health protection teams from the health protection agency and its partner organisations in the devolved administrations. • during uk alert levels and , clinicians dealing with suspected cases of pandemic influenza should ensure that the local health protection team is informed and involved from the outset. • the health protection agency and its partner organisations in the devolved administrations have established a network of more than laboratories across the uk which have been proficiency tested in molecular diagnosis of influenza a/h n . access to this service should be via local health protection teams. • if presentation is more than seven days after onset of illness, an 'acute' serum ( ml clotted blood) should be collected and a 'convalescent' sample ( ml clotted blood) obtained after an interval of not less than seven days. the two sera should be examined serologically for evidence of recent influenza infection. b. bacteriology patients with influenza-related pneumonia: • the following bacteriological tests should be performed: ( ) blood culture (preferably before antibiotic treatment is commenced) ( ) pneumococcal urine antigen ( ml urine sample). agents. acute serum should be collected and a 'convalescent' sample obtained after an interval not less than seven days (both ml clotted blood) and the two sera stored for subsequent testing. once a pandemic is established, virological investigations are not recommended routinely and in a pandemic situation may not be readily available. the diagnosis of influenza will be based on clinical findings. if influenza-related pneumonia is present, the degree of microbiological investigation will be directed by disease severity and the presence of co-morbidities. in influenza-related pneumonia, examination of sputum should be considered for patients who do not respond to empirical antibiotic therapy. this will be particularly relevant if staph. aureus is identified as a common influenza-related pneumonia pathogen during the early phase of the pandemic as, in contrast to s. pneumoniae and h. influenzae, antimicrobial susceptibilities of this organism are less predictable and empirical choices more speculative. a. virology not routinely recommended. b. bacteriology patients with influenza-related pneumonia: (i) non-severe pneumonia (curb- score , or ) • sputum samples should be sent for gram stain culture and antimicrobial susceptibility tests in patients who do not respond to empirical antibiotic therapy. (ii) severe pneumonia (curb- score , or ) • specific investigations should include: ( ) blood culture, preferably before antibiotic treatment is commenced. ( ) pneumococcal urine antigen ( ml urine). ( ) sputum gram stain, culture and antimicrobial susceptibility tests on samples obtained from patients who: (i) are able to expectorate purulent samples, and (ii) have not received prior antibiotic treatment. sputum specimens should be transported rapidly to the laboratory. ( ) paired serological examination for influenza/ other agents. 'acute' serum should be collected and a 'convalescent' sample obtained after an interval not less than seven days (both ml clotted blood) and the two sera stored for subsequent testing. ( ) tracheal or endotracheal aspirate samples, if available, should be sent for gram stain, culture and antimicrobial susceptibility testing. section . general management of adults admitted to hospital initial management will depend on the assessment of the reason for admission, the presence of complications, and the impact of the influenza on any pre-existing disease, or psychosocial factors. for instance, some elderly patients may require admission for social reasons. in broad terms, the most likely clinical reasons for admission will be (in order of frequency): • lower respiratory tract complications: non pneumonic bacterial exacerbation of chronic lung disease such as copd (possibly with a mixed viral infection) secondary bacterial pneumonia mixed bacterial and viral pneumonia primary viral pneumonia • cardiac complications: exacerbation of pre-existing cardiac disease with cardiac failure and/or arrhythmia primary myocarditis • other complications: exacerbation of other pre-existing disease, such as diabetes mellitus neurological complications rhabdomyolysis severe sinusitis the initial management is likely to most usually involve that of respiratory and cardiac complications, especially pneumonia and these are discussed below. management of other less common primary influenzal complications (such as rhabdomyolysis, encephalopathy) is not covered. all influenza patients admitted to hospital with abnormal cardiorespiratory symptoms and signs, including influenzarelated pneumonia, should have a chest radiograph and an electrocardiogram and should have oxygenation assessed by pulse oximetry, preferably whilst breathing air (see section ). those with sao < % should have arterial blood gas measurements, as should all patients with features of severe illness. knowledge of the inspired oxygen concentration is essential to the interpretation of blood gas measurements and should be clearly recorded with the blood gas result. continuous oxygen therapy is indicated for those patients with pao < kpa, hypotension with systolic bp < mmhg, metabolic acidosis with bicarbonate < mmol/l or respiratory distress with respiratory rate > /min . the aim of oxygen therapy should be to maintain pao at > kpa or sao > %. unless complicated by severe chronic obstructive pulmonary disease with ventilatory failure, high concentrations of oxygen of % or greater are indicated and can be safely used. high concentration oxygen therapy given to patients with pre-existing chronic obstructive pulmonary disease § . general management of adults admitted to hospital part . clinical management of adults referred to hospital pandemic flu. clinical management of patients with an influenza-like illness during an influenza pandemic s who may have co retention can reduce hypoxic drive and increase ventilation-perfusion mismatching. in such patients initial treatment with low oxygen concentrations ( %) should be progressively increased on the basis of repeated arterial blood gas measurements, the aim being to keep sao > % without causing a fall in arterial ph below . , in line with the management strategy recommended in the nice copd guidelines . non-invasive ventilation (niv) may be of value in patients with copd who are in acute hypercapnic respiratory failure , . the use of niv in patients with respiratory failure due to severe pneumonia but without co-existing copd has not been shown to influence mortality , . nevertheless, during an influenza pandemic when critical care level beds are in high demand, niv may be of value as a bridge to invasive ventilation in specific circumstances. in all instances, the risks of infection due to the dissemination of respiratory droplets related to the use of niv must be taken into account when deciding on management strategies. respiratory and/or critical care units experienced in the use of niv are best placed to ensure the appropriate infection control measures are adopted and observed at all times, including the use of personal protection equipment (ppe) (see uk infection control guidance for pandemic influenza) . all patients should be assessed for volume depletion and may require iv fluids. the potential for influenza to cause cardiac decompensation, either through exacerbation of pre-existing cardiac disease or from a primary myocarditis, should be borne in mind, with any complicating heart failure and arrhythmias being managed in the usual way. physiotherapy may be of benefit in selected patients with excess bronchial secretions, particularly those with concurrent chronic obstructive pulmonary disease. in cases of severe illness requiring prolonged hospital admission, increased nutritional support whether enteral, parenteral or via naso-gastric feeding should be arranged. • hypoxic patients should receive appropriate oxygen therapy with monitoring of oxygen saturations and inspired oxygen concentration with the aim to maintain pao > kpa and sao > %. high concentrations of oxygen can safely be given in uncomplicated pneumonia. • oxygen therapy in patients with pre-existing copd complicated by ventilatory failure should be guided by repeated arterial blood gas measurements. non-invasive ventilation may be helpful. • in patients without pre-existing copd who develop respiratory failure, niv may be of value as a bridge to invasive ventilation in specific circumstances when critical care level beds are in high demand. respiratory and/or critical care units experienced in the use of niv are best placed to ensure the appropriate infection control measures are adopted at all times. • patients should be assessed for cardiac complications and also volume depletion and their need for additional intravenous fluids. • nutritional support should be given in severe or prolonged illness. . . what monitoring should be conducted during a hospital stay? pulse, blood pressure, respiratory rate, temperature, oxygen saturation (with a recording of the inspired oxygen concentration at the same time) and mental status should be measured initially at least twice daily. this is most conveniently performed using an early warning score (ews) chart, which all ward staff should be familiar with. those with severe illness, requiring continuous oxygen or cardiovascular support, should be monitored more frequently. failure to improve clinically within hours should result in a full clinical reassessment and failure to improve over days is an indication to repeat the chest radiograph. • temperature, respiratory rate, pulse, blood pressure, mental status, oxygen saturation and inspired oxygen concentration should be monitored and recorded initially at least twice daily and more frequently in those with severe illness or requiring regular oxygen therapy. • an early warning score system is a convenient way to perform this. • in addition to a full clinical reassessment, a chest radiograph should be repeated in patients who are not progressing satisfactorily. there will be considerable pressure to discharge patients early during a pandemic. the type and availability of out-of-hospital facilities will dictate hospital discharge decisions. some guidance regarding simple parameters to review when considering hospital discharge can be obtained from a recent us prospective, multi-centre, observational cohort study of patients admitted to hospital with cap , and is offered as advice for all patients admitted with influenza-related respiratory complications. • patients should be reviewed before hours of discharge home. those with two or more of the following unstable clinical factors should be considered for continued hospital management: ( ) temperature > . ºc, ( ) heart rate > /min, ( ) respiratory rate > /min, ( ) systolic blood pressure < mmhg, ( ) oxygen saturation < %, ( ) inability to maintain oral intake, it is usual practice to arrange 'routine' hospital clinic follow up and repeat the chest radiograph at around six weeks after discharge for acute respiratory illness such as pneumonia. however, there is no evidence on which to base a recommendation regarding the value of this practice in patients who have otherwise recovered satisfactorily. it is also not known whether there is any value in arranging clinical follow up in a hospital clinic rather than with the patient's general practitioner. during an influenza pandemic situation, it is likely that only patients who developed complications or who had significant worsening of their underlying disease will be offered clinical review at one or other venue. at discharge, patients should be offered access to information about their take-home medication, smoking and lifestyle advice as appropriate, potential future complications and action to take in the event of a relapse of symptoms. • follow-up clinical review should be considered for all patients who suffered significant complications or who had significant worsening of their underlying disease, either with their general practitioner or in a hospital clinic. • at discharge or at follow up, patients should be offered access to information about their illness, take-home medication and any follow-up arrangements. • it is the responsibility of the hospital team to arrange the follow-up plan with the patient and the general practitioner. section . use of antivirals in hospitalised adults . . what drugs should be used for antiviral treatment during a pandemic? oseltamivir (neuraminidase inhibitor) will be the mainstay for therapy in the pandemic. the m inhibitors, amantadine and rimantadine, are unsuitable for use for treatment due to the rapid emergence of resistance together with sideeffects. from clinical trial data accrued to date and based on seasonal, interpandemic influenza, the anticipated positive effect of antivirals in a pandemic will be: (a) a reduction of illness duration by hours, and therefore more rapid mobilisation of affected individuals including essential workers; (b) a possible reduction in hospitalisation of infected individuals; (c) a reduction of subsequent antibiotic use by infected individuals. there is insufficient evidence accrued to date to determine the effect of antivirals, if any, on overall mortality. therefore the major utility of antivirals will be to maintain the essential workforce, and reduce hospitalisation and antibiotic treatment of complications. (neuraminidase inhibitors) during a pandemic? • individuals should only be considered for treatment with neuraminidase inhibitors if they have all of the following: ( ) an acute influenza-like illness ( ) fever (> ºc) and ( ) been symptomatic for two days or less • treatment schedule: adults: oseltamivir mg every hours for days. dose to be reduced by % if creatinine clearance is less than ml/minute. • exceptions: (i) patients who are unable to mount an adequate febrile response, e.g. the immunocompromised or very elderly, make still be eligible despite lack of documented fever. (ii) hospitalised patients who are severely ill, particularly if also immunocompromised, may benefit from antiviral treatment started more than hours from disease onset. this advice reflects the lack of robust evidence to guide the use of antivirals in these exceptional circumstances and places a high value on the potential benefits of antiviral therapy. drugs available for treatment and prevention of infection by influenza are summarised in table . . there are four drugs available, the older agents amantadine and rimantadine and the neuraminidase inhibitors oseltamivir and zanamivir. older agents: the older agents, amantadine and rimantadine (rimantadine is not currently licensed in the uk), are related substances that act by blocking the ion-channel function of the influenza virus m protein. this protein, although a minor surface constituent of the influenza virus particles, is essential for virus replication. these agents are only active against influenza type a. amantadine is not recommended by nice for treatment and/or prophylaxis of interpandemic influenza, so in the absence of national stockpiling, supplies of amantadine can be expected to be very low. h viruses in south east asia are resistant to amantadine, so this agent may play no role at all depending on the nature of the pandemic strain. two neuraminidase inhibitors so far have been developed to the level of entry into the formulary: zanamivir is a modification of neu ac en, a dehydrated neuraminic acid derivative. oseltamivir is a similar molecule except it has a cyclohexene ring and replaces a polyglycerol moiety with lipophilic sidechains. oseltamivir can be taken by mouth, whereas zanamivir must be inhaled, using a diskhaler device. an intravenous formulation of zanamivir has been developed but its efficacy has not been established. this may be relevant for the management of ventilator cases. both drugs are active against influenza type a as well as type b viruses. older agents. both amantadine and rimantadine are effective for the treatment of type a influenza virus infection if treatment is begun within hours of the onset of illness . historical data show that they can shorten the illness by approximately one day but their efficacy in preventing complications, hospitalisations, or deaths has never been established. although these drugs are effective, their use in clinical influenza treatment has been limited as a result of their proclivity to induce viral resistance, and their side-effect profile. several large clinical trials have demonstrated the utility of zanamivir and oseltamivir in treatment of adults with influenza in the community ( virtually all studies on the efficacy of neuraminidase inhibitors to reduce complications have been conducted with oseltamivir, and this drug has been shown to have some effect on outcomes other than time to recovery. in a meta-analysis of adults and adolescents with a virologically proven influenza illness, oseltamivir treatment reduced overall antibiotic use for any reason by . so far, the neuraminidase inhibitors have not been extensively investigated in patients who are at the highest risk of serious complications of influenza. such patients include the elderly and those with serious cardiopulmonary illness, such as chronic obstructive pulmonary disease. the neuraminidase inhibitors have not been associated with a reduction in mortality, but the clinical trials conducted so far have not been appropriate to measure this. it is not known for certain whether the neuraminidase inhibitors will be effective in pandemic influenza because their use has only been assessed in inter-pandemic influenza, where the virulence is moderate and there is some degree of host immunity. the antiviral activity is likely to be adequate; in vitro, all neuraminidase inhibitors have been demonstrated to have a broad spectrum of activity against multiple avian influenza viruses . the older agents, rimantadine and amantadine, were studied in both the hong kong pandemic and again when h n influenza appeared in a pandemic in . their efficacy has been reviewed by hayden . when the older agents were given for four to eight week periods as prophylaxis in a community setting, their protective efficacy against influenza illness averaged % compared with placebo. this compares with % efficacy observed with the same agents in studies during the interpandemic period. when amantadine or rimantadine are used to treat patients, resistant viruses emerge rapidly and approximately % of treated children or adults will shed resistant variants starting two to five days after the onset of treatment . the resistant viruses shed from these patients retain full virulence, infectivity and transmission potential. when contacts of cases treated with amantadine or rimantadine are given post-exposure prophylaxis with these older agents, the reduction in secondary cases is minimal . in contrast, the frequency of emergence of resistance during treatment with the neuraminidase inhibitors is reported to be low. however, during studies of experimentally induced influenza a/h n infection in healthy adults, % of participants shed viruses with a histidine to tyrosine substitution at position within the binding site of oseltamivir . in these cases the volunteers had increased influenza viral load within the nasopharynx but there was no deterioration of symptoms. so far, there have been no proven instances of transmission of oseltamivir or zanamivir-resistant variants in field clinical trials, but the experience is relatively small currently. sequence analysis of h n human isolates from north vietnam have revealed virus with a y (resistant) sequence. although the isolate was not fully resistant, its ic for oseltamivir was shifted upwards and it is therefore less susceptible to oseltamivir than other h n isolates that had been tested from the region. the patient from whom the virus was isolated was concurrently being treated with oseltamivir. both amantadine and rimantadine can cause nausea and vomiting in a small percentage of individuals receiving them (table . ). unfortunately amantadine is also associated with very unpleasant central nervous system side-effects including anxiety, depression, insomnia and hallucinations. the side-effects are dose-related and do resolve with discontinuation of the drug. in the case of the neuraminidase inhibitors, both drugs appear relatively safe. zanamivir has very few side-effects, but can result in bronchospasm which might be potentially serious in patients with asthma. oseltamivir requires dose-reduction in patients with low creatinine clearance (< ml/min). nausea occurs in % of oseltamivir recipients but is seldom severe enough to lead to drug discontinuation (see table . ). antimicrobial chemotherapy will be indicated primarily for respiratory complications due to secondary bacterial infections, principally influenza-related pneumonia. the majority of patients with exacerbations of chronic obstructive pulmonary disease (copd) and other chronic lung conditions due to secondary bacterial infections, such as bronchiectasis, will also require antimicrobial chemotherapy, as will some patients with severe sinusitis. few pneumonias and lower respiratory tract infections are defined microbiologically at initial assessment and hence most prescribing is empirical. in broad terms the antimicrobial management of these patients should follow the guidance offered in relevant national guidelines for the management of community-acquired pneumonia and copd, but modified in the light of the different range of pathogenic bacteria that may be implicated, specifically staph. aureus infection. in the minority of cases, the aetiology may be determined after hospital admission, thereby permitting modification of the initial empirical regimen. although the pathogens responsible for communityacquired pneumonia are diverse, in the case of bacterial pneumonia complicating influenza the principal pathogens which should be covered by any initial empirical antimicrobial therapy include s. pneumoniae, h. influenzae and staph. aureus. the latter is said to be more common with combined viral bacterial pneumonia, as some strains of staphylococci have synergistic effect with the virus. gram-negative enteric bacillary infection is also sometimes seen. exacerbations of copd will be largely associated with s. pneumoniae, h. influenzae, and moraxella catarrhalis. severity assessment and the association of pre-existing co-morbid disease is essential in predicting prognosis and in turn determines management, choice of antibiotic therapy and its method of administration (see section ). during an influenza pandemic this will be principally related to concerns about the local pattern of antimicrobial resistance of staph. aureus, and assessing the possibility of methicillin-resistant s. aureus (mrsa) being present locally. clinicians should be kept closely informed of any local shift in antimicrobial resistance patterns, both at the start and during a pandemic. staphylococcus aureus is widely resistant to penicillin and an increasing number are now methicillin-resistant (mrsa); when occurring in the community this generally reflects hospitalisation within the recent past or residence within a nursing home . hence, b-lactamase unstable penicillins (penicillin g, aminopenicillins) and, in the case of mrsa, isoxazolyl penicillins (flucloxacillin, cloxacillin) and cephalosporins, are inappropriate for such infections. the true incidence of resistance among pathogens in the community is difficult to estimate since most laboratory samples come from selected populations. with this limitation in mind, the presence of b-lactamase production among h. influenzae varies geographically but ranges from % to % , in various parts of the uk. m. catarrhalis has a high rate of b-lactamase production. antibiotic resistance among s. pneumoniae is of concern world wide, owing to the dominance of this organism as a cause of community-acquired pneumonia and because penicillin and macrolide resistance are frequently linked , . however, to date it is not a common enough problem in the uk to influence initial antimicrobial management decisions. recent data provided by the hpa of antimicrobial sensitivities of respiratory pathogens isolated from blood and respiratory samples during the last three to four years (robert george, personal communication) found macrolide resistance amongst about % methicillinsensitive staphylococcus aureus (mssa) isolates and % of s. pneumoniae. macrolides, apart from clarithromycin, have poor in vivo activity against h. influenzae. by contrast, tetracycline resistance was around % for s. pneumoniae, % for h. influenzae and % for mssa. fluoroquinolones have activity against methicillinsensitive staphylococcus aureus (mssa), with mic figures of . mg/l for ciprofloxacin, . mg/l for levofloxacin and . mg/l for moxifloxacin . modern fluoroquinolones (oral moxifloxacin and oral and iv levofloxacin currently licensed in the uk) are therefore a possible choice for secondary bacterial infections following influenza where mssa is a likely pathogen. a recent pharmacokinetic and pharmacodynamic in vitro study indicated that moxifloxacin mg od had advantages over ciprofloxacin mg bd or levofloxacin mg od in antimicrobial effects against staph. aureus . the quinolones, levofloxacin or moxifloxacin, also provide cover against s. pneumoniae and h. influenzae. mrsa is an unlikely pathogen in the uk in the context of community-acquired respiratory bacterial infection following influenza, and fluoroquinolones are not sufficiently active against mrsa. there are no robust research studies available to provide evidence-based guidance on the best empirical choice of antimicrobial therapy for bacterial complications of influenza. for these reasons the recommendations for treatment have been made on the basis of assessing a matrix of laboratory, clinical, pharmacokinetic and safety data, interpreted in an informed manner and taking account of other published guidelines . in those with chronic lung disease, particularly copd, bacterial exacerbation will be the commonest cause of admission. it is likely that all such patients sufficiently ill to require hospital admission with an exacerbation will require antibiotics. management of their underlying macrolide (erythromycin mg qds po or clarithromycin mg bd b po) or fluoroquinolone with enhanced pneumococcal activity (e.g. levofloxacin mg od po or moxifloxacin mg od po c ) if iv needed: co-amoxiclav . g tds iv or cefuroxime . g tds iv or cefotaxime g tds iv macrolide (erythromycin mg qds iv or clarithromycin mg bd b iv) or levofloxacin mg od iv c . hospital-treated, severe pneumonia co-amoxiclav . g tds iv or cefuroxime . g tds iv or cefotaxime g tds iv plus macrolide (erythromycin mg qds iv or clarithromycin mg bd b iv) fluoroquinolone with some enhanced pneumococcal activity (e.g. levofloxacin mg bd iv, po c plus, either macrolide (erythromycin mg qds iv or clarithromycin mg bd b iv) or b-lactamase stable antibiotic (co-amoxiclav . g tds iv or cefuroxime . g tds iv or cefotaxime g tds iv) a an alternative regimen is provided for those intolerant of or hypersensitive to the preferred regimen. b clarithromycin may be substituted for those with gastrointestinal intolerance to oral erythromycin and also has the benefit of twice daily dosage and better cover against h. influenzae. c levofloxacin and moxifloxacin are the only currently uk-licensed fluoroquinolones with enhanced activity against s. pneumoniae, in addition to cover for staph. aureus. levofloxacin comes in an oral and a parenteral formulation and is licensed for severe pneumonia. moxifloxacin comes in an oral formulation only in the uk and is not licensed for severe pneumonia. in the future, other fluoroquinolones such as gemifloxacin and gatifloxacin are likely to extend this choice, when licensed in the uk. abbreviations: od, once daily; bd, twice; tds, times; qds, times: iv, intravenous; po, oral. switch from parenteral drug to the equivalent oral preparation should be made as soon as clinically appropriate, in the absence of microbiologically confirmed infection. in the case of the parenteral cephalosporins, the oral switch to co-amoxiclav mg tds is recommended rather than to oral cephalosporins. condition, such as copd, should follow standard guidelines, including the use of corticosteroids if indicated. antibiotics should cover the likely bacterial pathogens, including s. pneumoniae, h. influenzae, m. catarrhalis and staph. aureus. oral therapy should be sufficient for those without adverse severity features and who are able to take oral medication. the preferred first choice of antibiotic for nonpneumonic bronchial infections should include an effective oral b-lactamase stable agent such as co-amoxiclav, or a tetracycline, such as doxycycline. a macrolide is an alternative for those intolerant of the preferred first choices, whilst remembering the possibility of antimicrobial resistance. clarithromycin has better activity against h. influenzae than azithromycin. a newer-generation fluroquinolone (e.g. levofloxacin or moxifloxacin) with enhanced activity against s. pneumoniae is an alternative choice if there is increased likelihood of resistance or local issues that dictate such a choice. • previously well adults with acute bronchitis complicating influenza, in the absence of pneumonia, do not routinely require antibiotics. • antibiotics should be considered in those previously well adults who develop worsening symptoms (recrudescent fever or increasing dyspnoea). • patients at high risk of complications or secondary infection (appendix ) should be considered for antibiotics in the presence of lower respiratory features. • most patients can be adequately treated with oral antibiotics. • the preferred choice includes co-amoxiclav or a tetracycline. • a macrolide such as clarithromycin (or erythromycin) or a fluoroquinolone active against s. pneumoniae and staph. aureus is an alternative choice in certain circumstances. patients will be suffering from primary viral pneumonia, or combined viral bacterial pneumonia, or secondary bacterial pneumonia. the features of each of these are covered in section . all patients with pneumonic involvement should receive antibiotics. the principles of antibiotic selection for nonsevere influenza-related pneumonia is similar to those for the management of sporadic community-acquired pneumonia in general , except that adequate cover for staph. aureus should be included in any empirical regimen. it is also not felt necessary to routinely provide cover for atypical pathogens (mycoplasma pneumoniae, chlamydia sp., coxiella burnetti, legionella sp.) during a pandemic as the large majority of patients will be hospitalised as a direct result of influenza and its complications caused by bacterial infection. for these reasons oral co-amoxiclav or a tetracycline such as doxycycline is the preferred regimen (table . ). when oral therapy is inappropriate, parenteral coamoxiclav or a second-or third-generation cephalosporin is offered as an alternative. based on in-vitro data, the activity of selected cephalosporins against mssa in the uk in descending rank order is cefuroxime (mic mg/l) > cefotaxime (mic mg/l) > ceftriaxone (mic mg/l) [robert george, personal communication]. only cefuroxime and cefotaxime are recommended as cephalosporins offering adequate mssa cover within an empirical regimen. a macrolide or one or the new fluoroquinolones are identified as alternatives in hospitalised patients, in specific circumstances. these include those intolerant of penicillins or where local microbiological surveillance suggests they are better choices. at the time of completing these guidelines, only levofloxacin and moxifloxacin are licensed and available in the uk for pneumonia. flucloxacillin is not recommended as part of an empirical regimen because its activity against a narrow spectrum of pathogens (predominantly staph. aureus) would require it to be used in combination with more than one other antibiotic. it is offered as the antibiotic of choice in confirmed methicillin-sensitive staph. aureus (mssa) infection. regardless of the regimen selected it is critical that the antibiotics be administered promptly (within four hours of admission), and in the case of the patient with severe pneumonia without delay, by the admitting doctor in the admissions ward or by the general practitioner if delays are expected in the hospital admission process. delays in administration of antibiotics are related adversely to mortality in some studies, particularly when managing elderly patients , . following initial assessment and empirical therapy, progress should be monitored carefully. the route and choice of antibiotic treatment will require adjustment, either by stepping up and broadening the spectrum of microbiological activity in the light of clinical deterioration or as a result of positive microbiological information, or stepping down with improvement as discussed below. • most patients can be adequately treated with oral antibiotics. • oral therapy with co-amoxiclav or a tetracycline is preferred. • when oral therapy is contra-indicated, recommended parenteral choices include intravenous co-amoxiclav, or a second or third generation cephalosporin (cefuroxime or cefotaxime respectively). • a macrolide (erythromycin or clarithromycin) or a fluoroquinolone active against s. pneumoniae and staph. aureus is an alternative regimen for those intolerant of penicillins. currently levofloxacin and moxifloxacin are the only recommended fluoroquinolones licensed in the uk. • antibiotics should be administered within four hours of admission. mortality is greatly increased in those with severe pneumonia (section ). the illness may progress before microbiological information is available. preferred and alternative initial treatment regimens are summarised in table . . the recommendation of broadspectrum b-lactam regimens plus a macrolide in those with severe influenza-related pneumonia is based on the following rationale: (a) while s. pneumoniae and staph. aureus remain the predominant pathogens, gram-negative enteric bacilli, although uncommon, carry a high mortality . (b) the recommended empirical regimen will offer double cover for the likely pathogens implicated in influenzarelated pneumonia and there is some evidence to indicate that combination therapy is associated with better outcomes in severe pneumonia . (c) although there is no evidence of an increased incidence of infection by atypical pathogens in influenzarelated pneumonia, in severe pneumonia it is felt necessary to include cover for atypical pathogens, particularly legionella sp. as it may not be possible at the outset to distinguish between patients with sporadic severe community-acquired pneumonia in whom legionella infection is important, and influenzarelated pneumonia. parenteral administration of antibiotic is recommended in those with severe community-acquired pneumonia regardless of the patient's ability or otherwise to take oral medication. this is to ensure prompt, high blood and lung concentrations of antibiotic. a fluoroquinolone is offered as an alternative, despite limited data on their use in severe pneumonia . at the time of writing, levofloxacin is the only licensed and available agent in the uk for severe pneumonia. it is marketed in parenteral and oral formulations. however, until more clinical experience is available we recommend combining it with another agent active against s. pneumoniae and staph. aureus such as a broad-spectrum b-lactam or macrolide when managing severe influenzarelated pneumonia. • patients with severe pneumonia should be treated immediately after diagnosis with parenteral antibiotics. • an intravenous combination of a broad-spectrum b-lactamase stable antibiotic such as co-amoxiclav or a second-(e.g. cefuroxime) or third-(e.g. cefotaxime) generation cephalosporin together with a macrolide (clarithromycin or erythromycin) is preferred. • an alternative regimen includes a fluoroquinolone with enhanced activity against pneumococci together with a broad-spectrum b-lactamase stable antibiotic or a macrolide. currently levofloxacin is the only such fluoroquinolone licenced in the uk. • patients who have been in hospital within the last few months have a higher chance of carrying mrsa as opposed to patients who have not been hospitalised recently. therefore due consideration should be given to the possibility of mrsa if they are known or suspected to have a staphylococcal pneumonia and/or are not responding to empirical therapy. . . when should the iv route be changed to oral? there can be no rigid recommendation concerning the timing of transfer to oral therapy and further studies of this area are needed . any decision must be individualised on the basis of assessing all factors, including the absence of any contraindications to oral administration, the availability of any microbiological information regarding aetiology of the infection and clear evidence that the patient is responding to initial therapy. the recommended guideline is that oral therapy be considered in a patient who has shown clear evidence of improvement and whose temperature has resolved for a period of hours. • patients treated initially with parenteral antibiotics should be transferred to an oral regimen as soon as clinical improvement occurs and the temperature has been normal for hours, providing there is no contraindication to the oral route. . . for how long should antibiotics be given? until there are more precise methods to reliably identify microbiological and clinical end-points, the duration of therapy will remain subject to clinical judgement and custom. for these reasons the duration of therapy will vary by individual patient, disease severity and speed of resolution. • for most patients admitted to hospital with nonsevere and uncomplicated pneumonia, seven days of appropriate antibiotics is recommended. • for those with severe, microbiologically undefined pneumonia, ten days treatment is proposed. this should be extended to days where s. aureus or gramnegative enteric bacilli pneumonia is suspected or confirmed. . . failure of initial empirical therapy in those patients who fail to respond to initial empirical therapy, several possibilities need to be considered, the first of which is whether the correct diagnosis has been made. radiographic review is recommended for the community-and hospital-managed patient. this may also indicate complications of pneumonia such as pleural effusion/empyema, lung abscess or worsening pneumonic shadowing, which will be more common in the presence of staphylococcal infection. the initial empirical antibiotic regimen may need to be reassessed. however, compliance with, and adequate absorption of an oral regimen should first be considered. microbiological data should be reviewed and further specimens examined, with a view to excluding staph. aureus and gram-negative bacillary infection. in the hospital-managed, non-severely ill patient, changing to a new fluoroquinolone such as levofloxacin provides a second alternative. in the severely ill patient already receiving a b-lactam/ clarithromycin regimen, it is recommended that further staphylococcal cover is added to include cover for mrsa . in addition, urgent referral to a respiratory physician should be made for clinical assessment including the possible need for bronchoscopic sampling. other rapid mrsa diagnostic techniques are in the evaluation stage. • for those with non-severe pneumonia in hospital on combination therapy, changing to a fluoroquinolone with effective pneumococcal and staphylococcal cover is an option. • adding further antibiotics effective against mrsa is an option for those with severe pneumonia not responding to combination antibiotic therapy. specific pathogen-directed antibiotic therapy . . what are the optimum antibiotic choices when specific pathogens have been identified? when a pathogen has been identified, specific therapy as summarised in table . is proposed. in transferring patients from empirical to pathogen-targeted therapy, the regimen and route of administration will be determined by the continued need for parenteral therapy and known drug intolerance. these recommendations are again based on a synthesis of information, which includes in vitro activity of the drugs, appropriate pharmacokinetics and clinical evidence of efficacy gleaned from a variety of studies. the choice of agent may be modified following the availability of sensitivity testing or following consultation with a specialist in microbiology, infectious disease or respiratory medicine. close liaison with the local microbiology service will be essential during a pandemic. currently s. pneumoniae highly resistant to penicillin (mic mg/l) is uncommon in the uk. however, it is important that the situation is monitored and in future § . use of antibiotics in hospitalised adults part . clinical management of adults referred to hospital pandemic flu. clinical management of patients with an influenza-like illness during an influenza pandemic s either ciprofloxacin mg bd iv or piperacillin g tds iv ± gentamicin or tobramycin (dose monitoring) higher doses of penicillins or alternative regimens may need to be considered. staphylooccus aureus is an uncommon cause of sporadic community-acquired pneumonia in the uk, but will assume much greater potential importance during a pandemic. most community isolates are methicillin-sensitive although the recent increase in mrsa in hospitalised patients may result in subsequent readmission with an mrsa infection, secondary to influenza. options for methicillin-sensitive and -resistant infections are based on parenteral administration in view of the serious nature of staphylococcal pneumonia. • if a specific pathogen has been identified, the antibiotic recommendations are summarised in children with high fever (> . ºc) and cough or influenzalike symptoms will be seen by a community health professional (a nurse or doctor if under seven years of age). if there are no features that put them at high risk of complications they should be treated with oseltamivir, and given advice on antipyretics and fluids. children under one year of age and those at risk of complications (appendix ) should be seen by a gp. children may be considered at increased risk of complications if they have: cough and fever (or influenza-like illness) and temperature > . ºc and either (i) chronic co-morbid disease (see appendix ) or (ii) one of the following features • breathing difficulties • severe earache • vomiting > hours • drowsiness these patients should be offered an antibiotic as well as oseltamivir (in those over one year of age) and advice on antipyretics and fluids. children under one year of age with none of the above features should be treated with antipyretics and fluids with a low threshold for antibiotics if they become more unwell. the most severely ill children should be referred for assessment for admission. in a pandemic situation, paediatric high dependency and intensive care beds are likely to fill quickly and will be insufficient to meet demand. children will have to be triaged by the senior paediatrician on duty in consultation with tertiary specialists in respiratory medicine, paediatric intensive care or paediatric infectious diseases. triage will be on the basis of the severity of the child's (a) acute and (b) co-existing disease and the likelihood of the child achieving full recovery. where admission is not possible § . general investigations for children in hospital part . clinical management of children referred to hospital pandemic flu. clinical management of patients with an influenza-like illness during an influenza pandemic s the tertiary specialists will provide advice and support on management to the general paediatrician. in the h n cases reported from vietnam all seven children had wbc < . (mean . ) and / had a lymphopenia < . (mean . ). six of the seven children died. in contrast, only two of the seven children reported from hong kong died but they were both leukopenic and lymphopenic. the survivors had a mean wbc of . and lymphocyte count of . . four of five cases reported from thailand were lymphopenic . in influenza a thrombocytopenia (< ) is found in % , . thrombocytopenia was found in four out of seven cases of h n infection in vietnamese children . liver transaminases are raised in % of influenza a patients and were raised in six out of six of those measured in the hong kong h n outbreak and five out of six in those measured in vietnam . c-reactive protein (crp) is unhelpful in influenza with values < in % ; < in % and > in only % . the cd /cd ratio was inverted in the two children and three adults in whom it was measured in the vietnam outbreak (mean . ; range . . ). two of these patients survived . • a full blood count with differential, urea, creatinine and electrolytes and liver enzymes and a blood culture should be done in all severely ill children. one of the largest studies of the value of chest radiography was undertaken in children aged between two months and five years with community-acquired pneumonia managed as outpatients with time to recovery as the main outcome . chest radiography did not affect the clinical outcome in these children with acute lower respiratory infection. this lack of effect was independent of clinicians' experience. there are no clinically identifiable subgroups of children within the who case definition of pneumonia who are likely to benefit from a chest radiograph. the authors concluded that routine use of chest radiography was not beneficial in ambulatory children aged over two months with acute lower respiratory tract infection (lrti). clinicians basing the diagnosis of lower respiratory infections in young infants on radiographic diagnosis should be aware that there is variation in intraobserver and interobserver agreement among radiologists on the radiographic features used for diagnosis. there is also variation in how specific radiological features are used in interpreting the radiograph. a recent study on standardization of cxr interpretation in paediatric pneumonia illustrates the importance of standardised training . the cardinal finding of consolidation for the diagnosis of pneumonia appears to be highly reliable and reasonably specific for bacterial pneumonia ( % of patients with alveolar shadowing had bacterial proven pneumonia) but overall chest radiography is too insensitive to be useful in differentiating between patients with bacterial pneumonia and those whose pneumonia is nonbacterial , . in the context of an influenza pandemic, a cxr will not distinguish viral pneumonia from viral illness with bacterial superinfection, and all children with signs of pneumonia should be treated with antibiotics. • a cxr should be performed in children who are hypoxic, have severe illness or who are deteriorating despite treatment. oxygen saturation (sao ) measurements provide a noninvasive estimate of arterial oxygenation. pulse oximetry will be a key tool in assessment and management and it is essential that it is used correctly and that users are aware of the possibility of artefactually low readings. the oximeter appears easy to use and requires no calibration. however, it requires a pulsatile signal from the patient. it is also highly subject to motion artefacts. to obtain a reliable reading: ( ) the child should be still and quiet. ( ) when using paediatric wrap around probes, the emitting and receiving diodes need to be carefully opposed. ( ) a good pulse signal (plethysmograph) should be obtained. ( ) once a signal is obtained, the saturation reading should be watched over at least seconds and a value recorded once an adequate stable trace is obtained. • pulse oximetry should be performed in every child being assessed for admission to hospital with pneumonia. to be read in conjunction with the corresponding section for adults (section in part ). as with adults, the extent of virological and microbiological investigations undertaken in children should vary according to the stage of the pandemic and additionally according to the severity of an individual case. it should be noted however, that the clinical features of influenza in children are less characteristic than in adults (see section ) and the need for special diagnostic tests is therefore greater , , the utility of rapid influenza tests has been demonstrated in studies where rapid knowledge of a diagnosis of influenza (within ten minutes) has been shown to have an impact on clinicians' behaviour with respect to antibiotic use, performance of other tests and admission to hospital , . it may be imagined that in a pandemic situation such a test could result in earlier use of antiviral therapy and a more rational approach to hospital admission and to prophylaxis of contacts. however, using a molecular reference standard, one test was shown to have low sensitivity ( %) but high specificity ( %) suggesting that its role might better be to 'rule in' influenza rather than 'ruling it out' . similar conclusions have been made with other commercial rapid tests , . as a reflection of this, rapid antigen tests were positive in only two of six patients with avian influenza a (h n ) . the need for bacteriological tests in cases of influenza with pneumonia is also logical and the range of pathogens similar to adults , , - except that legionella infection is extremely unlikely to occur in a previously healthy child and legionella-specific antigen testing is therefore unnecessary. the urinary pneumococcal antigen tests in children may lack both sensitivity and specificity and should be interpreted with care , . sputum collection in children is also unreliable although in older children (e.g. over years of age) it may be possible and should be handled as indicated for adults. a. virology all children: during an influenza pandemic children are likely to be admitted to hospital because of the severity of their disease and its complications or because of the impact of influenza on pre-existing disorders such as cardiac, respiratory or neurological disease. management of preexisting disorders is outside this guideline. • the most common reason for admission is likely to be: ( ) lower respiratory tract disease with either a viral or bacterial or mixed pneumonia. • other reasons for admission include: ( ) severe gastroenteritis ( ) cardiac disease viral myocarditis ( ) encephalitis children should be triaged to ward or hdu/picu after severity assessment (section ). an influenza pandemic is likely to occur in the winter months when other winter viruses responsible for paediatric morbidity and hospital admission are circulating (such as rsv and adenovirus). particularly in the early stages of a pandemic (uk alert levels ) it will be important to use rapid virological tests in an attempt to cohort influenzapositive and rsv-positive infants separately and to separate from other patients (see uk infection control guidance for pandemic influenza) . hypoxic infants and children may not appear cyanosed. agitation may be an indication of hypoxia. patients whose oxygen saturation is less than % while breathing air should be treated with oxygen given by nasal cannulae, head box, or face mask to maintain oxygen saturation above %. nasal cannulae do not deliver a fio more than around % even at flow rates of l/min in infants and l/min in older children. alternative methods of delivering higher concentrations of humidified oxygen such as a head box or a venturi face mask may be necessary. if sao > % cannot be maintained with an fio of % then additional support such as cpap, bipap or intubation and ventilation should be considered. • patients whose oxygen saturation is % or less while breathing air should be treated with oxygen given by nasal cannulae, head box, or face mask to maintain oxygen saturation above %. children who are unable to maintain their fluid intake due to breathlessness, fatigue or gastroenteritis need fluid therapy. where possible additional fluid should be by the enteral route, and where nasogastric tube feeds are used, the smallest tube should be passed down the smallest nostril to minimize effects on respiratory status. severely ill children may need intravenous fluids, and if the child is in oxygen therapy intravenous fluids should be given at % basal levels (to avoid complications of inappropriate adh secretion) and serum electrolytes should be monitored. the monitoring will depend on the child's condition. severely ill children will need continuous monitoring of heart rate, respiratory rate, oxygen saturation and neurological status. all children on oxygen therapy should have four-hourly monitoring including oxygen saturation. chest physiotherapy is not beneficial in previously healthy children with pneumonia. children with underlying conditions such as cystic fibrosis or neuromuscular weakness will benefit from intensive physiotherapy. children with influenza are generally pyrexial and may have some pain, including headache, chest pain, arthralgia, abdominal pain, and earache from associated otitis media. pleural pain may interfere with depth of breathing and may impair the ability to cough. antipyretics and analgesics can be used to keep the child comfortable and to help coughing. . . when can children be safely discharged from hospital? in a pandemic situation there will be great pressure on hospital beds. all children should be assessed for discharge at least twice daily. children should not remain in hospital if they are receiving therapy that could be given in the community. in previously healthy children suitable discharge criteria would be: ( ) child is clearly improving ( ) child is physiologically stable ( ) child can tolerate oral feeds ( ) respiratory rate is < /min (< /min in infants) ( ) awake oxygen saturation is > % on air. most children will make an uneventful recovery and not require follow up. those with a prolonged illness may be followed up by their general practitioner. only children with severe disease and/or at high risk of sequelae need hospital follow up. children with lobar collapse should have a follow-up cxr. follow-up cxrs after acute uncomplicated pneumonia are of no value where the patient is asymptomatic , . to be read in conjunction with the corresponding section for adults (section in part ) five antiviral agents are theoretically available for the therapy of influenza in children: the m ion channel inhibitors amantadine and rimantadine (both administered orally and for influenza a only), the neuraminidase inhibitors oseltamivir (administered orally) and zanamavir (administered through an inhaler), and ribavirin (aerosolised). the limitations of amantadine and rimantadine are detailed in section , particularly in the context of a pandemic where resistance may already be present . both have been shown to be effective in the treatment of influenza a in children . concerns exist about the development of resistance during therapy for both agents , . a household study showed that treatment and prophylaxis with rimantadine resulted in rapid selection and transmission of drug resistant virus . in a double-blind randomised, placebo controlled study, children ( years of age) received oseltamivir with a resultant reduction in the median duration of illness, incidence of otitis media as a complication of influenza ( % vs %) and the need for antibiotic prescriptions in those with influenza ( of , % vs of , %; p = . ) compared to placebo . the most common sideeffect was vomiting ( . %). a systematic review and meta-analyses published in , which included studies up to december , included only two studies of zanamivir and one study of oseltamivir in which these drugs were administered for treatment of influenza a or b in children under years of age . the reduction in the median time to alleviation of symptoms for influenza-positive children when compared with placebo was . day ( % ci: . . ) for zanamivir and . days ( . . ) for oseltamivir. across all ages a % ( %) relative reduction in complications requiring antibiotics was observed for zanamivir, and for children specifically a % relative reduction was observed for oseltamivir. this was updated through to december in a cochrane review . using its search criteria it identified two trials of oseltamivir (one in healthy children and one in children with asthma which was later published and only one with zanamivir. its conclusions were therefore the same with respect to median illness duration in healthy children. a significant reduction in complications (otitis media) was noted for oseltamivir while a trend to benefit was seen for zanamivir . vomiting was significantly more common among oseltamivir recipients than placebo recipients ( % vs. %). the review noted that there may be a difference in efficacy according to serotype, with oseltamivir showing a significant reduction in time to resolution for influenza a ( %) but not b ( . %) . with respect to children with asthma there was a trend to reduction in time to freedom from illness for oseltamivir recipients but this did not reach statistical significance. oseltamivir appeared to result in a more rapid improvement in pulmonary function, and was well tolerated in children with asthma , . the cochrane review concluded that oseltamivir was the preferred drug as it has shown a benefit with regard to secondary complications. it also concluded that there was no evidence of benefit in at-risk children (i.e. asthma). from the perspective of pandemic use however, it should be noted that there was no evidence of harm in this group. with regard to dosing of oseltamivir, pharmacokinetic studies have suggested that young children clear the drug faster than older children, adolescents and adults and therefore need higher doses , . the major practical issue with regard to zanamivir is its mode of administration limiting its use to children over the age of five years (fda guidance: over seven years of age) . the development of resistance to oseltamivir in children may be more common than appreciated and more common than seen in adults. in one study resistance mutations were documented in % of children . this has implications for widespread use in a pandemic situation. one particular issue with regard to paediatric use of oseltamivir is the apparent age limitation on its license (i.e. not for children under one year of age). this is particularly important because during epidemic years, of all children with influenza, it is children under six months of age who are most likely to be hospitalised . the basis for this exclusion appears to be that rat data have shown high mortality in infant rats at seven days of age when given a dose of mg/kg together with high brain levels of oseltamivir, assumed to reflect the immature blood brain barrier at this age. this is reflected in product literature and an fda alert although there are no published data. as a result, there are few human data in this age group as it was felt that it would be difficult to monitor cns toxicity in this age group. however, because of a fear of encephalopathy due to influenza in young children, japanese paediatricians § . use of antivirals in hospitalised children part . clinical management of children referred to hospital pandemic flu. clinical management of patients with an influenza-like illness during an influenza pandemic s have been using it in infants and data on consecutive infants from japan revealed no encephalopathy or mortality in recipients . a second japanese report where children under one year were treated ( mg/kg/day) showed similar efficacy for fever to a group of older children and no serious adverse effects . there are no data on the effectiveness of oseltamivir if given more than two days from onset of illness. it is likely to be less effective and in particular to have little or no effect after five to six days of illness unless the child is immunosuppressed. giving oseltamivir to sick hospitalised patients is theoretically likely to decrease their infectivity and so may be useful but there are no data to support this. in a double blind placebo controlled study children hospitalized with influenza who had been ill for hours or less and who had a temperature of . ºc or more were randomised to receive either ribavirin or placebo. sixtytwo patients ( in the placebo group, in the ribavirin group) had a confirmed diagnosis of influenza. the time to reduction of temperature to . ºc or less for the ribavirin group was . hours compared with . hours for the placebo group (p = . ). there were no other differences detected between groups . there have been no further published studies in the years since this report, thus ribavirin cannot be recommended at this time. • in the setting of a pandemic, children in the community should only be considered for treatment with antivirals if they have all of the following: ( ) an acute influenza-like illness ( ) fever (> . ºc) and ( ) been symptomatic for two days or less. • oseltamivir is the antiviral agent of choice. • treatment schedule for children over one year: body weight kg, i.e. < years: mg every h body weight > kg, i.e. years: mg every h body weight kg, i.e. > years: mg every h • in children who are severely ill in hospital oseltamivir may be used if the child has been symptomatic for less than six days. • oseltamivir may be considered for the treatment of infants under one year of age, especially those with severe influenza. this would need to be done following appropriate discussion with the parents highlighting the concerns from the animal data and the relative paucity of human data in this age group. section . use of antibiotics in hospitalised children . . who should get antibiotics? secondary bacterial infections, particularly pneumonia and otitis media, are common in children with influenza. a case control study during an outbreak of severe pneumococcal pneumonia demonstrated that patients with severe pneumonia were times more likely to have had an influenza-like illness and four times more likely to have positive influenza serology than controls . infections with staph. aureus and h. influenzae are also more common during influenza outbreaks. a randomized controlled trial of antibiotics in children aged four months to years presenting with influenzalike symptoms during an influenza epidemic showed a decreased incidence of pneumonia in the antibiotictreated group ( . % vs . %, p = . ) . there was no change in duration of fever or incidence of acute otitis media. interestingly only one out of seven of the cases of pneumonia in the placebo group was thought to be bacterial. the authors postulated that as bacterial proteases facilitate propogation and pathogenesis of influenza in a mouse model, decreasing bacterial numbers and hence protease levels in the lung may decrease viral pneumonia. another randomized trial of cephalosporins vs macrolides in japanese children with influenza-like symptoms showed faster alleviation of fever ( . ± . vs . ± . days, p = . ) in the macrolide group and a decrease in number with cxr evidence of pneumonia ( vs cases, p = . ; / had interstitial changes) . the authors postulate that anti-inflammatory effects of macrolides may be responsible. • children who (a) are at risk of complications of influenza or (b) have disease severe enough to merit hospital admission during an influenza pandemic should be treated with an antibiotic that will provide cover against s. pneumoniae, staph. aureus and h. influenzae. the antibiotics of choice must cover the likely pathogens as above. rarely a blood culture or pleural tap will provide the pathogen. the antibiotics should then be specifically tailored, e.g. iv benzylpenicillin or oral amoxicillin for s. pneumoniae and flucloxacillin or clindamycin for staph. aureus. part . clinical management of children referred to hospital § . use of antibiotics in hospitalised children s provisional guidelines from bis/bts/hpa in collaboration with the department of health, version ( october ) a recent randomized controlled trial of the equivalence of oral amoxicillin vs iv benzylpenicillin in children admitted to hospital with community-acquired pneumonia showed no difference in duration of illness or complications . oral antibiotics should be given provided oral fluids are tolerated. . . antibiotic choice for severe or complicated pneumonia? children who are severely ill with pneumonia complicating influenza should have a second agent which provides good cover for gram positive organisms added to the regime (e.g. clarithromycin or cefuroxime) and the drugs should be given intravenously to ensure high serum and tissue antibiotic levels. section . acknowledgements, committee members and affiliations chronic obstructive pulmonary disease (copd) including chronic bronchitis and emphysema, and such conditions as bronchiectasis, cystic fibrosis, interstitial lung fibrosis, pneumoconiosis and bronchopulmonary dysplasia (bpd). asthma requiring continuous or repeated use of inhaled or systemic steroids or with previous exacerbations requiring hospital admission. children who have previously been admitted to hospital for lower respiratory tract disease. chronic heart disease congenital heart disease, hypertension with cardiac complications, chronic heart failure and individuals requiring regular medication and/or follow-up for ischaemic heart disease. chronic renal disease nephrotic syndrome, chronic renal failure, renal transplantation. chronic liver disease cirrhosis, inflammatory bowel disease diabetes and chronic metabolic disorders diabetes mellitus requiring insulin or oral hypoglycaemic drugs. immunosuppression and malignancy due to disease or treatment: asplenia or splenic dysfunction, hiv infection at all stages, malignancy. patients undergoing chemotherapy leading to immunosuppression. individuals on or likely to be on systemic steroids for more than a month at a dose equivalent to prednisolone at mg or more per day (any age) or for children under kg a dose of mg or more per kg per day. long-stay residential care homes residents this does not include prisons, young offender institutions, university halls of residence. others doctors retain discretion in identifying additional individual patients who they recognise as at high risk of serious complications should they develop influenza; for example patients with haemoglobinopathies, neurological diseases with muscle weakness, cerebral palsy or children on long-term aspirin who are at increased risk of reye's syndrome. a the high-risk groups described in this appendix are largely based on data from interpandemic influenza. during the course of a pandemic, the definition of 'high-risk groups' may differ. if so, details of the 'high-risk' patient group will be altered according to relevant clinico-epidemiological data. users are strongly advised to refer to the latest version of these guidelines at all times. treat as severe pneumonia antibiotics not indicated < . kg - . mg/kg b.d. a winter's tale: coming to terms with winter respiratory illnesses. london: health protection agency the epidemiology and clinical impact of pandemic influenza the contribution of influenza to combined acute respiratory infections, hospital admissions, and deaths in winter pandemic versus epidemic influenza mortality: a pattern of changing age distribution delaying the international spread of pandemic influenza acute viral infections of upper respiratory tract in elderly people living in the community: comparative, prospective, population based study of disease burden contribution of influenza and respiratory syncytial virus to community cases of influenza-like illness: an observational study viral respiratory infections in the institutionalized elderly: clinical and epidemiologic findings does this patient have influenza? clinical signs and symptoms predicting influenza infection predicting influenza infections during epidemics with use of a clinical case definition the predictive value of influenza symptomatology in elderly people randomized, placebocontrolled studies of inhaled zanamivir in the treatment of influenza a and b: pooled efficacy analysis efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections. gg influenza study group efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. us oral neuraminidase study group the impact of influenza epidemics on mortality: introducing a severity index human influenza principles and practice of clinical virology clinical features of influenza age and asian influenza, rapid diagnosis of primary influenza pneumonia importance of staphylococcus aureus in pneumonia in the epidemic of influenza a should staff in long-stay hospitals for elderly patients be vaccinated against influenza? bacterial pneumonia during the hong kong influenza epidemic of influenza pneumonia the influence of bacterial superinfection on the clinical course of influenza. studies from the influenza epidemics in stockholm during pneumonia complicating asian influenza influenza a myocarditis developing in an adult liver transplant recipient despite vaccination: a case report and review of the literature rhabdomyolysis and myoglobinuric renal failure complicating influenza in a young adult acute myopathy associated with influenza a/texas/ / infection. isolation of virus from a muscle biopsy specimen high incidence of acute myositis with type a influenza virus infection in the elderly influenza and myoglobinuria in brothers myoglobinuria associated with influenza a infection a pregnant woman with influenza a encephalopathy in whom influenza a/hong kong virus (h ) was isolated from cerebrospinal fluid isolated lesions limited to the bilateral substantia nigra on mri associated with influenza a infection influenza virus and cns manifestations the spectrum of antecedent infections in guillain-barre syndrome: a casecontrol study myelitis associated with influenza a virus infection toxic shock syndrome complicating influenza a infection: a two-case report with one case of bacteremia and endocarditis toxic shock syndrome following influenza a infection acute parotitis associated with influenza type a: a report of twelve cases avian influenza: assessing the pandemic threat. who atypical avian influenza (h n ) fatal avian influenza a (h n ) in a child presenting with diarrhea followed by coma avian influenza a (h n ) infection in humans human disease from influenza a (h n ) avian influenza virus infection of children in vietnam and thailand prospective study of the viral aetiology and clinical course among children in the community with cough and fever nosocomial influenza in children recurrence of febrile seizures in the respiratory season is associated with influenza a influenza a and b virus infections in children influenza in children clinical predictors of influenza in children clinical features of influenza a and b in children and association with myositis the burden of influenza illness in children with asthma and other chronic medical conditions the impact of influenza a on children with disabilities the impact of influenza in children severe pneumococcal pneumonia in previously healthy children: the role of preceding influenza infection impact of the rapid diagnosis of influenza on physician decision-making and patient management in the pediatric emergency department: results of a randomized, prospective, controlled trial childhood severe acute respiratory syndrome in taiwan and how to differentiate it from childhood influenza infection clinical courses of croup caused by influenza and parainfluenza viruses prevalence of various respiratory viruses in the middle ear during acute otitis media influenza virus infection in infancy and early childhood welliver sr rc. a comparison of epidemiologic and immunologic features of bronchiolitis caused by influenza virus and respiratory syncytial virus references s provisional guidelines from bis/bts/hpa in collaboration with the department of health encephalopathy associated with influenza a influenza surveillance system of japan and acute encephalitis and encephalopathy in the influenza season reye's syndrome and aspirin reye's syndrome in the united states from through the puzzling picture of acute necrotizing encephalopathy after influenza a and b virus infection in young children acute necrotizing encephalopathy of childhood associated with influenza type b virus infection in a -year-old girl clinical characteristics of children with influenza a virus infection requiring hospitalization influenza a and meningococcal disease influenza pandemic contingency planning: operational guidance on the provision of healthcare in a community setting in england effect of influenza vaccination on disease progression among hiv-infected persons validation of a predictive rule for the management of community-acquired pneumonia assessment of pneumonia severity: a european perspective information leaflet and antibiotic prescribing strategies for acute lower respiratory tract infection: a randomized controlled trial diagnostic value of c reactive protein in infections of the lower respiratory tract: systematic review airway hyperreactivity and peripheral airway dysfunction in influenza a infection american college of chest physicians/national heart, lung, and blood institute national conference on oxygen therapy acute hypercapnic respiratory failure in patients with chronic obstructive lung disease: risk factors and use of guidelines for management instability on hospital discharge and the risk of adverse outcomes in patients with pneumonia pandemic influenza: is an antiviral response realistic? randomised trial of efficacy and safety of inhaled zanamivir in treatment of influenza a and b virus infections. the mist (management of influenza in the southern hemisphere trialists) study group efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. neuraminidase inhibitor flu treatment investigator group neuraminidase inhibitors for preventing and treating influenza in healthy adults oral oseltamivir treatment of influenza in children safety and efficacy of the neuraminidase inhibitor gg in experimental human influenza impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations comparison of efficacies of rwj- , zanamivir, and oseltamivir against h n , h n , and other avian influenza viruses study of -adamantanamine hydrochloride used prophylactically during the hong kong influenza epidemic in the family environment selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir a comparison of antimicrobial resistance rates in grampositive pathogens isolated in the uk from mrsa bacteraemia in patients on arrival in hospital: a cohort study in oxfordshire antimicrobial resistance in haemophilus influenzae from england and scotland in trends in the antimicrobial susceptibility of bacterial respiratory tract pathogensfindings of the alexander project antibiotic resistance among clinically important gram-positive bacteria in the uk a critical review of the fluoroquinolones: focus on respiratory infections antistaphylococcal effect related to the area under the curve/mic ratio in an in vitro dynamic model: predicted breakpoints versus clinically achievable values for seven fluoroquinolones quality of care, process, and outcomes in elderly patients with pneumonia community-acquired pneumonia in patients receiving home care prognosis and outcomes of patients with community-acquired pneumonia. a meta-analysis severe pneumonia and a second antibiotic the next generation: fluoroquinolones in the management of acute lower respiratory infection in adults comparison of versus days of antibiotic therapy for hospitalized patients with uncomplicated communityacquired pneumonia: a prospective, randomized, doubleblind study antibiotics in pandemic flu children with respiratory disease associated with metapneumovirus in hong kong avian influenza a (h n ) in patients in vietnam clinical features and rapid viral diagnosis of human disease associated with avian influenza a h n virus cases of influenza a (h n ) thailand randomised controlled trial of clinical outcome after chest radiograph in ambulatory acute lower-respiratory infection in children standardized interpretation of paediatric chest radiographs for the diagnosis of pneumonia in epidemiological studies reliability of the chest radiograph in the diagnosis of lower respiratory infections in young children comparison of radiological findings and microbial aetiology of childhood pneumonia accuracy of radiographic differentiation of bacterial from nonbacterial pneumonia rationalised prescribing for community acquired pneumonia: a closed loop audit comparison of clinical characteristics of influenza and respiratory syncytial virus infection in hospitalised children and adolescents influenzalike illness criteria were poorly related to laboratoryconfirmed influenza in a sentinel surveillance study effect of a rapid influenza diagnosis effect of rapid diagnosis of influenza virus type a on the emergency department management of febrile infants and toddlers near patient testing for influenza in children in primary care: comparison with laboratory test comparison of binax now and directigen for rapid detection of influenza a and b new point of care test is highly specific but less sensitive for influenza virus a and b in children and adults association of invasive pneumococcal disease with season, atmospheric conditions, air pollution, and the isolation of respiratory viruses fatal influenza a virus infection in a child vaccinated against influenza toxic shock syndrome. a newly recognized complication of influenza and influenzalike illness fulminant pneumonia caused by concomitant infection with influenza b virus and staphylococcus aureus preceding respiratory infection predisposing for primary and secondary invasive haemophilus influenzae type b disease performance of the binax now streptococcus pneumoniae urinary antigen assay for diagnosis of pneumonia in children with underlying pulmonary diseases in the absence of acute pneumococcal infection evaluation of rapid assay for detection of streptococcus pneumoniae urinary antigen among infants and young children with possible invasive pneumococcal disease the utility of chest radiography in the follow-up of pneumonia references s provisional guidelines from bis/bts/hpa in collaboration with the department of health value of radiological follow up of childhood pneumonia re-emergence of fatal human influenza a subtype h n disease recovery of drug-resistant influenza a virus during therapeutic use of rimantadine high frequency of resistant viruses harboring different mutations in amantadine-treated children with influenza emergence and apparent transmission of rimantadine-resistant influenza a virus in families effectiveness of neuraminidase inhibitors in treatment and prevention of influenza a and b: systematic review and meta-analyses of randomised controlled trials neuraminidase inhibitors for preventing and treating influenza in children oral oseltamivir improves pulmonary function and reduces exacerbation frequency for influenza-infected children with asthma pharmacokinetics of anti-influenza prodrug oseltamivir in children aged years resistant influenza a viruses in children treated with oseltamivir: descriptive study burden of interpandemic influenza in children younger than years: a -year prospective study experience with oseltamivir for infants younger than year old in japan oseltamivir phosphate in infants under year of age with influenza infection efficacy and safety of aerosolized ribavirin in young children hospitalized with influenza: a double-blind, multicenter, placebo-controlled trial efficacy of antibiotics against influenza-like illness in an influenza epidemic effect of maclorides on duration and resolution of symptoms and complication of pneumonia in children with influenza a randomised controlled equilanence trial to compare oral and intravenous treatment and the direct and indirect costs of treating children with community acquired pneumonia: pivot trial human influenza a h n virus related to a highly pathogenic avian influenza virus outbreak of avian influenza a (h n ) virus infection in hong kong in avian influenza a challenge to global health care structures in addition, antivirals may be considered in the following exceptional situations:(i) patients who are unable to mount an adequate febrile response, e.g. the immunocompromised or very elderly, may still be eligible for antiviral treatment despite the lack of documented fever. (ii) severely ill and immunosuppressed patients, including those on long-term corticosteroid therapy, may benefit from antiviral therapy commenced later than hours after the onset of ili. (iii) severely ill children < year old. (parents must be informed that oseltamivir is not licensed for children < year old.) the first recorded instance of human infection by avian influenza h n occurred in may in hong kong. the first patient was a -year old child who presented initially with symptoms of fever, sore throat and abdominal pain. he later developed reye's syndrome, ards, multi-organ failure and eventually died . a total of persons were subsequently infected before the outbreak ended in december , . half the patients were aged years and below and only two were aged over years. abdominal symptoms, such as diarrhoea, vomiting and abdominal pain, were described in ten ( %) patients. eleven ( %) had a severe illness characterised by pneumonia occurring within days of symptom onset, lymphopenia, deranged liver function tests and a high mortality [six ( %) of patients with pneumonia]. secondary bacterial infections were not identified as the cause of the pneumonias.the most recent human outbreak of influenza a (h n ) infection began in december . the clinical features of hospitalised patients infected by the re-emergent avian influenza a (h n ) in were similar to those described in patients in (table a . ). children and young adults were the main groups affected. gastrointestinal symptoms were common. the presence of lymphopenia and deranged liver function tests was again associated with a poorer prognosis .since december , over cases had been reported to the who . the mortality rate among hospitalised patients has been generally high (> %). death has occurred an average of ten days after the onset of illness and most patients have died of progressive respiratory failure.there has been a review of avian influenza a (h n ) infection in humans up until september . updated information can be found at www.who.int/csr/disease/avian_influenza/en/. key: cord- -w srv em authors: babuna, pius; yang, xiaohua; gyilbag, amatus; awudi, doris abra; ngmenbelle, david; bian, dehui title: the impact of covid- on the insurance industry date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: w srv em this study investigated the impact of covid- on the insurance industry by studying the case of ghana from march to june . with a parallel comparison to previous pandemics such as sars-cov, h n and mers, we developed outlines for simulating the impact of the pandemic on the insurance industry. the study used qualitative and quantitative interviews to estimate the impact of the pandemic. presently, the trend is an economic recession with decreasing profits but increasing claims. due to the cancellation of travels, events and other economic losses, the ghanaian insurance industry witnessed a loss currently estimated at gh Ȼ million. our comparison and forecast predicts a normalization of economic indicators from january . in the meantime, while the pandemic persists, insurers should adapt to working from remote locations, train and equip staff to work under social distancing regulations, enhance cybersecurity protocols and simplify claims/premium processing using e-payment channels. it will require the collaboration of the ghana ministry of health, banking sector, police department, customs excise and preventive service, other relevant ministries and the international community to bring the pandemic to a stop. abstract: this study investigated the impact of covid- on the insurance industry by studying the case of ghana from march to june . with a parallel comparison to previous pandemics such as sars-cov, h n and mers, we developed outlines for simulating the impact of the pandemic on the insurance industry. the study used qualitative and quantitative interviews to estimate the impact of the pandemic. presently, the trend is an economic recession with decreasing profits but increasing claims. due to the cancellation of travels, events and other economic losses, the ghanaian insurance industry witnessed a loss currently estimated at gh coronavirus disease, scientifically reclassified as covid- , has assumed global pandemic proportions [ ] . it attained a pandemic status declared by the world health organization (who) on march [ ] . the current spread of the virus at a fast rate compared to previous pandemics has resulted in a total lockdown of nations, ban on travels, public gatherings and closure of offices. there has been global closure of businesses as well as the loss of jobs and lives. the general economic situation is a global recession. in most instances, the insurance industry and governments all over the world have become the beacons of hope to which people look for rescue from total annihilation. however, due to the fast increase in infection cases greater than the recovery of infected people, the pandemic has overwhelmed many governments and financially weakened some insurance companies. the impact ȩ coronavirus disease (covid- ) dashboard cost efficiency of insurance firms in ghana efficiency, productivity and returns to scale economies in the non-life insurance market in south africa evaluating the cost efficiency of insurance companies in ghana backyard poultry flocks and salmonellosis: a recurring, yet preventable public health challenge the impact of the antonine plague the black death and its effect on fourteenth-and fifteenth-century art the black death: the great mortality of - . a brief history with documents updating the accounts: global mortality of the - "spanish" influenza pandemic novel origin of the pandemic influenza virus nucleoprotein gene segment world war i may have allowed the emergence of the geography and mortality of the influenza pandemic sequence of the pandemic influenza virus nonstructural gene (ns) segment and characterization of recombinant viruses bearing the ns genes origin of hiv type in colonial french equatorial africa? gender and monitoring the response to hiv/aids pandemic challenges in the development of an hiv- vaccine human immunodeficiency virus type , human protein interaction database at ncbi the emergence of hiv/aids in the americas and beyond a history of aids: looking back to see ahead novel swine-origin influenza virus a (h n ): the first pandemic of the st century the emergence of novel swine influenza viruses in north america cases of swine influenza in humans: a review of the literature swine influenza a (h n ) triple reassortant virus infection pathogenesis of swine influenza virus (thai isolates) in weanling pigs: an experimental trial the first pandemic of the st century sars-cov virus-host interactions and comparative etiologies of acute respiratory distress syndrome as determined by transcriptional and cytokine profiling of formalin-fixed paraffin-embedded tissues sars coronavirus vaccine development ebola outbreak in west africa: a neglected tropical disease estimating the future number of cases in the ebola epidemic-liberia and sierra leone the ebola epidemic: a global health emergency ebola outbreak: ethical use of unregistered interventions a comparative study of strains of ebola virus isolated from southern sudan and northern zaire in ebola hemorrhagic fever: tandala, zaire, - identification of the ebola virus in gabon in containing a hemorrhagic fever epidemic: the ebola experience in uganda laboratory diagnosis of ebola hemorrhagic fever during an outbreak in yambio, sudan newly discovered ebola virus associated with hemorrhagic fever outbreak in uganda human ebola outbreak resulting from direct exposure to fruit bats in luebo, democratic republic of congo ebola hemorrhagic fever ebola virus outbreaks in africa: past and present ebola haemorrhagic fever associated with novel virus strain covid- ) epidemics, the newest and biggest global health threats: what lessons have we learned? the economics of epidemic diseases pandemics of the poor and banking stability pandemic risk: how large are the expected losses? profitability shocks and recovery in time of crisis evidence from european banks tourism and covid- : impacts and implications for advancing and resetting industry and research the coronavirus and the great influenza pandemic: lessons from the 'spanish flu' for the coronavirus's potential effects on motality and economic activity growth dynamics: the myth of economic recovery aggregate and firm level stock returns during pnademics in real time financing hiv/aids programs in sub-saharan africa. health aff epidemics and economics: new and resurgent infectious diseases can have far-reaching economic repercussions assessing the impact of a pandemic on the life insurance industry in south africa acknowledgments: thanks to all authors for their efforts in conducting this research. the authors declare no conflict of interest. key: cord- -bnxczi t authors: pennington, mark title: hayek on complexity, uncertainty and pandemic response date: - - journal: rev austrian econ doi: . /s - - - sha: doc_id: cord_uid: bnxczi t this paper draws on hayek’s distinction between simple and complex phenomena to understand the nature of the challenge facing policymakers in responding to the new coronavirus pandemic. it shows that while government action is justifiable there may be few systemic mechanisms that enable policymakers to distinguish better from worse policy responses, or to make such distinctions in sufficient time. it then argues that this may be a more general characteristic of large-scale public policy making procedures and illustrates the importance of returning to a market-based political economy at the earliest convenience. the new coronavirus (covid ) pandemic that has engulfed the world in recent months has prompted unprecedented levels of government activism both in an attempt to control the virus and in attempts to curtail the economic damage arising from these policy measures. governments across many parts of the world have effectively 'closed down' economic systems in response to the health threat posed by the pandemic. in some countries meanwhile governments have also committed themselves to policy measures -such as paying the wages of private sectors employees -that have rarely if ever been seen before. this paper considers the challenge the pandemic presents to policy makers by drawing on f.a. hayek's distinction between simple and complex phenomena. it argues that while government action may be warranted, the complexities entailed in addressing the multiple socio-economic dimensions at stake mean that on many of these dimensions it may not be possible to discern the contours of an effective policy response. or, if such responses can be identified, to secure their implementation in a sufficiently timely manner. the paper then considers the implications of hayek's perspective for broader socio-economic challenges that policymakers are increasingly being urged to assume, with a focus on post-pandemic risk planning and arguments for post-pandemic industrial policy. the paper commences in section one by outlining hayek's distinction between simple and complex phenomena and how this is reflected in his critique of economic planning. it then proceeds in section two to consider some of the dimensions of complexity that underpin the coronavirus policy challenge. section three argues that while government action may be a justifiable response to the pandemic, there may be few systemic mechanisms that enable policymakers to avoid large scale errors and to assess the effectiveness of alternative policy measures. finally, section argues that a continuation of activist government in a post-pandemic political economy may work to perpetuate aspects of the knowledge poor environment that characterises the pandemic itself. a central aspect of hayek's social theory is the distinction he draws between simple and complex phenomena (for example hayek ) . simple phenomena are those where it may be possible from a given starting position to predict the outcomes that will be generated by the application of a stimulus into a system. scientific problems in some (though by no means all) parts of physics are of this type and they allow for the derivation of predictive, quantitative regularities by scientific analysts. complex phenomena by contrast, refer to systems where the elements that make up a greater whole do not interact in a linear fashion and where the number of elements and the character of their interaction may be too vast for them to be comprehended by scientific observers. while non-linear systems can be scientifically modelled the relevant relationships may not typically be characterised with sufficient quantitative precision. the most that analysts may do when faced with complex phenomena is to try to understand the general principles that allow an order to form between the various elements-not to predict successfully the precise form that the order will take. all that science may be able to achieve in the face of such phenomena is to predict a statistical range of possible outcomes. it is tempting to equate hayek's distinction between simple and complex phenomena with the difference between the subject matter of the natural and social sciences, but this would be mistaken (for a discussion see caldwell ) . while it is true that some natural sciences analyse simple systems, this is not always so. many of the phenomena analysed in biology or ecology for example, are closer to complex systems. in such cases natural scientists may discover the general principles such as the principles of ecological succession that drive processes of environmental change. typically, however, the scientists concerned may not be able to discern enough about the multiple contextual relationships between elements to predict successfully how ecosystems will evolve, given certain exogenous or endogenous changes to them (for example botkin ; scheiner and willig ) . turning to the socio-economic world, the challenge of scientific understanding relates to even more complex systems. knowledge of all the varied and changing economic and cultural conditions that confront multitudes of people may not be comprehended by any social scientist or group of such scientists. away from very basic forms of human society where the rhythms and routines of people might be observed and predicted with some accuracy by external observersin more complex social orders the most that social science may achieve is an understanding of the general principles of human interaction and the broad patterns they produce. what may not be predicted successfully are specific responses to specific events. economists may for example understand that if a good becomes scarcer in a market, various changes such as a rise in price and the search for new supplies or substitutes may be expected. they may not, however, predict successfully (other than by chance) what the specific responses will entail and the balance between the respective forces set in train (for a recent argument see kay and king ) . moreover, it may not even be possible to specify the range of likely responses because unlike the natural world the 'human elements' making up the social ecology are creative actors. on a hayekian view, it is for this reason that the modelling of social interaction in terms of the predicted behaviour of statistically 'representative agents' that characterises contemporary neo-classical economics is of questionable valuefor it is entrepreneurial outliers that drive processes of social change. while there may be 'orderliness' in society this does not equate to some static or fixed equilibrium state where change can only be accounted for through 'exogenous shocks' to an otherwise stable system. rather, social interaction should be understood as process of ceaseless and sometimes turbulent change brought about by the generation of new ideas, processes, and ways of doing things (for example, wagner ). this stance does not imply rejecting statistical modelling as a possible way to inform the day to day plans of individuals and organisations. since future decisions grow incrementally out of past decisions there are some regularities that people can rely on to navigate their way in the worldthough even here expectations will often be disappointed. longer term econometric forecasting may however be of little use because the building of reliable econometric models requires knowledge of the factors that will shape the future in advance of their emergence (parker and stacey : - ) . the key point that hayek takes from the distinction between simple and complex systems is that whereas the former can be subject to planning and control by a 'directive intelligence' the latter cannot be subject to such control owing to the overwhelming 'knowledge problem' that would face such an intelligence. whatever objectives people may have, whether pertaining to health, economic growth, environmental protection, or some combination of these, will to a large extent have to be achieved via indirect mechanisms. unless people choose a dramatically simpler form of social existence that might be more amenable to direction and control, then intelligent policy can only hope to find rules that allow for the many agents that make up complex social systems to adapt to the actions of others without having to know all of the factors that drive them. the mechanisms and rules that work most effectively in this regard will be those that provide relatively clear feedback to the agents and agencies concerned and enable relatively speedy adaptation to changing information about success and failure in reading situations at the local level. in brief, this analysis underlies hayek's case for a market economy based on rules of private property and contract, over a planned or centrally managed economy. a market economy should be understood as a complex adaptive system where property rights and freedom of contract provide rules that enable an intricate ecology of dispersed individuals and organisations to experiment in responding to their own circumstances and for the results of these experiments to be communicated to neighbouring actors via profit and loss accounting and market price signals. the resultant 'order' is an 'emergent' property of the constant interaction between the various elements in a context where no 'directive intelligence' could be aware of all the possible and continually changing margins for adjustment. contrary to some critical readings of hayek's ideas (for example, grossman and stiglitz ) , there is no suggestion that the relevant order in markets occurs instantaneously or that adaptations made are 'perfect'. rather, hayek's claim is a comparative one that market economies facilitate more learning and adjustment than would likely arise in a centrally managed alternative. neither is there any suggestion that prices communicate all necessary knowledge. hayek's argument is the more modest one that market prices communicate in an indirect way more knowledge than would be possible without them. price signals will always operate in a 'noisy' environment and given uncertainty about future states of the world entrepreneurs must try to understand whether shifts in prices reflect longer or shorter-term social trends and what the possible causes of these might be. part of hayek's case for the market economy is that competition operates as a discovery procedure where different social constructions of what prices mean, are tested against one another and the relative strength of these subjective readings revealed through the account of profit and loss (for example , hayek ; hayek a, b) . prices on this view are not 'given data' which are presented in their totality to actors. rather they present themselves as overlapping 'bits' of data that both affect and are affected by a process of social contestation and interaction where widely dispersed interpretations of economic possibilities continually tussle with one another. outside of such a rivalrous process the capacity to reveal the opportunity costs of alternative courses of action would be confined to the very limited imagination of a 'directive intelligence' or 'social planner'. it should be noted that none of these arguments are undermined by technological innovations such as for example the development of artificial intelligence or 'big data' gathering techniques which it is often suggested might allow for the replacement of market processes (for example cottrell and cockshott ; phillips and rozworski for a critique see hodgson ). on the one hand, these innovations increase the scope for decentralised agents -whether individuals, firms, or voluntary organisations, to increase the complexity of their own decision-making. this means that no matter how sophisticated the relevant technology becomes the complexity of the social system at the 'meta-level' will be higher than the cognitive capacities of any 'directive intelligence'. similarly, no matter how much data collection is facilitated by technology it will remain the case that the data at issue will not 'speak for themselves'. even if big data were to allow for a retrodictive understanding of the causes of socio-economic events this understanding will arrive 'too late' to act as a guide to effective decisionmaking. moreover, to the extent that it provides an understanding of the past different people will interpret the future implications of the relevant data in different ways. on a hayekian view, readings of data are no more than social constructions so the importance of competition in testing these different constructions against alternative readings remains paramount. absent competition there is likely to be an increased risk of large scale decision failure where should those empowered to make decisions err in their choices then the effects are likely to be felt across the whole of society, rather than being confined to a relatively smaller portion of the community in question. while the foregoing arguments are theoretical in nature, they are also empirically grounded claims that help to explain, at least in a qualitative sense, the superior performance of economies that rely on market processes relative to those that try to suppress them. though hayek develops a powerful case for the importance of market processes however, his perspective does not imply that there are market solutions to all socio-economic problems. in works such as the road to serfdom ( ) and the constitution of liberty ( ) hayek sets out an extensive range of government measures where public goods style challenges arise. dealing with infectious diseases such as the new coronavirus where these dynamics may be especially prevalent, may thus be a justifiable form of government action. nonetheless, understanding and evaluating any such action will require proper appreciation of the levels of complexity in play and whether there are effective feedback mechanisms available to policymakers to cope with the uncertainties at hand. on a hayekian view, the task is to find institutional configurations that allow for experimentation and feedback that is somewhat analogous to that provided by markets. with this challenge in mind this section sets out some of the complexities that may confront policymakers facing the coronavirus pandemic. the subsequent section turns to the existence or otherwise of mechanisms analogous to those in market processes that may enable decision-makers to avoid large scale errors and to learn from other decision-making nodes. as with other pandemics, a first layer of complexity that policymakers must contend with in addressing the new coronavirus concerns the epidemiology of the virus itself. epidemiological problems although involving natural science phenomena are not of the simple 'physics' type. while epidemiologists may discern the principles that govern how a virus spreads and perhaps simulate a range of possible outcomes -the precise manner of spread through a population will depend on a host of context specific variables that may not be accessible to the scientists or experts concerned. this challenge is seen most clearly perhaps in the problem of modelling the spread of the pandemic and the sometimes very different projections of the size and shape of the peak of the disease (for a discussion of this see ormerod ). will the pandemic peter out of its own accord without first having to affect a large percentage of the population? at what level of spread might 'herd immunity' be achieved? how is the spread of the virus affected by weather and geography? will there be a second wave of infections? and will the virus mutate into a weaker or stronger form? uncertainties surrounding answers to these and other such questions mean that modelling and data analysis will involve a good deal of subjective interpretation and scope for significant error. an additional layer of complexity arises because the virus which is itself a complex phenomenon is interacting with a further complex phenomenon represented by the various political, economic, cultural and institutional arrangements across the world that might affect the manner of spread. as ormerod ( ) notes, one of the key limitations of epidemiological models is that their projections often fail to account for human behaviour and changes in that behaviourincluding those induced by public policy. there is, for example, considerable uncertainty about how the new coronavirus will respond to various public policy interventions. it is unclear how 'lockdown' policies might affect the size of a possible second wave of transmission. on one scenario lockdowns might be essential to reducing the spread of the disease to the point where infections in any 'second wave' could be more easily managed and controlled. on the other hand, however, it could be that the success of lockdowns in limiting the spread of a first wave of the virus will only contribute to a much larger and potentially uncontrollable second wave of infections owing to the limited extent of herd immunity arising from the lockdown measures. still further complexity is injected into the policy conundrum by uncertainties about how different populations with different social attitudes, time horizons and belief systems may respond to the various policy measures that are adopted, or to news about developments that are affecting the spread of the virus. within this context, there is a distinct possibility for 'lucas effects' to arise. in macro-economic analysis these refer to situations where public policy measures might be counteracted by shifts in behaviour which are a response to the measures concerned (for example, lucas ). if for example policymakers seek to raise inflation in the hope of lowering unemployment, then this may lead to a shift in employers inflation expectations which may lead them to decrease employment. macro-economic models if they are to be useful to policymakers need, therefore, to factor in how changes in policy might change the expectations and behaviour of the agents on which the policy is supposed to act. in the specific context of pandemic response it is possible that if people come to believe that a vaccine is imminent or that herd immunity is close to being achieved they may start to behave in wayssuch as abandoning social distancing measuresthat make the immediate problem worse. on a hayekian view, however, there is a significant 'knowledge problem' for policymakers in understanding how expectations will be changed by the pattern of events or by policy interventionsand this problem is especially severe in a context of heterogenous individuals with divergent ideas whose actions cannot be reduced to those of a 'representative agent'. the complexities discussed thus far raise significant challenges for policymakers even if they concern themselves solely with managing the health effects of the virus. to approach pandemic response in such a way would be to see it as primarily a 'technological problem'where the task at hand is to allocate resources to achieve a singular 'technical' end. pandemic response, however, is not best understood as a narrowly technical exercise but as an 'economic problem' which involves allocating resources between multiple competing ends. in the context of health objectives there are complex and uncertain trade-offs to be made between the possible reduction of deaths from the coronavirus that might follow lock-down measures and the possible increased deaths arising from illnesses that might go undiagnosed or untreated because of such measures. away from the problem of trying to trade off deaths from these different sources, there are also costs to be considered pertaining to the possible deterioration in people's mental health as well as to possibilities such as increases in domestic violence that may also accompany prolonged periods of confinement and social isolation. turning away from these health-related trade-offs to broader socio-economic questions there is great uncertainty over the extent to which the socio-economic damage that may have been inflicted by a less controlled spread of the virus is matched or outweighed by the scale of the socio-economic costs associated with the measures being taken to contain it. part of this challenge can be understood as arising from tradeoffs between different sources of what higgs ( ) refers to as 'regime uncertainty'. on a hayekian view, one of the primary functions of social institutions such as private property rights and contract law is to provide a measure of certainty to decision-makers in an otherwise highly complex and uncertain world. agents operating in a market economy cannot be sure that their ex ante assessment of a decision situation will be confirmed ex postbut secure property rights do provide some degree of certainty that agents can retain the profits from decisions that turn out well and face the costs of those that turn out badly. regime uncertainty however arises precisely in contexts where the basis of social rules such as security of property itself becomes subject to uncertainty. in the context of pandemics regime uncertainty could arise from the failure of political authorities to act. an uncontrolled pandemic might lead to social dislocation and a break down in respect for the social norms and institutionssuch as respect for propertythat provide much of the glue sustaining social life. on the other hand, however, regime uncertainty might also arise from badly judged public policy interventions. there is a danger that political authorities may intervene in market relationships in unpredictable ways to a point that this destroys the confidence of people in the impartiality of the law. consider in this context the worker 'furlough schemes' that have been introduced in parts of europe and the united states. these schemes pay out a large proportion of the wage bill for employers in businesses that have been closed by lockdown policies. in a context where public health measures have effectively 'paused' the economic system there is a strong case for schemes of this kind. there is however also a danger that political pressures could be brought to bear on policymakers in ways that introduce significant arbitrariness in the operation of the schemes. the problem here is that any evidence of political favouritism may reduce the long term confidence of investors who in addition to navigating the inevitable uncertainties of business life may also fear having to anticipate potentially arbitrary interventions that favour some sectors over others. a different though related set of issues arise with the introduction of measures such as contact tracing schemes where there are concerns that personal data initially used to track those infected with the coronavirus might be used by political authorities as sources of information to be used against their opponents. away from these issues of regime uncertainty there are wider and equally complex challenges arising from attempts to manage the macro-economic consequences of the pandemic and the policies to control it. returning to the case of employment 'furloughs', while government spending may be necessary to support workers and employers in the immediate term there is also a danger that schemes of this kind may cause lasting economic damage if they are maintained for too long. if the effect of lock-down policies is to induce longer term changes in behaviour which may persist after the pandemic has passedsuch as a greater reliance on home working, reduced demand for office space or increasing popularity for online delivery in fields such as educationthen these changes may imply the need for significant economic restructuring and reallocations of labour and capital which an overly long furlough period would delay. such changes cannot occur instantaneously but must occur over time as entrepreneurs try to discover which combinations of labour and capital are best suited to the new circumstancesand while this process unfolds there will inevitably be 'unused capacity' as a proportion of labour and capital will be left unemployed or 'idle'. in these circumstances, keynesian inspired 'stimulus packages' and macro-economic interventions that seek to 'close the output gap' and to preserve the pre-pandemic pattern of employment by maintaining 'aggregate demand', are subject to the concerns raised by the hayekian critique of such measures in the context of financial or other economic crises (for a recent statement of these see white ) . more specifically, a focus on aggregate demand may obscure underlying shifts in the structure and distribution of demand across different sectors and hence the need for relative price adjustments to signal the need for changes in the structure of production. large scale public spending programmes that are not themselves subject to profit and loss signals risk delaying the necessary adjustments and indeed may lead to malinvestments. judging the timing for withdrawing furlough measures or macro-economic stimulus policies that seek to preserve pre-pandemic employment patterns will therefore be subject to a high level of both economic and political uncertainty and modelling efforts to time these decisions and their likely effects will involve a high degree of subjectivity and potential for significant error. complexity and pandemic response: avoiding systemic error and the scope for policy learning on a hayekian view, understanding society as a set of ordered though dynamic relationships rather than a static equilibrium means that justifying public policy responses to the complex dilemmas set out in the previous section does not require that these responses will be 'optimal' -precisely because the uncertainties and complexities at hand may preclude the identification of 'optimal solutions.' given the character of pandemics as public health problems involving potentially significant externalities, market solutions and those based on voluntary associations may not be viable so there are strong grounds for endorsing some form of public policy response (for example, ramanan and malani ) . nonetheless, the question that hayek's perspective might ask is whether there are any systemic mechanisms that may enable policy-makers to avoid large scale decision-making errors and to identify and act upon knowledge of relatively 'better' or 'worse' responses. turning first to the question of avoiding large scale error, it is important to recognise that as lindblom and other analysts of public administration have shown, states are not unitary hierarchies operating with a singular 'directive intelligence', but are better understood as networked structures where many different organisational 'brains' are linked together through bargaining and mutual adjustment (lindblom (lindblom , . unlike most market settings however, these are networked arrangements where competition is limited and where particular organisational nodes, or coalitions of actors may exercise a disproportionate or monopolistic influence over the network, as a whole (wagner (wagner , . in the specific case of pandemic response public health bodies and economic agencies such as treasuries and central banks are 'big players' within the social ecology that owing to their size and/or unique powers, have the potential to inflict large scale errors on the wider polity (koppl ) . it should be acknowledged here that expert epidemiological opinion and economic opinion over how to respond to the pandemic is not characterised by a consensus so in practice the decisions made by public health authorities, treasuries and politicians will reflect those of a dominant coalition in the jurisdictions concerned. within this context, an important institutional limitation on the scope for systemic error by 'big players' is that the world lacks an international administrative structure with the powers to enforce a 'global governance solution' to the pandemic. relative to what might be the case under the existing more fractured and decentralised governance regime a global governance approach might increase the likelihood of a large scale health or economic disaster should those who control public health bodies, treasuries and central banks err in their choice of policy measures. writing in the context of common pool resource management elinor ostrom makes a point that may be equally applicable to pandemic response. "where there is only a single governing authority, policy-makers have to experiment simultaneously with all the common pool resources within their jurisdiction with each policy change.... thus an experiment that is based on erroneous data about one key structural variable or one false assumption about how actors will react can lead to a very large disaster.... the important point is that if systems are relatively separable, allocating responsibility for experimenting with rules will not avoid failure but will drastically reduce the probability of immense failures for an entire region (ostrom : ) ." the current pattern of pandemic response does not rely heavily on global 'bigplayers' or a 'single governing authority'. rather, there is some level of decentralisation exercised largely through the powers of nation states and to a lesser extent within nation states where federal political systems are operative. it is perhaps significant in this regard that many countries started to introduce response measures, such as social distancing and travel restrictions, before international bodies such as the world health organisation made such recommendations, while others resisted implementing measures after the who declared a 'global pandemic'. similarly, it may be significant that in federal political systems such as the united states, some jurisdictions introduced lockdown measures before such recommendations were made by the federal centre for disease controlas did many private employers, while other states resisted these calls. nonetheless, it needs to be emphasised that while the relatively decentralised structures of international and in some cases national governance may reduce the risk of large-scale policy failure, the powers exercised by public health and economic agencies within nation states are such that the scope for error by 'big players' remains considerable. the problem here is that there a few mechanisms that enable an effective balance to be struck between the need to reduce the high transactions costs that may be associated with an excessively decentralised response to the virus with the systemic risks associated with over-centralisation. as coase ( ) points out, in market economies under normal circumstances the balance between centralisation and decentralisation is continually determined and re-determined through an ongoing process of competition embedded in profit and loss signals as firms of different sizes compete within one another and the process of mergers, demergers and new entrants unfolds. similarly, ostrom points to the importance of institutional diversity in addressing problems of scale where the existence of competing and overlapping decision centres whether private, communal or public allow multiple comparisons between governance regimes and knowledge of relative successes and failures in the supply and management of public goods to be spread through an experimental process (for example, ostrom ). this may be particularly important in the context of pandemic response because the management challenge at hand may not equate to a singular collective action problem. rather it may be that the spread of the virus requires responses to a range of multiple and more localised collective action problems the structure of which will vary according to geography, population density and the cultural characteristics and beliefs of the populations concerned. unfortunately, however, there may not be mechanisms to decipher what level of political and legislative decentralisation best matches these varying socio-environmental characteristics. this is not to say that there is no scope for determining such a balance. centralised trial and error and 'muddling through' by 'big-players' can lead to some changes in decision-making that reduce the scale of individual public decision failures. in both the united kingdom and the united states for example, the initial failure of national public health agencies to involve private and voluntary sector agents in the roll out of coronavirus testing appears to have been a key factor behind what was initially a miniscule number of completed tests. subsequent lobbying by private bodies and media commentary led to a reversal of this stance which was then followed by significant expansions in testing delivery (bbc news may , ). pointing to the success of centralised trial and error in such examples, however, may only serve to illustrate the broader weaknesses of such an approach when faced with more complex, multi-dimensional challenges. in the example just given, the focus of trial and error learning was confined to a very narrow 'technical' endi.e. how to increase the number of completed tests. problems of this kind may be more amenable to a centralised learning process because there is scope for 'before and after' type observations to discern the effect of particular interventions. learning of this kind may be much more problematic however, when the problems at hand are 'economic' in nature and involve many competing margins for adjustment that may only be revealed in a context where multiple governance models can coexist and where trial and error learning occurs in a more decentralised manner. with respect to broader matters of pandemic response therefore, such as the costs of decisions to lock down populations and businesses or to engage in economic policy measures to counteract the effects of such decisions, then the scope for institutional evolution may be very limited. owing to the 'emergency' nature of the pandemic, to all intents and purposes the inhabitants of nations may be 'stuck' with whatever institutional configurations they have. this may be a significant problem, because institutional configurations that work well under 'normal' circumstances may not be well adapted for pandemic response and the scope to avoid potentially large-scale decision failures associated with these may thus be limited. while the avoidance of large-scale policy failure is an important institutional consideration, from a hayekian view so too is the importance of generating counterfactuals to allow for policy-learning. as with the previous discussion this speaks to the value of a fractured governance regime based on nation states or varying degrees of federalism rather than a global governance approach. just as central economic planning deprives consumers and producers of the information generated by competitive experimentation in a market, so a global governance approach would deprive decision-makers of any sense of the possible opportunity costs associated with different responses to the virus. on this understanding, it may be a virtue of the predominantly nation-centric approach that while many countries have chosen to pursue 'lockdown' measures, others such as sweden have opted for a very different approach based on allowing a gradual spread of the virus through the population. the swedish approach may not be the 'right one' but without its existence or others like it there would be no comparative base against which to evaluate the policy measures adopted elsewhere, and potentially to learn from these. indeed, outside a context that allows for at least some level of decentralisation terms such as policy 'success' or 'failure' are meaningless. on a hayekian view, one cannot judge policy responses against a vision of an 'idealised' policy that might be implemented by omniscient agents because in conditions of complexity and uncertainty knowledge of such an ideal is elusive. the success or failure of a policy can only be determined through a process of endogenous comparisonand this requires a framework that allows for the generation of such comparisons. while the scope for counterfactuals generated by the fractured nature of international governance is important for policy learning, in the context of pandemic response it needs to be recognised that politicians and regulators in nation states and other levels of decisionmaking face a significant 'signal extraction problem' in deciphering what the results of various policy experiments may mean and whether any lessons can be applied elsewhere. as noted earlier, the prices, profits and losses generated in markets do not necessarily provide a transparent signal 'telling' decision-makers how to act. in market settings, however, the feedback received from consumer spending decisions on specific products is such that the profits/losses made relative to those of competitors, combined perhaps with knowledge from market research, provides a relatively clear signal that competitors should move in the direction of their rivals practices. relative to this situation the 'noise' around the different outcomes arising from various approaches to managing the coronavirus may be much more pronounced. thus, even if the swedish model produces satisfactory results from a swedish perspective it does not follow that the same results would or could be achieved with this model in countries such as the uk or france that have very different cultural traditions with which the policy would be interacting. similarly, it is hard to judge whether the apparent success of countries such as germany and switzerland in having a death rate far lower than that found in the uk follows from the characteristics of the populations infected by the disease, other factors such as housing conditions or the nature of urban form in these countries or, whether the lower death rates reflect instead the superiority of health care systems that make much greater use of private providers and market forces. if any of these factors are significant, then it is far from clear that any policy lesson from the pandemic could be implemented with sufficient speed, or indeed whether it could be implemented at all. the difficulty of interpreting policy results highlighted above is compounded by the question of what an appropriate time frame might be in which to make a comparative evaluation of the health and socio-economic effects of alternative policy measures. will countries that look to be performing relatively well with respect to death rates look to have chosen effective responses if a second and possibly larger wave of the virus arrives in the autumn/winter when the prevalence of some level of herd immunity might be desirable? with respect to economic evaluation, will countries that have adopted measures that have in the short term succeeded in reducing the spread of the virus by massively curtailing economic activity be able to sustain such measures if the virus remains a public health hazard over a number of years? given the complications that time frames introduce into the analysis it is hard to see how any policy lessons if they can be detected might be adopted with sufficient speed. moreover, it should be noted here that any short to medium term evaluations may change radically depending on whether an effective vaccine is found. lockdown measures that may have saved lives at great economic cost might still look to have been the best available response should a vaccine be developed relatively speedily. if a vaccine is not forthcoming, however, then those responses or non-responses that have not involved large scale economic contraction may turn out to be the most effective with respect to health and socio-economic objectives. finally, it should be emphasised that while the possible arrival of a vaccine may be affected by investments made by public and private agents, no matter how much private or public money is spent in this regard the discovery of a vaccine will to a significant degree lie beyond any authorities control. the conclusion that would seem to follow from this analysis is that the scope for both error avoidance and policy learning in the context of pandemic response is heavily constrained. the rationalistic models depicted in many public health and welfare economics accounts that conceptualise policy as a process wherein policymakers list the possible options they face, evaluate the options, and then select the option that generates the highest value are entirely inappropriate to this and indeed most other forms of government decision-making. in the specific case of pandemic response, the level of complexity and uncertainty may be so great that it is not possible for such calculations to be made. the data that would be needed to calculate in this manner either do not existat least not in 'concentrated or integrated form' (hayek : ) and, to the extent that there are institutional procedures that help to generate and communicate relevant data the relations between cause and effect and the micro-level connections that underlie such data are opaque. much of the response will therefore be based on centralised guesswork by 'big players' and while there may be no alternative other than for policymakers to rely on subjective interpretations of epidemiological and economic models to guide their decisions, these are fraught with the possibility of large scale error. now of course, scientific understanding in both the natural and social world is always highly imperfect and as new data emerge this may enable an evaluation of which models were more accurate in an ex post sense. the hayekian perspective presented here is not incompatible with this stance but it emphasises that should it be possible to explain retrospectively which policy responses have been more or less efficacious this will not necessarily inform policy-makers whether the same responses would work for a future such event. beyond perhaps some very basic and general lessons such as the importance of maintaining adaptable/flexible health care systems (which are desirable at all times), some (though not all) social distancing measures, and perhaps the wearing of face coverings it may be hard to discern what lessons should be learned from the current episode. this does not necessarily undermine the case for a public policy responsethough neither does it imply that voluntary measures are obviously inferior -but at the very least it suggests that expectations for publicly organised pandemic response should be modest. though it is not a conclusion that many citizens, politicians or social scientists may feel comfortable in accepting, the hayekian perspective suggests that policymakers may be operating in a fog of ignorance where insofar as tolerable responses are reached, these may to a large degree result from fortuitous accidents arising from a process of 'muddling through'. the analysis thus far has focussed on the challenge of discerning appropriate responses to the pandemic, but the hayekian perspective also points to important considerations for the post-pandemic world. if historical experience of crises whether wars or natural disasters are any guide to the post-pandemic political economy, then this period seems likely to be characterised by increasing calls for more government activism and control (on this see higgs ). on the one hand, these calls may be driven by demands for preventive measures to avoid anything like the present crisis happening again. on the other hand, states that have assumed significant control over resource allocation during the pandemic may be reluctant to relinquish their powers and may be encouraged to retain them by those who envisage significantly expanding the role of government in the economy. the concluding part of this paper briefly sets out why these forces should be questioned. while it is understandable that citizens and politicians should seek to avoid a repeat of current events, the hayekian perspective suggests that 'scientific management' of future risks is unlikely to be successful. that politicians and regulators were, prior to the current pandemic, overwhelmingly concerned with the threat of a 'climate emergency' and seem to have been taken aback by the new coronavirus, only serves to demonstrate that there is great uncertainty over which risks should be the focus of attention. neither are such oversights confined to governmental actorsas recently as january this year a variety of corporate bodies representing major business interests at the world economic forum were also citing climate change as the most important global risk, with the threat of infectious diseases rating much lower in the scale of priorities (world economic forum ). to point out these oversights is not of course, to say that climate change or other such risks should not be taken seriously. rather, it is to highlight the problem of assigning weightings to these risks in conditions of radical uncertainty. looking to the future, it is not the case that precautionary measures should be taken against all possible catastrophes because the accumulated costs of responding to every such possibility may be as great, or greater than that of the catastrophes to be avoided (on this see for example, martin and pindyck ) . it is, therefore, essential to choose from multiple conceivable disaster avoidance measures, which should be prioritised. should the focus of risk avoidance be on the possibility of further pandemics, climate change, the threat of nuclear terrorism, or bioterrorism? the problem here is that many of the parameters relevant to discerning these probabilities and the possible interactions between them are simply unknown. this challenge is surely significant in the context of known threats, but it is compounded by the possibility of unknown, unknowns. in conditions of radical uncertainty, it is not merely that actors may not know which possibility from a given set will occur but that the set itself may be unbounded and hence unknowable (knight ) . none of the above should be taken to imply that all scenario planning and spending based on such planning to account for future risks should be discarded. there is a limited, prudential case for private and public funding of measures to guard against future pandemics or other threats such as climate change. what the hayekian perspective suggests however, is that relatively little faith should be placed in these measures because given the nature of uncertainty, the next disaster to strike may well be one that has yet to be conceived. in the final analysis, 'what cannot be known, cannot be planned for' (hayek ) so there are grounds to be wary of granting authority to political agencies that justify their assumption of new powers on the basis of highly uncertain and perhaps unknowable likelihoods of future risks. moreover, insofar as authority is granted to public bodies rather than for example leaving these decisions to private insurance markets, then an important implication from the hayekian analysis is that this authority should be fractured and should where possible avoid reliance on global governance schemes. should the wrong risks be chosen by big players in a global governance structure then the negative consequences will be felt globally. in a more fractured regime on the other hand, unless all decision-making units perceive risks in the same way then the greater heterogeneity of decisions, may reduce though it may not eliminate, the possibility of system-wide failures of risk management. if there is reason to doubt the efficacy of centralised governance in strategic risk planning then the most effective and multipurpose 'insurance policy' that might account for the broadest range of future risks may be to sustain robust levels of economic growth. the resources generated by such growth may provide resilience against risks from multiple directions. in a context where states have recently assumed massive responsibilities for directing economic activity, however, many may argue that securing growth and the form it will take should be the responsibility of the state. there is a long line of thinking in the social democratic and progressive traditions, inspired by thinkers such as john dewey ( ) and john maynard keynes ( ) and reflected more recently by mariana mazzucato ( ) , which suggests that crisis situations require bold and radical experimentation by state agencies. on this view, only the state has the capacity to engage in the 'transformational' measures that might be required to 'jolt' society out of crises events. support for this worldview was evident prior to the current pandemic with the renewed enthusiasm across the political spectrum for various industrial policies, green 'new deals' and targeted protectionism, but post-pandemic these pressures may well grow in intensity (for example iipp ). on a hayekian view, however, these trends should be resisted. one reason for this is the danger of injecting a further source of 'regime uncertainty' into what may already be unstable political economic environments. in responding to the pandemic governments across many parts of the world have already engaged in socio-economic interventions of unprecedented scale, and as noted earlier both the socio-economic effects of these interventions and of measures to unwind them are subject to significant uncertainty and scope for systemic error. these policies have also followed in the wake of the massive interventions in financial markets by monetary authorities in the years since the crisis of . to embark on 'transformational' measures in such a context would be to generate an additional source of systemic risk and may further undermine the background foundations of competition and private contracting, in favour of a regime where discretionary political and bureaucratic power by 'big players' exercises a growing and unpredictable element in the calculations that private agents must make. the second and related reason to resist any post-pandemic expansion in governmental power is that this may recreate the severe knowledge problems that politicians have faced in choosing how to respond to the pandemic -on a near permanent basis. now, this is a bold conjecture, so it is important to be precise in specifying the content of the claim. part of the knowledge problem of pandemic response discussed in this paper is that the emergency nature of the situation severely limits the scope for policymakers to avoid large scale errors and to learn in a sufficiently timely manner. this is clearly not a characteristic that would be shared by measures such as industrial policies that can be implemented over a longer time scale and with greater scope for trial and error learning. nonetheless, from a hayekian perspective, the nature of this learning will be dominated by the 'muddling through' of 'big players' in a context that limits the generation of counterfactuals and which operates largely without guidance from competitive profit and loss signals. it is in this respect that 'transformational' public policies may replicate the knowledge poor environment that characterises the setting of pandemic response. compared to the decentralised experimentation that takes place in competitive markets the type of experimentation involved in state-centred schemes of economic 'transformation' lacks a systemic mechanism to decipher relatively better from relatively worse decisions. it is the systemic discipline provided by competition and profit and loss accounting that, while never guaranteeing successful investment or effective coordination, increases the chance of discovering beneficial investments and the shutting down of those that fail to add value. the greater pluralism of decisionmaking in markets compared to democratic or bureaucratic settings -the fact that in most markets multiple firms offer consumers different products and services -facilitates comparisons between alternatives. moreover, in these settings there is no need for agents to fully comprehend the reasons underlying their success or failure. the generation of profits and losses, combined with the existence of hard budget constraints, continually prods agents towards better decisions and away from relatively worse ones without needing to wait for complex factual and theoretical knowledge or the interpretation of data regarding cause-effect relationships. by contrast, state-dominated 'transformations' thwart the emergence of counterfactuals and knowledge of opportunity costs by limiting competition. as with pandemic response, the scale of the expenditures or the scope of the regulations concerned, and the lack of profit and loss signals attached to them, may block the communication of which 'bits' of expenditure or regulation are adding value. without profit and loss accounting policymakers must rely on centralised guesswork, or at best reliance on modelling procedures that if they ever do generate knowledge of cause-effect relationships may not do so with sufficient speed to shut down failing projects. this problem is compounded by the much softer budget constraints in the public sector that may enable policymakers to continue supporting ventures that fail to add value. even when particular firms or industries do make positive returns, if these have been supported by public funds then knowledge of the returns that might have been generated had tax payers been allowed to invest the capital elsewhere will be foregone. to the extent that 'transformational expenditures' work to promote growth, therefore, then as is the case with pandemic response, this may to large degree be the result of fortuitous accident. to illustrate the empirical relevance of this perspective, consider the arguments for industrial policy espoused recently by mazzucato ( ) . she maintains that because some of today's technological innovations had their origins in acts of government spending rather than private investments this demonstrates that 'directional planning' by the state can improve on market outcomes and that states should be bold in their willingness to spend on transformational projects. yet the evidence mazzucato cites simply fails to support these conclusions (see for example, mingardi ) . first, she ignores the opportunity costs of the massive cold war related military spending she claims was partly responsible for innovation and growth. while some of this expenditure may well have added value mazzucato offers no analysis of the multiple acts of military spending that failed to stimulate beneficial innovation, and which were not shut down. second, mazzucato fails to recognise that those elements of public spending that may have generated benefits were not 'planned'. at no point does she specify processes that demonstrate how 'directional intelligence' and 'strategic planning' led to specific instances of success. on the contrary, the success stories she refers tosuch as the development of various digital technologies, appear to have been unintended or accidental consequences emerging from essentially random spending in the defence sectorunintended consequences that were adapted to and seized upon by private agents operating in competitive markets guided by profit and loss signals (ibid). mazzucato is not alone in downplaying or ignoring opportunity costs and in failing to specify the processes that allow the 'directive intelligence' of the state to 'beat the market'. a similar problem besets the strands of political economy literature that favour targeted protectionism (for example chang ) . in this instance, the relative success of some countries that have pursued protectionist policies is touted as evidence in their favour without adequate discussion of the multiple examples where similar measures have failed to deliver success. moreover, where successes have occurred little if any account is given of the processes or mechanisms that could credibly connect the outcomes to specific acts of directive intelligence. it is simply assumed that the intervention in question was responsible for the outcome rather than arising despite the intervention, or as an accidental or unintended consequence from it (panagariya ). the hayekian perspective that has informed this paper does not claim that it is impossible for industrial policies, large public spending projects or targeted protectionism to generate positive results, any more than it claims that is impossible for governments to respond effectively to pandemics. as with pandemic response, what it suggests is that relative to markets there are few systemic mechanisms that enable decision-makers to learn whether their decisions add more, or less to public welfare than possible alternatives. from a hayekian perspective, what the dewey/keynes/ mazzucato case for state-based experimentation amounts to is the suggestion that if governments commit to spending enough public money on their favoured projects it would be remarkable if none of this expenditure did any good. yet, this position hardly amounts to an endorsement of the transformational potential of the state. that it may be necessary to rely on the 'muddling through' of public agencies when responding to a pandemic, does not imply continued deference to such agencies when the emergency has passed. open access this article is licensed under a creative commons attribution . international license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons licence, and indicate if changes were made. the images or other third party material in this article are included in the article's creative commons licence, unless indicated otherwise in a credit line to the material. if material is not included in the article's creative commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. to view a copy of this licence, visit http://creativecommons.org/licenses/by/ . /. discordant harmonies hayek's challenge bad samaritans the institutional structure of production calculation, complexity and planning, the socialist calculation debate once again the public and its problems uk suffers second highest death rate from coronavirus engineering the financial crisis on the impossibility of informationally efficient markets the road to serfdom the use of knowledge in society individualism and economic order the theory of complex phenomena the pretence of knowledge in hayek competition as a discovery procedure crisis and leviathan regime uncertainty: why the great depression lasted for so long and why prosperity returned after the war socialism against markets: a critique of two recent proposals radical uncertainty. london: the bridge street press risk, uncertainty and profit big players and the economic theory of expectations the intelligence of democracy: decision through mutual adjustment still muddling, not yet through econometric policy evaluation: a critique averting catastrophe: the strange economics of scylla and charybdis the entrepreneurial state a critique of mazzucato's entrepreneurial state understanding institutional diversity chaos, management and economics. london: institute of economic affairs the oxford handbook of health economics freedom ucl institute for innovation and public purpose (iipp) politics as a peculiar business macro-economics as systems theory austerian economics: does the vienna school favour fiscal deficit reduction even in a subpar economy the global risks report publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -oz eziy authors: munyikwa, michelle title: my covid‐ diary date: - - journal: anthropol today doi: . / - . sha: doc_id: cord_uid: oz eziy written in weekly instalments, michelle munyikwa's covid‐ diary reflects upon the experience of an unfolding pandemic from her dual role as a medical trainee and anthropologist living in the united states. her observations centre on everyday encounters with scenes or objects that reflect the growing crisis, from the absence of masks outside patient rooms to emergent forms of care through telemedicine. the diary follows the author as she experiences grief, ambivalence and disorientation in the first weeks of the pandemic. in this narrative, michelle munyikwa, an anthropologist and medical doctor-in-training, reflects on developments in the covid- pandemic in the form of a diary from philadelphia. how do you know when you are living through a crisis? crisis requires recognition -the point when a dawning awareness settles into an uneasy certainty. it may be the moment when you enter a store and find that the toilet paper or water you had intended to buy has gone -the empty shelf a signifier not only of what is to come, but of what has already happened. for me, that moment came when i could no longer easily don a mask to see patients. simultaneously reacting to and anticipating public panic, the hospital where i am a medical student had sequestered them in order to prevent theft and regulate use. in order to obtain one, you had to declare your intention to the unit secretary, who would look up the patient you were seeing and hand a mask to you only when she or he had verified you had a use for it. in an instant, the absent mask conveyed the impending change. over the last two weeks, the united states has undergone a transformation in its appreciation of the threat of covid- , the disease caused by the novel coronavirus sars-cov- . we have collectively struggled to make sense of the epidemic. scrolling social media feeds, one is inundated by reports from other countries, graphs and tables attempting to predict the future, and calls to understand the past of previous epidemics such that we might not repeat our errors. one is also bombarded by assertions that this is merely the flu, a media hoax or an example of the mass hysteria that the -hour news cycle can fuel. we live, and make choices, in an affectively saturated, information-rich (and often, truth-poor) environment. this uniquely st-century crisis is an object lesson in what it feels like to live through an emerging epidemic during what has often been described as an age of anxiety. how do we navigate unfolding uncertainty in a context where truth is wobbly and misinformation pervasive? i am a doctor-in-training and an anthropologist, currently completing clinical rotations, which means that i work in a different specialty every month. over my last few days in the hospital, i have watched the crisis unfold. hospitals are stripping down their staff to essential personnel, planning for the worst. teams that would normally see patients in large groups are paring down in the hopes of saving personal protective equipment (ppe), like masks and gowns, which are already in short supply. already, we have suspected cases in philadelphia, which was all but an eventuality, given the cases in new york. the question on everyone's mind is just how worried we should be. should we stock up for a doomsday scenario? or is this merely the flu, coupled with a politically inflected overreaction? i had been tracking the outbreak since its emergence in december. in january, i happened to be on a rotation in infectious diseases. my colleagues regarded the unfolding panic with an air of bemusement, more concerned about quotidian but deadly matters like the flu. still, i found myself sitting in on meetings where we discussed strategy with a growing sense of dread: how would we ensure that doctors out in the community felt adequately prepared? how many cases could we reasonably handle in our hospitals? could faster, more local tests be developed? this was before the virus reached other nations, let alone the united states, in significant numbers. throughout january and february, concern about an american covid- epidemic seemed tepid. most of my social networks were not talking about it, and i was only able to find communities talking about the virus in the hospital and online. this shifted around tuesday of last week, as more nations started to report cases and the case number went up substantially. soon, friends were contacting me about the virus, expressing their concern. the world health organization (who) recently announced that the worldwide death rate is . per cent, but all epidemiological evidence suggests that deaths are not evenly distributed. we also know that there is a high rate of nosocomial infection, with large quantities of healthcare workers getting infected. here in philadelphia, i am concerned by how our public health infrastructure and significant economic inequality will shape who is affected by the disease and who will die. philadelphia is often described as the poorest big city in the united states; . per cent of our resi-dents live below the federal poverty line, the highest rate among the nation's largest cities. while in a period of celebrated growth, the city is still recovering from the decline of manufacturing and its attendant public divestment and suburban flight, and the current landscape of the city is shaped by racialized class inequality and the assaults to public health that these dynamics produce. we also have a serious problem with hospitals; while there are many elite hospitals in philadelphia, that also means that we have a high concentration of complex, chronically ill patients, precisely those who will be at significant risk were covid- to become a significant public health problem here. like many american cities, we also lack a public hospital, and few ways to access care without concern for the massive, crushing bills that our specialized care foists upon patients. we will need to worry about the chronically ill and the fact that many american hospitals cannot handle a surge in patients at this time of year. in the best of times, patients can languish in the emergency department for hours while they wait for beds in increasingly crowded hospitals. in this first week, it feels as though there is nothing to do but wait, track the epidemic in other countries and hope the government pulls together a response. scepticism, anticipation, anxiety and disgust. other anthropologists have written extensively about the problems this epidemic lays bare, most notably the illumination of cleavages in our social fabric and the truly deadly implications of such divisions across the lines of race, class and national origin. this work has drawn attention to this pandemic's disregard for borders and the xenophobic and racist responses public domaina that contagion engenders. it highlights the ongoing negotiations around scientific expertise and practice and the dizzying array of projections and models that shape the daily response to the pandemic, particularly the infamous study from imperial college london. the situated labour of anthropologists has also drawn attention to the differential unfolding of this pandemic across different spaces and in local communities. as the sense of crisis transforms from a speculative possibility into a reality, i have also been struck by how overwhelming this is, in part because of a deluge of media that urges us to perform an affective reorientation to the present. affect theory offers us a language for examining the structures of feeling (williams [ ] ) that shape our response to the world. it helps us to understand the sense that we are living through history, situating our experience of the unfolding present (ahmed ; berlant ) . the lens of affect also helps us to understand how efforts to change the course of things necessarily entail attempts to manipulate such structures of feeling. as public opinion about covid- has oscillated between disgust, scepticism and anticipation, so too have the discursive strategies to combat each of these entrenched positions. as we navigate affectively shaped worlds, experts and laypeople alike engage in affective mitigation that tugs on the contours of the affective in order to transform individual sentiments and understanding. in other words, we attempt to transform one another's orientation to the epidemic in order to inform action that mitigates the crisis. scoffing on fox news, for example, politicians tug on concerns about immigrant invasions and the peril inherent in progressive politics to simultaneously maximize fear of the other and stoke confusion about the pandemic. affective mitigation also shapes our use of history, alternately stoking or taming a response through historical analogy: the flu, for example, or the sars (severe acute respiratory syndrome) and mers (middle east respiratory syndrome) events that never came to pass (arnett ). our response is characterized by a wild oscillation between scepticism and anticipation. scepticism has been attributed to members of the political right, whose news sources have projected the message that this epidemic is a fabrication of a panicked, over-anxious media. anticipation: the left, those plugged into the latest epidemiological models and projections. in the contemporary american moment, we can see that modes of preparation and prevention have failed to produce the desired effects. we find ourselves amidst a crisis that has been not only weeks, but decades in the making, with the sense that normative modes of prediction and anticipation have failed. we are daily negotiating emerging relations to expertise, authority and truth, which have always been at stake in the declaration and management of public health crises. this week, the picture is bleak. friends working in hospitals across america tell me of critical shortages of masks, sickened col-leagues and stolen equipment. due to concern about the possibility that medical students, perceived as young and healthy, could serve as asymptomatic vectors, schools around the country cancelled clinical rotations. i amalong with my classmates -at home, watching the pandemic from afar, as friends working in hospitals around the country supply me with a stream of updates. being away from the hospital, experiencing the pandemic through mediated resources, has shifted my sense of the crisis, making it at once more deeply felt and more distantly understood. doctors and advocates are organizing to halt detention, protect prisoners, feed and house the homeless and struggle to put together a social safety net hardy enough to withstand social distancing. we have seen beautiful acts of social solidarity, mutual aid and altruism. these acts balance the misery with hope, though they force us to question why they are necessary in the first place. so what does one do in the meantime? what are the stories one tells in dark times? how can a narrative of defeat enable a place for the living or envision an alternative future? (hartman ) we tell ourselves stories in order to live. (didion ) if i'm being honest, i suspect that there are no words that are adequate to the task of describing the slow-moving disaster we are living through. we often characterize this sensation as the ambiguous pleasure-paincuriosity of watching an accident unfold. i am reminded of a time when i was driving down the highway; as i approached, i saw an enormous plume of black smoke. whizzing by, it took a moment after i passed to realize that the smoke was emerging from an enormous fire in the engine of a car, which had been parked, strangely, in the opposite lane. only much later did i think to ask: what is a burning car doing on the highway? how did it come to be there? is everyone okay? there are harbingers of disaster around us: empty streets devoid of their usual traffic; a space on the shelf where your favourite bread normally dwells; cars piled full, mysteriously, with toilet paper; realizing just how often you have come to rely on small conveniences; a bizarre longing for hugs from strangers or quotidian, banal interactions. things are different. over the last week, nations around the world have locked down. the borders of the united states have closed; expatriates around the world have been encouraged to return home. here in philadelphia, we have continued to prepare for the worst. medical students, disconnected from clinical rotations, have organized to coordinate food deliveries and babysitting services for frontline providers. others have started collecting ppe, which is scarce, while still more gather to support local businesses that are suffering in the absence of foot traffic. there are efforts to aid the many people who are without housing and food, and campaigns to transform empty hotels into housing gain traction. letters circulate, some with thousands of signatures, imploring the ice (us immigration and customs enforcement) to decrease enforcement and the state to release prisoners. in moments like this, we turn to history (jones ). many of the articles circulated across my social media feeds encourage us to understand the past to orient our present response. we go clawing into the archive for lessons we wish we had already learned, and attempt to learn them too quickly, all at once. i may have read more about the - influenza pandemic in the last week than ever before in my life, and i am a student of medicine, history and anthropology. and yet, every day, another journalist uncovers these lessons with their moral: take this seriously. never forget. we, too, are vulnerable. perhaps one reason we tell ourselves these stories is because they convince us that we will, in fact, survive this. we hope that this means we might surmount the growing threat, for if others have lived to tell the tale of our devastating past, then perhaps there is hope for our future. but there is nothing to say that we are permanent presences on this earth, no reason to believe that we, unlike all other species, are not susceptible to extinction. that is not to say that the end of humanity is likely (however closely environmental collapse hovers, threatening to complete the job). it is, however, to suggest that the world that we have known up to this moment, no longer exists. returning to that normal ceased to be one of the possibilities many steps ago in this unfolding chain. its possibility was stifled most proximally by failures of government, but perhaps even more by the choices we made, entrenching rapacious capitalism, greed and immoral incompetence. we might have seen the proverbial smoke from a distance when we elected generations of leaders more invested in enriching the elite than strengthening the poor. when i am thinking about history, politics and its use, i often return to the poetic prose of saidiya hartman, whose historical imagination seeks to uncover but not redeem the past. she knows, as we all do, that we change nothing simply by noticing what has happened. after all, 'we all know better. it is much too late for the accounts of death to prevent other deaths; and it is much too early for such scenes of death to halt other crimes' (hartman ) . saidiya hartman was speaking, of course, of the not-quite-past of slavery and her repeated visits to the archive of that atrocity, saturated as it is with the tales of the dead whose loss we will never recuperate. as this pandemic visits devastation unevenly upon poor communities, people of colour and immigrants, the body count of racial capitalism mounts and we are left to account for it. if it is the case that we are always hanging in the balance between presence and absence when recounting the injustices of history, then what do we hope for with respect to telling these tales in the present? i want to believe that revisiting the lives that were unnecessarily lost years ago during the flu pandemic will spur us to do differently. i want to believe that being haunted by the archive of bodies piled in the streets might shift our perspective, such that we will successfully avoid what is to come. i want to think that knowing that this is all wrong may keep us from continuing to do it. i also wonder if by the time it occurs to us to marshal the evidence of the past, it is already too late. i fear that we are like i was: blinking into realization the image of a burning car on the road, long after i could have done anything about it. an image of destruction seared into my consciousness, for nought. when is it time to dream of another country or to embrace other strangers as allies or to make an opening, an overture, where there is none? when is it clear that the old life is over, a new one has begun, and there is no looking back? (hartman ) we're over , cases here in the united states, as many states have placed shelter in place orders and the economy has come to a grinding halt. hundreds of thousands have lost their jobs and the threat of economic disaster looms. politicians and citizens alike worry that our response is an overreaction. donald trump, concerned about stock prices, has been at the centre of a push to reopen the economy and loosen restrictions on those communities where disease prevalence is lower or allow lower-risk citizens to work. rallying around the cry that 'the cure cannot be worse than the disease', people desperate for economic relief suggest that we go back to the way things were, allowing the epidemic to run its course. perhaps, they suggest, we can merely isolate the 'at risk', allowing the rest of the country to go to work. this, despite the increasingly dire situation in new york and other cities around the country. this week has also seen the spread of covid- throughout africa, with a reported , + cases across the continent, likely an underestimate. i am now worried about the spread in these countries, which include my home nation of zimbabwe, where rumours surrounding our first death suggest that we are woefully underprepared for the task of fighting this pandemic. i worry about my extended family, who remain there, and what they will do if one of them becomes sick. while the conditions in countries with fewer resources will be dire, an abundance of wealth does not seem likely to prevent horrible outcomes in the united states, where we are quickly developing the worst epidemic in the industrialized world. in new york, massachusetts and michigan, medical students are being graduated early to help with the crisis. philadelphia-area doctors warn of an impending ventilator shortage, and the institution prepares guidance for the worst: rationing and the reality of preventable death. we are not there yet in philadelphia, but the anticipation permeates the entire health system. every day, hospital leadership sends new projections, attempting to calculate the impact of this pandemic -do we have enough beds? enough clinicians? enough gloves? -each time assuring us that we are ready. however, some projections are more terrifying than others, suggesting a flow of hundreds of patients a day into a hospital with just barely enough space for those patients we anticipate. my best friend, an emergency doctor, texts me news every day. 'intubated a -year-old woman today'; ' intubations in one shift, there's normally only one'; 'we're down to the donated ppe'. the hospital is a ghost town, with elective surgeries cancelled and other patients avoiding care for fear of contracting the virus. we are nowhere near the peak yet, so the hospital is the emptiest it has been in years. this feels like the calm before the storm. stories of young healthcare workers dying of respiratory failure circulate in my medical social circles. my mother, also a doctor, worries about the impending shortage at her hospital. it becomes clear that healthcare providers will be among those who bear the brunt of this, to say nothing of the poorly paid essential workers across many industries. hospitals around the country begin trialling hydroxychloroquine as prophylaxis, and as donald trump and scientists alike promote the possibility of the drug, we hope they are right. the debate around the drug reveals deep uncertainty about the proper course of treatment, bringing up important concerns about ethics, patient harm and medical responsibility. march- april: time compression, pandemic fatigue and the new normal as i am editing this, the united states has nearly , cases and over , deaths. the disease is now the largest cause of death in the country. my experience of the pandemic has transformed from a frenzy into a slow unfolding, each day simultaneously more terrible and mundane than the last. as we round out one month of sheltering in place, my experience of each day becomes more and more rapid, as i blink and days have passed. at the same time, it feels as if this pandemic has lasted a thousand lifetimes. this is in part because the nature of my work has changed so much, from intense labour in the hospital to digitally mediated interactions on video chatting platforms. i spend most of my day in front of a screen, like many of my peers, completing both school and volunteer work digitally. across the healthcare system, students and providers alike have been repurposed. psychiatrists and gynaecologists act as frontline providers in areas of the hospital where they usually do not work, while others pivot to telemedicine. as medical students, we have been forbidden from interacting with patients, but we continue to volunteer. some students participate in grocery delivery programmes, picking up an extra bag of food on their weekly trips and dropping them off for patients in need. others staff our tele-icu (intensive care unit), watching over intubated patients with a camera from a safe distance a mile away from the hospital and adjusting vent settings from afar -more a scene from science fiction than real life. i have signed up to a project attempting to address the social needs of patients in our massive healthcare system. a team of medical students and social workers has assembled to intervene in the social fallout from this disease, from unstable housing to domestic violence, health insurance woes to food insecurity. based on a referral from a doctor, the team calls to perform a screening: do you feel safe at home? do you have enough to eat? are you worried about paying your rent? my first call was to a woman who had lost her job and her insurance due to covid- related layoffs, just in time to contract the disease. or it should have been; i called her all morning, but her phone had already been disconnected. other patients, covid-positive and acting as caregivers for family members who were now at risk, needed help with food, making money, surviving. who will get my groceries if i can't leave my house and everyone who lives with me might also be contagious? can someone come to take care of my elderly grandmother who has dementia? can i go back to work? these conversations force athens airport, february : the covid- virus hell in italy is just beginning. i arrived in greece in early february before the chaos started; today, i am heading to kavála, the field base for my comparative project on the protest movements against the trans adriatic pipeline in greece and southern italy. out of habit, twice, perhaps three times, i say 'grazie' as i navigate airport procedures. it's enough to elicit worried looks and whispered comments among the bystanders. a sudden and uncomfortable feeling grips me. the next day, greece records its first covid- case, 'imported' from italy. ever since that announcement, an invisible wall has arisen between me and my greek neighbours. soon, it also affects my fieldwork. 'i don't speak to italians' i overhear while sitting in the car of one of my informants, as he calls a fellow activist and introduces me. next day, immediately after he posts a picture of us on facebook, the warnings fly: 'be careful! you're not even wearing masks!' though followed by smiley emojis, such 'joking' remarks are anything but. then there's the street vendor's inquisitive and concerned look when he places my accent, my neighbour's 'teasing' gesture of shielding himself from me by forming an x with his arms, and the pharmacist who suddenly steps back and denies me the much-requested disinfectant hand gel as it is destined 'only for local customers' -while grunting. in response, i speak as little as possible to avoid making mistakes in greek and to 'hide' my nationality. this hits me particularly hard as i'm usually warmly received in greece. i'm a southern italian who grew up in salento (puglia), where a variety of greek -'griko' -is still spoken. on this shore of the shared sea, griko tends to elicit admiration and self-celebratory comments about the durability of hellenism. suddenly i'm no longer called i ellinìda tis kato italias ('the greek from southern italy'). the distinction between purity and danger fills into symbolic -and physical -boundary maintenance, as mary douglas observed in her book purity and danger. abruptly, i'm simply italian and italian means 'polluted and polluting' -the enemy. meanwhile, gallows humour circulates via memes: 'not finding a seat on the bus? no problem. cough, say buongiorno a tutti -"good morning everyone [in italian]" -and sit wherever you want!' (facebook, february) . then again, irony can be a weapon as much as self-irony can be a defence: 'i'd say that if we keep coughing, we'll end up re-conquering the roman empire' (facebook, march) . however, as things in italy take a catastrophic turn, and as infections climb in greece, public expressions of concern and closeness towards italians follow. when the covid- nightmare started in matryx / pixabay.com questions of reciprocity, solidarity and obligation. every patient chart, every documented encounter, is an unflattering look into our devastatingly leaky social safety net. the virus continues to unmask the consequences of our late capitalist social order, which differentially exposes communities to death (taylor ) . in philadelphia, these are apparent in statistics collected by our public health officials, which reveal that it is easiest to get tested in our affluent neighbourhoods, despite a larger number of cases in poorer communities. to get a test outside of a hospital, you must wait in a drive-through line, leaving those without cars to scramble for other means of testing. meanwhile, my peers are still collecting ppe. my partner and i, not generally prone to crafting, pull out a long-neglected set of sewing machines to produce masks for ourselves and friends as the recommendations shift and community use of masks is encouraged. we draw on his expertise as an engineer to design and fabricate alternatives to n surgical masks, anticipating a day when our doctor and nurse friends will go to work to find protection absent. i'm reminded of a message my mother sent me early in the pandemic, as critical shortages of ppe became apparent and her daily work in the hospital revealed an overwhelming lack of preparedness. the message said simply: 'no gloves. no eyewear. no ppe. who's [this] s**thole country now?' it has become increasingly difficult to gain the distance from this pandemic that would allow me to make sense of it. at the same time, there has been a veritable boom in social theory since the pandemic began. every day, advertisements for webinars and digital lectures fill my inbox. calls for papers have already pivoted around this latest crisis, and i expect to see dozens of covid- -related panels at the next big conference. a prominent social theorist has already penned a book about the pandemic. i feel self-conscious about my dulled capacity to distance, to theorize, to make sense of something which is overwhelming and surreal. it is true that as anthropologists, we are precisely in the business of making sense of what is going on around us. perhaps it is a need for control, the will to know, that impels us to attempt to tame what ultimately can't be tamed. or it is worth noting that the federal poverty line is only one of the many ways of characterizing widespread precarity in the city of philadelphia, though it is most often cited. . here, i am thinking especially of some of the compelling contributions to somatosphere's covid- forum, particularly adia benton's elaboration of the racialized geography of blame also see: macgregor it is worth noting that it is not always the case that medical students are healthy and that this elides those who are living with chronic illness or are otherwise at risk. . i heard rumours before i started to see formal reporting, like nyoka ( ). also, a later account describes the family's perspective it is worth noting that the use of invasive ventilation for covid- is contested terrain, with considerable disagreement about when to intubate, the ethics of early intubation and the potential harm to patients of overly aggressive care affective economies years ago, another epidemic terrorized the city. the boston globe border promiscuity, illicit intimacies, and origin stories: or what contagion's bookends tell us about new infectious diseases and a racialized geography of blame. somatosphere (blog) cruel optimism the white album: essays venus in two acts history in a crisis -lessons for covid- novelty and uncertainty: social science contributions to a response to covid- covid- -struck family speaks of ordeal. the standard (blog) coronavirus: zimbabwean broadcaster zororo makamba died 'alone and scared'. bbc news counting coronavirus: delivering diagnostic certainty in a global emergency reality has endorsed bernie sanders. the new yorker the pew charitable trusts . philadelphia : state of the city keywords: a vocabulary of culture and society mona lisa protecting her environment from infection by covid- key: cord- -yxl a u authors: yadav, uday narayan; rayamajhee, binod; mistry, sabuj kanti; parsekar, shradha s.; mishra, shyam kumar title: a syndemic perspective on the management of non-communicable diseases amid the covid- pandemic in low- and middle-income countries date: - - journal: front public health doi: . /fpubh. . sha: doc_id: cord_uid: yxl a u the global coronavirus disease (covid- ) pandemic has greatly affected the lives of people living with non-communicable diseases (plwncds). the health of plwncds worsens when synergistic epidemics or “syndemics” occur due to the interaction between socioecological and biological factors, resulting in adverse outcomes. these interactions can affect the physical, emotional, and social well-being of plwncds. in this paper, we discuss the effects of the covid- syndemic on plwncds, particularly how it has exposed them to ncd risk factors and disrupted essential public health services. we conclude by reflecting on strategies and policies that deal with the covid- syndemic among plwncds in low- and middle-income countries. the entire world has been affected by the coronavirus disease (covid- ) pandemic caused by severe acute respiratory syndrome coronavirus (sars-cov- ), which has led to thousands of deaths each day. the covid- pandemic is one of the greatest public health calamities since world war ii and, despite best efforts, has been challenging to control ( ) . recognizing the rapid spread of covid- and the threats it poses, the world health organization (who) declared it an international public health emergency on january . this allowed countries to exert maximum effort and allot resources to limit the rapid transmission of sars-cov- . despite the low fatality rate and government efforts, people are living in uncertainty and fear, as there is no vaccine for covid- . covid- has weakened healthcare systems and economies, emptied open spaces, and filled hospitals ( ). the pandemic has separated many people from their family, friends, and workstations and has severely disrupted modern life. to mitigate this unprecedented pandemic, physical, and social distancing along with nationwide lockdowns and restrictions, have been implemented for the past few months in several countries ( ) . covid- is creating a profound impact on all parts of the community, including the physical and mental health of the public. the growing pandemic is augmenting existing mental health problems ( ), including loneliness, anxiety, paranoia, panic, depression, and hoarding, with long-term psychosocial impacts ( ) . social distancing, stress, and fear are the main factors behind these psychological problems, leading to a global increase in suicides ( ) . self-isolation and quarantine measures disproportionately affect people, especially older adults, migrants, laborers, refugees, people with chronic diseases, and marginalized and vulnerable populations ( ) . the covid- cataclysm has become the most serious problem worldwide, and its consequences have left no one untouched ( ) . the effects of a pandemic intensify due to its diverse nexus of intertwined biological and socioecological factors. this diverse nexus was coined a "syndemic" by medical anthropologist merrill singer in the s to describe the relationship between hiv/aids, substance use, and violence ( ) . a "syndemic" is defined as a synergistic interaction between socioecological and biological factors (figure ) , resulting in adverse health outcomes ( ) . the covid- pandemic has escalated into a syndemic due to several driving factors, such as overcrowding, loneliness, uncertainty, poor nutrition, and lack of access to health services; consequently, depression, suicide, domestic violence, and psychiatric illnesses have significantly increased ( ) . social determinants of health, such as poverty, social inequality, social stigma, and the environment where people live and work, greatly affect the intensity of the syndemic ( ) . additionally, xenophobia, ostracism, and racism are reported in many places. generally, people living in countries with higher social and economic inequalities have more coexisting non-communicable diseases (ncds) and are therefore more vulnerable to the syndemic impact of covid- . we argue that, for people living with ncds (plwncds), covid- is considered a syndemic-a synergistic pandemic that interacts with various pre-existing medical conditions and social, ecological, and political factors and exacerbates existing ncds. studies have reported higher proportions of frailty ( , ) , malnutrition ( ) , psychological problems ( ) , and coinfections, including antimicrobial resistance pathogens, among plwncds ( ) in low-and middle-income countries (lmics). ncds have been recognized as a key risk factor for covid- patients ( ); however, vulnerability to catching sars-cov- increases in the presence of other pre-existing factors. prevailing inequalities in the social determinants of health, including poor social, economic, and environmental conditions (e.g., social behavioral factors, physical environment, social marginalization, and supportive government policies; figure ) , have an impact on various aspects of life such as health, wellness, and financial status. for example, plwncds with comorbidities and higher social and economic deprivation are less likely to access health services during this pandemic. this results in worse health outcomes, such as poor quality of life, mortality, suicide ( , , ) , and increased hospitalization due to poor self-management ( , ) . during the covid- pandemic, plwncds from disadvantaged groups are less likely to receive healthcare compared to plwncds from socially advantaged groups. the disadvantaged population (particularly individuals from low socioeconomic conditions) have a high chance of falling sick ( ) , dying, and experiencing catastrophe. furthermore, socioeconomically deprived individuals who were dependent on daily wages have lost their jobs; this has pushed them further into poverty and poor health ( ) . a synergistic association between the severity of covid- and ncds was reported in china ( ) , which shows the negative effects of this syndemic. this suggests the urgency of a paradigm shift from a single-condition approach to a syndemic approach to tackle the current and future impacts of pandemics among plwncds in lmics. the pandemic is unlikely to end soon, and it is difficult to predict the arrival of the next pandemic, but the syndemic will certainly continue in lmics. in this paper, we discuss covid- among plwncds, exposure to ncd risk factors, and the disruption of essential public health services for ncds. it considers literature on this topic, following a search on google and pubmed to identify publications that considered populations with covid- and ncds. we conclude by reflecting on strategies and policies that deal with the covid- syndemic among plwncds in lmics. the global covid- pandemic has resulted in , , cases in countries and territories around the world and two international conveyances, with , fatalities as of july , ( ) . covid- cases are decreasing in many countries, but the opposite is true in lmics such as india and brazil. many seriously ill covid- patients had multiple comorbidities ( ) ; for instance, . % of those who died in hospitals in italy had comorbidities. the case fatality rate increases with age, especially in countries with a high percentage of older adults. the comorbidities were mostly ncds, such as hypertension, diabetes, cardiovascular disease, and chronic lung disease, especially chronic obstructive pulmonary disease ( , ) . the prevalence of comorbidities is higher among covid- patients compared to the general population who are not infected with coronavirus; for instance, % of the covid- patients in india and % of the covid- patients in china had comorbidities ( ) . the prevalence of comorbidities is expected to be similar in other lmics where the prevalence of ncds is high; however, there is a lack of literature on this topic from lmics. the health condition is more severe and mortality is higher among older adults with ncds ( ) and people with bacterial infections caused by antibiotic resistant pathogens, such as superinfections ( ) . ncds cause around % of deaths worldwide and are the primary cause of death in southeast asia among those aged to years ( ) . lmics have a large ncd burden; in some lmics, such as india, there is an early onset of ncds, thereby increasing the risk of covid- among young individuals ( ) . the addition of covid- to pre-existing ncds results in increased morbidity and mortality ( ). ncds can exhibit several characteristics with infectious manifestations, including parameters like a proinflammatory state and compromised innate immune response ( ) . this condition is further worsened because many plwncds have been deprived of treatment for their diseases since the onset of the covid- pandemic. preventive methods for this pandemic, such as physical/social distancing, lockdowns, self-isolation, and quarantine, may increase exposure to ncd risk factors, such as the increased use of tobacco products and alcohol as coping strategies ( ), increased reliance on unhealthy processed foods and barriers to physical activities ( ), which lead to weight gain ( ) . these factors increase the incidence of ncds and related mortality ( ) . moreover, financial crises and the lack of social contact might enhance the burden of anxiety and depression among plwncds. the economic slowdown predisposes people to malnourishment, which further increases the risk of infectious diseases ( ) . since the covid- pandemic began, prevention and treatment services around the globe have been severely impaired, and the disruption is worse in lmics. the results from a survey conducted by the who in countries ( ) revealed that plwncds were not able to access services for their health conditions, which made their lives even more difficult during this crisis. more than % of the surveyed countries reported partially or completely impaired services for ncds and related complications, particularly after the covid- trajectory changed from sporadic to community transmission. this is supported by the stories and pictures of plwncds captured in the news and social media of lmics, where people were unable to access basic medicines or care (particularly in areas with protracted lockdowns) for their chronic conditions. this problem is exacerbated by the reassignment of health staff from ncd facilities to covid- in all surveyed countries ( ) and the disruption of medical supplies and diagnostics as a result of nationwide lockdowns ( ) . for example, in india, some outpatient services have been temporarily closed, and hospitals have been converted into designated covid- care homes ( ) . this arrangement will have a further adverse effect on access to healthcare services and treatment adherence by plwncds. similar painful stories regarding plwncds have been reported in the news and social media platforms of many lmics, such as nepal, bangladesh, brazil, pakistan, ghana, and iran. governments in various countries have made efforts to focus on ncd services while tackling covid- , but only % of low-income countries have done so compared to % of highincome countries (hics) ( ) . this shows the global impact of covid- on the disruption of healthcare services for ncds. the interaction of covid- with other biological and social factors appears to increase the risk of complications, worsen health outcomes, and intensify the burden on healthcare professionals and health systems. on the one hand, there is a global rush to respond to covid- by increasing intensive care unit beds, installing ventilators, extending lockdowns, and adopting other containment measures. on the other hand, there is a disruption of routine health services, such as screening and diagnosis, supplies of essential medicines, and access to health service providers and support services. the covid- syndemic and other conditions have not only posed a challenge to health systems but have also exposed gaps within the healthcare delivery system in many hics (e.g., italy, spain, and the united states) and lmics (e.g., pakistan, india, nepal, bangladesh, mexico, and brazil). due to covid- , the priorities of health services have shifted; as a result, the progress required to achieve sustainable development goals is threatened ( ) . in the subsequent section, we describe strategies that are essential to overcoming and managing the syndemic condition. we divide these strategies into four broad categories (figure ) . the sudden lockdowns imposed by authorities caused panic in many countries. to avoid such situations, there should be a supply of basic needs, such as groceries and sanitary items. home delivery is an important strategy that can be implemented with the help of volunteers, especially for older adults and people with disabilities. misinformation and fake news on social media platforms are fuelling this panic. people should follow information from trusted sources such as government guidelines. additionally, authorities should disseminate the appropriate information to the general public in a timely manner. plwncds should be encouraged to monitor their symptoms, practice self-care, adhere to medication, seek healthcare services including counseling, practice physical distancing, wash their hands with soap, and wear masks. providing information on self-management behavior changes for ncds and covid- through sms and social media platforms is an important step. in this situation, health literacy (having the necessary information and skills to manage health) and activation (motivation and the ability to take action) can play an important role ( , ) in self-management ( ) of conditions among plwncds in lmics. promoting both the health literacy and empowerment of plwncds would enable patients to navigate health services, use technology to contact healthcare providers, develop problemsolving skills, and adhere to healthy lifestyle behaviors ( ) . healthy lifestyle activities must be promoted, such as eating nutritious foods and engaging in physical and wellness activities. individuals should have access to open spaces and be allowed to exercise at scheduled times while maintaining all precautionary measures, and plwncds could be given timecards for physical activity. the expansion of existing community health worker (chw) roles can be crucial to the self-management of ncds and covid- and to delivering basic services among plwncds during this extreme health workforce shortage, particularly in lmics with weak health systems. recovered covid- patients can also spread information on health and self-care management and help debunk the myths and lessen the stigma related to covid- . although countries (mostly developed ones) are trying to provide care through telemedicine, it is still in the formative stage. while telemedicine is a boon for developed nations when it comes to the diagnosis, treatment, self-management support, and surveillance of conditions, lmics with fragile health systems often struggle to launch telemedicine services. using digital healthcare platforms in the health system ( ) would greatly increase access to the services and information required by plwncds. this would, in turn, improve the management of chronic conditions and provide relief from emotional turmoil and stress ( ) . in fragmented health systems, chws can promote coordinated care by improving access to care and providing navigation support ( ) . chws can also carry out surveillance of risk factors and implement preventive and self-management strategies for plwncds, who are at high risk of covid- . potential chw roles in covid- management include community engagement, community sensitization, promoting isolation and quarantine, and performing contact tracing ( , ) . despite their huge potential in pandemic management, chws have been underutilized in the covid- pandemic, especially in countries where chws are available, such as bangladesh, india, and nepal. however, before involving chws in the covid- response, they must be provided with appropriate training and adequate personal protective equipment ( ) . while responding to covid- , the governments of lmics have failed to ensure health services for plwncds because of the blanket lockdown approach. insufficient attention has been paid to the unnoticed drivers of covid- -related mortality among plwncds. while governments enforce mitigating measures during this pandemic, they also need to develop strategies to map national-level data on ncd patients, as such data do not exist in many lmics. there is also a need to prepare care pathways for severely ill plwncds by engaging private and public healthcare institutions and delivering basic health services (e.g., screening, medical checkups, and pharmacy services) at the community level via mobile primary healthcare vans. in many lmics, out-ofpocket (oop) health expenditures are high and will rise further during the covid- pandemic ( ) . to reduce the burden of oop due to covid- , authorities should make provisions for free diagnostic and treatment facilities and focus on equitable, accessible, and affordable healthcare. these measures will prevent the deterioration of health among plwncds amid the covid- pandemic. a situational analysis of available resources and resource planning must be carried out. supportive packages should be provided to vulnerable groups, such as older adults, people with disabilities, and the unemployed. involving the private sector, civil society, academia, non-governmental, and governmental organizations through intersectoral coordination and teamwork would address the situation with a syndemic lens. hics can help lmics in setting up / helpline support to provide essential information and guidance related to the availability of services and contact in case of emergency. authorities should also consider imposing different levels of restrictions by mapping the incidence and active cases of covid- , such as by designating red, yellow, and green zones. providing an uninterrupted supply of funds is a major challenge for lmics during the covid- pandemic. international organizations, philanthropists, and industrialists through their corporate social responsibility should come forward to help countries facing a financial crisis. highquality research and data on effective interventions to prevent the spread of infection and treatment of active cases are also needed. moreover, authorities should impose taxes on items such as sweetened beverages, tobacco, and alcohol to subsidize prices or lower taxes for nutritious food items and ease movement restrictions for food production, processing, and delivery, which will indirectly lessen the use of unhealthy products. ncds increase vulnerability to covid- , and covid- increases ncd-related risk factors. the covid- pandemic may not be the last to threaten the global community. therefore, there is a need to understand the drivers of the syndemic and design safety nets. the health system must address not just one or some medical problems but ensure holistic care for those that need it, particularly plwncds. care for plwncds, who are at most risk of covid- , must be included in national response frameworks and plans so that the government can protect citizens' health and well-being during the current covid- pandemic and for similar crises in the future, otherwise, the interaction of covid- and ncds will result in disastrous effects that could be difficult to handle given the preexisting stress on healthcare delivery systems and impede progress in achieving the sustainable development goals. the governments of lmics are crippled by a lack of technical and financial resources to address this overwhelming problem. tackling the covid- syndemic is a matter of urgency. funding bodies that advocate for and want to be part of a change in lmics need to invest in prevention and health promotion programs that could address issues within a syndemic framework ( ). government agencies positioned to develop and implement policies must understand that asking citizens to sacrifice without providing appropriate support packages will not work. rather than gearing up for a vertical approach, governments, concerned stakeholders, development partners, and civil society must build synergy across healthcare platforms to tackle this crisis through a holistic approach. if they fail to do so, the post-pandemic era could experience a great divide in health equity that could be much worse than ever before, undoing the progress made in developing healthcare policies and strengthening healthcare systems and infrastructure. evidenceguided decisions must be made to overcome this formidable crisis in lmics. the original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s. association between climate variables and global transmission of sars-cov- the mental health consequences of covid- and physical distancing: the need for prevention and early intervention multidisciplinary research priorities for the covid- pandemic: a call for action for mental health science psychological interventions for people affected by the covid- epidemic covid -suicides: a global psychological pandemic sars control and psychological effects of quarantine a dose of drugs, a touch of violence, a case of aids: conceptualizing the sava syndemic the covid- pandemic and health inequalities the burden of covid- in people living with hiv: a syndemic perspective the potential impact of covid- on psychosis: a rapid review of contemporary epidemic and pandemic research psychosocial impact of covid- prevalence and determinants of frailty in the absence of disability among older population: a cross sectional study from rural communities in nepal prevalence of frailty and prefrailty among community-dwelling older adults in low-income and middle-income countries: a systematic review and metaanalysis transforming the food system to fight non-communicable diseases sociodemographic characteristics, lifestyle factors, multi-morbid conditions and depressive symptoms among nepalese older adults convergence of noncommunicable and infectious diseases in low-and middle-income countries does comorbidity increase the risk of patients with covid- : evidence from meta-analysis suicide risk and prevention during the covid- pandemic covid- suicides in pakistan, dying off not covid- fear but poverty?-the forthcoming economic challenges for a developing country medication management and adherence during the covid- pandemic: perspectives and experiences from low-and middle-income countries diabetes self-management amid covid- pandemic non-communicable disease management in vulnerable patients during covid- epidemiology working group for ncip epidemic response, chinese center for disease control and prevention covid- coronavirus pandemic covid- and non-communicable diseases prevention and control of non-communicable diseases in the covid- response novel coronavirus pandemic may worsen existing global noncommunicable disease crisis older people are at highest risk from covid- , but all must act to prevent community spread copenhegan: world health organisation reginal office for europe coronavirus disease superinfections, and antimicrobial development: what can we expect? covid- pandemic and challenges for socioeconomic issues, healthcare and national health programs in india world heart federeation. covid and cvd: world heart federation inflammatory responses and inflammation-associated diseases in organs prevalence, severity and mortality associated with copd and smoking in patients with covid- : a rapid systematic review and metaanalysis covid- significantly impacts health services for noncommunicable diseases: world health organisation impact of covid- pandemic on health system & sustainable development goal self-management of non-communicable diseases in low-and middle-income countries: a scoping review how health literacy and patient activation play their own unique role in self-management of chronic obstructive pulmonary disease (copd)? covid- : health literacy is an underestimated problem how to fight an infodemic global preparedness against covid- : we must leverage the power of digital health a patient navigator intervention to reduce hospital readmissions among high-risk safety-net patients: a randomized controlled trial community health workers for pandemic response: a rapid evidence synthesis prioritising the role of community health workers in the covid- response healthcare providers on the frontlines: a qualitative investigation of the social and emotional impact of delivering health services during sierra leone's ebola epidemic uny conceived the idea. uny, br, and sky drafted the manuscript. sp and skm provided the significant inputs.all authors approved the final version of manuscript. authors acknowledge the assistance of scientia prof. mark fort harris (executive director, centre for primary health care and equity, unsw, sydney) for providing expertise inputs in this piece. we greatly acknowledge mr. bhupendra lama from central department of microbiology, tribhuvan university, nepal for contribution in design of figure . key: cord- -ptqzvsdw authors: bansal, priya; bingemann, theresa a.; greenhawt, matthew; mosnaim, giselle; nanda, anil; oppenheimer, john; sharma, hemant; stukus, david; shaker, marcus title: clinician wellness during the covid- pandemic: extraordinary times and unusual challenges for the allergist/immunologist date: - - journal: j allergy clin immunol pract doi: . /j.jaip. . . sha: doc_id: cord_uid: ptqzvsdw the global spread of coronavirus disease (covid- ) has caused sudden and dramatic societal changes. the allergy/immunology community has quickly responded by mobilizing practice adjustments and embracing new paradigms of care to protect patients and staff from severe acute respiratory syndrome coronavirus exposure. social distancing is key to slowing contagion but adds to complexity of care and increases isolation and anxiety. uncertainty exists across a new covid- reality, and clinician well-being may be an underappreciated priority. wellness incorporates mental, physical, and spiritual health to protect against burnout, which impairs both coping and caregiving abilities. understanding the stressors that covid- is placing on clinicians can assist in recognizing what is needed to return to a point of wellness. clinicians can leverage easily accessible tools, including the strength-focused and meaning-oriented approach to resilience and transformation approach, wellness apps, mindfulness, and gratitude. realizing early warning signs of anxiety, depression, substance abuse, and posttraumatic stress disorder is important to access safe and confidential resources. implementing wellness strategies can improve flexibility, resilience, and outlook. historical parallels demonstrate that perseverance is as inevitable as pandemics and that we need not navigate this unprecedented time alone. despite global awareness of severe acute respiratory syndrome coronavirus (sars-cov- ) since december , coronavirus disease (covid- ) has become a global pandemic that caught the world unprepared in the early months of . it is now clear that sars-cov- is highly contagious, capable of causing severe pneumonia, acute respiratory distress syndrome, and death, particularly in vulnerable populations such as older adults and those with chronic medical conditions, such as cardiovascular disease, diabetes, respiratory disease, hypertension, and malignancy. , strategies are being implemented to "flatten the curve" of the pandemic to preserve capacity and not outpace the availability of precious health care resources. the current supply of personal protective equipment (ppe), intensive care unit beds, and ventilators may not be able to keep up with projected demands. , this nightmare scenario has been experienced internationally, with countries such as italy and spain overwhelmed, and looming concerns that this may occur in certain parts of the united states. for example, the percentage of symptomatic patients with covid- requiring intensive care unit care has been between % and %. demonstrating the rapidity of spread, the first recognized case of the pandemic in italy appears to have been a young man admitted in the lombardy region with atypical pneumonia on february , , and health care resources were overwhelmed within a few weeks. the timeline of the italian experience illustrates a major reason for covid- einduced anxiety around the world ( figure ). attempts to mitigate the impact of covid- have disrupted core aspects of society. social distancing is central to efforts to control the pandemic. however, to be effective, social distancing must be rapidly and universally adopted across a society, which sadly has occurred to varying degrees across the globe. risk perception is likely a significant lever on the degree to which populations embrace a social distancing approach. during a pandemic, both medical experts and governmental authorities require a high degree of accurate knowledge and trust to execute effective policies. tragically, there has been a vacuum of unified societal knowledge and trust throughout this pandemic. for example, a recent cross-sectional survey of the general public in the united states and the united kingdom found that, of us and uk adults, . % and . %, respectively, believed sars-cov- to be a bioterrorist weapon. when asked between february and march , , % of us and % of uk respondents thought the number of people who would die of covid- in their respective country would be fewer than persons. in response to the medical community, local government, and concerned citizen frustrations with currently available policies and demands for detailed accurate information, our knowledge of covid- is rapidly expanding. unfortunately, the spread of the virus also continues to rapidly increase, with the johns hopkins coronavirus resource center listing , total confirmed cases and , deaths as of . the case-fatality rate (cfr) of covid- is being scrutinized. early data from china estimated the cfr to be . % of symptomatic patients presenting for medical evaluation, with rates as high as % in vulnerable elderly populations. , in patients with critical illness, cfr has been reported to be as high as %. although cfrs may actually be much lower when mild and asymptomatic cases are considered, the italian cfr is . % (figure ). much of these data are hindered by lack of knowledge regarding the total number of cases. health care worker fatalities were noted early and continue to rise in the united states. , in an early report from china, . % of cases occurred in health care workers, and . % of these were classified as severe, with a cfr of . %. , in italy, more than physicians have died of covid- as of march , . despite this rising tide of illness, there is room for hope. although the pace of change demanded in our response to covid- is disorienting, it is important to note that, globally, , patients with confirmed cases have recovered as of march , . there is a growing awareness of the need to protect health care workers from sars-cov- infection. however, in addition to an urgent need to prevent infections related to patient care, there is also a growing need to address broader aspects of wellness among health care workers. the covid- pandemic has created sudden stressors across many domains of our lives that become apparent when viewed through different lenses, including the theory of knowledge ("you don't know what you don't know," information vs misinformation), appreciation of system capacity (both health and economic), understanding warranted and unwarranted variation, and human psychology. to survive covid- and its aftermath requires care directed toward our patients as well as ourselves and our families. although tending to personal wellness is always important, it has become even more crucial during these extraordinary times. understanding risks and consequences of burnout magnified by covid- ; identifying historical parallels of the pandemic while appreciating new challenges of social media; leveraging new technologies to care for patients, staff, colleagues, and ourselves while managing responsibilities at home; and using wellness resources at the american academy of allergy, asthma & immunology, the american college of allergy, asthma & immunology, the canadian society of allergy and clinical immunology, and state physician health programs as needed can help each of us navigate uncharted waters together, even while practicing social distancing. clinician wellness involves a number of factors including stress and burnout. these factors can impact negatively on patient care and lead to increased medical errors, malpractice risk, and early retirement. greater clinician stress may lead to higher rates of drug and alcohol addiction, divorce, and suicide. clinicians are more likely to have burnout symptoms than the general us workforce and are more likely to be dissatisfied with work-life balance. even before this pandemic, burnout rates among us physicians overall were estimated to be at around %. female physicians have higher rates of burnout. a figure . the coronavirus pandemic in italy. reproduced from livingston and bucher. j allergy clin immunol pract volume -, numberrecent survey revealed a burnout rate of % among us allergy and immunology physicians in the united ststes. higher rates of burnout may be associated with certain clinician attributes, including belief in service and sense of duty, perfectionism, and personal internalization of patient outcomes. day-to-day office-based stressors include clerical burden (eg, electronic medical record documentation), excessive nonclinical and clinical workloads, and practice inefficiencies. , although medical practice demands may contribute to burnout most significantly, personal and family stressors may add additional pressures. the current covid- pandemic has disrupted the health care system worldwide. a prolonged response to the pandemic will lead to additional stress for clinicians and their support staff and further permeate throughout the health care system. consequences of burnout are shown in figure . in the setting of a global pandemic it is normal to be frightened for one's own personal safety (and potential mortality), particularly with data emerging about airborne and fomite transmission, exposure risk from asymptomatic carriers, limited testing, and well-publicized issues regarding conflicting advice about what level of ppe is necessary or available. finding evidenced-based ppe recommendations is difficult; however, over a -week span, the centers for disease control and prevention downgraded the covid- risk from airborne to droplet (outside of an aerosol-generating procedure). changing recommendations have been a cause of anxiety for clinicians, compounded by employment termination concerns in some instances for wearing precautionary ppe. in a crisis, physicians may feel their medical oaths tested when confronted with ethical dilemmas that are intrinsic in rationed care due to equipment shortage or institutional policy of universal do not resuscitate status for covid- epositive patients. as the psychological stressors are evolving day by day, noneintensive care unit/emergency department physicians may be redeployed to less familiar (and critical) clinical areas. questions regarding the ethics of providing care outside of one's scope of practice, and the associated liability, are evolving. the american medical association released an update to its code of medical ethics on march , , specifically addressing these issues in opinion . and opinions . . and . . . these may help provide an ethical backdrop on how to approach such situations, though this still may not do much to leverage preserving one's own wellness and ability to persevere in such circumstances. in new york state, governor cuomo has introduced legislation limiting any malpractice liability to physicians practicing outside of their scope, except in cases of gross negligence (which remains nebulously defined). however, outside of new york, such liability protection is unclear and may cause justifiable concern. many hospitals and health care systems are recognizing the stress and strain on their clinicians. some have made counselors available and have been offering free access to online tools for meditation and relaxation. a plethora of such online tools exist, and sometimes a quick breather may serve as a way to recharge and regain some wellness, at least momentarily, when under stress. multiple businesses have recognized the heroic efforts of the medical community and are offering free services-sometimes just a free coffee and donut may be enough to show that one's efforts are being appreciated. the real concern is that in stressful times, there is a temptation to self-medicate or resort to less productive and more self-harmful solutions-drugs and alcohol in particular, which may increase the risk for suicide and domestic violence. physicians at baseline work high-stress jobs and are already prone toward issues, including marital problems, and substance abuse, that may become magnified in this particular crisis. change is difficult, and during covid- change has been rapid and associated with both uncertainty and with varying degrees of loss. guilt and grieving are also major considerations for our wellness. elizabeth kubler ross defined stages of grieving: denial, anger, bargaining, sadness, and acceptance. more recently, these stages have been updated to disbelief, yearning, anger, depression, and acceptance, with the depression peaking at approximately months postloss, and acceptance not until months postloss (figure ). some of these stages may be more identifiable, though loss in the midst of this crisis may be harder to define, and may vary considerably on the basis of personal experiences. when the disease was abroad, there may have been denial/disbelief as to the severity and yearning for limited effects on our society. as testing kits and ppe have been deficient, anger at the government and administration is being felt. physicians may find themselves bargaining for any way out as they are called to make life or death decisions. undoubtedly, how we practice allergy has already changed, and in addition to health risks physicians face the looming reality of economic loss and associated anxiety. as covid- becomes pervasive around us, there is a need to appreciate the potential for our own countertransference in considering our own personal and familial needs versus the needs of our patients and colleagues. this may be more difficult for some than for others. naturally, we will all likely experience some degree of guilt and grieving for a number of potential reasons. however, as we may all cycle through these aforementioned stages, there is the final stage of acceptance as we find our way forward. remind yourself this is a normal, healthy part of wellness, and things will hopefully change for the better. historically, one can draw an analogy to tuberculosis (tb). in the th century, tuberculosis was responsible for in deaths. like covid- , tb mortality also significantly impacted physicians. it was not until that dr edward l. trudeau discovered the tb bacterium that caused the disease, and in , when he opened the first sanatorium at saranac lake, ny, patients sat outdoors on the wide sun porches to take the "fresh air cure" and receive state-of-the art management of that era. unfortunately, fresh air did not cure tb, and it was not until simple public health social distancing that tb declined sharply in the s and s. the societal struggle with tb demonstrates several parallels with the covid- pandemic. foremost is the clear and present danger posed by an infectious agent for which curative therapy is currently unavailable and for which only symptomatic management can be provided. this creates challenges to both health and wellness, because fear, anxiety, and frustration can threaten to overtake a rational approach to managing the situation of the moment. a second parallel with tb is the temptation to embrace unproven therapies. for example, in the early s, interventions used to treat tb included "collapse therapies," in which physicians performed an elective pneumothorax, with the rationale for this procedure being to deprive the aerobic mycobacteria of oxygen, in an attempt to kill them. this procedure involved injecting oxygen or nitrogen into the chest cavity with increasing pressure until the lung collapsed. however, this collapse was not permanent, and it required repeating the procedure every few weeks. it has been estimated that more than , patients underwent this procedure in the years after this technique was developed, despite the fact that there were no rigorous studies conducted at the time to confirm its effectiveness. it was not until that albert schatz discovered streptomycin, which initially proved successful as tb monotherapy, but, over time, combination therapy was required. similarly, trials are actively ongoing to treat covid- , including new antivirals, the use of hydroxychloroquine with azithromycin, antieil- agents, and the development of vaccines to name just a few. we can learn from our past and realize that, even in the darkest times, there will be a bright future someday. as physicians our calling is to care for those in need. ultimately, validation of effective treatments will lead to greater physician empowerment. in the meantime, wellness tools and strategies can help to manage our fears and anxiety while we practice medicine with the tools we have in the moment. with billions of active users across various social media platforms such as facebook, twitter, and instagram, the manner in which we communicate and receive information has fundamentally changed. we have unprecedented instant access to information on a scale the world has never seen before. before the introduction of facebook in , including during the early stages of the internet, we relied on a limited number of vetted resources for information, namely major media outlets or the daily newspaper. in , however, we live in the age of "fakenews," and internet users need savviness and knowledge to identify factual information and ignore misinformation. the opinions of celebrities, accounts with large numbers of followers, and online influencers are artificially equated with those of actual medical experts. this constant stream of information (and misinformation) can be overwhelming for anyone, let alone clinicians already facing stressful challenges in their professional and personal lives. before covid- , internet addiction was already recognized as a growing problem contributing to social anxiety, attention deficit/hyperactivity disorder, and other aspects of wellness, which may only intensify during these trying times that are constantly reminding us of the stakes we face. during a global pandemic, social media utilization can be beneficial for updates of important information related to current precautions and best practices and provide connections to needed resources. it can also help to connect physicians with loved ones across the globe who are having similar fears and are socially distanced. there are simple, yet effective, strategies that merit review for all medical professionals who use social media in order to maximize benefit and mitigate risk (table i) . more information on managing social media during the pandemic is included in this article's online repository at www.jaciinpractice.org. there is a relative paucity of data and unknown prevalence regarding physician depression. systematic reviews of medical students and residents showed depression prevalence at % and %, respectively. , , a medscape survey of approximately , physicians revealed a rate of depression of % to %. unfortunately, clinicians likely have incentive to conceal symptoms of depression for fear of putting hospital privileges or medical licenses in peril. thus, the prevalence is likely to be underestimated. suicide rates for physicians are estimated to be higher than for the general public, and higher in female versus male physicians. , physicians are more likely than nonphysicians to succeed in suicide attempts. the medscape survey revealed that % to % of physicians had suicidal ideations and % to % had attempted suicide. risk factors for suicide include depression, being single, not having children, substance abuse, access to drugs, and associated stress and burnout. , this has unfortunately also affected our field of allergy and immunology. although the exact prevalence of alcohol and drug addiction among clinicians is not known, physicians are not immune to substance abuse or exempt from personal tragedy of the current opioid epidemic. unfortunately, stigma remains among clinicians reporting depression, substance abuse, addiction, and those attempting suicide. with the increasing stresses and uncertainty regarding covid- , the clinician may be at an even greater risk. in fact, more than % of health care workers in china during this current pandemic reported psychological distress including insomnia, anxiety, and depression. addressing these issues with a mental health care professional may be needed, and it is important to understand warning signs of depression, anxiety, posttraumatic stress disorder, alcoholism, and substance abuse. besides detection, understanding how to access safe and confidential resources to get help is key. in fact, most states have covid- is adding to nonpandemic stresses of allergy and immunology physicians in practice, regardless of the clinical setting. for example, allergic conditions and covid- symptoms have some overlap. lack of information regarding covid- testing also can increase anxiety of both clinician and patient. allergy and immunology services such as biologic therapy and immunoglobulin replacement therapy are medically necessary and keep patients out of the emergency department and hospital, potentially saving resources for the care of the covid- patient. however, recent guidance has suggested approaches such as telehealth when service reductions are required. appropriate triage during the pandemic allows for effective social distancing; however, economic realities of service adjustments are inescapable, and the consequences of managing reduced revenue will create challenges to staff retention and maintaining a practice. federal stimulus legislation may provide some relief of economic pressures during the pandemic. advice to improve resilience during this time is outlined in table ii . [ ] [ ] [ ] [ ] more information on wellness at work and cost-effectiveness of physician wellness is included in this article's online repository at www.jaci-inpractice.org. during the pandemic, school closures add a layer of complexity to finding a work-life balance. in addition, there are different family units, including single physician parent households, with various custody arrangements. parents of older children are coping with a unique set of stressors trying to help them navigate an uncertain landscape. high-schoolers currently applying to college are concerned because standardized college admissions tests and advanced placement examinations are being canceled, and they are unsure as to how this will affect their college admissions process. many college students are anxious about whether their summer internships will be canceled, whether graduate degree programs will understand and accept that many colleges and universities are only providing pass/fail grades this semester, and how they will complete courses that depend on face-to-face interactions, which range from the performing arts to chemistry labs. many seniors are grieving the loss of graduation ceremonies or are worried that their postcollege full-time job offers will be rescinded. across the spectrum of pediatrics, children with special needs require increased supervision, and parents may need to work in shifts to provide one-on-one attention. all these factors translate to added stress on clinicians and patients alike. working from home while supervising clinical and/or research activities is challenging and requires new workflows. in this setting, clinicians must balance electronic medical record communication and respond to urgent and routine messages. first, it is important to establish frequent, consistent video and/ or phone communication with staff and assign bite-sized tasks. breaking larger assignments into smaller concrete blocks can prevent overwhelming colleagues, increase empowerment, and nurture a sense of accomplishment and satisfaction. second, it is important to realize that everyone is adjusting to new pandemic realities. additional advice on working with kids at home is depicted in table iii . [ ] [ ] [ ] coping and wellness tools now more than ever, health care providers need to practice self-care. coping with rapidly changing recommendations can become overwhelming, while stress and anxiety can become insidious bedfellows escalating a cycle of tension both at home and at work. paradoxically, at a time when social distance is strongly encouraged, we can all find ourselves more interwoven with one another in a common struggle to persevere against an unimaginable global challenge. while we face the defining moment of our time, resilience, compassion, and serenity may be great assets. postpone nonessential patient visits and procedures create a practice task force for addressing and implementing changes train staff on implemented changes collaborate with other allergy and immunology colleagues review practice finances and plan for income changes overcommunicate with patients j allergy clin immunol pract volume -, number -many of us are filled with a mix of complicated emotions at this time. strategies that have worked for us in the past, like getting together in person with friends, family, or colleagues, are not available while practicing social distancing. this loss of personal connectivity leads to further struggles for many. at this time, we need to look for ways to connect virtually and ensure we are attending to clinician wellness. this pandemic is unlike anything most have experienced before; however, we are able to draw from our collective experience with previous tragedies and struggles, including september , , hurricane katrina, severe acute respiratory syndrome, and h n flu epidemics. the strength-focused and meaning-oriented approach to resilience and transformation, which is typically used by social workers after a crisis to help survivors develop resilience to get through and transform and grow in the process, can be used today in our present crisis. the framework uses mind, body, and spirit approaches to foster awareness, develop strength, and discover meaning. it addresses this through "emphasizing growth through pain" by focusing on what personal strengths may develop through the experience. it "teaches the mind-body-spirit connection" in recognizing that by taking care of our physical needs we can boost our mood and mental strength. furthermore, "developing an appreciation of nature," we are encouraged to appreciate the small things in life, appreciate our own life, and those of loved ones around us. by "facilitating cognitive reappraisal" we can develop new perspectives and remember resilient experiences during other crisis and past successes. "nourishing social support" allows us to improve and enhance our development and resilience while simultaneously having a sense of acceptance and connectedness while learning to recognize and appreciate the support offered from those around us. the final tenet of this approach includes "promoting the compassionate helper principle" in which we learn from traumatic experiences by extending compassion to ourselves and others. even in the best of times, health care professionals often do not seek assistance when they are experiencing stress, burnout, depression, and suicidality because of concerns regarding confidentiality, cost, time, licensing and career concerns, and stigma. pospos et al selected and evaluated several web-based resources according to the american psychiatric association "app evaluation framework" to be used as a starting point to address depression, stress, and suicidal ideation, noting that ideal interventions would be effective, "convenient, accessible, affordable, and confidential" and ideally would be used in conjunction with direct professional care. the resources chosen would inocorporate the treatment approaches used to address burnout among health care professionals: meditation, breath work, relaxation techniques, mindfulness training, cognitive-behavioral therapy, and suicide prevention. the applications it recommended include breath relax, headspace, moodgym, stress gym, stay alive, and virtual hope box. of note, the only one that has been assessed for efficacy in health care professionals was moodgym, which was shown to reduce suicidal ideation among medical interns. mindfulness-based therapy platforms can allow for a sense of community, connectedness, and a platform to share successes and promote resilience. additional wellness resources are outlined in table iv. at this time of social distancing it is important to maintain a schedule and your morning routine even if you do not have to leave the house. enjoy nature while maintaining social distances. take the time to connect with others virtually if you are feeling lonely via phone, email, and video platforms. when feeling overwhelmed by the number of people in the house, take some time for yourself in another room or go outside. use the resources mentioned in this article to get support digitally. if this does not suffice, please reach out for professional help. supports may be in place from local universities, the american medical association, and state and local professional societies. limiting your news and social media consumption that you find upsetting may also reduce stress. avoid using alcohol and other drugs to deal with your emotions-instead, use the skills that have enabled you to get through difficult situations in the past. practicing compassion with yourself and others is also helpful. initiating a gratitude practice has been shown to improve a sense of connection, quality, and amount of sleep and has improved well-being. this can be achieved through a gratitude journal in which you write daily entries about someone or something you are grateful for or listing good things daily, which has been shown to reduce symptoms of depression and improve well-being. engaging in a religious or spirituality practice has been associated with improved coping, strategies of acceptance, and less burnout in internal medicine and pediatric interns. finally, allowing time to debrief, meditate, or discuss challenging situations and grief can be helpful to prevent burnout. governmental and health care agencies, institutions, and professional societies can help by sharing and continually updating information and resources. communication that is concise, clear, transparent, timely, and thoughtful will help build a sense of control in health care providers. data from the h n pandemic revealed that sufficiency of information was associated with reduced worry. freeing providers from administrative tasks will allow peak performance for longer periods of time. leadership should encourage all providers to strive to live the tenets of physician wellness. conclusions "world war v" is clearly upon us, with all the attendant anxieties and disruptions one might imagine when fighting an invisible enemy on home turf. we are faced with a new reality that has changed our culture, implicit assumptions, and basic underpinnings of our daily work. mandated "stay-at-home" orders and self-quarantine social norms seem to have arrived overnight in some areas of the country, but a patchwork of inconsistency adds to a dizzying assessment of risk-and if we as medical experts find ourselves occasionally off balance, it is certain that our patients likely feel the same. clinician wellness can be an overlooked and marginalized aspect of our lives. in the daily hustle, self-care may often be a last priority as we continue to practice in a field of self-sacrifice and service to others. but if we do not realize it in the beginning, we will certainly realize it in the end that without self-care we will have nothing left to offer to anyone. the caregiver must take care of himself or herself if they want to do a good job taking care of others. covid- has arrived, and life is different. as we realize that we are in a seminal moment, that future generations may refer to "pre-covid" and "post-covid," we must also pause to reflect, to breathe, and to care for ourselves and our loved ones. this covid- pandemic will pass, and although sars-cov- may see a slow burn with seasonal encores in the next several years, the practice of allergy and immunology will continue to provide critical services, even as our infrastructure is temporarily reorganized during social distancing. as a specialty, allergy and immunology will continue to lead, and as our community comes together, we will persevere. take care of yourself. during these stressful times, medical professionals can use social media to benefit themselves as well as their patients. in addition to the centers for disease control and prevention, trusted medical organizations such as the american academy of allergy, asthma & immunology (aaaai), the national institute of allergy and infectious diseases, and the world health organization can be accessed for resources to help clinicians prepare but can also be used to curate and share information with others as well. clinicians should embrace the trusted relationships they have developed with their own patients as well as the desire of the general public and media to hear from experts. e those already active on social media can serve as a valuable resource to provide perspective, general information, and address misinformation. one example of conflicting reports from mainstream media that have circulated on social media during the covid- pandemic involves confusion regarding the risk of using corticosteroids during active infection, a topic that is pertinent to patients with asthma. in this example, professionals can use their role on social media to provide anticipatory guidance to patients with asthma by reinforcing the need to maintain inhaled corticosteroid controller medications to try and prevent exacerbations, and highlighting the importance of understanding when and how to start treatment should symptoms occur. in an online world filled with misinformation and fear mongering, clinicians can use their social media presence to promote preparedness, encourage positive behavior change, and spread accurate information instead of panic. e medical professionals who are not active on social media can still use these platforms to better understand the common questions or points of confusion being discussed. this can aid anticipatory guidance with individual patients who may not raise these concerns on their own during clinical encounters, or provide resources on practice web sites addressing frequently asked questions. it is also important for clinicians to recognize how their use of social media may impact their well-being. in addition, clinicians can seek out social media groups that provide professional and emotional support. e ,e there are countless examples of online groups that provide comfort and collegiality, which can be extremely important for those in community-based outpatient practices who may have limited interactions with colleagues and those who may have temporarily closed their practices because of the current social distancing guidelines. the physicians moms group on facebook is one of the more prominent examples, where more than , women share personal and professional stories with one another in a closed forum. now more than ever, it is important for all of us to be mindful of our social media habits, recognize when our online interactions encroach upon our well-being, and use social media in a positive manner. telehealth can minimize risk and promote safety, and newly developed aaaai resources exist to help the clinician get started. e -e creating a practice task force to assess recommendations from local, state, and federal governments, as well as medical societies, can be helpful at the onset. e obtaining ppe is essential, although challenging in the current rationed environment. in addition, collaborating with other local allergists and immunologists can facilitate idea exchange and highlight the reality that, even at a social distance, we are not alone. e engaging the health care team at the beginning of a workday will help to prevent many stressful situations and also help to lay a scaffold to quickly resolve problems that do arise. e at this time, social distancing is critical to mitigating covid- , as is routine and increased office and equipment cleaning. e from the business standpoint, cross-training employees and preparing for increased absenteeism is necessary. e reviewing practice finances including cash flow and having a plan for decreased income due to potentially less numbers of patients and procedures is necessary, and it is hoped that recent federal legislation will provide some respite. e specifically, the coronavirus aid, relief, and economic security (cares) act of , passed in the senate with bipartisan support on march , , may provide more than $ trillion in total relief and $ billion in support for small businesses. e it is important to remember that some allergists and immunologists may temporarily suspend in-office operations or provide care almost exclusively by telehealth, depending on various individual factors, including personal and professional. preparing for this possibility is advisable. e regarding patient care, overcommunication is preferred. e postponing nonessential appointments or procedures is recommended and necessary for social distancing to be effective; however, patient-specific decisions should still be determined by the individual clinician's clinical judgment. e ,e patients may be more or less concerned about the covid- pandemic than their clinicians, and may be receiving information (and misinformation) from various sources. reinforcing the concept of social distancing as well as the importance of adequate sleep, exercise (with social distance in mind), and diet is sound advice. discussing the ways in which the practice is adapting care in the covid- pandemic era includes active communication methods such as health insurance portability and accountability act secure text messaging and email software; social media updates via platforms such as facebook, twitter, and instagram; consistently updating the practice website; and placing wellmarked educational signage. these interventions can help alleviate patient concerns. of note, avoidance of stigmatizing groups of people due to suspected or actual infection is fundamental. e ,e the effect of clinician wellness and wellness programs may be life-changing and life-saving. unfortunately, even outside of a pandemic the risk of burnout and consequences of ignoring aspects of wellness are underappreciated and often undervalued. although cost-effectiveness analyses can be a useful analytical tool to understand whether financial trade-offs are worth gains in quality of life, the health and economic consequences of ignoring personal wellness in the practice of medicine have not been well studied. in the medscape physician compensation report, primary care providers earned an average of $ k per year and average annual specialist compensation was $ k. e in this report of , respondents across þ specialties, annual compensation for allergy and immunology was $ k. although physicians spent an average of to hours in patient care, % of respondents spent hours or more on paperwork and administration per week. e this represents a dramatic increase from , where % of physicians spent about to hours on paperwork. e although most felt rewarded by either patient relationships, problem solving, or making the world a better place, % of physicians reported that nothing about their job was rewarding. e seventy-three percent of allergy and immunology physicians would choose medicine again, with % of those preferring to remain in their chosen field of practice. e to illustrate the potential cost-effectiveness of clinician wellness, we constructed a simple markov model evaluating a cohort of physicians earning the mean salary for allergy and immunology, working hours per week in direct patient care, with hours per week spent on administrative tasks. e although the health state utility of wellness is unknown, we explored plausible disutility (eg, negative health detriment from an action) ranges of % to % compared with an idealized practice of worklife balance over a -year model horizon, starting practice at age years. future costs and utilities were uniformly discounted at % per annum, with all-cause age-adjusted mortality incorporated into the model and -year cycle length. e , e when considering medical practice, cost-effective care is defined as care costing less than $ , /quality-adjusted lifeyear (qaly), with a qaly measured by the relative trade-off between a perfect year of wellness and challenges associated with burnout resulting from inattention to personal wellness. e in this wellness model, a % equal reduction in health state utility and compensation demonstrated cost-effectiveness of wellness of $ , per qaly, a % disutilty with % compensation reduction cost $ , per qaly, whereas a % health disutility with % compensation reduction cost $ , per qaly. at a % relative disutility of wellness, a % reduction in compensation cost $ , per qaly. findings from the physician cost-effectiveness wellness model confirmed that attention to wellness can be a cost-effective prospect, even if requiring a reduction in compensation. the north american allergy and immunology professional societies-the aaaai, the american college of allergy, asthma & immunology, and the canadian society of allergy and clinical immunology-are providing real-time resources to help on-the-ground clinicians navigate the covid- pandemic. although challenges to allergists/immunologists vary contextually by private, hospital, or academic practice, societal leadership and collegial support is crucial. these organizations are uniquely positioned to provide resources for contingency planning, advocacy, education, and research priorities during these challenging times. recently, the aaaai, the american college of allergy, asthma & immunology, and the canadian society of allergy and clinical immunology endorsed a framework for covid- contingency planning in the allergy and immunology clinics in addition to distributing and/or promoting videos, podcasts, social media outreach, community forums, and virtual journal club. e through leveraging global health expertise, these allergy societies have taken action, such as mobilizing a covid- task force charged with real-time monitoring of a fluid and ever-changing pandemic and initiating rapid response communication of critical information. during this time, coordinated messaging from north american allergy and immunology societies can play a pivotal role in advocacy at the federal and state levels to address issues such as expanding coverage for telehealth services nationwide and mitigating the financial impact of the pandemic on private practices. e -e how new strategies and novel paradigms of care delivery can help allergy/immunology clinic contingency planning can allow for compliance with local and state regulations being increasingly required to defer nonessential medical services during shelter-in-place mandates. e through this pandemic the ability to persevere will both require and nourish resilience-a key wellness tool. the rapid adoption of telehealth is a critical component of covid- care. without a doubt, the advent of telehealth in the past few years will be a saving grace, and the rapid incorporation of this service into daily practice will no doubt be a lasting legacy of covid- . although it is not always a perfect surrogate for an in-office visit, when viewing the current situation as temporary, it may allow most care to resume without too much interruption outside of certain parts of the physical examination and certain procedures. many regulations regarding telehealth have been relaxed during the pandemic, allowing for practice across state lines without having to have a license in that state, with use of less hippa-compliant vehicles for communication, and ensuring that video visits can be reimbursed at the same level as an in-office visit for the same issue. e ,e ,e telehealth services can also provide access to aspects of care unavailable with in-person visits, such as creating the avenue for virtual home-visits and, despite social distancing, providing a different view into patient and family needs in the more personal context of their own home. telehealth may also create conversations with multiple family members to better inform practice-individuals who can inform care and help to promote adherence in ways that may not happen with conventional visits. e an added telehealth benefit may also be improved overall productivity from individual clinicians as well. e following the pandemic, the ability to conserve some of the more relaxed telehealth standards could be of significant benefit to expanding the reach of a practice into lesser served areas as well. e this crisis will certainly foster creativity in rethinking the way that we deliver care and provide an opportunity to do things better for our patients. there are a few practical examples of this. economic models have been previously published that have noted the safety of home biologic agent administration, e lack of necessity to activate emergency medical services and seek emergency care after using epinephrine if the patient stabilizes, e and the necessity for screening even high-risk infants for early peanut introduction under the national institute of allergy and immunological diseases guidelines. e ,e a better understanding of what services prove essential, where patient preferences may leverage shared decision making, e and what aspects of care can be reduced or shifted from an in-office to a telehealth or at-home platform will maximize health and economic outcomes of care during the pandemic. these approaches will allow our specialty to better focus on increasing the value of the care we provide and expand the access to that care. covid- -new insights on a rapidly changing epidemic covid- ) situation summary characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention covid- : pandemic contingency planning for the allergy and immunology clinic coronavirus disease (covid- ) in italy covid- and italy: what next? engaging patient partners in state of the art allergy care: finding balance when discussing risk knowledge and perceptions of covid- among the general public in the united states and the united kingdom: a cross-sectional online survey covid- search results a fiasco in the making? as the coronavirus pandemic takes hold, we are making decisions without reliable data more than doctors in italy have now died from coronavirus online library of quality improvement and redesign tools. sense of profound knowledge provider health and wellness burnout and satisfaction with work-life balance among us physicians relative to the general us population burnout in chairs of obstetrics and gynecology: diagnosis, treatment, and prevention physician resilience and burnout: can you make the switch? addressing physician burnout: the way forward federation of state physician health programs. state programs ama code of medical ethics: guidance in a pandemic continuing temporary suspension and modification of laws relating to the disaster emergency on death and dying an empirical examination of the stage theory of grief trudeau-founder of a sanatorium for treatment of tuberculosis collapse therapy of pulmonary tuberculosis in new england states lobar collapse therapy using endobronchial valves as a new complementary approach to treat cavities in multidrug-resistant tuberculosis and difficult-to-treat tuberculosis: a case series streptomycin, a substance exhibiting antibiotic activity against gram positive and gram negative bacteria the internet and medical decision making: can it replace the role of health care providers? the science of fake news internet addiction or excessive internet use prevalence of depression, depressive symptoms, and suicidal ideation among medical students: a systematic review and meta-analysis prevalence of depression and depressive symptoms among resident physicians: a systematic review and meta-analysis medscape national physician burnout and suicide report taking their own lives -the high rate of physician suicide experts address risk of physician suicide factors associated with mental health outcomes among health care workers exposed to coronavirus disease coronavirus disease (covid- ) with a focus on older adults: a guide for allergists and immunologists and patients. resources for a/i clinicians during the covid- pandemic texas allergy, asthma, and immunology society statement. available from: www.taais.org. accessed use of telemedicine during the covid- pandemic. resources for a/i clinicians during the covid- pandemic available from: www.aaaai.org seven tips for running your practice in the coronavirus crisis. available from: www.medscape covid- : pandemic. small business resources. resources for a/i clinicians during the covid- pandemic how to master working from home-while under quarantine with kids how to work from home with kids around how to work from home with kids (without losing it) the strength-focused and meaning-oriented approach to resilience and transformation (smart): a body-mind-spirit approach to trauma management web-based tools and mobile applications to mitigate burnout, depression, and suicidality among healthcare students and professionals: a systematic review american psychiatric association web-based cognitive behavioral therapy intervention for the prevention of suicidal ideation in medical interns: a randomized clinical trial mental health strategies to combat the psychological impact of covid- beyond paranoia and panic available from: https:// edhub.ama-assn.org/steps-forward institute of healthcare improvement. improving health and health care worldwide. available from: www.ihi.org alliance for academic internal medicine. wellness and resiliency. charm online wellness program we're here for you ten percent happier. coronavirus sanity guide make every effort to connect digitally with other people coping with stress during the -ncov outbreak resources for healthcare professionals coping with the covid- pandemic counting blessings versus burdens: an experimental investigation of gratitude and subjective well-being in daily life a qualitative analysis of the three good things intervention in healthcare workers correlation of burnout syndrome with specific coping strategies, behaviors, and spiritual attitudes among interns at yale university cultivating a way of being and doing: individual strategies for physician well-being and resilience general hospital staff worries, perceived sufficiency of information and associated psychological distress during the a/h n influenza pandemic accessed march , . references e . stukus dr. how dr google is impacting parental medical decision making advantages and challenges of social media in pediatrics use of social network sites for communication among health professionals: systematic review how health care professionals use social media to create virtual communities: an integrative review aaaai telemedicine toolkit use of telemedicine during the covid- pandemic. resources for a/i clinicians during the covid- pandemic telemedicine in the era of covid- seven tips for running your practice in the coronavirus crisis provider health and wellness covid- : pandemic. small business resources. resources for a/i clinicians during the covid- pandemic current economic relief opportunities for us small business impacted by the covid- outbreak in the cares act texas allergy, asthma, and immunology society statement coronavirus disease (covid- ) with a focus on older adults: a guide for allergists and immunologists and patients. resources for a/i clinicians during the covid- pandemic medscape physician compensation report a primer on cost-effectiveness in the allergy clinic available from: www.bls/gov united states life tables covid- : pandemic contingency planning for the allergy and immunology clinic resources for a/i clinicians during the covid- pandemic telemedicine is as effective as in-person visits for patients with asthma telemedicine and emerging technologies for health care in allergy/immunology estimation of health and economic benefits of clinic versus home administration of omalizumab and mepolizumab an economic evaluation of immediate vs non-immediate activation of emergency medical services after epinephrine use for peanut-induced anaphylaxis to screen or not to screen": comparing the health and economic benefits of early peanut introduction strategies in five countries determining levers of cost-effectiveness for screening infants at high risk for peanut sensitization before early peanut introduction development and acceptability of a shared decision-making tool for commercial peanut allergy therapies key: cord- -rozpps v authors: faye, c.; wade, c.; dione, i. d. title: a dissymmetry in the figures related to the covid- pandemic in the world: what factors explain the difference between africa and the rest of the world? date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: rozpps v humanity has experienced outbreaks for millennia, from epidemics limited to pandemics that have claimed many victims and changed the course of civilizations. the advent of vaccines has eradicated some of the serious pathogens and reduced many others. however, pandemics are still part of our modern world, as we continue to have pandemics as devastating as hiv and as alarming as severe acute respiratory syndrome, ebola and the middle east respiratory syndrome. the covid- epidemic with -exponential contamination curves reaching million confirmed cases should not have come as a surprise, nor should it have been the last pandemic in the world. in this article, we try to summarize the lost opportunities as well as the lessons learned, hoping that we can do better in the future. the objective of this study is to relate the situation of covid- in african countries with those of the countries most affected by the pandemic. it also allows us to verify how, according to the observed situation, the african ecosystem seems to be much more resilient compared to that of other continents where the number of deaths is in the thousands. to verify this, the diagnosed morbidity and mortality reported for different states of the world are compared to the ages of life and the average annual temperature of these states. the results show that the less dramatic balance of the african continent compared to other continents is partly linked to the relatively high temperatures on the continent but also to the relatively young character of its population. humanity has experienced outbreaks for millennia, from epidemics limited to universal pandemics that have claimed many victims and changed the course of civilizations. the advent of vaccines has eradicated some of the serious human pathogens and mitigated many others. however, pandemics are still part of our modern world, as we continue to have pandemics as devastating as hiv and as alarming as severe acute respiratory syndrome, ebola and middle east respiratory syndrome (saqr and wasson, ) . the covid- epidemic with exponential curves reaching million confirmed cases should not have come as a surprise. however, we seemed to ignore the past. (peeri et al., ; morse, ) . unfortunately, covid- is not the last pandemic in the world and we need to learn what we missed and how to avoid failures. today. while border closures and travel restrictions within countries may be helpful, this is much less effective than in the past. pandemics require a stronger who with sufficient resources (morse, ) . failure to manage a pandemic in one country can have repercussions for the entire planet; therefore, pandemics require more solidarity and coordination so that fragile countries can find the resources to treat, isolate and combat severe epidemics. there are good signs that such efforts are being implemented (for example, the european union has announced eur billion to combat the current pandemic in developing countries) and, hopefully, these efforts are being consolidated to become systemic, proactive and organized. in other words, pandemics require global efforts with a strong and resourceful world health organisation. having appeared in china in the city of wuhan, covid- , initially a zoonosis, has spread throughout most of the world to become a pandemic affecting all social strata and relatively all ages of life. today, more than million people are affected and the spread of covid- continues to grow beyond the world's best performing health systems. however, it is clear that the geography of covid- disease shows significant disparities between countries and age groups in terms of the level of disease and the extent of mortality. this differentiated prevalence prompts reflection on possible explanations by taking into account a set of endogenous and exogenous factors (geographical, environmental, biological, socio-cultural, political contexts, etc.) . new epidemiological trends on transmission and mortality in africa and the most affected regions of the world suggest that better studies of this infection in sub-saharan africa than in other regions of the world are needed. the covid- pandemic has lower rates of local transmission and mortality in africa, the region where the virus was the last to arrive (imaralu, ) . the daily statistics emanating from the high infectious property of the new strain of coronavirus covid- , particularly its rapid worldwide transmission and the nature of the resulting deaths sweeping across countries, call for concerted efforts to limit local transmission in already colonized territories. there is currently no known consensual cure for covid- infection and there is currently no evidence to recommend specific anti-covid- treatment for patients confirmed to have this disease (who, a). the news of very high mortality rates in industrialized countries with stronger health systems and sophisticated infrastructure is cause for concern (who, b). facilities and equipment in industrialized countries that have so far provided assistance to developing countries are overwhelmed and not even sufficient to meet the current challenges facing these countries. as of april , , , confirmed cases of covid- -positive persons and , deaths worldwide had been reported to who (who, c) . there was concern about the impact of this virus on african nations, given the weakness of prevailing health systems with suboptimal infrastructural support (who, c). the recent mass exodus of health workers to europe and the americas and the continuing security threats of terrorism and violent crime make this new deadly viral threat a source of concern for governments in this subregion (imaralu, ) . on the basis of the above, the social and health implications of intervention measures to limit the spread of covid- virus should be considered and interventions carefully planned . this study thus proposes a diachronic reading of the evolution of covid- with as inputs the diagnosed morbidity and mortality reported in different states of the world on the one hand, and on the other hand the life expectancy and the average annual temperature of these states for a comparative study in order to draw all the specificities generated. this contribution focuses on the factors explaining this disparity in a statistical, sociodemographic and geographical analysis. it is based on a statistical treatment of aggregated data with a plural input taking into account the specificities of the prevalence of covid- at the level of the countries of the world. the covid- statistics used in this study are from the world health organization database and are as of monday, april , (https://www.weather-atlas.com or http://data.un.org/data.aspx?d=clino=elementcode% a figure ). for this study, countries were selected, countries in africa (these are indeed the african countries that have counted the most cases of covid- as of monday april ) and countries generally located in other continents ( countries in europe, in america, in asia, in oceania). indeed, these are the countries in the world that have counted the most cases of covid- as of monday april . the objective of this study is to relate the situation of covid- in african countries with those of the countries most affected by the pandemic. it also allows us to verify in what way the african ecosystem seems, according to the observed situation, much more resistant compared to that of other continents where the number of deaths is counted in thousands. to verify this state of affairs, two key hypotheses are raised: one natural (this is the average annual temperature of the country) and the other anthropogenic (this is the structure of the population). according to several scientists, the less dramatic balance of the african continent compared to other continents would be linked to the relatively high temperatures on the continent but also to the relatively young character of its population. to carry out this correlation study, the data used are shown in the following table. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. . it reduces the number of variables to those that are the most significant among a set of variables and is used to find a link between variables and individuals in order to group them into homogeneous regions. one of the objectives of pca is to obtain useful information from a data matrix, and to provide a graphical representation of the data to facilitate analysis. the mathematical procedure of principal component analysis is actually a multivariate statistical method of data processing. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint we subjected all the variables studied for the different countries under study to a principal components analysis, in order to determine the affinities between these countries and to deduce the most characteristic parameters. to do this, a correlation matrix was used and the components were determined according to the type of rotation of the orthogonal axes. the first factorial axis (f ) of this representation is such that it determines the maximum inertia of the cloud and thus the variance. the second axis (f ) perpendicular to the first expresses the maximum remaining variance. the third axis, always perpendicular to the other two, is defined by the maximum remaining inertia; etc. principal component analysis, or pca, is a method of reducing the number of variables allowing the geometric representation of observations and variables. this reduction is only possible if the initial variables are not independent and have non-zero correlation coefficients (bouroche and saporta, ) . the method was applied to countries ( in africa and in other continents) and variables which are: the covid- situation on monday april (confirmed cases and reported deaths), the mean annual temperature and the structure of the proportion ( to years, to years and over years). the final reconstitution of the distribution of the countries allowed us to define the factor axes or factors responsible for this distribution and consequently, to highlight the affinities between the different countries and to deduce the variables linked to the covid- pandemic that best characterize them. analysis of tables and and the eigenvalue curve ( figure. ), shows that the first three factors represent the maximum amount of information. thus the first three factor axes express . % of the total variance, with . % for the first factor, . % for the second and . % for the third factor (table and figure ). this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint there is an inverse relationship between the covid- pandemic (confirmed cases and reported deaths) and temperature, suggesting that generally the warmer a country is, the less likely it is to be affected by the coronavirus pandemic, and vice versa. the opposing relationship between the covid- pandemic (confirmed cases and reported deaths) and the proportion of elderly (and/or young) is apparent, suggesting that generally the younger a country's population is (and therefore the fewer vulnerable people), the less likely it is to be affected by the coronavirus pandemic, and vice versa. the number of confirmed cases is well correlated with the number of deaths, weakly correlated with the ageing character of the population and negatively correlated with the average temperature of the country and the youthful character of the countries' population. the axes , and thus selected highlight their relations with the parameters studied (table ) . the correlation matrix of the covid- pandemic variables and variance weight factors (table ) and figure. show that axis (main axis of inertia) which represents more than . % variance is very well positively correlated with the mean annual temperature of the country and the proportion of young people in the total population of the country. it is also weakly but this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / negatively correlated with the number of confirmed covid- cases, the number of reported deaths and the proportion of elderly in the total population. axis , with . % variance, is positively related, strongly with the number of confirmed covid- cases, the number of reported deaths and the proportion of elderly in the total population, weakly with the average annual temperature of the country and the proportion of young people in the total population of the country. it is negatively correlated, albeit weakly, with the proportion of the elderly in the total population. as for axis , which represents almost . % of the variance, it shows only a positive but weak correlation with the number of confirmed covid- cases and the mean annual temperature of the country. its correlation with the number of reported deaths and the proportion of young and old in the total population remains negative. the correlation of the covid- pandemic variables studied with this axis, whether positive or negative, is weak. these different characteristics of the covid- pandemic-related variables and of the countries studied are represented in circles and planes, respectively (figures and ) , which illustrate the projection of the variables and the variables on factorial planes and . each variable related to the covid- pandemic is associated with a point whose coordinate on a factorial axis is a measure of the correlation between that variable and the factor (axis or axis or axis ). projected on a factorial plane, the variables studied fit into a side plane ( figure ). they are all the closer to the side of the plane the more the variable is well represented by the factorial plane, i.e. the variable is well correlated with the two factors making up this plane. .. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. in plans i-ii and i-iii ( . % of cumulative inertia), axis i is determined by variables related to the covid- pandemic such as the mean annual temperature of the country and the proportion of young people in the total population, which are opposed to the number of confirmed covid- cases, the number of reported deaths and the proportion of elderly people in the total population. the purpose of this representation is to provide approximate planar images of the cloud of the countries located in the plane. thus, the x-axis represents the thermal component (mean annual temperature of the country) and the anthropogenic component (proportion of young people in the total population) of the countries, while the y-axis represents their profile (in terms of number of confirmed covid- cases and number of reported deaths). indeed, a country represented on the positive part of axis generally has a high temperature and a young character of its population; this is the case, for example, of african countries. in the u.s. plan, plan i-ii highlights three groups. the first group is made up of the countries that have recorded the greatest number of cases of contamination and deaths (e.g. united states, spain, italy, germany, france, etc.). these are the countries with the highest form values (a, p, kg , l and l). in this group, the united states stands out clearly from the others due to its higher number of contamination and deaths. the second group is made up of european countries (belgium, netherlands, switzerland...), american countries (canada, brazil, peru...), asian countries (israel, south korea, japan...) and oceania (australia) which have recorded a lower number of cases of contamination and deaths than those in the first group, despite certain common characteristics (such as temperature and the ageing of the population). the last group is made up of african countries with the lowest number of cases and deaths related to covid- . these countries also benefit from a high temperature and a young population. for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. what analysis can be made of this cpa figure , which distinguishes three categories of countries? • the first category (usually - ) and the second category (usually - ) are made up of the european, american and asian countries most affected by the covid- pandemic. these countries are generally located in the temperate zone (where temperatures are relatively mild and conducive to the easy spread of the pandemic). in addition, they are countries with an aging population, and therefore a high number of vulnerable people), hence the high number of deaths related to the pandemic. however, there are some exceptions because among these countries there are a few that are located in the tropical zone, such as brazil, and are in this group. some african countries, such as mauritius, are also located in the group, due to its low average annual temperature, which brings it closer to countries in the temperate zone. • the third category (generally - ) consists strictly of african countries selected for this study (those most affected by the covid- pandemic). these countries are generally located in the tropical zone (whose temperatures are relatively high and unfavourable to the spread of the pandemic). in the early stages of the epidemic, the speed of contagion decreases with the temperature of the country or region and high temperatures reduce the initial rates of contagion (demongeot et al. , ) . containment policies and other rules of expulsion should take into account climatic heterogeneities in order to adapt public health decisions to possible geographical or seasonal gradients. in addition, these are for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / countries with young populations (i.e., with very few vulnerable people), hence the low number of pandemic-related deaths. ultimately, the principal component analysis (pca) synthesized the information contained in table by crossing countries (individuals) and variables (quantitative). it produced a summary of information (figures , , and ) by establishing similarity between the selected countries, searching for homogeneous groups of countries, identifying a typology of countries and variables related to the covid- pandemic studied, and also identifying linkage budgets between variables related to the covid- pandemic, using synthetic parameters or variables. the cpa has generally established the linkages between these two typologies (kouani et al., ) . in conclusion, we note that the cpa has the advantage, on the one hand, of summarizing the set of correlated initial parameters into a reduced number of uncorrelated factors. on the other hand, it has enabled us to highlight similarities or oppositions between parameters and subbasins (faye, ; baba-hamed and bouanan, ) what analysis can be made of this cpa figure , which distinguishes three categories of countries? • the first category (usually - ) and the second category (usually - ) are made up of the european, american and asian countries most affected by the covid- pandemic. these countries are generally located in the temperate zone (where temperatures are relatively mild and conducive to the easy spread of the pandemic). in addition, they are countries with an aging population, and therefore a high number of vulnerable people), hence the high number of deaths related to the pandemic. however, there are some exceptions because among these countries there are a few that are located in the tropical zone, such as brazil, and are in this group. some african countries, such as mauritius, are also located in the group, due to its low average annual temperature, which brings it closer to countries in the temperate zone. • the third category (generally - ) consists strictly of african countries selected for this study (those most affected by the covid- pandemic). these countries are generally located in the tropical zone (whose temperatures are relatively high and unfavourable to the spread of the pandemic). in the early stages of the epidemic, the speed of contagion decreases with the temperature of the country or region and high temperatures reduce the initial rates of contagion (demongeot et al. , ) . containment policies and other rules of expulsion should take into account climatic heterogeneities in order to adapt public health decisions to possible geographical or seasonal gradients. in addition, these are countries with young populations (i.e., with very few vulnerable people), hence the low number of pandemic-related deaths. ultimately, the principal component analysis (pca) synthesized the information contained in table by crossing countries (individuals) and variables (quantitative). it produced a summary of information (figures , , and ) by establishing similarity between the selected countries, searching for homogeneous groups of countries, identifying a typology of countries and variables related to the covid- pandemic studied, and also identifying linkage budgets between variables related to the covid- pandemic, using synthetic parameters or variables. the cpa has generally established the linkages between these two typologies (kouani et al., ) . in conclusion, we note that the cpa has the advantage, on the one hand, of summarizing the set of correlated initial parameters into a reduced number of uncorrelated factors. on the other hand, it has enabled us to highlight similarities or oppositions between parameters and subbasins (faye, ; baba-hamed and bouanan, ). for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / two months after the first cases of covid- appeared in africa, the spread of the disease appears to be progressing more slowly than elsewhere. since the first cases of covid- infection detected in africa in mid-february, as of may , there have been just over , reported cases (including those already cured) and deaths in africa, compared with over , , cases of illness and , deaths worldwide (who, d) . statistically, many experts still point to the african anomaly and link it to climate, geography and, in the most extreme cases, even to a kind of biological resilience (savana, ) . africa, with per cent of the world's population, is home to only . per cent of the world's sick and . per cent of its dead. better still, with already more than , recoveries, it seems to be much more resistant than others to covid- . for the time being, in any case, no one denies that the spread of the virus seems to be singularly slow on the continent, and many reasons are cited to try to explain this (marbot, ) . climate: like influenza, coronavirus is believed to be a disease that thrives in the cold season and does not tolerate heat, drought, or even heavy sun exposure. the hypothesis seems to be supported by the fact that the countries most affected by the pandemic have a rather temperate climate and that most cases are concentrated either in the extreme north of the continent or in the extreme south, where heat and drought are less overwhelming. on the research side, a british study confirms that, on average, fewer respiratory illnesses are found in hot and dry countries, and an american report of april states that the half-life of the virus, i.e., the period required for its infectious power to be halved, may increase from to hours if heat and humidity increase (marbot, ) . researchers nevertheless remain very cautious, like the director of international affairs at the pasteur institute, pierre-marie girard, who stresses that during in vitro experiments it was found that the coronavirus "multiplied very well in heat". sun, heat and humidity could weaken the covid- virus. according to a study of the american government, presented thursday april in washington, the virus responsible for the pandemic of covid- weakens in a hot and humid atmosphere as well as under the rays of the sun. "our most striking observation to date is the powerful effect that sunlight seems to have in killing the virus, both on surfaces and in the air," said a senior department of homeland security official bill bryan ( ). despite this, health minister olivier véran was sceptical and the who believes that high temperatures do not prevent the virus from being contracted. the youth of the population: this is the other major explanation put forward. in englishspeaking countries, it has even become a slogan: "the virus isold and cold and africa is young and hot". doctors confirm that the majority of severe cases of covid- involve people over years of age, which would be fortunate for the continent, where the median age is . years and % of the population is under years of age. it is also pointed out that one of the hardest hit countries, italy, has . per cent of its population aged and over, compared to per cent in africa. there is almost unanimous agreement on this hypothesis, but scientists qualify it by pointing out that although the african population is young, it is unfortunately more affected than others by diseases such as hiv or malnutrition, which can make it vulnerable. finally, some researchers note that in europe and the united states the elderly often live among themselves in old people's homes, which encourages the spread, whereas in africa they more frequently live with their families. this could protect them. average, and that cities such as lagos or abuja have record population densities. today, this position must be put into perspective because in some countries, it can be observed that most cases of infection concern localities with dense populations, including cities. another rational explanation that is difficult to circumvent is that the african population moves less, on average, than that of many advanced countries, and the risks of contamination are therefore necessarily lower. as a reminder, there is only one african airport in the list of the world's sites with the highest concentration of air traffic: johannesburg. the experience of epidemics: as many point out, this is not the first epidemic in africa, and there have been far more deadly ones, including the recent ebola crises. healthcare workers and populations alike are therefore used to dealing with health crises, lessons have been learned and "good practices" have been put in place. certain methods of detection, isolation of patients, and precautions during care developed previously are duplicable in the face of the coronavirus. the authorities also took the measure of the danger more quickly than others and put in place very early on the control or closure of borders, distancing or containment. this led dr moumouni kinda, who has faced several crises with the non-governmental organization alima, to say, "epidemics like ebola have given us experience on communication and awareness, which are key points in breaking the chains of transmission of the virus. for some african scientists, the continent also has the advantage of practicing true solidarity. when one country lacks masks or test kits, neighbouring countries that are less affected are likely to provide them. lesotho, which does not yet have an operational laboratory, has its samples tested in south africa, and a network for detecting seasonal influenza, used against covid- , already brings together some countries on the continent. without being overly optimistic, it must be said that solidarity sometimes seems to work better in africa than in certain richer regions, where we see the major laboratories jealously watching over their discoveries in the hope of being able to market a treatment or a vaccine. not to mention a donald trump trying to get his hands on the patents of drugs under development for the sole (financial) benefit of the united states...on a much more local scale, it is also pointed out that the community-based functioning of many african populations makes it possible to better convey prevention messages, but also to detect patients more quickly, since few people are likely to be left to their own devices. this hypothesis is the subject of much controversy, and the who, in particular, is very cautious. however, some doctors have noted some disturbing coincidences: there are reportedly fewer coronavirus contaminations in the countries most affected by malaria" or tuberculosis. or in those that massively vaccinate their population with bcg. would contracting certain diseases be a barrier to covid- ? it will take time to prove it, but many doctors believe that antimalarial treatments such as chloroquine have some effectiveness. that's partly why french professor didier raoult and teams like the drug discovery and development centre (h d) at the university of cape town are giving priority to testing antimalarial drugs. the who is critical, noting that some countries such as burkina faso, nigeria and senegal, where malaria is devastating, are not spared by the virus. more recently ( april), the malagasy president announced that his country was in possession of a "vita malagasy" remedy (made in madagascar) with preventive and curative virtues against the coronavirus. covid-organics, the name given to this treatment, is an herbal tea made from dried artemisia leaves, produced by the malagasy institute for applied research (imra). despite who warnings, member countries of the economic community of west african states (ecowas) will now be able to treat their for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / coronavirus patients with covid-organics, and test the effectiveness of this improved traditional remedy proposed by imra. faced with the fight against the covid- pandemic, africans have chosen to put forward the unity and solidarity of africa. madagascar was able to demonstrate to the world that we africans can cooperate and help each other not only in an economic situation but above all in a health and humanitarian situation. a "genetic" immunity: what if africans were protected by their dna, which, for some reason yet to be determined, would be more robust against the coronavirus? the hypothesis is far from unanimous -at the pasteur institute, pierre-marie girard "doesn't really see why" such a specificity would exist -and will take time to be explored. the cameroonian professor christian happi, specialist in genomics, who divides his time between harvard university and nigeria, does not completely rule out this possibility: "africans are exposed to many diseases, so it is possible that their bodies react better. you'll have to look for antibodies to find out, but it's possible. after ebola, we saw that many people in nigeria had been exposed to the disease but had not developed it. » another version of the virus: an idea that is similar to the previous one: since it now seems that several different strains of covid- are present on the planet (up to eight distinct forms), perhaps the one present in africa is less aggressive? this could also explain the fact that there seem to be more asymptomatic cases there than elsewhere. the hypothesis remains audacious insofar as the virus arrived through patients who contracted it elsewhere. could it have mutated afterwards? the who does not rule out the idea, but stresses that in order to validate it it will be necessary to sequence the genome of covid- , which is currently underway. better masks: when asked about the specificities that could work in favour of africa, matshidisomoeti, who africa director, points out that the continent "has a very active and competent textile industry", especially in brazzaville, where the organization's offices are located. this particularity perhaps allows the population to benefit from more and better quality cloth masks than in some rich countries, where scarcity is the rule. in conclusion, the scientists point out that what probably explains the low number of cases observed on the continent is, above all, the fact that most countries took drastic protection measures very early on. and perhaps also the fact that because the disease initially affected people who were travelling, rather better informed than average and living mostly in cities, it was easier to identify the first cases than in other epidemics. but the modesty of the figures continues to amaze, as congolese biologist francine ntoumi notes: "in some countries on the continent, people eat bats, people live on top of each other... in fact, everything is done to make it explode, but it doesn't. "it's up to african scientists to find out why. however, caution should be exercised in the face of the figures because even if africa is not the continent most affected by covid- , the damage could be considerable, according to virologist denis chopera. in addition, the contamination rate would be underestimated due to the lack of medical facilities. in the context of this sars-cov- virus, transmission can take place during the last days of viral incubation, before symptoms appear or at least are significant. this is a viral strategy that has certainly allowed the virus to spread so impressively. another risk of under-evaluating cases is the lack of diagnostic tests or one of the reagents that make them up. given the international demand, the whole world is struggling to obtain everything necessary to fight the pandemic and africa is not always in an ideal position to be able to negotiate prices compared to other regions of the world. at the moment, patient management is going relatively well in the hospitals that have been identified to play this role and the system is not overwhelmed, although some tools, such as respirators, are sorely lacking. at present (as of may , ), just under ( ) deaths for approximately times the number of identified confirmed cases, which would correspond to for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint a lethality of . %. although the global case-fatality rate is generally higher ( %), severe cases are more easily identified than non-symptomatic or minimally symptomatic cases, and it is possible that several foci of the infection have not been identified. if this is the case and the virus is insidiously transmitted in the population, it is likely that hospital infrastructures will be rapidly overwhelmed when the weakest are affected. globally, deaths due to covid- are lower among young people, including women and children, but higher among the elderly and people with chronic diseases. the pandemic appears to have lower local transmission and mortality rates in africa, the region with the youngest median age of the population and where the virus arrived last. while special efforts should be made to protect the elderly and infirm from infection, preventive measures among women (especially pregnant women) must provide access to emergency care to prevent the maternal mortality caused by covid- . similar to the crisis of the late s, the current crisis will have an impact on international relations. the structural changes already seen in the globalisation process can be expected to accelerate. in general, the world needs serious investment in research and development to understand current epidemics and to prepare for possible future ones. we need to prepare our health care infrastructure, develop new diagnostic and therapeutic solutions, invest in broadspectrum vaccines and antivirals, and fund research infrastructure and pandemic predictability. we need more social science research to help understand the social aspects of the pandemic, to foster engagement and trust in our communities, to improve our education to be more adaptive and to target misinformation. we need each other more than ever with greater compassion, solidarity and collaboration. a global pandemic requires global efforts. there will be future severe pandemics. who, d : coronavirus disease (covid- ) situation report - data as received by who from national authorities by : cest, may this report has been reformatted to improve accessibility for persons with visual impairment. p. https://www.who.int/emergencies/diseases/novel-coronavirus- /situation-reports for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / for use under a cc license. this article is a us government work. it is not subject to copyright under usc and is also made available (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / : caractérisation d'un bassin versant par l'analyse statistique des paramètres morphométriques : cas du bassin versant de la tafna temperature decreases spread parameters of the new covid- case dynamics a principal component regression method for estimating low flow index méthode d'analyse statistique de données morphométriques : corrélation de paramètres morphométriques et influence sur l'écoulement des sous-bassins du fleuve sénégal temporal evolution of groundwater composition in an alluvial aquifer (pisuerga river, spain) by principal component analysis clinical features of patients infected with novel coronavirus in wuhan : emerging statistics on the epidemiology of covid- : making prevention in pregnancy less grievous than the disease analyse en composantes principales une méthode factorielle pour traiter les données didactiques. radisma : coronavirus : décryptage des hypothèses qui expliqueraient la faible contamination en afrique du mai à h pandemic influenza: studying the lessons of history covid- ) epidemics, the newest and biggest global health threats: what lessons have we learned? application of principal components analyse to the study of co -rich thermaineral waters in the aqufère system of alto guadalentin (spain) covid- : lost opportunities and lessons for the future covid- : l'exception africaine à l'épreuve des statistiques exploration des séries chronologiques d'analyse de la qualité des eaux de surface dans le bassin de la tafna en algérie. revue des sciences de l'eau who, a : world health organization. clinical management of severe acute respiratory infection (sari) when covid- disease is suspected: interim guidance who, b : world health organization. health systems in africa: community perceptions and perspectives. the report of a multi-country study. who. geneva; situation report- . who. geneva; key: cord- - gl v authors: ferriss, j. stuart; rose, steve; rungruang, bunja; urban, renata; spencer, ryan; uppal, shitanshu; sinno, abdulrahman k.; duska, linda; walsh, christine title: society of gynecologic oncology recommendations for fellowship education during the covid- pandemic and beyond: innovating programs to optimize trainee success date: - - journal: gynecol oncol doi: . /j.ygyno. . . sha: doc_id: cord_uid: gl v in approximately ten months' time, the novel coronavirus, severe acute respiratory syndrome coronavirus (sars-cov- ), has infected over million people and caused over one million deaths worldwide. the impact of this virus on our health, relationships, and careers is difficult to overstate. as the economic realities for academic medical centers come into focus, we must recommit to our core missions of patient care, education, and research. fellowship education programs in gynecologic oncology have quickly adapted to the “new normal” of social distancing using video conferencing platforms to continue clinical and didactic teaching. united in a time of crisis, we have embraced systemic change by developing and delivering collaborative educational content, overcoming the limitations imposed by institutional silos. additional innovations are needed in order to overcome the losses in program surgical volume and research opportunities. with the end of the viral pandemic nowhere in sight, program directors can rethink how education is best delivered and potentially overhaul aspects of fellowship curriculum and content. similarly, restrictions on travel and the need for social distancing has transformed the fellowship interview season from an in-person to a virtual experience. during this time of unprecedented and rapid change, program directors should be particularly mindful of the needs and health of their trainees and consider tailoring their educational experiences accordingly. • the novel coronavirus pandemic has disrupted medical education at all levels. • fellowship programs must adapt to the realities of social distancing, workforce redeployments, and laboratory closures. • the integration of teleconferencing into clinical practice and learning provides both challenges and growth opportunities. in approximately ten months' time, the novel coronavirus, severe acute respiratory syndrome coronavirus (sars-cov- ), has infected over million people and caused over one million deaths worldwide. the impact of this virus on our health, relationships, and careers is difficult to overstate. as the economic realities for academic medical centers come into focus, we must recommit to our core missions of patient care, education, and research. fellowship education programs in gynecologic oncology have quickly adapted to the "new normal" of social distancing using video conferencing platforms to continue clinical and didactic teaching. united in a time of crisis, we have embraced systemic change by developing and delivering collaborative educational content, overcoming the limitations imposed by institutional silos. additional innovations are needed in order to overcome the losses in program surgical volume and research opportunities. with the end of the viral pandemic nowhere in sight, program directors can rethink how education is best delivered and potentially overhaul aspects of fellowship curriculum and content. similarly, restrictions on travel and the need for social distancing has transformed the fellowship interview season from an in-person to a virtual experience. during this time of unprecedented and rapid change, program directors should be particularly mindful of the needs and health of their trainees and consider tailoring their educational experiences accordingly. © elsevier inc. all rights reserved. between january and october of , there were an estimated million cases of severe acute respiratory syndrome coronavirus (sars-cov- ) and over one million deaths worldwide [ ] . in the united states (us), there were over million documented cases and over , deaths- % of whom were black americans [ , ] . among healthcare workers in the u.s., there were over , cases and deaths [ ] . given the lack of immunity in the population or any effective therapy, health systems braced for an influx of extremely ill patients. many facilities lacked sufficient supplies of personal protective equipment (ppe) needed in a pandemic. local governments, particularly those with swiftly rising case numbers, instituted an array of social control measures: stay at home orders, social distancing rules limiting gatherings, and wearing masks in public places. these new rules fundamentally changed the daily practice of medicine in three ways: telemedicine was rapidly adopted, hospitals increased the threshold for what required admission, and non-urgent interventions and procedures were halted [ ] . many states limited or suspended most elective procedures, including surgery, in an effort to conserve ppe, ventilators, beds and the workforce. as a result of these measures, many facilities saw overall patient volumes fall - % and a sharp increase in critically ill patients [ ] . the american college of surgeons and the society of gynecologic oncology (sgo) each issued guidance for safely triaging elective procedures [ , ] . with increasing numbers of patients needing intensive, complex care for several weeks at a time, many centers redeployed physicians from procedural areas to support critical care. the economic impact on hospitals has been substantial with some systems reporting hundreds of millions of dollars in losses and analysts have predicted hundreds of hospitals may close [ , ] . medical education has rapidly changed in the face of this pandemic and the new reality in which we live. this has impacted gynecologic oncology fellowship programs, as surgical cases and cancer care have been disrupted at every academic center. limiting patient care to essential personnel has sidelined our learners and interrupted their education causing training programs to adapt quickly [ ] . with the end of the viral pandemic nowhere in sight, program directors can rethink how education is best delivered and potentially overhaul aspects of the fellowship curriculum. selecting the next generation of fellows while transitioning from in-person to virtual interview formats is also critical. gynecologic oncology programs and fellowships have made great strides in adapting to a rapidly evolving health care environment. this paper summarizes the changes that have taken place in fellowship education at the beginning of the pandemic and provides resources and recommendations for fellows, faculty, and program directors moving forward. the accreditation council for graduate medical education (acgme) provides oversight regarding programmatic details and learner assessments for us gynecologic oncology fellowships. early in the covid- crisis, acgme quickly established three stages of operation for each sponsoring institution dependent upon the degree to which normal operations had been interrupted [ ] . with each stage, more program requirements were set aside. this allowed institutions the flexibility to redeploy fellows to areas of increased clinical need in the event pandemic emergency status (stage ) was declared. as the pandemic progressed, acgme also relaxed other trainee requirements given the time spent on covid- planning and response. for the - academic year, milestones reporting and clinical competency committee meetings for non-graduating fellows were made optional, and the fellow and faculty surveys (while still available) were also deemed optional. acgme suspended accreditation site visits and all program level self-study activities. however, summative evaluations for graduating fellows and program evaluation committee meetings were still required and allowed to be conducted remotely. acgme accelerated the inclusion of fellows in telemedicine visits and expanded the definition of supervision to allow for remote monitoring. based upon responses about the impact of the pandemic from programs in the annual update "major changes and other updates" section of the accreditation data system, the review committees will may make further changes to accreditation requirements in the specialty. updated acgme requirements can be found at https://www.acgme.org/covid- . the american board of obstetrics and gynecology (abog) sets board certification (thus educational) standards in us gynecologic oncology programs. the pandemic has impacted timing of the subspecialty qualifying and certifying examinations. given the travel restrictions and social distancing requirements, the subspecialty certification examinations were moved from april to november and later postponed again until [ ] . the subspecialty qualifying examination was moved from june , to july , to allow for social distancing in the testing centers. currently, abog allows programs flexibility if fellows need to be redeployed. this includes allowing research fellows to be reassigned to clinical duties without requiring the research time to be made up. time spent in quarantine or working from home due to covid- is considered clinical experience. if a fellow needs time to care for a family member, partner, or dependent with covid- , this can be considered clinical experience as well. abog also allows fellows the opportunity to postpone their qualifying examination to without additional fees. as many labs were shut down during the pandemic, programs and fellows can request an extension to complete their research thesis and the eligibility period for fellows has been extended by one year due to the disruption. abog also allows for programs to extend training, if necessary, though makes clear that the fellowship program has final authority to decide if a fellow meets the graduation requirement. the latest information can be found at https://www.abog.org/covid- -updates. every aspect of fellowship training has been affected by the covid- pandemic. from decreased surgical case volumes and lab closures, to the disruption of daily rounds, didactics, and conference schedules, the fellowship learning environment looks very different today than ten months ago. in a survey of members of sgo, % of respondents reported a % or greater reduction in surgical volume due to the pandemic [ ] . the efforts to minimize exposure to covid- (for both patients and learners) and to conserve ppe will further reduce fellow participation in surgical cases. for example, in some centers fellows may have previously joined several overlapping cases each day during the portions critical to their learning. this model allows other portions of the same procedure to benefit resident education. minimizing changeover of surgical teams does use less ppe, but also limits the number of learners able to benefit from each case. despite these trends, several centers have been able to maintain surgical services for cancer patients [ ] . when surgical cases can proceed, every effort should be made to maximize learning opportunities for fellows. this can be achieved by allowing the fellow to focus on the most critical portions of a procedure while balancing other priorities such as minimizing the use of ppe. for example, in a robotic case the fellow will use less ppe at the console while the faculty and surgical technician remain bedside for the duration of the procedure. additionally, selected radical procedures can be used to maximize learning with two fellows (without other learners) with the faculty immediately available for guidance. fellows are also balancing their training priorities with that of obstetrics and gynecology residents, who require adequate surgical experience. conversely, fellows may be asked to "step up" to the supervisory level as fully trained obstetrician gynecologists depending on attending availability and health. each program will have to decide how best to manage the competing interests of fellow education and the directive to conserve resources as well as decrease workplace exposures. in the months since the initial wave of the pandemic, many metropolitan centers have returned to near normal, while other areas are just now experiencing widespread community infection [ ] . thus, the implementation of these types of educational strategies to mitigate the impact on fellow surgical education will vary based on each program's local burden of disease. these realities create new challenges in gynecologic oncology training, yet programs have an opportunity to design and implement competence-based assessment of surgical milestones. for instance, the university of miami has incorporated a structured surgical case review into the educational curriculum. this is based on the hypothesis that systematic immediate and delayed feedback maximize the surgical learning environment [ ] . minimally invasive and open procedures performed by fellows are recorded, reviewed, and critiqued by an attending physician not involved in the case. for open procedures, recording can be done utilizing action cameras with image stabilization technology mounted on a head strap or with camera attachments fitted on operating room light handles. specific procedures are selected to maintain feasibility due to the large time commitment required for editing and providing feedback on a lengthy surgical video. expectations are set preoperatively based upon predetermined competencies listed on a surgical review worksheet. an example worksheet used for small bowel resection and anastomosis is shown in table . it is imperative that this is available to trainees prior to the operation. postoperatively, rough video editing to select for the procedure in question is performed, and the resultant clip is reviewed with the trainee for both self-assessment and educator feedback on areas for improvement. this provides an opportunity for secondary reinforcement and feedback for the trainee surgeon. participation of co-fellows in this process results in group benefit, especially for less common surgical procedures. the current implementation of this assessment is as a surgical performance improvement tool, and not to directly establish competence for individual procedures. as worksheets for each procedure are developed further, this tool will be used to complement traditional assessments of surgical competence. published surgical videos are also incorporated into the curriculum to supplement direct observation and provide a blended experience beyond the apprenticeship model. computer-based surgical simulators, which are available for standard and robotic-assisted laparoscopy and dry lab training are useful, especially if used as part of an integrated educational module [ ] . participation in surgical simulation has been shown to improve participants self-rated ability, and objective measures of skill [ ] . known barriers to trainee participation in surgical simulation (lack of time, access, and supervision) should be addressed when possible [ ] . a multiplatform approach is essential as several studies demonstrate skills developed with traditional laparoscopic simulation are not transferrable to the robotic platform [ ] . virtual reality simulation is readily available on modern robotic systems and is shown to be as effective as dry lab simulation without the need for a complicated logistical setup [ ] . while surgical simulation is a helpful adjunct, it does not replace the hands on learning essential to our field. utilization of telemedicine has increased dramatically during the covid- outbreak. a virtual approach can minimize disruption to table structured surgical case review worksheet. instructions for reviewer: for each of the following procedural steps, please use the following scale: ( ) the fellow is unable to identify the correct steps to the procedure ( ) the fellow is unable to perform the procedure ( ) the fellow is able to perform the procedure with significant guidance ( ) the fellow is able to perform the procedure with minimal correction ( ) the fellow has mastered the procedure . identifies limits of bowel resection . identifies distance from water shed areas . identifies vasculature within the mesentery . selects appropriate stapler length and staple height . creates hole in mesentery in correct location and direction . fires stapler with control . resects the bowel off the mesentery . identifies antimesenteric end for enterotomy and creates appropriately sized enterotomy . orients the bowel correctly and fires intraluminal stapler checking for staple line bleeding as stapler is removed . lines up the bowel in the ta stapler . closes the mesenteric defect inpatient, ambulatory, and chemotherapy education for fellows. the johns hopkins hospital model of telemedicine implementation for inpatient rounds presents an innovative and safe opportunity to continue fellow participation in perioperative care [ ] . in this model, a single health care provider conducts bedside rounds and, with patient consent, projects the clinical interaction using an approved synchronous audiovisual link to the remainder of the team at offsite locations. each member of the team has a specified task (e.g. pre-rounding, documentation, order entry), which keeps everyone engaged. with practice, this model allows medical education on the inpatient service to continue. fellows can also remain engaged in ambulatory telemedicine encounters using platforms that allow more than one provider to be in the virtual patient room. this is particularly useful in chemotherapy clearance encounters and recapitulates the familiar clinic workflow. given the unproven nature of these clinical education formats, routine assessment of clinical milestones should be undertaken to ensure appropriate progression. the research enterprise at many academic institutions has been severely affected by the covid- pandemic. like clinical services, research efforts that are not deemed essential have been shifted to remote operations or shut down entirely. most centers followed a similar set of guiding principles: noncritical research must be performed remotely, strict adherence to social distancing, and new projects that require in-person presence are not permitted, excluding all covid- -related basic and clinical research [ ] . with most research stopped, lab supplies such as ppe, pipettes, and reagents have been redeployed to augment clinical areas. additionally, clinical research efforts have been scaled back with many centers stopping enrollments to selected clinical trials [ ] . during this time of disruption, many gynecologic oncology fellows in their research year were prevented from completing lab projects related to their thesis. moreover, some research fellows have been redeployed to clinical roles further limiting their ability to focus on scholarly work. while redeployments are meant to be temporary, the time away from research is unlikely to be recaptured. as a result, program directors and fellows will need to understand the limits of the changes allowed by abog regarding extensions and exceptions of the thesis requirement. the impact these interruptions will have on fellows beyond completion of the thesis is unknown. further, programs lack a systematic way to track and assess research competency as the current acgme milestones in gynecologic oncology are largely focused on the thesis project [ ] . assessment tools focused on research competency for clinical fellows are urgently needed. the covid- pandemic has significantly affected medical education, necessitating innovation. to minimize educational gaps created by social distancing and limitations on clinical encounters, novel approaches to remote instruction have become increasingly utilized. due to social distancing, video-based conferencing has emerged as the primary delivery method for didactics and clinical education and has been shown to be useful and highly acceptable among millennial learners [ , ] . several applications exist, such as google hangouts or meet, gotomeeting, microsoft teams, skype, webex, and zoom. each are adaptable for a variety of educational conferences [ ] . this live video feed format allows the lecturer to view the attendee list, see trainee responses, and ask directed questions to individuals, simulating an in-person meeting from a safe distance. video-based lectures should be focused, with clearly defined learning objectives, rather than covering vast amounts of material, as adult learner attention spans wane after - min [ ] . utilization of the live chat function for questions and comments minimizes participant talk-over and interruptions. use of online audience response systems promotes active participation from remote learners, which is known to improve performance. this also provides the lecturer an opportunity to assess content understanding and knowledge deficits [ ] . keeping learners engaged remotely is important as it helps prevent distractions and multitasking with clinical work. these platforms are accessible from computers, tablets, and smartphones allowing learner engagement from any location. e-learning technologies allow for individualized learning plans in which trainees can tailor the content, sequence, and pace to meet their personal learning objectives [ ] . video-based conferences can be recorded and stored on a cloud account, accessible by fellows for later review outside of scheduled didactics. this flexibility also allows fellowship programs to overcome the educational barriers of traditional trainee schedules and off-site clinical rotations [ ] . the flipped classroom strategy can be easily adapted to remote fellow education. in this online asynchronous instruction method, fellows are provided with a pre-recorded video lecture that is viewed prior to the scheduled didactic conference. the didactic session is then replaced with a live video conference that can be focused on synthesis, application, and case-based discussion [ ] . this well-studied teaching method has been shown to improve knowledge acquisition with no increase in preparation time and is preferred by trainees [ , ] . in addition to pre-recorded video lectures, several other online resources exist for asynchronous learning assignments. online elearning courses and webinars are available through several national websites, encompassing a variety of topics. podcasts, which are prerecorded audio files, are another means to engage millennial learners as a supplemental resource [ ] . surgical video libraries are also beneficial, with self-review of videos encouraged. these resources can be utilized asynchronously in a flipped classroom format, for later high-yield content review and faculty commentary in a live video-based didactic session [ ] . prior to the covid- pandemic, several modalities were already available for virtual education content, including society-curated content, video libraries, and podcasts. since the pandemic, online resource content has grown dramatically. sgo has developed substantial content useful to both faculty and fellows, including a useful summary of educational resources. in addition to sgo, national societies including american society of clinical oncology (asco), international gynecologic cancer society (igcs), and others have created online educational repositories that include resources related to our field as well as covid- specific resources ( table ) . the current crisis has also provided opportunity for multiinstitutional collaborations for programs to share virtual educational content. gyoedu (www.gyoedu.org) is a free, collaborative effort to pool fellowship program resources and has resulted in a robust and evolving educational repository, including live and pre-recorded video-based lectures, study summaries, and clinical trial timelines, as well as a planned question bank. the promotion of wellness is closely tied to reducing burnout, a condition in physicians associated with impaired coping and caregiving abilities, and shown to occur with high prevalence in gynecologic oncologists [ ] . the sgo review on burnout frames wellness as a conscious, self-directed and evolving process of achieving full potential [ ] . for our trainees, the covid- pandemic has not only created barriers to the achievement of their full academic, clinical, and personal potentials, it also brings existing inequalities and their associated barriers into sharp focus. fellows have endured significant changes in their training and education in recent months. these changes are likely to persist for the foreseeable future. a perceived reduction in academic productivity may subsequently impact their candidacy for jobs or subspecialty certification. the need to promote social distancing has prompted many conferences to be held virtually. although essential continuing medical education remains available, there is reduced opportunity for fellows to present to their colleagues and peers, an important skill in professional development. there is also an accompanying reduction in fellow participation in national committees as well as decreased networking opportunities, which are crucial for job searches. at the institutional level, the initiation of hiring freezes and reduced physician compensation may significantly impact job prospects for our graduating fellows and future junior attendings [ ] . the status of fellows as senior trainees allow them to be eligible for redeployment to care for covid- patients. as cancer patients have been disproportionately affected by covid- , our fellows may be caring for patients suffering from cancer-related complications as well as covid- [ ] . although our fellows are taught the importance of communication skills, it is likely that few were prepared to have goals of care conversations while in full ppe, and with family available only through virtual means [ , ] . the covid- pandemic has also exposed disturbing health care and societal disparities in both the incidence and mortality of hispanic and black patients [ ] . anti-asian hostilities during the pandemic have also increased in the u.s. and elsewhere and may adversely affect our asian and asian american medical students, residents, and fellows [ ] . the national outrage over police brutality against countless black individuals, and its impact on our trainees of color should be acknowledged. these tragic and unfortunate events may perpetuate an atmosphere of anxiety and distress for our underrepresented minority trainees that must not be ignored. we should encourage open dialogue with our fellows and provide them with a supportive working and learning environment [ ] . gynecologic oncology program directors and faculty should educate themselves about systemic racism and social inequalities that have been underestimated and underrecognized in academics and medicine. most academic medical centers have an office of diversity and inclusion with numerous resources available [ ] . what can we do to help our gynecologic oncology fellows complete their training and achieve their full potential? each learner's progress in clinical, surgical, and research performance should be assessed, and subsequent rotations may require revision to tailor the learning experience. for example, this may involve reevaluation of research projects and consideration of alternative work in order to satisfy abog thesis requirements. further, clinical rotations may need to be repeated and some electives may need to be set aside to focus on the acquisition of core skills. in rare cases, training may need to be extended until competency can be attained. this process entails careful review of regulatory and board requirements, as well as open and frank discussions with each fellow to meet them where they are in the learning process. faculty must be prepared to have honest conversations with fellows about personal sources of stress and anxiety. program directors should review the signs and symptoms of burnout and maintain heightened awareness. the covid- pandemic has had widespread impact on the economyfellows may have partners with job loss and new income limitations, may be facing loss of social support or childcare, have fears of infecting their family, and face reduced access to essential services such as grocery stores or pharmacies. while these impacts can be significant regardless of gender, the majority of our fellows are female and women physicians are known to be disproportionately affected by a lack of child care [ ] . faculty should be willing to share resources with fellows as they become available to other administrators and staff. finally, conduct early and honest conversations about each fellow's career goals and be an advocate for them in creating professional networks and advancement opportunities. during the gynecologic oncology interview season (beginning fellowship in ), applicants vied for positions, and applicants matched into their st or nd rank . % percent of the time [ ] . the data from the national residency match program (nrmp) program director survey found unanimous agreement among program directors citing these factors as critical in making their rank list: interaction with faculty during the interview and visit, interpersonal skills, and interactions with house staff during interview and visit. with varying degrees of state mandated limitations on gatherings and travel related to covid- , the gynecologic oncology fellowship interview season was converted to a virtual encounter. this was done to minimize exposure risk for both faculty and candidates as well as provide an equal opportunity to all candidates. assessment of interpersonal interactions is a critical part of candidate assessments. it is currently unclear if this can be done adequately using video interactions. based on reports that half of the firms in the business world were already using some form of video interviewing prior to the covid- crisis, it appears that other industries might have overcome the hesitancy of using virtual interviews [ ] . the ability to communicate calmly, succinctly, clearly and articulate opinions, positions, and lessons learned from life experiences can be assessed through a video interaction. although data are lacking evaluating the implementation of video interviews during residency or fellowship selections, a few studies from the pre-covid era seem to suggest that both interviewers and applicants had a favorable view of this format. in one [ ] . data from the surgical oncology fellowship interview season showed that all faculty interviewers felt candidates were able to convey themselves "well" or "very well" through the video interview platform, and % of candidates felt the same [ ] . two studies exclusively explored the applicant's point of view regarding video interviews. first, a survey study of internal medicine applicants revealed a high level of satisfaction with a majority of candidates reporting that the video interview (and the virtual materials prepared by the program) were sufficient to make a ranking decision [ ] . second, a survey in following video interviews for orthopedic fellowships demonstrated that % of candidates felt they presented themselves satisfactorily to the program. the same percentage stated that the video interview gave them an adequate understanding of the program [ ] . one notable weakness in the video interview is a decreased likelihood to give an accurate assessment of a candidate's ability to interact in a group. this skill is essential as team-based approaches are the norm for care provided in oncology service lines. these shortcomings can be overcome if letters of recommendation mention the leadership skills of a candidate or how the candidate functions in a team-setting. moreover, interviewers could deliberately include questions about the candidate's group communication style, self-assessment of strengths and weaknesses in team settings, as well as lessons learned from successes and failures in those situations. another significant drawback to virtual interviews is that applicants do not get to visit the city, medical center, and campus where they would be working and living for the forthcoming - years. in a study of urology residency interviews, candidates expressed that while they had a similarly good understanding of the program with video interviews and in-person interviews, they were significantly less satisfied with the medical facilities and city after video interviews. candidates overwhelmingly stated that in-person interviews were better to develop rapport [ ] . a virtual reception could allow applicants a forum to discuss these issues. there are some strategies that could be used to overcome the challenges of hosting a virtual reception with - applicants and - current fellows on a single video-based group. many popular video conferencing software allow the creation of virtual rooms. virtual rooms can then host a smaller subset of applicants [ , ] with each room hosted by one fellow for - min. alternatively, in a question and answer format, all participants and fellows remain in one single meeting. applicants ask questions by unmuting themselves or using the chat function. fellows then take turns answering questions and expressing their views on the subject. there are concerns that fellowship programs may be tempted to default to keeping candidates from their own program during the recruitment season. there is certainly no harm in keeping a resident at the same institution for fellowship; however, a diversity of training experiences is beneficial to propagate ideas and techniques and to enlarge networks among candidates and institutions. covid- has likely opened doors for video interviewing in medicine that may not close again. in an informal survey conducted prior to the fellowship interview season through the sgo program directors network, fellowship directors reported that they planned to increase the number of interviews to a median of . (range - ), up from . (range - ) in the interview season. fellowship directors anticipated that it would be more challenging to assess interpersonal skills of the candidates with virtual interviews. programs planned to address these concerns with an increased use of structured interview questions, more interviewers, and augmented information regarding the location and culture of the program. the sgo program directors network has initiated a follow up survey regarding the programmatic experiences of the interview season now that it has come to a close. results are forthcoming. in preparing for the video interview season in gynecologic oncology, there are several vital elements to maximize success and enjoyment of the process (table ) . months before the interview, if possible, consider updates to the fellowship program website and available electronic materials. consider virtual tours of the campus, medical center, and the city. if available, engage an institution audio-visual department for high-resolution photographs and professional video segments. many institutions are now investing in creating shared resources for programs to use during the recruitment season. fellows or faculty may want to share photos/videos from their personal archives to give applicants a flavor of their lives in the city and around the medical centers. select a video-conference platform early with input from information technology (it) specialists at your institution. it is best to use what is familiar to the institution in case troubleshooting is required. most videoconferencing platforms offer similar functionality. the interview day should be laid out well in advance. it will likely require greater detail and planning of time, as it will not be possible to guide candidates throughout the interview day physically. also, a back-up method of contact is critical -usually in the form of a cell phone. set a limit on the number of times you will try to contact the candidate if the video stream is lost or unusable. you do not want to use five of your twenty interview minutes just trying to connect. during the interview day, turn off as many alerts as possible. close other browser tabs and applications as this can affect the video streaming quality. dress for an in-person interview and frame yourself from the chest up. ideally make eye contact with the camera -not the screen. this is challenging and requires practice. active listening is a useful skill during in-person interactions but is even more critical during video interviews. finally, practice, practice, practice. that goes for both table tips for successful video interviewing. ➢ use the platform supported by your institution. ➢ test the webcam and audio on the device. ➢ have earbuds with microphone available in the event of microphone trouble. ➢ ensure that your computer is charged or plugged in. ➢ ensure you have a stable internet connection. ➢ pay attention to time zones. location ➢ take note of the backdrop and lighting at the time of day for the interviews. we recommend no beds, bathrooms, or kitchens. ➢ choose a quiet, private location without clutter or distractions. ➢ ensure others will not be walking around in the background. ➢ ensure childcare and pet care as needed. on the day of the interview ➢ have paper copies of the interview materials and a pen. ➢ minimize computer applications and browser tabs. ➢ turn off email and phone alerts (it's loud through the microphone). ➢ dress for a regular interview. ➢ frame yourself from the chest up. ➢ look at the camera -not the screen. ➢ use active listening. ➢ avoid interrupting. ➢ place sticky notes on your computer with questions to avoid having to look down often. ➢ maintain good posture and consider using a stationary chair or locking your swivel chair. ➢ do not eat or drink during the interview. have a bottle of water nearby during short breaks. practice ➢ practice interviews with your faculty members. ➢ record yourself and watch the play-back. candidates and programs. anxiety and unfamiliarity with the format will prevent you from presenting the best version of yourself and your program. programs should do mock interview sessions and give feedback to each other about their sound level, distracting noises, privacy of each location, body language, background, presentation on screen, and framing. while video interviewing has been on the fringes, it is primetime now, and the candidates are most likely to benefit from the process for two reasons. first, virtual interviews significantly reduce the cost involved in the application process. a survey study estimated that obstetrics and gynecology applicants spent nearly dollars per interview, with an average of interviews per candidate. thus, the average applicant spent close to $ , [ ] . second, virtual interviews might reduce the number of days away from training due to elimination of travel time. however, if candidates start to accept more interview offers, due to reduced cost, the time saved might be offset. in the aftermath of the sars-co-v pandemic, healthcare as we know it will not be the same, and academic institutions will continue to grapple with delivering high quality graduate medical education in the "new normal." [ , ] which of these acute adaptations that have been made during the pandemic should be kept? there is no doubt that virtual learning offers new and exciting opportunities that are deserving of further development. a physical presence is not essential for conducting most academic activities including lectures, grand rounds, multidisciplinary cancer conferences, tumor boards, and journal clubs [ , ] . even after the pandemic, these activities can and should continue to be conducted on these platforms, allowing the inclusion of learners who may not be able to attend in person. in the future, such platforms could allow multi-institutional events to take place. for example, a multi-institutional tumor board could be held with screen sharing technology allowing radiology images and pathology slides to be shown as part of case discussion. other possibilities include multiinstitutional grand rounds presentations given by experts in the field who might not otherwise be available to a smaller institution. even weekly fellowship didactics could be coordinated among several institutions realizing new efficiencies. the development and rapid uptake of telemedicine will forever change clinical practice. while post treatment surveillance for cancer patients has been practiced for decades, it requires a significant investment of time and effort for both the clinician and the patient. patients have embraced telemedicine visits during the pandemic, but it is not clear that this enthusiasm will continue, nor that this uptake has been universal across the socio-economic spectrum [ ] . additionally, there are no data regarding how this change in the provider and patient interaction will affect the patient provider relationship, or if remote only cancer surveillance is safe in the long term. nevertheless, there is no doubt that telemedicine is likely here to stay, as some patients who are at low risk of recurrence can have telemedicine integrated into (but not replace) their follow up. we will need to work to include trainees at all levels in this process, so that they can continue to learn how to care for patients, manage problems, and recognize the symptoms of recurrence, even when those women are not physically present. there is no doubt that training has suffered in two areas where adaptation has been less successful: research and surgery. research laboratories in some parts of the country have begun to open slowly with limited personnel allowed in the laboratory. during the early peaks of the pandemic, many cancer centers significantly limited or temporarily halted their clinical trials programs. even some quality improvement research projects were put on hold due to the all-encompassing focus on the pandemic. fellowship programs must mitigate and manage the fellowship research requirement during this time and beyond. flexibility from accreditation and certification bodies will be essential. surgical training is a hands-on experience. advanced surgical technique needs to be repetitively practiced for fellows to become efficient and confident attendings. the potential reduction in cases experienced by select senior fellows during the last - months of their fellowship in may have adversely impacted surgical volume and selfconfidence as they move into their first attending positions. as part of our adaptation, we should establish formal mentorship programs for new faculty and make senior clinicians available to mentor and assist new faculty with complex procedures [ ] . additionally, in the coming months surgeons are likely to be asked to work extended operating room hours during the week and weekend to clear the backlog of cases. efficiency in the operating room means less time for teaching trainees at all levels, and it is not clear how this extended educational hiatus will affect surgical training moving forward. data from the - acgme fellow case logs may be a valuable resource to measure the impact the pandemic has had on surgical training. the focus on wellness is another aspect of the pandemic that should be further developed and sustained. attention to physical wellness should be coupled with the acknowledgement that stress impacts work performance and the work-life continuum. underrepresented minorities in medicine experience additional stressors that deserve our attention as well. recognizing the stress of the pandemic at all levels, most health systems have increased their messaging and resources for work life balance, mental health, and self-directed learning [ , , ] . this increased attention should also apply to our fellows. as faculty, we must continue to de-stigmatize the need to ask for help with stress management, learn to recognize the manifestations of stress in ourselves and our trainees, and be aware of the available resources for management. converting the fellowship interview process to a virtual format will have a far-reaching impact that cannot be measured at this time. there is no doubt that there are multiple positives to this process, many of which are listed above. additionally, many candidates will choose to investigate programs that they might not have otherwise considered due to cost constraints. this opportunity may result in a more diverse pool of applicants for programs that traditionally interview limited cohorts due to geography. how these apparent benefits affect the success of the match for an individual program, for good or bad, may not be evident for years. though much remains unknown, the lessons learned during the covid- pandemic have resulted in rapid and creative adaptation of new techniques to contemporize existing educational paradigms. moving forward, we can develop many of the positive aspects of these adaptations, including virtual learning and multi-disciplinary conferences. these opportunities can and should remain part of our training programs. the focus on wellness and attention to stress should also carry forward, as we have learned the importance of preventing burnout to both the health of our trainees as well as our patients. finally, the loss of the last few months of surgical training for our graduates may be the impetus we need to create a mentorship program for young attendings that was sorely needed even before the pandemic began. the covid- pandemic has challenged us to become more creative and to think of new, and potentially more efficient and better, ways to train gynecologic oncologists that can only benefit us in the future. drs. ferriss, walsh, and rose participated in the conceptualization of the manuscript. all authors participated in writing the original draft, as well as review and editing of the final manuscript. ru reports royalties from uptodate, cw reports research funding from merck and advisory board participation with astrazeneca and genentech. all other authors report no relevant competing interests. covid- ) cdc.gov the covid racial data tracker online: covid tracking project will be the year that medicine was saved? the new york times pandemic hits academic hospitals hard, inside higer ed recommendations for management of elective surgical procedures online, american college of surgeons surgical considerations for gynecologic oncologists during the covid- pandemic maryland hospitals turn to salary cuts, furloughs amid financial crunch from coronavirus coronavirus strains cash-strapped hospitals, could cause up to to close within a year peabody's paradox: balancing patient care and medical education in a pandemic response to pandemic crisis online, accreditation council for graduate medical education updates online impact of covid- on the practice of gynecologic oncology perioperative feedback in surgical training: a systematic review incorporating simulation into gynecologic surgical training total laparoscopic hysterectomy: evaluation of an evidence-based educational strategy using a novel simulated suture and knot-tying challenge, the "holiotomy motivation to access laparoscopic skills training: results of a canadian survey of obstetrics and gynecology residents surgical crosstraining with surgery naive learners: implications for resident training a pilot study of surgical training using a virtual robotic surgery simulator when to operate, hesitate and reintegrate: society of gynecologic oncology surgical considerations during the covid- pandemic the covid- pandemic and research shutdown: staying safe and productive conducting clinical trials in the time of a pandemic the gynecologic oncology milestone project www.acgme.org, acgme innovation in response to the covid- pandemic crisis evaluating the usefulness and utility of a webinar as a platform to educate students on a uk clinical academic programme to the point: medical education, technology, and the millennial learner practical techniques to adapt surgical resident education to the covid- era the impact of e-learning in medical education using technology to maintain the education of residents during the covid- pandemic student perceptions of a simulation-based flipped classroom for the surgery clerkship: a mixed-methods study podcasting in medical education: how long should an educational podcast be? burnout and associated factors among members of the society of gynecologic oncology stress and burnout among gynecologic oncologists: a society of gynecologic oncology evidence-based review and recommendations covid- is reducing physician compensation, job options healthcare finance news cancer patients in sars-cov- infection: a nationwide analysis in china advanced communication: a critical component of high quality gynecologic cancer care: a society of gynecologic oncology evidence based review and guide facing covid- in italy -ethics, logistics, and therapeutics on the epidemic's front line hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease -covid-net, states psychological impact of anti-asian stigma due to the covid- pandemic: a call for research, practice, and policy responses creating real change at academic medical centers -how social movements can be timely catalysts office of diversity, inclusion, and health equity resources women physicians and the covid- pandemic results of the nrmp program director survey specialties matching service online: national residency matching program the growing popularity of video interviewing online residency interview video conferencing virtual surgical fellowship recruitment during covid- and its implications for resident/fellow recruitment in the future videoconference interviewing: tips for success videoconference interviews for an adult reconstruction fellowship: lessons learned randomized evaluation of a web based interview process for urology resident selection obstetrics and gynecology fellowship interview preferences envisioning graduate medical education in adapting the educational environment for cardiovascular fellows-in-training during the covid- pandemic medical and surgical education challenges and innovations in the covid- era: a systematic review key: cord- -jh gkpiz authors: druml, christiane title: covid- and ethical preparedness? date: - - journal: wien klin wochenschr doi: . /s - - - sha: doc_id: cord_uid: jh gkpiz mankind has to prepare for a pandemic with respect to medical and practical aspects, but also with respect to ethical issues. there are various ethical guidelines for managing infectious disease outbreaks, but they do not apply to the specific aspects of the covid- pandemic, since they were formulated after the different kinds of outbreaks of avian influenza and ebola. today we are confronted with completely new issues endangering our fundamental human rights. as covid- is spreading all over the world, we are in a desperate situation to find treatment solutions; however, despite the urgency, scientific rules have to be applied as bad science is unethical since it might be harmful for patients. fake news and alternative facts might not be easily recognized and are also threatening scientific values. pandemics might be leading to a meltdown of the health system if no measures are being taken constraining fundamental human rights. tracking of persons is violating human rights as well if not accepted on a voluntary basis. a failure to have safeguards for times of crisis leads to a scarcity of medicinal products and goods resulting in a nationalistic approach and ignorance of international solidarity. and last but not least selective measures and triage in intensive care have to be taught to young physicians and nursing staff in medical schools in order to be prepared in times of an infectious disease outbreak and scarcity of resources. mankind has learned to live with infectious disease outbreaks. history is full of diseases, such as the plague, smallpox or cholera ravaging continents in times where there were no therapies or economic ways to battle them [ ] . the medical, economic and social achievements of the past years have made a change. still, every outbreak is a challenge as if it was the first one. one reason is the nature of man, putting preparations off when menacing scenarios are not an immediate threat. bill gates stated some years ago at the munich security conference that he "views the threat of deadly pandemics right up there with nuclear war and climate change", and "that we need to prepare for epidemics the way the military prepares for war" (https://www.gatesfoundation.org/ media-center/speeches/ / /bill-gates-munich-security-conference). it is obvious that the world has not been guided by the same conviction [ ] . a pandemic like the novel coronavirus disease sars-cov- changes the perception of our life and decisions in our health systems rapidly. in italy, where the increase of critically ill patients has been exponential for weeks, intensive care unit (icu) beds were scarce, and overworked physicians had to decide over life and death [ ] . we saw the same developments in other parts of the world, although the pandemic has not affected all countries equally. there are recent guidelines for managing ethical issues in infectious disease outbreaks, but they are not a practical tool for the physician at the bedside [ ] or are relevant only for specific issues, such as research (https://www.nuffieldbioethics.org/ publications/research-in-global-health-emergencies). in outbreaks, decisions must be made quickly, even when there is yet no evidence. the challenge is to prepare practical solutions for times of epidemics. pandemic is not pandemic. avian influenza and the most recent outbreak of ebola, which took place in africa represent the main background for current ethical guidance documents. since then, many topics have dramatically changed and we are confronted with completely new and expanding issues, which increase with time and location of the worldwide spread of the coronavirus. one can predict that key issues and ethical guidelines will look much different after the end of the coronavirus pandemic; however, we do need an ethical decision-making framework which guides us in providing systematic and practical answers to ethical questions. what are the new ethical issues we face? the uniqueness of covid- is that it is new and unknown in its properties, highly contagious, and there are no specific drugs nor vaccines to treat the patients or prevent infection. all the identified potential drugs and antivirals have to be screened to find out if they are an option; however, they are not made specifically for the coronavirus, many are not licensed treatments yet. that means they have to undergo a standard clinical trial research program to expand the indications or to get the market authorization. even in a desperate situation and the given pressure of public and governments for speed as with covid- , it is necessary to compare the identified options with the local standard of care in large randomized controlled clinical trials in as many countries as possible to generate valid results quickly and as scientifically sound as possible. small trials or compassionate use programs will not be able to provide robust data in a comparable time and are thus not giving proper scientific evaluation, which is ethically unacceptable. bad science is unethical and dangerous since it might be harmful for patients. drugs, such as hydroxychloroquine have well-documented risks; administering the drug outside of any adequate clinical trial for covid- would be unjustifiable without any clear clinical benefit [ ] . access to clinical information and rapid data sharing is essential. it is a lifesaving necessity, representing a tremendous advantage of knowledge crucial for saving life. but how can we differentiate between reliable information and alternative facts? fake news might be disguised, can discriminate and harm humans, destroy trust in the medical system and counteract the necessary acts to mitigate or suppress an outbreak. fake news and myths, not specific for times of crisis, aggravate the situation [ ] . the internet and social media are its breeding ground. how can we recognize them? we do not have effective drugs against the coronavirus, and the first weeks of this outbreak in wuhan showed that the death toll was rising, a meltdown of the health system needed to be avoided. governments had to resort to means as old as civilization in times of an epidemic, namely isolation and quarantine of persons to protect the vulnerable and to preserve the health system, in particular icus. isolation and quarantine, the restriction of free movement are all measures breaching fundamental human rights. a breach which is only acceptable if it is based on the rule of law and observes the principle of proportionality, if only the less severe means are to be used. governmental decisions raise concern regarding the relationship between the liberty of individuals and societal needs. all restrictions have to be limited for the time of crisis and obligatorily they have to be lifted as soon as the outbreak is over [ ] . governments try to flatten the curve of contagion to avoid a meltdown of the health care system by requiring the population to stay at home, to practice social distancing. smart phones allow persons to be tracked and to observe if persons keep their quarantine. in some countries from early on tracking of persons via the smartphone provider is being practiced [ ] . this poses a breach of the fundamental right of privacy and acceptance depends on the voluntariness or the obligation of the use of the relevant smartphone application. a great part of the population accepts this intrusion understanding that one has to act, but how will we be assured that the fundamental human rights are reestablished once the crisis is over? another feature we can see is the nationalistic approach to and withdrawing from international solidarity. in a world, where international trade is a global mantra, a pandemic leads to a sudden critical shortage of goods, such as test kits and protective gear [ ] . there are few producers worldwide and they act according to the motto "everybody for himself" while frontiers are closed. the recent past has already shown dependency on vital drugs. china produces % of the heparin used worldwide. african swine fever has diminished the supply chain leading to highly reduced swine population and low quality of heparin [ ] . although in the european union a great number of companies have concessions for production, profit was perceived to be too low to manufacture. covid- and ethical preparedness? where are the safeguards to hinder shortcomings in times of crisis? general ethical principles are well known, but there is considerable ignorance about the specific applicability in crisis. many of us live in countries offering a public health system where nobody questions the boundless availability of high-tech measures and interventions. germany and austria are the countries with the highest per capita number of icu beds. but the sheer amount of patients flooding the hospitals in countries like italy, spain or france requiring intensive care treatment made us aware that we needed to prepare ethical guidelines for scarce resources and triage. times of a pandemic are not the place for starting capacity building and training in this field. curricula of medical schools have an obligation of teaching specific knowledge. furthermore (young) physicians and nurses do have to train in their daily work deliberations for difficult decision making. decisions for which they are not prepared in the sudden situation of an outbreak, especially when they have not trained their intellectual and emotional capacity in this field in good times to have them at hand in bad times [ ] . the general ethical principles are always the same, namely justice and solidarity, beneficence, non-maleficence and autonomy. ethical preparedness is as relevant as the provision of surgical masks or swabs, or the formulation of relevant laws to encounter urgencies in the field of public health. let us keep this in mind, also after the end of this pandemic, whenever it may come. in a slight change of that what bill gates said in munich: "the fact that a global pandemic has (. . . ) occurred in recent history shouldn't be mistaken for evidence that a deadly pandemic will not occur (again) in the future". funding open access funding provided by medical university of vienna. conflict of interest c. druml declares that she has no competing interests. open access this article is licensed under a creative commons attribution . international license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons licence, and indicate if changes were made. the images or other third party material in this article are included in the article's creative commons licence, unless indicated otherwise in a credit line to the material. if material is not included in the article's creative commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. to view a copy of this licence, visit http://creativecommons.org/licenses/by/ . /. historical linkages: epidemic threat, economic risk, and xenophobia responding to covid- -a once-in-a-century pandemic? facing covid- in italy-ethics, logistics, and therapeutics on the epidemic's front line world health organization. guidance for managing ethical issues in infectious disease outbreaks. geneva: world health organization drug evaluation during the covid- pandemic -ncov, fake news, and racism can a virus undermine human rights? covid- phonelocationtracking: yes, it'shappening now-here's what you should know. forbes covid- : protecting health-care workers imminent risk of a global shortage of heparin caused by the african swine fever afflicting the chinese pig herd fairallocationofscarcemedicalresources in the time of covid- key: cord- - vna uyo authors: goldfarb, elizabeth v. title: participant stress in the covid- era and beyond date: - - journal: nat rev neurosci doi: . /s - - - sha: doc_id: cord_uid: vna uyo the covid- pandemic represents a worldwide stressor. considering the influence of stress on research participants during this time and beyond may provide new insights and benefit the broader field of human neuroscience. as human neuroscience researchers, we invite people, with their disparate backgrounds, to participate in experi ments to help us uncover fundamental truths about the brain. we are now in the midst of a global pandemic that is changing our lives and the lives of our participants. for those of us who are currently able to work with human participants (in person or online), stress related to the pandemic may have farreaching and unanticipated effects on the data collected during this period. although the pandemic highlights the importance of stress as a factor in everyday life, stress and its neuro biological sequelae are not unique to the pandemic. indeed, stress can be routinely considered and measured in human neuroscience research. however, outside studies explicitly designed to measure stress or affec tive processes, stress is not typically considered. here, i discuss why and how stress should be considered in the design and interpretation of human neuroscience studies during the pandemic and moving forward. the stress of a pandemic stress is classically described as a response to something novel, unpredictable and uncontrollable -all features of the covid pandemic. the fear of illness for ourselves and our loved ones for an unknown period of time has been combined with, for example, prolonged disruptions to daily routine, education, child care, occupation and income that have resulted from efforts to limit the spread of the virus . in the united states, these challenges have been disproportionately faced by black and indigenous people and other people of colour, who are also systema tically exposed to more stressful experiences , . isolation and lack of social support can also trigger maladap tive coping behaviours such as increased substance use that can potentiate risk for covid related complications and interact with stress pathways to alter brain circuitry and cognitive function . if having participants put their arm in a bucket of icy water for a few minutes (a common laboratory stress induction protocol) is sufficient to change participants' behaviour and brain responses , one can imagine the scale of the impact that covid related stress may have on the data being collected now. stress leads to changes in neuronal structure and function throughout the brain. these effects are espe cially pronounced when a stressor is experienced repeat edly or over a long time period, known as chronic stress (which may characterize participants' experiences of the pandemic). research across different species has shown that chronic stress impairs prefrontal and hippocampal circuits (inducing dendritic atrophy and spine loss), and strengthens responses in the amygdala , . these changes occur together with effects on myriad cognitive pro cesses, including attention, reward processing, learning, working memory, long term memory, decision making, strategy selection and top down regulation of emotion . the clinical research community has emphasized the importance of considering the pandemic as a multi dimensional stressor to understand mental health consequences . here, i suggest that this consideration extends beyond clinical science: all the data that are cur rently being collected from human participants are likely to be influenced by this sustained stress exposure. when designing studies to examine stress effects, a 'control group' is typically included to match a 'stress group' in as many ways as possible, short of the stress exposure. this enables us to draw conclusions about the specific con tributions of stress to the behavioural construct or neural process of interest. however, as practically all humans are now exposed to the pandemic, there is no temporally matched control group (although longitudinal studies may be able to consider pre pandemic versus post pandemic differences). crucially, experiences of and reactions to the challenges associated with the pandemic are highly vari able. for example, one participant may have been socially isolated yet had no changes in their employment; another may have grieved the loss of a loved one, taken on new caregiving roles, experienced income loss and increased their alcohol use; and yet another may have had fewer commitments and enjoyed more time with family. to better understand human data, and how they may be modulated by stressors like the pandemic, researchers can leverage tools developed by the stress field . subjective measures. several well validated instruments have been developed to measure the number of stressors people experience and the extent of psychological dis tress they cause, typically including an assessment of when they occurred during the lifespan . these can be implemented using self report or interviews by trained personnel. more recently, techniques such as ecolo gical momentary assessment (ema) use smartphone prompts to track daily fluctuations in experiences of and responses to stressful events. coping behaviours are also relevant to measure, as some responses, such as escala ting alcohol or drug use, can in turn influence behaviour and brain responses . although self report measures rely on conscious insight and willingness to describe what may be stigmatized responses, they can help to predict later health outcomes and can feasibly be incorporated into online and in person experiments. testing kits are widely used to measure stress related hormones in samples of saliva, plasma or hair. although salivary and plasma cortisol are frequently used to measure acute stress responses in the laboratory, they can also provide insight into more prolonged stress states. for example, basal cortisol levels at different times of day are altered with past stress exposure , stress related psychopathology and chronic drug use . although obtaining saliva and plasma (poten tially infectious agents) may be challenging during the pandemic, these measures are routinely used in the stress field, providing a rich comparison data set against which to interpret new data. the body's stress response can also be assessed through measures of autonomic function. tools to measure autonomic responses include arm cuffs to quantify systolic and diastolic blood pressure, as well as electrocardiograms (ecgs) that can provide ambulatory indices of pulse and heart rate variability. these auto nomic functions also adapt with chronic stress and drug use , . given the lack of need for bodily fluid samples to assess autonomic responses, such measures would prob ably be more practicable than neuroendocrine analyses during the pandemic. acute stress challenges. laboratory stressors are frequently used as experimental interventions and can also be used as assays for adaptations in acute stress responses result ing from chronic stress exposure. participants' reactivity profiles to acute stress can be heightened, blunted or show atypical recovery patterns as a function of their stress histories and biological backgrounds . there are various techniques for inducing stress responses in the labora tory, including physical, psychological and cogni tive chal lenges . by measuring subjective, neuroendocrine and/or autonomic responses before and after such procedures, researchers can quantify acute stress reactivity. beyond studies explicitly designed to examine effects of stress, obtaining stress measures provides opportunities for novel insights into brain and behavioural data. careful assessment of individuals' stress profiles may enable researchers to account for unanticipated sources of variance. this approach can also allow researchers to interpret indivi dual differences and divide participants into meaning ful cohorts, leading to the discovery of novel ways in which neural and behavioural processes are associated with stress. the need to consider the affective and physiological context in which people participate in research does not end with the end of covid . we cannot assume that participants always complete our experiments in a neutral state, or that they have comparable histo ries of stressful experiences. individual differences in stress and coping might explain hitherto unknown boundary conditions for reproducing effects in human neuro science, and improve ecological validity by indicating how these processes may occur in the stress rich context of everyday life. going forward, participant level stress profiles can include assessment of remote stress experiences (including the pandemic) as well as in the experimental moment stress reacti vity. broadly consi dering potential stress effects provides opportunities to identify more brain functions that may be susce ptible to stress, elucidate neural factors that determine whether stress is associated with enhanced or impaired function and uncover protective processes that promote resilience. knowing what we do about how stress alters fundamental neural processes, examining the effects of the pandemic and other stressors on data from human participants creates an opening to gain crucial insight into the mechanisms of the human brain. mental health and clinical psychological science in the time of covid- : challenges, opportunities, and a call to action assessment of covid- hospitalizations by race/ethnicity in states collision of the covid- and addiction epidemics drug-induced stress responses and addiction risk and relapse enhancing memory with stress: progress, challenges, and opportunities stress weakens prefrontal networks: molecular insults to higher cognition stress effects on neuronal structure: hippocampus, amygdala, and prefrontal cortex the effects of chronic stress on the human brain: from neurotoxicity, to vulnerability, to opportunity more than a feeling: a unified view of stress measurement for population science effects of stress throughout the lifespan on the brain, behaviour and cognition the author gratefully acknowledges m. d. rosenberg and d. v. clewett for helpful discussions. the authors declare no competing interests. key: cord- -nmmz tke authors: verma, surabhi; gustafsson, anders title: investigating the emerging covid- research trends in the field of business and management: a bibliometric analysis approach date: - - journal: j bus res doi: . /j.jbusres. . . sha: doc_id: cord_uid: nmmz tke the covid- pandemic has been labeled as a black swan event that caused a ripple effect on every aspect of human life. despite the short time span of the pandemic—only four and half months so far—a rather large volume of research pertaining to covid- has been published ( articles indexed in scopus and the web of science). this article presents the findings of a bibliometric study of covid- literature in the business and management domain to identify current areas of research and propose a way forward. the analysis of the published literature identified four main research themes and sub-themes. the findings and propositions of this study suggest that covid- will be the catalyst of several long- and short-term policy changes and requires the theoretical and empirical attention of researchers. the offered propositions will act as a roadmap to potential research opportunities. the coronavirus disease (covid- ) is a human social and economic crisis that has attacked the core of human existence. it continues to spread uncontrollably around the world; as of may , , , , people had been infected globally (who, ) . the outbreak is predicted to reach its peak in june , declining only from july onwards (who, ) . the covid- pandemic has affected all segments of the population, especially vulnerable groups such as the old, the infirm, the disabled, the marginalized and the poverty-stricken (donthu & gustafsson, ) . in response to the pandemic outbreak, the leaders of many countries decided to save lives before saving the economy, declaring sudden or phased lockdowns in their countries. policies like "social distancing" and "stay-at-home" were implemented overnight, which severely damaged several businesses across industries (donthu & gustafsson, ; leite, hodgkinson, & gruber, ) . according to the world trade organization (wto, ), world trade was already experienced a slump in , and then the covid- pandemic precipitated a global financial crisis. early estimates have predicted that major economies will lose around . to . percent of their gross domestic product (gdp) during due to the covid- pandemic (wto, ) . it is becoming challenging for most businesses across the world to keep their financial wheels rolling, given reduced revenues and the high level of uncertainty. it is thus of the utmost importance for businesses to conduct proper assessment and feasibility analyses of their business models (donthu & gustafsson, ) . covid- has also pushed businesses across the world to rapidly operate in newer and more resilient ways. as firms change their priorities in response to old challenges like real-time decision-making, workforce productivity, business continuity, and security risks, newer challenges introduced by the pandemic are testing businesses' resilience as they attempt to lay a foundation for the future (ivanov, ) . to help business practitioners and researchers understand the impact of the pandemic on future economic growth, this study analyzed a corpus of covid- and business and management articles to address questions like the following: what are the growth trajectories and trends of publications in the early phase of the covid- pandemic outbreak? what are the topical foci for research regarding covid- and businesses? this review captures the current state of research about covid- through a systematic literature review and develops propositions to guide future research. it can be described as a prescriptive study that reviews articles pertaining to covid- and aims to provide a reference point for practitioners and researchers alike. the paper includes sections delineating the methodology, results, discussion, conclusion, and future research avenues. bibliometric analysis is an expedient approach to examine the evolution of research domains, including topics and authors, based on the disciplines' social, intellectual, and conceptual structures (donthu, kumar, & pattnaik, ) . researchers have used this technique in a range of disciplines, like strategic management (ferreira, fernandes, & ratten, ) , corporate social responsibility (bhattacharyya & verma, ) , medicine (liao et al., ) , and corporate universities (singh, verma, & chaurasia, ) . although a few recent bibliometric studies have addressed the impact of covid- (chahrour et al., ; hossain, ; park, cook, lim, sun, & dickens, ) , each study has its own set of limitations. chahrour et al. ( ) only examined the most influential observational studies and therapeutic trials described in articles published in the pubmed and world health organization (who) databases. also, they did not study the intellectual structure of the research area. the bibliometric analysis performed by park et al. ( ) included only the pubmed database and the therapeutic aspects of the pandemic. hossain ( ) collated articles published only in the web of science (wos) database and reported that researchers largely targeted biological topics, such as those related to genetics, epidemiology, and zoonosis. importantly, hossain ( ) pointed out the necessity of extending the covid- pandemicrelated research to the field of socioeconomics. to overcome the limitations of these earlier works, this study utilized the science mapping approach to understand the topical foci of the field of covid- and business research ( figure ). the science mapping approach helps researchers to understand the extent of a topic, its emergent trends, and its evolution over time (singh et al., ) . it is a holistic approach that provides better insights than a traditional literature review because it minimizes the potential subjectivity of the researcher (bhattacharyya & verma, ) . this bibliometric study is novel in several respects. first, it applied the science mapping approach (consisting of bibliometric literature and scientometric analyses) in the emerging research domain of covid- and business to minimize subjectivity and bias. second, the research extended the science mapping approach with an in-depth analysis of the identified research themes. third, it analyzed the research topics, identified significant research gaps, and provided future avenues in the research domain of covid- and business. to address the research questions of this study, we identified several research articles published within the business and management field. figure summarizes the research design. the publications was obtained using the scopus and wos databases. data acquisition from existing literature is crucial in the science mapping approach since it determines the dataset of articles from which pertinent conclusions will be drawn (singh et al., ) . we selected both the scopus and wos databases to ensure a wider range of high-quality peer-reviewed journals in the domain of business and management compared to ebsco, google scholar, or others (ferreira et al., ) . we retrieved existing literature related to covid- in the business management domain from the scopus and wos databases using keywords related to covid- (hossain, ) : " -ncov" or "covid- " or "coronavirus disease " or "novel coronavirus pneumonia" or "ncp" or " novel coronavirus" or "sars-cov- " or " novel coronavirus diseases" or "novel coronavirus" or "pneumonia." the keyword search in scopus and wos was set to include titles, abstracts, and keywords in order to retrieve all relevant publications. the search period was set to include articles published between january , , and may , . only english-language publications were considered for the review process. [insert figure here] the initial search yielded over , papers, but narrowing the results to only the business research area yielded papers published in the scopus and wos databases. of these, articles were duplicates (i.e., indexed in both databases) and thus were excluded from further analysis (homrich, galvao, abadia, indicates the adaptability and openness of researchers across the world to understand contemporary issues like the impact of covid- on business. further, the results indicate that this field is still evolving and is in its initial stage, as there are no dominant authors yet. also, researchers with different backgrounds have contributed to the field. in order to identify emerging themes related to covid- in the articles identified in the business research area, we performed a co-word analysis of keywords using vosviewer. co-word analysis applies text-mining techniques to the titles, abstracts, and keywords of articles (van eck & waltman, ). coword links identify multiple keywords that occur together in the same articles. the relationship between keywords is determined based on the number of articles in which the keywords occur together (van eck & waltman, ) . to perform a co-word analysis, we combined the datasets retrieved from the scopus and wos databases and converted them into a microsoft word file for data cleaning and preprocessing. we manually eliminated the duplicate articles from the file and removed coding errors in the sources, affiliations, and cited references for further analysis. for example, we corrected duplication errors such as two different forms of the same author's name (e.g., "lee s." and "lee s.j.") through the data cleaning process. further, we standardized keywords to ensure unification and consistency (i.e., singular/plural). after data cleaning, we conducted data analysis to understand the evolution of the corpus of covid- literature in the business and management domain during using bibexcel and vosviewer. bibexcel is a data analysis tool used for descriptive analysis of data (ferreira et al., ) . we used it in this study because of its high flexibility for data modification in databases like wos and scopus. further, we employed the visualization tool vosviewer, which collected all the keywords from the dataset and created a co-word network. this network helped us to understand the research interests and relationships among keywords. it was from this analysis that the prominent research themes emerged. the study identified themes and sub-themes ( figure and table ). each theme and sub-theme is discussed in detail in the findings and discussion section. [insert figure here] in comparison with the global financial crisis, the covid- pandemic is associated with several new challenges, given that major economic activities have been stifled. the extent of covid- spread across the world has heightened uncertainty regarding consumption and investment among different stakeholders, like consumers, trade partners, suppliers, and investors (donthu & gustafsson, ) . increasing the length of the lockdown and travel restrictions (national and international) are severely affecting the general economy. the covid- crisis is generating spillover effects throughout global and regional supply chains, disrupting demand and supply (pantano, pizzi, scarpi, & dennis, ) . additionally, social distancing policies have almost destroyed service industries, like travel and tourism and hospitality, which could trigger a recession (donthu & gustafsson, ) . the severe global challenges posed by covid- can be tackled using a range of digital technologies, like the internet of things, artificial intelligence, big data analytics, and drones (donthu & gustafsson, ) . this study tried to examine the impact of covid- on different facets of businesses through bibliometric analysis and identified four major discourses ( table ) including impact of covid- on overall business, technologies, supply chain management, and the service industry. [insert table here] the covid- pandemic has already had dramatic, rippling effects across global economic activities in every region of the world (bofinger et al., ) . in order to flatten the curve of infection rates, several countries across the world have imposed widespread restrictions (e.g., lockdowns, quarantines, and closure of physical shops and businesses) to protect the functioning of healthcare systems (michie, ) . understandably, these closures have had an immense, immediate impact on the economic activity in almost every sector. for example, activities involving direct contact between consumers and service providers have been adversely affected by restrictions on movement and social distancing (giritli & olofsson, ) . the closure of the economy has also increased the risks associated with investments by households and businesses. many companies are either facing bankruptcy or reducing their production capacity, which has led to higher unemployment and underemployment (bofinger et al., ) . a prolonged lockdown period also increases the risk of a massive increase in corporate and governmental debts, leading to fundamental financial imbalances that could prolong the recovery period from the covid- crisis (donthu & gustafsson, ) . during the covid- crisis, businesses are working faster to ensure a competitive advantage (lee, venkataraman, heim, roth, & chilingerian, ). in order to solve emerging problems, firms are embracing methods and processes that are responsive rather than reactive to the crisis (chesbrough, right governance (graves & karabayeva, ; lee et al., ) . they are quicker to decide where to invest and reallocate their resources. in addition, firms are pushed to create new product/services and radically adapt in order to remain visible, agile, and productive (chesbrough, ; kim, ) . the covid- crisis has seriously threatened the potential for innovation and discouraged start-ups that could have been viable under normal circumstances (kuckertz et al., ) . a high percentage of startups are poised to go out of business in a few months as the capital and revenue required to sustain them are quickly drying up (bofinger et al., ) . therefore, until the covid- pandemic is over, survival must be the primary focus of start-ups and regulators. further, the crisis has brought about a change in the investment patterns of venture capital firms, which are shifting their focus to start-ups operating in sectors like online grocery delivery, healthcare, fast-moving consumer goods, and home entertainment. (kuckertz et al., ). the creativity and experimentation of start-ups is highly dependent on intense personal and social exchanges between stakeholders. the pandemic-induced lockdown has reduced the opportunities for direct communication and spontaneous encounters, resulting in deleterious impacts on start-ups' growth curves (bofinger et al., ) . according to the wto ( ), trade in will plunge by - % or - % according to the optimistic and pessimistic scenarios, respectively. further, the recovery in is uncertain and will depend on the duration of the covid- pandemic and the effectiveness of policy responses (evenett, ) . despite the closure of international borders, maintaining trade flow is crucial to ensure access to essential goods like medicine and food in addition to supporting jobs and economic activities (ozili & arun, ) . covid- is severely affecting service trades, threatening permanent closure (garvey & carnovale, ) . however, some service trades, like information technology services, are booming because employees are able to work from home (evenett, ) . the covid- crisis has affected around . billion employees (monitor, ) . people across the world are unable to work because they are being asked to isolate or quarantine themselves. due to covid- lockdowns, businesses have increased layoffs and working hours and reduced wages (dey & loewenstein, ) . many employees have been affected by low wages, or loss of income. sectors like travel and tourism, food services, retail, manufacturing, and business and administrative activities are at the highest risk of unemployment and under-employment (bell & blanchflower, ) . covid- is disrupting the economies of many countries by reducing economic activities across multiple sectors, leading to decreases in employment, and reducing revenue streams for several businesses (dey & loewenstein, ; woodside, ) . during this crisis, understanding people's risk perceptions is critical for risk communication (aven & bouder, ) . the risk perception of covid- is influenced by several societal, cultural, and psychological factors and affect one's preparedness and planning (giritli & olofsson, ) . therefore, risk communication should be based on factors like risk attitude, risk perception, and trust in communicating authorities. further, risk perceptions can affect how individuals evaluate threats and information communicated by authorities (aven & bouder, ) . during the covid- pandemic, big data and advanced analytics are helping to detect surface indicators related to the pandemic (guo et al., ) . specifically, real-time big-data-driven insights have helped policymakers and researchers to comprehend and forecast the reach and impact of the covid- outbreak. real-time covid- trackers are helping epidemiologists, scientists, health workers, and policy-makers make more informed decisions to fight the pandemic by aggregating and synthesizing incident big data (hancox, ). further, real-time analysis of gps data indicating people's movement within a certain locality is helping the government understand the population's compliance with social distancing mandates (chen, ) . big data analytics are also helping many leaders to make difficult decisions that affect staff, customers, and operational capacity. for example, firms are leveraging their internal and external data on, for example, customers' contact history, employees' information, business operations monitoring, and social media to understand different scenarios for sustainable development during and after the covid- pandemic (donthu & gustafsson, ) . during the covid- pandemic, digital innovations quickly became the buttresses of personal and professional life (panigutti, perotti, & pedreschi, ) . connected digital devices enable both remote work and education. additionally, chatbots are providing instant life-saving information, partially relieving overwhelmed health systems (leite et al., ) . further, geolocation information systems are helping health workers and researchers to track and map the spread of the virus. firms and governments are designing and piloting fast, responsive frameworks to implement emerging technologies, like data policy, digital trade, iot, ai, drones, autonomous vehicles, blockchain telemedicine, and environmental innovations (panigutti et al., ) . the public health emergency of covid- confronting global healthcare systems has prompted the development of digital health solutions to mitigate the impact of the pandemic (panigutti et al., ) . these digital healthcare systems include telehealth; robust surveillance systems; technology-driven diagnostic and clinical decision-making tools; wearable tracking devices to measure physiological parameters like temperature, heart rate, and sleep-duration; and interactive chat services providing information about covid- (leite et al., ) . telemedicine administered through virtual chatbots and webbots is emerging as a viable option for communication and safe medical care. digital healthcare solutions are helping to detect, report, and provide surveillance and rapid response for covid- cases (panigutti et al., ) . further, they are helping with the creation of geospatial dashboards that display pertinent information at the national and international scales to track covid- statistics in real time (panigutti et al., ) . according to the who director general, the world is fighting not only an epidemic but also an "infodemic" (who, ). this infodemic is causing an over-abundance of information related to the covid- situation, not all of which is accurate (yu, li, yu, he, & zhou, ) . such uncertainty can create confusion and distrust among people and, ultimately, hamper an effective public health response. the covid- infodemic has largely dealt with the cause and origin of the novel coronavirus, its symptoms and transmission patterns, available treatments and cures, and the effectiveness of interventions by health authorities (krause, freiling, beets, & brossard, ) . in response to this, social media and search engine giants, like facebook, google, pinterest, twitter, and youtube, are filtering out unfounded medical advice, hoaxes, and other false information that could risk public health (krause et al., ) . along with several challenges, the infodemic is also creating opportunities to identify and adopt new preparedness and response tools to fight covid- . according to wells et al. ( ) , the covid- pandemic has led to a global socio-technical crisis and several alternative futures. it is globally, rapidly, and pervasively disrupting existing practices (huynh, ) and is quickly emerging as a catalytic and meta-transition event that challenges and reshapes the legitimacy and efficacy of existing political and economic structures (sendak et al., ; woodside, ) . these socio-technical changes will redefine future business activities and ecological burdens (huynh, ) . the covid- crisis continues to globally disrupt manufacturing and supply chains, with severe consequences for consumers, businesses, societies, and the global economy (ivanov, ) . the global production system has been badly affected due to surges in demand for essential goods, factory shutdowns, panic-buying, and shifts in consumer preference (e.g., online over physical shopping ; ivanov, ) . companies are modifying the supply chain by carefully managing interdependent factors, like localization, complexity reduction, dual-sourcing, and investing in advanced manufacturing technologies (garvey & carnovale, ) . apart from these initiatives, manufacturing firms are taking measures to ensure business continuity. these measures include cross-functional controls and coordination on a global and regional level, increase in safety stocks and shift inventories, pivot freight models, improved customer support programs, rebound measures for demand returns, and quick reactions to changing sources of demand in order to secure revenue streams (ivanov & dolgui, ) . the viral outbreak has paralyzed the tourism industry, leading to job losses and devastating economies that are highly dependent on tourism (boulos & geraghty, ) . tourism and cities have strongly intertwined economic, social, and environmental relationships, which shape localities, landscapes, and regions. according to the united nations world tourism organization (untwo), this pandemic has led to a potential loss of usd - billion for the travel and tourism industry (unwto, ), as several countries and regions have imposed entry and exit bans and other restrictions, which have decreased willingness to travel (higgins-desbiolles, ). closure of educational institutes due to the pandemic has not only affected students and teachers but also created economic and social consequences related to digital learning, internet facilities, childcare, food insecurity, healthcare, and housing (arora & srinivasan, ) . as of may , , . billion (approximately . percent) students across countries have been affected by the closure of educational institutes (zhang, wang, yang, & wang, ). educational institutes are opting to conduct classes through internet, digital devices and online platforms (like group video programs) (arora & srinivasan, ) . the covid- crisis is affecting all service sectors due to either spikes or surges in demand. for example, while the retail, tourism, and aviation sectors have been badly affected due to the closure of services to mitigate the risk, food retailers and grocery stores are struggling with rising demand as consumers are trying to stock up for long periods of isolation (addo, jiaming, kulbo, & liangqiang, ) . essential service workers are working in grim and testing working environments, continuously exposed to the virus with no choice but to work (frazer, merrilees, nathan, & thaichon, ) . therefore, essential services need to consider the direct and indirect impacts on employees' occupational safety and health. as the covid- crisis continues to impact businesses in the next few years, economic, societal, and technological changes will become unavoidable for survival. given this backdrop, the current study presents a bibliometric review of papers on the ramifications of covid- in the domain of business and management in order to delineate this emerging research field and summarize the available knowledge. this sub-section provides a synopsis of the four main clusters discussed in section . the synthesis of four distinct research streams in the covid- domain reveals several new opportunities for future practice and research work (table ). due to fears of a financial collapse and new recession, resilient businesses and sturdy government leadership are urgent and critical (giritli & olofsson, ). short-, medium-, and long-term plans are required to rebalance and re-energize the economy (michie, ) . in addition, socioeconomic risk assessments and strategies for robust and sustainable business models are required across every sector. the covid- pandemic is radically changing the demand pattern for products/services, which has in turn increased the risk of fragility in global and regional supply chains and networks (lee et al., ) . to sustain and position themselves for the "new normal," firms should improve their operational resilience, accelerate end-to-end value chain digitization, rapidly increase the transparency of capital and operating expenses, embrace remote work, reimagine sustainable operations, and ensure competitive advantage. in addition, start-ups need to be more flexible and adapt their business models to dynamic markets. policy measures will only be successful if they are complemented by an entrepreneurial ecosystem. further, policy-makers need to implement measures to protect start-ups and adopt or discard policies in the future based on the knowledge derived from crisis situations (kuckertz et al., ) . based on this, we propose the following: proposition a: the covid- crisis not only requires short-, medium-, and long-term plans to rebalance the economy but also raises a clarion call for robust and sustainable business strategies across every sector. proposition b: the covid- crisis demands new operating models to meet changing demand patterns and remain agile and productive. [insert table reforms in trade policy during the covid- pandemic will help to reduce the negative economic and social impact of the virus, which will eventually help to build resilience and ensure economic recovery. for instance, reforms in trade policy can reduce the need for close contact between transporters, traders, and officials, helping to maintain social distancing and limiting the spread of the virus (carnevale & hatak, ) . further, to mitigate disruptions in the regional and global value chain, interventions in logistics operations are required. the impact of this pandemic on employment is unprecedented and will continue to increase; therefore, economies urgently need to implement policy measures to boost the demand for labor. the new labor policies should effectively consider health protection measures and economic support on both the demand and supply sides (bell & blanchflower, ) . also, businesses should pay special attention to building capacity and updating employees' technological skills (carnevale & hatak, ) . based on this, we propose the following: proposition c: reforms in trade policies are required to reduce the negative impact of the covid- crisis. proposition d: changes in existing labor policies are needed to boost the demand for labor. in the covid- crisis, digital technologies, like the internet of things, ai, and blockchain are becoming essential for economic and social functioning (huynh, ) . drones can be used for surveillance to ensure safety guidelines are being followed and to spray disinfectants on affected areas (leite et al., ) . ai-powered tools could be used to obviate the need for manual temperature checks and distance analysis panigutti et al., ) . data-driven insights have the potential to facilitate accurate prediction of impacts and can make the difference between a misstep and a strong continuity response in these uncertain times (hancox, ) . although these emerging technologies have immense potential as equalizers, without the right governance, they could intensify the digital divide in society. further, these technologies are associated with critical privacy and security issues and urgently require a global baseline consensus on security (panigutti et al., ) . the right information related to the pandemic is key for the success of mitigation measures, but the infodemic has exacerbated the crisis, propagating misinformation through social media platforms and other channels (huynh, ) . it should not be doubted that the covid- pandemic has affected relationships within socio-technical systems at the landscape and regime levels. global stabilization agents, such as the wto, world bank, and united nations, can help to create checks and balances and attempt to ensure a return to business as usual (sendak et al., ) . based on this, we propose the following: proposition b: resisting the social-technical meta-transition is essential in the covid- crisis. this sudden shift in the global production system has raised questions about the resilience of global and local value chains and has caused firms to rethink and transform their overall approach to manufacturing and the supply chain model. companies should launch strategic initiatives to create more resilient supply chains. the operation model should be adjusted to enable more flexible and decentralized manufacturing with a consistent risk management system. also, cross-industry collaboration models need to be redefined, and product portfolios require thorough reviews to reduce complexity. based on this, we propose the following: proposition a: the covid- crisis demands resilient strategies to reduce manufacturing complexities. proposition b: modification of existing supply chain measures is required to ensure business continuity while dealing with the covid- crisis. the covid- pandemic will have a long-lasting effect on international tourism due to travel restrictions and changes in people's risk perception of overseas travel. this global epidemic has impacted tourist destinations, leading hotels, restaurants and bars, theme parks, museums, trade fairs, and cultural and sports events to be deserted (boulos & geraghty, ) . the authorities responsible for providing different services should provide clear and consistent guidance to workers to ensure compliance (frazer et al., ) . in the education sector, sudden switching of teaching styles is creating several challenges, like changes to learning plans, acclimatization issues with new online platforms, and conversion of lessons and hands-on learning materials to remote learning and communication (zhang et al., ) . along with these technical challenges, many students and parents do not have access to the proper technologies for distance learning, like the internet and digital devices, or the necessary skills to handle them. based on this, we propose the following: proposition a: the covid- crisis requires robust strategies in different service industries to ensure compliance. proposition b: switching from existing teaching styles is required to reduce the challenges of learning while dealing with the covid- crisis. the objective of this paper was to explore emerging research trends regarding the impacts of covid- on business and management using bibliometric and science mapping approaches. this article contributes to research on covid- by elucidating the theoretical evolution of covid- research and its linkages with multiple economic, social, and technological factors. broadly, the findings and propositions of this article contribute to the epistemological discourse on collective knowledge about the impact of covid- on business and management by examining the most productive authors. in addition, the results show how knowledge is evolving over time based on the use of keywords. importantly, an understanding of the contributions of the most productive scholars and their research helps other researchers build on their work by choosing and following a line of inquiry. ivanov, the most productive researcher in this area, has mainly focused on the short-and long-term impacts of epidemic outbreaks on global supply chains and intertwined supply networks' resilience. ivanov's publications help identify different elements of risk preparedness, mitigation, and recovery policies. this study outlines several research propositions that can serve as a foundation for future research in the area of covid- . there are several theoretical, conceptual, and empirical research opportunities to understand the development of a new paradigm and advancement of existing theories within the business domain due to the disruption caused by the covid- pandemic. additional empirical research opportunities have been created by the emergence of a body of knowledge regarding covid- and subsequent modifications to this knowledge. this is the first academic work to recommend a set of propositions for future research work intended to advance this body of knowledge. this study could benefit managers interested in adopting a proactive approach to understand which changes in strategies, services, and products are required to meet unprecedented demands and develop sustainable business practices. a major practical lesson is that the covid- crisis is quite complex and has caused not only changes in existing business models but also a need to understand and observe transitions in the economy, business, and society. the propositions discussed above suggest that, to mitigate the covid- crisis, managers require forward thinking, new strategies, and re-planning on several fronts. the propositions give managers and decision-makers a variety of practical insights into the challenges posed by covid- and actions and reforms that must be carried out at the economic, social, and technological levels. the propositions also help managers to predict the need for advanced technologies, supply chain resilience, and organizational agility to achieve the right growth trajectory for growth. the economic consequences of the covid- crisis require urgent policy responses from the government to support individuals and businesses alike. properly designed policy reforms are critical for reducing global market distortions. governmental and industrial policy-makers play a paramount role in formulating short-, medium-, and long-term plans. governments must be adaptable as the circumstances of the covid- crisis evolve. the findings and propositions of this study demonstrate that governments should reform existing economic policies to meet individuals' immediate health, food, and other basic needs; maintain political and economic stability; and protect social cohesion. the propositions could help governments and policy-makers to respond effectively to future crises by reevaluating rules and regulations, increasing their digital footprint, and revisiting supply chains. the propositions could also help government agencies identify potential changes to policy tools to resolve medical and economic issues and restore shuttered services, like education, trade, hospitality, and travel and tourism. tables and provide synopses of the new research sub-areas related to covid- and business management. these synopses should provide a solid basis for advancing research in these domains. the evolution of the covid- literature in the business domain exhibits a distinct pattern. first, the diversity of topics and sub-topics addressed by scholars related to the covid- crisis is exponentially increasing, indicating that the virus has impacted our present and future way of life on various fronts. the impact of covid- on business and management is continuously attracting researchers, who are bringing new perspectives on research. second, while the diversity of research areas is increasing, a few broad research sub-topics are emerging more significantly. these core topics include the impacts of covid- on the economy, value chain, supply chain management, innovation, service industry, and employment. thus, the bibliometric results of this study provide evidence that covid- is gradually emerging as a discourse in the business area. the identified core topics serve as pathways for practitioners and academicians aiming to conduct future research. this bibliometric study revealed that, in a short time span (four and a half months), unique documents were published in scopus and wos from different journals, different institutes, and different countries. the findings identify the most active authors and sub-areas of research on business aspects related to covid- . thus, this study has helped identify potential covid- knowledge domains in the field of business and management. lastly, co-word analysis based on keywords provided insights into the main research themes/sub-areas related to the impact of covid- . the covid- crisis will have short-, medium-, and long-term effects on various aspects of society and businesses. this study is an early attempt to gain perceptive insights into the intellectual structure of covid- research in the arena of business using bibliometric analysis. the findings of this study complement existing subjective and evaluative literature reviews on covid- research. journals covered in the scopus and wos databases are published and reviewed each year to ensure their high quality. this bibliometric study utilized only these databases to collect data, but the absence of other databases, like google scholar, ebsco, and pubmed, may have influenced the data representation. therefore, future studies need to amply cover these databases in order to collect more comprehensive data and avoid bias. covid- : fear appeal favoring purchase behavior towards personal protective equipment impact of pandemic covid- on the teaching-learning process: a study of higher education teachers the covid- pandemic: how can risk science help us and uk labour markets before and during the covid- crash the intellectual contours of corporate social responsibility literature economic implications of the corona crisis and economic policy measures geographical tracking and mapping of coronavirus disease covid- /severe acute respiratory syndrome coronavirus (sars-cov- ) epidemic and associated events around the world: how st century gis technologies are supporting the global fight against outbreaks and epidemics employee adjustment and well-being in the era of covid- : implications for human resource management a bibliometric analysis of covid- research activity: a call for increased output covid- : a revelation-a reply to ian mitroff to recover faster from covid- , open up: managerial implications from an open innovation perspective how many workers are employed in sectors directly affected by covid- shutdowns, where do they work, and how much do they earn? effects of covid- on business and research forty-five years of journal of business research: a bibliometric analysis sicken thy neighbour: the initial trade policy response to covid- a co-citation bibliometric analysis of strategic management research creating effective franchising relationships: challenges of managing mature franchisees the rippled newsvendor: a new inventory framework for modelling supply chain risk severity in the presence of risk propagation managing the covid- pandemic through individual responsibility: the consequences of a world risk society and enhanced ethopolitics managing virtual workers-strategies for success a hybrid machine learning framework for analyzing human decision-making through learning preferences robustness in machine learning explanations: does it matter? socialising tourism for social and ecological justice after covid- the circular economy umbrella: trends and gaps on integrating pathways current status of global research on novel coronavirus disease (covid- ): a bibliometric analysis and knowledge mapping the covid- risk perception: a survey on socioeconomics and media attention predicting the impacts of epidemic outbreaks on global supply chains: a simulationbased analysis on the coronavirus outbreak (covid- /sars-cov- ) case viability of intertwined supply networks: extending the supply chain resilience angles towards survivability. a position paper motivated by covid- outbreak the impact of covid- on consumers: preparing for digital sales i'll trade you diamonds for toilet paper: consumer reacting, coping and adapting behaviors in the covid- pandemic fact-checking as risk communication: the multi-layered risk of misinformation in times of covid- new development: 'healing at a distance'-telemedicine and covid- a bibliometric analysis and visualization of medical big data research the covid- crisis-and the future of the economy and economics covid- and the world of work spillover of covid- : impact on the global economy doctor xai: an ontology-based approach to blackbox sequential data classification explanations competing during a pandemic? retailers' ups and downs during the covid- outbreak a systematic review of covid- epidemiology based on current evidence the human body is a black box" supporting clinical decision-making with deep learning mapping the themes and intellectual structure of corporate university: co-citation and cluster analyses international tourism and covid- software survey: vosviewer, a computer program for bibliometric mapping impact of international travel and border control measures on the global spread of the novel coronavirus outbreak interventions as experiments: connecting the dots in forecasting and overcoming pandemics, global warming, corruption, civil rights violations, misogyny, income inequality, and guns who announces covid- outbreak a pandemic trade set to plunge as covid- pandemic upends global economy communication related health crisis on social media key: cord- - qfeoayb authors: lin, leesa; mccloud, rachel f.; bigman, cabral a.; viswanath, kasisomayajula title: tuning in and catching on? examining the relationship between pandemic communication and awareness and knowledge of mers in the usa date: - - journal: j public health (oxf) doi: . /pubmed/fdw sha: doc_id: cord_uid: qfeoayb background: large-scale influenza outbreaks over the last decade, such as sars and h n , have brought to global attention the importance of emergency risk communication and prompted the international community to develop communication responses. since pandemic outbreaks are relatively infrequent, there is a dearth of evidence addressing the following questions: (i) have the resources invested in strategic and routine communication for past pandemic outbreaks yielded public health preparedness benefits? (ii) have past efforts sensitized people to pay attention to new pandemic threats? the middle east respiratory syndrome (mers) that was followed closely by major media outlets in the usa provides an opportunity to examine the relationship between exposure to public communication about epidemics and public awareness and knowledge about new risks. methods: in december, , we surveyed a nationally representative sample of american adults and examined the associations between people's awareness to prior pandemics and their awareness of and knowledge about mers. results: awareness of prior pandemics was significantly associated with awareness and knowledge of mers. the most common sources from which people first heard about mers were also identified. conclusions: communication inequalities were observed between racial/ethnic and socioeconomic positions, suggesting a need for more effective pandemic communication. public health practitioners face unique challenges when developing and implementing risk communication in times of emergencies, as there is limited information on the nature of the threat (including limited data regarding mortality and morbidity, transmission modes, and prevention measures), limited response time, the potential for severe health and economic consequences, media hype and public concern. all of these factors coalesce and intertwine with the diverse social and individual characteristics of the audience when developing emergency risk communication strategy. - the need for effective communication plans that enable coherent, credible and timely communication and community engagement during public health emergencies is increasingly being seen as integral to emergency response and planning. , one area where emergency response and planning is key is with large-scale disease outbreaks. over the last decade, there has been a succession of large-scale outbreaks of influenza, including the sars, avian flu (h n ), new bird flu (h n ) and h n pandemics. these outbreaks raised fears among both scientists and laypeople that an emerging influenza outbreak could repeat the devastation of the spanish flu of . governments and public health agencies recognize the importance of emergency risk communication and have invested significant resources in the development and implementation of public health and communication responses to these outbreaks. the stakes of conducting emergency risk communication are even higher during the early stages of an outbreak, as a treatment and/or vaccine is unlikely to be available for at least several weeks or months after the start of a pandemic. emergency risk communication, such as raising awareness of the disease and promoting health prevention behaviors like hand washing, social distancing and cautioning vigilance among others, plays a vital role in controlling disease transmission. , , one key importance is to study the association between social and individual factors and communication inequalities-differences among people from different socioeconomic positions (seps), racial, ethnic and geographical backgrounds, to understand how individuals access, interpret and act on messages they have received , , - and to identify the best ways to quickly and effectively reach diverse populations with important preventive information. for example, low sep individuals have been found to have lower levels of awareness and knowledge regarding pandemics, leading to poorer behavioral responses when dealing with an outbreak. , - however, as pandemic outbreaks are relatively infrequent, there has been a lack of evidence assessing whether the efforts and resources invested in the strategic risk communication during past pandemic outbreaks yielded public health benefits that improved preparedness. gaining an understanding of whether or not the messages emphasized during the response to previous pandemics helped the public, particularly members of low sep populations, become more aware and better prepared is invaluable. therefore, the question that remains to be answered is: does an awareness of past epidemic risk communication help people become more health aware of an emerging epidemic, or, on the contrary, have the past few pandemic communication experiences created a 'boy cries wolf ' effect, making people less attentive to information provided concerning pandemic outbreaks? , in late , the middle east respiratory syndrome (mers), a viral illness caused by a coronavirus, was first reported in saudi arabia. although this particular virus had a very low probability of impacting the usa, major media outlets followed it closely, providing the american general public with an opportunity to become familiar with the outbreak. in this study, we assessed people's awareness of previous pandemic outbreaks and how that awareness affected their awareness and knowledge of mers. we identified other predictors of mers awareness and knowledge and investigated the information sources from which people who had heard of mers first learned about it. we also identified a subgroup of people who had have not heard of most or all risk communication messages regarding five pandemics (i.e. sars, avian flu (h n ), new bird flu (h n ), h n , and mers) which have erupted in the past decade. the analyses in this paper will help inform and calibrate strategic risk communication during a future pandemic. the data for this study, collected from to december , were drawn from a nationally representative sample of us adults aged and older. the survey instrument was adapted from previously tested communication surveys we developed based on focus groups, cognitive testing results and the national cancer institute health information national trends survey. - respondents participated in knowledge networks' knowledgepanel w and were recruited using a dual sampling frame, which is a combination of random digit dial and address-based sampling, thus allowing for sampling of individuals with no telephone landlines. once recruited into the study, participants completed an internetbased survey in their home including questions about demographics, pandemic awareness and mers-specific topics. households were provided with internet access and necessary hardware if needed. post-stratification weights were used to adjust for non-coverage and non-responder bias. the survey included an online field experiment that is not the focus of this analysis, including the experimental conditions as a covariate did not materially alter the pattern of findings and therefore they are not reported in this analysis. independent variables † awareness of previous pandemic outbreaks was assessed by asking the participants: 'have you heard of [ ] sars, [ ] h n or swine flu, [ ] bird flu or avian flu (h n ), [ ] new bird flu or influenza a(h n ) and [ ] mers (also called mers-cov, middle east respiratory syndrome, novel coronavirus, or ncov), in the past years?' two awareness variables were created based on respondents' answers: † awareness of pandemic outbreaks prior to mers: respondents were categorized into three groups based on their response to diseases ( ) to ( ): low (heard of outbreaks), medium (heard of three outbreaks) and high (heard of all four outbreaks). † low pandemic awareness: including mers and the four prior pandemics listed above, those who have heard of only one or none of any of them were labeled to be having low pandemic awareness. † age and gender. † race/ethnicity: non-hispanic white, non-hispanic black and hispanic † sep was measured by their household income ($ , $ - , $ - , $ ) and education (bachelor's degree or higher, some college, high school, less than high school). for the purpose of this study, to measure respondents' knowledge about mers and to ensure its accuracy and equal accessibility to all, we referred to centers for disease control and to account for randomly guessed responses, correct answers are discounted if the respondents also selected incorrect answers. a score of was given if the following correct statements were checked: [someone can get mers from] 'being in close contact with someone who has mers (within arm's length of someone)' and 'no, there is not a vaccine against mers' and none of the following wrong options were checked: [someone can get mers from] 'eating chicken', 'coming in contact with chicken', 'eating pigs', 'coming in contact with pigs' or 'none of the above.' a score of was given if either one of the two correct statements and none of the wrong ones were checked. a score of was given to any other combination of responses. † source of initial mers information: participants were asked to report the source where they first learned about mers. a descriptive analysis was conducted to explore the characteristics of the surveyed sample (table ). in table , logistic and ordered logistic regressions, respectively, were conducted to evaluate the associations between awareness of previous pandemic outbreaks in the past years, socio-demographic factors and (i) awareness of mers (model ) and (ii) knowledge levels about mers (model ). using cross-tabulations and x , we identified the associations between respondents' socio-demographic characteristics and the sources from which they first received the information about mers. lastly, we ran logistic regression to determine the predictors of having very little awareness of previous major pandemic outbreaks (including mers) in the past decade. the associations between low awareness of previous pandemic outbreaks and socio-demographic factors were examined, and the results are presented in table . stata w version was used for all analyses. there were respondents who participated in the study, reflecting a response rate of . %. these respondents had a high awareness of the four pandemic outbreaks that affected international communities prior to mers. the prior pandemics were sars, h n , avian flu (h n ) and the new bird flu (h n ). more than half of the sample ( %) had heard of all four of them and about ninety percent ( %) were aware of at least two outbreaks. specifically, the recent h n pandemics are the best known outbreaks among the sample population, % (n ¼ ) of them have heard of h n , followed by avian flu (h n ) ( %, n ¼ ), sars ( %, n ¼ ) and the new bird flu (h n ) ( %, n ¼ ). only one-third of the respondents had heard of mers ( %, n ¼ ); among those who have heard of mers, more than half ( %) received a knowledge score of , one quarter had a knowledge score of , and the rest ( %), those who had no or incorrect knowledge about how mers spreads, received a score of . more information on sample characteristics is presented in table . to inform future pandemics risk communication strategies for future pandemics, we further investigated the following: (i) among those who had heard of mers, what were the sources they used to first learn about it? (ii) among those who have low awareness of pandemics, who are they and what are their background characteristics? our data showed that national news network ( %) and local news television stations ( %), family and friends ( %) and internet-based search engine such as google or bing ( %) are the most commonly used information sources from which the respondents first learned about mers. social media such as facebook, twitter, googleþ, etc. had only minimal contributions as sources of pandemic information (, %). forty percent of those who had heard of mers said that they could not recall where they first learned about the virus. people with low awareness of pandemics in the past decade among the surveyed population, % (n ¼ ) had never heard of any of the pandemic outbreaks which had occurred in the past decade, including mers and the four pandemics prior to it, as discussed above, and % (n ¼ ) had only heard of one outbreak, of which most respondents reported hearing of h n . the logistic regression analysis, seen in what is already known on this topic? the need for effective communication plans that enable coherent, credible and timely communication and community engagement during public health emergencies is increasingly being seen as integral to emergency response and planning. , taking population diversity into consideration when developing risk communication plans has been shown to improve responding agencies' risk communication capabilities and, ultimately, the effectiveness of the response, especially in communities with limited local capacity. , this lesson was reinforced by the experience of recent international pandemic outbreaks of diseases and viruses such as the sars, avian flu and h n when the constructs of strategic risk communication such as public awareness, media exposure and knowledge about specific threats were further identified and assessed. , , , , - studies confirmed that awareness of media reporting about current threats, general news exposure, people's attitudes and beliefs and people's knowledge about a specific threat are positively associated with a person's knowledge about a specific threat and their adoption of recommended prevention behaviors. , , , - main finding of this study in this study, awareness of prior pandemics was significantly associated with both awareness of a new threat, mers, and higher knowledge levels regarding it; racial disparities were found in awareness and knowledge levels of mers. there was no evidence that having heard about pandemics that occurred prior to mers had a 'boy cries wolf ' effect, in which people tuned out information about mers. however, we found that individuals who were younger, had lower income or had less than a bachelor's degree were more likely to report having no awareness of previous pandemics compared with their counterparts. national and local tv networks were the most commonly used information sources from which people first heard about mers. this finding is consistent with previous studies, in which national news networks and/or local news television stations were found to be the most effective channels through which to convey public health messages, while the impact of social media was found to be surprisingly small. what this study adds? increasing awareness alone may not be enough to prompt preventive action, particularly among diverse groups. pandemic communication need to contain clear, comprehensible information about the pandemic offered through trusted, commonly accessed media channels, such as national and local tv networks. customizing messages about risk to one's intended audience and communicating these messages to them via appropriate information channels are instrumental to running an effective communication campaign. - it is notable that minority participants had both lower awareness of and less correct knowledge about mers and that individuals with lower education and lower income were less likely to have an awareness of any pandemic, indicating the presence of communication inequalities in pandemic awareness among these subgroups. more research is needed on the awareness and knowledge of future pandemics in a diverse low sep sample to best understand the impact of communication inequalities and how to address them through targeted campaigns. the current findings indicate a need to pay attention to segments that may not be actively seeking out information and to deliver it via channels that they use. given the fact that few people reported that they had first learned about mers through social media, our data suggested that national media such as tv are still important and social media, at least in times of pandemics, appear to be less effective. emergency risk communication has to be strategic, evidence-based and must take into account potential communication inequality. the data for this study are cross-sectional in nature and thus limit us from drawing a causal relationship between the independent and dependent variables. nevertheless, this study finds a link between having heard of prior pandemics and knowledge and awareness of a subsequent pandemic (i.e. mers) that should be further investigated. future studies using experimental, longitudinal or case -control designs could help provide evidence for causal relationships. although the data rely on self-reporting, our survey items were adopted from widely tested national surveys and validated by cognitive testing. the response rate for the survey was . %. poststratification weights were used to adjust for non-coverage and non-responder bias. in the case of the / h n flu pandemics, mexicans and other latinos living in the usa were more likely to be stigmatized by non-hispanic americans as carriers of the virus, partly because of news reports on the outbreak's alleged origin in mexican pig farms. hispanic americans also reported higher levels of risk perceptions of the flu. therefore, in light of the origin of mers, it could be useful for emergency risk communication scientists to further investigate the possible association between knowledge and awareness levels of the mers virus and subsets of populations in the usa with potential personal or family ties to the outbreak regions (e.g. middle eastern migrants). this study found that awareness of past pandemics was associated with higher awareness of and correct knowledge about the / mers outbreak. despite these associations, the overall level of awareness of this new threat was low and communication inequalities were observed between racial/ ethnic and low sep groups. results suggest that awareness of past pandemics might indicate that an individual is more likely to have heard about a new threat, and that more research is needed to discover barriers to awareness that may be present in lower sep samples. emergency risk communication has to be strategic, evidence based and must take into account potential communication inequality. this project was funded by the harvard school of public health preparedness and emergency response center (harvard perrc)-linking assessment and measurement to performance in phep systems (lamps), cdc grant number: po tp - . the content of this publication as well as the views and discussions expressed in this paper are solely those of the authors and do not necessarily represent the views of any partner organizations, the cdc or the us department of health and human services nor does mention of trade names, commercial practices or organizations imply endorsement by the us government. race, ethnicity, language, social class, and health communication inequalities: a nationally-representative cross-sectional study media use and communication inequalities in a public health emergency: a case study of - pandemic influenza a virus subtype h n the h n pandemic: media frames, stigmatization and coping implementation of nonpharmaceutical interventions by new york city public schools to prevent influenza a communication inequalities during public health disasters: katrina's wake communications in public health emergency preparedness: a systematic review of the literature what have we learned about communication inequalities during the h n pandemic: a systematic review of the literature preparing racially and ethnically diverse communities for public health emergencies individual differences in behavioral reactions to h n during a later stage of the epidemic statement to the press: world now at the start of influenza pandemic. geneva: world health organization socioeconomic status, demographics, beliefs and a(h n ) vaccine uptake in the united states socioeconomic status and health communication inequalities in japan: a nationwide crosssectional survey communications under uncertainty: communication behaviors of diverse audiences during the a(h n ) incidence of spring and summer getting vaccinated or not getting vaccinated? different reasons for getting vaccinated against seasonal or pandemic influenza early responses to h n in southern mainland china awareness, anxiety, compliance: community perceptions and response to the threat and reality of an influenza pandemic chinese urban-rural disparity in pandemic (h n ) vaccination coverage rate and associated determinants: a cross-sectional telephone survey public health communications and alert fatigue implications of public understanding of avian influenza for fostering effective risk communication health information national trends survey (hints) : final report. bethesda, md: national cancer institute hints ): final report. bethesda, md: national cancer institute health information national trends survey middle east respiratory syndrome (mers) effective health risk communication about pandemic influenza for vulnerable populations disaster planning and risk communication with vulnerable communities: lessons from hurricane katrina infectious diseases and governance of global risks through public communication and participation perceived threat, risk perception, and efficacy beliefs related to sars and other (emerging) infectious diseases: results of an international survey mass media and population health: a macrosocial view early response to the emergence of influenza a(h n ) virus in humans in china: the central role of prompt information sharing and public communication the impact of communications about swine flu (influenza a hiniv) on public responses to the outbreak: results from national telephone surveys in the uk situational awareness and health protective responses to pandemic influenza a (h n ) in hong kong: a cross-sectional study community psychological and behavioral responses through the first wave of the influenza a(h n ) pandemic in hong kong knowledge and practices towards influenza a (h n ) among adults in three residential areas in tampin negeri sembilan: a cross sectional survey surveillance of perceptions, knowledge, attitudes and behaviors of the italian adult population ( - years) during the - a/h n influenza pandemic preventive behaviors, beliefs, and anxieties in relation to the swine flu outbreak among college students aged - years knowledge, attitudes, and behaviors of low-income women considered high priority for receiving the novel influenza a (h n ) vaccine. matern child health h n preventive health behaviors in a university setting socioecological and message framing factors influencing maternal influenza immunization among minority women message framing strategies to increase influenza immunization uptake among pregnant african american women patient knowledge and recall of health information following exposure to 'facts and myths' message format variations message formats and their influence on perceived risks of tobacco use: a pilot formative research project in india providing health messages to hispanics/latinos: understanding the importance of language, trust in health information sources, and media use did h n influenza prevention messages reach the vulnerable population along the mississippi gulf coast? trust influences response to public health messages during a bioterrorist event public risk perceptions and preventive behaviors during the h n influenza pandemic key: cord- -im y lg authors: pace, bruno di; benson, john r.; malata, charles m. title: breast reconstruction and the covid- pandemic: adapting practice date: - - journal: j plast reconstr aesthet surg doi: . /j.bjps. . . sha: doc_id: cord_uid: im y lg nan we thank dr cavalcante and colleagues for their constructive comments in response to our viewpoint on breast reconstruction during the covid- pandemic. we welcome discussion of this timesensitive issue within the context of a different healthcare system which they base on an electronic survey of brazilian surgeons over a two-month period. a common concern is the backlog of patients, who will eventually require reconstruction, and the psychological impact of delayed reconstructive procedures -whether for partial or whole breast restitution. restrictions imposed at the start of the pandemic are being gradually eased but re-introduction of breast reconstruction is a challenge for healthcare providers at the present time, especially with fears of a second wave of infection and other-site cancers still awaiting curative surgery. furthermore, resumption of 'normal' practice is arguably more difficult in those units where rates of immediate breast reconstruction (ibr) pre-covid- were high; it is noteworthy that overall rates of breast reconstruction in brazil were % before the pandemic, a figure that is higher than recorded in the uk national mastectomy and breast reconstruction audit ( %). issuance of covid- specific guidelines by the association of breast surgery in the uk had a dramatic effect on ibr with only % of units reporting continuation of this practice during the pandemic (abs national audit -preliminary data). the questionnaire sent out to brazilian surgeons about reconstructive practice during the pandemic had a response rate of just over one-third; it is unclear whether this questionnaire addressed intentional or actual reconstructive practice during the pandemic with two-thirds ( %) of surgeons supporting ibr using predominantly implant-based techniques (permanent or temporary tissue expanders). it is reassuring that only % of surgeons would advocate complex flap-based reconstructive procedures during the active phase of the pandemic and this concurs with our viewpoint. of interest, just over half of brazilian surgeons were opposed to therapeutic mammoplasty; this procedure can avoid complete mastectomy in some patients with larger breasts and hence negate any requirement for ibr. furthermore, the contralateral side could be done at a later date -perhaps after breast irradiation as this can disrupt initial symmetry from a simultaneous balancing procedure. we agree with our brazilian colleagues that reconstructive procedures should be undertaken on a discretionary basis related to individual patient needs/preferences, local circumstances and critically operative capacity together with the phase of the pandemic. we are now witnessing a resurgence of infection in some parts of the world and this will affect reconstructive practice if operative capacity becomes restricted once again. we would argue that implantbased reconstruction should largely be dependent on operative capacity rather than concerns about potential complications, prolonged hospital stays and re-admission. reconstruction with tissue flaps (myocutaneous or otherwise) might be acceptable during the recovery phase if resources are adequate in terms of staff and facilities. standard operating procedures should be adopted to streamline patient care and pre-emptively document management plans for any complications. remarkably there is no indication of pandemic stage at the time of this electronic survey; south america has lagged behind europe by approximately - months for phase of disease. moreover, the response rate might have been higher with use of the total design method permitting a more representative cross-sectional sample. nonetheless, more than surgeons belonging to the brazilian society of mastology submitted responses and presumably these were a mixture of plastic and breast oncological surgeons. we agree with cavalcante and colleagues that carefully designed strategies are required as we move into the next phase of the covid- pandemic. these must minimise the strain on healthcare systems, maximise patient safety and provide optimum cancer care. surgical practice must be dynamic and adapt to changing circumstances with close co-operation between breast and plastic surgeons working synergistically within a multidisciplinary team. resumption of reconstructive practice should closely mirror national guidelines and exercise due caution to minimise risks of complications whilst addressing clinical need and patient expectations. the latter must be realistic with appropriate selection of patients and adherence to a fully informed consent process that reflects the additional risks associated with covid- . breast reconstruction and the covid- pandemic: a viewpoint national mastectomy and breast reconstruction audit statement from the association of breast surgery th march : confidential advice for health professionals utilizing the total design method in medicine: maximizing response rates in long, non-incentivized, personal questionnaire postal surveys the authors have no financial interests to declare in relation to the content of this article and have received no external support related to this article. no funding was received for this work. key: cord- - zbxjmxu authors: shao, connie title: the covid trolley dilemma date: - - journal: am j surg doi: . /j.amjsurg. . . sha: doc_id: cord_uid: zbxjmxu nan due to the covid- pandemic, hospital systems have had to drastically reduce the number of surgeries being performed, and in many cases eliminate certain procedures altogether. restricting our current surgical volume is an attempt to decrease exposures for our patients and healthcare workers while preserving personal protective equipment. as the first wave of this pandemic subsides, hospital systems are faced with prioritizing which surgical services can resume while simultaneously minimizing the disruption of ongoing care for the remaining covid- patients. this is all while ensuring our patient population at home is able to receive appropriate care. surgical management of patients is seldom "elective". the effects of general anesthesia, the trauma of undergoing an incision, is a physical breach unwanted by those who can avoid it. however, in the era of limited resources in a pandemic, this word has developed a new meaning. "elective" -a normally one-dimensional word reflective of whether a surgery is an emergency or not now has an added dimension of temporality. how does one quantify an emergency? will this patient survive one week, one month, one pandemic without undergoing surgery? in a medical structure now limited by resources, as well as patient and provider exposure, guidelines have been disseminated by multiple bodies. cms created guidelines to guide surgical management stratified by local covid- disease burden, resource availability, and patient disease severity. hospitals now function with a new set of perioperative management to limit exposure of healthcare workers ( ). guidelines on surgical management of oncologic care were previously established with years of literature to support and create the nccn guidelines. patients requiring oncologic surgery now face a "double jeopardy" of increased exposure to covid- due to frequent interactions with medical facilities, but also worse outcomes associated with delaying surgery. acs created a set of guidelines relying on anticipated phases of the pandemic: guidelines have also been created on a federal and state-wide level. but who will enforce? at a time when hospitals are furloughing staff, reducing salaries for staff, and scrambling for ppe for their employees, it would be in the financial interest of keeping a hospital running to proceed with elective surgeries in an effort to help mend the expected deficits of hundreds of millions per hospital. but how will these tenuous months be remembered in history? as certain areas in the country have the resources to resume elective surgery, how will they be remembered in a time when other, heavily affected parts of the country struggle with unmet needs for goods and services? ( ) how will public opinion change as institutions protect their financial interests over the wellbeing of their neighbors? as the federal government makes decisions to re-open the economy, how will each state be remembered for their own autonomous decisions to do what is best for their citizens based on the data they have? on the other hand, restricting surgical management to those who will perish along some unknown sliding scale of urgency has lasting consequences. more than million surgeries were done in the united states in ( ), with an estimate that over % of these surgeries are considered elective ( ) . with an estimated three-month delay of elective cases, almost million cases will be delayed, some for the entire three-month course, resulting in both immediate and repercussive effects. delaying resection for clinical stage i non-small cell lung cancer by weeks or greater after radiologic findings concerning for lung cancer is independently associated with increased rates of upstaging and decreased median survival ( ) . those who are anxious to come into a hospital setting with abdominal pain present days later with gangrenous, perforated appendicitis and cholecystitis. patients with delayed elective aneurysm repairs wait at home with increasing risk of rupture. as the immediate wave of morbidity and mortality associated directly with the covid- pandemic subsides, the effects of delaying both diagnosis and surgery will be revealed. • inpatient populations, increasingly consistent of critically ill patients, will overwhelm nursing care facilities and home health nursing. with furloughed clinic staff and patient populations unfamiliar with how to interact with telemedicine, many will present with preventable complications after months of no preventive medical attention. patients with chronic conditions will present with hypertensive strokes, copd exacerbations, diabetic neuropathies with subsequent wounds/impaired healing. many of these issues will be mitigated by the chemotherapy, medical management, telemedicine, and eprescribing, but there will be those lost to a world without medical care for months. in a world currently controlled by scarcity, it seems an unfair decision to have to make -who will be seen, who will be treated, who will be sent home with hopes for a successful course of conservative management, who will perish. but with limited resources on multiple frontsfinances, staffing, hospital resources, critical care availability -scarcity is a reality. with multiple forces at play, it becomes increasing important to recognize why we became physicians. our purpose is to heal, to do what is best for patients. the hospital exists as a locus for patient care, its bottom line is not the reason why we became physicians. there will be losses, but the greatest loss is that of life. recently, a patient with plans for elective repair of his ventral hernia presented to the emergency department with incarcerated bowel in his hernia. his exquisite tenderness and skin changes required emergent repair. with penetrating fear in his eyes, he told his surgical team of his siblings who had both gotten sick and passed in the last year. his fear of becoming sick or dying was recognized and acknowledged -who wouldn't be afraid in his position; but he was safe now, in the care of physicians who knew exactly how to fix the cause of his pain. there was no better place for him to have his problem than in the hospital. now he was here, and everything else was in our hands. his trembling grip and imploring gaze made clear his fear felt seen but was not mitigated. as a surgeon, bringing patients' anxiety and fear into quiescence is as close as one can come to a nonsurgical remedy, knowing that the true resolution of their fear happens under the blade of a knife and the curtain of sedation. he was emergently brought to the operating room and underwent induction of general anesthesia. the circulating nurse was painting his abdomen in betadine when his rhythm suddenly changed from normal sinus to ventricular tachycardia, then fibrillation. compressions started. a crash cart appeared. the room populated within minutes. he became profoundly hypoxic. after half an hour of acls, he finally regained return of spontaneous circulation. his bedside ekg and echo showed antero-lateral infarction with a hypokinetic septal wall consistent with ischemia of his left anterior descending coronary artery -he had suffered a massive heart attack. his road toward recovery now led him to ecmo and the catheterization lab. had his elective procedure continued with its normal timeline of pre-operative workup, a stress echo would have brought his underlying cardiac pathology to light and likely led to a pre-operative pci or surgery. he would have had smoking cessation counseling, he would not have known a world in which he had chest compressions, cannulation for ecmo, or emergent catheterization to salvage a dying heart. for the determinists, perhaps a world without a pandemic would have still resulted in these events in some other way. but to extend one's hand to a patient in treacherous waters and watch a buoy become an anchor places the weight of unseen costs of this pandemic on a very personal set of shoulders. how long should we continue to delay care to ensure we are doing what is best for all of our patients? this pandemic has proven itself to be a trolley problem incarnate. the trolley problem is a classic thought experiment introduced in -to watch a train go down the main track and kill five people, or to flip a switch for the trolley to go down a side track, killing only one, but then becoming directly responsible for that person's death. while typical variants include changing the number of people on each track or making one of the possible victims the switchman's family member, the current variant brings a tremendous number of considerations: as the train moves forward, the number of people on both the main and side tracks increases, but the actual number at each track is unknown. the mortality and morbidity associated with being in the way of the trolley is also unknown. some may survive only to be injured, others may survive with no sign of injury at all. there are groups of people demanding that it is a violation of their rights to not be positioned on the main track. they are eventually on the main track and their occupation of resources puts additional people on the side track. the governing body supplying funding for the trolley, reopens ticket sales for additional passengers, who find themselves on the main track in the path of the trolley. investing in the trolley also lengthens the tracks, increasing the amount of time before the trolley hits and thus the number of people on either track. the tracks do not target isolated groups of people; rather, there is an infinite number of options that will result in morbidity and mortality in both groups to varying degrees. • the number of subsequent groups of people on main and side tracks (i.e. second and third waves) are dictated by current decisions with an impact that can be anticipated but not predictable. the trolley dilemma engages the praxis of our intentions and hopes for our patients. what will come of loosened shelter-in-place orders as economies suffer? how long will our patients wait at home until their elective surgeries become urgent? how long can you treat a patient's cancer with chemotherapy before their cancer becomes unresectable? how will patients be affected by increasing length of stay by several days for follow up studies to avoid returning to clinic, or by decreasing length of stay for patients who are sent home from the hospital with monitoring devices and telehealth to decrease exposure? with data and guidelines changing continuously, it is important to maintain ongoing, transparent discussions of frameworks developed by different institutions to provide care for our patients. to have some understanding of how the tracks of the trolley populate requires an understanding of pandemic modeling. alabama has been fortunate enough to be trending somewhere between the early and late phase recovery of the acs guidelines. the decision to start caring for patients who have been getting sicker at home is based on an incredibly complicated trolley dilemma in which the focus is on damage control, both actively and in anticipation. though the current burden of the pandemic is different in every state, eventually each will need to determine whether it is an appropriate time to resume "elective" cases, as well as tier which cases are to be resumed at which time. as the acs described, "understanding both the local facility capabilities (e.g., beds, testing, operating rooms [ors]) as well as potential constraints (e.g., workforce, supply chain), while keeping an eye on potential subsequent waves of covid- will continue to be important." due to strict measures, both institutionally and on a policy level, the spread of covid in alabama has maintained a steady state for two weeks, as seen by a ro value consistently around . ro reflects the infectivity of the virus -the general concept is simplified and described below: for the increase in i to be , = = − , therefore * = , which will be defined as ro. if ro < , then < , which means that the number of infections is decreasing. at the beginning of the pandemic, it was said that each person infected - people (ro = . - . ), with additional reports showing r values between . and . , leading to the extremely rapid growth of the of -ncov outbreak as compared to the sars epidemic where r was estimated to be between . to . ( ). to make ro < , * < , one or more of the following are needed: • decrease in i (daily rate of contacts per infective) • decrease in s (number of susceptible, which decreases with herd immunity, vaccination) • increase in r (shorten the number of days people are infectious, currently thought to be around days) while herd immunity (sufficient decrease in s) is not attained and i increases again when stay-at-home policies are lifted, the rate of infection will again become exponential. additionally, to attain herd immunity while in anticipation of a vaccine requires all to become afflicted with covid- , for which there is currently a mortality rate of % ( ). sars and mers were both contained by restricting i -however, while case fatality rates were higher, covid- has proven to be more infectious ( ), resulting in a higher overall number of deaths, especially given the speculation of silent spread by asymptomatic carriers and the survival of those who are infected and capable of further spread. in addition, there is no clear evidence on permanent immunity against covid- . until testing capabilities are able to select and isolate only those who are known to be infected with covid- or the development of a vaccine can successfully reduce s, spread can only be minimized by decreasing i not only through containment of the symptomatic, but additionally by restricting interactions among the symptomatic and asymptomatic alike. when the state-wide shelter-in-place order was instituted in alabama / at pm, the anticipated icu bed needs went from , on / to on / based on ihme covid- projections. the statewide shelter-in-place policy protects those in and out of the hospital, but mostly those who are not yet inpatient and who will need to come to the hospital. consequently, new cases have been stabilizing. the estimated ro value depicted in the graph above was calculated using bayesian statistical analysis of the data provided from covidtracking.com and reported in the new york times ( ) . the rate of infectivity has dropped due to timely action on both a state and city level. the pandemic is far from over -additional surges are expected to recur as states begin loosening shelter-in-place policies. the spanish flu lasted two years, infected million worldwide and killed - million. a significant number of mortalities occurred during the second wave ( ), thought to be caused by a mutated version of the virus. mutations aside, the relaxation of shelter-in-place policies will result in an inevitable recurrence of exponential increase in infections. as we attempt to open our doors to take care of those trapped by the pandemic getting sick at home, it becomes increasingly important to invest in measures to reduce the burden of the pandemic until testing or a vaccine is widely available. as with all forms of prevention, the benefit of shelter-in-place orders can never truly be measured, only estimated in theory -an avoidance of devastation is just a normal day taken for granted. guidelines, such as those created by acs, for careful and precarious resumption of local "elective" surgeries are moot when conservation efforts are overrun by an uncontrolled ro. at a time that we do not have herd immunity and a vaccine does not yet exist, government-mandated orders are necessary to protect our patients, ourselves, and those who will become our patients. as this pandemic continues to force us to question everything we thought was certain, including certainty itself, it is important now more than ever that we move forward in a concerted effort. the purpose of creating a trolley is to serve people, just as money was created as a tool to serve people. to become subjugated to a system that we created to serve us is to lose who we are to what we are. we exist as a precious microcosm of life in a vast, infinite nothingness -do we not exist purely for love, for family, for passion, for beauty? as this pandemic passes, will our woes not be counted by those that we have lost -a scar in our mortality, our roots, our identity? the cost of this pandemic is high in so many seen and unseen ways. may this fork in the tracks be short and merciful. surgery during the covid- pandemic: a comprehensive overview and perioperative care elective surgery in the time of covid- surgeries in hospital-based ambulatory surgery and hospital inpatient settings emergency-to-elective surgery ratio: a global indicator of access to surgical care effects of delayed surgical resection on short-term and long-term outcomes in clinical stage i non-small cell lung cancer the novel coronavirus, -ncov, is highly contagious and more infectious than initially estimated mortality analyses. johns hopkins coronavirus resource center available at latest map and case count. the new york times pandemic influenza: three waves i am a resident at the university of alabama where dr. herb chen, the editor-in-chief of the american journal of surgery, is the chairman. i otherwise have no conflicts of interest key: cord- - a odok authors: journeay, w shane; burnstein, matthew d title: pandemic influenza: implications for occupational medicine date: - - journal: j occup med toxicol doi: . / - - - sha: doc_id: cord_uid: a odok this article reviews the biological and occupational medicine literature related to h n pandemic influenza and its impact on infection control, cost and business continuity in settings outside the health care community. the literature on h n biology is reviewed including the treatment and infection control mechanisms as they pertain to occupational medicine. planning activity for the potential arrival of pandemic avian influenza is growing rapidly. much has been published on the molecular biology of h n but there remains a paucity of literature on the occupational medicine impacts to organizations. this review summarizes some of the basic science surrounding h n influenza and raises some key concerns in pandemic planning for the occupational medicine professional. workplaces other than health care settings will be impacted greatly by an h n pandemic and the occupational physician will play an essential role in corporate preparation, response, and business continuity strategies. the occupational medicine community has been adressing occupational diseases of epidemic proportions since ramazzini first studied injured workers. traditionally, these diseases have been musculoskeletal, psychiatric or toxicologic in nature. when the etiology of these conditions has been identified, appropriate measures have been taken to mitigate the risk of becoming ill or injured. occupational health specialists are therefore quite adept at looking at prevention when the causative factors are known and their mechanism of action understood. however, when the process is poorly understood, as is the case with pandemic influenza, determining the most appropriate prevention and mitigation strategy is more complex. despite this uncertainty, government agencies and businesses are taking measures to address the impact of a potential pandemic influenza on their workforce [ , ] . the field of occupational medicine is being consulted to assist in mitigating the impact of an avian influenza pandemic on their human resources, business continuity and also the societal impact associated with essential services and disease transmission. this article will outline the nature of pandemic avian influenza and some of the unique considerations related to the occupational environment outside the health care setting. occupational medicine professionals are uniquely positioned to provide information on the potential impact of a pandemic influenza. indeed, infectious disease may disproportionately impact the occupational environment. this is due to factors associated with transmission such as the proximity of co-workers to one another in the workplace, during the daily commute to work, or simply dealing face to face with customers. of particular concern is the health and safety of those health care professionals caring for infected patients. the recent experience with severe acute respiratory syndrome (sars) provides some useful insight into the consequences of a novel infection on a modern society and more specifically on the health care community. there are many similarities between the sars epidemic and the anticipated experience with avian influenza. both have been associated with food and animals. in the early stages of sars, more than a third of infected humans were food handlers [ ] , and it was later inferred that the sars coronavirus had originated in civet cats, and that the first transmission of infection to humans may have occurred in those workers handling civet cats [ ] . however, the greatest impact of sars was subsequently felt in health care workers where they were estimated to have accounted for over % of total sars cases in singapore and % in canada [ ] . thus, not only are individuals working closely with infected animal hosts at risk for first line crossover transmission of an emerging virus but they are also at risk of acquiring the virus from coworkers, or in the case of health care professionals, from patients. influenza are single stranded rna viruses and are part of the orthomyxoviradae family [ ] . influenza a and b can recur in individuals because of their ongoing mutation. antigenic drifts can occur in seasonal influenza and if sufficient mutations arise in the surface proteins hemagluttinin or neuraminidase, it can result in a novel strain. thus 'h' and 'n' components determine the different potential subtypes of a given influenza virus, and at present a total of h variants exist while n subtypes have been identified. the ongoing emergence of small but significant mutations can lead to epidemics which we experience as seasonal influenza. the yearly influenza vaccination program is based on correctly determining which of these subtle changes (drift) will become predominant. pandemic influenza, such as the suspected h n avian influenza, occurs as a result of major changes in surface proteins of influenza viruses known as an antigenic shift. this novel strain which is present in animals still requires further modification before it can effectively spread among the human population. this situation can be created via transmission from a different species with frequent exposure leading to adaptation, or from genetic reassortment [ ] . the process of reassortment happens when an individual simultaneously has both human and avian influenza subtypes. this allows for a recombination of viral components, leading to a new viral form with the potential for efficient transmission between humans. this form of the virus would still contain avian viral surface proteins. when this occurs humans have minimal or no immunity against the virus, enabling a large geographic spread of disease with high attack rates [ , ] . it should be noted that h n is not the only avian influenza that has the capacity to affect humans. h n is slowly progressing globally, and while less pathogenic than h n , has caused illness in poultry workers. to date, neither of these avian influenzas has gained the capacity to spread efficiently from human to human. pandemic influenza occurs when a new strain of human influenza arises that humans have minimal or absent preexisting natural immunity, which causes disease, can be easily transmitted from person to person, and is globally widespread (on continents at one time) [ ] or exhibits community level outbreaks in two who regions. in today's globalized economy and interdependent supply chain, the work force is particularly sensitive to pandemic infections and it is also a key mechanism for the geographic spread of a pandemic. on average, we experience a pandemic about every thirty years. indeed, in the th century, there were three pandemic influenza outbreaks which included: the spanish influenza ( ) ( ) ( ) , asian influenza ( ) ( ) and the hong kong influenza ( ) ( ) [ ] . this is not to suggest that simply because years have passed since the last pandemic, we are overdue; it is simply meant to point out that pandemics are relatively common events given the right conditions. the current strain of influenza considered to have pandemic potential is the highly pathogenic h n strain of avian influenza which has spread from asia to europe. moreover, its transmission to humans has intensified concerns that a novel strain will emerge leading to human infections of pandemic proportions [ ] . the three criteria that are required to enable a pandemic include: ) the presence of a new viral strain that is capable of infecting humans, ) ability to be transmitted from person to person, and ) availability of a susceptible global population [ ] . thus, should a new viral strain emerge, the global workforce provides and ideal vehicle in which transmission from person to person can occur within a susceptible global population. the ability of h n to propagate between humans after an initial infection has not been established and its probability is unknown. thus avian influenza has currently not developed into a pandemic [ , ] . however, it is generally accepted that this will occur; it is a matter of "when, not if". when this occurs, the health care system will be particularly susceptible to pandemic influenza events. this is because patients with influenza will place an enormous burden on already fully taxed health care services and because health care professionals will come into direct contact with infected patients rendering them susceptible to acquiring the virus. however, there are no industries that would be left unaffected by an avian influenza pandemic, and therefore public health agencies, government, and industry will need to consider the level of interdependence they share. it is generally accepted that transmission of the influenza virus occurs by host inhalation of viral droplets usually greater than μm in size [ , ] . a recent review of the mechanism of influenza transmission concluded that the virus is primarily transmitted at close quarters [ ] . it can also be transmitted by coming into contact with viral laden fomites. both of these methods are of great concern in the workplace, due to use of communal equipment and also in areas where employees work in close proximity. therefore, infection control measures will need to vary between industries. for example, staff that work in isolation or even outdoors could be at far less risk of transmission than having many employees in a single room such as a telecommunications call center where individuals are separated by small distances. moreover, unlike seasonal influenza which has an incubation period of one to four days (average two), avian influenza has an incubation period ranging from two to eight days [ ] . this has implications for staffing schedules and return to work policy when developing guidelines for pandemic influenza in the workplace. once again the nature of the control measures and advisement to employees may vary considerably depending on the physical layout of the worksite. it is well established that occupational disease is already an enormous contributor to the economic and human resource strain on our health care systems. many mechanisms are in place to prevent or manage such disease which may include ergonomic initiatives, exposure limits, and corporate health and wellness programs. at the same time, the workplace is one of the key pillars of societal function, such that the health of a workplace is vital to the health and functioning of our interdependent society. this is particularly true when one considers such essential services as health care, energy, communications, and food supply sectors. in the event of a pandemic influenza absenteeism will be an enormous challenge. employees will not be present due to reasons such as: infection and illness from the pandemic influenza strain, exclusion from work while suffering an illness that is mistaken for or treated empirically as influenza, caring for sick relatives, caring for children in the event of day care and school closures by governments, loss of public transportation and based on the fear of real or perceived risk of infection at work or during travel [ ] . the public health agency of canada is predicting total work absenteeism of to % during the whole disease wave with the peak work absence ranging from to %. while it is tempting to look at absenteeism from within a single organization, the functioning of a company is almost always dependent on external clients, supply chains, or multi-national locations. thus, a large manufacturing plant in united states may require final product detailing in another region of the country, which in turn receives its raw materials from asia or south america. "just on time" delivery processes have created a society in which most companies (including health care institutions) have less than a few weeks supply of essential goods (including medications). little is known about the global timing and progression of h n avian influenza at present but it is entirely possible that while an organization in north america is healthy, its supplier abroad is experiencing a disease wave leading to uncoordinated business efforts. each company has an obligation to ensure that occupational transmission is attenuated and planned for, but this will also require cooperation with governments that may impose social and travel restrictions to suppress the spread of the disease while still maintaining business continuity and societal function. pandemic influenza, will have the capacity to disrupt services and supply chains and thus requires significant planning and foresight from occupational medicine professionals to help mitigate the health and economic impacts to their organizations and to the functioning of society [ ] . as with any occupational disease, the interventions available to health professionals can be considered as engineering or administrative controls. as well, pharmaceutical controls (prophylaxis) for avian influenza may provide an important role in prevention. however, there is limited clinical evidence for the effectiveness of currently available medications or vaccines. vaccination strategies, such as the annual influenza vaccine programs, have been the traditional first line of defense against viral infections. research is currently being devoted to the development of vaccines as a possible intervention for pandemic influenza. the need for a rapidly deliverable vaccine for pandemic influenza has become more urgent since de jong et al. [ ] reported the emergence of oseltamivir resistance to h n . given the current to month development time, it is unlikely that a vaccination will be available during the first wave of a pandemic. the impact of antigenic drift on vaccination for influenza is an on ongoing challenge and is the reason vaccination for seasonal influenza must be administered annually to protect against the new antigenic strain. increased demand for vaccine during a pandemic influenza may be tempered by the supply. specifically, the substrate used for vaccine manufacturing for all major suppliers worldwide is chicken eggs [ ] . during a pandemic several times the current supply of eggs would be required. what is even more challenging is that h n , which is the current predicted pandemic strain, is lethal in eggs and is also a biosafety level pathogen which decreases the potential of scaling up the manufacture of vaccine for international deployment [ ] . one must also consider that poultry workers may be at increased risk of exposure to pandemic influenza zoonotically or may also be stretched from a human resource perspective when measures need to be taken to curb a poultry influenza outbreak [ ] . acambis labs, and others, are working on the development of a universal influenza vaccination that is based on more stable surface proteins such as m e, which is found on the surface of all influenza a strains. the first vaccine approved by the us food and drug administration for pandemic influenza is a reverse genetics vaccine and demonstrated low immunogenicity except for high doses with an adjuvant [ ] . when this was approved by the fda it was noted that the vaccine would not be marketed to the general public but rather stockpiled by governments [ ] . it has previously been suggested that an appropriate vaccine will likely not be determined until the initial phase of a pandemic [ ] . furthermore, once a vaccine is developed a mechanism needs to be put in place that can provide an adequate supply at an affordable cost globally in lock step with the progression of the pandemic. a unique challenge for the occupational medicine physician in the event of a pandemic outbreak is to determine who gets priority for receiving vaccination. maintenance of essential services will be central to the continuity of a functioning society. health care workers and workers in critical occupations will be a priority for vaccination programs, once available. decisions on vaccination programs are complicated by the eventual timing of the disease wave, number of employees, nature of the work environment, and the availability of vaccine. for example, should employees who are in close proximity to one another be given priority or only those critical to maintaining business continuity? the public health agency of canada has created priority lists for receipt of vaccinations [ ] . not surprisingly health care workers are part of group , followed by key societal decision makers and critical protection and utility workers (police, fire fighters, sewage workers, public transportation and communications). another treatment option is the use of anti-viral medications. the two main classes of antivirals available at present are the neuraminidase inhibitors and the adamantanes. there has been an emergence of resistance to adamantanes for seasonal influenza [ ] leading many to reconsider them as agents in the treatment of pandemic avian influenza [ ] . in preliminary studies using oseltamivir [ ] or zanamivir [ ] , patients showed a reduc-tion in the duration of symptoms ranging from - days. whether a - day reduction in symptoms will translate into reduced absenteeism, cost-savings and disease transmission is unknown. additionally, the cost-benefit of stockpiling anti-virals for treatment of pandemic influenza remains unknown. as noted previously, oseltamivir has also demonstrated resistance [ ] . adding to the complexity of managing h n treatment, is once again the manner in which one decides who receives the medication and the fact that the modest reduction in influenza symptoms will depend on timing of administration of the drug. in individuals with confirmed h n influenza that were treated with oseltamivir, mortality was still close to % [ ] . it has also been noted by tambyah [ ] , that despite guidelines from the world health organization concerning the use of anti-virals in pandemic avian influenza, there remains little 'level ' clinical evidence to support such guidelines. more recently, a group in singapore has gathered a set of practical guidelines for clinicians encountering h n avian influenza in humans [ ] . despite the lack of scientific evidence for their effectiveness in a pandemic situation, governments and many employers are stockpiling anti-virals to be used not only as therapy for ill individuals, but also as prophylaxis for critical staff. this may be driven by the recognition that once the pandemic is recognized, it will be nearly impossible to purchase these products. it reflects a significant investment: at approximately $ /pill, an eight week course would cost over $ per employee. a company of employees would need to invest $ , on a product which they hope they will never use, is unproven, and has a limited shelf life. again, one is faced with decisions regarding dispensing medication -to all workers, critical workers, families? non-pharmaceutical controls while the world waits for an effective pharmaceutical intervention, non-pharmaceutical controls will need to be considered to combat the spread of illness in the community and the workplace. low [ ] has outlined and adapted [ ] five non-pharmaceutical public health interventions that would aid in the mitigation of pandemic influenza. they include: hand hygiene and respiratory etiquette, human surveillance, rapid viral diagnosis, provider and patient use of masks and other personal protective equipment and isolation of the sick. all of these interventions will need to be coordinated at organizational and government levels due to the tremendous interrelationships affected by a pandemic. some of the above interventions have some unique implications from an occupational medicine perspective. hygiene and respiratory etiquette are particularly effective in reducing the spread of infectious disease and represent a key defense against nosocomial infection in hospitals. this also applies to a workplace where people are in close proximity to one another where viral droplets may exist in the air and on equipment or surfaces used by multiple people each day. the spread of infection between employees is one possible transmission pathway, however the occupational medicine professionals of large and complex organizations must also consider the families of the employees and the consumers of products where interaction occurs with the public. protection of the consumer raises the issue of due diligence which can be complex for service oriented organizations. hand washing, social distancing and respiratory etiquette, if normalized and rigorously adopted, may provide the most effective (certainly most cost effective) means of protection. the role of personal protective equipment in reducing the spread of pandemic influenza is one of considerable debate. both the perceived and/or real efficacy of such measures and the cost associated with the provision of such materials are legitimate concerns for those coordinating pandemic plans in the workplace. the gold standard for particulate inhalation in most cases is the use of the n respirator. droplet transmission is thought to be the primary mode of transmission and is the basis of guidelines for health professionals coming within feet of patients during seasonal influenza [ , ] . therefore, because n respirators can trap more than % of airborne particles [ , ] , experience from their use in seasonal influenza supports some effectiveness of their application to pandemic avian influenza. regardless of the real or perceived protection that n respirators provide to employees from transmitting or contracting h n influenza via inhalation, many challenges exist with the use of such protective equipment. n respirators require fit testing, need to be replaced, and tend to be uncomfortable which create opportunities for their improper and therefore ineffective use. moreover, the n respirators would impose a large cost to an organization who decides they will outfit their employees with them in the event of a pandemic. this cost is imposed by buying a stockpile of the respirators, and the provision of fit-testing for each and every employee issued a respirator. consider an organization that decides that during a two week pandemic disease wave they will issue n masks to employees. each respirator unit has a cost of $ , and because the respirators need to be changed every - hours, each employee working an -hour day will require masks per day. therefore, each employee would require masks over -weeks ( working days), leading to a cost of $ per employee for a total of $ k for employees for two weeks. this does not include the cost associated with fit-testing which takes approximately -minutes per person, which would therefore require hours of time to fit test employees. furthermore, a trained professional is required to perform the fit testing procedure. finally, does the employer provide n masks for the families of the employees such that protection is afforded to the family and the employee at home? all of these measures will vary as the risk of transmission will depend upon the nature of the worksite and the controls put in place. for example, teleworking would greatly reduce the number of employees that congregate at the worksite. not all industries will have this luxury. creating an environment in which employees are comfortable and confident of their safety in the workplace is critical in enhancing their work attendance. fear will be rampant, and employee education well in advance of the event will be vital in reducing the spread of disease, myths, and ensuring corporate and social stability. indeed addressing both real and perceived risk of infection may be the most crucial factor in maintaining business continuity in the face of a pandemic. the scientific community is devoting a great deal of effort and research funding towards what is considered by many to be an inevitable pandemic. it has also been suggested that even the most stringent non-pharmaceutical interventions are unlikely to prevent the pandemic or alter the underlying biological susceptibility of a population to a pandemic virus [ ] . however, the prevention and management of disease transmission in the occupational environment will play a central role in the health and economic burden of pandemic influenza. with a longstanding record of applying the latest science to appropriate engineering and administrative disease controls, the occupational medicine community can utilize these concepts to prepare for and mitigate the potential impact on industry and society. pandemic influenza preparedness: a survey of businesses planning for avian influenza consensus document on the epidemiology of severe acute respiratory syndrome (sars) molecular evolution analysis and geographic investigation of severe acute respiratory syndrome coronavirus-like virus in palm civets at an animal market and on farms emerging infections among health care workers: the severe acute respiratory syndrome (sars) experience influenza and the pandemic threat pandemic planning: non-pharmaceutical interventions updating the accounts: global mortality of the - 'spanish' influenza pandemic avian flu from an occupational health perspective clinical manifestations and consequences of influenza transmission of influenza a in human beings avian influenza a (h n ) infection in humans. the writing committee of the world health organization (who) consultation on human influenza a/h business continuity management and pandemic influenza roundtable discussion: corporate pandemic preparedness oseltamivir resistance during treatment of influenza a (h n ) infection update on influenza vaccines pandemic influenza planning: shouldn't swine and poultry workers be included? vaccine safety and immunogenicity of an inactivated split-viron influenza a/vietnam/ / (h n ) vaccine: phase i randomised trial are we ready for pandemic influenza? public health agency of canada: preparing for the pandemic vaccine response -annex d. ottawa: public health agency of canada the emergence of adamantane resistance in influenza a (h ) viruses in australia and regionally in update on influenza anti-virals efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial zanamivir for treatment of influenza a and b infection in high-risk patients: a pooled analysis of randomized controlled trials the working committee of the who: consultation on human influenza a/h avian influenza a (h n ) infection in humans practical management of avian influenza in humans non-pharmaceutical public health interventions for pandemic influenza: an evaluation of the evidence base transmission of influenza: implications for control in health care settings influenza transmission and the role of personal protective respiratory equipment: an assessment of evidence. ottawa: council of canadian academies at the time this paper was submitted to this journal the who and many governments are monitoring an outbreak of h n swine influenza which has recently been declared a pandemic. cases have been confirmed here in nova scotia, united states, uk, spain and israel with the epicenter in mexico where over people have died. while much of the literature focused on the future possibility of h n avian influenza pandemic, the h n swine influenza strain was not of immediate concern to the international community until the current outbreak in mexico. the authors declare that they have no competing interests. wsj conceived, researched, wrote and edited the manuscript. mdb provided background information, guidance and editing. both authors reviewed and approved the final submitted manuscript. key: cord- -v o uayk authors: bjursell, cecilia title: the covid- pandemic as disjuncture: lifelong learning in a context of fear date: - - journal: int rev educ doi: . /s - - -w sha: doc_id: cord_uid: v o uayk the covid- pandemic has caused a number of fundamental changes in different societies, and can therefore be understood as creating “disjuncture” in our lives. disjuncture is a concept proposed by adult educator peter jarvis to describe the phenomenon of what happens when an individual is confronted with an experience that conflicts with her/his previous understanding of the world. faced with a situation that creates disjuncture, the person is compelled to find new knowledge and new ways of doing things; i.e., he/she must embark on a learning process. the recent introduction of social distancing as a measure aiming to reduce transmission of the covid- virus has dramatically changed people’s behaviour, but this measure does not only have preventive and desirable effects. there is an associated risk for increased isolation among the older generations of the population, as well as a change in intergenerational relationships. although the current pandemic (as disjuncture) may potentially initiate major learning processes in the human collective, we should remember that disjuncture is often theorised within neutral, or even positive, contexts. in a context of fear, however, learning may result in a narrowing of mindsets and a rejection of collective efforts and solidarity between generations. in terms of the types of learning triggered by the current pandemic (as disjuncture), one problem is non-reflective learning, which primarily occurs on a behavioural level. we need to recognise this and engage in reflective learning if we are to make the choices that will lead to a society that is worth living in for all generations. our goal must be to learn to be a person in a post-pandemic society. the covid- pandemic has created a major "disjuncture" in our existence. within a short period of time, our lives have been turned upside down, in a way no one could have imagined. on march , the world health organization (who) officially classified the spread of a novel coronavirus, sars-cov- , as a pandemic, prompting many communities to act by closing their borders and imposing curfews on the movement of people. to reduce the spread of infection, national governments recommended that their citizens should engage in "social distancing". social distancing means keeping a physical distance (in the current pandemic, the stipulated space varies between . to metres) from other human beings. the term refers to measures that people can/should take to reduce personal proximity, an integral part of their social interaction with other people, and thus help reduce the transmission of an infectious disease such as the coronavirus. these directives to change what was hitherto entirely "normal" behaviour among human beings has caused "disjuncture" in people's lives; namely, a disharmony between the world as we knew it and the state of the world during the current pandemic. disjuncture is a concept proposed by adult educator peter jarvis to describe the phenomenon of what happens when an individual is confronted with an experience that conflicts with her/his previous understanding of the world. our lives comprise a series of experiences made up in such a way that our biography appears as continuous experience added to by each unique episode of learning which we call an experience. but each of these unique episodes begins with the same type of question […] : why has this occurred? how do i do this? what does this mean? and so on. it can be cognitive, emotional or a combination of the two: it is this that i call disjuncture (jarvis a, p. ). according to lifelong learning theory, disjuncture triggers learning, but what is it that we learn during a pandemic? italian philosopher giorgio agamben argues that panic has paralysed his country (italy) and that people have sacrifice [d] practically everything -the normal conditions of life, social relationships, work, even friendships, affections, and religious and political convictions -to the danger of getting sick (agamben ) . fear and panic can have serious long-term outcomes for individuals and society, including the worsening of existing problems, such as isolation among the older generations of the population and the gap between generations. it therefore seems likely that an examination of the changes that occur during a pandemic will be key to understanding the learning that takes place in a context of fear. as this article is being written during an ongoing pandemic, readers should bear in mind that the situation may change dramatically and we do not know how this might impact people's learning at different points in time. the discussion in this paper is intended to inform and stimulate debate and further research. the purpose of this article is to revisit the concept of disjuncture (jarvis a) and to invoke lifelong learning theories because they have the potential to: ( ) allow us to conceptualise the current pandemic as a learning process; ( ) connect the the holistic concept of lifelong learning is discussed in more detail in the next section. briefly, in practical terms, it comprises "cradle-to-grave" learning throughout a person's life and includes formal, nonformal and informal learning. formal learning occurs in education or training institutions (e.g. schools), non-formal learning (e.g. swimming classes, amateur music etc.) takes place outside the formal system; and informal learning is experience-based and often accidental, occurring e.g. at home, during a leisure activity or in the workplace. a doctoral student at the university of chicago who investigated this found the earliest mention in english in , but the first use of its current meaning in in the context of airborne illness and sars (waxman ) . footnote (continued) practice of social distancing to ongoing, long-term changes in society; and ( ) highlight certain risks and possibilities which need to be addressed if our goal is to support people's engagement in the kind of learning that is directed towards achieving a better post-pandemic life and a better post-pandemic society. when lifelong learning became a central concept in global policy half a century ago, its proponents highlighted that: ( ) learning is not only about child development, but continues throughout adult life; and ( ) learning takes place in every context, not just within the confines of the school classroom. one of the seminal reports marking the establishment of lifelong learning as a concept was learning to be: the world of education today and tomorrow (faure et al. ) . often referred to as "the faure report", it emphasised a humanist, holistic vision of education that was applicable to all members of society. since the release of this report, lifelong learning policies have addressed social problems on a global scale in conjunction with the emergence of key institutions in this field. moosung lee and tom friedrich ( ) discuss differences in underlying ideology between the united nations educational, scientific and cultural organization (unesco) on the one hand, and the organisation for economic cooperation and development (oecd), the european union (eu), and the world bank on the other. while unesco has had its own unique impact on international discussions, contemporary ideologies with respect to lifelong learning advanced by the other three organisations have been dominated by a neoliberal capitalist perspective (ibid.). this is unfortunate, because unesco's enlightenment tradition (which is based on rationalism, progress, freedom, emancipation, and the concept of human beings as masters of their own destiny) is at odds with, and is actually undermined by, the utilitarian view of education that comes with adopting a neoliberal capitalist perspective (elfert ) . this conflict is of particular interest during a pandemic such as the one we are currently experiencing, because many people will lose or have already lost their jobs, which is likely to strengthen the utilitarian view of education even more. maren elfert (ibid.) argues that the adoption of such an instrumental approach presents an obstacle to placing education in a wider societal context for those who aim to solve social problems on a global scale. instead of reducing the process of education to the mere creation of productive economic units, the purpose of education should be to offer learning opportunities which foster the development of people who think critically, but not cynically, which then enables them to act as responsible citizens (stanistreet ) . one effort in particular that should be made to effectively address social problems, namely, the promotion of an intergenerational society, is discussed later in this article. the concept of lifelong learning may lead to some confusion because in addition to being a core policy concept, it can also be invoked to refer both to an individual's spectrum of learning and to institutions which offer educational opportunities (jarvis (jarvis , . a singular focus on institutions which offer formal education is too narrow, because learning also takes place in professional settings, work environments, and in groups and gatherings of various kinds. it is therefore impossible to create a fully institutionalised system of lifelong learning; irrespective of where learning takes place, such learning must be recognised as part of the person's total learning. a shift in terminology from education to learning entails a shift in meaning and focus. it might be said that education gives the active part to the teacher, while learning represents the active learner's perspective. we thus observe a shift in focus from formal education to how an individual creates and transforms experiences into knowledge, skills, attitudes and values at every age, throughout this individual's life. another drawback that can be associated with an instrumental/utilitarian approach to education is that it excludes the possibility of adopting a holistic understanding of human learning. if one is to understand learning as something which grows out of the experience of living, being and becoming, this demands that one understands that the self is shaped through thinking and doing over time, and is embedded in overlapping and contradictory life-worlds (jarvis (jarvis , a . as a philosophy of education, lifelong learning awards the individual's learning a central position and highlights the fact that this must be the starting point if we are to properly understand what learning is about. learning must be understood in its entirety and as the result of interaction between the individual and the individual's environment. it is important to note that it is the learner who enters situations that provide experiences by which learning takes place (jarvis ). jarvis emphasises the point that, by starting with the learner (and not with what is being learned) we are led to the understanding that the learner's biography is changed as a result of learning, irrespective of the person's age. when experience is processed, it is integrated into the person's being. this entails that a person experiences being and becoming in a lifelong process. jarvis opposes the dualistic view of the division between body and soul because, he claims, it is impossible to separate one from the other (jarvis ). to ground learning in the framework of being, rather than in a framework of having, entails that one accepts fluidity and dynamic movement as one strives to grasp one's manner of existing (su ) . to think of learning as the mere acquisition of knowledge is, therefore, insufficient. learning takes place by means of lived relationships in a cultural context, as instantiated by a particular society. each individual person's process of shaping their identity is key to learning, because lifelong learning involves the continued development of a new understanding of "the self", something which also entails a re-negotiation of one's identity. during the current pandemic, many activities have moved online, including, for example, adult education. even though teaching as such takes place in much the same manner as previously, this move to a digital environment entails a great deal of change and demands new competencies from teachers. these changes are so substantial that they give rise to questions concerning the individual's perception of their self and their professional performance as teachers. this shift from the classroom to a digital environment via the internet is not just a practical issue; it also entails a shift from one state of existence to another. in a similar manner, the implementation of a lockdown and social distancing creates a state of existence which prompts people to reflect on their selves and their situation. this can influence their perceptions of themselves and others. a pandemic such as the one we are currently experiencing influences individual people's lives as well as the behaviour displayed by society as a whole. according to the terminology used in the context of lifelong learning as a philosophy of education, we thus conclude that a pandemic causes a disjuncture. disjuncture has meanwhile become an established concept in lifelong learning which is used to explain a condition that enables learning. peter jarvis ( b) proposed that learning in our everyday lives is often triggered by a gap between our expectations and an experience, i.e. disjuncture. disjuncture refers to a state of disequilibrium, where we feel uneasy, out of our depth. in response to this feeling, we seek change -in order to achieve equilibrium and stability again. the process of striving towards a new state of equilibrium triggers the learning that takes place: indeed, this state of disequilibrium is a fundamental cause of learning that is inextricably intertwined with being-in-the-world: it is a part of the human condition (jarvis (jarvis [ , p. ). disjuncture, the gap between what we know and what we experience, provokes within us our initiative to understand and deal with particular situations, so that we can return to a harmonious state (jarvis b), albeit a new one. in other words, the need to learn is a fundamental need. as mentioned above, our learning takes place in interaction with our physical and social surroundings. learning can be said to be the bridge that links the self to the world. when disjuncture occurs, a person may perceive a sense of detachment from the former self, because it no longer fits the new situation. learning is the activity that enables a person to deal with disharmony and involves the movement from one state of being to another. this transition from one state to another requires that learning reformats a person's previous knowledge and experience in relation to the new experience in a manner that could not be understood (by the individual) in terms of previously existing frameworks. eventually, the individual will initiate a concluding phase of the learning process when new knowledge is incorporated into her/his state of being and new frameworks emerge. by means of the process thus described, we say that the individual has learned something. this could also be regarded as the end of the learning process initiated by the disjuncture. however, it is in fact also part of the continuous flow of learning that takes place throughout a person's life and thus sets a new direction for future learning. in his book on learning in later life, peter jarvis notes that it is recognized here that more than ever before in the history of humankind we have the opportunity to create our own biography through the choices that we make and we recognize that learning is the force through which our biographies develop and expand (jarvis (jarvis [ , p. ). being (and learning) always occurs in relation to a social situation. jarvis states that being is driven by the moral imperative about achieving potential as human beings for the community in which we live (jarvis b) . engagement in the social world cannot be mastered by instinct. instead, it has to be mastered by learning if we are to obtain the knowledge that is needed to cope with living in the world. a pandemic such as the one we are currently experiencing presents a new social situation, and we need the process of learning to deal with the situation. however, there is also a risk that learning will not take place. with respect to an analysis of the effects of a pandemic as disjuncture, a typology of learning and non-learning is, therefore, of some help. the analysis i present below is guided by three categories of responses to new experiences, namely: ( ) non-learning; ( ) nonreflective learning; and ( ) reflective learning (jarvis (jarvis [ ). within each category, there are three types of learning or non-learning (table ) . first, the three types of non-learning are presumption, non-consideration and rejection. the three different types of non-learning all refer to the fact that people do not always learn from their experiences. "presumption" is a typical response to an experience that is familiar to the individual and the individual knows what to do, and therefore, there is no need for change. non-learning can also occur when a person experiences something that could be a potential learning experience, but either because they do not understand the situation or they are not conscious of the situation ("non-consideration") learning fails to take place. in addition, non-learning may be the case in situations where the person is aware of the potential for learning but they reject this possibility (hence the label "rejection"). the three types of non-reflective learning include preconscious learning, skills learning and memorisation. "preconscious learning" takes place when an individual monitors their actions on a low level of consciousness, such as when driving a car. "skills learning" occurs when skills are acquired in action through imitation. "memorisation" is the process of verbal imitation, for example, when a person memorises the words of the instructor so as to be able to reproduce them at a later time. nonreflective learning represents processes associated with social reproduction. these processes are commonly on the level of bodily experience, in contrast to the level of communicative interaction. lastly, the three types of reflective learning are contemplation, reflective skills learning and experimental learning. "contemplation" consists of focused thinking about an experience as one reaches a conclusion about the experience. "reflective skills learning" involves learning a skill whilst simultaneously learning the concepts that undergird the practice that one is engaged in, thus providing one with an understanding of why a skill should be performed in a certain way. "experimental learning" occurs when theory is tried out in practice, and leads to new practical knowledge for the individuals' everyday life. it should be noted that the non-reflective and reflective forms of learning can lead to either conformity or to change and innovation. furthermore, as stated above, individuals learn in relation to a social situation, and, as argued in this article, the introduction of social distancing changes the character of our social situation. lifelong learning is, as explained above, embedded in a cultural context. when a pandemic such as the one we are currently experiencing causes disjuncture, people find themselves in a situation where a major learning process is initiated. the point of interest in this article is the introduction of regulations for social distancing and how these regulations have already affected relationships as well as their longerterm effect. soon after the outbreak of the covid- pandemic, social distancing was introduced in several countries as a general code of conduct to maintain a physical distance between oneself and others. in addition, people who are over the age of have been identified as an especially "vulnerable group" who should stay at home and avoid social contact, even within the family. thus, the practice of social distancing has had, and continues to have, an impact particularly on people over the age of , but it also impacts other age groups in society. this is a situation where the elders of society are perceived as constituting a problem to be dealt with by means of special measures. potentially, this may, for example, contribute to strengthening ageism. in fact, categorising people by the label of being "over the age of " in these national directives may in itself be a kind of ageism, since age is the only variable at play. certain governmental actions, such as the introduction of social distancing, will inevitably cause re-actions in society. these re-actions may be understood as expressions of learning processes, and they demonstrate that humans develop in ways which are often beneficial for the community, such as people's engagement in volunteering and performing acts of solidarity. however, certain other re-actions also reveal prejudices and negative perceptions which are sometimes associated with age. one aspect that we cannot review yet (since the pandemic is still ongoing at the time of writing), is how we will live together after the pandemic is over. nevertheless, we do know that our supposedly established models of coexistence have been challenged; not least by the phenomenon of social distancing. it is highly probable that these new social rules will have a long-term impact on interaction patterns and on the level of trust in society, even after the current pandemic is over. trust is a central concept in understanding how social ties serve as a resource in society. john field, professor emeritus in education at the university of stirling, has published a number of thoughts on the social effects of the lockdown on his blog (field a (field , b . he reports that studies of social capital, including preliminary results from a number of covid- studies, show that the higher the level of social capital that is enjoyed within a society, the lower the rate of transmission of infection (field a ). field also mentions that when the variable of "income" is included in the analysis, it has been observed that people with a high income or high-speed internet access are more likely to follow directives about staying at home. a combination of high income and high-speed internet could thus explain a high propensity for people to stay at home (chiou and tucker ) . "social capital" should, however, not be confused with "social connectedness"; i.e., the structure and interaction patterns of social networks. the structure of social networks can also be used to understand the spread of disease (kuchler et al. ). the primary results of these studies show that the disease is spread within families and between friends, i.e. among people who know each other well and trust each other. while this observation lends credence to the idea of keeping a physical distance, it is expected that in the longer term, this will entail a number of deep-rooted changes in the ways that social bonds are made, reinforced, and broken (field b) . one direct, concrete effect of the kind of social distancing currently stipulated within our societies is isolation and loneliness. in several countries worldwide, isolation and loneliness already constituted a problem among the older generations in society before the current pandemic. socio-demographic changes, the crisis of the welfare state, and breakdowns in social norms have been identified as causing separation between generations (donati ) . from research in the domain of healthcare, we know that loneliness has a negative impact on a person's health. examples from the current situation caused by the implementation of social distancing include the presence of negative emotions. besides anger, covid- "is associated with anxiety, depression, distress, sleep disturbances and suicidality" (sher , p. ) . these increased in china during the initial covid- epidemic, while positive emotions and life satisfaction decreased (ibid.). in the care of older adults, profound isolation has become the norm. the extreme loneliness felt by many older people raises concern, because it is a known risk factor for poor health outcomes. however, some degree of social connectedness and information sharing between care facilities and families can be maintained with the support of digital tools (edelman et al. ; eghtesadi ) . in addition to global and national initiatives that are aimed at preventing the spread of covid- , it is suggested in the literature that agencies setting up prevention regimes, such as who and national health authorities, also need to address the issue of social isolation so as to prevent the health hazard effects that are associated with social isolation. supporting intergenerational relationships is one way in which societies can deal with issues of loneliness and promote well-being. matthew kaplan and mariano sánchez ( , p. ) refer to "seven imperatives to justify our interest" in intergenerational issues: ( ) demographic changes; ( ) mutual support and reciprocal care in the family and in the community; ( ) active aging; ( ) improving social cohesion; ( ) making communities more "livable"; ( ) ensuring cultural continuity; and ( ) strengthening our relational nature (ibid., pp. - ) . a loss of intergenerational contextual continuity is not only a problem for older generations; it also has consequences for the life courses of young people (donati ) . the perspective with respect to the concept of "generation" that is usually found in the field of intergenerational relationships is different from "generation" as a social category, which is comparable to the notion of "social class" or "cohort". by employing the concept in the context of generational theory, we draw attention to the dynamics of socialisation and generativity that exist in the relationships between members of different generations (lüscher et al. ) . the point of using the term intergenerational is found in its prefix, inter -which highlights that which is between -i.e., the relationship (sánchez and díaz ) . however, the social advantages that can be built by strengthening bonds between generations are currently being put at risk because the measures adopted by society in response to the pandemic affect interpersonal contacts and restrict the spaces where social encounters can take place. in response to this situation, a group of international scholars and practitioners have joined forces in support of a manifesto entitled intergenerationality adds up lives (barragán et al. ) , which was published on april . in view of the fact that social distancing can have serious negative effects on people and society, the next section provides an analysis of the covid- pandemic as disjuncture and what this entails in terms of learning. to frame a pandemic as disjuncture, and thereby as a learning process, is one way of approaching an understanding of what it is that is going on, and how a pandemic might change us and society in a post-pandemic era (in the present case, the covid- pandemic). the typology of "non-learning", "non-reflective learning", and "reflective learning" (jarvis (jarvis [ ) described above (and summarised in table ) will inform the analysis that follows with respect to becoming, during and after a pandemic more generally, but also with respect to the covid- pandemic specifically. as with all such typologies, it is important to acknowledge the possibility of varying overlaps between the types, and although this typology may be a bit schematic, it is a useful way of structuring an analysis. with respect to the first type, "non-learning", it would be difficult to imagine someone who is not aware of the current global pandemic, but although a person whose reaction to the experience is non-learning is likely to recognise a disjuncture, they may still reject the learning potential of the situation and merely wait for things to get back to normal. "normal" is attractive because normal circumstances correspond to our previous experiences where we knew what to do and how to act. nonlearning is, therefore, one highly probable outcome after the current pandemic. with regard to intergenerational relationships, non-learning entails that we will return to behaving in the same way as we did before the current pandemic. the second type of learning, "non-reflective learning", can be said to represent the learning that does not involve conscious thought and is not mediated by means of language. instead, it refers to learning that takes place at a preconscious and bodily level. it may transpire that this is the most interesting type of learning occurring during the covid- pandemic. consequently, it is discussed in more detail below. "reflective learning" refers to situations where people consciously think about something and make an intentional effort try to understand why things are the way they are. this includes drawing on knowledge which is relevant to how a situation might be mastered and reaching conclusions which, in turn, become part of a new frame of reference. for example, a recurring reflective practice which has emerged in my own network in response to the current pandemic generates insight into how we can use digital tools in meetings with colleagues around the world. we have learned to provide online courses, conduct academic theses defences and convene board meetings, and these online activities have worked surprisingly well. there are many people who now understand the potential of combining online and faceto-face meetings to save time reduce travelling, and many of us want to see online options as a permanent alternative to "traditional" ways of working, in a post-pandemic society. the same conclusions have been reached in many private settings, where digital tools now connect family members separated by social distancing. but while it is easy to recognise the existence of learning on the level of functionality (for example, how to use digital tools), what is less frequently discussed is learning that concerns the understanding of cultural context and the self. furthermore, issues such as how the current situation might change our view of age and/ or of social interaction also remain a topic that has, so far, been neglected. in fact, this area of human experience might primarily be subject to examination on the nonreflective level, as discussed below. returning to "non-reflective learning", it is interesting to note that the covid- pandemic and the recommendations and directives that have been issued with respect to social distancing have already changed the way in which we behave. when people over years of age self-isolate at home, other people have to go food shopping for them. thus, their children or grandchildren may only meet them in the carpark or outside the house when they hand over the shopping bags. there are a number of neighbourhood volunteer groups who have organised themselves via the internet who are willing to help people who do not have a "social safety net" within their family to fall back on in the current situation. numerous businesses have adapted their procedures and offer new types of services which are suited to times when social distancing is being practised, such as delivery of groceries and special hours for older people in shops, or online healthcare. in many instances, people have helped other people out and have shown a willingness to care for others. we thus note that these new behaviours and services which emerge during a pandemic constitute examples of learning where people develop in a positive way. at the same time, however, there exists a great deal of concern and even fear in society. this fear is also a driving force which may influence how individuals, companies and society behave and what they concern themselves with. on the one hand, the current pandemic has contributed to supporting relationships between the generations and between people in general, as demonstrated, for example, by volunteer services and acts of solidarity. on the other hand, however, different interests have been pitted against each other, for example by putting the economy in competition with public health and the protection of people from the virus. these tensions between competing interests create fear, and it is important that we acknowledge that fear is a negative driving force to be reckoned with in our efforts to direct events and developments associated with the current pandemic in a constructive manner. fear is an emotion which emerges when one's environment or some specific object is apprehended as a threat. this emotion may arise in response to an actual or an imagined threat. if the threat is real, our instinctive fear may well assist us in behaving in a manner which will allow us to avoid a risk or move ourselves away from a dangerous situation. unfortunately, however, fear itself can give rise to dangerous situations, for example, when people arm themselves with weapons out of fear of attack, but the weapon itself then creates unsafe situations. fear can also give rise to conflict, be a driving force for political change, and even influence what and how people learn. there are a large number of things to be fearful of during a pandemic, which also give rise to concern for the future. for example, the fact that we live in a globalised society may well create the feeling that we are all "citizens or the world" and that we have a shared responsibility to help each other. however, fear may cause some people to view others as a threat to their well-being. if we become bogged down with fear, we run the risk of entering a downward spiral of behaviour that puts our future development in jeopardy. the emotion of fear is a natural emotion, and sometimes a necessary one. fear is a driving force which can be exploited in different ways. but when fear gives rise to a persistent concern which dominates how we live our lives, then it is perhaps time to take a step back and ponder the consequences. there is a risk that the outcomes of the learning that takes place during a pandemic, in a context of fear, are not behaviours and ideas that contribute to the improvement of individuals and society. instead, such learning may cause isolation and loneliness, and lead to the "dehumanisation" of communities. in their manifesto, Ángel barragán and colleagues ( ) warn that "preventive" attitudes regarding limiting contact between people of different ages, and especially between the young and the elderly, may reshape our social bonds and reduce inter-age relationships during the current pandemic and in the future. they argue that society needs to adapt existing policies that promote intergenerational contact to include new modes of communication and expand the range of opportunities where people of different ages can come into contact with each other. the intergenerational perspective proposed in the manifesto argues for the implementation of a new social model that integrates visions of people of all ages, and promotes the establishment of meeting spaces where people can interact with each other. in practical terms, this can be done by designing public services and community spaces that actually encourage interaction across generations. this may serve as a fruitful model for "learning to be a person" in a post-covid- society worth living in. if we perceive the current pandemic as disjuncture, we are confronted with a disconnect between the world as we knew it and the world as it is. the disjuncture between an individual's experience and a situation, which cannot be understood based on this experience, is the beginning of a learning process. in other words, the current pandemic does not only cause change, a transfer from one state to another, but is in effect a disjuncture that triggers learning, which entails a reshaping of the individual's frame of reference. the individual who faces a crisis and survives it will not be the exact same individual that s/he was before the crisis. this learning, as peter jarvis points out (jarvis ), lies at the heart of the processes through which we develop our own humanity. notwithstanding this observation, in certain lifelong learning theories, it is assumed that the individual will strive to become his or her best self. however, in the discussion presented above, questions have been raised regarding whether nonreflective learning can result in outcomes that are not conducive to the benefit of the individual or society. one view is to regard a pandemic as a crisis that leads to feelings of fear, prompting people to act on this fear without thinking of the (shortterm or long-term) consequences of their behaviour. the other view is to regard a pandemic as an opportunity to develop our own humanity and engage in constructive patterns of behaviour. to ensure that the outcome of the learning process we are currently engaged in is a positive one, we should engage with ideas about the world as we would like it to be. lifelong learning is based on a view that includes the concept of "unfolding potential", and is based on a fluid co-existence between being and becoming. learning is concerned with where we are and where we are going. the covid- pandemic has created a disjuncture which holds the potential to initiate major learning processes in the human collective. however, the relation between age, isolation, situation and learning is complex, and future studies are needed to better understand how they affect each other. a central assumption in lifelong learning, as a philosophy of education, is that learning starts with the individual, but always takes place in relation to an environment. the argument presented in this article endorses this assumption. consequently, the community and collective are emphasised as central elements, based on the idea that we constitute each other's environments. just as we belong together in society, we also become together. the covid- pandemic has created a disjuncture that introduced fear and uncertainty in this process of becoming. one dilemma i have addressed in this article is the introduction of social distancing as a protective measure. while measures which are intended to protect vulnerable groups, including the directive or recommendation to practise social distancing, make sense in terms of curbing infection rates, they may simultaneously increase the isolation experienced by members of older generations before the outbreak of the pandemic. it is important to remember that for this group, isolation was already a serious problem before the outbreak of the current pandemic. the other, related, dilemma is that there is also a risk that non-reflective learning takes place, the potential outcome of which is the strengthening or normalisation of a disconnection between generations. by verbalising this risk, and by consciously moving from non-reflective learning to reflective learning, we can identify and understand patterns of what takes place in a society which is subject to a pandemic. this is an important task, because, although lifelong learning theories tend to assume that all learning is good learning, the outcomes of learning during a pandemic may well result in the construction of a society that we do not want to live in. based on this insight, it is up to each person to ask themselves: how do we make the choices that will lead to a world worth living in, for all generations? funding open access funding provided by jönköping university. open access this article is licensed under a creative commons attribution . international license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons licence, and indicate if changes were made. the images or other third party material in this article are included in the article's creative commons licence, unless indicated otherwise in a credit line to the material. if material is not included in the article's creative commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. to view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/ . /. translated into english by adam kotsko. itself.blog [blog post intergenerationality adds up lives. manifesto marking the forms of capital social distancing, internet access and inequality report to unesco of the international commission on education for the twenty-first century intergenerational solidarity: old and new scenarios, challenges and prospects mitigating the effects of a pandemic: facilitating improved nursing home care delivery through technology breaking social isolation amidst covid- : a viewpoint on improving access to technology in long-term care facilities unesco, the faure report, the delors report, and the political utopia of lifelong learning learning to be: the world of education today and tomorrow social capital and the lockdown ( ). thelearningprofessor [blog post social capital and the lockdown ( ): how isolation is affecting our social bonds. thelearningprofessor adult education & lifelong learning towards a philosophy of human learning. an existentialist perspective learning to be a person in society teaching, learning and education in late modernity. the selected works of peter jarvis learning from everyday life from adult education to lifelong learning and beyond learning in later life. an introduction for educators and carers intergenerational programmes and policies in ageing societies the geographic spread of covid- correlates with structure of social networks as measured by facebook. nber working paper no. . cambridge continuously reaffirmed, subtly accommodated, obviously missing and fallaciously critiqued: ideologies in unesco's lifelong learning policy. international journal of lifelong education generations, intergenerational relationships, generational policy: a multilingual compendium preconscious. in merriam-webster.com medical dictionary a dictionary of epidemiology intergenerational relationships covid- , anxiety, sleep disturbances and suicide. letter to the editor resources of hope: towards a revaluing of education lifelong learning as being: the heideggerian perspective the surprisingly deep-and often troubling-history of "social distancing who press briefing on covid- key: cord- -ms wz bz authors: flyvbjerg, bent title: the law of regression to the tail: how to survive covid- , the climate crisis, and other disasters date: - - journal: environ sci policy doi: . /j.envsci. . . sha: doc_id: cord_uid: ms wz bz regression to the mean is nice and reliable. regression to the tail is reliably scary. we live in the age of regression to the tail. it is only a matter of time until a pandemic worse than covid- will hit us, and climate more extreme than any we have seen. what are the basic principles that generate such extreme risk, and for navigating it, for government, business, and the public? sir francis galton coined the term "regression to the mean" -or "regression towards mediocrity," as he originally called it, sometimes also called "reversion to the mean." it is now a widely used concept in statistics, describing how measurements of a sample mean will tend towards the population mean when done in sufficient numbers, although there may be large variations in individual measurements. galton illustrated his principle by the example that parents who are tall tend to have children who grow up to be shorter than their parents, closer to the mean of the population, and vice versa for short parents. in another example, made famous by nobel-prize winner in economics daniel kahneman, pilots who performed well on recent flights tended to perform less well on later flights, closer to the mean of performance over many flights. this was not because the pilots' skills had deteriorated, but because their recent good performance was due not to an improvement of skills but to lucky combinations of random events. there is nothing as practical as a theory that is correct. regression to the mean has been proven mathematically for many types of statistics and is highly useful in health, insurance, schools, on factory floors, in casinos, and in risk management, e.g., for flight safety. but regression to the mean presupposes that a population mean exists. for some random events of great social consequence this is not the case. size-distributions of pandemics, floods, wildfires, earthquakes, wars, and terrorist attacks, e.g., have no population mean, or the mean is ill defined due to infinite variance. in other words, mean and/or variance do not exist. regression to the mean is a meaningless concept for such distributions, whereas what one might call "regression to the tail" is meaningful and consequential. regression to the tail applies to any distribution with non-vanishing probability density towards infinity. the frequency of new extremes and how much they exceed previous records is decisive for how fat-tailed a distribution will be, e.g., whether it will have infinite (non-existent) variance and mean. above a certain frequency and size of extremes, the mean increases with more events measured, with the mean eventually approaching infinity instead of converging. in this case, regression to the mean means regression to infinity, i.e., a non-existent mean. deep although galton's theory proved right, the example he used to illustrate it proved flawed, because the height of a child is not statistically independent of the height of its parents, due to genetics unknown to galton. nevertheless, it is clear what galton was trying to prove and it turns out he was right, including for statistically correct examples. "fat tailed" is not a well-defined, or even consistently used, concept in statistics and mathematics, not to speak of social science and psychology. a common definition specifies fat tails as the tails of a probability distribution with a large skewness or kurtosis, relative to that of a normal (gaussian) distribution. the larger the skewness or kurtosis, the more fat-tailed the distribution is said to be, with the most fat-tailed distributions, e.g., pareto distributions, having not only infinite skewness and kurtosis but also infinitei.e., non-existentvariance and mean. the terms "heavy tailed" and "long tailed" are sometimes used synonymously with "fat tailed." for the science of fat tails, see mandelbrot ( ) ; mandelbrot and hudson ( ) ; taleb ( , clauset et al. ( ), and west ( ) . disasterse.g., pandemics, floods, droughts, wildfires, earthquakes, landslides, avalanches, tsunamis, and warstend to follow this type of distribution. so do crime, terrorist attacks, blackouts, financial markets, debt, bankruptcies, and cybercrime, together with less disastrous but financially highly risky ventures like hosting the olympics, building nuclear power plants, high-speed rail systems, hydroelectric dams, new cities, and even something as apparently innocuous as procuring new it systems, the latter being a serious bug in current worldwide digitization efforts. i suggest we name this phenomenonthat events return to the tail in sufficient size and frequency for the mean to not converge -"the law of regression to the tail." the law depicts a situation with many extreme events, and no matter how extreme the most extreme event is, there will always be an event even more extreme than this. it is only a matter of time until it appears. i further suggest that regression to the tail is the new normal. we live in the age of regression to the tail. tail risks are becoming increasingly important and common because of a more interconnected and fragile global system of human interaction for travel, commerce, finance, etc., but also because the walls are coming down between natural and human systems, with humans impacting nature at a global scale for the first time in history, not least in terms of climate change. the pandemic and the climate crisis are presently the two most significant manifestations of the law and age of regression to the tail. prudent decision makers will not count on luckor on conventional gaussian risk management, which is worse than counting on luck, because it gives a false sense of securitywhen faced with risks that follow the law of regression to the tail. instead, decision makers will want to do two things: (a) "cut the tail," to reduce risk by mitigation, and (b) practice the precautionary principle, i.e., avoid tail risk altogether by taking a cautious approach. in any given situation, prudent decision makers and their risk managers must be able to decide whether they face a situation with regression to the mean (mild gaussian risk) or regression to the tail (extreme fat-tailed risk), andmost importantlyto never mistake the latter for the former. this is a difficult task, because a host of cognitive and other biasesincluding simple wishful thinking and power structures that do not welcome truthtrick us into seeing mild risk when risk is in effect wild. to illustrate, consider the current covid- pandemic. cirillo and taleb, argue that pandemics (measured by number of deaths) seem to follow a generalized pareto distribution, i.e., a classic fat-tailed distribution. the law of regression to the tail is consequently pertinent, with three important implications. first, the covid- pandemic was entirely predictable. indeed, the pandemic was predicted years ago by people as different as nassim nicholas taleb, author of incerto, philanthropist bill gates, and numerous epidemiologists who have, deservedly, had a field day as what-did-i-say prophets, after being ignored for years by government, business, and media. second, if you understand regression to the tail it is clear what the main mitigating measures should be once a pandemic develops, namely: (a) cut the tail (by breaking the chain of transmissions through, e.g., lockdowns, personal protection equipment like face masks, testing, development of vaccines, etc.) and (b) the precautionary principle (rather a lockdown too many than one too few) -rolled out immediately, at speed, and at scale, worldwide. why does regression to the tail suggest precisely these measures before others? because the measures derive directly from tail characteristics, including the fact that the spread of pandemics follow an exponential growth curve. the tail therefore needs to be mitigated immediately and directly, and the mentioned measures do this most effectively. if the measures are ignored, the consequences are dire, because , covid- infections today will be , infections just nine days later, and , infections another nine days after that, etc., following exponential growth. to illustrate, consider the uk's slow response to the pandemic. giving evidence before the uk house of commons science and technology select committeein june , the prime minister's former top scientific adviser on the coronavirus outbreak and leader of imperial college's covid- response team, professor neil ferguson, testified, "had we introduced lockdown measures a week earlier, we would have then reduced the final death toll by at least a half," which translates into a minimum of , uk lives lost unnecessarily due to sluggish government (hughes, ) . for perspective, even if the uk had introduced lockdown measures a week earlier they would still have been slower than most other european nations, including neighboring denmark and norway. at the time of writing, excess deaths from the virus in the uk was , , compared with in denmark and zero in norway, and higher than for any other european country with data (ritchie et al., ) . britain's favorite crisis heuristic -"keep calm and carry on" -proved entirely imprudent in the face of regression to the tail. "act now, at speed, and at scale," is the prudent response. this holds true not only for pandemics, but for the climate crisis and other systemic tail risks. however, lockdowns, masks, testing, etc. happen to be contested measures. in the united states, wearing a face mask was politicized and became yet another issue polarizing an already heavily polarized nation. not until july would us president donald trump wear a face mask in public, just as he openly questioned the value of testing and lockdowns. in the united kingdom, prime minister boris johnson explained on national tv that lockdowns and telling people what to do would not sit well with the british liberal tradition. brits should be trusted to use common sense, which for the prime minister himself meantalso documented on tvcontinuing to shake hands well into the second week of march (mason, ; mcguinness, ) . at a downing street press conference the prime minister explained his approach, in what can most benevolently be describednot only in hindsight, but at the timeas a tragically misguided attempt to instill trust with the public: "i can tell you that i'm shaking hands continuously … i was at a hospital the other night where i think there were actually a few coronavirus patients and i shook hands with everybody, you'll be pleased to know, and i continue to shake hands" (express and star, ). unsurprisingly, the prime minister was soon infected, and in turn likely infected others, before ending up in intensive care for an entirely avoidable near-death experience (bbc, ). for johnson, as for anyone, the virus clearly did not care whether he measure of deaths from covid- and the best measure for cross-national comparison. it is calculated for a country or a city as deaths during the pandemic minus the average number of deaths over the previous five years for the same period. it measures, in short, how many more people died during the pandemic, compared with before. it is not a perfect measure, but the best there is for now. during the pandemic in the uk, it was common to see people, including highly educated commentators, trying to explain the steep number of uk deaths by a high level of obesity and general low level of health in the uk population compared with other nations. such explanations are misguided. it is not that obesity and general health do not matter. but they are of marginal importance in the early stages of a pandemic when speed and exponential growth of infections is all-important, as rightly pointed out by professor neil ferguson above. contested the measures to mitigate it or not, or whether he acted foolishly or not. such is the nature of fat-tailed risk. it is what it is. you will find it difficult to postulate another reality in the face of it. it will not be ignored or swept under the carpet. nor will it be mastered by post-truth bluster or a stiff upper lip. leaders who depend on such artifices to govern will appear incompetent when faced with fat-tailed risk, as happened for johnson and trump. contested or not, the most effective measures for mitigating pandemic fat-tailed risks are cutting the tail and general precaution, enacted immediately, at speed, and at scale. initially, the measures need to be implemented across the board. this unfortunately has grave consequences for the economy. but to not implement the measures, or to do so inefficiently, has even graver consequences. to illustrate, at the time of writing just over , people had died from covid- in the united states. the us government sets the economic value of a saved life at million dollars for policy prioritization. that's . trillion dollars destroyed by covid- , growing at - billion dollars a day at the time of writing. that is massive wealth destruction and the numbers show that from even a narrow costbenefit point of view it makes good sense to mitigate as described. as long as it costs less than one billion dollars to save lives, mitigation should continue, from a cost-benefit perspective, and you can save a lot of lives for one billion dollars in a pandemic, if the money is spent on the right measures. billions, or even millions, spent up front will save trillions later, as a general heuristic, which derives directly from the exponential nature of virus growth. nevertheless, lockdowns must be eased as quickly as possible to limit damage to economic and social life, without letting the virus loose again. as soon as data are available that allow the calculation of viral reproduction numbers for specific geographies and communities, measures can be targeted more precisely, limiting unnecessary damage to the economy and social affairs. for example, once initial lockdowns have brought the virus under control, further lockdowns will be necessary only in an ad hoc manner for geographies, communities, and time periods for which infections have spiked up again. in theory, it might be possible for whole nations to bring the virus under control solely by the use of face masks, possibly combined with social distancing, with everyone using masks at first, until the viral reproduction number has been brought below , after which the use of masks can ease up, to be reintroduced only for geographies, communities, and time periods for which the viral reproduction number climbs back above , until the number has been driven below again, etc. for such measures, the difference between success and failure will be small, viz., the difference between being just below or just above a viral reproduction number of , which stresses the importance of getting the measures right. following this type of approach, negative economic and social consequences from the pandemic can be significantly reduced. third, contingencies must be in place to allow speedy scale-up. when leaders finally understood that covid- was a fat-tailed phenomenon and began to make the proper decisions, it turned out that health services, government, and businesses were dismally underprepared, to a degree that things as basic as supplies of face masks, gowns, and other protective gear for health workers immediately ran out. similarly, testing and tracking capacity was not in place, but had to be developed in fits and starts. the lack of reserves made it impossible to scale up mitigation quickly and effectively, resulting in a failure to curb the virus just like a bank without reserves would fail in a crisis. innovative thinking is needed for both mitigation measures and contingencies, especially before the fat tail strikes. once it does, things will often be too hectic to allow for effective innovation. e.g., when a virus is spreading exponentially through a population, it is too late to think about better and more protective gear, tracking, testing, etc., although some thinking and innovation "on your feet" may be possible and valuable. but it would be like building the proverbial airplane while flying it, which is not a good idea, but which was nevertheless the situation for covid- . ex ante innovative thinking and preparedness were almost entirely absent, which is a main reason for the dismal outcome of the pandemic in many countries, including the united states and the united kingdom. after the pandemic, full-on innovation will be very much needed again, regarding the steps humanity must make to lead economies and societies to recovery and a better future, including better management of tail risk. more about this below. table shows a top ten list of phenomena that are subject to the law of regression to the tail, ranked by the fatness of tails. all phenomena in the table have infinite variance, i.e., they are highly fat tailed. we see that the fattest tailindicating the largest and most frequent regressions to the tailare found for earthquakes (measured by intensity), which for good reasons are often considered the archetypical case of a power-law distributed deep disaster. pandemics (measured by number of deaths) are somewhere in the middle, and electricity blackouts (measured by number of customers affected) at the bottom, but still very fat-tailed and impactful. we note that floods and forest fires are both subject to regression to the tail. the same holds for droughts, hurricanes, landslides, ice melt, sea-level changes, and other phenomena closely related to the climate crisis, not included on the list. this tells us that understanding regression to the tail and how to mitigate its specific manifestations for climate will be key to mitigating the climate crisis. here it is worth remembering that regression to the tail for the climate crisis will be just as indifferent to human ignorance and folly as we saw regression to the tail was for covid- above. we either cut the tail and practice the precautionary principle for the climate crisis, or we die in large numbers and destroy our economic and social fabric, again. rebuilding the economy after the covid- pandemic will be subject to the law of regression to the tail, if less dramatically so than the pandemic itself. loss of life will hopefully soon fade as a main risk. but financial fragility, wealth destruction, and problems with debt will table top phenomena that are subject to the law of regression to the tail, ranked after fatness of tails. the higher on the list, the fatter the tail, and the larger and more frequent regressions to the tail will be. all phenomena have infinite variance. the table shows phenomena for which data were available. if the average r in a population is greater than , the infection will spread exponentially. if r is less than , the infection will spread only slowly, and will eventually die out. the higher the value of r above , the faster an epidemic will spread through a population. continue to be key risks for a while. the massive stimulus spending programmes that governments use to restart economies in recession typically comprise giant construction and investment projects with fat-tailed financial risks, like multi-billiondollar megaprojects in it, transport, energy, water, education, housing, health, and defense (flyvbjerg, ) . some projects are more fat-tailed than others, i.e., they are more susceptible to the law of regression to the tail. data analytics should be used to separate fat-tailed projects from thin-tailed ones, and stick with the latter whenever possible. we know how to do this. for instance, nuclear power plants are bespoke, slow to build, and fat tailed for financial and safety risks; whereas wind farms and energy storage are modular, fast, and thin tailed. by choosing wind over nuclear, the risk of regression to the tail will be significantly reduced, and climate goals will be achieved sooner. every investment alternative must be assessed in this manner to ensure that stimulus spending becomes a boost instead of a drag on the economy. the latter is happening more often than we like to think (ansar et al., (ansar et al., , (ansar et al., , detter and fölster, ; flyvbjerg, ; kanter, ; ren, ) . in addition to this, leaders should think about investment priorities coming out of the crisis and how to best restart the economy, taking into account what we have learnt from the crisis. such priorities include: the crisis has brought many health and care facilities, including for the elderly, to a breaking point, revealing that the safety of both employees and patients was compromised in ways that most would not have imagined. there will be a requirement to invest in people and facilities to rebuild these services. the crisis must be used to accelerate the transition to an electric, zero-carbon economy. this includes (a) investments in renewable energy (and maybe nuclear, if it can be made fast and safe) for powering industry and households; (b) electrification of trains, trucks, public transport, and cars; and (c) investments to improve true sustainability of farming, food manufacture, housing, and commercial real estate. we are unlikely to return to the same state of the world as when we entered the pandemic. remote working has the potential to become more prevalent after the crisis. investments might shift from face-to-face working (and lower the cost of office real estate and time for commuting). stimulus spending should focus investments on the enablers of this new approach to work, e.g., g rollouts, broadband infrastructure, satellites for global reach, server farms for adequate capacity, etc. few investments have historically been made to change the demand for transportation infrastructure. investments have tended to expand supply-side capacity following the heuristic "predict and provide". lockdowns and stay-at-home measures have reduced traffic and pollution levels. the gradual restart of the economy should be used to prevent traffic demand from returning to pre-crisis levels, turning the focus upside down from supply-side to demand-side management, following the heuristic "predict and prevent." there is likely to be a host of post-pandemic litigation, including massive class-action suits, to recoup losses or seek redress for negligence. to prevent this from running amok and hampering the restart of the economy, comprehensive compensation and settlement schemes should be designed and ready for implementation. the above measures and priorities do not lessen the urgency for prudence, here understood as aristotelian phronesis (flyvbjerg, ; flyvbjerg et al., ) . in fact, it raises its importance, especially asarguably and sadlyphronesis does not characterize senior and middle management decision making more generally and at times of crisis. this is the case for even top political leaders like presidents and prime ministers, as we saw above, despite the fact that they need phronesis more than anyone, or their citizens will suffer for the lack of it, as they do at present. rescher ( : ) rightly observes that randomness is best influenced by prudence. with the extreme randomness generated by regression to the tail, prudence therefore becomes particularly important, in the shape of common caution, hedging one's bets, keeping contingencies, providing insurance for all, and similar prudent measures. finally, to be effective, prudence must be based on dialogue and deliberation, something stressed already by aristotle. the social and economic infrastructure must be in place to facilitate the development of new, future approaches to pandemics and the climate crisis, shaping a new world in the process. if nothing else, efforts to prepare for and avoid the next pandemic would need a very strong, persistent, and ongoing rhetoric to be funded over time to keep attention on fat-tail phenomena alive and institutionalize it across policy, business, and everyday life, in the absence of events which justify such expenditure. this is another front on which we have failed miserably in the past and on which we cannot afford to fail in the future, as the world gets evermore connected. we are lucky that the covid- pandemic is not worse than it isspecifically that mortality for those infected is not higherbecause everything we know about pandemics tells us mortality might as well have been significantly higher, and that sooner or later there will be a pandemic like that, worse than the worst to date. that's the nature of fattailed risk as depicted by the law of regression to the tail. a positive way to view covid- is to see it as a much-needed opportunity for humanity to exercise its skills in managing regression to the tail. we need those skills to survive as a species and to build a world that is worth surviving in. covid- may be seen as a dress rehearsal for how to deal with the climate crisis; a crash course in how to mitigate regression to the tail. when we study the pandemic carefully it offers us the basic principles needed to mitigate other fat-tailed risks, the climate crisis included. seen from this perspective, despite its indisputable tragedy, covid- is a much-needed, large-scale survival exercise for humankind on planet earth. mitigating the climate crisis involves "thinking in long time scales while acting with furious urgency," as observed by mingle ( : ) . science tells us we have maybe a decade or two where we can still influence global warming, ice melt, and sea level change. then it will be too late. missing this window of opportunity is a scary prospect. the good news is, however, that covid- has served as a wake-up call and has demonstrated that the world, or at least parts of it, are capable of the speedy, concerted effort and massive involvement from government, science, business, and banks that are necessary to solve an urgent problem that threatens humanity as such. we did not know this pre-covid- , because the ability had never been tested. the covid- pandemic has taught us what to do and not to do in the face of regression to the tail. two lessons stand out. first, everyone needs to be honest about, and keep in mind, that there will be more extreme events in the future. there will be more pandemics, and one of these will be worse than covid- . this uncomfortable fact follows directly from the fat-tailed distribution of pandemics and the associated law of regression to the tail. second, once leaders and citizens understand that pandemics involve regression to the tail, they will also understand how to handle the next pandemic. specifically, four effective mitigation measures apply, when faced with regression to the tail: a) cutting the tail, by eliminating specific tail risks; b) using the precautionary principle, i.e., avoiding tail risk by taking a cautious approach; c) making sure the necessary contingencies are in place; and d) acting immediately, at blitz-like speed, and at scale, when the tail rears. the two lessons and four measures are general. they derive directly from the mathematical and statistical properties of fat-tailed distributions and apply not only to pandemics, but to all phenomena that are subject to the law of regression to the tail, for instance: floods, droughts, wildfires, earthquakes, landslides, tsunamis, wars, avalanches, crime, terrorist attacks, blackouts, big infrastructure projects, and more. in sum, covid- is a stark reminder of three things. first, extreme events will haunt humankind, over and over. it is only a matter of time until an event will occur that is more extreme than the most extreme to date. this is the "law of regression to the tail." second, historically we have been dismal at managing regression to the tail, today maybe more than ever with the lean, optimized, and highly interconnected global system we have created. third, with the tail risks currently facing humanity in terms of, e.g., climate, the pandemic, rebuilding the economy after the pandemic, and global debt, we cannot afford leadership that ignores or underestimates regression to the tail. using covid- to truly understand the basic principles of regression to the tail, and then putting those principles effectively to work in mitigating the major risks we currently faceparamountly the climate crisismay well be key to our survival as a species, or at least survival of life as we know it. if we do this, covid- would not be a wasted crisis. the author reports no declarations of interest. should we build more large dams? the actual costs of hydropower megaproject development does infrastructure investment lead to economic growth or economic fragility? evidence from china big is fragile: an attempt at theorizing scale coronavirus: boris johnson says 'it could have gone either way'. bbc news tail risk of contagious diseases. arxiv power-law distributions in empirical data express and star, . boris johnson's coronavirus timeline. express and star news making social science matter: why social inquiry fails and how it can succeed again the oxford handbook of megaproject management real social science: applied phronesis digitization disasters: towards a theory of it investment risk regression to the tail: why the olympics blow up power law in firms bankruptcy earlier lockdown could have halved uk deaths, says pm's exadviser. the financial times move: putting america's infrastructure back in the lead heavy-tailed distribution of cyber-risks the applicability of power-law frequency statistics to floods fractals and scaling in finance the (mis)behavior of markets boris johnson boasted of shaking hands on day sage warned not to. the guardian coronavirus: boris johnson was shaking hands as some scientists were calling for it to stop a world without ice. the new your review of books power laws, pareto distributions and zipf's law biggest infrastructure bubble ever? city and nation building with debt-financed megaprojects in china luck: the brilliant randomness of everyday life excess mortality from the coronavirus pandemic (covid- ). our world in data incerto. penguin random house statistical consequences of fat tails: real world preasymptotics, epistemology, and applications (technical incerto) scale: the universal laws of life and death in organisms, cities, and companies. weidenfeld and nicolson the author wishes to thank dr. alexander budzier, professor henrik flyvbjerg, professor carissa véliz, and the review team at the journal for highly useful comments and suggestions for improvements to an earlier version of the paper. key: cord- -h au h authors: adiga, aniruddha; chen, jiangzhuo; marathe, madhav; mortveit, henning; venkatramanan, srinivasan; vullikanti, anil title: data-driven modeling for different stages of pandemic response date: - - journal: nan doi: nan sha: doc_id: cord_uid: h au h some of the key questions of interest during the covid- pandemic (and all outbreaks) include: where did the disease start, how is it spreading, who is at risk, and how to control the spread. there are a large number of complex factors driving the spread of pandemics, and, as a result, multiple modeling techniques play an increasingly important role in shaping public policy and decision making. as different countries and regions go through phases of the pandemic, the questions and data availability also changes. especially of interest is aligning model development and data collection to support response efforts at each stage of the pandemic. the covid- pandemic has been unprecedented in terms of real-time collection and dissemination of a number of diverse datasets, ranging from disease outcomes, to mobility, behaviors, and socio-economic factors. the data sets have been critical from the perspective of disease modeling and analytics to support policymakers in real-time. in this overview article, we survey the data landscape around covid- , with a focus on how such datasets have aided modeling and response through different stages so far in the pandemic. we also discuss some of the current challenges and the needs that will arise as we plan our way out of the pandemic. as the sars-cov- pandemic has demonstrated, the spread of a highly infectious disease is a complex dynamical process. a large number of factors are at play as infectious diseases spread, including variable individual susceptibility to the pathogen (e.g., by age and health conditions), variable individual behaviors (e.g., compliance with social distancing and the use of masks), differing response strategies implemented by governments (e.g., school and workplace closure policies and criteria for testing), and potential availability of pharmaceutical interventions. governments have been forced to respond to the rapidly changing dynamics of the pandemic, and are becoming increasingly reliant on different modeling and analytical techniques to understand, forecast, plan and respond; this includes statistical methods and decision support methods using multi-agent models, such as: (i) forecasting epidemic outcomes (e.g., case counts, mortality and hospital demands), using a diverse set of data-driven methods e.g., arima type time series forecasting, bayesian techniques and deep learning, e.g., [ ] [ ] [ ] [ ] [ ] , (ii) disease surveillance, e.g., [ , ] , and (iii) counter-factual analysis of epidemics using multi-agent models, e.g., [ ] [ ] [ ] [ ] [ ] [ ] ; indeed, the results of [ , ] were very influential in the early decisions for lockdowns in a number of countries. the specific questions of interest change with the stage of the pandemic. in the pre-pandemic stage, the focus was on understanding how the outbreak started, epidemic parameters, and the risk of importation to different regions. once outbreaks started-the acceleration stage, the focus is on determining the growth rates, the differences in spatio-temporal characteristics, and testing bias. in the mitigation stage, the questions are focused on non-prophylactic interventions, such as school and work place closures and other social-distancing strategies, determining the demand for healthcare resources, and testing and tracing. in the suppression stage, the focus shifts to using prophylactic interventions, combined with better tracing. these phases are not linear, and overlap with each other. for instance, the acceleration and mitigation stages of the pandemic might overlap spatially, temporally as well as within certain social groups. different kinds of models are appropriate at different stages, and for addressing different kinds of questions. for instance, statistical and machine learning models are very useful in forecasting and short term projections. however, they are not very effective for longer-term projections, understanding the effects of different kinds of interventions, and counter-factual analysis. mechanistic models are very useful for such questions. simple compartmental type models, and their extensions, namely, structured metapopulation models are useful for several population level questions. however, once the outbreak has spread, and complex individual and community level behaviors are at play, multi-agent models are most effective, since they allow for a more systematic representation of complex social interactions, individual and collective behavioral adaptation and public policies. as with any mathematical modeling effort, data plays a big role in the utility of such models. till recently, data on infectious diseases was very hard to obtain due to various issues, such as privacy and sensitivity of the data (since it is information about individual health), and logistics of collecting such data. the data landscape during the sars-cov- pandemic has been very different: a large number of datasets are becoming available, ranging from disease outcomes (e.g., time series of the number of confirmed cases, deaths, and hospitalizations), some characteristics of their locations and demographics, healthcare infrastructure capacity (e.g., number of icu beds, number of healthcare personnel, and ventilators), and various kinds of behaviors (e.g., level of social distancing, usage of ppes); see [ ] [ ] [ ] for comprehensive surveys on available datasets. however, using these datasets for developing good models, and addressing important public health questions remains challenging. the goal of this article is to use the widely accepted stages of a pandemic as a guiding framework to highlight a few important problems that require attention in each of these stages. we will aim to provide a succinct model-agnostic formulation while identifying the key datasets needed, how they can be used, and the challenges arising in that process. we will also use sars-cov- as a case study unfolding in real-time, and highlight some interesting peer-reviewed and preprint literature that pertains to each of these problems. an important point to note is the necessity of randomly sampled data, e.g. data needed to assess the number of active cases and various demographics of individuals that were affected. census provides an excellent rationale. it is the only way one can develop rigorous estimates of various epidemiologically relevant quantities. there have been numerous surveys on the different types of datasets available for sars-cov- , e.g., [ ] [ ] [ ] [ ] , as well as different kinds of modeling approaches. however, they do not describe how these models become relevant through the phases of pandemic response. an earlier similar attempt to summarize such responsedriven modeling efforts can be found in [ ] , based on the -h n experience, this paper builds on their work and discusses these phases in the present context and the sars-cov- pandemic. although the paper touches upon different aspects of model-based decision making, we refer the readers to a companion article in the same special issue [ ] for a focused review of models used for projection and forecasting. multiple organizations including cdc and who have their frameworks for preparing and planning response to a pandemic. for instance, the pandemic intervals framework from cdc describes the stages in the context of an influenza pandemic; these are illustrated in figure . these six stages span investigation, recognition and initiation in the early phase, followed by most of the disease spread occurring during the acceleration and deceleration stages. they also provide indicators for identifying when the pandemic has progressed from one stage to the next [ ] . as envisioned, risk evaluation (i.e., using tools like influenza risk assessment tool (irat) and pandemic severity assessment framework (psaf)) and early case identification characterize the first three stages, while non-pharmaceutical interventions (npis) and available figure : cdc pandemic intervals framework and who phases for influenza pandemic therapeutics become central to the acceleration stage. the deceleration is facilitated by mass vaccination programs, exhaustion of susceptible population, or unsuitability of environmental conditions (such as weather). a similar framework is laid out in who's pandemic continuum and phases of pandemic alert . while such frameworks aid in streamlining the response efforts of these organizations, they also enable effective messaging. to the best of our knowledge, there has not been a similar characterization of mathematical modeling efforts that go hand in hand with supporting the response. for summarizing the key models, we consider four of the stages of pandemic response mentioned in section : pre-pandemic, acceleration, mitigation and suppression. here we provide the key problems in each stage, the datasets needed, the main tools and techniques used, and pertinent challenges. we structure our discussion based on our experience with modeling the spread of covid- in the us, done in collaboration with local and federal agencies. • acceleration (section ): this stage is relevant once the epidemic takes root within a country. there is usually a big lag in surveillance and response efforts, and the key questions are to model spread patterns at different spatio-temporal scales, and to derive short-term forecasts and projections. a broad class of datasets is used for developing models, including mobility, populations, land-use, and activities. these are combined with various kinds of time series data and covariates such as weather for forecasting. • mitigation (section ): in this stage, different interventions, which are mostly non-pharmaceutical in the case of a novel pathogen, are implemented by government agencies, once the outbreak has taken hold within the population. this stage involves understanding the impact of interventions on case counts and health infrastructure demands, taking individual behaviors into account. the additional datasets needed in this stage include those on behavioral changes and hospital capacities. • suppression (section ): this stage involves designing methods to control the outbreak by contact tracing & isolation and vaccination. data on contact tracing, associated biases, vaccine production schedules, and compliance & hesitancy are needed in this stage. figure gives an overview of this framework and summarizes the data needs in these stages. these stages also align well with the focus of the various modeling working groups organized by cdc which include epidemic parameter estimation, international spread risk, sub-national spread forecasting, impact of interventions, healthcare systems, and university modeling. in reality, one should note that these stages may overlap, and may vary based on geographical factors and response efforts. moreover, specific problems can be approached prospectively in earlier stages, or retrospectively during later stages. this framework is thus meant to be more conceptual than interpreted along a linear timeline. results from such stages are very useful for policymakers to guide real-time response. consider a novel pathogen emerging in human populations that is detected through early cases involving unusual symptoms or unknown etiology. such outbreaks are characterized by some kind of spillover event, mostly through zoonotic means, like in the case of covid- or past influenza pandemics (e.g., swine flu and avian flu). a similar scenario can occur when an incidence of a well-documented disease with no known vaccine or therapeutics emerges in some part of the world, causing severe outcomes or fatalities (e.g., ebola and zika.) regardless of the development status of the country where the pathogen emerged, such outbreaks now contains the risk of causing a worldwide pandemic due to the global connectivity induced by human travel. two questions become relevant at this stage: what are the epidemiological attributes of this disease, and what are the risks of importation to a different country? while the first question involves biological and clinical investigations, the latter is more related with societal and environmental factors. one of the crucial tasks during early disease investigation is to ascertain the transmission and severity of the disease. these are important dimensions along which the pandemic potential is characterized because together they determine the overall disease burden, as demonstrated within the pandemic severity assessment framework [ ] . in addition to risk assessment for right-sizing response, they are integral to developing meaningful disease models. formulation let Θ = {θ t , θ s } represent the transmission and severity parameters of interest. they can be further subdivided into sojourn time parameters θ δ · and transition probability parameters θ p · . here Θ corresponds to a continuous time markov chain (ctmc) on the disease states. the problem formulation can be represented as follows: given Π(Θ), the prior distribution on the disease parameters and a dataset d, estimate the posterior distribution p(Θ|d) over all possible values of Θ. in a model-specific form, this can be expressed as p(Θ|d, m) where m is a statistical, compartmental or agent-based disease model. in order to estimate the disease parameters sufficiently, line lists for individual confirmed cases is ideal. such datasets contain, for each record, the date of confirmation, possible date of onset, severity (hospitalization/icu) status, and date of recovery/discharge/death. furthermore, age-and demographic/comorbidity information allow development of models that are age-and risk group stratified. one such crowdsourced line list was compiled during the early stages of covid- [ ] and later released by cdc for us cases [ ] . data from detailed clinical investigations from other countries such as china, south korea, and singapore was also used to parameterize these models [ ] . in the absence of such datasets, past parameter estimates of similar diseases (e.g., sars, mers) were used for early analyses. modeling approaches for a model agnostic approach, the delays and probabilities are obtained by various techniques, including bayesian and ordinary least squares fitting to various delay distributions. for a particular disease model, these are estimated through model calibration techniques such as mcmc and particle filtering approaches. a summary of community estimates of various disease parameters is provided at https://github.com/midas-network/covid- . further such estimates allow the design of pandemic planning scenarios varying in levels of impact, as seen in the cdc scenarios page . see [ ] [ ] [ ] for methods and results related to estimating covid- disease parameters from real data. current models use a large set of disease parameters for modeling covid- dynamics; they can be broadly classified as transmission parameters and hospital resource parameters. for instance in our work, we currently use parameters (with explanations) shown in table . challenges often these parameters are model specific, and hence one needs to be careful when reusing parameter estimates from literature. they are related but not identifiable with respect to population level measures such as basic reproductive number r (or effective reproductive number r eff ) and doubling time which allow tracking the rate of epidemic growth. also the estimation is hindered by inherent biases in case ascertainment rate, reporting delays and other gaps in the surveillance system. aligning different data streams (e.g., outpatient surveillance, hospitalization rates, mortality records) is in itself challenging. when a disease outbreak occurs in some part of the world, it is imperative for most countries to estimate their risk of importation through spatial proximity or international travel. such measures are incredibly valuable in setting a timeline for preparation efforts, and initiating health checks at the borders. over centuries, pandemics have spread faster and faster across the globe, making it all the more important to characterize this risk as early as possible. formulation let c be the set of countries, and g = {c, e} an international network, where edges (often weighted and directed) in e represent some notion of connectivity. the importation risk problem can be formulated as below: given c o ∈ c the country of origin with an initial case at time , and c i the country of interest, using g, estimate the expected time taken t i for the first cases to arrive in country c i . in its probabilistic form, the same can be expressed as estimating the probability p i (t) of seeing the first case in country c i by time t. data needs assuming we have initial case reports from the origin country, the first data needed is a network that connects the countries of the world to represent human travel. the most common source of such information is the airline network datasets, from sources such as iata, oag, and openflights; [ ] provides a systematic review of how airline passenger data has been used for infectious disease modeling. these datasets could either capture static measures such as number of seats available or flight schedules, or a dynamic count of passengers per month along each itinerary. since the latter has intrinsic delays in collection and reporting, for an ongoing pandemic they may not be representative. during such times, data on ongoing travel restrictions [ ] become important to incorporate. multi-modal traffic will also be important to incorporate for countries that share land borders or have heavy maritime traffic. for diseases such as zika, where establishment risk is more relevant, data on vector abundance or prevailing weather conditions are appropriate. modeling approaches simple structural measures on networks (such as degree, pagerank) could provide static indicators of vulnerability of countries. by transforming the weighted, directed edges into probabilities, one can use simple contagion models (e.g., independent cascades) to simulate disease spread and empirically estimate expected time of arrival. global metapopulation models (gleam) that combine seir type dynamics with an airline network have also been used in the past for estimating importation risk. brockmann and helbing [ ] used a similar framework to quantify effective distance on the network which seemed to be well correlated with time of arrival for multiple pandemics in the past; this has been extended to covid- [ , ] . in [ ] , the authors employ air travel volume obtained through iata from ten major cities across china to rank various countries along with the idvi to convey their vulnerability. [ ] consider the task of forecasting international and domestic spread of covid- and employ official airline group (oag) data for determining air traffic to various countries, and [ ] fit a generalized linear model for observed number of cases in various countries as a function of air traffic volume obtained from oag data to determine countries with potential risk of under-detection. also, [ ] provide africa-specific case-study of vulnerability and preparedness using data from civil aviation administration of china. challenges note that arrival of an infected traveler will precede a local transmission event in a country. hence the former is more appropriate to quantify in early stages. also, the formulation is agnostic to whether it is the first infected arrival or first detected case. however, in real world, the former is difficult to observe, while the latter is influenced by security measures at ports of entry (land, sea, air) and the ease of identification for the pathogen. for instance, in the case of covid- , the long incubation period and the high likelihood of asymptomaticity could have resulted in many infected travelers being missed by health checks at poes. we also noticed potential administrative delays in reporting by multiple countries fearing travel restrictions. as the epidemic takes root within a country, it may enter the acceleration phase. depending on the testing infrastructure and agility of surveillance system, response efforts might lag or lead the rapid growth in case rate. under such a scenario, two crucial questions emerge that pertain to how the disease may spread spatially/socially and how the case rate may grow over time. within the country, there is need to model the spatial spread of the disease at different scales: state, county, and community levels. similar to the importation risk, such models may provide an estimate of when cases may emerge in different parts of the country. when coupled with vulnerability indicators (socioeconomic, demographic, co-morbidities) they provide a framework for assessing the heterogeneous impact the disease may have across the country. detailed agent-based models for urban centers may help identify hotspots and potential case clusters that may emerge (e.g., correctional facilities, nursing homes, food processing plants, etc. in the case of covid- ). formulation given a population representation p at appropriate scale and a disease model m per entity (individual or sub-region), model the disease spread under different assumptions of underlying connectivity c and disease parameters Θ. the result will be a spatio-temporal spread model that results in z s,t , the time series of disease states over time for region s. data needs some of the common datasets needed by most modeling approaches include: ( ) social and spatial representation, which includes census, and population data, which are available from census departments (see, e.g., [ ] ), and landscan [ ] , ( ) connectivity between regions (commuter, airline, road/rail/river), e.g., [ , ] , ( ) data on locations, including points of interest, e.g., openstreetmap [ ] , and ( ) activity data, e.g., the american time use survey [ ] . these datasets help capture where people reside and how they move around, and come in contact with each other. while some of these are static, more dynamic measures, such as from gps traces, become relevant as individuals change their behavior during a pandemic. modeling approaches different kinds of structured metapopulation models [ , [ ] [ ] [ ] [ ] , and agent based models [ ] [ ] [ ] [ ] [ ] have been used in the past to model the sub-national spread; we refer to [ , , ] for surveys on different modeling approaches. these models incorporate typical mixing patterns, which result from detailed activities and co-location (in the case of agent based models), and different modes of travel and commuting (in the case of metapopulation models). challenges while metapopulation models can be built relatively rapidly, agent based models are much harder-the datasets need to be assembled at a large scale, with detailed construction pipelines, see, e.g., [ ] [ ] [ ] [ ] [ ] . since detailed individual activities drive the dynamics in agent based models, schools and workplaces have to be modeled, in order to make predictions meaningful. such models will get reused at different stages of the outbreak, so they need to be generic enough to incorporate dynamically evolving disease information. finally, a common challenge across modeling paradigms is the ability to calibrate to the dynamically evolving spatio-temporal data from the outbreak-this is especially challenging in the presence of reporting biases and data insufficiency issues. given the early growth of cases within the country (or sub-region), there is need for quantifying the rate of increase in comparable terms across the duration of the outbreak (accounting for the exponential nature of such processes). these estimates also serve as references, when evaluating the impact of various interventions. as an extension, such methods and more sophisticated time series methods can be used to produce short-term forecasts for disease evolution. formulation given the disease time series data within the country z s,t until data horizon t , provide scale-independent growth rate measures g s (t ), and forecastsẐ s,u for u ∈ [t, t + ∆t ], where ∆t is the forecast horizon. data needs models at this stage require datasets such as ( ) time series data on different kinds of disease outcomes, including case counts, mortality, hospitalizations, along with attributes, such as age, gender and location, e.g., [ ] [ ] [ ] [ ] [ ] , ( ) any associated data for reporting bias (total tests, test positivity rate) [ ] , which need to be incorporated into the models, as these biases can have a significant impact on the dynamics, and ( ) exogenous regressors (mobility, weather), which have been shown to have a significant impact on other diseases, such as influenza, e.g., [ ] . modeling approaches even before building statistical or mechanistic time series forecasting methods, one can derive insights through analytical measures of the time series data. for instance, the effective reproductive number, estimated from the time series [ ] can serve as a scale-independent metric to compare the outbreaks across space and time. additionally multiple statistical methods ranging from autoregressive models to deep learning techniques can be applied to the time series data, with additional exogenous variables as input. while such methods perform reasonably for short-term targets, mechanistic approaches as described earlier can provide better long-term projections. various ensembling techniques have also been developed in the recent past to combine such multi-model forecasts to provide a single robust forecast with better uncertainty quantification. one such effort that combines more than methods for covid- can be found at the covid forecasting hub . we also point to the companion paper for more details on projection and forecasting models. challenges data on epidemic outcomes usually has a lot of uncertainties and errors, including missing data, collection bias, and backfill. for forecasting tasks, these time series data need to be near real-time, else one needs to do both nowcasting, as well as forecasting. other exogenous regressors can provide valuable lead time, due to inherent delays in disease dynamics from exposure to case identification. such frameworks need to be generalized to accommodate qualitative inputs on future policies (shutdowns, mask mandates, etc.), as well as behaviors, as we discuss in the next section. once the outbreak has taken hold within the population, local, state and national governments attempt to mitigate and control its spread by considering different kinds of interventions. unfortunately, as the covid- pandemic has shown, there is a significant delay in the time taken by governments to respond. as a result, this has caused a large number of cases, a fraction of which lead to hospitalizations. two key questions in this stage are: ( ) how to evaluate different kinds of interventions, and choose the most effective ones, and ( ) how to estimate the healthcare infrastructure demand, and how to mitigate it. the effectiveness of an intervention (e.g., social distancing) depends on how individuals respond to them, and the level of compliance. the health resource demand depends on the specific interventions which are implemented. as a result, both these questions are connected, and require models which incorporate appropriate behavioral responses. in the initial stages, only non-prophylactic interventions are available, such as: social distancing, school and workplace closures, and use of ppes, since no vaccinations and anti-virals are available. as mentioned above, such analyses are almost entirely model based, and the specific model depends on the nature of the intervention and the population being studied. formulation given a model, denoted abstractly as m, the general goals are ( ) to evaluate the impact of an intervention (e.g., school and workplace closure, and other social distancing strategies) on different epidemic outcomes (e.g., average outbreak size, peak size, and time to peak), and ( ) find the most effective intervention from a suite of interventions, with given resource constraints. the specific formulation depends crucially on the model and type of intervention. even for a single intervention, evaluating its impact is quite challenging, since there are a number of sources of uncertainty, and a number of parameters associated with the intervention (e.g., when to start school closure, how long, and how to restart). therefore, finding uncertainty bounds is a key part of the problem. data needs while all the data needs from the previous stages for developing a model are still there, representation of different kinds of behaviors is a crucial component of the models in this stage; this includes: use of ppes, compliance to social distancing measures, and level of mobility. statistics on such behaviors are available at a fairly detailed level (e.g., counties and daily) from multiple sources, such as ( ) the covid- impact analysis platform from the university of maryland [ ] , which gives metrics related to social distancing activities, including level of staying home, outside county trips, outside state trips, ( ) changes in mobility associated with different kinds of activities from google [ ] , and other sources, ( ) survey data on different kinds of behaviors, such as usage of masks [ ] . modeling approaches as mentioned above, such analyses are almost entirely model based, including structured metapopulation models [ , [ ] [ ] [ ] [ ] , and agent based models [ ] [ ] [ ] [ ] [ ] . different kinds of behaviors relevant to such interventions, including compliance with using ppes and compliance to social distancing guidelines, need to be incorporated into these models. since there is a great deal of heterogeneity in such behaviors, it is conceptually easiest to incorporate them into agent based models, since individual agents are represented. however, calibration, simulation and analysis of such models pose significant computational challenges. on the other hand, the simulation of metapopulation models is much easier, but such behaviors cannot be directly represented-instead, modelers have to estimate the effect of different behaviors on the disease model parameters, which can pose modeling challenges. challenges there are a number of challenges in using data on behaviors, which depends on the specific datasets. much of the data available for covid- is estimated through indirect sources, e.g., through cell phone and online activities, and crowd-sourced platforms. this can provide large spatio-temporal datasets, but have unknown biases and uncertainties. on the other hand, survey data is often more reliable, and provides several covariates, but is typically very sparse. handling such uncertainties, rigorous sensitivity analysis, and incorporating the uncertainties into the analysis of the simulation outputs are important steps for modelers. the covid- pandemic has led to a significant increase in hospitalizations. hospitals are typically optimized to run near capacity, so there have been fears that the hospital capacities would not be adequate, especially in several countries in asia, but also in some regions in the us. nosocomial transmission could further increase this burden. formulation the overall problem is to estimate the demand for hospital resources within a populationthis includes the number of hospitalizations, and more refined types of resources, such as icus, ccus, medical personnel and equipment, such as ventilators. an important issue is whether the capacity of hospitals within the region would be overrun by the demand, when this is expected to happen, and how to design strategies to meet the demand-this could be through augmenting the capacities at existing hospitals, or building new facilities. timing is of essence, and projections of when the demands exceed capacity are important for governments to plan. the demands for hospitalization and other health resources can be estimated from the epidemic models mentioned earlier, by incorporating suitable health states, e.g., [ , ] ; in addition to the inputs needed for setting up the models for case counts, datasets are needed for hospitalization rates and durations of hospital stay, icu care, and ventilation. the other important inputs for this component are hospital capacity, and the referral regions (which represent where patients travel for hospitalization). different public and commercial datasets provide such information, e.g., [ , ] . modeling approaches demand for health resources is typically incorporated into both metapopulation and agent based models, by having a fraction of the infectious individuals transition into a hospitalization state. an important issue to consider is what happens if there is a shortage of hospital capacity. studying this requires modeling the hospital infrastructure, i.e., different kinds of hospitals within the region, and which hospital a patient goes to. there is typically limited data on this, and data on hospital referral regions, or voronoi tesselation can be used. understanding the regimes in which hospital demand exceeds capacity is an important question to study. nosocomial transmission is typically much harder to study, since it requires more detailed modeling of processes within hospitals. challenges there is a lot of uncertainty and variability in all the datasets involved in this process, making its modeling difficult. for instance, forecasts of the number of cases and hospitalizations have huge uncertainty bounds for medium or long term horizon, which is the kind of input necessary for understanding hospital demands, and whether there would be any deficits. the suppression stage involves methods to control the outbreak, including reducing the incidence rate and potentially leading to the eradication of the disease in the end. eradication in case of covid- appears unlikely as of now, what is more likely is that this will become part of seasonal human coronaviruses that will mutate continuously much like the influenza virus. contact tracing problem refers to the ability to trace the neighbors of an infected individual. ideally, if one is successful, each neighbor of an infected neighbor would be identified and isolated from the larger population to reduce the growth of a pandemic. in some cases, each such neighbor could be tested to see if the individual has contracted the disease. contact tracing is the workhorse in epidemiology and has been immensely successful in controlling slow moving diseases. when combined with vaccination and other pharmaceutical interventions, it provides the best way to control and suppress an epidemic. formulation the basic contact tracing problem is stated as follows: given a social contact network g(v, e) and subset of nodes s ⊂ v that are infected and a subset s ⊂ s of nodes identified as infected, find all neighbors of s. here a neighbor means an individual who is likely to have a substantial contact with the infected person. one then tests them (if tests are available), and following that, isolates these neighbors, or vaccinates them or administers anti-viral. the measures of effectiveness for the problem include: (i) maximizing the size of s , (ii) maximizing the size of set n (s ) ⊆ n (s), i.e. the potential number of neighbors of set s , (iii) doing this within a short period of time so that these neighbors either do not become infectious, or they minimize the number of days that they are infectious, while they are still interacting in the community in a normal manner, (iv) the eventual goal is to try and reduce the incidence rate in the community-thus if all the neighbors of s cannot be identified, one aims to identify those individuals who when isolated/treated lead to a large impact; (v) and finally verifying that these individuals indeed came in contact with the infected individuals and thus can be asked to isolate or be treated. data needs data needed for the contact tracing problem includes: (i) a line list of individuals who are currently known to be infected (this is needed in case of human based contact tracing). in the real world, when carrying out human contact tracers based deployment, one interviews all the individuals who are known to be infectious and reaches out to their contacts. modeling approaches human contact tracing is routinely done in epidemiology. most states in the us have hired such contact tracers. they obtain the daily incidence report from the state health departments and then proceed to contact the individuals who are confirmed to be infected. earlier, human contact tracers used to go from house to house and identify the potential neighbors through a well defined interview process. although very effective it is very time consuming and labor intensive. phones were used extensively in the last - years as they allow the contact tracers to reach individuals. they are helpful but have the downside that it might be hard to reach all individuals. during covid- outbreak, for the first time, societies and governments have considered and deployed digital contact tracing tools [ ] [ ] [ ] [ ] [ ] . these can be quite effective but also have certain weaknesses, including, privacy, accuracy, and limited market penetration of the digital apps. challenges these include: (i) inability to identify everyone who is infectious (the set s) -this is virtually impossible for covid- like disease unless the incidence rate has come down drastically and for the reason that many individuals are infected but asymptomatic; (ii) identifying all contacts of s (or s ) -this is hard since individuals cannot recall everyone they met, certain folks that they were in close proximity might have been in stores or social events and thus not known to individuals in the set s. furthermore, even if a person is able to identify the contacts, it is often hard to reach all the individuals due to resource constraints (each human tracer can only contact a small number of individuals. the overall goal of the vaccine allocation problem is to allocate vaccine efficiently and in a timely manner to reduce the overall burden of the pandemic. formulation the basic version of the problem can be cast in a very simple manner (for networked models): given a graph g(v, e) and a budget b on the number of vaccines available, find a set s of size b to vaccinate so as to optimize certain measure of effectiveness. the measure of effectiveness can be (i) minimizing the total number of individuals infected (or maximizing the total number of uninfected individuals); (ii) minimizing the total number of deaths (or maximizing the total number of deaths averted); (iii) optimizing the above quantities but keeping in mind certain equity and fairness criteria (across socio-demographic groups, e.g. age, race, income); (iv) taking into account vaccine hesitancy of individuals; (v) taking into account the fact that all vaccines are not available at the start of the pandemic, and when they become available, one gets limited number of doses each month; (vi) deciding how to share the stockpile between countries, state, and other organizations; (vii) taking into account efficacy of the vaccine. data needs as in other problems, vaccine allocation problems need as input a good representation of the system; network based, meta-population based and compartmental mass action models can be used. one other key input is the vaccine budget, i.e., the production schedule and timeline, which serves as the constraint for the allocation problem. additional data on prevailing vaccine sentiment and past compliance to seasonal/neonatal vaccinations are useful to estimate coverage. modeling approaches the problem has been studied actively in the literature; network science community has focused on optimal allocation schemes, while public health community has focused on using meta-population models and assessing certain fixed allocation schemes based on socio-economic and demographic considerations. game theoretic approaches that try and understand strategic behavior of individuals and organization has also been studied. challenges the problem is computationally challenging and thus most of the time simulation based optimization techniques are used. challenge to the optimization approach comes from the fact that the optimal allocation scheme might be hard to compute or hard to implement. other challenges include fairness criteria (e.g. the optimal set might be a specific group) and also multiple objectives that one needs to balance. while the above sections provide an overview of salient modeling questions that arise during the key stages of a pandemic, mathematical and computational model development is equally if not more important as we approach the post-pandemic (or more appropriately inter-pandemic) phase. often referred to as peace time efforts, this phase allows modelers to retrospectively assess individual and collective models on how they performed during the pandemic. in order to encourage continued development and identifying data gaps, synthetic forecasting challenge exercises [ ] may be conducted where multiple modeling groups are invited to forecast synthetic scenarios with varying levels of data availability. another set of models that are quite relevant for policymakers during the winding down stages, are those that help assess overall health burden and economic costs of the pandemic. epideep: exploiting embeddings for epidemic forecasting an arima model to forecast the spread and the final size of covid- epidemic in italy (first version on ssrn march) real-time epidemic forecasting: challenges and opportunities accuracy of real-time multi-model ensemble forecasts for seasonal influenza in the u.s realtime forecasting of infectious disease dynamics with a stochastic semi-mechanistic model healthmap the use of social media in public health surveillance. western pacific surveillance and response journal : wpsar the effect of travel restrictions on the spread of the novel coronavirus (covid- ) outbreak basic prediction methodology for covid- : estimation and sensitivity considerations. medrxiv covid- outbreak on the diamond princess cruise ship: estimating the epidemic potential and effectiveness of public health countermeasures impact of non-pharmaceutical interventions (npis) to reduce covid mortality and healthcare demand. imperial college technical report modelling disease outbreaks in realistic urban social networks computational epidemiology forecasting covid- impact on hospital bed-days, icudays, ventilator-days and deaths by us state in the next months open data resources for fighting covid- data-driven methods to monitor, model, forecast and control covid- pandemic: leveraging data science, epidemiology and control theory covid- datasets: a survey and future challenges. medrxiv mathematical modeling of epidemic diseases the use of mathematical models to inform influenza pandemic preparedness and response mathematical models for covid- pandemic: a comparative analysis updated preparedness and response framework for influenza pandemics novel framework for assessing epidemiologic effects of influenza epidemics and pandemics covid- pandemic planning scenarios epidemiological data from the covid- outbreak, real-time case information covid- case surveillance public use data -data -centers for disease control and prevention covid- patients' clinical characteristics, discharge rate, and fatality rate of meta-analysis estimating the generation interval for coronavirus disease (covid- ) based on symptom onset data the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application estimating clinical severity of covid- from the transmission dynamics in wuhan, china the use and reporting of airline passenger data for infectious disease modelling: a systematic review flight cancellations related to -ncov (covid- ) the hidden geometry of complex, network-driven contagion phenomena potential for global spread of a novel coronavirus from china forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study. the lancet using predicted imports of -ncov cases to determine locations that may not be identifying all imported cases. medrxiv preparedness and vulnerability of african countries against introductions of -ncov. medrxiv creating synthetic baseline populations openstreetmap american time use survey multiscale mobility networks and the spatial spreading of infectious diseases optimizing spatial allocation of seasonal influenza vaccine under temporal constraints assessing the international spreading risk associated with the west african ebola outbreak spread of zika virus in the americas structure of social contact networks and their impact on epidemics generation and analysis of large synthetic social contact networks modelling disease outbreaks in realistic urban social networks containing pandemic influenza at the source report : impact of non-pharmaceutical interventions (npis) to reduce covid mortality and healthcare demand the structure and function of complex networks a public data lake for analysis of covid- data midas network. midas novel coronavirus repository covid- ) data in the united states covid- impact analysis platform covid- surveillance dashboard the covid tracking project absolute humidity and the seasonal onset of influenza in the continental united states epiestim: a package to estimate time varying reproduction numbers from epidemic curves. r package version google covid- community mobility reports mask-wearing survey data impact of social distancing measures on coronavirus disease healthcare demand, central texas, usa current hospital capacity estimates -snapshot total hospital bed occupancy quantifying the effects of contact tracing, testing, and containment covid- epidemic in switzerland: on the importance of testing, contact tracing and isolation quantifying sars-cov- transmission suggests epidemic control with digital contact tracing isolation and contact tracing can tip the scale to containment of covid- in populations with social distancing. available at ssrn privacy sensitive protocols and mechanisms for mobile contact tracing the rapidd ebola forecasting challenge: synthesis and lessons learnt acknowledgments. the authors would like to thank members of the biocomplexity covid- response team and network systems science and advanced computing (nssac) division for their thoughtful comments and suggestions related to epidemic modeling and response support. we thank members of the biocomplexity institute and initiative, university of virginia for useful discussion and suggestions. this key: cord- -hspek authors: timmis, kenneth; brüssow, harald title: the covid‐ pandemic: some lessons learned about crisis preparedness and management, and the need for international benchmarking to reduce deficits date: - - journal: environ microbiol doi: . / - . sha: doc_id: cord_uid: hspek nan if, despite the explicit warning of the world health organization in that 'the world is ill-prepared to respond to a severe influenza pandemic or to any similarly global, sustained and threatening public-health emergency' (https://apps.who.int/gb/ebwha/pdf_files/wha /a _ en.pdf), it was not apparent to those in charge, and to the general public-i.e., those suffering from covid- infections and the funders of health services (tax/insurance payers)-that existing health systems had inherent vulnerabilities which could prove to be devastating when seriously stressed, the sars-cov- pandemic (e.g., see brüssow, ) has brutally exposed it now. in some countries, preparedness, despite being officially considered to be of strong operational readiness against health emergencies (kandel et al., ) , was inadequate at multiple levels (e.g., horton, ) . similarly, a fundamental lack of preparedness is the case for a number of impending non-health crises (e.g., global warming, poverty, the soil crisis, etc.). once we are over the covid- pandemic, important questions will be: what have we learned/can we learn and how can we improve our systems? below, we argue for the necessity for major realignment of crisis responsiveness, and indeed of health system operationality, based on international benchmarking and adequately funded preparedness. international benchmarking is mandatory, because it has become clear that there is a wide range of effectiveness in the ability of different countries with developed economies to respond to this crisis (and probably others), and the tax-paying public has no compelling reason to tolerate perpetuation of factors underlying poor responses to crises. disparity in country/regional responses to sars-cov- leaving aside for the moment decisions about whether to robustly contain the outbreak-to kill it by throttling-the classical strategy of infection control, but which leaves most of the population susceptible to a new outbreak, or attempt to manage an outbreak to achieve herd immunity and a population unsusceptible to a repeat outbreak, it is obviously imperative to know how the outbreak is spreading and how effective are any containment measures that are instituted, so that a change in course of action remains an option. widespread testing for the viral pathogen, with correct sampling and analysis procedures, is thus essential. this enables, inter alia, calculation of reliable mortality (case fatality) rates, which ordinarily play a key role in determining crisis response policy, calculation of the basic reproduction number, r , and reliable modelling of transmission and mortality trends. there have been enormous differences in testing coverages among countries. early predictions of transmission and mortality trends are only as good as the adequacy of the information fed into models so, with inadequate testing, prediction of trends are unreliable. mortality-based policy formulation for sars-cov- responses in some countries was based on incomplete information. • diagnostics and widespread testing are the basis of informed policy development for crisis management of infectious disease epi/pandemics and must become its centrepiece the disparity of sars-cov- testing coverage in different countries is much discussed but the reasons are sometimes rather opaque. there are many tests available (e.g., see https://www.finddx.org/covid- /pipeline/), so one bottleneck would appear to be a limitation in authorized testing facilities. scaling up testing in existing official centres requires not only acquisition of the appropriate instrumentation and reagents, but also of competent personnel disposing of the necessary expertise, which may constitute a bottleneck. however, it is abundantly clear that the instrumentation and expertise needed to carry out sars-cov- testing are widespread in academic research laboratories, as is the eagerness of many research groups to contribute to efforts to combat the pandemic. while issues of safety, quality control, logistics, data reporting and security and so on, need to be addressed, a failure in some countries to harness early in the crisis the expertise and enthusiasm of young researchers to fulfil a key need and, with it, the opportunity to acquire data that could have resulted in responses that saved lives, is regrettable. paradoxically, while there have been frantic efforts to open new hospital facilities to accommodate covid- patients, and to recruit the health professionals needed to operate them, there has been an indiscriminate closing of research institutes capable of carrying out diagnostic work, and thus of identifying infected and, importantly for frontline health professionals, non-infected individuals. • rapidly developing pandemics necessitate rapid responses. getting diagnostics and testing facilities up and running that are able to handle large numbers of samples are key to efforts to manage the disease. crisis preparedness demands not only formulation of strategies to enable rapid scale up official facilities, but also advance identification of relevant available resources outside of the health system, and strategies of how to promptly and effectively harness them. widespread testing for viral rna must be complemented by widespread testing, or at least the testing of sentinels of the population, for anti-viral antibodies. this is essential for relating the dynamics of infection to virus shedding (being infectious = infective for others) and to symptom development. and if (and this is a big if) the presence of antiviral antibodies reflects protective immunity, antibody testing is essential for herd immunity policy scenarios, to provide the data needed for monitoring and modelling immune population densities/granularity, and also for identification of those in the population who are in principle protected and hence able to return to normality and spearhead safe exit strategies from lockdown measures. • contingency planning requires identification of facilities or alliances able to promptly develop, produce in quantity and distribute easy-to-use antiviral antibody tests. patients having contracted covid- are grouped into three categories: in the china outbreak, % experienced mild, % severe and % critical infections (wu and mcgoogan, ) . for those requiring hospitalization, and those with the most acute symptoms requiring intensive care, two key variables in treatment capacity seem to be bed availability generally, and in intensive care units particularly (images of patients lying on the floors of some hospitals made this abundantly clear to the entire world), on one hand, and ventilator/intubation tube availability for patients needing intubation, on the other. there are enormous differences between countries in terms the availability of hospital beds/ population (e.g., japan . , germany . , france . , switzerland . , italy . , uk/canada/denmark . , india . : https:// data.oecd.org/healtheqt/hospital-beds.htm), icu beds/ population, and numbers of available ventilators/intubation tubes (here, ventilators can be considered a proxy for any other clinical device that may be needed in a health crisis). an insufficiency of beds (and often health professionals) also resulted in 'non-critical' interventions being postponed in some countries, and who, among critically ill patients suffering from different ailments, should be given an icu bed. there are different reasons for insufficient beds and clinical devices. but the fact remains: some countries manage better than others; some countries do not have enough beds for even small increases representing normal fluctuations in patient needs and anticipated seasonal variations, let alone exceptional demands made by epidemics. • it is essential to increase bed, especially icu bed, capacities in many countries, in order to reduce stress situations where patients cannot receive required treatment, and to prevent hospitals from being overwhelmed in times of crisis, when there is a spike in patients requiring hospitalization. one new development triggered by the covid- pandemic was the creation of so-called 'fangcang shelter hospitals'-rapidly constructed, large scale, low cost, temporary hospitals, by converting existing public venues into healthcare facilities in wuhan to manage the rapidly increasing covid- patient numbers (chen et al., ) . instead of being delivered to regular hospitals, covid- patients were sent to shelter hospitals, where they were isolated and received basic medical care and frequent monitoring. patients whose mild disease state transitioned to severe were then transferred to regular hospitals where they received intensive care. although new emergency hospitals have been created in other countries, the purpose of these is generally to receive spillover from traditional hospitals, when these become overwhelmed by patient numbers. the purpose of fangcang shelter hospitals is, in contrast, to centralize clinical management of the epi/pandemic outside of the traditional hospital system. covid- patients are channelled to shelter hospitals, thereby minimizing viral ingress into hospitals and infection of health professionals, and helping to maintain staffing levels and normal functioning of outpatient and inpatient facilities. it is important to note that shelter hospitals constitute low-cost clinical settings-they require fewer health professionals and diagnostic-treatment infrastructure than normal hospitals, because all patients have the same clinical issue and most have only mild-to-moderate disease-and thereby relieve pressure on traditional hospitals with sophisticated infrastructure in limited capacity that constitute high-cost clinical settings (the creation of parallel low-cost clinical settings to relieve pressure on limited capacity high cost clinical settings is more broadly applicable over and above epi/pandemic response situations: see timmis and timmis, , for an example in primary healthcare). • shelter hospitals should be incorporated into pandemic planning as the primary destination for pandemic patients, to allow traditional hospitals to continue functioning as normal as possible (or normally as long as possible). it may seem so trivially obvious to say, but obviously needs saying because it was not apparent from the health system responses of a number of countries: those most at risk of infection are those in contact with the infected, i.e., front-line doctors and nurses. and as they become infected, the numbers of available health professionals left to treat patients goes down as patient numbers go up. and, of course, infected health professionals become transmitters of infection among one another, and to uninfected patients, since in the hectic reality of emergencies, they may not always be able to practice adequate physical distancing. this obviously means that the greatest protection from infection must be accorded the front-line professionals. however, there were substantive differences between countries in terms of the availability and use of best practice protective clothing (personal protective equipment, ppe) in the early days of the covid- crisis; these differences were mainly in different degrees of deficiencies. the incomplete protection of front-line health professionals that occurred in a number of countries in the early days of the crisis, and that resulted in many infections and some deaths, is an unacceptable deficit in their health systems, particularly since the covid- outbreak was, from end of january , a predictable disaster of international magnitude. then there are those one might designate accessory front-line professionals: those who transport infected individuals, like ambulance drivers, non-medical workers in hospitals, and so forth, carers ministering to people in care homes or in private homes, and others like some pharmacy and supermarket staff who, because of the nature of their work, come into physical contact with many people and cannot always achieve prescribed physical distancing. these are also particularly vulnerable to infection and to becoming infection transmitters. since the people they care for are, because of their ages and underlying morbidities, often themselves particularly vulnerable to severe outcomes, infected carers may, unknowingly and unwillingly, become 'angels of death'. accessory front-line professionals thus also require best ppe. there are wide regional and occupational differences in the availability and use of such clothing by these professionals. in addition to the issue of ppe, there is the issue of hygiene in the workplace-the surfaces that become contaminated and sources of infection. while traditionally these have been cleaned by auxiliary staff, such people are themselves at considerable risk of being infected in such environments and, as a result, there may be an insufficient number to continue carrying out this task, thereby raising infection risk. robots are in principle able to carry out various mechanical operations, so might take an increasing share in disinfection of high-risk, high touch areas (e.g., robot-controlled noncontact ultraviolet surface disinfection), and indeed other hospital tasks, such as delivering medications and food, diagnostic sample collection and transport, and so forth, (yang et al., ) , that may reduce both the work burden of overstretched staff and their infection risk. • the incorporation of robots into appropriate hospital operations should be energetically explored leadership in times of crisis is crucial to ongoing damage limitation and outcome severity, quite apart from its importance in planning crisis preparedness. although we need to look back when all this is over, and take stock of what went right, what was wrong, and what went wrong (i.e., to perform a gap analysis), at this point it seems that most countries were on their own, acting largely independently of others during the sars-cov- outbreak, at least in the early days. however, a pandemic is by definition an international crisis, requiring an international response (national-self-interest-policies may even be counterproductive in times of pandemics). extensive and effective cooperation, coordination and sharing of resources were not evident (e.g., see herszenhorn and wheaton, ) . leadership quality and effectiveness varies significantly among countries and among relevant international agencies. where leadership is suboptimal, dissemination of misinformation flourishes, and people are subjected to unnecessary levels of uncertainty and associated stress. • effective and decisive, biomedical science-guided, national and international leadership and coordination is absolutely crucial in pandemics, to prevent-hindermanage-minimize damage, acquire-integrate-learn from collective experience, make recommendations for crisis management, publish best practice procedures and standards. there is significant room for improvement. it is well known that experts have been warning of impending deadly epi/pandemics, including coronavirus outbreaks, for a long time (e.g., turinici and danchin, ; ge et al., ; menachery et al., ; https:// www.ted.com/talks/bill_gates_the_next_outbreak_we_re_ not_ready?language=en; editorial ( ) predicting pandemics, lancet doi: https://doi.org/ . /s - ( ) - ; https://apps.who.int/gpmb/assets/annual_ report/gpmb_annualreport_ .pdf; https://www. weforum.org/agenda/ / /a-visual-history-ofpandemics/). now while the nature, evolution, timing and source of novel emerging infectious agents is uncertain, pandemics are always counteracted by the same timehonoured strategy: interruption of infection chains and anticipation of a surge in need for treatment of acute disease (here, we are nearly in the same situation as in the world confronted by spanish flu in ). we, therefore, only need one epidemic preparedness. despite this, the sars-cov- outbreak has clearly exposed how unprepared we were. there are multiple reasons for this, including. contingency planning is long term, lacks immediacy and 'wow factor' and so may not always enjoy high political priority, and thus is often neglected a primordial responsibility of government is to protect its citizens. this includes effective contingency planning for pandemics. however, due to the global nature of pandemics, coordination with neighbours (and factoring in potential flashpoints located more distantly, such as refugee camps in greece and elsewhere, which could become, if not cared for, sources of a second wave of infection when the first is over), and intergovernmental cooperation is essential. adequate contingency planning for deadly and devastating infectious disease outbreaks is not an optional policy, and the public have the right to insist on it, even if it becomes politically or economically expedient to neglect. for the public-the key stakeholders in this-transparency is essential and it must have access to information on the current state of preparedness, and future plans of government, and those of different political parties during election campaigns. trusted biomedical science organizations must support the public in this by providing expert scrutiny and assessment. governments must become accountable for the efforts they make to protect us. • governments must engage the public in issues of crisis preparedness and publish their contingency plans for scrutiny. • scientific organizations should have press/web groups that become trusted sources for evidencebased information for the public. catastrophe prediction/management expertise is not always at the heart of government, and thus able to inform and influence policy governments establish the presence of experts in key posts for topics they consider to be vital for informed policy and legislative activities. such experts exert an influence in policy development by providing input that is upto-the-minute in a changing world. while some governments contain epidemic/catastrophe experts, others do not. without such expertise, responses to catastrophes will generally be slow, ad hoc and inadequate, as has been the case in some countries in responding to the sars-cov- outbreak. for governments to fulfil their responsibilities to protect their citizens, it is essential that they have expert-informed contingency planning. learned societies and academies also have a major responsibility to seek to inform and influence government. the royal society, uk, and the american society for microbiology exemplify strategic influencing of national and international policy; other learned societies could be more proactive. • expert scientists must be embedded in the heart of government to enable development of evidencebased informed policies contingency planning involves inter alia the acquisition and maintenance of resources, such as beds, icu capacity, stocks of ventilators, protective clothing, and so forth, in the case of pandemics (e.g., kain and fowler, ) , that are by definition surplus to day-to-day requirements, and that will only be used if and when the catastrophe occurs. it also includes the development of generic platforms for rapid responses; in the case of pandemics, the development and testing of diagnostics, vaccine candidates, and effective treatments (see also below). this entails a significant recurring budgetary commitment. political and economic viewpoints that such costs are not cost-effective are fundamentally flawed because they generally only take into account the immediate cost elements, not the potential overall cost of the crisis and all its knock-on effects. these are being brutally revealed by the unfolding sars-cov- outbreak which, at this still early stage, is involving governmental support of national economies amounting collectively to trillions of dollars. and this is only the tip of the economic iceberg. bankruptcies, loss of employment, recession, loss of tax revenues, large scale deterioration of existing medical conditions in populations, potentially wide-scale deterioration of mental health, and so forth, and the economic costs of these, also need to be taken into account when reflecting on the cost of the contingency planning insurance policy. as an illustration of knock-on effects, global economic estimates of the benefits of vaccination have also shown that they extend well beyond those estimated from prevention of the specific disease in vaccinated individuals (bloom, ) . it is also worth comparing crisis preparedness costs with military expenditures. the latter are indeed budgetary commitments for preparedness for another type of crisis, namely a military conflict (excepting countries that use their military for internal affairs). and, as is the case in epi/pandemic preparedness, a considerable fraction of military resources is dedicated to surveillance operations. while accepting that military expenditures are also justified in terms of deterrence of hostile actions, and a multitude of non-combat roles armed forces may undertake, it is not self-evident that future military conflicts may result in losses of life and economic damage as high as the current covid- pandemic. in any case, in terms of protecting citizens, it should be abundantly clear that effective contingency preparedness for pandemics, and other crises, should be equated with military preparedness, and budgeted accordingly. • the principle of citizen protection demands that governments budget for adequate crisis preparedness in the same way that they budget for military preparedness. it is simply one of several essential 'insurance premiums' to which the state must commit. from earlier infectious disease outbreaks, we can assume that the most probable source of a new pandemic will be an animal virus, probably a coronavirus, whose natural host is a wild animal, possibly a bat (e.g., see brüssow, ) , that mutates and, as a result, becomes infectious for humans, or for an intermediate host, from which it subsequently jumps to humans. close contacts between humans and the animal host provide the opportunities for transmission. reducing such close contacts will reduce the probability of spillover and thus of an outbreak. close contacts between wild animals and humans occur in wet markets in asia, small-scale mixed farming activities with ducks and pigs, and so forth, or when humans encroach into wildlife habitats, e.g., through ecotourism, or destroy wildlife habitats for economic activities, forcing wildlife to enter human habitats (e.g., the destruction of rainforest for palm oil cultivation appears to have catalyzed a nipah virus outbreak; brüssow, ) . in any case, although pathogen:host interactions underlying disease are generally well studied, current knowledge about the ecology of infectious agentswhere pathogens are and what they are doing prior to infection of humans, especially those having alternative hosts, and how they are circulating and evolving new pathogenic and host-range potentialis inadequate. in order to transit from response mode to pro-active ecological measures to prevent outbreaks from occurring, there needs to be a major research effort to obtain a fundamental understanding of pathogen ecology (see e.g. timmis, ) . • greater efforts are needed to reduce human:wildlife contacts and habitat overlaps, in order to decrease the probability of viral pandemics • effective outbreak prevention measures require acquisition of fundamental knowledge about pathogen ecology contingency planning and the public memory. it is human nature that, once this crisis is over, people, except those who lost loved ones, employment, and so forth, will generally want to forget it as quickly as possible and get back to normal. the number of individuals who try to keep it in the forefront of memory, in order to institute new measures that adequately protect us from the next crisis, and there will undoubtedly be new crises (see above), will be few and far between. some, not all, leading politicians who now (often for the first time) insist that their responses are being guided by the best scientific evidence and advice, as though it were the most natural thing in the world, will quietly shed themselves of their scientific credentials and revert to business as usual, even when unpleasant issues like global warming, the antibiotic resistance crisis, our vulnerability to terrorist and cyber-attacks, again come to the fore. in order that our collective memory retains the crucial need for crisis preparedness, it is essential that each year governments publish updated and independently audited contingency plans. literacy. and the public-the central stakeholders in, and funders of, government policy/actions-must be able to understand the issues and personally evaluate the sometimes vague policy statements they hear. to do this, society must become knowledgeable about/literate in such things. in the case of infectious disease crises, such as the one currently ravaging humanity, and the contingency plans necessary for these, literacy in relevant microbiology topics is, as we have previously argued, essential (timmis et al., ) . interrupting the transmission chain in a pandemic may require lock-down, which imposes major personal sacrifices on the public, including confinement: loss of freedom of movement/social activities/family visits; closure of workplaces/loss of employment and income, resulting in economic hardship/increases in debt; closure of schools/ places of worship/hospitality venues/fitness studios/clubs of all sorts; restrictions on shopping; and elevated stress/ worsening of psychiatric conditions. it is, therefore, crucial that such measures are accepted and supported by the public. for this, people must be engaged and presented with coherent lock-down plans that are convincingly justified, in order to solicit compliance, solidarity and sharing of responsibilities. federal structures, like those in the usa, germany and switzerland may lead to uncoordinated actions in different parts of the country that are unsettling and unconvincing, because the public perceives them as arbitrary. such countries require coherent national plans that are consistent for the entire country. of course, all people in lock-down want an exit as soon as possible, and it is essential for governments to develop and communicate as soon as possible their exit strategy, and the determining parameters and assumptions upon which it is based. interestingly, some members of the public favour staggered exit plans, which implies a willingness to accept an infection risk. it will, therefore, be important for the government to have a public discussion on different risk scenarios, to obtain, present and discuss human/economic cost:benefit estimates (e.g., human lives against cost in loss of income /economic prosperity underlying the lock-down versus herd immunity approach-how much unemployment averts how many deaths or years of productive life when considering the age structure of death). and this discussion needs to take place in the context of the probabilities of loss of life through other adverse causes, such as annual influenza epidemics. family-friend contacts with terminally ill patients. one of the most shocking aspects of the covid- pandemic is the daily reporting of relatives of terminally ill patients who are unable to be with their loved ones at the end, and to pay last respects before burial. while this may be understandable in the context of patient isolation, social distancing, and the unbelievable hectic in overwhelmed icus, serious effort should be made to find a solution, perhaps moving terminally ill patients to an environment that permits both end-of-life patient care and limited safe contact with loved ones. • governments must publish annual audited overviews of the national state of crisis preparedness, with critical analyses of its strengths and weaknesses and plans to address the weaknesses • governments and education ministries must raise public awareness of crisis potential and promote understanding of key elements of crisis management, inter alia through investing in school curricula changes and public information campaigns that increase literacy in topics such as microbiology and public health • governments should involve civil society in discussing restrictive measures because this increases compliance and the solidarity to shoulder the consequences. achievement of optimal preparedness for, and operational responses to, a pandemic demands two things: international benchmarking and transparency/accountability in health systems (and of those who regulate and finance them). this includes chains of command and shared administrative responsibilities, procurement services, reliance on external suppliers of essential materials, and so forth. the disparities in responses we have listed above, that demonstrate significant differences between countries in the ability to respond to pandemics, are not justifiable in terms of operational efficiency, protection of frontline professionals, clinical outcome, and so forth, and cannot be allowed to persist, to be manifested again in future crises. health systems worldwide largely operate within narrow national perspectives, with little interest in better systems elsewhere. we urgently need objective and transparent benchmarking, and automatic mandating of adoption of the best practices in the world, where feasible. transparency and convincing justification for failure to adopt the benchmark must become the norm. of course, different health systems operate in different frameworks-payers, insurance, authorization and recommendation agencies, and so forth-but the tail cannot be allowed to wag the dog. existing frameworks can no longer be accepted as default excuses not to improve. they must be adapted to allow adoption of the benchmarks, where possible, not the other way round. in the final analysis, there are only two elements relevant: the person in the icu, who pays tax/insurance, and hence for the health system, and the government, which is responsible for health system functioning/evolution and protection of its citizens. both of their goals are in principle aligned, so there should be no controversy: provision of the best achievable health system that is adequately prepared for catastrophic pandemics. • governments and health systems must subject national health systems, and national health system crisis preparedness, to international benchmark scrutiny, and transparently strive for attainment of best international standards. it is the responsibility of government to protect its citizens and the role of industry to innovate and create commercial products and services. these two goals are not always aligned for current clinical exigences. but to provide a vital health system, government and industry must align and form alliances that create synergies. there are, of course, many successful examples of such beneficial alliances. however, there is sometimes an unrealistic perception of the role of industry, particularly by some governments when confronted with a crisis for which they are not prepared, as articulated in the generic cry: why do not we have a vaccine for this, why do not we have a drug for that? for example, regulatory and payment hurdles incentivize industry to develop cancer drugs rather than antimicrobials, so it is irrational and unwarranted to complain about the poor state of pipelines for new antivirals in the time of covid- , of antimicrobials in the time of the antimicrobial resistance crisis. if industry is to realign its research priorities towards current clinical priorities, it needs incentives to do so, e.g., through adequately funded creative governmentindustry-academia-clinical-regulatory strategic alliances. we have previously proposed a mechanism to create novel pipelines for accelerated discovery of new drugs and diagnostics (timmis et al., ; and, simultaneously, to promote long-term revival of struggling economies, interestingly in response to a financial crisis-that of -which the sars-cov- pandemic will again unleash with considerable severity). this proposal calls for the use of infrastructure budgets (not overstretched research-education-health budgets) to be targeted to the creation of new strategic national/ regional alliances between (i) cell biology and microbial diversity research groups, to discover and develop new diagnostics, drug targets and assays, and new drug leads from new microbes, (ii) biochemical engineers, chemists and pharma, to produce, evaluate and develop drug candidates, (iii) pharma, clinical research and regulatory agencies to assess clinical efficacy and safety of, and develop new drug candidates. in the context of the sars-cov- pandemic, an alliance between virology, cell biology, microbial diversity, and synthetic microbiology groups in upstream discovery would accelerate new antiviral discovery and populate antiviral drug pipelines, but also pipelines of new antimicrobials urgently needed for the treatment of bacterial superinfections responsible for some of the covid- mortalities. and: while advanced age, underlying co-morbidities and infection dose are identified as predisposing factors for development of severe covid- disease, deaths among young healthy individuals also occur for reasons currently unknown. once predisposing factors for this group have been elucidated, diagnostics to identify young people at risk, especially those most exposed to sars-cov- , will be needed in order to reduce their exposure. vaccines, despite their proven value in protecting against disease and their much-heralded pivotal importance for lockdown exit and herd immunity, are the cinderellas of clinical practice and, in normal times, not only attract little interest from governments but also are controversial, due to negative publicity from vociferous anti-vaccine groups propagating unfounded claims. the development and use of a number of current vaccines/vaccine candidates are orchestrated and funded, not by industry and public health systems, but by philanthropic organizations, like the gates foundation, working with agencies like cepi (coalition for epidemic preparedness innovations) and gavi (global alliance for vaccines and immunizations). indeed, the gates foundation is also playing a leading role in the search for, and development of, a vaccine against covid- (https://www.gatesfoundation.org/ media-center/press-releases/ / /bill-and-melinda-gates-foundation-dedicates-additional-funding-to-the-novel-coronavirus-response). however, it is the duty of national governments and international organizations, as part of their pandemic preparedness, to finance vaccine development platforms that are able to rapidly create new vaccines in response to an outbreak. once a new vaccine candidate is shown to be safe and protective, its rapid large-scale production and distribution requires the infrastructure of large pharmaceutical companies. as epidemics cannot be planned, industrial managers cannot be expected to promote projects without a market. governments must therefore intervene to maintain the interest and technical capacity of industry in developing vaccines and antibiotics (a smouldering fire) by creating a market in form of governmental orders. assessments of value-for-money of these strategic alliances must be made in the context of the global costs of pandemics like that of sars-cov- . • pandemic preparedness requires rapid creation, production and distribution of effective materials for diagnosis, prophylaxis and therapy. this necessitates significant long-term investment in research and development involving unconventional alliances of disparate academic science and medical research groups, industry, philanthropic foundations, vaccine enabling coalitions, and crisis preparedness taskforces. there is great diversity in stress resilience (e.g., the ability to deal with peaks of illness) of different health systems, with some being at least regionally overwhelmed during the winter influenza season. the less resilient systems will generally be the first to become overwhelmed in a health crisis. while there are numerous parameters involved in health system resilience, and experts know most of the pinch points and solutions that can deal with these (but also what is uncertain and what needs to be understood before effective 'solutions' can be formulated), three elements worth consideration in efforts to increase health system resilience are discussed here. healthcare systems are by and large extremely large, complex, heavily bureaucratic and fragmented. the often system-wide, multi-level consultations, decisions and responses needed in times of emergencies are challenging and often slow, usually slower than crisis development, which means that healthcare systems follow and react to events, rather than managing them. crises are in some ways analogous to wars, and bureaucracies are not designed to manage wars, which is the job of the military. in crises, we need crisis strategy-tactics specialists, a taskforce with short, well defined and effective chains of command, tasked with overriding normal procedures and taking charge of supply chains and requisitioning of assets, (re)deployment of personnel, organization and prioritization of allocation of infrastructure, managing logistics, and so forth. these could be specially trained taskforces of existing staff within healthcare systems, external taskforces or combinations of both. of course, for taskforces to operate optimally, they, together with the best available scientific minds, must also plan in advance the required resources, supply chains, personnel, strategic options, and so forth. they must also organize regular 'infection games'/public health manoeurvres (https://www.ted.com/talks/bill_gates_the_ next_outbreak_we_re_not_ready?language=en) = crisis 'fire drills', to train nationally and transnationally, refresh skills and explore and anticipate unexpected events to ensure preparedness, so that appropriate responses can be rolled out rapidly anywhere, independently of national borders. another, mandatory, task for the taskforce would be to conduct regular 'stress tests' of healthcare system resilience, as have been instituted for banks to ensure that they have adequate resources (= resilience) to withstand crises. such stress tests should be designed by health experts, epidemiologists-modellers, procurement agencies, representatives of the diagnostics-vaccine-drug industry, and so forth, and the design and implementation of the stress tests overseen by the taskforce. • national crisis task forces consisting of dedicated strategy-tactics specialists need to be established to plan crisis preparedness, make recommendations to improve health system resilience, and carry out regular crisis "fire drills" and stress tests. an important aspect of the sars-cov- outbreak is that, in most countries, it has become more difficult to obtain consultations with primary healthcare clinics/physicians, because of social distancing practices, illness or involvement in crisis management (e.g., see keesara et al., ) . as time goes on, the inability to access many primary healthcare services leads to progressive worsening of existing and new conditions in some individuals. access to primary healthcare, which in some countries was already unsatisfactory before covid- , is becoming a new crisis. this has resulted in the 'flight to the web' for information (sometimes obtaining disinformation in the process): the web is becoming a substitute for clinical consultations, in terms of obtaining information relating to symptoms experienced. this will ultimately have a significant impact on how the public views the computer as a facilitator-mediator of primary healthcare. while classical telemedicine-the ad hoc consultation of a remote, unknown physician who can advise on the symptoms presented-may be helpful in times of inadequate access to regular primary healthcare facilities, it cannot replace clinical advice informed by patient case histories and personal knowledge of the patient. reduced access to primary healthcare below a certain threshold constitutes itself a significant health hazard and is counter to a government's duty to protect its citizens. what to do to increase resilience of primary health care and increase access? one important contribution will be the 'digital healthcare revolution' (keesara et al., ) , i.e., some traditional one-on-one meetings between patient and doctor being replaced by web-based consultations. but also imagine teleconsultations based on (i) complete personal case histories, combined with (ii) up-to-date population epidemiological information, combined with (iii) individual patient best practice recommendations based on precision medicine analyses/predictions: welcome to the national clinical informatics centre (ncic; timmis and timmis, ) , informing in real time a virtual doctor, a clinically-programed, ai-evolving server. this doctor, interfacing with both the patient and ncic, diagnoses according to detailed case history and patient symptom input via computer (and aided, where necessary, by diagnostic information obtained through in-home patient self-diagnosis with apparatus/diagnostic materials promptly delivered by a medical logistics service), and makes treatment recommendations (timmis, ) . in some countries/regions, access to primary healthcare already involves significant waiting periods. the additional restrictions on access to primary healthcare resulting from the sars-cov- outbreak are resulting in further suffering and frustration that will surely make the prospect of a consultation with a virtual doctor providing personalized medicine, who is instantly available / , an increasingly attractive future possibility. of course, many health issues cannot be handled remotely via the web (though the proportion will increase steadily with the development of informatic infrastructure and easy-to-use home diagnostics), and will result in referral to a clinician. but, web-based consultations can significantly reduce numbers of patients requiring clinician consultations and the associated stress on the health system. • it is essential that health systems urgently develop centralized, secure informatic infrastructure needed to underpin web-based machine learning-facilitated precision medicine, and evolve web-based consultations, available on demand / , as an integral mainstream component of primary healthcare services. the current sars-cov- outbreak has brutally exposed the current vulnerability of society to pandemics, even those that have been long predicted and anticipated (ge et al., ; menachery et al., ) . most healthcare systems have not evolved for resilience in times of catastrophe, nor for effective rapid responses to pandemics. a key principle steering evolution has been value-for-money within a fixed budget; contingency planning within this framework (outlays for materials that may never be used) may be considered to be a nuisance that diminishes what can otherwise be done with limited funds, and so to a greater or lesser extent may be postponed. for this reason, it is crucial that budgets for contingency planning are separate from health system budgets. equally important, it has emphasized the fact that some healthcare systems have for a long time been on the edge of the cliff, just waiting for an event to push them over. their adaptation to changing needs has often been through a 'sticking plaster' response. evolution has been ad hoc, via responses to new developments and challenges, and often led to fragmentation rather than coherence. the lessons to be learned are thus not only to take scientifically-founded pandemic predictions seriously into account in policy elaboration, but also to streamline and institute changes in healthcare systems that impose an evolutionary trajectory that increases coherence, efficiency and preparedness, and the necessary mechanisms to maintain these as new exigencies arise (e.g., see timmis and timmis, ) . and, especially because this crisis has revealed enormous disparities in responsiveness, effectiveness and the quality of responses in different countries, both preparedness for pandemics and the general improvement of healthcare mandate international benchmarking for contingency planning and the evolution of healthcare systems. comparisons/benchmarking within countries-within single systems-is no longer acceptable. many healthcare systems need substantive improvements through strategic investments, in most cases targeted to system changes, not just extra funding of existing services. and above all, they need crisis taskforces embedded in them that can prepare for, and take charge in times of, impending catastrophes. another lesson learned is that the sars-cov- outbreak has revealed new synergy potentials, such as the manufacture of ventilators by engineering companies not normally active in the manufacture of medical devices. it is not unreasonable to assume that new innovations can and will emerge from new interactions between creative engineers and clinicians. for example, best practice for breathing difficulty and poor blood oxygenation is intubation and ventilation. the paucity of ventilators is a 'critical control point' for best treatment practice in some hospitals, which has been discussed above. anecdotal evidence suggests that, of those individuals who die, despite best treatment practice involving intubation, the cause of death is often due to superinfection by antibiotic resistant bacteria (vincent et al., ) . the cause of this may indeed be intubation, causing perturbation of normal lung physiology and creating susceptibility to superinfection. there are, however, less invasive means of increasing blood oxygen levels. perhaps engineers, together with clinicians, will devise new or improved non-invasive approaches to blood oxygenation. and once creative engineers from the non-medical field start to expertly scrutinize current medical devices, perhaps we will see new approaches and new designs that significantly advance medical practice. but perhaps the most important lesson learned is about our frontline health professionals ministering to covid- patients, especially those with severe disease. these clinicians and nurses who willingly and selflessly work long, sometimes multiple shifts to the point of utter exhaustion, often not able to see their families for long periods because of the danger of infecting them, always under unbelievable stress working in what are essentially war zones with the accompanying horrors (e.g. see http:// www.sixthtone.com/news/ /i-spent-seven-weeksin-a-wuhan-icu.-heres-what-i-learned?utm_source=sfmc& utm_medium=email&utm_campaign= _agenda_ weekly- april &utm_term=&emailtype=newsletter), sometimes without adequate protective clothing and always in danger of contracting covid- , sometimes becoming infected, and sometimes paying the ultimate price. these are the heroes of the pandemic, the faces of resilience of covid- healthcare, exceptional citizens demonstrating exceptional fortitude, personal sacrifice and professional dedication: they are our role models of the st century. real estimates of mortality following covid- infection valuing vaccines: deficiencies and remedies on viruses, bats and men: a natural history of food-borne viral infections the novel coronavirus-a snapshot of current knowledge fangcang shelter hospitals: a novel concept for responding to public health emergencies isolation and characterisation of a bat sars-like coronavirus that uses the ace receptor offline: covid- and the nhs: "a national scandal preparing intensive care for the next pandemic influenza health security capacities in the context of covid- outbreak: an analysis of international health regulations annual report data from countries covid- and health care's digital revolution a sars-like cluster of circulating bat coronaviruses shows potential for human emergence estimating case fatality rates of covid- the diy digital medical centre biological land mines: bioterrorism underscores major knowledge deficits in the ecology of infectious agents the home clinic or all in a day's work of dr the urgent need for microbiology literacy in society pipelines for new chemicals: a strategy to create new value chains and stimulate innovation-based economic revival in southern european countries the sars case study. an alarm clock prevalence and outcomes of infection among patients in intensive care units in characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china combatting covid- -the role of robotics in managing public health and infectious diseases key: cord- -iqa pxda authors: deng, shichang; wang, wangshuai; xie, peihong; chao, yifan; zhu, jingru title: perceived severity of covid- and post-pandemic consumption willingness: the roles of boredom and sensation-seeking date: - - journal: front psychol doi: . /fpsyg. . sha: doc_id: cord_uid: iqa pxda the covid- pandemic restricts people’s activities and makes consumer businesses suffered. this study explored the relationship between the perceived severity of covid- and the post-pandemic consumption willingness. study surveyed chinese people in march , found the perceived severity of covid- during the pandemic significantly increased the willingness to consume post-pandemic, and boredom stemming from limited activities and sensation-seeking expressions mediated this effect. study conducted an experiment with participants in august , found a high level of perceived severity of covid- and the experience of life tedium during the pandemic significantly increased individuals’ impulsive buying tendencies after the pandemic. the results suggested the level of perceived severity of covid- may influence people’s post-pandemic consumption patterns. no one could have predicted the second decade of the st century would begin with a global super pandemic. in just a few months, the novel coronavirus (covid- ) swallowed more than , lives and infected more than , people in china. the chinese government established unprecedented measures and suspended almost all social activities throughout the country to combat the virus. although these measures have effectively slowed down the spread of the virus, society has paid a considerable price, especially consumer enterprises. the iresearch consulting group ( ) report stated that businesses such as catering, tourism, and transportation were struck during the pandemic due to the order to enforce social distancing, with the net consumer population falling by more than %. a column analysis of beijing business daily ( ) also reported the sharp drop in customers from the pandemic led to small and medium-sized retailing and catering enterprises to lose nearly % of their income, leaving many businesses in decay. the pandemic hit china's consumer economy hard in the first quarter of , creating a secondary disaster from with the pandemic gradually controlled in china, many chinese businesses have their hopes on a consumption rebound after the pandemic. the ministry of commerce of china reported a rebound in consumption in april (people's news, ) . many business analysts also agree that a spending spree may occur after the pandemic (beijing business daily, ; iresearch consulting group, ) . however, what is the psychological reasons for the rise in consumer willingness after the pandemic? existing research lacks an explanation. this study explores the psychological mechanisms between the perceived severity of covid- and the post-pandemic consumption willingness. we found that during the pandemic, the perceived severity of covid- leads to an increase in boredom state and sensation-seeking expression, which makes the purchasing activity after the pandemic becomes more attractive. we hope this study could provide a reference for similar follow-up researches and consumer enterprises' postpandemic business planning. the covid- pandemic quickly made headlines in global media after dr. zhong nanshan indicated on the china central television (cctv) news channel that "it can affirm that this novel coronavirus has human-to-human transmission" on january , , and the public soon began to realize the seriousness of the coronavirus. wuhan city quickly locked down on january after dr. zhong's interview. a week later, all provinces and regions across china launched a first-level public health emergency response (xinhua news agency, ). local governments quickly initiated a series of rigorous control methods, such as comprehensive screening and quarantining suspected cases, close monitoring and tracking their contacts, and actively promoting scientific knowledge and expert consensus on coronavirus prevention. however, at the same time, many rumors about the pandemic spread rapidly through online social media, generating a great deal of panic . 's survey of , chinese people in february showed the perceived severity of covid- was as high as . out of (sd = . ), which demonstrated that these pandemic-related incidents put people on high alert and led to a dramatic increase in the perceived severity of covid- . the health belief model proposes that perceived severity refers to an individual's subjective perception of a disease's serious state, which is influenced by a range of factors related to the current existing reality and anticipation of future events (green and murphy, ) . weinstein ( ) demonstrated that a high perceived severity of disease causes proactive health-protection behaviors. "washing hands frequently, wearing masks, not gathering and going out" are the covid- control requirements strongly advocated by the chinese government (xinhua news agency, ). chinese people actively followed the above pandemic-control instructions when the perceived severity of covid- increased, obeying social distancing rules and locking themselves at home. the survey of showed that chinese people's social participation levels during the pandemic were as low as . out of (sd = . ) since february . although people's proactive health-protection behaviors do effectively slowed the spread of coronavirus, the limited activities have also caused a sudden increase in psychological pressure, resulting in different degrees of mental stress xiang et al., ; zhang et al., ) . this study paid particular attention to a psychological consequence of limited activities for a long time: boredom. boredom is an aversive experience of wanting but not being able to engage in satisfying activities, which occurs when people are unable to focus on desired tasks (eastwood et al., ) . boredom can be seen as a situational state that lacks novel stimuli over a period of time, and low arousal is the most dominant feature of boredom (van hooft and van hooff, ) . the arousal theory states that individuals need a certain amount of external stimulation to maintain the desired activities required by the body; otherwise, they may feel uncomfortable (reisenzein, ). individuals prefer a moderate level of stimulus; being in a high or low degree of arousal for a long time causes discomfort. a higher level of arousal makes people feel excited, but it also makes them feel nervous, anxious, and irritable. a lower level of arousal makes people feel relaxed; however, it may also cause weariness, depression, and most importantly, boredom (picard et al., ) . a high level of perceived severity of covid- makes most chinese people exhibit active health-protection behaviors and stay at home, which significantly limits the social activities people can enjoy. simple and repetitive external stimuli reduce individuals' arousal levels and create boredom (van tilburg and igou, ) . long-term activity limitations made people experienced repetitive and monotonous external stimuli; consequently, people's arousal levels during the pandemic were far below the average (chao et al., ) . although the optimal amount of external stimulation preferred by each individual varies, the long social distancing period has generally caused high levels of boredom in most of the population . there were always those who ventured onto the streets and even gathered to play mahjong during the pandemic, despite government calls to reduce going out and gathering (npr, ). the above cases demonstrate that the pandemic restrictions significantly increased people's boredom. long-term boredom states can cause individuals to actively seek out more and stronger complex external stimuli (reisenzein, ) . we suggest that the boredom stemming from limited activities during the pandemic leads to an increase in sensationseeking expression. sensation-seeking refers to people's desire for a novel, exciting, and complicated feeling or experience (zuckerman, ) . most researchers conceptualize sensationseeking as a stable trait (zuckerman and aluja, ) . however, the degree of expression of this trait may be affected by a long period of boredom due to limited activities. trait activation theory highlights that situational cues may affect how an individual expresses his or her traits (tett and burnett, ) . lynne-landsman et al. ( ) found that the social environment influences an individual's sensation-seeking expression. lydon-staley et al. ( ) also showed that individuals express higher than usual sensation-seeking behaviors during the days they consume alcohol, demonstrating that sensation-seeking expression has a within-person variability. therefore, although the trait of sensation-seeking is relatively stable, one's expression of sensation-seeking may change depending on the situation. as stated above, elevated perceived severity of covid- led to active health-protective behaviors that made people afraid to leave their homes. consequently, the monotony of repetitive life from activity limitations reduced people's arousal levels and increased people's feelings of boredom (chao et al., ) , which resulted in increased sensation-seeking expressions (dahlen et al., ; jiang et al., ; jee et al., ) . those processes let people need more and stronger external stimuli to achieve the desired state of arousal; otherwise, people may feel unpleasant (zhang et al., ) . the above mental changes provide a psychological basis for the increased post-pandemic consumption willingness. people's increased boredom from limited activities and sensationseeking expressions during the pandemic gave us good reason to speculate that people's willingness to consume and impulsive buying tendencies may climb significantly after the pandemic is effectively controlled. by satisfying an individual's needs through payment, consumption is an effective means to elevate arousal levels (batra and ghoshal, ; koles et al., ) . yan et al. ( ) demonstrated that individuals' willingness to consume would greatly increase if they try to seek external stimuli to enhance their arousal. sundström et al. ( ) found that boredom is one of the primary motivators driving people's buying behavior. consumers are easily attracted by stimuli, such as advertisements and discounts, when they are bored. deng and gao ( ) also showed that sensation-seeking makes individuals actively pursue complex stimuli, so a high level of sensationseeking expression may result in a significant willingness to consume. as stated above, during the pandemic, a high level of perceived severity of covid- made people reluctant to engage with the outside world . the long period of physical and psychological limitations severely deprived people of external stimuli, resulting in increased boredom and sensationseeking expressions (chao et al., ; droit-volet et al., ; kim, ) . we suggest that after the covid- pandemic is effectively controlled, people are highly likely to engage in a variety of consumption activities precisely because shopping is a complex stimulus that can relieve consumers' boredom state (sundström et al., ) and satisfy their sensation-seeking needs (punj, ; deng and gao, ) . we hypothesize the following based on the above reasoning: h : the perceived severity of covid- during the pandemic will increase the post-pandemic consumption willingness. h : the above effect is mediated by boredom from limited activities and sensation-seeking expressions. boredom states and sensation-seeking expressions are usually associated with impulse buying because it is a strong psychological stimulus that brings great satisfaction (dahlen et al., ; iyer et al., ) . we speculate that since the perceived severity of covid- made an increase in boredom and sensation-seeking expression, it is very likely that the perceived severity of covid- will lead to an elevated impulsivity buying tendency after the pandemic is effectively controlled. the experience of life tedium during the pandemic will play a moderating role in this impact. during the quarantine, many people were restless because of the tedium of life, but many people also found new pleasures, such as cooking or learning a new musical instrument (droit-volet et al., ) . due to the experience of life tedium greatly improves one's boredom states and sensation-seeking expressions, we suggest that the impulse buying tendency after the pandemic may decrease if an individual's prolonged homestay was filled with new things. conversely, an individual's tendency to impulsively buying after the pandemic may significantly increase if he or she felt life was tedious during a long period of quarantine. we hypothesized the following based on the above reasoning: h : high levels of perceived severity of covid- and experience of life tedium during the pandemic significantly increased individuals' impulse buying tendency after the pandemic. we tested the three above hypotheses through two studies. a questionnaire modeling tested h and h , which provided an aggregate survey of the relationship between perceived severity of covid- and post-pandemic consumption willingness, as well as the mediators between them. a behavioral experiment tested h , which provided evidence of how the perceived severity of covid- and the experience of life tedium during the pandemic affected one's impulse buying tendency after the pandemic. study aims to use the questionnaire modeling method to test h and h (i.e., whether perceived severity of covid- increased ones' post-pandemic consumption willingness through the mediating roles of boredom from limited activities and sensation-seeking expressions). we conducted this study in march . at this time, the number of new covid- cases in china has been gradually decreasing, but the overall situation of the pandemic is still serious. we posted a set of questionnaires on a chinese web-based survey platform on march , . within days, people responded in full for a small cash reward. the participants ( females, mage = . , sd = . ) came from all regions in china. among them, were students ( . %), had formal jobs ( . %), had part-time jobs ( . %), were freelance ( . %), and were unemployed ( . %). we asked participants to respond to the questionnaires in the following order (see supplementary material for full items). referring to the "covid- pandemic perception questionnaire ( nd round), " published by the sun yat-sen university team ( ), items suitable for the topic of this study were selected after authors' discussion (e.g., "i often suspect that people around me may be infected by the coronavirus.") participants responded on a -point likert scale from (very much disagree) to (very much agree), with higher scores indicating a higher level of perceived severity of covid- . in this study, the items have a good unidimensional structural validity (goodness-of-fit of cfa: χ = . , df = , rmsea = . , srmr = . , cfi = . , tli = . ), with factor loading between . and . and the cronbach's α is . . we adopted the low arousal subscale of the chinese multidimensional state boredom scale (cmsbs), which was developed by liu et al. ( ) . the cmsbs contains five subscales: inattentiveness, perceived slowing of time, low arousal, high arousal, and a desire to engage in more exciting activities. of these, the low arousal state best suits this study because compared with the other four subscales, it best described a low mental arousal state. this subscale consists of items. the phrase "during the period of home staying" was added to each item, for example, "during the period of home staying, everything is repetitive and boring for me because of the restrictions on my activities." participants responded on a -point likert scale from (very much disagree) to (very much agree), with higher scores indicating a higher boredom state during the pandemic. in this study, the cronbach's α of this subscale is . . several instruments have been developed for different research purposes for assessing sensation-seeking. the -item sensation-seeking scale form v (sss-v) is the most widely used among these instruments (zuckerman and aluja, ) . however, large-scale surveys require a shorter measurement tool, and sensation-seeking expression closely relates to an individual's culture (wang et al., ; agrusa et al., ) . therefore, we adopted the chinese brief sensation-seeking scale in this study, which hoyle et al. ( ) derived from the sss-v and chen et al. ( ) culturally adapted. this scale consists of items and mainly measures the behavioral tendencies of sensationseeking individuals. the phrase "during the pandemic" was added before each item to evaluate participants' sensationseeking expressions during that period, for example, "during the pandemic, i always liked to do things that i had not done before." participants responded on a -point likert scale from (very much disagree) to (very much agree), with higher scores indicating a higher sensation-seeking tendency during the pandemic. the cronbach's α of this scale was . in this study. six items were developed to measure this variable based on the general psychometric procedure, i.e., when the pandemic is over, ". . .i want to go out and eat some delicious food", ". . .i want to have more shopping and buying", ". . .i will compensate for my pent-up spend desire and satisfy myself by buying more things", ". . .my consumption desire will increase significantly than before the pandemic", ". . .i want to buy something that i haven't bought before", and". . .i will spend more and have fun in time." participants responded on a -point likert scale from (very much disagree) to (very much agree), with higher scores indicating a higher post-pandemic consumption willingness. the items have a good unidimensional structural validity (goodnessof-fit of confirmatory factor analysis: χ = . , df = , rmsea = . , srmr = . , cfi = . , tli = . ) in this study, with factor loading between . and . and the cronbach's α is . . considering the pandemic affected many people's financial income, which is a significant consumption-related factor, this study also asks the question "has the pandemic affected your economic income?" participants answered on a -point likert scale from (no impact at all) to (the impact is huge). furthermore, considering that life satisfaction during the pandemic may also affect the post-pandemic consumption willingness, this study adopted a single-item scale developed by cheung and lucas ( ) (i.e., "in general, are you satisfied with your life situation during the pandemic?") participants responded on a -point likert scale from (very much disagree) to (very much agree). first, we examined the differences of post-pandemic consumption willingness between demographic variables. an independent t-test found the score of females on post-pandemic consumption willingness (m females = . , sd = . ) was slightly higher than that of males (m males = . , sd = . ), but the difference was not significant [t( ) = . , p = . , cohen's d = . ]. the correlation between age and post-pandemic consumption willingness also failed to reach a significant level (r = − . , p = . ). those results demonstrated that the post-pandemic consumption willingness is a general trend, with little change in demographics. next, table shows the pearson correlations between variables. a significant positive correlation can be found between the perceived severity of covid- and post-pandemic consumption willingness (r = . , p < . ). furthermore, there were also significant positive correlations between boredom from limited activities (r = . , p < . ) and sensation-seeking expressions (r = . , p < . ) regarding the post-pandemic consumption willingness. in addition, the impact of the pandemic on income significantly and positively correlated with the post-pandemic consumption willingness, but the effect size was at a low level (r = . , p < . ). life satisfaction during the pandemic did not significantly correlate with the post-pandemic consumption willingness (r = . , p = . ). the results suggested little relationship exists between the two control variables and the dependent variable. we used a structural equation model to further test h and h based on hayes' ( ) model . our model contained both observed and latent variables and was computed with bootstrapping through maximum-likelihood estimation. the model's goodness-of-fit was acceptable (χ = . , df = , rmsea = . , srmr = . , cfi = . , tli = . ). the results indicated the perceived severity of covid- had led to a significant increase in boredom from limited activities (β = . , p < . ), which then result in a significant rise in sensationseeking expressions (β = . , p < . ), and eventually made a significantly elevation in post-pandemic consumption willingness (β = . , p < . ). figure also shown that the effect of boredom from limited activities on post-pandemic consumption willingness was not significant (β = . , p = . ), as well as the indirect effect through boredom only (β = . , p = . ). therefore, the indirect effects of the perceived severity of covid- on post-pandemic consumption willingness were realized through sensation-seeking expressions only (β = . , p < . ), and boredom and sensation-seeking expressions in succession (β = . , p < . ). the total indirect effects (β = . , p < . ) account for almost half of the total effects (β = . , p < . ). study supports h and h . it shows a general trend that the perceived severity of covid- could lead to increased boredom from limited activities, then result in heightened sensation-seeking expressions. as a consequence, these changes led to a raised post-pandemic consumption willingness. the results of study indicate that in march , in which the pandemic in china was still severe, the perceived severity of covid- was closely related with a climbed post-pandemic consumption willingness. boredom and sensation-seeking expressions are often associated with impulsive consumption (dahlen et al., ; sundström et al., ) , so does the perceived severity of covid- makes people more likely to consume impulsively after the pandemic? we examined this speculation in study . study aims to replicate and extend the findings of study . we examined whether the perceived severity of covid- and the experience of life tedium during the pandemic elevated people's impulsive buying tendencies after the pandemic was effectively controlled by manipulating these two variables (i.e., test h ). we conducted a behavioral experiment in august . at this time, the pandemic has been brought under control in most parts of china, with only a few sporadic new cases. participants ( people, females, mage = . , sd = . ) from a chinese web-based survey platform were randomly assigned to a (perceived severity of covid- : severe vs. not severe) × (experience of life tedium: tedious vs. not tedious) between-subjects design from august - , . in the manipulation of the perceived severity of covid- , the severe group watched a -s news video that emphasizing the virus was still serious in china. the not-severe group watched a similar length video; however, that video stating the covid- pandemic was effectively controlled in china. both news videos were clipped from authoritative chinese media outlets (see supplementary material). in the manipulation of the experience of life tedium during the pandemic, the tedious group was asked to describe in detail "how your life was repetitive and tedious during the long period of home staying." the not-tedious group was asked "how your life was full of new things during the long period of home staying." next, all participants were required to respond to the following items from (very much disagree) to (very much agree). three items from xin ( ) were adopted to measure participants' perceived severity of covid- (e.g., "i feel that if i am not careful, my family or i am very likely to infected by the coronavirus, " "i feel that the current pandemic situation is very serious, " and "i feel that it is tough to control the pandemic effectively.") the cronbach's α of those three items is . . two items from study were used to measure participants' experience of life tedium during the pandemic (one from the boredom scale: "during the period of home staying, everything is repetitive and boring for me because of the restrictions on my activities" and one from the sensation-seeking scale: "during the period of home staying, i would do anything as long as it exciting and stimulating.") the cronbach's α of those two items is . . participants were first asked to read the following text: "now, except for a few regions, the pandemic in china has been effectively controlled. in your community, several large shopping malls are planning a large-scale shopping festival, and they will cater to all aspects of the consumer needs such as household figure | perceived severity of covid- results in an increased post-pandemic consumption willingness through the mediating roles of boredom from limited activities and sensation-seeking expressions (study ). numbers are the standardized path coefficient, ***p < . . goods, entertainment, leisure, sports, and many more." then, participants were required to respond to the following five items revised from sharma et al. ( ) : in this shopping festival, i ". . .will not think too much before buying what i like"; ". . .will buy things if i like it"; ". . .will tempted to choose what i like"; ". . .will not think too much about the consequences of choosing what i like"; and ". . .will chose what i like as quickly as possible, before i change my mind." the cronbach's α of those items is . . independent t-tests showed the manipulation of the perceived severity of covid- [m severe (not severe) = . ( . ), sd severe (not severe) = . ( . ), t( ) = . , p < . , cohen's d = . ] and the experience of life tedium during the pandemic [m tedious (not tedious) = . ( . ), sd tedious (not tedious) = . ( . ), t( ) = . , p < . , cohen's d = . ] were both effective. a × anova on impulsive buying tendencies after the pandemic revealed two significant main effects [perceived severity of covid- : f( , ) = . , p < . , η p = . ; experience of life tedium during the pandemic: f( , ) = . , p < . , η p = . ] and a significant interaction [f( , ) = . , p = . , η p = . ]. post hoc tests found that participants' post-pandemic impulsive buying tendencies was the highest in the condition of high perceived severity of covid- and high experience of life tedium during the pandemic (m severe and tedious = . , sd = . ), which was significantly higher than the condition of high perceived severity and low experience of life tedium the results of study support h . the perceived severity of covid- and the experience of life tedium during the pandemic jointly influenced people's impulsive buying tendencies after the pandemic. it indicates that in august , in which the pandemic in china was basically controlled, people are more likely to satisfy their stimulus-seeking needs through impulse consumption if they are at high levels of both variables. studies have shown that whether in china , the united kingdom (chronopoulos et al., ) , scandinavia countries (andersen et al., ) , or the united states (cox et al., ) , the covid- pandemic limited consumers' activity and led to a significant decline in spending. our findings suggest this phenomenon may change after the pandemic is adequately controlled. based on the survey results of people (study ) in march , we see that individuals' post-pandemic consumption willingness is relatively high ( . out of , sd = . ), which implies people's spending may bounce back after the pandemic. we suggest the psychological basis for this potential postpandemic consumption rebound is that individuals are motivated to seek external stimuli to relieve the boredom stemmed from limited activities and to satisfy their sensation-seeking needs. the arousal theory demonstrates that simple and repetitive stimuli reduce individuals' arousal levels. in the long run, people may actively seek out more significant and complicated external stimuli to restore their desired arousal level. during the pandemic, a high perceived level of severity of covid- led people to be afraid of contact with the outside world, resulting in minimal activities that individuals could participate in. low-level stimulation for months made people more likely to feel bored, anxious, and irritable (chao et al., ; xiang et al., ; zhang et al., ) . consumption is an activity that can quickly lead to novel stimuli. di muro and murray ( ) found that consumers experiencing negative emotions prefer to choose goods that are inconsistent with their current arousal level. those consumers attempt to escape their emotional discomfort and find their preferred optimal arousal level through consumption. the results of study demonstrate the high levels of boredom from limited activities and sensationseeking expressions have a strong positive effect on people's postpandemic consumption willingness. during the international workers' day holiday (may ) in , china saw a significant rebound in tourism numbers (financial times, ) , which suggests people are very likely to meet their demand for external stimulus through consumption. our findings echoed other independent studies. based on samples from the united states, kim ( ) found the perceived threat of covid- has a close relationship with variety-seeking because the pandemic limited individuals' activity, therefore people display a high motivation to increase freedom and restore control. it suggests that the impact of the perceived severity of covid- is cross-cultural. study confirms the perceived severity of covid- is strongly associated with increased boredom and sensationseeking expressions during the pandemic, which is often closely related to impulsive buying behaviors (dahlen et al., ; deng and gao, ; sundström et al., ) . study found significant main and interaction effects of both the perceived severity of covid- and the experience of life tedium during the pandemic on impulse buying tendencies. individuals are highly likely to exhibit an impulsive buying tendency in cases when both of the above variables are at a high level. study echoes the findings of , which states impulsive consumption is a typical behavior people often present during public health emergencies. moreover, found the pandemic's severity positively affects people's impulsive consumption, and individuals' perceived control and materialism mediate this effect. our study complements another path of this effect, that is, perceived severity of covid- and experience of life tedium during the pandemic can also lead to an increased impulsive buying tendency. it demonstrated that the perceived severity of covid- might affect not only the willingness to consume after the pandemic, but also people's consumption patterns in the future. extending the findings of study , we speculate that in addition to impulsive buying tendencies, the perceived severity of covid- and experience of life tedium during the pandemic may also increase a variety of impulsive behaviors. van rooij et al. ( ) found that in the united states, impulsivity during the pandemic led to a violation in coronavirus control measures. mesa vieira et al. ( ) also found that a sharp rise in the divorce rate in china during the pandemic may be associated with increased impulsive decisions. the results of study suggest that lowering the perceived severity of covid- and experience of life tedium during the pandemic could alleviate people's impulsivity, thereby reducing the likelihood of making poor decisions. for consumer businesses, it is important to not only prepare for the rapid rebound in consumption after the pandemic, but also to prepare a plan for the normalization of consumption after the rebound weakens. in other words, consumer enterprises must understand that the rebound in consumption will not stem from a sudden increase in society's spending power, but from the urgent need for consumers to relieve their boredom from limited activities and satisfy sensation-seeking needs. therefore, consumer enterprises should conduct more forward-looking marketing research and understand consumers' psychological changes to make the right decisions. we also advocate that consumers be rational in their purchasing after the pandemic and beware of impulsive buying decisions and overconsumption. on the one hand, after longterm low levels of arousal, moderate consumption could help people restore their perceptual stimulation to their ideal arousal levels. on the other hand, excessive consumption may lead to negative results, such as excessive debt and resource waste (deng and gao, ; lee and ahn, ) . future research should pay attention to the differences in consumption willingness between regions. in china, the covid- outbreak was centered in wuhan city, hubei province. people in the epicenter of the pandemic experienced stricter control measures and had a much higher perceived severity of covid- (dai et al., ) . the yerkes-dodson law states that either too high or too low levels of psychological stimulation are not conducive to achieving the best mental state. wuhan city lifted its lockdown on april , . after scary days and nights, will the spending spree of those in the epicenter be more vigorous, or will it be business as usual? it is subject to follow-up observation. future studies should also focus on the pandemic's longterm impact on consumer behavior. the covid- pandemic caused long-term, continuous, high-intensity, and traumatic group psychological stress to the people of china and to the world. it could change many people's views of consumption, making some consumer industries decline while others rise. what new consumption drivers will form by this profound collective memory of a generation? this question is beyond the scope of this study and is left for subsequent studies to explore. there are three limitations to this study. first, this study lacks distinctions between different consumption types. the pandemic impacted human connection, leaving a significant portion of the population apprehensive about socializing. therefore, the consumption scenario is better further subdivided into socially based consumption (e.g., bar parties) and non-socially based consumption (e.g., traveling alone), because of the psychological basis of these consumption activities is different. second, selecting a subscale may not be a good choice for evaluating low arousal states of boredom. these measurements constitute various dimensions, in addition to being highly variable depending on the time of day the individual responds (adan and guàrdia, ) . therefore, a multidimensional measure approach should be incorporated to measure low arousal states of boredom to assess the fine effect of the perceived severity of covid- on this variable. third, both the arousal state and sensation-seeking closely relate to the individual difference in circadian typology, which associates with various psychological symptoms (prat and adan, ) . therefore, circadian typology may determine mediation. this study only used questionnaires at a rough level to investigate people's overall levels of boredom. follow-up studies should fully consider the circadian changes of an individual's activation to obtain more accurate results. the datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. the studies involving human participants were reviewed and approved by the research ethics board of shanghai university of international business and economics. the patients/participants provided their written informed consent to participate in this study. sd and ww devised the project, the main conceptual ideas, and proof outline. px worked out most of the technical details and performed the numerical calculations. jz collected the research data. sd, ww, and yc wrote the manuscript. all authors contributed to the article and approved the submitted version. circadian variations of self-reported activation: a multidimensional approach sensation seeking, culture, and the valuation of experiential services. event manag pandemic, shutdown and consumer spending: lessons from scandinavian policy responses to covid- . arxiv prepr [preprint fill up your senses: a theory of self-worth restoration through high-intensity sensory consumption beijing business report on the fight against the pandemic psychological distress and state boredom during the covid- outbreak in china: the role of meaning in life and media use brief sensation seeking scale for chinese -cultural adaptation and psychometric assessment assessing the validity of single-item life satisfaction measures: results from three large samples consumer spending responses to the covid- pandemic: an assessment of great britain. ssrn prepr initial impacts of the pandemic on consumer behavior: evidence from linked income, spending, and savings data. ssrn prepr boredom proneness in anger and aggression: effects of impulsiveness and sensation seeking psychological impact of the coronavirus disease (covid- ) outbreak on healthcare workers in china big five personality and impulsive buying: the mediation of self-control and sensation seeking an arousal regulation explanation of mood effects on consumer choice time and covid- stress in the lockdown situation: time free the unengaged mind china tourism numbers bounce back during labour day holiday health belief model introduction to mediation, moderation, and conditional process analysis, st edn a rebound in consumption after the pandemic, short-term "retaliation" or long-term change? impulse buying: a metaanalytic review interaction effects between comt and bdnf polymorphisms on boredom susceptibility of sensation seeking traits brain responses to repeated visual experience among low and high sensation seekers: role of boredom susceptibility impact of the perceived threat of covid- on variety-seeking compensatory consumption and consumer compromises: a state-of-the-art review anti-consumption, materialism, and consumer well-being chinese public's knowledge, perceived severity, and perceived controllability of the covid- and their associations with emotional and behavioural reactions, social participation, and precautionary behaviour: a national survey how does a public health emergency motivate people's impulsive consumption? an empirical study during the covid- outbreak in china progression of mental health services during the covid- outbreak in china the chinese version of the multidimensional state boredom scale(msbs): it's applicability in chinese college students within-person variability in sensation-seeking during daily life: positive associations with alcohol use and self-defined risky behaviors is sensation seeking a stable trait or does it change over time? covid- : the forgotten priorities of the pandemic china's red banners take on coronavirus. even mahjong gets a mention the ministry of commerce: china's consumer market showed an accelerated recovery in april multiple arousal theory and daily-life electrodermal activity asymmetry relationships among circadian typology, psychological symptoms, and sensation seeking impulse buying and variety seeking: similarities and differences a nationwide survey of psychological distress among chinese people in the covid- epidemic: implications and policy recommendations varieties of cognition-arousal theory exploring impulse buying in services: toward an integrative framework covid- pandemic perception questionnaire clicking the boredom away -exploring impulse fashion buying behavior online a personality trait-based interactionist model of job performance compliance with covid- mitigation measures in the united states. ssrn prepr boredom begs to differ: differentiation from other negative emotions immediate psychological responses and associated factors during the initial stage of the coronavirus disease (covid- ) epidemic among the general population in china test of sensation seeking in a chinese sample perceived probability, perceived severity, and healthprotective behavior timely mental health care for the novel coronavirus outbreak is urgently needed public perception of epidemic risk and economic confidence survey (in chinese) fighting covid- : china in action an arousal-based explanation of affect dynamics analysis and suggestions on the dynamic changes of residents' consumption under the covid- pandemic situation (in chinese) recommended psychological crisis intervention response to the novel coronavirus pneumonia outbreak in china: a model of west china hospital sensation-seeking and domainspecific risk-taking behavior among adolescents: risk perceptions and expected benefits as mediators sensation seeking measures of sensation seeking the following grants funded this research: the foundation of humanities and social science of the ministry of education of the people's republic of china ( yjc ), shanghai foundation of philosophy and social science ( egl ), national natural science foundation of china ( ), and shanghai "early bright" project ( cg and cg ). we thank the editor and two reviewers for their suggestions on the revision for the earlier version of the manuscript. the supplementary material for this article can be found online at: https://www.frontiersin.org/articles/ . /fpsyg. . /full#supplementary-material key: cord- -auq msc authors: deora, harsh; mishra, shashwat; tripathi, manjul; garg, kanwaljeet; tandon, vivek; borkar, sachin; varshney, nagesh; raut, rupesh; chaurasia, bipin; chandra, p sarat; kale, s. s. title: adapting neurosurgery practice during the covid- pandemic in the indian subcontinent date: - - journal: world neurosurg doi: . /j.wneu. . . sha: doc_id: cord_uid: auq msc abstract background the covid- pandemic has changed the practice of neurosurgery. significant resources have been dedicated to it. the pandemic in the indian subcontinent, when compared to the rest of the world, is relatively delayed. the neurosurgical practice cannot remain unaffected by hugely disruptive measures such as a lockdown. the inevitable rise in covid infections with its gradual relaxation continues to pose a risk for health care providers. therefore, it is imperative to evaluate whether the pandemic has had a discernible effect on the same especially in terms of practice modifications in private establishments and publicly funded hospitals, the emotional impact on the surgeon, and the influence of social media on the psyche of the surgeon. material and methods an online questionnaire-based survey was prepared, with questions related to the covid specific themes of precautions taken in outpatient services and operation theaters, the influence of social media, the economic loss incurred, and the perceptible impact of telemedicine and webinars. the links to the survey were mailed to neurosurgeons in private and public practice all over the country. the responses were anonymized to ensure free and unbiased answers to the survey questions. results a total of responses were received from all over the indian sub-continent. the median age of respondents was years (range - yrs) and the post-residency experience was years (range - yrs). respondents were an equitable mix of public and private practitioners. % of the respondents were practicing restricted outpatient services, more in public institutions (p= . ) which also had a higher incidence of tele-outpatient services( % vs %). wearing surgical masks, n- masks, and gloves were the most commonly practised precautionary measures in outpatient services(> %). while private practitioners were continuing elective cases( %), public institutes were more cautious with only emergencies being operated( %). the greatest fear among all practitioners was passing the infection to the family ( %). social media was helpful for brainstorming queries and updating practice modifications, but some surgeons admitted to receiving threats upon social media platforms( . %). depression and economic losses were palpable for approximately % neurosurgeons. conclusion the survey highlights the perception of the neurosurgeons towards the pandemic and the difference in public-private practice. suspension of elective procedures, severe curtailment of the regular outpatient appointments, drastic modifications of the normal opd/or practices and apprehensions related to inadequacy of safety provided by ppe usage and financial losses of private establishments were some of the visible themes in our survey results. though telemedicine has not been as widely adopted as expected, yet online education has been favourably received. the covid- pandemic has changed the practice of neurosurgery. significant resources have been dedicated to it. the pandemic in the indian subcontinent, when compared to the rest of the world, is relatively delayed. the neurosurgical practice cannot remain unaffected by hugely disruptive measures such as a lockdown. the inevitable rise in covid infections with its gradual relaxation continues to pose a risk for health care providers. therefore, it is imperative to evaluate whether the pandemic has had a discernible effect on the same especially in terms of practice modifications in private establishments and publicly funded hospitals, the emotional impact on the surgeon, and the influence of social media on the psyche of the surgeon. an online questionnaire-based survey was prepared, with questions related to the covid specific themes of precautions taken in outpatient services and operation theaters, the influence of social media, the economic loss incurred, and the perceptible impact of telemedicine and webinars. the links to the survey were mailed to neurosurgeons in private and public practice all over the country. the responses were anonymized to ensure free and unbiased answers to the survey questions. a total of responses were received from all over the indian sub-continent. the median age of respondents was years (range - yrs) and the post-residency experience was years (range - yrs). respondents were an equitable mix of public and private practitioners. % of the respondents were practicing restricted outpatient services, more in public institutions (p= . ) which also had a higher incidence of tele-outpatient services( % vs %). wearing surgical masks, n- masks, and gloves were the most commonly practised precautionary measures in outpatient services(> %). while private practitioners were continuing elective cases( %), public institutes were more cautious with only emergencies being operated( %). the greatest fear among all practitioners was passing the infection to the family ( %). social media was helpful for brainstorming queries and updating practice modifications, but some surgeons admitted to receiving threats upon social media platforms( . %). depression and economic losses were palpable for approximately % neurosurgeons. the survey highlights the perception of the neurosurgeons towards the pandemic and the difference in public-private practice. suspension of elective procedures, severe curtailment of the regular outpatient appointments, drastic modifications of the normal opd/or practices and apprehensions related to inadequacy of safety provided by ppe usage and financial losses of private establishments were some of the visible themes in our survey results. though introduction "i understand that it's hard for everyone, but one cannot give in to emotions... we'll have to draw lessons from the current crisis and now we'll have to work on overcoming it." the covid- pandemic has irrevocably challenged the traditional perspectives and practices of neurosurgery. medical services have been heavily scaled down during the lockdown as a huge amount of resources were deployed to face the emerging epidemic. hospitals rapidly reduced scheduled clinical and surgical activities and were forced to postpone non-emergent procedures. during this period, a significant shrinkage in access to the emergency department for both minor and major pathologies has been observed, together with the precipitous decline in outpatient appointments . perhaps the fear of contagion prevented patients, even with severe symptoms, from seeking care. alternatively, patients may also have experienced difficulties in accessing medical services given the extraordinary commitment to treat the new disease and curbs on mobility of people . the lockdown imposed to contain the contagion had some unavoidable adverse consequences for healthcare delivery . in this context, the effect of the disease and its influence on the health care system continues to be felt daily , . the neurosurgical practice is not untouched by the current situation. there are reports from various parts of the world including europe and north america regarding the change in the neurosurgical practice during covid pandemic [ ] [ ] [ ] [ ] . neurosurgical patients needing intensive care may have suffered as most of the resources like icu beds, ventilators and intensivists were diverted to the care of covid patients . however, there are some major differences in the developed and developing world (e.g. indian subcontinent); a large and dense population, limited resources, and already strained health infrastructure , . recently, there are a few publications from the developing world describing the perception of neurosurgeons about pandemic and changes in the neurosurgical practice in the pandemic but there is none from indian subcontinent [ ] [ ] [ ] [ ] [ ] . hence, there was a need felt to understand the effect of the covid epidemic on neurosurgical practice in the indian subcontinent. moreover, there is a fear of an alarming rise in the number of cases of violence against medical personnel owing to a fear of contagion or frustration with the increasingly hamstrung healthcare system in the indian subcontinent. we surveyed the practicing neurosurgeons in the indian subcontinent about the changes in the neurosurgical practice during this pandemic. we also discuss unconventional issues like the loss of economic remuneration, mental health worries, the impact of social media, and the surge of surveys and webinars. our primary intent here was to explore the disparity, if any, between private and publicly funded institutions, concerning the patterns of clinical neurosurgical practice and the use of personal protective equipment (ppe) during direct patient exposure. we also discuss the use of telemedicine in indian subcontinent. we prepared a comprehensive online questionnaire with questions with multiple choice answers and circulated the same in various social media groups, focused email lists, and direct messaging platforms consisting of neurosurgeons from the indian subcontinent (india, pakistan, bhutan, bangladesh, nepal, sri lanka). the total number of recipients of the survey was approximately . the respondents were anonymized concerning name, place of practice, sex, and country of origin in order to have an unbiased opinion. data was collected using google forms® software online. questions were divided into three broad areas: . the pattern of neurosurgical practice during covid- pandemic . influence of social media and electronic learning platforms on neurosurgeons and their mental health . the financial and emotional impact of the epidemic on neurosurgeons the statistical analysis was primarily descriptive. data compiled on the online google spreadsheet was analysed with the "r" language. the categorical variables were examined using chi-square statistics and the continuous variables were compared using welch's t test. the responses collected on likert scale patterns were studied using the non-parametric tests (wilcox rank sum test and kruskal-wallis test). statistically significant differences have been reported. we received a total of responses from a total of potential recipients ( . % response rate) from the survey which received responses between from st may to th may . the respondents were equally distributed among government and private institutions ( vs respondents) ( table ) and were of varying duration of experience following residency ( figure ). the median age of the respondents was years (range - yrs) and the median post-residency experience was years ((range - yrs). most of the neurosurgeons had approximately a median of beds (interquartile range = ) to manage per head ( figure ) with private neurosurgeons having more beds to manage per head than those in public institutions. there was a noticeable change in the outdoor patient department (opd) practices of neurosurgeons with most of them either restricting opd ( . %) or opting for tele-opd ( . %). some stopped the opd services completely ( . %) . at the other end of spectrum were a similar number of surgeons who continued their regular opd practices( . %) ( table ) . interestingly, the practice varied with the number of neurosurgeons in a group. whereas single/sole practicing neurosurgeons opted for restriction of opd numbers or follow-up cases or continued unchanged, groups with > neurosurgeons either stopped opd completely or relied completely on tele-opd. this can be attributed to the fact that most of the large neurosurgical practice groups belonged to public institutions and were obligated to close outpatient departments following government directives. this is corroborated by observations when the opd practices of private and public institutions were compared. twenty six percent of the government/public practitioners had stopped opd completely and the same proportion had opted for tele-opd services. in contrast only % of private practitioners had found it feasible to suspend their opds; . % had started tele-opd (table ). these differences in the changing patterns of outpatient services were significant (p< . ) when compared across groups. this needs to be interpreted in the context that most respondents ( . %) worked in smaller (< surgeons) groups. it is reflective of the type of neurosurgery practice in our subcontinent which is still considerably individualized in the private sector. while government institutions had an almost equitable distribution of the number of neurosurgeons between > and < groups ( vs ), private practice was dominated by teams comprising - neurosurgeons per team ( figure d , table ). in outpatient clinics, ordinary surgical masks were being used primarily, although the respondents believed that ideally n masks with gown/gloves and prior screening of cases need to be adopted ( figure ). many neurosurgeons even expected glass barriers to be erected between patients and themselves or even the use of full ppe kits in opd for maximal protection. however, these protective measures were being implemented sparingly when examined against the expectation of the clinicians ( figure , table ). surprisingly face shields were not popular either in usage or expectations in opd probably because their prolonged use was considered to be cumbersome. this is even though face shields made with surgical sterilization wraps also made to meet fda criteria report a bfe (bacterial filtration efficacy) of . %- . %. apart from this, practice more or less matched expectations both in public and private practice. in operation theatres (ot) too, the operative strategy had shifted from elective and emergencies to doing mainly emergencies and occasional elective cases during the pandemic ( figure , table ). here too, while government hospitals did either only emergencies or emergencies with covid testing, non-government organizations continued to do occasional electives or had their practice unchanged i.e. continued to do electives too (table ) . there was no difference in terms of the expectation of ot precautions with donning/doffing area, full ppe usage, and face shields/goggles being expected by both private and government institutions ( figure , table ). in terms of practice, however, the private practitioner was more careful and had higher usage of donning/doffing area ( . %vs . %), full ppe usage ( . % vs %) and face shields/goggles( . % vs . %) when compared to government institutions. one of the biggest concerns among practitioners during this time was passing the infection to family members with > % of all respondents wanting to prevent the same ( figure ). this was way higher than the fear of getting infected and financial losses (table ). regarding their outlook towards the resumption of clinical practice many felt the same would be restricted for the foreseeable future ( . %) while a substantial number of them were uncertain ( . %). in the absence of government regulations most wanted to continue semielective and elective cases with testing for covid ( . %) or do only very restricted practice like only emergency cases ( %) ( table ) . about a quarter of the respondents were mentally depressed during the past six weeks of the lockdown period following the declaration of the covid pandemic measures. social media was rife with fake news claiming false treatments and more than % of respondents seem to have encountered such news daily (table ). however, ppes and prophylactic medications like hydroxychloroquine were also discussed frequently by neurosurgeons on social media as the pandemic struck the subcontinent. most respondents (> %) found social media to be useful in deciding workflow and planning during the pandemic (table ). most respondents denied facing any threats from the community during the covid pandemic, in contrast to the social media stories. however, % of the respondents admitted that they felt discriminated against or encountered hostility on social media during the pandemic with % never reporting the same and % choosing not to respond to the same . an overwhelming majority of respondents ( . %) felt that an 'infodemic' of papers and surveys on covid- had accompanied the pandemic, perhaps more than can be humanly absorbed. about two-thirds of the respondents expected a greater role in telemedicine in the post covid era. most of the respondents were aware of the neurological manifestations of covid- ( . %) and recounted names of reputed journals (nejm, lancet, jama, nature) as their popular sources of scientific information on the pandemic. almost . % of the respondents remarked that webinars were a good source of learning during this phase of social distancing (table ) . most of the neurosurgeons reported economic losses during this period with only . % reporting no loss. the salaried surgeons face a deduction in the salary ranging from - % while private practitioners face setbacks as they need to meet the running cost of the infrastructure. the estimated losses ranged from usd to usd (inr , to , , rupees per month. average monthly salary of a neurosurgeon in india has been estimated to be usd (range from usd to usd) . this should be interpreted carefully as the losses not only meant salaries but erosion of savings and investment valuations. covid- has infected almost , , people worldwide as of this writing and has spread to more than countries across the globe , . as of now, india has more than , cases and is just behind the us, brazil and russia in terms of caseload. the surge of cases in india has been delayed perhaps due to the strict lockdown implemented by the government in the initial period which was inevitably lifted due to socio-economic compulsions. this was important to collect and streamline the resources and increase public awareness necessary to counter the epidemic. the relaxation of the lockdown and increased covid testing has led to an expected recent rise in the number of cases in india. the experience from most countries including india, brazil and russia shows that the pandemic has been disproportionately severe in densely populated metropolitan centres. high population density is one of the most important factors responsible for the uncontrolled spread of the virus with a maximum number of cases seen in metropolitan cities with population more than million (mumbai and new delhi). similarly, st. petersburg in russia and rio de janeiro and sao paulo in brazil have borne the brunt of disease.this is probably attributable to the prolonged and close contact between the infected and susceptible population, occasioned by the crowded nature of these urban centres. thus, a short term dispersion of the population outside crowded urban centres may be a useful middle path strategy vis a vis an absolute lockdown. while most of the developed nations in europe and scores of us states have seen enough progress in their fight against the virus to focus on how best to reopen their economies, the developing nations of brazil india and russia have seen a surge in cases and now place - th in the list of cases overall. however, the response in all these nations has been different. while india initiated an early lockdown and had a spike of cases later, brazil had a partial lockdown and later lifted the same. russia on the other hand had a partial economic shutdown imposed in late march helped slow the outbreak and prevent the nation's health care system from being overwhelmed. the nationwide lockdown was later needed and encouraged provincial governors to consider reopening industries and construction sites. one of the common factors in all these nations is the incapability to sustain long periods of lockdown due to economic factors which has led to a late increase in cases. developed nations on the other hand have had resources to sustain a lockdown and thus have been able to contain the spread and reopen early (usa, italy and spain). given the serious public health risk, medical practice has changed remarkably during this pandemic. although the virus primarily affects the respiratory system, the neurological manifestations of the covid are now well recognised . though, neurosurgery is not at the forefront of the medical battle against this pandemic, neurosurgical practice and training is not insulated from this epidemic. many organizations have advocated against operating elective cases during this time , , as more and more resources are being claimed by the response to the pandemic. we sought to highlight a seldom explored disparity between the response of private establishments and public hospitals offering neurosurgical services as they grapple with this pandemic. we also intended to examine the effect of social media, the economic losses incurred and the most effective sources of information for a neurosurgeon in the indian subcontinent during this pandemic. all the neurosurgical societies worldover including indian society have responded to this pandemic by making changes in the existing protocols and reorganizing the neurosurgical activities , , . focus has been shifted to triaging patients on the basis of pathology into those needing emergent or elective care , though not many pathologies are amenable to elective management in neurosurgery. scoring system for triaging patients for spine surgery in the setting of limited resources has also been developed . our survey similarly reflected the global trend towards postponing non emergent surgeries. there was a noticeable difference between the outpatient practices being followed at private and government institutions. quite unexpectedly, neurosurgeons in larger practice groups (> neurosurgeons) saw a much sterner closure of normal outpatient services. this may be because most of such large practice groups belonged to public institutions and were obligated to close outpatient departments following government directives. many government hospitals were declared covid centers by the government and even the specialists were kept ready to take care of the patients admitted with a diagnosis of covid. this policy resulted from the strategy of 'preserving' the 'manpower' for the worst. operative strategy in government hospitals was adapted to the directions issued by the neurological society of india and other organizations , . private practitioners too scaled down their operation to occasional electives with very few continuing unchanged. these policy decisions are not insulated from the financial implications being faced by the respondents. private practitioners needed to continue the practice to remain financially viable and government institutions needed to balance the risk of operating emergencies with the high risk of iatrogenic transmission, given the larger caseload and active covid- cases being treated at most of the public hospitals. it was interesting to note that neurosurgeons were most anxious about passing the infection to their families. however, this does not mean that the neurosurgeons were not worried about their safety. even in the immediate future most of them envisage doing only emergencies and semi-elective with covid testing implying their commitment towards preventing transmission of the virus and keeping themselves safe (table ). these concerns were also reflected when we enquired about practice outside the regulation umbrella. eight hundred million indians have limited access to secondary and tertiary care, having to travel mostly to metropolitan centres for superspecialty care . telemedicine provides a potential solution to mitigate this deficiency, more so, during the mobility restrictions due to the covid pandemic. telemedicine has been the predominant mode of patient follow up and has significantly replaced outdoor visits to neurosurgery departments in most of the developed world . one major centre from the us reported that % of visits to neurosurgery departments were deferred to a later date and more than % of the remaining visits were successfully converted to virtual . another centre reported a -fold increase in the use of telemedicine after the shelter-in-place measures were initiated with a significant increase in the mean number of patients evaluated via telemedicine per week across all divisions of neurosurgery ( . to . patients/week) . they reported that both the established patient visits and new patient visits increased significantly. however telemedicine services were offered by only . % of neurosurgeons in our survey, which is quite low. there are many reasons responsible for this low figure. first, not many indian patients have access to the internet at home except for smartphones, and are uncomfortable with various platforms like zoom Ⓡ and webex Ⓡ etc for telemedicine are concerned. secondly, telemedicine facilities were practically nonexistent in india before covid pandemic began and it is difficult to ensure rapid adoption of a relatively new service both for the patients and doctors. third, most of the patients do not have any medical insurance and few of those who have it are covered under various schemes run by the government. in both the scenarios there is no remuneration for the physician that leads to low initiative on the part of the neurosurgeons to offer teleopd services. the increased risk of malpractice suits with teleopd and undefined regulations further discourage remote consultations. use of ppe has been recommended during interaction and transfer of patients presenting with neurosurgical emergencies as well as during neurosurgical surgeries and procedures for confirmed and suspected patients with covid- . most of the respondents across different set ups felt the need to use ppe during patient encounters in opd as well as during surgery in operation theatre. however, there was a difference in the felt need and practice regarding the use of ppe found amongst the respondents of our survey ( tables , ) . there might be several reasons for this observation. the supply of ppe was initially erratic due to disruption of the global supply chains. the ordinary ppe suits often become very uncomfortable for the surgeon during involved and prolonged neurosurgical procedures, discouraging its use. private practitioners were more punctilious in terms of ppe usage. these observations may be attributed to diversion of ppes in large public hospitals to other departments that were facing higher caseloads of covid patients or suspects. mental health has been an often-neglected issue among neurosurgeons. physicians and medical students had higher rates of burnout and depression than the general population . before the covid pandemic, physicians were able to mitigate their stress levels with social and familial interactions. currently, the stress extends outside of the realm of healthcare facilities. physicians worrying about infecting their families and contaminating their homes may choose to self-isolate or face the guilt of potentially infecting a family member . this was reflected in our survey too with the primary concern being not spreading the infection to families and around % neurosurgeons feeling depressed during this time. a recent survey involving respondents from countries found that % of the respondents felt tense, . % were unhappy, % experienced insomnia, almost % had headaches, and % had suicidal ideation during the pandemic . fourteen percent of the respondents were found to have scores consistent with depression on self-reporting questionnaire- . various factors identified by this study to be associated with higher risk of depression included those who did not receive guidance about self-protection, those who did not feel safe with provided personal protective equipment, and those whose families considered their workplace unsafe. a recent report from china has highlighted a welcome response that there was no ripple effect or violence against doctors when they started resuming their routine neurosurgical outpatient clinics after lockdown of three months. in contrast, at least % of the respondents in our survey admitted to receiving unwelcome and intimidatory messages via social media during this pandemic, though it is difficult to ascribe all this to covid pandemic. majority of these threats specific to covid pandemic resulted from misplaced apprehension of the general public that healthcare workers could carry the infection into the neighbourhood . the other reasons for hostility could be the delay in the treatment of patients who require neurosurgical attention due to the difficulties posed by suspension of regular services, any survey suffers from many limitations with the foremost being selection bias. this was not an epidemiological study and does not allow concluding the actual prevalence and incidence of the variables investigated. it does allow, though, to conclude the perception of neurosurgeons about the covid- health emergency concerning the actual epidemiology data. another shortcoming is that the perceptions are likely to change over time as the pandemic is evolving and no survey can possibly surmount this limitation. however, we do not expect major changes in the perception and practices of the surgeons as the risk of catching the disease remains high till we pass the pandemic. in an area with more than neurosurgeons we were able to generate only respondents. despite this, we are the first survey to analyze seldom asked questions on mental health, social media impact, and differences among private and public centers which has somehow lost in this pandemic. neurosurgical fraternity in developing countries cannot insulate itself from the implications of the covid pandemic and must adapt rapidly to the changed scenario in healthcare delivery. suspension of elective procedures, severe curtailment of the regular outpatient appointments, drastic modifications of the normal opd/or practices and apprehensions related to inadequacy of safety provided by ppe usage and financial losses of private establishments were some of the visible themes in our survey results. though telemedicine has not been as widely adopted as expected, yet online education has been favourably received. ) names of each author who received specific funding ) specific material support given: nil neurosurgery in the storm of covid- : suggestions from the lombardy region, italy (ex malo bonum) are we forgetting non-covid- -related diseases during lockdown? projecting the transmission dynamics of sars-cov- through the postpandemic period neurosurgical practice during the severe acute respiratory syndrome coronavirus (sars-cov- ) pandemic: a worldwide survey. world neurosurg impact of covid lockdown on orthopaedic surgeons in india: a survey neurosurgeon salary in india | payscale neurosurgery and neurology practices during the novel covid- pandemic: a consensus statement from india letter: adaptation under fire: two harvard neurosurgical services during the covid- pandemic letter to the editor: neurosurgical practice in covid- pandemic: from the view of academic departments in india, japan and china letter: maintaining neurosurgical resident education and safety during the covid- pandemic scoring system to triage patients for spine surgery in the setting of limited resources: application to the coronavirus disease (covid- ) pandemic and beyond. world neurosurg information for laboratories about coronavirus (covid- ) telemedicine in the indian context: an overview. stud health technol inform telehealth and telemedicine in the covid- era: a world of opportunities for the neurosurgeons telemedicine in neurosurgery: lessons learned and transformation of care during the covid- pandemic. world neurosurg burnout among u.s. medical students, residents, and early career physicians relative to the general u.s. population covid -depression and neurosurgeons. world neurosurg clinical findings in a group of patients infected with the novel coronavirus (sars-cov- ) outside of wuhan, china: retrospective case series telemedicine has not been as widely adopted as expected, yet online education has been favourably received. nil key: cord- -xg d dex authors: coleman, brian c; kean, jacob; brandt, cynthia a; peduzzi, peter; kerns, robert d title: adapting to disruption of research during the covid- pandemic while testing nonpharmacological approaches to pain management date: - - journal: transl behav med doi: . /tbm/ibaa sha: doc_id: cord_uid: xg d dex the covid- pandemic has slowed research progress, with particularly disruptive effects on investigations of addressing urgent public health challenges, such as chronic pain. the national institutes of health (nih) department of defense (dod) department of veterans affairs (va) pain management collaboratory (pmc) supports large-scale, multisite, embedded pragmatic clinical trials (pcts) in military and veteran health systems. the pmc rapidly developed and enacted a plan to address key issues in response to the covid- pandemic. the pmc tracked and collaborated in developing plans for addressing covid- impacts across multiple domains and characterized the impact of covid- on pct operations, including delays in recruitment and revisions of study protocols. a harmonized participant questionnaire will facilitate later meta-analyses and cross-study comparisons of the impact of covid- across all pcts. the pandemic has affected intervention delivery, outcomes, regulatory and ethics issues, participant recruitment, and study design. the pmc took concrete steps to ensure scientific rigor while encouraging flexibility in the pcts, while paying close attention to minimizing the burden on research participants, investigators, and clinical care teams. sudden changes in the delivery of pain management interventions will probably alter treatment effects measured via pmc pcts. through the use of harmonized instruments and surveys, we are capturing these changes and plan to monitor the impact on research practices, as well as on health outcomes. analyses of patient-reported measures over time will inform potential relationships between chronic pain, mental health, and various socioeconomic stressors common among americans during the covid- pandemic. by late winter of , the covid- pandemic had overtaken our lives, changing how we live, work, and take care of each other. the enormity and gravity of covid- have eclipsed thousands of carefully planned research projects underway, affecting the conduct-and, probably, outcomes-of thousands of clinical studies of numerous health conditions [ ] . amid the breakneck pace of efforts to stem the disruption from covid- , we must pause to recognize that its urgency punctuated other ongoing and serious crises. two of them are the opioid epidemic [ ] and the enormous, unsolved problem of managing chronic pain [ , ] . these issues are interdependent: insufficient and underinformed pain management can contribute to minimally effective (and potentially addictive) prescriptions and/or unproven procedures. these complex problems require complex and multipronged solutions in a rapidly changing, overtaxed health care environment. each challenge has also revealed pressure points in health systems that may worsen health disparities [ ] . chronic pain and its management are significant concerns for military service members and veterans living in the usa, many of whom were among the . million active military deployed since in operations enduring freedom, iraqi freedom, and new dawn in iraq and afghanistan [ ] [ ] [ ] . among this population, chronic pain frequently coexists with other problems, including mental illness, substance abuse, and sleep disturbances [ ] [ ] [ ] . research has adapting to disruption of research during the covid- pandemic while testing nonpharmacological approaches to pain management brian c. coleman, , , , jacob kean, , , cynthia a. brandt, , , , , peter peduzzi, , robert d. kerns, , on behalf of the nih-dod-va pain management collaboratory shown that evidence-based, nonpharmacological approaches to pain management, including complementary and integrative health approaches, reduce pain intensity and heighten physical and emotional function and well-being-with minimal risks compared to the use of opioids. however, currently, there is insufficient evidence for maximally effective use of these modalities (as well as for multimodal, integrated therapies) in routine clinical management of chronic pain [ , ] . the national institutes of health (nih) department of defense (dod) department of veterans affairs (va) pain management collaboratory (pmc) is currently supporting large-scale, multisite, embedded pragmatic clinical trials (pcts) in military and veteran health systems to evaluate nonpharmacological approaches and integrated pain care models to manage pain and important comorbidities [ ] . pcts offer the opportunity to develop and test interventions in "real-world" health care environments: a strategy that blurs the distinction between research and care and which thus offers the opportunity for rapid implementation of effective practices within study populations in their usual-care health systems [ ] . formed in , the pmc consists of a research core of pcts, a coordinating center (pain management collaboratory coordinating center [pmc ]), seven domain-oriented work groups, a military treatment facility engagement committee (mtfec), and a steering committee, which operate within two integrated health systems: the veterans health administration (vha) and the defense health agency (dha). currently, years into its efforts, most pmc pcts are transitioning between their planning (ug ) phase and implementation (uh ) phase. in this current crisis within a crisis, the pmc is aggressively developing and enacting a plan to address key issues in response to the covid- pandemic. the pmc pcts are unique in context, approach to pain management, timeline, and national organizational policies and guidance. by nature of being embedded within two geographically distributed health systems that serve similar populations but that have distinct practices, there is variation in the policies and cultures affecting postponement of care, suspension of face-to-face visits, suspension of elective procedures and surgery, and transitioning to use of virtual care. military treatment facility policies are issued by dha, while vha policies are issued by a national central office and carried out by regional veterans integrated service networks and medical centers. funding complexities that have arisen during the pandemic have been addressed and coordinated by the three pmc sponsors: the nih, dod, and va, facilitated by collaboratory leadership. the pmc pcts vary in their size and complexity-their geographical distribution and federated approach to guidance complicate a simple and centralized characterization of the impact of covid- , due to influences by regional, state, and local impacts of the pandemic. beginning in january , as the covid- pandemic unfolded, we recognized the importance of tracking its effects across the pcts while using the pmc work groups as a vehicle for communication and documentation of effects of the pandemic. particularly engaged were work groups focused on biostatistics and study design; phenotyping; stakeholder engagement and ethical and regulatory issues; availability of covid- relevant data in electronic health records (ehrs); and implementation-science approaches for tracking covid- impacts. although the pmc is a large, mainly decentralized effort, our culture emphasizes the vitality of good communication; collaborative, congenial relationships (including defined mechanisms for conflict resolution); and cross-collaboratory standards, where feasible. we thus sought to harmonize covid- tracking measures at the pmc level, as we did for previous processes in place for participant phenotyping and pmc clinical-outcome measures. we tracked covid- impacts across multiple domains and characterized the impact of covid- on pct operations. specific domains that were tracked include intervention delivery, data collection, trial integrity, clinical outcomes, regulatory approval, study recruitment, and statistical analyses. pmc work group project managers updated the internal tracking measure as needed based upon formal and informal discussion with work group members and pct investigators and with oversight from pmc leadership. frequent review and discussion involved members of the pct investigative teams, the coordinating center, the steering committee, the mtfec, and pmc sponsoring organizations. it seems likely that patient-reported outcome data may be clouded by the effect of covid- on pain as an experience and, thus, also affect mental health, substance use, and access to care. we, thus, decided collectively to capture patient experiences related to covid- and coalesced a harmonized set of covid- patient-reported measures to be used across all pcts to facilitate later meta-analyses and cross-study comparisons of the impact of covid- . we developed questions to assess the impact of covid- on an individual's psychosocial, functional, and financial status. we identified these factors as potential mediators influencing treatment effects noted in clinical research across the covid- pandemic period. although these data are applicable to pain-related outcomes, we structured our questions without direct attribution to pain status to allow for broad interpretation and application [ ] . these included the covid- -relevant behavioral and social science domains for clinical or population research and covid- -related measurement protocols currently in use as part of the phenx toolkit. the rapidly evolving pandemic brought heightened focus of frequent pmc work group discussions, which unearthed both immediate and longer-term issues related to effects of the pandemic on the management of chronic pain and our ability to test and deliver integrated care solutions to individuals in at-risk military and veteran populations. as social isolation imposed by the pandemic raises the risk for substance use and addiction and probably exacerbates existing mental health conditions [ ] , the pmc's focus on nonpharmacological therapies takes on a new level of urgency. because pain is a complex, multidimensional personal and social experience, it is especially important to consider potential impacts of changes in socially relevant phenotyping variables, such as employment, income, emotional, and mental health, on pct research participants. this focus resonates with growing interest and prioritization of attention to social determinants of health by the u.s. department of health and human services [ ] . herein, we report initial findings that reveal an array of actual and potential impacts of the covid- pandemic on pct operations and outcomes. when necessary and/or appropriate, pcts made protocol changes, as guided by the regulatory board and sponsoring organization direction and as-needed consultations with pmc biostatisticians. effects varied widely: some pcts experienced little to no effect, whereas others were forced to temporarily suspend research activities (table ) . the pmc pcts are testing a range of pain management interventions that have been affected by the covid- pandemic in both anticipated and unanticipated ways. nonurgent and nonemergent face-to-face care, including surgeries, have been postponed in accordance with federal/state guidelines and facility-level directives during the covid- pandemic. as a result, trials involving peri-operative interventions or interventions highly dependent on in-person, hands-on care-such as chiropractic care and physical therapy-became temporarily unavailable or at least greatly disrupted. the increasing availability and use of virtual care, which was already a priority for both dha and vha, has accelerated out of necessity given the rapid unfolding of the pandemic and is having a range of effects on the availability and method of delivery of pain management approaches. a shift to all-virtual care for interventions with a history of virtual delivery (such as psychological approaches) and for interventions where robust telehealth approaches had not been established (such as chiropractic care and physical therapy) may affect scientific rigor. geographic variability across these health systems may affect the availability and use of virtual care based upon differences in the robustness of pre-covid- telehealth implementation and social-distancing timelines among states: a potential mediator of treatment effectiveness being tracked centrally by the pmc. as one example, in a pmc study assessing technologyassisted care delivery, the digitalization of usual-care processes resulted in fewer differences between the treatment and control conditions than when the trial was proposed. the cooperative pain education and self-management: expanding treatment for realworld access (copes extra) study was originally designed to compare the effectiveness of an interactive voice-response based cognitive behavioral therapy (cbt) pain self-management intervention (copes) with in-person cbt, for reducing pain and improving function for veterans with chronic pain [ ] . however, in the context of covid- , in-person cbt is now being delivered virtually, over the phone and by videoconference. thus, one key potential advantage of copes (the ability to participate in treatment from home relative to in-person cbt) is no longer relevant, although other differences remain. the asynchronous nature of copes may render it a lower burden treatment because patients can participate at their convenience, not only during business hours but also with reduced treatment-session time. the trial will examine asynchronous delivery of copes without real-time contact with a therapist to synchronous cbt for chronic pain delivered by a therapist over the phone or via videoconferencing. anticipated reductions in clinical encounters due to the suspension of many face-to-face interventions and rapid transition to telehealth interventions may result in missing phenotyping and outcome data in participant ehrs, complicating analyses. one pmc pct, the smart stepped care management for low back pain in military health systems, employs a sequential, multiple-assignment, randomized trial (smart) design, an adaptive approach of the va stepped care model [ ] , adopted as the standard of care in dha as well. in this study, the intervention components have been affected very differently by the pandemic based upon changes to delivery media-ranging from a minimal impact in a remotely delivered lifestyle intervention to a major impact on face-to-face physical therapy. from a research perspective, we can expect potential alterations in the strength of treatment effects based on changes in delivery media, as well as individuals' preference to talk about issues related to covid- rather than pain management during cbt. from the perspective of research participants, these shifts might be positive (e.g., reducing cost and travel barriers) or negative (e.g., decreased access to care from poor connectivity and insufficient digital literacy). like other groups conducting clinical, community-, and population-based research studies, pmc pcts have the responsibility to remain in timely and open communication with their institutional review boards and sponsoring agencies. in the current environment, it remains important that pcts document and make formal requests for project modifications as detailed by federal regulations for research with human subjects ( cfr . (a)( ), cfr . (a)( )(iii)). for those pcts experiencing a shift to virtual care, additional regulations affect both care delivery and data collection, including the use of approved delivery media. such considerations were done in close contact with pct investigators, sponsoring organizations and their program officers, relevant staff from institutional review boards and data-safety monitoring boards, pmc leadership, and work groups. ethical issues arise related to research participants' capacity to be informed, with changes in consent processes involving the use of sophisticated virtual processes (e.g., receiving/sending encrypted email and smartphone screen capture of informed consent documents) and changes in delivery media from internally hosted applications to third-party software applications. these tasks and modifications may make it difficult for some study participants to fully comprehend informed consent materials. realities of the pandemic period noted above are likely to lead to changes in participant recruitment. these effects may include increased interest in participating in the pmc pcts as a function of limited availability of some pain interventions due to restrictions from the pandemic. a characteristic feature of the pmc is that all the pcts are embedded within federated data systems consisting of linked ehrs. decreases in the frequency of clinical encounters that result in missing ehr data may dampen recruitment efforts since many of the pcts rely on ehr data as a means of determining eligibility, as well as secondary outcomes and endpoints. some pcts are seeing increases in stakeholder engagement due to streamlined communication channels and sponsor interest in maintaining care in the pandemic. for example, vha has expressed particular interest in supporting virtual psychotherapy for veterans with pain. it is unclear whether these effects on outcomes, and others as-yet not observed, will be temporary or long lasting. the pandemic has introduced difficult methodological issues that affect the assessment and inferences about treatment effectiveness. one major challenge is changes in the delivery of interventions, which affect treatment fidelity, require changes in study designs (e.g., smart, discussed above) along with sample size reconsiderations, and introduce temporal changes in the assessment of treatment effectiveness. other challenges include assessing moderating and mediating effects of covid- and its impact on the fidelity of interventions, particularly usual care, for which data available may differ from prepandemic times of measurement. there are no simple solutions to these problems. new frameworks and innovative solutions are needed to address these methodological challenges. to address some of these problems, the food and drug administration has recently issued a recommendation document titled "statistical considerations for clinical trials during the covid- public health emergency" [ ] . the guidance document proposes trial mitigation and analysis strategies to address the impact of covid- . although this is a guidance document for industry, some of the strategies could be useful for trials studying nonpharmacological interventions for pain. disruptions to research can be brought on by a range of unpredictable events due to severe weather events or other emergencies. but long-lasting, systemic interference on a broad scale has made the covid- pandemic unique. in addition to imparting substantial health impacts and loss of life, the crisis is forcing us to adjust norms and even responsibilities. our health care system has prioritized attention to contending with the still poorly understood behavior and effects of covid- , leaving many health conditions undermanaged, by necessity, through altered standards of care, as well as reduced routine health services. covid- has added fuel to already raging fires-the opioid epidemic and chronic pain, which remain major public health challenges. as a group, people living with chronic pain have the largest global morbidity measured by years lived in disability [ ] . chronic pain especially affects veterans, military service members, and their families [ ] whose livelihoods have collided with the opioid epidemic in various ways, including increased risk for opioid-use disorder. inadequate recognition of chronic pain as a complex multifactorial experience with frequent comorbidities has resulted in many people receiving suboptimal treatment for years-long episodes of discomfort, disability, and psychological distress. this is even though nonpharmacological approaches have been shown to be effective for managing chronic pain [ ] . unfortunately, the covid- pandemic has disrupted pain patients' routine medical office visits, elective pain intervention procedures, physical therapy, chiropractic care, and medication trials, putting these individuals at risk. the pmc's pragmatic research program is being conducted within large, integrated health systems that provide care to millions of veterans and military service members. as such, our work that is embedded within this large ecosystem has implications for helping substantial numbers of people disabled by the burdens of chronic pain. as the covid- pandemic hit, we have taken concrete steps to ensure rigor in our ongoing work to implement effective strategies for managing chronic pain while paying close attention to minimizing the burden on research participants, investigators, and clinical care teams. similar actions can be reapplied in the case of future disruptions to research activities. a benefit of pragmatic approaches is their characteristic ability to "learn" within actual health environments through a bidirectional model of research and practice that involves diverse, real-world populations (e.g., relaxed eligibility criteria) and, often, community-based providers. pcts test the efficacy of interventions in real-world contexts, and the approach can also be used to compare effects across health care settings. the covid- pandemic forced changes in the delivery of pain management interventions and will likely alter treatment effects. through the use of harmonized instruments and surveys, we are capturing these changes and plan to monitor the impact on research practices, as well as on health outcomes over time. however, health care remains a very fluid environment due to the novelty of covid- and, thus, we cannot assess when a "new normal" will arrive. shifts in care delivery emergent during the covid- pandemic (e.g., virtual care) may offer some benefit through increased access to care, but it is likely that a greater, less sanguine impact will be the deepening of care disparities. many people living with chronic pain share features of those hardest hit by covid- : low socioeconomic status, underlying health conditions, low health literacy, and limited access to health care. the digital divide may also likely contribute to undertreatment of at-risk populations due to lack of access to high-speed internet, as well as lacking knowledge and familiarity with online tools and treatment modalities [ ] . thus, we are considering these issues as potential confounders to pct findings in a changed environment of research and care. we are also considering pros and cons of virtual care platforms that offer high security (e.g., va video link), ease of use (zoom), or asynchronous delivery (interactive voice response via telephone). regional differences elicited by state-to-state variation in actions and policies amid the covid- pandemic will have effects on both the conduct and outcomes of pmc pcts that have multiple sites. we are preparing for additional, potentially multiple waves of covid- across the nation over the coming months, should they emerge. our actions now will guide those efforts, including recognizing and embracing permanent or temporary changes to consent procedures and wider adoption of virtual therapies in routine clinical care. we are fortunate that pragmatic research approaches, flexible by design, offer opportunities to capture changes and to understand their effects on chronic pain and other health indicators. we are especially concerned, however, about the potential increased harm to people living with chronic pain and believe that our research to identify and implement effective, low-risk treatment is especially timely. analyses of patient-reported measures over time will inform potential relationships between chronic pain, mental health, and various socioeconomic stressors common among americans during the covid- pandemic. we hope that our forthcoming data from the pcts will inform future use of interventions to manage chronic pain and provide relief to millions of people caught within several crises at once. these findings should also help us understand interrelationship(s) of pandemic stressors and comorbidity on pain as a complex, multimodal experience. tbm ethical approval: this article does not contain any studies with human participants performed by any of the authors. this article does not contain any studies with animals performed by any of the authors. informed consent: this study does not involve human participants and informed consent was, therefore, not required. preserving clinical trial integrity during the coronavirus pandemic a brief history of the opioid epidemic and strategies for pain medicine national pain strategy: a comprehensive population health-level strategy for pain racial health disparities and covid- -caution and context prevalence of chronic pain and high-impact chronic pain among adults-united states prevalence of chronic pain, posttraumatic stress disorder, and persistent postconcussive symptoms in oif/oef veterans: polytrauma clinical triad the musculoskeletal diagnosis cohort: examining pain and pain care among veterans persistent pain and comorbidity among operation enduring freedom/operation iraqi freedom/operation new dawn veterans chronic pain and sleep disturbances: a pragmatic review of their relationships, comorbidities, and treatments managing patients with chronic pain during the covid- outbreak: considerations for the rapid introduction of remotely supported (ehealth) pain management services nih-dod-va pain management collaboratory practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy integrating health research into disaster response: the new nih disaster research response program the psychological impact of quarantine and how to reduce it: rapid review of the evidence healthy people interactive voice response-based self-management for chronic back pain: the copes noninferiority randomized trial implementation of the veterans health administration national pain management strategy statistical considerations for clinical trials during the covid- public health emergency: guidance for industry pain and the global burden of disease relieving pain in america: a blueprint for transforming prevention, care, education, and research clinical policy recommendations from the vha state-of-the-art conference on non-pharmacological approaches to chronic musculoskeletal pain impact of the digital divide in the age of covid- conflicts of interest: all authors declare that they have no conflicts of interest.authors' contributions: b.c.c. and j.k. proposed the presented ideas and led drafting of the manuscript. all authors developed the methods, discussed the results, and provided critical revision of the manuscript. key: cord- - rfb b authors: fell, michael j.; pagel, laura; chen, chien-fei; goldberg, matthew h.; herberz, mario; huebner, gesche m.; sareen, siddharth; hahnel, ulf j.j. title: validity of energy social research during and after covid- : challenges, considerations, and responses date: - - journal: energy res soc sci doi: . /j.erss. . sha: doc_id: cord_uid: rfb b measures to control the spread of coronavirus disease (covid- ) are having unprecedented impacts on people’s lives around the world. in this paper, we argue that those conducting social research in the energy domain should give special consideration to the internal and external validity of their work conducted during this pandemic period. we set out a number of principles that researchers can consider to give themselves and research users greater confidence that findings and recommendations will still be applicable in years to come. largely grounded in existing good practice guidance, our recommendations include collecting and reporting additional supporting contextual data, reviewing aspects of research design for vulnerability to validity challenges, and building in longitudinal elements where feasible. we suggest that these approaches also bring a number of opportunities to generate new insights. however, we caution that a more systemic challenge to validity of knowledge produced during this period may result from changes in the kinds of social research that it is practicable to pursue. the coronavirus disease (covid- ) pandemic is having tragic health consequences around the world, and measures to combat it are impacting people's lives in unprecedented ways. there is, as yet, no clarity on when and how measures such as suspension of certain businesses and physical distancing might end completely, or need to be reintroduced. the timescales required to develop a vaccine and deploy it globally suggest this could be well into and possibly later. during this time, the validity of energy social science research faces additional threats. validity generally refers to the truth of a knowledge claim or inference [ ] . national and global events continuously shape social worlds. but the magnitude, speed, and reach of the changes to our lives are of a different order to anything that most people alive today have experienced. given the scale and rapidity of change, how can we ensure that conclusions drawn from data collected during the pandemic are valid, representative, generalisable to a post-pandemic world, and comparable to the pre-pandemic one? while the answer is inherently unknowable [ ] , our aim in writing this paper is to highlight principles that we believe energy social science researchers can take to help mitigate this uncertainty, and ease future interpretation of research findings in the context of the progressing pandemic. broadly speaking, these principles involve giving consideration to possible impacts of the pandemic and associated response measures on findings; adjusting research design and data collection to reflect this; and reporting extra contextual detail. we argue that researchers who take reasonable steps in these areas will be able to ensure greater confidence in the validity of the work they conduct during this period. through consciously enhanced transparency for the 'extended peer community' that post-normal science scholars have long espoused [ , ] , their contributions will be better positioned to help address future challenges on the validity of findings by reviewers and users. we co-produced these principles as energy researchers who represent a variety of relevant disciplinary perspectives and subject interests, and are based in a range of institutions and countries. this allowed us to balance the will to draw on a breadth of input across the field, with the need to share these principles in a timely fashion. we set them out in the hope that researchers will find them helpful, but recognise that applicability will vary across energy social science research. our recommendations are likely to be most applicable to researchers employing quantitative research methods that are often restricted in the amount of contextual data they are able to collect [ ] . however, we hope that as a set of considerations they will be helpful to a broad range of energy social science scholars to employ as they see fit. the next section of this paper sets out the key challenges we identify for validity during the covid- pandemic, and justifies our focus on social science research in energy. we then expand on steps that researchers can take to address these challenges, and provide a simple checklist that can be applied by scholars in order to address the impacts of the pandemic on their research. we finally highlight additional opportunities these steps can yield, but also point out important potential implications for the nature of knowledge generated by contemporary research. decisions about validity inherently concern tradeoffs and priorities of a given research study [ ] . for instance, a researcher might prioritize internal validity (or "the degree to which a study establishes the cause-and-effect relationship" [ ] ) by conducting a randomized controlled laboratory experiment. artificial laboratory conditions enable strong experimental control, but limit generalizability across diverse, complex real-world situations. a field study, in contrast, might prioritize external validity (or "the generalization of research findings [...] to settings and populations other than those studied" [ ] ), but surrenders some ability to control and measure variables. both of these forms of validity are important. if we cannot trust the findings of a study because of methodological problems or unaccounted-for variables, generalisability is irrelevant. and findings that only apply in exceptionally narrow circumstances offer very limited value in applied research settings. external validity tends to be given special weight in applied research, including most energy research, where the generalisability of findings, and therefore any resulting conclusions and recommendations for action, often has primacy. our point of departure here is the impact of the covid- pandemic and associated response measures on internal, external, and subsidiary forms of validity. we argue that the pandemic merits explicit consideration for validity for a number of reasons. first, the response to covid- represents a departure from ordinary circumstances that is unprecedented in terms of its global nature, rapidity, diversity, and severity of impacts. at the time of writing in may , over countries and several billion people were under some form of lockdown, with restricted rights to movement and public assembly. in many cases, schools, non-essential businesses and hospitality venues were closed. evidence of prevalent psychological distress and anxiety had begun to emerge [ , ] . such a situation is far removed from the conditions under which knowledge is ordinarily produced and applied, and questions around the validity of findings generated during this circumstance are inevitable. second, an important consideration for external validity is how stable findings are over time. while there is always uncertainty about how closely the future will resemble the present, we argue that this uncertainty is now especially high. movement restrictions have already left millions of people unemployed, with millions more at risk of losing their jobs as businesses contract or close [ ] . governmental support packages are building up unprecedented levels of national debt that will have to be paid for, with little clarity around the effect this will have for public services and taxes. while some effects such as quarantine measures will be shorter-term, it is unknown whether the pandemic itself and associated consequences will result in long-term effects on the individual and societal level. realistic and symbolic threats induced by the pandemic are likely to affect individuals' values, identity, and worldviews and thus could exert long-term effects on various dimensions [ ] . moreover, research on past societal crises has shown that pandemic-related effects such as large-scale unemployment can lead to long-term effects on mental health [ ] ). taken together with the scale of current impacts, we believe this increased uncertainty in the short, medium, and long term justifies special consideration of validity of social research and, furthermore, a higher burden of proof on claims to such validity. why is a particular focus on energy studies important? energy use plays a prominent role in many aspects of human life. any changes on the scale being experienced during the pandemic have significant impacts not only on patterns of interaction with energy systems, but also on how people relate to and prioritise those systems. much energy research conducted today aims to inform transitions to clean, low-carbon energy systems that work for people and society. although research conducted now can shed light on how the extraordinary measures in place might impact energy use (such as evidence of reduced weekday electricity use [ ] and changing usage patterns [ ] ), it is challenging to disentangle these impacts from those that result from measures deployable absent a pandemic. moreover, the impact of such a drastic, globally shared experience impacts discursive and normative registers, with undetermined implications for public commitment to low-carbon energy transitions that become interwoven with other drivers of change pathways. although many of the principles we set out next could simply be viewed as good research practice, we think that they merit explicit attention during this pandemic and its aftermath. we argue that they are especially important for those domains of energy social research that claim broad generalisability to their findings and insights, with limited focus on context. for example, we think the points raised here are generally more applicable to survey-based than ethnographic research. by bringing these recommendations together here, we hope to stimulate a more consistent response by social researchers, allowing greater commensurability and comparability across studies in the future. furthermore, we recognise that scholars using social research approaches in energy have a wide variety of backgrounds and levels of experience. what we suggest may be self-evident to some, although for these we hope it will be helpful to have a checklist to compare their own responses against. to others, we hope it will provide both a prompt to consider challenges to validity, and a handy set of responses to consider. we have argued that challenges to the validity of social science energy research presented by the covid- pandemic warrant special recognition. we now lay out a set of principles for researchers to consider bringing to their practice for the duration of the pandemic period and its aftermath to help bolster the validity of their work, and to ensure that future use of their findings and recommendations is facilitated by requisite information to aid correct interpretation. our recommendations address data collection and the reporting of study conditions and context, as well as considerations for study designs in order to ensure high validity of energy social science research conducted during and after the pandemic. given the large number of possible new factors to be taken into account, we propose a 'core and consider' approach, allowing researchers in the field to prioritise and justify the measures they want to take to account for potential pandemic-related influences. where possible, we have drawn on existing good practice guidance, which itself has developed through conventional processes of cross-field engagement [ ] . while we think the validity challenges we have raised here are important, we also recognise that any responses to them must fit within existing research plans, budgets, timelines, labour constraints, and the heightened need for affective care, including researchers' own wellbeing under personal stress-inducing conditions. any response must be both proportionate to the anticipated vulnerability to validity challenges of the kind set out in the previous section. ethical and data protection concerns, while not directly related to validity, must be borne prominently in mind. any changes to planned research should not, unless it is explicitly justified, introduce collection of categories of data that are more sensitive than those that were originally (or would ordinarily be) planned and/or approved. this means, for example, that researchers should not (without careful thought and justification) begin to collect data on physical or mental health unless this was intended anyway. researchers should be mindful of the extra burden to participants that introducing additional data collection could bring. extra sensitivity is called for on the part of researchers to the potential impacts of collecting data on topics which may be more upsetting now than would ordinarily be the case. we suggest that additional and/or modified variables may need to be collected and reported for studies carried out during or after the covid- pandemic in order to account for the impact of the pandemic on research validity. already, researchers shouldand many doreport contextual factors of any study, and consider how these might impact the study findings [ ] [ ] [ ] . given the large number of possible new factors to be taken into account, we suggest researchers take a 'core and consider' approach. government restrictions and relevant demographic variables at the level of the unit of analysis (e.g., individuals or households) are core additional variables that should be reported and discussed. other factors should be considered for additional reporting depending on the precise topic of research. as in all studies, reporting of contextual factors should encompass date(s), place(s), and duration of data collection. as a core concern, we suggest that this should now be supplemented with information on pandemic-related national and local policies that were in force at the time and place of data collection. this could include factors such as levels of restriction of people's freedom to move around outside the home, including self-imposed precautionary behaviour, and the open/closed status of specific relevant services such as schools and certain businesses. significant changes in any of these measures during data collection should also be reported. researchers may consider it to be important for context to give a sense of the severity of the pandemic (including health, social and economic impacts, as relevant). we suggest using official government references for a description of such policies and impacts where possible, in ways that are cognizant of their rapid temporal evolution. a further core consideration is that local and national pandemic response measures affect individuals and households in diverse ways; specifying the national policies during data collection alone does not explain effects at the individual (or other analytical) level. more specific effects can be captured by measuring application of and compliance with response measures on the respective analytical level, and/or through collection of additional demographic variables from which application could be inferred. the nature and detail of measures will differ by locality, but could include whether someone is considered a 'key worker' (and hence still regularly leaves the home during lockdown) or comes under a highrisk category and has to observe stricter measures. other standard demographic variables may need amendment depending on the study aims. for instance, employment status can include categories such as being placed on government-subsidised furlough, working reduced hours, or working fully from home. other variables that might ordinarily have been judged as having limited importance, might gain relevance. impacts of the covid- pandemic are thought to be exacerbating existing inequalities in many societies, such as energy poverty issues [ ] . a key variable in many studies will likely be the financial situation of the individual, household, or other unit of interest. capturing information on recent (and risk of future) changes in factors such as income (including transfer payments), changes in employment status, increased receipt of benefits, or self-reported financial satisfaction may take on greater importance. unexpected deprivation from work income may have differential effects on energy-related measures, relative to foreseeable prolonged unemployment periods; while this is a consideration in samples at any time, it is likely to be especially common now. differentiated impacts on variables such as health, income or employment situation are already evident across individuals, notably across ethnicities, gender and income groups [ , ] . disaggregating on the basis of such variables, while always beneficial, may now be of more acute importance given heightened inequalities. at the individual level, we anticipate that covid- response measures will be associated with important changes in behaviour, as well as cognitive, affective, and other social and material dimensions [ ] . changes in energy-related behaviours and decision-making due to changes in daily routines, work and mobility might be more apparent and measurable, but changes in decisions and actions triggered by pandemic-related shifts in energy-related beliefs, attitudes, emotions, and judgments may be just as important to apprehend. for energy social science research focusing on the aforementioned dimensions it is important to assess to what extent these variables are different from a "normal" scenario and whether potential changes are durable or ephemeral. epidemiological research demonstrates the effect that pandemic response measures and consequences such as unemployment exert over time on personal well-being [ ] ). while empirical research on specific covid- measures is emergent, existing theoretical research on the psychological consequences of the crisis indicates that the fallout on current generations will linger in complex ways over time [ ] .the inability to accurately predict how such changes might be associated with energy-relevant outcomes, or which changes might be more or less enduring [ ] , makes it all the more important to capture and consider them in the long run. where additional measures are included, we suggest the use of standardized approaches to the extent possible, such as widely used and validated scales employed in regular national surveys. this will allow commensurability with pre-covid- levels, while minimising construct and instrument validity challenges and the resource-intensive efforts associated with developing new measures (which require substantial testing to ensure scale reliability and validity). we show an initial mapping of variables as 'core' and 'consider' , in table . we also provide a checklist (see appendix) suggesting where and how to report those additional variables (and other considerations) in studies. when thinking about the potential effects of the covid- pandemic on the validity of research findings, it is also important to consider how it might affect research design. in this section, we briefly introduce issues relating to study design, sample selection and recruitment, and data collection methodology, as well as implications for interpretation of findings. suggestions on ways to report such considerations are also provided in the checklist (see appendix). it is likely that the pandemic will affect non-experimental research in different ways than it will affect experimental research. research focused on identifying associations might be especially vulnerable to threats to internal and external validity. more specifically, if the pandemic affects both the independent and dependent variables of interest, it can induce a spurious correlation (confounding; [ ] ). for instance, the pandemic might harm mental health and increase energy usage, making it appear as though the variables are related when they might not be, absent the pandemic. researchers can address this concern in the way that is typically recommended for addressing confounding: anticipate how the pandemic might affect your variables of interest, measure this set of variables, and test whether they affect the study's primary results [ , ] . the idea that 'correlation is not causation' is wellknown --but worth keeping salient especially at times when non-experimental research is being planned or altered at short notice. experimental designs are still potentially vulnerable to other pandemic-induced issues. experiments, by design, manipulate a specific variable of interest. for example, an experiment aiming to improve people's motivation to purchase or support renewable energy by means of messaging strategies might focus on the harm caused by fossil fuels to increase people's fossil fuel risk perceptions. however, the salience of such risks, and therefore their malleability, may be substantially decreased if people are preoccupied with other worries related to covid- . thus, researchers should consider such influences and, if possible, take measures to ensure that they can indeed manipulate the causal variable of interest in an effective and meaningful way. this is an empirical question for each manipulated variable, but we advise that researchers attempt to anticipate such issues and design their research accordingly. a clear consequence of the pandemic is that it will make it more difficult to conduct betweenand within-country comparisons where covid- impacts and restrictions are different. for example, home energy usage will be higher in places where people are required to stay at home. a useful rule of thumb is, wherever reasonably possible, researchers should contextualize their research by considering how political and cultural circumstances might affect their results (see section "capture and report on extra relevant data"; [ ] ). it would be even better to anticipate how such factors might affect results and design the study to mitigate them, such as collecting a sample that is relatively homogeneous in orders to stay at home, limit travel, or any variable that might substantively affect the results. if substantial heterogeneity of restrictions is anticipated within a sample, increasing sample size to maintain statistical power should be considered. independent of study type, a powerful way to get a measure of stability and validity of findings over time is to build longitudinal elements into the research design. first, researchers could consider building replications into their research plan. this can be done by intentionally splitting data collection over waves separated by a period of time. this allows for comparison of the variables of interest over the two waves. variables that remain constant over this period are likely to be relatively less affected by pandemic response measures than those which show variation. this approach lends itself particularly well to collaborations between research groups, which could consider teaming up to add variables of interest reciprocally onto the end of each other's studies, saving on budget and potentially introducing opportunities for new analyses. please refer to the section "capture and report extra relevant data" for more information on variable dimensions to consider. another possible approach to demonstrate the robustness of research findings over time could be through attempting to reproduce previous research findings --either of related research by the researcher themselves, or of previously well-reproduced effects. the extent to which previous findings are reproduced, or change, could help 'calibrate' the more recent research and give some insight into whether or not the domain of interest is more or less impacted by the pandemic and the corresponding response (also accepting that failure to reproduce findings is not an unusual occurrence even under normal circumstances [ ] ). data collection with a given research method could produce different findings now compared to before pandemic-related restriction measures were put into place. for example, research conducted online could be more heavily influenced by distracting factors of the participant's environment. where people are confined to their homes, completing a survey or conducting an interview in a standardized way might be more difficult than before. this consideration is especially important, since persisting restrictions of contact might result in a shift towards more research being conducted online versus in person. it is thus recommended to explore the possibility of using more than one method to investigate the same research question, and to record potential limitations specific to a data collection method to account for their influence on the validity of the findings. this is another area where collaboration between research groups with complementary interests could bring significant additional value by allowing testing of the same research question through different approaches and in different settings [ ] [ ] [ ] . while elaborating on additional or alternative methods, it is again important to consider ethical aspects. as mentioned earlier, the extra sensitivity of collected data has to be thought through, and in terms of data collection methods, researchers and analysts should make sure that data privacy and confidentiality is not undermined by new approaches [ ] . in the previous subsection we already highlighted the importance of giving due consideration to contextual factors. in respect of covid- , this means paying particular attention to the extent to which pandemic response measures (and changes in them across time and the sample) might have contributed to the observation of particular results. if possible, researchers should attempt to communicate and justify their best estimate as to the impact such factors could have had on findings. for example, if little systematic difference is observed in an outcome variable across groups who were substantially differently impacted by pandemic response measures, this could be offered in support of a case that the impact of covid- of that particular variable could be small. as in many areas of research, transparency is likely to be key in allowing users to make informed judgements of their own. any recommendations for policy, practice, or further research should be similarly transparent and include appropriate caveats on the context of the findings to which they relate. employing the principles set out above presents a number of opportunities that go beyond simply mitigating threats to validity, and could help generate new insights or improve research practice in general. the introduction of longitudinal elements can provide important insights on stable and dynamic determinants of energy-relevant outcomes, especially if combined with new contextual, behavioural, and other data that may not previously have been collected. such longitudinal studies could moreover contribute to the research question whether observed changes on the individual and societal level are caused by the pandemic itself (e.g., due to perceived threats and vulnerability) or by associated measures and consequences (e.g., due to lockdown and job loss) and thus provide insights into short-term and long-term effects of the pandemic. moreover, where collected data suggests that different groups of people have been (or will be) systematically exposed to different conditions as a result of the pandemic, natural experiments could be possible. natural experiments provide a powerful opportunity to investigate causal associations which may otherwise be difficult or impossible to control for (for an example see: [ ] ). these fleeting windows of opportunity can provide novel research opportunities and should be considered by energy researchers. the same window of opportunity will likely extend to policy interventions introduced in the wake of the pandemic to aid economic recovery. we already highlighted the possible benefits that could accrue from collaboration with other groups to facilitate replication and support validity, but there is also a wider convergence research opportunity in energy social studies during and after covid- . convergence research is a way of addressing complex problems through highly integrated interdisciplinary approaches [ ] . given the range and scale of current and anticipated impacts of the pandemic, such an approach is likely to be especially valuable, and opportunities to build inter-and transdisciplinary collaborations should be proactively sought. such collaboration may also provide a route to adding in important contextual data, for example through matching datasets. finally, we suggest that responding to validity challenges presented by the covid- crisis is an opportunity for the energy research field to step up and embrace practices around transparency and reproducibility that are now seen as standard practice in other areas of research. for reasons likely connected with the multidisciplinary and applied nature of most energy research, tools such as reporting guidelines and pre-registration of analysis plans are still rarely employed [ ] . it is possible that the particularly pressing need to demonstrate validity at present will result in familiarity with, and adoption of, tools that subsequently become standard practice for an increasing number of energy researchers, potentially enhancing the overall validity of research in the field. in much of the social sciences, knowledge on the most severe and pressing problems is often difficult to create and therefore constitutes a smaller proportion of thematic scholarship than its implications merit. the flip side of this is that 'low-hanging fruits' can suffer from excessive coverage. this impacts the 'body of knowledge' validity, which we define as the representativeness of research in a field relative to the real-world problems the field is concerned with [ ] . energy social science research, with its diverse methodologies, spatial and scalar foci, and associated differences of requisite time and effort, is no stranger to these tendencies. consider, for instance, the wealth of scholarship on local and urban energy initiatives in the uk, home to many energy research scholars, versus the relatively thin body of work on energy practices in rural sub-saharan africa. both issues merit attention and are generative for conceptual insight, but the latter affects over a billion people, many of whom experience relatively severe degrees of energy poverty, and yet hardly registers in terms of volume in relevant energy social science research. we detect a risk that curtailment of field-based empirical research, especially in regions that face severe energy challenges and may be heavily impacted by the epidemic, will exacerbate existing biases in representation in terms of volume (more desk study over ethnographic research than usual), methodology (potentially more conceptual work over evidence-based research) and regional coverage (less pandemic-impacted areas over more pandemic-impacted areas). to some extent, this is a perennial problem in any interdisciplinary or transdisciplinary field of study: ethnographic work in challenging regions with marginalised populations takes time and the classics on such topics that have accumulated over the years (in quite large numbers) consequently receive considerable attention. it is similarly evident in other fields of energy research, such as modelling, and outside of the energy domain. yet research today is heavily metricised, and most scholars with access to most global peer-reviewed scholarship are based in global north institutions and typically urban contexts, often with pressure to publish frequently. this leads to the double jeopardy of being pressed for time to focus on short-term impact, and of being far more likely to access highly-cited and highvolume segments of the scholarship one engages with. since the pace of research outputs has escalated, few scholars are positioned to navigate a body of knowledge with adequate care to balance its in-built biases of representation. already, we see moves to run online surveys and study social perceptions; even with all the appropriate caveats and the best of informed intentions, these contribute to a likely disbalance by volume of the sort of concerns that will get platformed in energy research journals in the short-to medium-term. how much coverage of marginalised, hard-to-access concerns -such as migrants cast adrift with little energy access, subsistence farmers with crop loss and inability to pay for fuel costs -will be lost and substituted by low-hanging fruit? such exacerbation of an existing bias can cloud future accounts and understandings of the true effects of a pandemic on the subject of energy research, i.e., on the global lived experience of energy. but it is not inevitable -it is an artefact of choices we make as an epistemic community. informed by recognition of likely biases, our choices (and those of funders, who can prioritise research on marginalised research areas) can embody normative commitment to proportionally match research coverage to real-world problems. we can productively draw on approaches such as convergence research highlighted above. this drive captures the essence of our contribution, which is to work toward a reflexive understanding of our role as a scholarly community at this time of crisis and opportunity. in this paper we have set out what we see as important challenges to the validity --internal, external, and of other forms --of social research in energy associated with the covid- pandemic and measures put in place to control it. we have suggested a number of principles we think researchers should consider applying to give themselves and the users of their work confidence that the findings and recommendations they present will still be valid in the years to come. these focus mainly on the collecting and reporting of additional contextual data, and the review of research design elements to ensure they are as robust as possible to pandemic-related impacts. we think that these principles can be employed with relatively minimal impact on resources and timescales required for research. they even present some opportunities both to enrich insight into social aspects of energy, and draw attention to measures to improve research transparency that are still as-yet under-used in the energy field. however, we also need to be mindful that due to limits on the kind of research approaches that can be employed during the pandemic, there are likely to be important gaps in the knowledge generated during this period. we all hope that the period of direct applicability of this paper will be as short as possible, and that measures to control the spread of covid- will soon no longer be needed. nonetheless, we also think that the considerations we raise here have enduring relevance for energy social science in general, and the potential to contribute to more widespread use of transparent, contextually aware and valid research practices in the longterm. the authors declare no conflicts of interest. table : checklist of items to report or consider reporting in relation to covid- pandemic validity challenges. report: main details of covid- response measures in action at the time/place of data collection, at least including: level of freedom to move around in public; degree to which schools and businesses are open. methods "at the time of data collection, public movement in the uk was severely restricted by government measures to combat the covid- pandemic. people were instructed to stay at home at all times, except for doing essential shopping, one period of daily exercise, working outside the home if work at home was impossible, and providing support to vulnerable people. all schools, hospitality venues and nonessential shops were closed." consider reporting: how covid- restrictions are applying to individual participants. results "in our sample, % of participants reported staying at home at all times except for when conducting essential shopping and exercise. a further % also reported leaving home to undertake work or volunteering. % of the sample reported staying at home at all times." consider tailoring of the following aspects of the research: research design methods "in response to the rapidly changing circumstances connected with the response to the covid- pandemic, we introduced a longitudinal element to our data collection. the survey was administered over two waves separated by two months, allowing us to check whether any of the key independent variables changed over this time, and whether this was associated with any change in the outcome." data collected (see table for suggested dimensions) methods "in addition to employment status, we also collected data on the extent to which those in employment were working from home." consider possible implications for: findings discussion "we found a strong association between altruism and stated willingness to participate over both waves of the study. however, the association was weaker in the second wave, which, combined with the change in reported application of covid- response measures (while other variables remained stable), suggests that conditions surrounding the covid- pandemic could have affected this finding." conclusion "our findings suggest that policymakers should prioritise energy saving messaging framed in terms of benefits to the local environment. however, our participants reported spending more time in their local area as a result of covid- control measures which could have influenced our result. we therefore recommend that the effectiveness of such messaging be carefully monitored." experimental and quasi-experimental designs for generalized causal inference uncertainty, complexity and post-normal science extended peer communities and the ascendance of post-normal politics european energy poverty metrics: scales, prospects and limits establishing the internal and external validity of experimental studies theory-testing, generalization, and the problem of external validity a nationwide survey of psychological distress among chinese people in the covid- epidemic: implications and policy recommendations americans' risk perceptions and emotional responses to covid- covid- ) from pandemic to recovery: local employment and economic development conducting social psychological research in the wake of covid- long-term effects of youth unemployment on mental health: does an economic crisis make a difference? new data suggest covid- is shifting the burden of energy costs to households promoting novelty, rigor, and style in energy social science: towards codes of practice for appropriate methods and research design the importance of heterogeneity in large-scale replications the importance of social relations in shaping energy demand using in-home displays to provide smart meter feedback about household electricity consumption: a randomized control trial comparing kilowatts, cost, and social norms measures to tackle the covid- outbreak impact on energy poverty: preliminary analysis based on the italian and spanish experiences ethnicity and covid- : an urgent public health research priority how are americans coping with the covid- crisis? key findings from household survey survey tool and guidance: behavioural insights on covid- , who what sticks? ephemerality, permanence and local transition pathways, environmental innovation and societal transitions three conditions under which experiments and observational studies produce comparable causal estimates: new findings from withinstudy comparisons can nonrandomized experiments yield accurate answers? a randomized experiment comparing random and nonrandom assignments estimating the reproducibility of psychological science many labs : investigating variation in replicability across samples and settings crowdsourcing hypothesis tests: making transparent how design choices shape research results scientific utopia iii: crowdsourcing science on the responsible use of digital data to tackle the covid- pandemic mask-wearing increases after a government recommendation: a natural experiment in the us during the covid- pandemic convergence research in the age of big data: team science, institutional strategies, and beyond how to improve transparency when theories become tools: toward a framework for pragmatic validity while this work did not receive any dedicated funding in its own right, the individual authors gratefully acknowledge funding as follows. key: cord- -l f gp authors: nan title: oral and poster manuscripts date: - - journal: influenza other respir viruses doi: . /j. - . . .x sha: doc_id: cord_uid: l f gp nan pandemic influenza h n (h n pdm) virus of swine-origin causes mild disease, but occasionally is associated with acute respiratory distress syndrome and death. , it is important to understand the pathogenesis of this new disease. previously we showed a comparable virus tropism and host innate immune responses between h n pdm and seasonal h n influenza virus in the human respiratory tract, however h n pdm virus differed from seasonal h n influenza virus in its ability to replicate in human conjunctiva, suggesting subtle differences in receptor-binding profile and highlighting the potential role of the conjunctiva as an additional route of infection. we now compare the tropism and host responses elicited by pandemic h n with that of related swine influenza viruses and a pandemic-swine reassortant virus in ex vivo and in vitro cultures of the human respiratory tract and conjunctiva. we have used recombinant virus to investigate the role of the hemagglutinin (ha) and neuraminidase (na) of h n pdm virus in its conjunctival tropism. these findings are relevant for understanding transmission and therapy. fragments of human conjunctiva, bronchi, and lung tissues were cut into - mm fragments within h of collection and infected with influenza a viruses at a titer of tcid ⁄ ml. viruses investigated included h n pdm (a ⁄ hk ⁄ ⁄ ), swine h n virus (a ⁄ swine ⁄ hk ⁄ ⁄ ), which shares a common derivation for seven genes with h n pdm, a natural swine reassortant h n (a ⁄ swine ⁄ hk ⁄ ⁄ ), which has acquired the na gene from h n pdm and other swine influenza h n viruses. reverse genetics derived recombinant viruses with ha and na gene segments of seasonal h n and pandemic h n swapped were also studied. lung fragments were cultured at °c in culture plates; conjunctival and bronchial biopsies were cultured in air-liquid interface at and °c respectively. tissue fragments were infected for h and incubated for , , and h post infection. infectious viral yield was assessed by titration in mdck cells. the infected tissues were fixed with formalin and analyzed by immunohistochemistry for influenza antigen. cytokines profiles induced by influenza virus infected respiratory epithelial cells in vitro were measured by quantitative rt-pcr and elisa. we found comparable replication in seasonal and pandemic h n viruses in human respiratory tract, while the swine influenza a ⁄ swine ⁄ hk ⁄ ⁄ (h n ) virus and a ⁄ swine ⁄ hk ⁄ ⁄ (h n ) virus failed to infect and replicate in human lung ex vivo culture, but it replicated productively in human bronchus ex vivo. interestingly, the swine reassortant influenza h n (a ⁄ swine ⁄ hk ⁄ ⁄ ) virus (with the na from h n pdm) infected and productivity replicated in lung ex vivo and in vitro. pandemic h n pdm virus, but not seasonal h n virus, was able to infect ex vivo cultures of human conjunctiva, suggesting subtle differences in receptor binding profile in h n pdm, seasonal viruses, and the swine related h n viruses. using reverse genetics derived recombinant viruses, we were able to demonstrate that the ha and na segments of h n pdm, but not the polymerase genes, were required for the conjunctival tropism of h n pdm ( figure ). in contrast with highly pathogenic influenza h n virus, which induced high cytokine and chemokine decretion, the related swine viruses, a ⁄ swine ⁄ hk ⁄ ⁄ (h n ), as well as the swine pandemic reassortant virus, a ⁄ swine ⁄ hk ⁄ ⁄ (h n ) we studied were similar to h n pdm and seasonal influenza viruses in their intrinsic capacity for cytokine dysregulation. collectively, our results suggest that pandemic h n pdm virus differs in modest but subtle ways from seasonal h n virus in its intrinsic virulence for humans, findings that are in accord with the epidemiology of the pandemic to date. the ha and na gene segments are key to the conjunctival tropism manifested by the h n pdm virus. the pandemic reassortant influenza h n (a ⁄ swine ⁄ hk ⁄ ⁄ ) virus isolated from swine with the na from h n pdm shares with h n pdm the capacity for productive replication in lung ex vivo and in vitro. these findings are relevant for understanding transmission and therapy. isolation of influenza viruses from specimens is traditionally performed in two classical systems: embryonated chicken eggs and mdck cell culture. nevertheless, several publications are dedicated to the theme of alternative cell culture systems, which may be used for influenza virus isolation and cultivation. [ ] [ ] [ ] this is in part because mdck cells are of animal origin, which means that they cannot be used as a proper model for estimating interactions between a human virus and a human cell culture as a host. a variety of human monolayer and suspension cell cultures have been tested on their capability to support influenza virus replication. among them, some support influenza a virus growth as well as mdck cells do, others support replication of a virus, but do not enable the formation of mature viral particles, whereas others show only a weak level of replication or are not permissive at all. caco- cells, for example, represent a good substitute for mdck cells, because it has been shown that the rate of viral isolation in caco- cells is as effective as in mdck, and sometimes is even better. the success of viral replication is determined not only by the cell culture type, but also by the virus itself. despite the accepted view that it is the type of receptor that defines the interaction between the virus and the host cell, there is evidence that it is not the only factor that predetermines the fate of the cell. the fate of the infected cell can also differ. a series of articles show that apoptosis is the most probable mechanism of cell killing by influenza viruses. , influenza a viruses of different subtypes induce apoptosis to a different extent (e.g. h viruses provoke more strong apoptotic response than h viruses do ). nevertheless, it has been demonstrated that caco- cells do not follow the apoptotic pathway and die through necrosis. the sjpl cell line also dies through necrotic pathway and not apoptosis. the aim of our work was to compare growth characteristics of different flu viruses (e.g. avian, swine, and human) in various human and animal cell cultures and to evaluate their influence on cell culture growth. the parameters measured in the study were as follows: cytopathic changes of cell cultures following virus infection, hemagglutinin production, np synthesis, the dose-dependent effect of infection on cell proliferation, and the ability of viruses to induce apoptosis. influenza viruses used included: highly pathogenic avian h n a ⁄ kurgan ⁄ ⁄ , low pathogenic avian h n a ⁄ gull ⁄ kostanai ⁄ ⁄ , swine h n a ⁄ swine ⁄ ⁄ , human h n v a ⁄ california ⁄ ⁄ , human h n v a ⁄ saint-petersburg ⁄ ⁄ , human h n a ⁄ brisbane ⁄ ⁄ , and human h n a ⁄ brisbane ⁄ ⁄ . the viruses were propagated in -days embryonated chicken eggs, the allantoic fluid was collected, the aliquots were made and stored at ) °c for further use. to evaluate tcid for each virus on all cell cultures, -well plates were used. the cells were seeded ae ml per well (concentration of - ae · cells ⁄ ml). the confluent -h old monolayer was used for viral inoculation. the cells were washed twice with serum-free medium, then ae ml of tenfold viral dilutions from viral aliquots were added and left for min for contact at °c. the cells were then washed to remove the non-attached particles, and the wells were filled with tpck-trypsin ( lg ⁄ ml)-containing medium without bovine fetal serum. the plates were observed daily for cytopathic effect, and the results were evaluated at h after infection for cytopathic effect and by reaction of hemagglutination with suspension of chicken erythrocytes ( ae %). infection of suspension cell cultures was done in centrifuge tubes. cells (concentration - · ) were inoculated with viral dilutions (moi = - ). after min of contact, cells were washed, resuspended in rpmi with trypsin and fetal serum, and seeded in -well plates ( ml in each well). the results were fixed after h, calculating the number of cells grown and estimating the rate of apoptosis by hoechst- staining. cells were grown in -well plates with seeding concentration · cells ⁄ ml. one millilitre of cell suspension was placed in each well, inoculated with viral dilution (moi = - ) and left for h. after, the cells were detached from plastic with versene and calculated in fuks-rosental camera to evaluate the number of cells. the monoclonal antibodies obtained in research institute of influenza towards viral nucleoprotein np were used following the standard protocol described in. for all viruses tested, mdck turned out to be more permissive than sp cell culture. avian viruses, independently of their pathogenicity, replicated efficiently on both animal cultures tested. human h n and h n viruses demonstrated weaker replication in sp cells. the most significant differences were seen for swine influenza and pandemic h n v viruses which replicated in mdck cells at the rates comparable with other viruses, but showed poorer growth in sp cell line (see table ). human cell lines displayed clear differences in their susceptibility to viruses of various origins. avian influenza viruses replicated in all cell lines except girardi heart, and the most intense replication rate was observed for ecv- , l- , and rd lines. a- and a- were poorly infected, as well as all suspension cell lines tested. seasonal human h n , as well as h n viruses, replicated in all cell cultures tested, but the rate of infectivity was rather low in practically all cultures tested with the exception of rd and t- g cell lines. strikingly, swine influenza virus and human pandemic h n v viruses didn't replicate well in any of human lines tested. a weak replication rate was observed in ecv- , rd, and t- g, but in general, human cell lines were the titers produced by swine and pandemic influenza viruses are shaded in grey. *low-pathogenic avian influenza virus; **highly-pathogenic avian influenza virus poorly susceptible to pandemic h n v. swine influenza virus differed because it infected weakly a- and girardi heart cell cultures, which was not the case for h n v viruses. our study has shown that all influenza viruses were able to induce apoptosis in the cell cultures tested. the degradation of chromatin found in the nucleus with hoechst- staining was seen before the first symptoms of cytopathic effect (cpe) in monolayer of cells. in cell cultures where the cpe was not visible, high doses of virus still induced apoptotic response. the process of apoptosis is rather well studied in mdck cells and some other cell types, so we've focused on three human monolayer cell cultures that are relatively poorly studied: a- , ecv- , and flech. these cell cultures are less susceptible to viral infection, and besides, it was interesting to find out whether the viruses that do not cause any cpe do infect these cultures. a- turned out to be most sensitive to apoptotic response, while flech turned out to demonstrate weak reaction. time needed for apoptosis induction by different flu viruses also varied. the earliest apoptosis was noted for h n and h n viruses and h n viruses induced apoptosis at about h postinfection. it is well-known that apoptosis can be induced only by a reproducing virus, and that uv-kills viruses that are not capable of it. we tested whether swine and pandemic h n v viruses (that do not show cpe in these cultures) do replicate in them and induce apoptosis with the help of monoclonal antibodies against viral np. the obtained data show that they indeed do replicate in these cell cultures, as we observed np fluorescence, and that they also induce apoptosis (see table ). we've shown earlier thus, we've tested the ability of swine and pandemic h n v viruses in this aspect. it was shown that these viruses were comparable with the effect seen for seasonal h n virus. moreover, swine influenza virus induced stronger apoptotic response in hemablastoid cell lines in comparison with pandemic h n v viruses, which also have a swine origin. we also checked the ability of flu viruses to influence monolayer cell cultures growth. the data clearly indicated that only ecv- endothelial line and t- g glioblastoma line displayed cell proliferation in response to low moi. apoptosis wasn't registered in these stimulated cultures, apparently because the moi was very low. all the other monolayer cultures didn't respond to low moi by stimulation of their proliferation. interaction between an influenza virus particle and a host cell can follow several scenarios. cpe seen in infected cells is accompanied with high rates of viral particles production and leads to cell death. the death itself may be through apoptotic or necrotic pathways. , also, infection process in low doses can stimulate cell proliferation -the effect seen for hemablastoid lines, histiocytes, peripheral blood cell lines, , and in glioblastoma and endothelial cell lines as it was described here. considering the origin of ecv line, these cells bear all the antigenic, biochemical, and physiological traits of umbilical cord and are actively used in pharmacological tests as well as glioblastoma cells; they also are of special interest for oncogenesis studies. table . replication, apoptosis induction, and np synthesis of influenza viruses in a- , ecv- and flech cell cultures. the numbers represent the log tcid ⁄ ae ml calculated by reed-muench method as described in. the ()) symbol means that no cpe could be observed in any dilution and no hemagglutination could be registered. the (+) symbol means that apoptosis was observed with hoechst- staining though the productive replication and production of progeny viruses in human cell lines was generally low, it is evident that viral infection does occur in these cells, even for swine and h n v viruses. it can be demonstrated by the presence of np de novo synthesis and by stimulation of virus-induced apoptosis. in fact, we observe a contradiction: avian influenza viruses actively reproduce in human cell lines, but we do not see their vast spreading in human population, while h n v viruses that hardly replicate in all human cultures tested have caused the latest pandemic. influenza viruses continue to cause problems globally in humans and their livestock, particularly poultry and pigs, as a consequence of antigenic drift and shift, resulting frequently and unpredictably in novel mutant and reassortant strains, some of which acquire the ability to cross species barriers and become pathogenic in their new hosts. long-term surveillance of influenza in migratory waterfowl in north america and europe have established the importance of anseriformes (waterfowl) and charadriiformes (gull and shorebird) in the perpetuation of all known subtypes of influenza a viruses. the available evidence suggests that each of the hemagglutinin (ha) and nine neuraminidase (na) subtype combinations exist in harmony with their natural hosts, cause no overt disease, and are shed predominantly in the feces. , in this study we determined the subtypes and prevalence of low-pathogenic influenza a viruses present on the territory of kazakhstan in - and further analysed the ha and na genes of these isolates in order to obtain a more detailed knowledge about the genetic variation of influenza a virus in their natural hosts. (institute for biological safety problems, gvardeiskiy, zhambyl oblast, kazakhstan)). samples that were identified as influenza a virus positive by matrix rrt-pcr were thawed, mixed with an equal volume of phosphate buffered saline containing antibiotics (penicillin u ⁄ ml, streptomycin mg ⁄ ml, and gentamicin lg ⁄ ml), incubated for minutes at room temperature, and centrifuged at g for minutes. the supernatant ( ae ml ⁄ egg) was inoculated into the allantoic cavity of four -day old embryonated hens' eggs as described in european union council directive ⁄ ⁄ eec. embryonic death within the first hour of incubation was considered as non-specific, and these eggs were discarded. after incubation at °c for days the allantoic fluid was harvested and tested by haemagglutination (ha) assay as describe in european union council directive ⁄ ⁄ eec. in the cases where no influenza a virus was detected on the initial virus isolation attempt, the allantoic fluid was passaged twice in embryonated hens eggs. the number of virus passages in embryonated eggs was limited to the maximum two to limit laboratory manipulation. a sample was considered negative when the second passage ha test was negative. the subtypes of the virus isolates were determined by conventional haemagglutination inhibition (hi) test and neuraminidase inhibition (ni) test, as describe in european union council directive ⁄ ⁄ eec. rna extraction and pcr with specific primers rna was extracted from infective allantoic fluid using rneasy mini kit (qiagene, gmbh, germany) according to the manufacturer's instructions. the rna was converted to full-length cdna using reverse transcriptase. the rt mix comprised ae ll of dmpc water, ll of · first strand buffer (invitrogen), ae ll of mm dntp mix (amersham biosciences), ll of mm uni primer, u of rnaguard (amersham biosciences), u of mmlv reverse transcriptase (invitrogen) and ll rna solution in total volume of ll. the reactions were incubated at °c for minutes followed by inactivation of the enzyme at °c for min. pcr amplification with ha and na gene specific primers was performed to amplify the product containing the full length ns gene. twenty-five microliter pcr-mix contained · platinum taq buffer (invitrogen), lm dntp, ae mm mgcl , nm each of fw primer and rw primer, u platinum taq dna polymerase (invitrogen) and ll cdna. reactions were placed in a thermal cycler at °c for min, then cycled times between °c seconds, annealing at °c for seconds, and elongation at °c for seconds and were finally kept at °c until later use. sequences of the purified pcr products were determined using gene specific primers and bigdye terminator version ae chemistry (applied biosystems, foster city, ca), according to the manufacturer's instructions. reactions were run on a abi tm dna analyzer (applied biosystems). sequencing was performed at least twice in each direction. after sequencing, assembly of sequences, removal of low quality sequence data, nucleotide sequence translation into protein sequence, additional multiple sequence alignments, and processing were performed with the bioedit software version ae ae ae with an engine based on the custal w algorithm. the phylogenetic analysis, based on complete gene nucleotide sequences were conducted using molecular evolutionary genetics analysis (mega, version ae ) software using neighbor joining tree inference analysis with the tamura-nei c-model, with bootstrap replications to assign confidence levels to branches. [ ] [ ] [ ] [ ] ha and na sequences obtained from genbank the ha and na gene was analyzed both with selected number of influenza isolates and in comparison with virus genes obtained from genbank were used in phylogenetic studies [ ] . the nucleotide sequence data obtained in this study has been submitted to the genbank database and is available under accession numbers fj , fj ae , fj , fj , gu -gu for ha and fj , fj ae , fj , fj , gu -gu for na. avian influenza prevalence in our study h , h , and h influenza a virus subtypes were found to circulate at the same time, in the same geographic region in the kazakhstan. this finding most likely indicates the existence of a large reservoir of different influenza a viruses in kazakhstan. we analyzed the ha and na gene sequences of the eight influenza a viruses isolated in kazakhstan together with selected number of isolates, reported between year to , and previously published in the genbank. phylogenetic analysis of the h ha gene showed that all viruses separated into the american and eurasian lineages ( figure ). an evolutionary tree suggests that north american isolates have diverged extensively from those circulating in other parts of the world. geographic barriers which determine flyway outlay may prevent the gene pools from extensive mixing. the lack of correlation between date of isolation and evolutionary distance suggests that different h ha genes co circulate in a fashion similar to avian h ha genes and influenza c genes, implying the absence of selective pressure by antibody that would give a significant advantage to antigenic variants. analysis of phylogenetic relationships among the ha ha genes reported in this study clearly shows that viruses belong to the western pacific flyway, one of the major migratory flyways in this region that have subsequently spread throughout eurasia. these findings provide further evidence of the dynamic influenza virus gene pool in this region. along the western pacific migratory flyway, the influenza virus gene pool in the domestic waterfowl of southern china has 'mixed' longitudinally with viruses isolated from japan, mongolia, and siberia. however, it appears that there has also been 'mixing' latitudinally through overlapping migratory flyways, thereby facilitating interaction between the influenza virus gene pool in domestic waterfowl in the eastern and western extremities of the eurasian continent. this helps to explain the latitudinal spread of the qinghai-like (clade ae ) h n virus in the last years, while h n outbreaks in korea and japan may represent the longitudinally transmitting pathway. ha of subtype h so far has been found exclusively in shorebirds, such as gulls, and in a pilot whale (potentially a spillover from shorebirds), but not in other avian species that are natural hosts of influenza a virus, such as ducks and geese; therefore the study of the evolution of these viruses is very interesting. phylogenetic analysis h ha gene revealed three significantly different evolutionary lines: an american line, a european line, and a line comprising the isolates from america and eurasia. further we analyzed na genes of influenza viruses (figure ) . the na gene is important both because of its functional role in promoting the dissemination of the virus during infection, and because, like ha, it is a principal target of the immune system. it was shown that phylogeny of na genes of influenza have the same properties as hemagglutinin. na genes of kazakhstanian viruses belong to eurasian lineage of virus evolution. obtained data are important for surveillance and diagnostics because some of the lpai viruses examined in this study can infect and be shed by chickens and turkeys and may have epidemiology potential during further recombination with other influenza viruses. influenza virus is divided into different subtypes based on hemagglutinin (ha) and neuraminidase (na) on the virus surface. within each subtype, ha continues to mutate and produce immunologically distinct strains, as antigenic drift. the continuous mutation of influenza virus (iv) is important for annual epidemics and occasional pandemics of disease in humans. antigenic drift requires vaccines to be updated to correspond with the dominant epidemic strains. in humans, ivs show both antigenic drift frequently. in contrast, ivs from birds are in evolutionary stasis, and they show little amino acid changes. , the reason is that ivs in bird intestine are not subjected to strong immune selection. hemagglutinin (ha) gene of influenza a virus encodes the major surface antigen, which is the target for the protective neutralizing antibody response that is generated by infection or vaccination. in humans, influenza a viruses show antigenic drift with amino acid changes in the globular head of the ha so as to evade herd immunity of the population. on the contrary, avian influenza a viruses show evolutionary stasis in wild birds. h aivs have occurred frequently in chicken farms in the world. although vaccination is not permitted, h n aivs have circulated in taiwan for a time. the seroprevalence in chicken flocks reaches about % in the field. h n aivs invades internal organs, such as kidney and lung. thus, viruses in chicken flocks are pressured into antibody selection. here, we report that h n aivs in the field have showed evolutional changes instead of evolutional stasis. in response to requests from poultry farmers for diagnostic investigations of illness in poultry flocks, the authors did necropsy at the pen-site. after careful examination, tracheae were taken and kept in cold for virus isolation in the laboratory. for avian influenza virus isolation, trachea was homogenized : in tpb with antibiotics. the homogenate was frozen and thawed three times and then centrifuged at g for minutes. the supernatant was passed through a ae lm filter. the homogenate was examined for the presence of virus by inoculation into five -to -day-old specific-pathogen-free (spf) chicken eggs for two passages. thirteen h n aivs were isolated in this laboratory during and from different parts of taiwan. besides the viruses isolated in this laboratory, the ha sequences of chicken h n aivs were from the genbank. the accession numbers of hemagglutinin of aiv reference strains included in this study were as the following: g ⁄ , dq ; g ⁄ , dq ; ⁄ , dq ; na ⁄ , dq ; ⁄ , dq ; ⁄ , dq ; ns ⁄ , dq ; sp ⁄ , dq ; ⁄ , dq ; ⁄ , dq ; ⁄ , dq ; ⁄ , dq ; ⁄ , dq ; ⁄ , dq ; pf ⁄ , dq ; pf ⁄ , dq ; pf ⁄ , dq ; a ⁄ , dq ; ⁄ , dq ; ⁄ , dq ; ⁄ , dq ; ⁄ , dq ; ⁄ , dq ; ch ⁄ , dq ; ⁄ , dq ; a ⁄ , dq and ⁄ , dq . the viruses isolated were propagated in the allantoic cavities of -day-old embryonated spf eggs for hour. the virus rna was extracted using qiaamp viral rna miniprep kit (qiagen) . six-week-old balb ⁄ c mice were injected emulsion intraperitoneally with lg of purified and concentrated a ⁄ chicken ⁄ taiwan ⁄ v ⁄ (h n ) virion with complete freund's adjuvant. every two weeks, the mice were boosted supplementary five times with lg of virion in incomplete freund's adjuvant. when the mice were boosted, blood was collected from tail vein and tested by the western blot assay to check the antibody titers. the mice were then injected intraperitoneally with lg of virion at week . five days after the last injection, the splenocytes in the mice were fused with myeloma cells (sp ⁄ -ag ). one week before fusion, the myeloma cell line was expended in dmem medium (hyclone laboratories, logan, ut) with % fetal bovine serum at °c to ensure they were in the exponential growth phase. the spleen cells from immunized mice were washed, harvested, and mixed with the previously prepared myeloma cells and fused by gradually adding % polyethylene glycol- . the resulting pellet was plated into well tissue culture plates. only the fused cells grew in medium with hypoxanthine-aminopterin-thymidine (hat). with fresh medium replacement over weeks, the hybridomas were ready for screening. hightiter monoclonal antibody (mab) preparations were obtained from the ascetic fluid of mice injected with the selected hybridoma clones. the antibody from mouse ascetic fluids was purified by precipitation with ammonium sulfate, then aliquoted and frozen at ) °c, avoiding repeated freezing and thawing. eventually, six mabs were obtained and named ch -d , eb -b , eb -e , eb -f , ff -f , and ff -f , respectively. the hi test was performed following a standard method. all the viruses were diluted twofold and reacted with % chicken erythrocytes in the v-bottomed microtiter plate by the hemagglutination test. after agglutination, four hemagglutinating units of a ⁄ chicken ⁄ taiwan ⁄ v ⁄ (h n ) and ascetic fluids from the immunized mice of the six mabs were prepared for hi test. hi titers of or more were regarded as positive. the cases submitted for diagnosis from chicken farms had respiratory signs, increase in mortality, or drop in egg production (e.g. egg production dropped from % to %). the extent of drop in egg production depended on the chicken ages. for example, the age of case was weeks, a stage of increasing egg production. however, after h n aiv infection, the egg production decreased % instead of increasing and then stayed at % for a week. the infected chickens showed signs of decreasing activity, anorexia from g per bird to g per bird, and respiratory signs. case showed infection in the second floor first and then transmitted to third and fourth floor, indicating that the virus transmitted by air or human movement. however, most cases showed air borne transmission from one flock to another in spite of enforcing restrictions of persons entering the poultry pens and changing clothes and booths. in most cases, males' mortality was higher than that of female pen mates. by comparing the sequences of ha of those h n viruses, we found that amino acid changes in ha were higher than those in ha , showing that antigenic changes on the globular head of ha molecule rather than randomly on the whole ha protein, indicating that h n viruses in taiwan had been selected in the presence of antibody pressure. the aa residues and changes that showed yearly trends were the followings: a- s, i s, v i, n s, e k, l m, e d, q k, a v, or t, s n, s r, k n, y d, n t, s i, g d, l v, i v, g e, t n, g s, a v, k e, d n, i m, and m i. however, their significance on antigenic variation was previously unknown. by hemagglutinination inhibition (hi) assays, except mab ch -d , all other monoclonal antibodies elicited from v ⁄ showed different hi titers with the different h n viruses (table ). however, those mabs showed negative hi to and , the early h n strains. this indicated that the epitopes recognized by those mabs were undergoing antigenic drift. introduction aquatic birds are recognized as the natural reservoirs of the influenza a virus as all known subtypes (h -h , n -n ) have been found in them. phylogenetic analyses of influenza viruses found in other animals revealed that all were directly or indirectly derived from viruses resident in aquatic birds. however, the prevalence, movement, and evolutionary dynamics of influenza viruses in these avian hosts have not been well defined. southern china was hypothesized to be an 'epicenter' for the generation of human pandemic influenza viruses as all major influenza pandemic viruses in the th century emerged from this region. the ecological background that facilitates the occurrence of these pandemic influenza strains has not been fully explored. in the past two decades, four lineages, belonging to h n , h n , and h n viruses, have become established and long-term endemic in different types of poultry in this region. [ ] [ ] [ ] some of these viruses were disseminated to many countries in eurasia and africa and have continued to cause sporadic human infection, posing a persistent pandemic threat to the world. in the mean time, the endemic influenza lineages have undergone extensive genetic reassortment events giving rise to many variants, dramatically increasing the genetic diversity of the influenza virus in this region. questions remain as to how and where these viruses emerged, and what were the sources of the gene segments incorporated within the novel reassortant variants of the h n , h n , and h n virus lineages. to address these questions, surveillance of influenza in migratory and domestic (sentinel) ducks has been conducted since at poyang lake, the biggest fresh-water lake and the major migratory bird aggregation site in southern china. the aim of this study is to identify the prevalence, seasonality, and movement of virus between migratory and domestic ducks. migratory ducks were captured during over-wintering, from november to march. cloacal swabs and blood samples were collected from each individual bird. all birds were released after sampling. to observe the interaction between migratory ducks and domestic birds, we also sampled domestic ducks from two duck farms (designated as sentinel ducks) surrounded by rice fields and inaccessible to other types of poultry, but accessible to migratory birds. that is, the sentinel ducks share the same water body with migratory ducks and have the chance to spread viruses to each other. for sentinel ducks, sampling was conducted fortnightly, all year-round, on the two farms from august onwards. cloacal swabs and fresh fecal droppings were taken. about birds were randomly sampled fortnightly from these farmed ducks. all swabs were soaked in vials containing ae ml transport medium with antibiotics and kept on ice-packs during sampling and immediately stored in ) °c freezers for further use. blood samples from migratory ducks were treated according to methods previously described. serological survey and virus subtyping in migratory and sentinel ducks used hemagglutination inhibition (hi) and neuraminidase inhibition (ni) tests as previously described. for isolates that were not identified by reference antisera, subtypes were determined by rt-pcr using subtype specific ha and na diagnostic primers. prevalence and seasonal patterns of influenza virus in migratory and sentinel ducks during during - a total of cloacal swabs from migratory ducks and cloacal or fecal swabs from sentinel ducks were collected at poyang lake. from these specimens, influenza isolates were obtained from migra- tory ducks and from sentinel ducks; isolation rates of ae % and ae %, respectively (table ) . it was noted in sentinel ducks that virus occurrence formed a seasonal peak from november to february, which completely overlapped the over-wintering months of migratory ducks. this suggests that virus movement or transmission between migratory and sentinel ducks occurred during this period at poyang lake. thirty positive samples (hi titer ‡ ) were identified from blood samples collected during november and december in . among these, samples were positive to h , were positive to h , were positive to h , and were positive to h . one serum sample was positive to both h and h , which suggested co-infection of influenza virus in migratory ducks might occur in natural conditions. poyang lake, which is located in the northeastern part of jiangxi province, is the largest freshwater lake in china and is part of the eastern asia-australia migration route. every year, hundreds of thousands of migratory ducks congregate at poyang lake during the migration season. recent farming practice involves raising domestic waterfowl in dense populations in the poyang lake region. farmraised domestic waterfowl are allowed to feed in and share the same water body with migratory birds, thereby facilitating direct interactions between domestic waterfowl and freeranging migratory birds. this makes poyang lake an ideal site to observe the dynamics of influenza virus interactions between migratory and sentinel ducks in southern china. in our longitudinal surveillance during [ ] [ ] [ ] [ ] [ ] [ ] , the overall virus isolation rate from migratory ducks was less than %, which suggests a low prevalence of viral infection during the birds' southern migration. similar results have been observed in taiwan, which is also an important stopover site for migratory birds along the eastern asia-australia migration route during years of surveillance. the overlap in seasonal patterns of virus infection between migratory and sentinel ducks found in our study suggests that virus movement or transmission between migratory and sentinel ducks occurred during the period of time migratory birds were at poyang lake. the ha subtypes harbored in migratory and sentinel ducks were similar in our study. for migratory ducks, h , h , h were the predominant subtypes, while h , h , and h were the major subtypes in sentinel ducks. hpai h n was only detected from migratory ducks in early on two sampling occasions. from phylogenetic analyses the h n viruses isolated from migratory ducks were closely related to the viruses endemic in domestic poultry in southern china. therefore, it appears that h n viruses endemic in domestic poultry could be transmitted to migratory ducks via close contact in southern china. only lp h viruses were detected from sentinel ducks at poyang lake during this period. whether h n virus infection was absent from sentinel ducks at poyang lake needs further investigation. serological surveys provided further evidence for the prevalence of aiv in migratory ducks at poyang lake. the serological results in did not match well with the epidemiological results during [ ] [ ] [ ] [ ] [ ] [ ] , which suggests that influenza virus infection in migratory birds could be influenced by multiple factors, such as host immune status, population size, spatial and temporal variations, and migration routes. southern china has the biggest domestic duck population in the world. our study demonstrates that dynamic interactions between migratory ducks and sentinel ducks occurred frequently throughout the surveillance period. thus, sentinel ducks could be treated as intermediate hosts between the ''real gene pool'' from migratory ducks and domestic poultry in the whole influenza virus ecosystem. a sentinel duck sampling system may be a feasible method to represent the viruses in the natural gene pool and a baseline for virus or gene interactions between migratory and domestic ducks. further investigations and surveillance are required to better understand the role of the domestic duck population in facilitating virus interactions and the generation of genetic diversity. two distinct lineages of h n influenza viruses represented by a ⁄ chicken ⁄ beijing ⁄ ⁄ (ck ⁄ bei-like) and a ⁄ quail ⁄ hong kong ⁄ g ⁄ (g -like) have become established and endemic in poultry in southern china. these established h n lineages continue evolving to generate many different reassortant variants (or genotypes) , and are causing sporadic cases of human infection. , studies of h n viruses isolated from pigs in hong kong and shandong province have also raised the possibility of reassortment with human-like viruses from pigs. , in addition, h n viruses isolated beyond the late s had preferential binding with a- , -neuacgal human-like receptors. these observations suggest that the h n influenza viruses still have pandemic potential. unlike highly pathogenic h n influenza viruses that have been rarely detected in the live-poultry markets in hong kong since , h n viruses are still frequently isolated in our surveillance program. therefore, we try to understand the continuing evolution of h n viruses through genetic characterization and phylogenetic analyses of the viruses isolated in hong kong live-poultry markets from to . a total of terrestrial poultry were sampled at different live-poultry markets in the hong kong sar between january and december . of those samples, were from chickens and the others were from minor poultry species including chukar, pheasant, guinea fowl, silky chicken, and pigeon. fecal droppings, cloacal and tracheal swabs, drinking water, and environmental samples from cages were collected into transport medium. viruses were isolated in -to -day old embryonated eggs as described previously. virus isolates from positive sampling occasions were selected for sequence analysis. rna extraction, cdna synthesis, and pcr were carried out as described previously. dna sequencing was performed using bigdye terminator v ae cycle sequencing kit on an abi dna analyzer (applied biosystems) following manufacturer's instructions. all sequences were assembled and edited with lasergene ae (dnastar, madison, wi) software. sequence alignment and residue analysis were performed with the bioedit sequence alignment editor, version ae . all eight gene segments of sequenced viruses were characterized and analyzed phylogenetically together with virus sequence data available in public databases. maximum-likelihood trees were constructed using garli ae . estimates of the phylogenies were calculated by performing neighbor-joining bootstrap replicates using paup* ae . systematic surveillance of live-poultry in hong kong from to resulted in h n isolates from samples (overall isolation rate, ae %) ( table ). there were strains isolated from chicken samples (isolation rate, ae %). of these viruses, four were isolated from tracheal swabs (isolation rate, ae %), while isolates were isolated from cloacal or fecal swabs (isolation rate, ae %). an additional isolates were collected from drinking water samples (isolation rate, ae %). there were strains of h n viruses isolated from minor poultry samples (isolation rate, ae %) ( table ) . of these viruses, only one was isolated from tracheal swabs (isolation rate, ae %), whereas strains of viruses were isolated from cloacal or fecal swabs (isolation rate, ae %). the isolation rate in drinking water in minor poultry was again higher when compared with other sampling methods with strains isolated from drinking water samples (isolation rate, %). taken together, these findings suggest that the h n viruses mainly replicated in the intestinal tract of chickens and minor poultry species. also, the high isolation rate in drinking water samples could be a sensitive indicator for monitoring the prevalence of h n viruses in the field. to better understand the evolutionary pathway of h n viruses in southern china, representative viruses, isolated from hong kong live-poultry markets from to , were sequenced and genetically characterized. phylogenetic analysis of the h ha gene revealed that ck ⁄ bei-like viruses were predominant and one chicken isolate had a g -like ha gene ( figure ). this is the first time the g like h ha gene has been detected in chickens from livepoultry markets in hong kong. the ck ⁄ bei-like lineage is further divided into two subgroups as previously described. subgroup is represented by qa ⁄ st ⁄ ⁄ and subgroup is represented by dk ⁄ hk ⁄ y ⁄ . all h n viruses in this study belonged to subgroup of the ck ⁄ bei-like lineage except for the virus with the g -like ha gene. phylogenetic analysis of the na gene also showed a similar evolutionary pattern to the ha gene with all viruses clustered within the ck ⁄ bei-like lineage. these results revealed that ck ⁄ bei-like viruses are predominant in both chickens and minor poultry. all of the pb , pa, np, ns and m genes clustered with those of h n lineage viruses previously prevailing in ter- restrial poultry in southern china. phylogenetic analysis of the pb gene revealed three different lineages; g -like (n = ), ck ⁄ sh ⁄ f ⁄ -like (n = ), and unknown avian (n = ). the sh ⁄ f ⁄ -like lineage (or f ⁄ -like) was previously reported in eastern china and was used previously for vaccine production in an intensive vaccination program. this pb gene lineage was also distinguishable from the ck ⁄ bei-like lineage and its presence in the viral genome may be due to reassortment between the vaccine strain and field isolates, followed by selective establishment in terrestrial poultry. gene constellation analyses of the viruses revealed six genotypes. thirty-four of the viruses analyzed belonged to two genotypes, b and b , which were also the prevailing reassortants found in other provinces in southern china since . the remaining sixteen viruses belonged to four novel genotypes that have not been identified before in this region. characterization of h n influenza viruses isolated from live poultry in hong kong markets from a year surveillance program revealed that ck ⁄ bei-like viruses were predominant in southern china and were continuing to evolve. two recognized and four novel genotypes were identified in this study. one characterized virus, ck ⁄ hk ⁄ nt ⁄ , had a g like ha gene (the first time this has been detected in hong kong poultry markets) that showed a close relationship with two human h n strains isolated in . g -like viruses were usually detected and caused outbreaks in chickens of middle eastern and european countries, [ ] [ ] [ ] and minor poultry, mainly quail, in southern china. whether the g -like virus was transmitted from china to middle eastern and european countries, as the highly pathogenic h n virus did in the last five years, or vice versa, is still unknown. since the ck ⁄ hk ⁄ nt ⁄ strain clustered with other g -like strains isolated previously in minor poultry in southern china, the g -like viruses in chicken may be due to interspecies transmission from minor poultry species. genetic studies demonstrated that reassortants with genotypes b and b persistently occurred in either chickens or other minor poultry species from to . other genotypes that were prevalent in southern china might be being gradually replaced and four novel genotypes were identified in this study. these novel genotypes were generated through reassortment of viruses with different lineages. a newly emerged f ⁄ -like lineage originating from eastern china is responsible for generation of some of the novel genotypes found in this study. the ck ⁄ bei-like lineage is gradually being replaced by f ⁄ -like lineages which are becoming dominant in northern and eastern china. , animal experiments have also demonstrated that f ⁄ -like viruses are more effective in replication and transmission in chickens compared with ck ⁄ bei-like viruses. since the f ⁄ -like lineage of the pb gene has been introduced into southern china, this newly emerged lineage may have a higher tendency to replace the rnp genes in the circulating ck ⁄ bei-like viruses and subsequently become the endemic virus in terrestrial poultry. in vietnam, the modelling of the pandemic h n progression estimates that ( - ) pigs might be exposed to the virus on the basis of cases among swine owners ( - ). a poor level of biosecurity, high animal densities, and a mix of species could increase the risk of influenza virus flow, persistence, and emergence on swine and poultry farms. this study was set up in the red river delta, where a third of the national pig husbandry is produced. the aims are to give preliminary information of the epidemiological state of swine influenza and in order to further assess the risk of infection of swiv, through cross-species transmissions from poultry to pigs. this paper will present the preliminary results on swiv and the risk factors of pig seropositivity in vietnam. a cross-sectional study was conducted in two provinces of the red river delta in april . pig farms were randomly selected from nine communes representative of at risk area of avian h n . in each farm, pig and poultry were sampled and collected to virological and serological analyses. interviews were conducted in all farms by trained interviewees. questionnaires included closed and open questions on ª blackwell publishing ltd, influenza and other respiratory viruses, (suppl. ), - livestock husbandry ⁄ management and household characteristics, such as herd size and structure, health history and vaccination, pig housing, watering and feeding system, reproduction, purchasing of animals, biosecurity measures, pig contact with poultry, and environmental factors. the virological detection assay was performed on pools of nasal swab specimens from pigs. we investigated whether real-time rt-pcr assay could detect gene m on pools of nasal swab specimens before attempting virus isolation from individual nasal swab specimens. the poultry and pig sera were tested against influenza type a with an enzyme-like immunosorbant assay (elisa) competition test idvetª. this commercial kit is designed to specifically detect antibodies directed against the np protein antigen of influenza type a viruses. the positive serum samples were examined in hemagglutination inhibition (hi) to determine antibody titers and subtypes. the hi test was tailored for h , h , and h subtypes in pigs and h and h subtypes in poultry. seroneutralization tests by pseudo particles were used to test the presence of antibodies directed against h subtype. we analysed the data for relationships between influenza a serological status (the outcome variable) and possible risk factors using r version ae ae (r development core team). the statistical unit was the individual. initially, the quantitative variables were encoded into categorical variables according to the quartiles or median. descriptive statistics (e.g., means or medians, proportions, standard deviations) were calculated for all herd-level and commune level predictors to assist in the subsequent modeling process. we also performed the independence test among all variables to determine if variables were dependant. then, univariate analysis of potential risk factors for the pigs being positive for swiv and estimation of odds ratios were performed using generalised linear mixed models with binary outcome and logit link function for each herd-level and commune-level variable to determine which variables were individually associated with influenza a seropositivity at a significance level of p < ae . herd and commune of residence were included as a random effect to account for the correlation of observations at the herd level. the third stage of the analyses included the four herdlevel variables found to be significantly (p < ae ) associated with influenza a seropositivity. an automatic process using all possible associations between the selected variables was computed into a mixed logistic regression models, with random effects. when two variables were collinear, as determined before, only one variable was likely to enter the multivariable model, and therefore, the selection of which collinear variable to enter the model was guided by biological plausibility and statistical significance. all of the pools of nasal swabs were rt-pcr negative. the maximal possible prevalence considering perfect diagnostic tests would be of ae % at a confidence level of %, in an infinite population within these regions (win-episcope ae ). six hundred-and-nine pig sera were tested in nonvaccinating farms. the herd seroprevalence of swine influenza in the commune previously infected by the avian h n in the red river delta raised by ae % [ ae ; ae ] in april . but among seropositive farms, only four had at least two seropositive pigs. the within-herd seroprevalence is very low, and no seropositivity was detected in the majority of farms. estimates had large confidence intervals due to small sample sizes. the individual seroprevalence raised ae % [ ae ; ae ]. the subtyping of seropositive sera is still in process. descriptive statistical analyses on five major risk factors of swiv: farm size, breeding vs. fattening, purchasing, percentage of family income, and poultry production, were conducted. based on this analysis, three types of farming systems were identified and included in mixed models ( table ) . percentage of family income by pig production and poultry production were not differentiating factors for this typology. whereas types and seem to be specialized in fattening, the type produces and might sell piglets on the farm site. the exploration of the different variance components indicated that the random effect variances were mainly associated with the herd, while the commune did not seem to have any effect. therefore we included in all models only the herd as a random effect. the random effect term for herd was modelled, assuming a normal distribution with a table . typology of farming system type : large fattening farms largest scale production, with more than pigs per year specialized in fattening, and purchase more than pigs per year type : small fattening farms small scale of production, with less than pigs per year specialized in fattening, and purchase less than pigs per year type : medium breeding-fattening farms medium scale of production, with less than pigs per year breeding and fattening piglets, with rare purchase common variance [$n( ,r herd)]. the univariate analyses were conducted on variables and typology variables, with herd as random effect. some coefficient or confidence intervals were inconsistent because of small effectives, especially for the percentage of self-product culture or the pig freegrazing because of the lack of positive results in the dataset. the only one significant (p value < ae ) parameter was the percentage of pig sales in the familial annual income. surprisingly, common risk factors of swine influenza infection, such as farm size, animal movements, and sanitary parameters got low odds ratio individually (without being significant); the typology provides the hypothesis of complex interactions effects that increase the risk of infection. as shown in table , the farming system type got a higher seroprevalence of ae % [ ae - ae ] and a higher risk indicator, with or = ae (p-value = ae ) in comparison with type . this finding was not significant. in the multivariate mixed model, the percentage of familial income provided by pig production was the only one significant variable, with or = ae [ ae - ae ]. the focus on diseased animals in the winter-time is usually required in order to increase the likelihood to isolate the virus, although the isolation rate on healthy or clinical samples never exceed %. the season and the lack of disease reports might explain the difficulties to detect influenza viruses. additionally, the pooling method tends to decrease the isolation rate because of a dilution effect, potential presence of pcr assay inhibitors, or uneven distribution of virus in the sample. our seroprevalence results must be confirmed and the subtypes identified, especially because we found only one positive animal in a few farms that could be attributed to false positive results of the elisa test (performances are not known). these preliminary results are in favor of a virus circulation at low level in the spring, but must be completed by further surveys in the winter and before the new year (têt celebration) when pig production, trade, and movement increase at their maximum. no clear prior information on the expected prevalence of swine influenza in vietnam, tests sensitivity, and speci-ficity could be obtained from literature or reliable sources. bayesian methods will be carried out in the future in order to compute prevalence and ⁄ or to estimate the probabilities of freedom. the risk factors analysis was limited by the lack of positive results. further studies are necessary to identify the at-risk season and type of farming systems at risk of swine influenza infection. however, this investigation of risk factors leads to the hypothesis that medium size breeding-fattening farms had a higher risk than large or small size fattening farms. further investigation are needed to precise this typology. the risk of swiv infection increases with a combination of three major factors. poultry production does not seem to play any role on swine infection. the generalized linear mixed model afforded to take into account all the non investigated parameters at the herd level. although we investigated the most common risk factors of swine influenza infection covering different kind of fields, the herd random effect might explain risk variations. mixed models have become a frequently used tool in epidemiology. due to software limitations, random effects are often assumed to be normally distributed. since random effects are not observed, the accuracy of this assumption is difficult to check. further studies, such as case-control or cohort studies could help to identify more precisely risk factors of swine influenza seropositivity, as these study designs are more adapted than cross-sectional studies. the concept that swine are a mixing-vessel for the reassortment of influenza viruses and for the emergence of pandemic influenza viruses has been re-enforced by the emergence of the recent pandemic. the pandemic h n virus of (h n pdm) is believed to have emerged through the reassortment of north american triple reassortant and eurasian avian-like swine influenza viruses. since the immediate precursor of this pandemic virus has not yet been identified, it is not possible to be definite whether the reassortment leading to the pandemic occurred in swine, but swine influenza viruses are the nearest known ancestors of each gene segment of h n pdm. , the mechanisms of pandemic emergence are not clear. it is believed that the pandemics of and arose through reassortment of the pre-existing human seasonal influenza virus with avian influenza viruses, and swine have been proposed to be a possible intermediate host where such reassortment between human and avian viruses may take place. the pandemic was the first to arise for over years and the first to occur after the understanding that pandemics arise from animal influenza viruses. systematic studies of influenza virus ecology and evolution in swine are, therefore, important in order to understand the dynamics of pandemic emergence. furthermore, since swine are the likely host within which h n pdm virus originated, it was predicted that this virus would readily infect swine and may reassort with endemic swine influenza viruses. these predictions have now been confirmed with reports of h n pdm being detected in pigs in many countries and reassortment with endemic swine influenza virus being confirmed. while h n pdm has been genetically and antigenically stable in humans, reassortment between h n pdm, which is well adapted to transmission in humans, and other avian or swine viruses may lead to the origin of novel viruses posing a threat to public health. in addition to endemic swine virus lineages, avian influenza viruses such as h n and highly pathogenic avian influenza (hpai) h n have also been occasionally identified in pigs in parts of asia. , it has been shown that h n pdm readily reassorts with h n to generate viable progeny in vitro. it is therefore essential to monitor the ecology, evolution, and biological characteristics of swine influenza viruses so that their continued evolution and zoonotic and pandemic potential can be monitored. there is however, a paucity of surveillance data on swine influenza viruses worldwide. this is in part related to the negative commercial consequences that may arise from detection of influenza in a swine herd leading to a major economic loss to the producer. here we outline a surveillance system that has been in place in hong kong for the last decade, based on sampling animals arriving at an abattoir in hong kong. we demonstrate the feasibility of such surveillance in an abattoir setting and compare methods used for detection influenza viruses in swine. virus isolation was carried out by inoculation into mdck cells and by allantoic inoculation in embryonated eggs as previously described. virus isolates were subtyped by haemagglutination inhibition tests using specific antisera and genetically characterized by sequencing and phylogenetic analysis of the haemagglutin gene. , virus detection by rt-pcr a subset of recent specimens was tested in parallel by real time pcr using the biorobot universal system (qiagen) that enables fully-automated viral nucleic acid extraction and downstream reaction setup in a -well plate format. total viral nucleic acids were extracted in a -well plate format with the qiaamp virus biorobot mdx kit (qiagen) on the biorobot universal system (qiagen) according to the manufacturer's instructions. briefly, ll of sample was lysed in ll buffer al, supplemented with ae lg carrier rna in a s block (qiagen), which placed the samples into a well plate format. after protease digestion, samples were transferred to silica based membrane in well plate format for binding. following two washing steps, rna was eluted in ll of elution buffer (buffer ave) into a well elution microplate cl (qiagen) . for the synthesis of cdna, ll of purified rna was used in a ll reaction containing ll of · buffer, ae nm of each deoxynucleotide triphosphate (dntp), mm dithiothreitol, lg random primer, u of rnaseout recombinant ribonuclease inhibitor, and u of superscript iii reverse transcriptase (all from invitrogen). reactions were performed in the geneamp thermocycler (applied biosystems) with the following parameters: minutes at °c, minutes at °c, and soak at °c. subsequent to the reactions, ll of cdna was diluted ⁄ by adding ll of ae buffer (qiagen) . real-time pcr was performed using the power sybrÒ green pcr master mix (applied biosystems) according to the manufacturer's instructions. briefly, ll of ⁄ diluted cdna was amplified in a ll reaction containing ae ll of · power sybr green pcr master mix, nm of forward primer m c ( ¢-ctt cta acc gag gtc gaa acg- ¢) and nm of reverse primer m r ( ¢-agg gca ttt tgg aca aag ⁄ t cgt cta- ¢). the primers have been designed to amplify the sequences in the conserved region of influenza a virus matrix gene, thereby detecting viruses from different species including swine influenza viruses. real-time pcr was performed in the abi fast system (applied biosystems) with the following cycling conditions: minutes at °c once, seconds at °c, and minutes at °c for cycles, followed by melting curve analysis with seconds at °c, minutes at °c, and seconds at °c. in each assay, serially diluted plasmids containing the full length m gene cloned from a ⁄ vietnam ⁄ ⁄ (h n ) were included as standards to perform absolute quantification. a manual baseline was set from cycles - and a manual cycle threshold (ct) was set at ae . samples that were positive or unequivocal results from the real-time pcr were confirmed by performing gel electrophoresis on the pcr products. positive visual identification was made in the presence of the target pcr product at bp in length. a total of tracheal and nasal swabs were processed during the years january -april and yielded influenza virus isolates, an overall virus isolation rate of ae %. of these, were subtype h (classical swine, eurasian avian-like swine, and triple-reassortant), were human-like h viruses, and were eurasian avianlike swine h n viruses. culture in mdck cells yielded % of h subtype viruses, % of the human seasonal-like h n viruses, and ae % of the avian-like eurasian swine h n viruses. culture in embryonated eggs yielded ae % of the h subtype viruses, % of the human seasonal-like h n viruses, and ae % of eurasian avian-like swine h n viruses ( figure ). tracheal and nasal swabs each gave comparable overall virus isolation rates ( ae %). however, isolation rates for human-like h n viruses were ae fold higher in nasal swabs ( ae % versus ae % respectively; p = ae ) ( figure ) . a parallel evaluation of rt-pcr and culture was carried out in specimens. rt-pcr detected ⁄ ( %) of the culture positive specimens. rt-pcr was also positive in ⁄ ( ae %) culture negative specimens, but all these specimens had very low virus load in the rt pcr tests. virus could not be cultured from these culture negative specimens even by attempts at virus re-isolation from the frozen specimen. surveillance in an abattoir setting provides an acceptable yield of influenza viruses and is a feasible method of swine influenza surveillance. sampling in a large abattoir setting allows surveillance to be carried out anonymously with no negative consequences to the supplier. the supply-chain of pigs to the hong kong abattoir involves pigs being trucked in over long distances and may provide opportunity for virus amplification during transport. thus, virus isolation rates may be lower in more vertically integrated and homogenous production and slaughter systems where less mixing of pigs occurs. our results indicate that mdck cell culture is essential for optimizing virus isolation during swine influenza surveillance. allantoic inoculation of embryonated eggs by itself is sub-optimal for isolation of swine influenza viruses. it is however possible that inoculation of embryonated eggs by the amniotic route may lead to better isolation rates than allantoic inoculation. rt-pcr detection is an alternative method for virus detection. but the additional specimens detected by rt-pcr did not yield culturable virus, even following attempts at re-isolation and sequential passage. the rt-pcr positive ⁄ virus isolation negative specimens had very low virus load, and this may be the explanation for the inability to isolate such viruses. in addition, rt-pcr did not detect all viruses isolated by culture. tracheal and nasal swabs gave comparable isolation rates with the exception of human-like h n viruses which were more frequently isolated from nasal swabs. this may suggest that, in contrast to endemic swine influenza virus lineages, these human-like h n viruses are less adapted to replication in the lower respiratory tract. in summary, collection of nasal or tracheal swabs in an abattoir setting together with virus isolation in mdck cells provides a feasible approach to surveillance of swine influenza viruses. kong, kong, - introduction wild waterfowl are the natural reservoir of influenza a viruses (aiv), and they play an important role in the genesis of pandemic influenza. it is suggested that the pandemic virus was purely derived from avian virus, which adapted to humans and caused efficient human-to-human transmission, while the pandemics of and had acquired the viral haemagglutinin, pb polymerase, and in , the neuraminidase gene segments from the avian gene pool. the major regional outbreaks of highly pathogenic avian influenza (hpai) h n in asia, europe, and africa highlight the potential role played by migratory waterfowl in disseminating highly pathogenic influenza viruses. therefore defining the influenza virus gene-pool in wild birds is of vital importance. surveillance was carried out - times weekly from to during the winter months of october to april in the hong kong mai po nature reserve and lok ma chau, hong kong. the hong kong mai po nature reserve and lok ma chau are along the east asia-australian flyway where a peak of more than ducks and grebes congregate every winter. fecal droppings were collected and transported in vials containing ae ml of vtm, which was prepared from m ( ae g ⁄ l), penicillin g ( · u ⁄ l), polymyxin b ( · u ⁄ l), gentamicin ( mg ⁄ l), nystatin ( ae · u ⁄ l), ofloxacin hcl ( mg ⁄ l), and sulfamethoxazole ( g ⁄ l). an aliquot of ll from each swab sample was inoculated into the allantoic cavity of a -to -day-old chicken embryonated egg, and incubated for days at °c. positive ha isolates were subtyped using standard antisera , and rt-pcr was performed with the used of one-step rt-pcr assay (invitrogen) described earlier, followed by sequencing on abi prism xl dna analyzer. the determination of species of origin was performed by dna barcoding of the mitochondrial cyto-chrome oxidase i gene from dna extracted from the fecal droppings. during the -year surveillance period, a total of influenza viruses were isolated from samples collected, an overall isolation rate of ae %. a total of isolates were obtained from specimens collected during the winter period coinciding with the southern migration of waterfowl along the east asian flyway and one isolate obtained from samples collected in spring during the period when northern migration of waterfowl took place along the east asian-australasian flyway. the isolation in hong kong was slightly lower than a similar study conducted in south korea in which the isolation rate of migratory birds was ae % in - . this suggested a slightly lower prevalence of influenza virus present in hong kong as the birds migrated southwards. the viruses isolated in hong kong, representing hemagglutinin (ha) subtypes of h -h and neuramidinase (na) subtypes of n -n , were all from wild waterfowl ( table ) . out of the twelve ha subtypes isolated, h and h were the two subtypes that were isolated frequently every year for h and in six out of seven years for h , respectively. h and h viruses accounted for ae % and ae % of all virus isolated, respectively. on the other hand, h , h , and h were the least prevalence ( ae %) and were only isolated once in years. of the na subtypes, n and n were isolated most often ( ae % and ae % of all isolates, respectively) and n was the least ( ae %). november was the month that had the highest prevalence of influenza virus ( ae % of samples being positive) compared to only ae % in march. the subtype's variation was the most diverse in december during our years of surveillance. this suggested that more of these wild migratory birds may be carrying influenza virus when they arrive in hong kong. however the continued isolation of viruses suggests continued circulation of these viruses in the vicinity of mai po. the study of dna barcoding for the mitochondrial cytochrome oxidase i gene retrieved from fecal droppings revealed that the isolates originated mainly ( ae %) from birds of the order anseriform, family anatidae including eurasian wigeon, northern shoveler, northern pintail, common teal, and garganey. non-anseriformes which were found to have shed aiv viruses were cormorant, grey heron, and stint. none of the water samples collected from the ponds where these birds congregate were found to be positive for the virus. phylogenetic analyses of the ha gene of the lpai h viruses isolated in this study clustered with that of the other lpai h viruses isolated from hokkaido, mongolia, and siberia and were not closely related to the hpai h n . satellite tracking of eurasian wigeons and northern pintails in dec and revealed their flyway from hong kong to as far north as eastern russia, eastern mongolia, and northern china. no hpai h n viruses were isolated in this study from apparently healthy birds. however, as part of the surveillance of dead wild birds carried out by the department of agricultural, fisheries and conservation of the government of hong kong during this same period, over dead wild birds were tested positive for hpai h n and has been reported elsewhere. our influenza surveillance in hong kong has revealed a diversity of influenza virus subtypes the migratory waterfowl infected within the region. the result of the phylogenetic analysis correlated with the findings from satellite tracking that viruses isolated in hong kong were closely related to those isolated in areas along the migratory route. no healthy bird was isolated with hpai h n, although dead wild birds have been regularly found to have hpai h n virus, suggesting that infected birds might not live for a long period. introduction a novel swine-origin h n influenza virus emerged in mexico in april and rapidly spread worldwide, causing the first influenza pandemic of the st century. most confirmed human cases of h n ⁄ influenza have been uncomplicated and mild, but the increasing number of cases and affected persons worldwide warrant optimal prevention and treatment measures. today, almost all of the pandemic h n ⁄ viruses tested are resistant to m blockers. therefore, only the neuraminidase (na) inhibitors are currently recommended for treatment of this pandemic influenza. for the control of influenza infection, the clinical use of oseltamivir has increased substantially during the pandemic. to date, the majority of tested clinical isolates have remained susceptible to na inhibitors, oseltamivir and zanamivir, but oseltamivir-resistant variants with h y na mutation (n numbering) have been isolated from individuals taking prophylaxis, from immunocompromised patients, and from a few community clusters. , in view of the high prevalence of oseltamivirresistant seasonal h n influenza viruses in - , the isolation of resistant h n ⁄ viruses without known oseltamivir exposure raised great concern about the transmissibility and fitness of these resistant viruses. here we studied the transmissibility of a closely matched pair of pandemic h n ⁄ clinical isolates, one oseltamivir-sensitive and one resistant, in both direct contact and respiratory droplets routes among ferrets. viral fitness was evaluated by co-infecting a ferret with both the oseltamivir-sensitive and -resistant viruses. the viruses were also characterized by full genome sequencing, susceptibility to na inhibitors, and growth in mdck and mdck-siat cells. oseltamivir-resistant influenza a ⁄ denmark ⁄ ⁄ (h n ) virus (a ⁄ dm ⁄ ⁄ ) was isolated from the throat swab of a patient who had influenza-like symptoms and received post-exposure oseltamivir prophylaxis ( mg once daily). wild-type influenza a ⁄ denmark ⁄ ⁄ (h n ) virus (a ⁄ dm ⁄ ⁄ ) was isolated from a patient in the same cluster of infection as the a ⁄ dm ⁄ ⁄ virus. to assess growth kinetics of viruses, confluent mdck or mdck siat cell monolayers were infected with viruses at a multiplicity of infection (moi) of approximately ae pfu ⁄ cell (single-step) or ae pfu ⁄ cell (multi-step). supernatants were collected every h or h p.i. for time points. a modified fluorometric assay using the fluorogenic substrate ¢-( -methylumbelliferyl)a-d-n-acetylneuraminic acid (munana) was used to determine viral na activity. the drug concentration required to inhibit % of the na enzymatic activity (ic ) was determined by plotting the percent inhibition of na activity as a function of compound concentration calculated in the graphpad prism (la jolla, ca) software from the inhibitor-response curve. na enzyme kinetics were determined by measuring na activity every seconds for minutes under the same conditions as above, when all viruses were standardized to an equivalent dose of ae pfu ⁄ ml. the k m and v max were calculated by fitting the data to the appropriate michaelis-menten equations using nonlinear regression in the graphpad prism software. young adult ferrets ( - months of age) were obtained from the ferret breeding program at st. jude children's research hospital. all ferrets were seronegative for influenza a h n and h n viruses and for influenza b viruses. for transmission studies, the donor ferrets were lightly anesthetized with isoflurane and inoculated intranasally with tcid virus in ae ml sterile pbs . after the donor ferrets were confirmed to shed virus on day p.i., each donor was then housed in the same cage with two naïve direct-contact ferrets. two additional recipient ferrets were placed in an adjacent cage isolated from the donor's cage by a two layers of wire mesh (approximately cm apart) that prevented physical contact but allowed the passage of respiratory droplets. ferret weight and temperature were recorded daily for days. nasal washes were collected from donors and recipients on day , , , , , , , and p.i. by flushing both nostrils with ae ml pbs, and tcid titers were determined in mdck cells. serum samples were collected weeks after virus inoculation, and were tested for seroconvention by hi assay. full genome sequencing revealed that the pair of h n ⁄ viruses differed only at na amino acid position , where the pandemic a ⁄ dm ⁄ ⁄ virus had an h y amino acid mutation caused by a single t-to-c nucleotide substitution at codon . the wild-type a ⁄ dm ⁄ ⁄ was susceptible to oseltamivir carboxylate (mean ic : ae nm), but the a ⁄ dm ⁄ ⁄ carrying the h y na mutation had ic values approximately - times of the wild-type viruses (mean ic : nm). the ic of zanamivir was comparable for both viruses and were uniformly low (mean ic £ ae nm). the h y na mutation confers resistance to oseltamivir carboxylate but did not alter susceptibility to zanamivir. to understand the impact of the h y mutation on the na enzymatic properties, na enzyme kinetics was determined. the na of the oseltamivir-resistant virus had a slightly higher k m (mean = lm) and lower v max (mean = u ⁄ sec) than na of the sensitive virus (k m , mean = lm; vmax, mean = u ⁄ sec). the results suggested that the h y na mutation reduced na affinity for substrate and na catalytic activity, although the function of na was not severely impaired. to further evaluate the impact of the h y na mutation on virus growth in vitro, single-and multi-cycle growth studies of both viruses were performed in mdck and mdck-siat cells. in the both single-and multiple-cycle growth curves, the two viruses reached comparable levels eventually, but the initial growth of the resistant virus was significantly delayed by at least - logs in comparison to that of wild-type virus (p < ae ). the donor ferrets inoculated with wild-type a ⁄ dm ⁄ ⁄ or oseltamivir-resistant virus shed virus productively until day or day p.i., with a peak virus titer comparable to that of a ⁄ dm ⁄ ⁄ virus (table ). in a ⁄ dm ⁄ ⁄ virus group, two of direct-contact ferrets the weight loss in ferrets is the maximum percentage loss compared with the initial weight. virus shedding is indicated as number of virus-shedding animals ⁄ total number; mean peak virus titer (log tcid ⁄ ml) in nasal wash samples is indicated in parentheses. serum hemagglutination inhibition (hi) titer to homologous virus in ferret serum was determined on day p.i. duan et al. and of respiratory droplet-contact ferrets were infected through virus transmission, as indicated by the virus titers and inflammatory cell counts in their nasal washes and also by sero-conversion. under identical conditions, in a ⁄ dm ⁄ ⁄ group, only of direct-contact ferrets were infected through virus transmission, but neither respiratory droplet-contact ferrets was infected, as confirmed by the absence of sero-conversion (table ) . virus shedding in the direct-contact ferrets was lower and peaked after a longer interval in this group than in the oseltamivir-sensitive a ⁄ dm ⁄ ⁄ group (table ) , but the resistant viruses appeared to cause a similar disease course in ferrets without apparent attenuation of clinical signs. these results showed that an oseltamivir-resistant h y mutant of pandemic h n virus, a ⁄ dm ⁄ ⁄ virus could be only transmitted efficiently by direct contact. to compare the relative fitness, growth capability, and transmissibility of the sensitive and resistant h n ⁄ viruses within host, a donor ferret was co-inoculated with a : ratio of the sensitive and resistant viruses, and another two naive ferrets were housed with the donor to test direct contact. during co-infection, the pattern of virus shedding and the clinical signs were similar to those in ferrets inoculated with either a ⁄ dm ⁄ ⁄ or a ⁄ dm ⁄ ⁄ virus (table ). in the inoculated donor ferret, the virus population in the nasal washes remained mixed but wild-type viruses outgrew the resistant virus progressively ( figure ). two of direct-contact ferrets were infected through virus transmission, but only wild-type virus was detected in both direct-contact ferrets ( figure ). in summary, oseltamivir-sensitive a ⁄ dm ⁄ ⁄ virus possessed better growth capability in the upper respiratory tract than did resistant a ⁄ dm ⁄ ⁄ virus, and thus had an advantage in directcontact transmission. our study determined the comparative transmissibility of two naturally circulating oseltamivir-sensitive and -resistant pandemic h n ⁄ viruses; we demonstrated inefficient respiratory-droplet transmission of an oseltamivir-resistant h y mutant of pandemic h n virus among ferrets, although it retained efficient direct-contact transmission. we suggest that the lower fitness of resistant virus within the host along with its reduced na function and delayed growth in vitro may in part explain its less efficient transmission. notably, the h y mutant of h n ⁄ used in this study was the first oseltamivir-resistant h n ⁄ isolate from a patient on oseltamivir prophylaxis to be characterized for transmissibility. our observation in the animal model is consistent with the epidemiological data collected from humans, which showed no evidence of predominant or continued circulation of oseltamivir-resistant viruses. as this study was undertaken, additional h y mutants of h n ⁄ viruses have emerged in the absence of oseltamivir use. , the emergence of these viruses should raise concerns as to whether resistant h n ⁄ viruses will acquire greater fitness and spread worldwide as the naturally resistant h n viruses did during the - season. two independent studies have evaluated the pathogenecity and transmission of other oseltamivir-resistant pandemic h n ⁄ clinical isolates in the animal models. , one of the studies, which also used an oseltamivir-resistant virus isolated from a patient under oseltamivir prophylaxis, observed similar results as ours: although the respiratory-droplet route of transmission was not investigated, it was shown that the resistant isolate was transmitted though direct-contact route and was as virulent as wild-type virus in ferrets. in another study, two oseltamivir-resistant isolates were transmitted through the respiratory-droplet route in ferrets, and the dynamics of transmission were different between the two isolates. apparently, these two oseltamivir-resistant isolates were still unequal in their transmissibility and were disparate from the resistant isolate in our study. the isolation history of the two resistant isolates was unclear in this study, and this would be an important factor to understand the fitness of drug-resistant viruses. further studies with more clinical isolates of diverse isolation background are warranted to identify how these novel h y mutants of pandemic h n ⁄ virus have changed to retain their full transmissibility. taken together, all these related studies underline the necessity of continuous monitoring of drug resistance and characterization of potential evolving viral proteins. this study was supported by contract hhsn c from the national institute of allergy and infectious diseases, national institutes of pigs have been considered as hypothetical ''mixing vessels'' facilitating the genesis of pandemic influenza viruses. , the pandemic h n ⁄ virus (ph n ⁄ ) contained a very unique genetic combination and was thought to be of swine origin, as each of its eight gene segments had been found to be circulating in pig populations for more than a decade. however, such a gene constellation had not been found previously in pig herds all around the world. only after its initial emergence in humans has this virus been repeatedly detected in pigs, and found to further reassort with other swine influenza virus. [ ] [ ] [ ] a primary question remaining to be answered is whether the ph n ⁄ -like and their genetically related viruses could become established in pig populations, thereby posing novel threats to public health. despite the fact that ph n ⁄ first appeared in mexico and the united states, and six of its eight gene segments were derived from the established north american triple reassortant swine influenza virus (trig), its neuraminidase (na) and matrix protein (m) genes belonged to the eurasian avian-like swine lineage (ea), which had never been detected in north america previously. , likewise, the trig-like viruses were never reported in europe. in contrast, both lineages of virus were frequently detected in asia, and reassortants between them have also been documented in recent years. , this has given rise to a complicated ecological situation, i.e. the simultaneous prevalence of multiple genotypes of h n and h n viruses in pigs. , among them, two representative reassortants showed the most similar genotypic characterization to the ph n ⁄ virus, the sw ⁄ hk ⁄ ⁄ (h n ) and sw ⁄ hk ⁄ ⁄ (h n ), which respectively harbor seven and six gene segments closely related to the pandemic strains. , to understand their in vivo characteristics and zoonotic potential, these two viruses, together with a human prototype strain and a swine ph n ⁄ -like isolate, were chosen for a study of their pathogenicity and transmissibility in domestic pigs, ferrets, and mice. the prototype ph n ⁄ virus, a ⁄ california ⁄ ⁄ (ca ), was provided by the world health organization collaborating centers for reference and research on influenza (atlanta, ga, usa). three ph n ⁄ -related swine influenza viruses were isolated through our surveillance program in south china as previously described. , the a ⁄ swine ⁄ guangdong ⁄ ⁄ (h n , gd ) virus was a ph n ⁄ -like swine isolate. a ⁄ swine ⁄ hong kong ⁄ ⁄ (h n , hk ), the closest pandemic ancestor known to date, possesses an m gene derived from the ea lineage, with the other gene segments from trig viruses. a ⁄ swine ⁄ hong kong ⁄ ⁄ (h n , hk ), a recent pandemic reassortant progeny, had a ph n ⁄ like na gene (also belonging to the ea lineage), an ea-like hemagglutinin (ha) gene, and six trig-like internal genes. all viruses were propagated in madin-darby canine kidney (mdck) cells for three passages, and their titers were determined by plaque assays. all experiments with live viruses were conducted in biosafety level (bsl- ) containment laboratories. pigs ( - week old, n = - ) and ferrets ( month old, male, n = ) were intranasally infected with pfu of each virus, and mice ( ) ( ) week old, female balb ⁄ c, n = ) with a dose of pfu. naïve uninfected pigs (n = ) were co-housed in the same cage with the inoculated ones from each group. body weights and clinical signs were recorded daily. virus replication was determined by titration of the virus in nasal and rectal swabs (pigs), nasal washes (ferrets), as well as from lungs and other organs (pigs and mice). seroconversion was tested by hemagglutination inhibition (hi) assays. histopathological and immunohistochemical analysis were performed as previously described. statistical analysis was performed by mean analysis with pasw statistics (spss inc., chicago, il, usa). the probability of a significant difference was computed using anova (analysis of variance). results were considered significant at p < ae . the pathogenicity of the four viruses tested differed significantly in inoculated mice. animals infected with pfu of hk experienced the most severe body weight loss ( ae ± ae %) but started to recover after days post-infection (dpi). hk caused similar peak body weight loss ( ae ± ae % on dpi) in mice as did ca ( ae ± ae %, on dpi), but the onset of clinical signs and weight loss (on dpi) was day later than those caused by the other three viruses. the gd -infected group suffered the least body weight loss ( ae ± ae %, dpi) and was the earliest to recover. although all four viruses were detected in the lungs with comparable virus titers on dpi (p > ae ), mice inoculated with gd consistently showed the lowest lung index (lung weight ⁄ body weight, %) on , , and dpi (p < ae ), suggesting the slightest injury and consolidation of the lungs. in concordance with the body weight change, the lung index from the hk group was higher than that from any other groups on and dpi, indicating the marked virulence of hk in mice. notably, virus titer of hk in the nasal turbinate was lower than the other groups both on and dpi (p < ae ), but virus replication in the lower respiratory tract was either higher (in the trachea) or similar (in the lungs). observations of the body weight changes caused by infection of ph n ⁄ or its genetically related swine viruses in ferrets have come to a similar conclusion as that for the mouse experiment. after nasal inoculation with pfu of each virus, all groups of ferrets experienced transient body weight loss for - days, except for those infected with gd , which showed no significant weight loss (p > ae ). although ferrets from the ca -infected group reached their peak weight loss ( ae ± ae %, dpi) one day earlier than those from the hk and hk groups, they began to regain body weight quickly thereafter. hk -infected ferrets also recovered rapidly and their body weights reached the same level as those of the gd -infected group at dpi. comparatively, ferrets inoculated with hk had the most retarded body weight recovery, which did not get back to the baseline level until dpi. hk was only detectable in the nasal wash on dpi, whereas the duration of virus shedding for gd , hk , and ca was - days. by combining the data obtained from the virus titration in the mouse turbinate and ferret nasal washes, a possible conclusion can be made that hk may have lower transmissibility than the other three viruses. after inoculation or exposure by direct contact (physical contact) with the ph n ⁄ virus and its close relatives, most pigs experience no or mild symptoms, such as slight loss of appetite and inactivity. body weight loss was only recorded in pigs inoculated with hk during the second week post-inoculation, but not in their contact pigs or in the other groups. diarrhea was observed intermittently in each of the inoculated or contact groups throughout the experiment, and viruses could be recovered in the rectal swabs, saliva, drinking water, and environmental swabs (inner cage walls accessible to the pigs) at various time points. however, virus titers in the positive rectal swabs were just slightly above the detection limit, while those from the environment sometimes could be higher. whether these viruses can replicate in the digestive tract or were just carried-over by contaminated foods and water requires further investigation. although virus could be detected in the nasal swabs of all infected or contact animals, the lowest peak titer was from pigs inoculated or in contact with hk ( ae - ae log tcid ⁄ ml lower than the other groups), suggesting unfavorable replication in the nasal cavity for this virus. postmortem examination on and dpi revealed that pigs infected with hk had the most extensive gross lesions in the lungs, and histochemical staining of viral nucleoprotein (np) in lung tissues on dpi also suggested the best replication for hk in the lower respiratory tract. on days post-contact (dpc), all pigs exposed to the inoculated animals developed sero-conversions (hi = - ) except for one from the gd contact group. however, on dpc, its hi titer reached , indicating slower seroconversion. this study revealed that both the pandemic h n and its genetically related swine viruses could readily infect mice, ferrets, and pigs causing mild to moderate clinical symptoms. they could also transmit efficiently between pigs. when compared with the pandemic stains and its reassortant progeny (hk ), the hk (h n ) virus containing the ea-like m gene in the genetic context of the trig virus showed consistently higher virulence in all three mammalian models tested, but it is still unknown what might happen if such a virus further reassorts to obtain the pandemic-like or ea-like na gene. however, our findings suggest that pigs could likely maintain the prevalence of different genotypes of pandemic-related influenza viruses, and highlight the zoonotic potential of multiple strains of swine influenza virus. pandemic influenza viruses emerge from the animal reservoirs. among the three pandemics that occurred in the last century, we learned that the h n and the h n pandemic viruses emerged by reassortment between circulating human virus and avian-origin influenza virus(es). studies on the emergence of the catastrophic spanish h n virus suggest that the virus may have obtained all of its eight gene segments from the avian reservoir, , or alternatively is a reassortant between mammalian and a previously circulating human influenza virus. over years since the last pandemic, the first pandemic in the st century arose in and was caused by a swine-origin influenza virus containing a unique gene combination, with gene segments derived from the circulating north america ''triple reassortant'' (pb , pb , pa, ha, np, and ns) and the ''eurasian'' (na and m) swine influenza viruses. , analysis of the pandemic h n viruses failed to identify known molecular markers predictive of adaptation to humans. the ''triple reassortant'' swine influenza viruses emerged in late s in north america is a reassortant between classical swine (descendent of the virus after adaptation in swine population), avian, and human influenza viruses. the eurasian influenza virus was originally an avian influenza virus that was introduced into the european swine population in the late s. , while incidents of zoonotic infection with triple reassortant or eurasian influenza in humans have been reported, , sustained human-to-human transmission has never been established. these results suggest that the unique gene combination seen with the pandemic h n viruses may confer its transmissibility among humans. we have carried out systematic prospective surveillance of swine influenza in southern china over that last years through samples routinely collected at an abattoir in hong kong. during this time, the surveillance results suggest co-circulation of classical swine h n , triple reassortant h n , eurasian swine h n , and a range of reassortants between these three virus lineages. , ferrets have been reported as a suitable model for the study of influenza transmission as they are naturally susceptible to influenza infection, exhibit similar clinical signs (including sneezing), and possess receptor distribution in the airway similar to that of humans. [ ] [ ] [ ] to identify molecular determinants that enable sustained human-to-human transmission, we compared the pandemic virus with genetically related swine influenza viruses obtained from this surveillance program for their ability to transmit from ferret to ferret by direct contact or aerosol transmission. viruses human h n influenza virus [a ⁄ wuhan ⁄ ⁄ (wuhan )] and pandemic h n influenza viruses [a ⁄ california ⁄ ⁄ (ca )] were included for the study. swine influenza viruses that are genetically related with the pandemic h n virus were selected from our surveillance system, including classical swine-like influenza virus a ⁄ sw ⁄ hk ⁄ ⁄ (h n ) (swhk ), triple reassortant-like a ⁄ sw ⁄ arkansas ⁄ ⁄ (h n ) (swar ), and one reassortant between triple reassortant and eurasia swine influenza viruses [a ⁄ sw ⁄ hk ⁄ ⁄ (h n ) (swhk )]. swhk contains seven gene segments (pb ,pb ,pa,ha,np,m,ns) closely related to the pandemic h n viruses. transmissibility was tested in -to -month-old male ferrets obtained from triple f farm (sayre, pa); all ferrets were tested to have hi titer £ against human seasonal influenza h n (a ⁄ tennessee ⁄ ⁄ ), h n (a ⁄ brisbane ⁄ ⁄ ), and influenza b (b ⁄ florida ⁄ ⁄ ) prior the experiments. in each virus group, three ferrets were inoculated with tcid of the virus. at day postinoculation (dpi), we introduced one naïve direct contact ferret to share the cage with inoculated ferret, and one naïve aerosol contact ferret into the adjacent compartment of the cage separated by a double-layered perforated divider. nasal washes were collected every other day and tested for influenza virus antigen and to determine viral titers (tcid ). weight changes, temperature, and clinical signs were monitored daily. transmission is defined by detection of virus from nasal washes and ⁄ or by seroconversion (> fold rise in the post-sera collected after - days post contact). experiments were performed in the p + laboratory at st. jude children's research hospital. all studies were conducted under applicable laws and guidelines and after approval from the st. jude children's research hospital animal care and use committee. at tcid inoculation dose, all viruses replicated efficiently in the ferret upper respiratory tract with peak titers detected from inoculated ferrets at dpi. lower peak titers were detected from swhk and swhk inoculated ferrets, however, the differences were not statistically significant (table ) . tissues collected from inoculated ferrets at dpi showed that pandemic h n and swine influenza viruses replicated both in the upper and lower respiratory tract of the ferrets, while the replication of human seasonal influenza wuhan was restricted in the upper respiratory tract. direct contact transmission from inoculated donor ferrets to their cage-mates was observed for all viruses studied, albeit at different efficiency. human seasonal influenza (wuhan ) and pandemic h n viruses (ca ) transmitted most efficiently via direct contact route as the virus can be detected on dpi from direct contact ferrets, and the peak titers were detected on dpi from direct contacts. moderate direct contact transmission efficiency was detected from swar and swhk viruses as the virus can be detected from direct contact ferrets at dpi, with peak titers detected at dpi or dpi. classical swine-like swhk showed least efficient contact transmission as virus could be detected from all direct contacts only at dpi, and the peak titer detected on dpi. aerosol transmission was detected in groups of human seasonal influenza virus wuhan ( ⁄ ), pandemic h n influenza virus ca ( ⁄ ), as well as swine precursor virus swhk ( ⁄ ). transmission of wuhan and ca to aerosol contacts was detected at dpi or dpi, while transmission of swhk was detected later at dpi, suggesting that the swhk virus possessed aerosol transmission potential, but may require further adaptation to acquire efficient aerosol transmissibility. in addition to viral detection from nasal washes, we also detected viruses from the rectal swabs of ferrets inoculated or infected with pandemic h n viruses (ca ) or classical swine-like virus (swhk ), which share the common origin for the ha, np, and ns gene segments. while many of the swine influenza viruses studied were able to transmit via the direct contact route, swhk , which shares a common genetic derivation for seven genes with h n pdm, possessed capacity for aerosol transmission, albeit of moderate efficiency. swhk differed from swine triple reassortant viruses in the origins of its m gene. it is possible that the m gene derived from eurasian avian- like swine viruses also contributes to the transmissibility of h n pdm influenza viruses. outbreaks of highly pathogenic avian influenza (hpai) of the h n subtype are of extreme concern to global health organisations as human infection can result in severe acute respiratory distress syndrome, multi-organ failure, and coma. hpai viruses of either h or h subtypes contain a characteristic multi-basic cleavage site in the hemagglutinin glycoprotein as well as other virulence factors that expand the viral tropism beyond the respiratory tract of poultry. there is also emerging evidence of viral rna or antigen in multiple organs and the cns of humans infected with h n that is consistent with systemic infection , and raises the question of the role of the cleavage site in dissemination of the virus in this species. the majority of human cases with h n have involved contact with sick or contaminated poultry and exposure to respiratory secretions of birds that can be inhaled and ingested. particular risk factors for h n infection include bathing with sick birds, improper hand washing after handling sick birds, or slaughtering poultry. viral inoculum may also be consumed directly during a variety of religious and cultural practices, such as drinking contaminated duck blood and kissing of merit release birds. h n infection is lethal in % of human cases, and the pathogenetic mechanisms leading to this level of mortality are unclear. to date cases have been reported to the who, although many more people have potentially been exposed to h n through contact with infected bird populations. some studies have suggested that genetic factors may predispose an individual to severe h n disease, but little is known about the influence of route of virus exposure on morbidity and mortality. in ferrets, an animal model frequently used to study influenza because of its similar disease profile to humans, swayne et al. observed that exposure to a virulent h n strain a ⁄ vietnam ⁄ ⁄ by intra-gastric gavage did not lead to disease and did not generate an antibody response, whereas ferrets that experienced a more natural exposure by being fed contaminated meat developed severe signs of infection. in this study we further assessed the disease profile of h n following a natural oral exposure in the ferret model. to achieve this inoculation condition, conscious ferrets voluntarily consumed a liquid inoculum of h n hpai strain a ⁄ vietnam ⁄ ⁄ . as a comparison anesthetised ferrets were exposed by intranasal administration of inoculum and the ensuing disease profiles of the different routes of infection were compared. eight ferrets per group were inoculated with egg infectious dose of a ⁄ vietnam ⁄ ⁄ in a volume of ll that was given to the nares of anaesthetized ferrets to establish a total respiratory tract (trt) infection or voluntarily consumed by conscious ferrets to establish an oral infection. ferrets were culled at a predetermined humane endpoint that was defined as either a > % weight loss and ⁄ or evidence of neurological signs, discussed in ; animals that did not reach the humane endpoint were euthanased on day after challenge. nasal washes and oral swabs collected during the course of infection and organ homogenates were assessed for the presence of replicating virus by growth in embryonated-chicken eggs; viral loads were determined by titration on vero cells and expressed as tcid . tissue samples were fixed with formalin and embedded in paraffin for sectioning. viral lesions were identified by hematoxylin and eosin staining of the sections and the presence of viral antigen in the sections was determined by staining with antibody to influenza a nucleoprotein. pre-and post-exposure antibody responses were assessed by hemagglutination-inhibition assays using irradiated a ⁄ vietnam ⁄ ⁄ virus. the majority ( %) of ferrets infected by the trt route rapidly became inactive, developed severe disease, and were euthanased at the humane endpoint following infection ( figure ). ferrets infected orally had an improved chance of survival, as only % of animals developed severe disease (figure ), and the surviving ferrets were more active than ferrets infected by the trt throughout the stage of acute infection (data not shown). the improved survival rate and wellbeing of ferrets infected orally was not a result of poor infection rates by this route, as of surviving ferrets developed h specific antibodies by day post-infection, and they did not have pre-existing antibodies to h n (data not shown). the two ferrets that developed severe disease after oral infection had similar disease profiles to ferrets infected by the trt route; they both progressed to a > % weight loss and exhibited neurological signs (data not shown). viral loads in organs of these two ferrets confirmed dissemination to extra-pulmonary sites (table ) : replicating virus was detected at high titres in the spleen, pancreas, liver, and brain. similar findings were recorded in ferrets with trt infections in this study (not shown) and elsewhere. viral load in nasal washes and oral swabs taken at days , , and post-infection by the oral route did not correlate with the development of severe disease, and virus was isolated only sporadically and at low titre from the nasopharynx of these animals (data not shown). interestingly, the two ferrets with severe disease after being infected orally had no detectable viral antigen or lesions in the olfactory epithelium and bulb (table ) , whereas of ferrets culled after infection by the trt route had lesions and viral antigen in both the olfactory epithelium and bulb (data not shown). trt oral figure . percentage of ferrets that survived infection after oral or trt infection. ferrets were exposed to a ⁄ vietnam ⁄ ⁄ by the total respiratory tract (trt) route (circles) or the oral route (triangles). the percentages of ferrets that survived infection are indicated at each day following challenge. ferrets exposed orally were more likely to survive h n infection than ferrets exposed to the same dose of virus by the trt. the improved survival rates that were observed after an oral infection could be a consequence of low-level viral replication in the upper respiratory tract in combination with delivery of a substantial portion of the inoculum directly to the stomach where it may have been inactivated by the harsh environment of the gastro-intestinal tract. most ferrets infected orally developed an h -specific antibody response which differs from the studies of swayne et al. in which ferrets gavaged with a liquid inoculum neither developed signs of disease nor an antibody response. however swayne et al. administered virus to anaesthetized ferrets by gastric gavage that would have bypassed the oropharynx. in our study virus was administered to the oral cavity directly and would have had access to the oropharynx. low level of replication at this site may have been sufficient to trigger an antibody response. the two ferrets that developed severe disease following oral infection had a similar profile of viral dissemination as ferrets infected by the trt route. differences were seen in the olfactory epithelium and bulb as lesions, and viral antigen did not occur in these sites following oral infection, although cerebral involvement was identified. one route of dissemination of h n into the cns may be by transport within nerves through the olfactory bulb into the cerebrum. due to the absence of lesions and antigen in these sites following oral infection the spread of virus into the brain in these two animals may be occurring through involvement of other cranial nerves or the hematagenous routes. nasal turbinates ) ae ) ) ) ) pharyngeal lymph node interactions of oseltamivir-sensitive and -resistant highly pathogenic h n influenza viruses in a ferret model < ae b ) + + + + olfactory epithelium nd a nd ) ) ) ) olfactory bulb nd nd ) ) ) ) trachea < ae ) ) nd ) nd lung ) < ae + + ) + spleen ae ) + + ) + small intestine ) ) ) ) ) + pancreas ) ae + ) + + the pandemic potential of highly pathogenic h n influenza viruses remains a serious public health concern. while the neuraminidase (na) inhibitors are currently our first treatment option, the possibility of the emergence of virulent and transmissible drug-resistant h n variants has important implications. clinically derived drug-resistant viruses have carried mutations that are na subtype-specific and differ with the na inhibitor used. the most commonly observed mutations are h y and n s in the influenza a n na subtype (n numbering here and throughout the text); e a ⁄ g ⁄ d ⁄ v and r k in the n na subtype; and r k and d n in influenza b viruses. h n influenza viruses isolated from untreated patients are susceptible to the na inhibitors oseltamivir and zanamivir, although oseltamivir-resistant variants with the h y na mutation have been reported in five patients after , or before drug treatment; and the isolation of two oseltamivir-resistant h n viruses with n s na mutation from an egyptian girl and her uncle after oseltamivir treatment were described. the impact of drug resistance would depend on the fitness (i.e., infectivity in vitro, virulence, and transmissibility in vivo) of the drug-resistant virus. if the resistance mutation only modestly reduces the virus' biological fitness and does not impair its replication efficiency and transmissibility, the effectiveness of antiviral treatment can be significantly impaired. the recombinant wild-type h n influenza a ⁄ vietnam ⁄ ⁄ (vn-wt), a ⁄ turkey ⁄ ⁄ (tk-wt) viruses, and oseltamivir-resistant viruses with h y na mutation (vn-h y and tk-h y) were generated by using the -plasmid reverse genetics system. susceptibility to na inhibitors was tested by using a fluorescence-based na enzyme inhibition assay with munana substrate at a final concentration of lm. viral fitness was studied in vivo in a ferret model: groups of three ferrets were lightly anesthetized with isoflurane and inoculated intranasally with vn-wt, vn-h y, or mixtures of the two at a different ratios at a dose of pfu in ae ml pbs; they were inoculated with tk-wt, tk-h y, or mixtures of the two at a different ratios at a dose of pfu in ae ml pbs. respiratory signs (labored breezing, sneezing, wheezing, and nasal discharge), neurologic signs (hind-limb paresis, ataxia, torticollis, and tremor), relative inactivity index, weight, and body temperature were recorded daily. virus replication in the upper respiratory tract (urt) was determined on days , , and p.i. the competitive fitness (i.e., co-inoculation of ferrets with different ratios of oseltamivir-resistant and -sensitive h n viruses) was evaluated by the proportion of clones in day- nasal washes that contained the h y na mutation. na mutations were analyzed by sequence analysis of individual clones ($ clones ⁄ sample) created by ligation of purified pcr products extracted from nasal wash samples into a topo vector. introduction of the h y na mutation conferred high resistance to oseltamivir carboxylate in vitro; the mean ic of the vn-h y and tk-h y viruses was and times, respectively, that of the corresponding wildtype viruses. the oseltamivir ic of the tk-wt virus was $ times that of the vn-wt virus. all four recombinant h n viruses were susceptible to zanamivir. introduction of the h y na mutation reduced $ % and % of the na activity of vn-h y and tk-h y viruses, respectively, as compared to the wild-type virus activity (p < ae ; two-tailed t-test). all ferrets inoculated with either vn-wt or vn-h y virus exhibited acute disease signs (high fever, marked weight loss, anorexia, extreme lethargy), rapid progression, and death by day - p.i., and no differences in clinical signs and replication in the urt of ferrets were observed between wild-type and oseltamivir-resistant viruses ( table ) . both of the tk viruses caused milder illness than did the vn viruses, despite a much higher dose ( pfu ⁄ ferret), and the tk-h y virus caused less weight loss and fever than the tk-wt virus (table ) . however, competitive fitness experiments revealed a disparity in the growth capacity of vn-h y and tk-h y viruses as compared to their wild-type counterparts: clonal analysis established the uncompromised fitness of vn-h y virus and the impaired fitness of tk-h y virus (table ) . although, the trend towards an increase ⁄decrease in the frequency of the h y na mutation relative to the wild-type was statistically significant (p > ae ) for two studied groups only. mutations within the na catalytic (r k) and framework (e a ⁄ k, i l, h l, n s) sites or near the na active enzyme site (v i, i t ⁄ v, q h, k n, a t) emerged spontaneously (without drug pressure) in both pairs of viruses (results not shown). the na substitutions i v and e a could exert compensatory effect on the fitness of vn-h y and tk-h y viruses. the lethality and continuing circulation of h n influenza viruses warrants an urgent search for an optimal therapy. our results showed that the h y na mutation affects the fitness of two h n influenza viruses differently: the oseltamivir-resistant a ⁄ vietnam ⁄ ⁄ -like virus outgrew its wild-type counterpart, while the oseltamivir-resistant a ⁄ turkey ⁄ ⁄ -like virus showed less fitness than its wild-type counterpart. we used a novel approach to compare the fitness of oseltamivir-sensitive and -resistant influenza viruses that included analysis of virus-virus interactions within the host (competitive fitness) during co-infection with these viruses. although mixed populations were present in the urt of ferrets on day p.i., the fitness of vn-h y virus was uncompromised as compared to that of its drug-sensitive counterpart, while that of tk-h y virus was impaired. a minor population of na inhibitor-resistant variants may gain a replication advantage under suboptimal therapy in two ways: (i) preexisting variants less sensitive to the drug are selected from the quasispecies population, leading to an increase of the number of resistant clones, and (ii) outgrowing variants may acquire additional compensatory mutations that enhance their fitness. it is possible that use of antiviral drugs (particularly at suboptimal concentration) against mixtures of oseltamivir-resistant and sensitive viruses will promote the spread of drug-resistant variants * ferrets in all groups inoculated with a ⁄ vietnam ⁄ ⁄ virus died by day - p.i. and were observed once daily for days. ** results obtained from one ferret. *** by inhibiting drug-sensitive variants that are competing with them for the dominance in the infected host. the influence of multiple genes on the fitness of viruses carrying h na mutation cannot be excluded. in our study we focused on additional na mutations, and sequence analysis of individual na clones was done to identify potential host-dependent and compensatory na mutations. we found that the na mutations e a and n s, which confer cross-resistance to oseltamivir and zanamivir, , can emerge spontaneously in clade . h n influenza virus in ferrets. further, we observed that mutations at na catalytic (r k) and framework (i l and n s) sites and in close proximity to the na enzyme active site (v i, i t ⁄ v, q h, k n, a t) emerged without drug pressure in both pairs of h n viruses. compensatory mutations in na or other genes may mitigate any fitness cost imposed by resistance mutations. our study identified six potential compensatory na changes (d v, f s, i v, e a, h l, and f s) that may affect the fitness of viruses with the h y na mutation. we suggest that na mutations at residues i v and e a are of importance. interestingly, we observed differences in predominance of i v and e a na mutations in different genetic backgrounds: i v mutation was identified in a ⁄ vietnam ⁄ ⁄ (h n )-like and e a in a ⁄ turkey ⁄ ⁄ (h n )-like genetic background. moreover, i v na mutation was identified only when ferrets were inoculated with the mixtures of vn-wt and vn-h y viruses, but not in ferrets inoculated with vn-h y virus. none of the potential compensatory na mutations was identified in the original inoculum used to infect ferrets. the h y na mutation causes a large shift in the position of the side chain of the neighboring e residue, which must form a salt bridge with r to accommodate the large hydrophobic pentyl ether group of oseltamivir. residue i is located near the na active site, and although it does not alter polarity, it results in a shorter side-chain and, thus, may indirectly affect the residues in the na active site. we suggest that antigenic and genetic diversity, virulence, the degree of na functional loss, and differences in host immune response and genetic background can contribute to the observed differences in the fitness of h n influenza viruses. therefore, the risk of emergence of drugresistant influenza viruses with uncompromised fitness should be monitored closely and considered in pandemic planning. this study was supported by contract hhsn c from the national institute of allergy and infectious diseases, national institutes of health, and by the american lebanese syrian associated charities (alsac). the data presented in the manuscript have been published at: govorkova ea, ilyushina na, marathe bm, mcclaren laninamivir (r- ) is a strong na inhibitor against various influenza viruses, including oseltamivir-resistant viruses. [ ] [ ] [ ] [ ] [ ] [ ] we discovered a single intranasal administration of laninamivir octanoate (cs- ), a prodrug of laninamivir, showed a superior anti-virus efficacy in mouse and ferret infection models compared to repeated administra-tion of oseltamivir and zanamivir. [ ] [ ] [ ] this suggested that cs- works as a novel long-acting na inhibitor of influenza virus in vivo. a single inhalation of cs- proved noninferiority in adult patients and significantly superior in child patients, compared to an approved dosage regimen of oseltamivir for treatment. cs- has been commercially available as an inhaled drug, inavir Ò , for the treatment of influenza in japan since october . the long-acting characteristics of cs- are explained by several reasons. first, cs- was quickly hydrolyzed to an active metabolite, laninamivir, after an intranasal administration to mice, and was retained for a long time as laninamivir in target organs, such as lung and trachea. however, with an intranasal administration of laninamivir, it disappeared quickly and did not demonstrate its longlasting characteristics. another reason is a strong binding of laninamivir to nas of seasonal influenza viruses compared to other three na inhibitors, oseltamivir carboxylate, zanamivir, and peramivir. in the following, the tight-binding ability of laninamivir to pandemic (h n ) na, as well as to the seasonal influenza virus nas, was demonstrated. in addition, we present a hypothesis of the mechanism of the long-lasting property of cs- in mouse based on a localization of an enzyme that hydrolyzes cs- to laninamivir. the influenza viruses, pandemic(h n ) (inf ), a ⁄ new caledonia ⁄ ⁄ (h n ), a ⁄ panama ⁄ ⁄ (h n ), and b ⁄ mie ⁄ ⁄ were treated with excess na inhibitors, such as oseltamivir carboxylate, zanamivir, peramivir, and laninamivir, and then unbound na inhibitors were removed from the mixtures with a bio-spin column bio-gel p- (bio-rad laboratories, hercules, ca, usa). the na substrate, -methylumbelliferyl-n-acetyl-a-d-neuraminic acid (nacalai tesque, japan) was added to the virus-na inhibitor complex, and the na activities were followed for hours at room temperature by measuring the fluorescence at an excitation wavelength of nm and an emission wavelength of nm. the enzyme which hydrolyzes cs- to laninamivir was partially purified from rat lungs using ion exchange column chromatography, and almost all bands separated by an sdspolyacrylamide gel electrophoresis were identified by mass spectrometry. the gene expression profiles of the enzyme were investigated by the bioexpress database (genelogic inc., gaithersburg, md, usa). the enzyme gene cloned from mouse lung mrna was transiently expressed in cos cells. antiserum to the esterase was prepared by immunizing rabbits, and immunostaining was done using histomouse-tm-max kit (invitorgen corp., carlsbad, ca, usa) according to the manufacturer's manual. binding stability of na inhibitors to the four viruses are shown in figure the enzyme that hydrolyzes cs- to laninamivir in rat lungs was identified as carboxyesterase. this esterase was shown to be expressed in epithelial cells of rat lung by in situ hybridization. the mouse homolog of the rat esterase was carboxylesterase (ces ). the mrna of the mouse ces was shown to be highly expressed in lung and liver by the gene expression profile, and ces was also found to contain signal sequences for retention in endoplasmic reticulum (er) and golgi at the c-terminus. the cloned ces gene and the ces gene lacking the signal sequence were exogenously expressed in the cos cells. the cs- -hydrolyzing activity associated with the cos cells expressing ces was recovered from the culture sup of the cos cells expressing ces lacking the retention signal sequence. localization of ces was immunohistologically confirmed inside the airway epithelium cells of mice, which are the target cells for influenza virus infection. the long acting property of intranasal administration of cs- in mice can be explained both by the long retention of laninamivir in the respiratory tract and by the stable binding of laninamivir to influenza virus na. again, stable binding of laninamivir to na of pandemic (h n ) virus was also observed similar to that of seasonal h n virus. the following are speculated as the mechanisms for the long-lasting characteristics of cs- in mice. we explain the mechanism by clarifying a cs- hydrolyzing enzyme and its localization inside cells. the hypothesis of the mechanism is presented in figure . briefly, hydrophilic laninamivir may not enter easily inside cells, whereas hydrophobic cs- may enter inside cells. ces with er ⁄ golgi retention signal hydrolyzes octanoate of cs- figure . difference of binding stabilities of various na inhibitors to influenza virus neuraminidases. the na substrate was added to the influenza virus-na inhibitor complex (oseltamivir carboxylate, n; zanamivir, h; peramivir, s; laninamivir, •; distilled water, ¤), and the na reaction was followed for minutes. the background (only the na substrate [d] ) is also shown. a part of data from. to generate the hydrophilic drug, laninamivir, and then it is trapped inside er ⁄ golgi because of its high hydrophilicity. the glycoprotein, na, which matures in er ⁄ golgi, meets laninamivir there and efficiently makes a stable complex with it. there are some questions that remain. how does cs- move from the cell membrane to er ⁄ golgi? is laninamivir indeed trapped inside er ⁄ golgi, and does it make a complex with na in mice? we are now making an attempt to clarify these concerns. in our study, we have explored the antiviral potential of two newly synthesized compounds to provide protection against the novel pandemic influenza virus h n ( ) strain. the compounds were reconstituted in dimethylsulphoxide (dmso), and so the initial studies began with cytotoxicity determination of solvent on uninfected and untreated madin-darby canine kidney (mdck) cells. on obtaining an upper limit for dmso, the compounds were tested for estimation of their maximum non-toxic dose to the mdck cells. thereafter, the effective dose of the compounds was evaluated and validated by a number of assays and gene expression profiling at both nucleic acid and protein level. we found that these newly synthesized compounds possess potent inhibitory activity towards the novel pandemic influenza h n ( ) virus. these findings are being evaluated in vivo for a better understanding of their inhibitory capabilities and also their effect on the host metabolism. this will be required in the course of development of new drugs for use in the prophylaxis and treatment against the influenza virus. the mdck cell line (from nccs, pune) was maintained in · dmem media (sigma, st. louis, mo, usa) supplemented with % fetal calf serum and antibiotics viz. unit ⁄ ml penicillin and lg ⁄ ml streptomycin at °c ⁄ % co . the synthesized compounds used in this study were kindly provided by the department of chemistry, university of delhi, delhi, india. the pandemic influenza h n ( ) virus was isolated and propagated in the allantoic cavities of embryonated chicken eggs during the pandemic period. the virus stocks were prepared and stored at ) °c. plaque assay was performed as previously described by hui et al., . briefly, ae · mdck cells ⁄ ml were seeded in six-well plates and maintained in dmem for hours at °c ⁄ %co . the monolayer of the cells was inoculated with serially diluted virus samples for minutes at °c ⁄ %co . subsequently, a mixture of agar overlay was added, and the plates were incubated at °c for days or until formation of plaques. the plaques were visualized after removal of the agar plug and staining with ae % crystal violet or neutral red solution. the virus titre was expressed as plaque forming unit (pfu) per milliliter. the in vitro cytotoxicity analysis was performed to determine the % cytotoxic concentration (cc ) of the compounds on mdck cells. the compounds were dissolved in dimethylsulfoxide (dmso), and so a prior cytotoxicity analysis was performed to determine the toxic concentration of dmso on the cells. various concentrations of compounds were mixed with dmem containing % fcs before addition to the preformed monolayer of mdck cells in -well plates. a series of suitable controls for in vitro cc determination was included in every plate, and the plates were incubated in the optimum environment for mdck cell culture. the cc of test compounds was analyzed by estimation of percentage cell viability of the compound-and mocktreated mdck cells by performing a colorimetric assay using tetrazolium salt -( , -dimethylthiazol- -yl)- , diphenyl tetrazolium bromide (mtt) at end-point of hours post-incubation. the assay was performed as described by mosman . briefly, mtt stock at a concentration of ae mg ⁄ ml was prepared in · pbs. the media was aspirated from the wells and ll of mtt dye from the stock was added to each well. following incubation at °c ⁄ % co for - hours, the dye was very carefully removed from the wells, and the cells were incubated with ll of stop solution (dmso) per well at °c ⁄ % co for hour. the absorbance of the supernatants from each well was measured at nm, and the percentage cell viability was calculated. madin-darby canine kidney cells were maintained overnight in a -well tissue culture plate at °c ⁄ % co . the cells were inoculated with various virus dilutions at °c ⁄ % co for minutes and observed for cytopathic effect (cpe). the media from the experimental wells were aspirated after - hours of infection and were subjected to plaque assay. the percentage cell viability was determined by performing mtt assay. the results of both these tests were used to assess tcid of the virus. the pre-formed monolayer of mdck cells was inoculated with the -fold dilution corresponding to tcid of the virus for hour at °c ⁄ co . the experimental setup included control wells for the cells, virus, and compound. meanwhile, the concentrated stocks of the synthesized compounds were diluted with dmem (with % fcs) to various concentrations within their respective cc ranges. one hour post-infection, the cells were incubated with these diluted solutions. the cells were observed at various time intervals post-inoculation for cpe, and ll media was collected from each experimental well for performing hemagglutination test. after h, the media was collected for plaque assay and the cells were subjected to mtt cell viability assay. preformed monolayers of mdck cells were infected with virus and treated with the respective inhibitory concentration of the compounds. forty-eight to hours post-incubation, total cellular rna was isolated using ribozol (amresco, solon, oh, usa) and treated with lg ⁄ ml of dnase (promega, madison, usa). the concentration and quality of the rna from each well were determined by measuring their absorbance at and nm. one microgram of the cdna synthesized from each rna sample was used for sybr green-based real-time pcr detection of the ha gene of pandemic influenza h n ( ) virus. as a control, human glyceraldehyde- -phosphate dehydrogenase (hgapdh) was also amplified using gene specific primers. , immunoblotting immunoblotting was performed to further validate the antiviral potential of the compounds. the experimental protocol was the same as for real time rt-pcr analysis. the cells were harvested hours post-treatment with the compounds to prepare whole cell lysates in mammalian cell lysis buffer [ ae m nacl, ae m tris cl (ph ae ), ae m edta (ph ae ), m m protease inhibitor cocktail, lg ⁄ ml pmsf]. the protein concentration was determined by bca protein assay. the cell lysates were fractionated on % polyacrylamide for western blotting. the blot was developed using sheep monoclonal antibody (santa cruz biotechnology, ca, usa) against ha protein of influenza virus and horseradish peroxide conjugated rabbit-anti sheep igg ( : dilutions) as secondary antibody. the median cytotoxic concentration for compound meuh came out to be lm, and that for flh was lm. compounds showing potent antiviral effect on the pandemic influenza h n ( ) virus propagation in madindarby canine kidney cells ( figure ). the viral titres remained constant in cells treated with the compounds, while they increased in the untreated virus infected cells. ed for the compounds meuh and flh were and lm, respectively. fifty-two percent (meuh) and % (flh) inhibition against the pandemic influenza h n ( ) virus was achieved using ed of the test compounds. both the compounds were able to reduce the rna levels of the ha gene by approximately - %, whereas approximately % inhibition was seen when both the compounds were used in combination. similar results were obtained by the immunoblotting analysis ( figure ). antiviral therapy has shown to be a promising tool in the management of various respiratory diseases, including those caused by influenza viruses. we have already shown inhibition of influenza virus replication in our earlier studies using catalytic nucleic acids, which can be used as an approach in the development of new therapeutic strategy. these therapies are very useful as the influenza virus vaccines need annual renewals due to frequent genetic drifts in the viral surface proteins. in pandemic situations the existing vaccines do not provide complete protection against the novel virus as the population generally remains naïve for the newly mutated surface antigens. the antiviral drugs play an important role in the control of novel viral strains for which there are no vaccines available. however, the key obstruction in the extensive use of antiviral drugs is their cost and relative therapeutic efficacy provided. two classes of drugs were being used for treatment and control of the influenza virus infection in humans, the m ionchannel blockers , (amantadine and rimantadine), which prevent viral uncoating, and the neuraminidase inhibitors , (zanamivir and oseltmivir), which prevent the release of influenza virions from the cytoplasmic membrane. but widespread resistance to these antiviral drugs , has limited their use. thus, novel drugs are required for the effective therapy against the emerging strains of influenza virus. the novel chemical compounds used in our study were tested for their antiviral efficacy against the pandemic influenza h n ( ) virus. a reduction in the cpe in compound treated virus infected mdck cells indicated presence of antiviral activity in chemical compounds. the persistence of constant viral titers in the compound treated cells provided evidence for the interference posed by the compounds in the replication of influenza virus. inhibition in the ha gene expression further validated our hypothesis for the antiviral effect of compounds. the efficacy of these compounds in animal models is currently being validated in our laboratory. further, molecular studies are required to ameliorate the awareness regarding the mode of action of these chemical compounds against the viruses. and is now licensed in japan, while another, laninamivir, is being developed as an inhaled prodrug. resistance to nais among circulating influenza viruses was previously low (< % worldwide). [ ] [ ] [ ] however, the - influenza season was marked by a worldwide emergence of oseltamivir-resistant seasonal influenza a (h n ) viruses with the h y (h y in n numbering) in the na. [ ] [ ] [ ] [ ] [ ] [ ] the prevalence of oseltamivir resistance was even higher in the subsequent - influenza season with many countries reporting up to % oseltamivir resistance, seasonal and pandemic influenza viruses collected globally between october , and september , were submitted to the who collaborating center for surveillance, epidemiology and control of influenza at the centers for disease control and prevention (cdc) in atlanta, ga, usa, and propagated in madin-darby canine kidney (mdck) cells (atcc, manassas, va, usa). reference viruses representative of oseltamivir-sensitive and -resistant seasonal and pandemic viruses were also propagated in mdck cells. susceptibilities of virus isolates to the nais oseltamivir carboxylate (hoffman-la roche, basel, switzerland) and zanamivir (glaxosmithkline, uxbridge, uk) were assessed in the chemiluminescent ni assay using the na-star tm kit (applied biosystems, foster city, ca, usa) as previously described. additionally, subsets of virus isolates were tested for susceptibility to peramivir (biocryst pharmaceuticals, birmingham, al, usa). fifty percent inhibitory concentration (ic ) values were calculated using jaspr curve fitting software, an in-house program developed at cdc. curve fitting in jaspr was done using the equation: v = vmax · ( ) ([i] ⁄ (ki + [i]))), where vmax is the maximum rate of metabolism, [i] is the inhibitor concentration, v is the response being inhibited, and ki is the ic for the inhibition curve. box-and-whisker plot analyses of log-transformed ic s were performed for each virus type ⁄ subtype and nai using sas . software (sas institute, cary, nc, usa) to identify viruses with extreme ic values (outliers). outliers were characterized based on a statistical cutoff of ic greater than three interquartile ranges from the th percentile. outliers were subjected to genetic analysis by pyrosequencing and ⁄ or conventional sequencing to detect known or novel markers of nai resistance. those harboring previously characterized mutations in the na associated with nai resistance were considered drug-resistant; their descriptive statistics were determined separately from naisusceptible viruses. descriptive statistics to compute the mean, median, and standard deviation (sd), and a one-way analysis of variance were performed on original scale ic data, using sas . software (sas institute) for each nai and virus among seasonal influenza a (h n ) viruses tested for oseltamivir susceptibility (n = ), ( ae %) were outliers for the drug (table ) and harbored the oseltamivir-resistance conferring h y mutation in the na. by contrast, only a small proportion ( ae %) of tested h n pdm viruses (n = ) were resistant to oseltamivir. all influenza a (h n ) viruses (n = ) were sensitive to oseltamivir except for one outlier, a ⁄ ontario ⁄ rv ⁄ with d v mutation in the na, whose ic of ae nm was beyond the statistical cut-value off and > -fold the mean ic for the drug ( ae nm). all influenza b viruses (n = ) were sensitive to oseltamivir with exception of an outlier b ⁄ texas ⁄ ⁄ , with d e (d e in n numbering) mutation in the na, whose ic was beyond the cut-off, but only fourfold greater than the mean ic for the drug. all virus types ⁄ subtypes tested for zanamivir were sensitive to the drug (table ) , except for some outliers among seasonal influenza a (h n ) and a (h n ) outliers. the seasonal influenza a (h n ) outliers included a ⁄ thailand ⁄ ⁄ (h n ) and a ⁄ hawaii ⁄ ⁄ (h n ), both with combined h y and d d ⁄ g mutations in their na. the presence of concurrent mutations at na residues h and d in seasonal influenza a (h n ) virus isolates substantially enhances resistance to oseltamivir and peramivir and ⁄ or zanamivir, however, the changes at d are typically cell-derived and not present in clinical specimens. influenza a (h n ) outliers for zanamivir included a ⁄ ontario ⁄ rv ⁄ with d v mutation in the na, as well as a ⁄ maryland ⁄ ⁄ and a ⁄ vladivostok ⁄ ⁄ with d g and mixed d d ⁄ g mutations, respectively. some mild outliers for zanamivir among a (h n ) viruses with ic beyond the statistical cutoff but < -fold mean ic for the drug were also identified; their genetic analysis revealed presence of wildtype and mutant sequences at residue namely, d d ⁄ g, d d ⁄ n, or d d ⁄ a. mutations at residue d of the na are associated with reduced susceptibility to zanamivir in a (h n ) viruses, but were reported to be cell-culture derived in recent h n viruses. all virus isolates tested for peramivir (n = ) were sensitive to the drug, except for h y variants among seasonal influenza a (h n ) and h n pdm viruses, which exhibited reduced susceptibility to the drug. in addition, one influenza a (h n ) isolate, a ⁄ ontario ⁄ rv ⁄ with d v mutation in the na, showed reduced susceptibility to peramivir. the ic values determined in functional ni assays provide valuable information for detection of resistant viruses, but should not be used to draw direct correlations with drug concentrations needed to inhibit virus replication in the infected human host, as clinical data to support such inferences are inadequate. nevertheless, combining elevated ic values with the presence of established molecular markers of resistance in the na of virus isolates and their matching clinical specimens provides a reliable and reasonably comprehensive approach of identifying nai-resistant isolates for surveillance purposes. in this study, outliers with elevated ic values for oseltamivir among seasonal influenza a (h n ) and h n pdm viruses were confirmed to be oseltamivir-resistant based on the presence of the h y mutation in the na. outliers for oseltamivir and ⁄ or zanamivir among influenza a (h n ) viruses in this study were shown to harbor mutations at d , which were earlier associated with reduced susceptibility to zanamivir, and were cell-culture derived. the effects of d mutations on nai susceptibility appear to be strain-specific; however, there are no conclusive supporting data and further investigations are required. outliers among the influenza a viruses in this study exhibited changes in the na, derived naturally or through cell-culture, which altered their susceptibility to nais. however, mild outliers for oseltamivir and ⁄ or zanamivir among influenza a viruses with slightly elevated ic s, but without apparent changes in the na are sometimes identified. in such instances it is imperative to exclude the potential presence of influenza b among such outliers, using conclusive genetic tests such as real time pcr, since influenza b viruses exhibit higher ic values for oseltamivir and zanamivir than influenza a viruses. viruses exhibiting such mixes are typically excluded from statistical analyses of ic s for respective drugs and virus type ⁄ subtype. establishment of a clinically relevant ic cutoff value which could be used to differentiate statistical outliers from truly resistant viruses is imperative. global surveillance for nai susceptibility of influenza viruses circulating globally should be sustained to reflect the impact of seasonal and pandemic of influenza, given the limited pharmaceutical options available for control of influenza infections. nasopharyngeal swab specimens from patients with acute respiratory infection were collected at influenza sentinel surveillance units (outpatient and hospital-based) all over mongolia. specimens were transported to the virology laboratory, nccd, ulaanbaatar, and rt-rt pcr positive samples were grown in a mdck cell culture according to the protocol developed by cdc. and influenza virus gene segment (m genes) sequencing ( strains-genbank accession numbers: cy , cy , cy , cy , cy , cy , and cy ) and influenza virus gene segment (na gene) sequencing ( strains genbank accession numbers: cy and cy ) by the standard methods with applied biosystems xl genetic analyzer using primers supplied by who collaboration centers. a chemiluminescent na inhibition assay was performed with veritas microplate luminometer using the commercially available kit, na-star (applied biosystems, foster city, ca, usa), according to the manufacturers protocol. the na inhibitor susceptibility of influenza virus isolates was expressed at the concentration of na inhibitor needed to reduce na enzyme activity by % (ic ). oseltamivir carboxylate, was provided by f. hoffman-la roche ltd (basel, switzerland). na inhibition assay data were analyzed using robosage software comparing test data with the data produced by the reference na inhibitor sensitive and resistance strains, which were provided by the who influenza collaboration center, melbourne, australia. all viruses tested were sensitive to oseltamivir with two exceptions: a seasonal influenza virus a ⁄ ulaanbaatar ⁄ ⁄ (h n ) with ae nm ic value and a pandemic influenza virus a ⁄ dundgovi ⁄ ⁄ (h n ) with ae nm ic value ( figure ). there was oseltamivir resistance detected in ae % ( ⁄ ) of seasonal a (h n ) and in ae % ( ⁄ ) of a (h n ) pdm viruses. the oseltamivirresistant viruses were collected from untreated patients. in total, influenza b viruses were analyzed by na inhibition assay and all were sensitive to oseltamivir. the na of both oseltamivir-resistant strains contained h y mutation based on the sequencing analysis. the difference in the na amino-acid sequences between the mongolian oseltamivir-resistant viruses and the respective oseltamivir-sensitive reference viruses is shown in table all a(h n ) viruses analyzed for m channel inhibitor resistance by pyrosequencing contained the s n mutation and, thus, were resistant to this class of anti-influenza drugs. the segment sequencing revealed that seasonal a(h n ) viruses possess the common s n mutation. of note, a single strain a ⁄ zavkhan ⁄ ⁄ (h n ) contained an unusual s d change in the m protein. our study shows that the same prevalence [ ae % ( ⁄ )] of seasonal a(h n ) viruses with h y mutation in ⁄ season in mongolia with the published data for ⁄ season from japan. , however the prevalence of oseltamivir resistance in japan has dramatically increased in ⁄ season to % ( ⁄ ). the observed double mutations: h y and d g in a ⁄ ulaanbaatar ⁄ ⁄ (h n ) strain, which have been also found in japan in ⁄ season. the patient from whom the oseltamivir resistant seasonal influenza h n virus has been isolated was a -year-old boy, living in ulaanbaatar, the capital city, without history of using oseltamivir. the patient from whom the oseltamivir resistant a(h n )pdm virus was isolated was a year-old man, residing in the dundgovi, the southern province, also without history of antiviral treatment. according to the who data, isolation of the pandemic viruses carrying h y change from untreated patients has been uncommon. circulation of amantadine-resistant seasonal a (h n ) viruses has been increasing in mongolia since ⁄ influenza season. all pandemic influenza a(h n ) strains ( ) tested were resistant to m channel inhibitors due to the presence of the s n mutation in the m protein. among seasonal a(h n ) viruses, one contained a s d change whereas the others had s n, the well established marker of resistance to both amantadine and rimantadine. this is the first report of detecting the s d change in the seasonal a(h n ) viruses. according to the cdc data (unpublished), the s d change conferred the drug resistance in the a(h n ) viruses according to the virus yield reduction assay. it is essential to continue the antiviral resistance surveillance of influenza virus strains circulating in mongolia to ensure the efficiency of a proper clinical management of influenza patients. (conferred by the s n mutation). of note, the genotype and genotype dual resistant viruses from asia appear to be genetically similar to those previously reported dual resistant viruses from hong kong, sar. , the genotype virus was the only dual resistant virus with a nearly complete c genome. oseltamivir-resistance for this virus appears to be the result of a reassortment as demonstrated by the presence of the oseltamivir-resistant clade b na gene. although the detection of dual resistant seasonal influenza a (h n ) viruses is still rare, there has been an increased prevalence of dual resistance viruses during the last three seasons: . % ( of tested in - ), . % ( of in - ) , and % ( of in - ) (v p < . ). while the continued circulation or co-circulation of seasonal a (h n ) viruses is uncertain, the emergence of dual resistant influenza viruses in five countries does present a public health concern, especially since dual resistant viruses would limit the options for antiviral treatment to a single licensed antiviral drug: zanamivir. moreover, the markers of resistance seen in seasonal a (h n ) viruses also confer resistance in the more widely circulating pandemic a (h n ) virus. and, since the acquisition of mutations in influenza a viruses typically occur through drug selection, spontaneous mutation, or genetic reassortment with another drug resistant influenza a viruses, the detection of influenza a (h n ) viruses that are resistant to both adamantanes and oseltamivir warrants close monitoring, even if only detected at low frequency. new antiviral agents and strategies for antiviral therapy are likely to be necessary in the future. heightening concern that drug resistance will likewise become prominent in pandemic viral strains and highlighting the need for antiviral drug resistance surveillance. the h y mutation in h n neuraminidase is the most common mutation conferring resistance. however, due to the high mutation rates of viruses, new mutations can be expected that will also render viral neuraminidase less sensitive to antiviral drugs. pcr methods can be used to detect previously identified mutations; however, functional neuraminidase enzyme activity inhibition testing is necessary for detecting drug resistance that results from novel mutations. the two neuraminidase enzyme inhibition assays using either the fluorescent munana or chemiluminescent na-star Ò substrate are robust tools for ni susceptibility testing. the munan-a-based assay is broadly used by many groups, including many regional health organizations for ni susceptibility testing, yet no standardized protocol or dedicated kit has been in place for this assay, making comparison of data generated between different laboratories difficult. borrowing from multiple neuraminidase inhibitor susceptibility network (nisn)-published munana-based neuraminidase assay protocols, we have developed a kit-based fluorescent neuraminidase assay that offers both standardization and off-the-shelf quality-controlled reagents for ni susceptibility testing and other neuraminidase assay applications. the na-fluor tm influenza neuraminidase assay reagents and protocols were optimized in comparison to published nisn protocols according to the criteria of assay performance, ease-of-use, consideration of historically used assay conditions, reagent storage stability, and environmental impact. our optimized assay conditions consists of lm munana, ae mm mes, mm cacl , and ph ae in a ll assay volume, and performing the assay for minutes at °c following a minutes preincubation of drug with the virus. these conditions are consistent with the majority of published influenza ni screening data in publication. the standard na-fluor tm assay workflow for screening viral isolates for sensitivity to nis includes first titering the viral sample by neuraminidase activity to determine optimal virus concentration to be used in subsequent ic determination assays. the na-fluor tm assay is an ideal tool for titering virus based on neuraminidase activity in the viral coat. titering of viral samples prior to running the ic determination assays insured that assays would be performed within the fluorescence detection dynamic range of both the assay and the fluorometric instrument being used. viral titers giving rfus in the range of - were used for subsequent assays. comparison to traditional munana assays a primary goal of developing a standardized munana assay was to provide a standardized protocol and set of reagents that would allow for comparison of ni surveillance data between laboratories and over time. in addition, the assay should provide data comparable to historical data sets based on traditional munana-based protocols. to insure that our newly developed na-fluor tm assay met these criteria we performed side-by-side comparisons of the na-fluor tm assay to munana-based nisn protocols, as well as our na-xtd tm and na-star Ò chemiluminescent neuraminidase assays to compare assay sensitivity and dynamic range and for ni ic determination with multiple viral isolates. for all assay comparisons, assays were performed according to respective published protocols. for direct comparison of results, an equivalent amount of virus (and concomitant neuraminidase activity) was used for each assay. the na-fluor tm assay provides low-end sensitivity (by signal to noise ratio) and dynamic range similar to nisnpublished, munana-based protocols (data not shown). these assays all show a low-end detection of approximately ae u ⁄ well and dynamic range of - orders of magnitude when performed simultaneously side-by-side using serial dilutions of bacterial (clostridium perfringes) neuraminidase. these assays show approximately onefold less dynamic range and approximately fivefold less low-end sensitivity than chemiluminescent assays under these conditions. given the large amount of archived ni inhibition data for viral isolates over the past decade, it is very important for a standardized assay to generate data similar to established protocols so that data can be compared in relative terms. when run side-by-side, na-fluor tm assay provided oseltamivir carboxylate and zanamivir ic values similar to nisn-published, munana-based protocols. ic values vary somewhat for munana assays versus chemiluminescent assays depending on the viral isolate, as previously described. the na-fluor tm assay also exhibited similar sensitivity for detecting ni sensitive virus compared to nisn-published fluorescent assays as shown in figure . the large shift in ic values between oseltamivir-sensitive and resistant virus using the na-fluor tm assay enables detection of mutant virus in mixed viral samples ( figure ). this capability is critical for identifying resistant virus in clinical isolates presenting mixed populations of resistant and sensitive virus during ni susceptibility surveillance. several characteristics of the na-fluor tm assay make it an ideal assay for processing large numbers of viral isolates for ni sensitivity surveillance or for using the assay for high throughput screening for lead discovery of new antiviral reagents. the na-fluor tm assay signal was found to remain stable for up to hours after stop solution addition when stored at room temperature and for several days when stored at °c (data not shown). ic values did not change over these times, indicating that the assay is compatible with processing many samples in a short time frame. the na-fluor tm assay was also found to be highly reproducible giving a z' of ae or above indicating that the assay can be used confidently to identify nis in high throughput screening mode. the assay can tolerate up to % dmso, a common compound delivery reagent used in high throughput screens (data not shown). we have developed a standardized na-fluor tm assay suggested protocol that gives data similar to established mun-ana protocols. however, we have also found that several protocol adaptations can be made that generate comparable data while allowing the user more flexibility in assay mode, use of additional reagents, and to meet user-specified assay time requirements. the na-fluor tm assay can be run in either the standard minutes ⁄ °c endpoint mode described above or as real-time kinetic assay with repeated reads taken over time without the addition of stop solution, which both serves to terminate neuraminidase activity and to enhance the fluorescence of the product. for typical ni-sensitive viral strains, the rate of munana substrate turnover at °c is linear for at least hours (data not shown). as would be expected, rates of substrate turnover decrease in the presence of nis reflected in a decreased slope exhibited by real-time kinetic reads. real-time acquired rfus are typically - fold lower than rfus acquired after addition of stop solution at the same time point. ic values obtained using slope analysis for real-time assays are similar to values obtained by endpoint analysis. whether run in real-time or end-point mode, the linear rate of substrate turnover allows the user to run the assay for shorter or longer assay times than the standard protocol without compromise to assay performance. the na-fluor tm assay is also compatible with standard methods used in many laboratories to inactivate virus. we have shown that ni ic values for multiple viral strains remain unchanged when the assay is performed in the presence of ae % np- or % triton x- (data not shown). similar results are also obtained by adjusting the na-fluor tm stop solution to % ethanol prior to addition for assay termination. the assay is unaffected by phenol red concentrations present in cell culture media. we have developed a standardized munana-based fluorescent neuraminidase assay, the na-fluor tm influenza neuraminidase assay kit, which has been optimized for ni susceptibility screening. the assay provides data that can be compared to data generated using traditional munanabased protocols. the assay is economical, highly reproducible, easy to use, and environmentally friendly. the assay is flexible and amendable to user-specific adaptations including assay mode, assay timing, and reagent compatibility. trademarks ⁄ licensing ª life technologies corporation. all rights reserved. relenza is a registered trademark of glaxo- to test the prophylactic potency of h -vhhb, mice were treated intranasally with pbs, lg of h -vhhb, or negative control rsv-vhhb at , , or hours before infection with one ld of nibrg- ma virus. body weight loss was monitored daily, and on day mice were sacrificed to determine the viral load in the lungs. all mice that received h -vhhb retained their original body weight, whereas those receiving pbs or rsv-vhhb gradually lost weight (data not shown). intranasal administration of h -vhhb at or hours before challenge resulted in undetectable lung virus titers. when animals were treated with h -vhhb hours before challenge, virus titers were fold lower compared to pbs and rsv-vhhb treated mice, and three out of seven animals still had undetectable virus titers ( figure ). we next determined if h -vhhb nanobody Ò could be also be used therapeutically. we administered lg of this nanobody Ò intranasally to mice up to hours after chal-lenge with ld of nibrg- ma virus. four days after challenge, animals that received h -vhhb , , or hours after challenge had significantly higher body weight (data not shown) and lower lung virus loads than control mice. although mice treated with h -vhhb nanobody Ò hours after challenge were not clinically protected compared to control mice, they had significantly lower lung virus titers (figure ). to identify the ha amino acid residues that are potentially involved in h -vhh binding, escape viruses were selected by growth and plaque purification of nibrg- ma virus in the presence of h -vhhm or h -vhhb nanobodies Ò . the ha sequences of six independently isolated h -vhhm escape viruses revealed substitution of a lysine by a glutamic acid residue at position in ha (h numbering). in addition, two h -vhhm escape mutants carried an n d and four carried an n s substitution. the three-dimensional structure of nibrg- ha shows that n d ⁄ s and k e are close to each other as part of the corresponding antigenic site b in h ha. , interestingly, the n d ⁄ s mutations remove an n-glycosylation site, which is surmised to have evolved in h n ha as a strategy to mask an antigenic site. escape viruses selected in the presence of h -vhhb carried k n (n = ) or k e (n = ) substitutions. these results indicate that residues in antigenic site b, at the top of ha and very close to the receptor binding domain (rbd), are essential for neutralization of the virus by h -vhhm ⁄ b nanobodies Ò (figure ). the virus titer was measured in lung homogenates prepared on day after challenge. the x axis refers to the time points in hours relative to the challenge (time = hours) when ha-specific nanobodies (h -vhhb), control nanobodies (rsv-vhhb) or pbs was administered to the mice. # below detection limit, n not determined [n = - mice per condition: p values < ae (*)]. here we demonstrated that prophylactic and therapeutic treatment with llama-derived immunoglobulin single variable domain fragments is effective to control infection with h n influenza virus in a mouse model. we demonstrate that pulmonary delivery is a highly effective route of administration to treat or prevent influenza virus infection. in addition, we demonstrate that a homobivalent h -vhhb has powerful h n -neutralizing activity in vivo. it is important to note that we used a mouse-adapted derivative of the non-highly pathogenic nibrg- virus in our challenge model. nevertheless, this virus induces severe morbidity and lethality in mice. compared to conventional neutralizing monoclonal antibodies, vhhs offer the advantage that they are easy to produce in escherichia coli, typically with high yield. in addition, their small size ( kda for a monovalent vhh) and high folding capacity allow the generation of oligovalent vhh derivatives. in vitro escape selection revealed that a k e substitution in ha abolished the neutralizing effect of h -vhhm ⁄ b. a lys or arg residue at this position is conserved in all human h n virus isolates. of note, all selected escape mutants contained a glutamic acid or serine residue at position , which suggests that the conserved positively charged amino acid is important for neutralization by h -vhh nanobodies Ò . interestingly, escape mutants selected with h -vhhm also carried an n d ⁄ s co-mutation that removes an n-glycosylation site in this antigenic site of ha. the predicted n-glycosylation site at n in a ⁄ hong kong ⁄ ⁄ ha was shown to be glycosylated and may have evolved to mask an antigenic site near the rbd. , the selected amino acid changes are located near the receptor binding site of ha. therefore, it is possible that enhanced receptor binding properties of these escape viruses contribute to or are responsible for the loss of neutralizing activity of h -vhh nanobodies Ò . , we conclude that influenza virus neutralizing nanobodies Ò have considerable potential for the treatment of h n virus infections. although we focused on vhhs that presumably recognizes an epitope near the rbd, it is possible to select vhh molecules that bind to other epitopes in ha, including more conserved domains. more, a novel na (i m) substitution was discovered in a series of specimens from a patient. for the amantadine resistance, samples were tested, and all of them were confirmed to be resistant. we collected respiratory specimens from patients who had been clinically refractory to antiviral treatment since october upon ethical approval from the relevant institutions. to investigate the resistant pattern, sequence analysis to the na and matrix (m ) genes were conducted by reverse transcription (rt)-pcr and sequencing reaction. the obtained sequences were analyzed by the influenza sequences and epitopes database, which was developed in korea. eleven patients were found to be having oseltamivir-resistant pandemic (h n ) viruses with the h y substitution in the viral na genes (tables and ). some cases were associated with oseltamivir treatment on the basis of h y change from the oseltamivir-sensitive genotypes to oseltamivir-resistant genotypes in consecutive samples from the same patient. furthermore, a novel na (i m) substitution that may be associated with oseltamivir resistance was detected in specimens from one patient (patient g) who had myelodysplasia and received oseltamivir and peramivir (tables and ). in addition, we obtained viruses from clinical specimens (patients a and c) and evaluated antiviral susceptibility by measuring the dose of oseltamivir and zanamivir required for % inhibition (ic ) of na activity. these viruses (from patients a and c) were resistant only to oseltamivir (ic ae and ae nmol ⁄ l, respectively). susceptibility to zanamivir was not altered whether na contained y or h (ic ae and ae nmol ⁄ l, respectively). one isolate of pandemic (h n ) virus with an oseltamivir-sensitive genotype (h in its na) was susceptible to oseltamivir (ic ae nmol ⁄ l) and zanamivir (ic ae nmol ⁄ l). patients with oseltamivir-resistant pandemic (h n ) were treated during hospitalization with oseltamivir alone or with a combination of other antiviral drugs ( we found patients of oseltamivir resistance with h y mutation in the na gene of pandemic (h n ) virus through the surveillance of patient refractory to antiviral treatment. in addition, novel amino acid change (i to m) at position in the na gene, which might influence oseltamivir susceptibility, was detected in sequential specimens of a patient. these data showed that generation of oseltamivir resistance could be associated with oseltamivir treatment. therefore, it needs to strengthen the antiviral monitoring by supplementation of the clinical data including antiviral treatment. during the pandemic, oral oseltamivir was the primary antiviral medication used for treatment of hospitalized patients with ph n infection. many physicians worried that clinical deterioration or failure to respond to treatment with oseltamivir was due to either oseltamivir resistance or oseltamivir failure. in the united states, two investigational intravenous (iv) nais were available during - : peramivir through emergency use authorization and zanamivir by investigational new drug application. peramivir would be an option for patients with oseltamivir failure, but would not be appropriate for patients infected with h y oseltamivir resistant mutants. iv zanamivir was available in limited supply, but would be appropriate for severely ill patients infected with an oseltamivir-resistant ph n virus. during the pandemic, clinicians had few options for antiviral resistance testing in the united states. to respond to this need, the us centers for disease control and prevention (cdc) offered antiviral resistance testing for patients suspected to have clinical failure due to oseltamivir resistance. we describe the methods that cdc used to prioritize patients for testing during the pandemic and to detect markers for oseltamivir resistance, as well as the results from this testing. to facilitate decisions on which patients to test, we developed testing algorithms that were shared with state labora-tories, epidemiologists, and the emergency operation center at cdc. we prioritized patients who might benefit the most from antiviral testing given the inherent delay in providing antiviral results, e.g. patients who might have prolonged ph n shedding. patients that were critically ill [intensive care unit (icu) admission] or patients with severe immunocompromising conditions with clinical evidence for oseltamivir treatment failure (persistent detection of virus and clinical unresponsiveness to the drug) were prioritized. in addition, we tested specimens from patients that failed oseltamivir chemoprophylaxis. standard forms with information regarding specimen and minimal clinical information were collected on all patients. all protocols were validated and approved by clinical laboratory improvement amendments, e.g. quality standards to ensure accuracy, reliability, and timeliness of patient test results. information collected on patients was deemed public health response, not research, at cdc. clinical specimens, confirmed as pandemic influenza a (h n ), were tested for the h y mutation in the na using pyrosequencing. results were returned to sender within - hours of specimen receipt. from october until july , a total of specimens from patients were submitted for testing. viruses from ( %) of patients had h y mutation in the na in at least one submitted specimen. clinical information was available for patients (table ) . most patients had received oseltamivir for treatment prior to obtaining the specimen sent for antiviral testing. four patients received oseltamivir for chemoprophylaxis, all were immunosuppressed, and all had the h y mutant; duration of chemoprophylaxis until ph n infection was detected varied ( - days). among the patients with an h y mutant who were treated with oseltamivir, the median time on oseltamivir prior to collection of specimen with h y mutation was days (range - days). three patients were part of a hospital cluster of oseltamivir-resistant virus infections and were infected with h y mutants prior to oseltamivir treatment. patients with immunocompromising conditions accounted for almost half of all patient specimens tested, but they accounted for the majority of oseltamivir-resistant ph n virus infections (table ) ; among individuals with severe immunocompromising conditions and clinical failure while on oseltamivir therapy, ( %) had the h y mutant detected. among the immunosuppressed patients with an oseltamivir-resistant virus, ( %) had hematologic malignancies reported. in contrast, among the subset of icu patients without immunocompromising conditions and clinical failure while on oseltamivir therapy, we found little resistance: ( ae %) of icu patients had oseltamivir resistance detected. during the pandemic, we were able to provide timely and useful information to clinicians regarding suspected cases of oseltamivir resistance. our testing algorithm limited the number of specimens to specimens from the highest risk patients that would benefit the most from antiviral treatment. such an approach allowed us to offer this service without compromising our public health duties. in addition, the information we collected on patients from this service complimented our data on the national surveillance for antiviral resistance. we also performed national antiviral resistance surveillance from april to july . overall, resistant ph n viruses were identified from april to july in the united states among tested samples, including specimens described above, surveillance specimens, and resistant viruses reported in the literature. further studies to understand risk factors for oseltamivir-resistant ph n infection in patients with severe immunocompromising conditions are needed. while efforts to provide antiviral testing technology and materials to state laboratories are ongoing, clinicians still have limited options for such testing. rapid and inexpensive assays that could be performed by clinical laboratories, especially those caring for immunosuppressed patients, would be useful to inform patient care. the applied biosystems Ò na-xtd tm influenza neuraminidase assay kit provides the next-generation na-xtd tm , -dioxetane chemiluminescent neuraminidase (na) substrate, together with all necessary assay reagents and microplates, to quantitate sensitivity of influenza virus isolates to neuraminidase inhibitors. like the na-star Ò influenza neuraminidase inhibitor resistance detection kit, the na-xtd tm influenza neuraminidase assay provides highly sensitive detection of influenza neuraminidase activity. in addition, the na-xtd tm assay provides extended-glow light emission that eliminates the need for reagent injection and enables signal measurement either immediately or up to several hours after assay completion. the na-xtd tm assay is also used to quantitate influenza na activity directly in cellbased virus cultures to monitor viral growth or inhibition. global monitoring of influenza strains for resistance to neuraminidase inhibitors (nis) is essential for understanding their efficacy for seasonal, pandemic, or avian influenza, and studying the epidemiology of viral strains and resistance mutations. functional neuraminidase inhibition assays enable detection of any resistance mutation, making them extremely important for global monitoring of virus sensitivity to nis. the first-generation chemiluminescent na-star Ò influenza neuraminidase inhibitor resistance detection kit has been widely used for virus ni sensitivity assays, - including identification of a ⁄ h n pandemic virus resistant to oseltamivir. , in addition, this assay has been used for identification of new ni compounds, ni characterization, studies of virus transmission, drug delivery, na quantitation of virus-like particles, and cell-based virus quantitation. neuraminidase assays performed with chemiluminescent , -dioxetane substrates, including na-star Ò and na-xtd tm substrates, typically provide -to- -fold higher sensitivity by signal-to-noise ratio than assays performed with the fluorescent munana substrate. in addition, chemiluminescent assays provide linear results over - order of magnitude of neuraminidase concentration compared to - orders of magnitude with the fluorescent assay. the high assay sensitivity achieved with chemiluminescent assays enables use of lower concentrations of viral stocks, and the wide assay range minimizes the need to pre-titer virus stocks prior to ic determination. chemiluminescent reactions result in conversion of chemical energy to light energy, as light emission. the na-xtd tm substrate is a , -dioxetane structure bearing a sialic acid cleavable group. to perform the na-xtd assay, virus dilutions (from cell culture supernatant) are pre-incubated in the presence of neuraminidase inhibitor. then na-xtd substrate is added and incubated for minutes for substrate cleavage to proceed. finally, light emission is triggered upon addition of na-xtd accelerator, which provides a ph shift and a proprietary polymeric enhancer, both required for efficient light emission. chemiluminescent assays are performed in solid white microplates, and light emission is measured in a luminometer. the na-xtd tm substrate has a single structural difference from the na-star Ò substrate that provides a much longer-lasting chemiluminescent signal, with a signal half-life of approximately hours (not shown), compared to $ minutes with the na-star assay, eliminating the need for luminometer instruments equipped with reagent injectors and enabling more convenient batch-mode processing of assay plates. the na-xtd tm assay kit also provides a new accelerator solution, containing a next-generation polymer enhancer, and a triton Ò x- -containing sample prep buffer providing enhanced na activity. read-time flexibility is demonstrated by determination of oseltamivir ic values using data collected over hours after addition of na-xtd tm accelerator. although signal intensity slowly decreases over time, the ic curves and values are identical at each time point, shown using influenza b ⁄ lee ⁄ ( figure ) . triton x- detergent at % has been shown to inactivate flu virus while increasing neuraminidase activity. the addition of na sample prep buffer (containing % triton x- ) to virus stocks (at ⁄ volume, achieving a final concentration of %) provides increase in na activity up to fourfold, but is not consistently observed, and seems to be most effective with more concentrated virus stocks. ic values are unaffected by the addition of triton x- to the virus stock prior to virus dilution (not shown), so the assay is compatible with known virus inactivation reagents. assay sensitivity and ic values determined with the na-xtd assay have been compared to those obtained with both the chemiluminescent na-star assay and the fluorescent na-fluor assay (not shown). the chemiluminescent assays provide -to -fold higher sensitivity by signal-to-noise ratio, depending on the virus strain, wider assay dynamic range, and better low-end detection limit than the fluorescent assay. the wide assay range with the chemiluminescent assays enables determination of ic values over a range of virus concentrations, eliminating the need to titer virus prior to performing ic determination assays. ic values obtained with the na-xtd assay are nearly identical to those obtained with the na-star assay, with both oseltamivir and zanamivir neuraminidase inhibitors, and tend to be slightly lower than ic values obtained with the fluorescent assay. viral na quantitation provides a convenient read-out to measure viral growth or inhibition, including inhibition in the presence of inhibitory compounds or antibodies, described as accelerated viral inhibition with na as readout assay (avina). bation in the presence of varying concentrations of oseltamivir carboxylate. samples of culture media were assayed hours later. quantitation of na activity with the na-xtd tm assay demonstrates inhibition of viral growth by oseltamivir carboxylate in cell culture ( figure ). different volumes of culture media were assayed with the na-xtd assay, either in the culture plate or in a separate assay plate (not shown). performing the assay using the entire well contents ( ll) reduces assay sensitivity due to the high concentration of phenol red. assaying a smaller volume of culture medium (either in culture plate or a separate assay plate) provides higher sensitivity, and enables temporal monitoring or use of remaining culture medium for other assays. the applied biosystems Ò na-xtd tm influenza neuraminidase assay kit is a next-generation chemiluminescent neuraminidase assay providing high assay sensitivity and ''glow'' light emission kinetics for improved ease-ofuse. the applied biosystems Ò na-fluor tm influenza neuraminidase assay kit, based on the fluorescent mun-ana substrate, has also been developed to complement the na-xtd tm and na-star Ò chemiluminescence assays, for users lacking luminometer instrumentation or choosing to use fluorescence assay detection. together these kits offer: • standardized reagents and protocols • choice of detection technology • simple instrumentation requirements • high sensitivity for use with low virus concentrations • compatibility with batch-mode processing and largescale assay throughput • broad specificity of influenza detection • flexibility in assay format • additional na assay applications -cell-based viral assays, screening for new nis, detection of na from other organisms functional neuraminidase inhibition assays enable detection of any resistance mutation and are extremely important in conjunction with sequence-based screening assays for global monitoring of virus isolates for ni resistance mutations, including known and new mutations. together, these assays provide highly sensitive, convenient and versatile assay systems with standardized assay reagents, and simple assay protocols for influenza researchers. over hospitalizations and deaths in the us annually are attributable to seasonal influenza, primarily in chronically ill persons and the elderly. - following the emergence of pandemic h n influenza, severe illnesses have also been observed in children and young healthy adults. the occurrences of staphylococcal and pneumococcal pneumonia complicating influenza pandemics are well described. [ ] [ ] [ ] although temporal associations of bacterial pneumonia and influenza circulation have been reported, there is little precise data on rates of bacterial complications of seasonal or pandemic influenza. the study of bacterial lung infection has been hampered by insensitive tests for invasive disease and the difficulty of interpreting routinely obtained sputum culture results. , procalcitonin (proct), the prohormone of calcitonin, can discriminate viral and bacterial infections. this -aminoacid precursor protein normally produced by neuroendocrine cells of the lungs and thyroid gland was first shown to be elevated in bacterial infections in patients with pulmonary injury and pneumonitis. stimuli of proct include tnf-a, endotoxin, and other bacterial products. several studies indicate that bacterial infections commonly induce hyperprocalcitonemia, but that viral infections, including h n , are associated with only minimal increases. , , of note, proct induction is attenuated by viral-induced interferon-c. a meta-analysis of studies comparing proct and crp as markers for bacterial infection found that proct was more sensitive and specific than crp for differentiating bacterial from other causes of inflammation. , therefore, we measured proct levels in patients with seasonal and pandemic influenza and compared results with conventional methods for bacterial diagnosis. adults ‡ years of age admitted to rochester general hospital (rgh) from november st to june th for two winter seasons ( - ) with an admitting diagnosis compatible with acute respiratory tract infection were recruited for the study. patients were screened within hours of admission, and those with prior antibiotic use, immunosupression, or pregnancy were excluded. subjects or their legal guardian provided written informed consent. the study was approved by the university of rochester and rgh research subjects review board. at enrollment demographic, clinical and laboratory information was collected. influenza testing included nosethroat swabs (nts) for rapid antigen, viral culture, and reverse transcription-polymerase chain reaction (rt-pcr) and serology. testing for bacterial pathogens included blood cultures, sputum for culture and gram stain, nts for mycoplasma pneumoniae and chlamydophila pneumoniae pcr, s. pneumoniae antigen testing, and pneumococcal serology. if patients were unable to expectorate, sputum was induced with normal saline and bronchodilators. specimens were considered adequate by the standard criteria of > neutrophils (pmns) and < epithelial cells per high power field. serum was collected at admission and hospital day for proct measurements. influenza infection was defined a positive result for any of the following tests: . cloned proteins were coated on eia plates at ug ⁄ ml in bicarbonate buffer. after overnight incubation, plates were washed and two-fold dilutions of serum were incubated overnight at room temperature. plates were washed and incubated with alkaline phosphatase conjugate for hours, followed by substrate. a greater than or equal to fourfold rise in titer was considered evidence of infection with s. pneumoniae. urinary antigen for s. pneumoniae samples were assayed for antigen using the binax now kit. (binax inc, scarborough, me, usa). the proct was measured using time resolved amplified cryptate emission technology (kryptor pct; brahms, henningsdorf, germany). functional sensitivity is ae ng ⁄ ml (normal levels are ae ± ae ng ⁄ ml). mycoplasma and chlamydia pcr real-time pcr targeting the p adhesion gene for m. pneumoniae and the ompa gene for c. pneumoniae was used to detect atypical bacteria. results fifty-one of ( ae %) illnesses evaluated tested positive for influenza virus. of these, were due to ''seasonal influenza'' ( influenza a ⁄ h n and influenza b), and were identified as ''pandemic influenza'' ( h n ). demographics of both groups were similar: mean ages ± and ± years, respectively, and equivalent sex and racial characteristics. other than a higher incidence of underlying lung disease in the seasonal group ( % versus %, p = ae ), pre-existing medical conditions including obesity were similar. symptoms, physical findings, and discharge diagnoses did not differ, and chest radiographs (cxr) showed infiltrates in % and % of seasonal and pandemic subjects, respectively. two pandemic and one seasonal influenza patient developed respiratory failure, and none died. overall, bacterial infections were diagnosed in ( %) subjects ( -seasonal and -pandemic), and none were bacteremic. bacterial infections included: -s. pneumoniae, -m. pneumoniae, -s. aureus, and -h. influenzae. all seasonal patients were diagnosed with asthma or bronchitis, whereas three pandemic patients had pneumonia. mean serum proct (ng ⁄ ml) levels in seasonal versus pandemic patients on admission and day were: ae ± ae versus ae ± ae and ae ± ae versus ae ± ae , respectively, and were not significantly different (table ) . several patients in the pandemic group had high proct levels, and there was a trend toward more pandemic patients having admission proct values ‡ ae ng ⁄ ml than seasonal subjects [ ( %) versus ( %), p = ae ] ( figure a , b). of the four patients with proc-t > ae ng ⁄ ml, two had dense infiltrates on cxr, one had a peripheral wbc of ⁄ ml with a threefold increase in s. pneumoniae antibody, and one developed respiratory failure associated with copd exacerbation. reliable sputum samples (within hours of antibiotics) were collected in only ( %) subjects. of these, proct was ‡ ae ng ⁄ ml in two with influenza alone and three associated with bacterial infection, and < ae ng ⁄ ml in with influenza alone and five associated with bacterial infection. in the with reliable sputa and accepting the conventional bacterial diagnosis, sensitivity of a proc-t ‡ ae ng ⁄ ml for bacterial infection was %, specificity %, positive predictive value %, and negative predictive value %. notably, one patient considered to have influenza alone (proct - ae ng ⁄ ml) had group a streptococcus and s. aureus in a contaminated sputum and bilateral infiltrates on cxr. three of five patients with bacterial infections and proct < ae ng ⁄ ml had a clinical diagnosis of bronchitis. mean proct values were significantly higher in patients with infiltrates versus those with atelectasis or no acute disease on cxr ( ae ± ae ng ⁄ ml versus ae ± ae ng ⁄ ml, p = ae ). combining patients with proct values ‡ ae ng ⁄ ml with those having positive bacterial tests, rates of bacterial infection associated with seasonal and pandemic influenza were % and %, respectively. notably, antibiotics were administered to % of subjects despite % having no acute disease on cxr. in our study, bacterial infections were diagnosed in approximately % of adults hospitalized with influenza with no significant difference in rates noted between seasonal and pandemic influenza infected subjects. previous reports of bacterial infection rates of - % with seasonal influenza are difficult to compare with recent studies of pandemic influenza, because the latter tended to focus on more severely ill patients. [ ] [ ] [ ] bacterial pneumonia has been suspected or diagnosed in - % of patients in intensive care associated with h n infection and up to % of patients who died. , despite aggressive pursuit of specimens for bacterial testing, diagnoses could be confirmed in only ( ae %) of patients using conventional methodology. given the difficulty in establishing a diagnosis of bacterial infection, elevated proct values may be helpful to identify patients at high risk for invasive disease. in a study of patients with severe h n or bacterial infection necessitating intensive care, a threshold proct level of ae ng ⁄ ml, demonstrated % sensitivity and % specificity for bacterial infection. among patients with h n associated pneumonia, many of whom had respiratory failure, a threshold proct value of ae ng ⁄ ml provided a sensitivity of % and specificity of % for bacterial infection. access to samples from lower airways in ventilated patients in these studies may have improved recovery of bacteria and account for the different results we observed. it should be noted that none of our patients were bacteremic, which is a very strong stimulus for proct release. proct levels have been used successfully to guide therapy in community acquired pneumonia, and our data showing high proct levels in patients with infiltrates on cxr suggests proct may be most useful for excluding invasive disease. , elevated proct levels were not observed in patients with purulent sputum and clear cxr. it is notable that a proct level of < ae ng ⁄ ml did not exclude patients with bacterial bronchitis since proct has been used to guide antibiotic therapy in copd exacerbations. while it could be argued that healthy patients with bacterial bronchitis do not require antibiotic treatment, physician behavior in our study indicates antibiotics are frequently prescribed. combining patients with proct values ‡ ae ng ⁄ ml and those with a positive bacterial test, approximately % in patients in our study had bacterial complications associated with influenza infection. efforts should be made to curtail antibiotic use in hemodynamically stable patients with clear cxrs. given physician discomfort regarding discontinuing antibiotics, proct measurements in combination with routine bacterial cultures should be useful tools to guide therapy. influenza, mrsa, cytokines: diagnosis, treatment, prevention -a possible strategy for outpatient care we started the antiviral treatment of influenza in humans using neuraminidase inhibitors on january , in a successful attempt to cure a -year-old patient. since then, we have used the inhalant antiviral drug zanamivir, and later (october , ) changed to the use of oseltamivir with systemic bioavailability for treating patients with influenza. after years of experience with antiviral treatment of outpatients, we highlight the importance of early diagnosis and early treatment. the necessity of an earliest possible diagnosis was confirmed in the pandemic of . large hospitals reported that patients with an h n ⁄ infection had to be treated with extracorporeal membrane oxygenation. we are convinced this is due to delayed recognition of infection in most cases. valuable time is lost when the patient with a sudden onset has to be brought to a hospital for emergency treatment. the point at which the patient goes to the doctor is decisive, and this problem of timing and the delivery of early treatment is not specific to germany. in our medical office, we assessed patients with suspected influenza (to date seasonal infections, and in , h n ⁄ ) through clinical diagnosis, and then proven by point of care rapid test (quickvue; quidel, san diego, ca, usa) followed by pcr. all of the patients undergo concomitant lab tests: leukopenia, serum iron level, and the humoral inflammation status [sum of the c-reactive protein (crp) and fibrinogen levels]. because of the constant threat of a bacterial superinfection, a bacterial swab and antibiogram is carried out on every patient. in all cases positive for influenza, oseltamivir was given immediately. nowadays it is important that a double infection with influenza and mrsa must be recognized immediately and treatment started at once with antivirals and, when appropriate, with a suitable antibiotic. we pay particular attention to an extremely low iron level (signum mali ominis). in addition we monitor oxygen saturation and the course of the humoral inflammation status every - hours for every of our outpatients. among our patients with seasonal influenza, we saw within hours, within hours, and within hours after disease onset. for pandemic influenza, it was patients within hours, within hours, and two within hours. for all patients, we measured crp < ae mg and fibrinogen < mg ⁄ dl ( hours), crp < mg and fibrinogen < mg ⁄ dl ( hours), and crp > mg and fibrinogen < mg ⁄ dl ( hours, only seasonal cases). antibiotics were necessary in cases, heparin and oxygen administration in cases. one hundred forty-eight patients had a superinfection following influenza. the most common strains were haemophilus parainfluenzae and staphylococcus aureus. the subsequent use of a suitable antibiotic was only necessary in % of the patients. in all cases diagnosed, treatment (including heparin and oxygen administration) and monitoring were conducted in our medical office. none of our patients (seasonal and pandemic) had to be admitted to hospital. the early decision of whether or not antiviral and antibacterial treatment is taking effect is the only way the threat of a cytokine storm can be averted. not only does the primary care physician have to be aware of the pathophysiology involved, but also the necessary diagnostic and therapeutic options have to be made available to him. the result will lead to a saving of both lives and healthcare costs. this applies both in epidemic as well as in pandemic times. today we know that influenza leaves behind a defenceless immune system, and that the proteases of s. aureus contribute to influenza associated pneumonia. mark von itzstein, who discovered neuraminidase inhibitors, emphasized the synergistic cooperation of viruses and bacteria (personal communication, ). mrsa and influenza viruses are posing problems worldwide. the case of a -year-old boy with h n ⁄ infection demonstrates how fatal developments can be prevented. due to his constantly recurring colds, we had already detected the mrsa colonization years earlier and had always worked on boosting his general health and resistance. both the patient and his family were included in dealing with the problem. the patient was, and is, always vaccinated early with a virosomal vaccine (baxter). during the oktoberfest in munich in september , when h n infections were increasingly occurring, we learned that our patient had come down with an extremely acute feverish illness. with the help of the rapid test, we diagnosed an h n ⁄ virus infection and started treatment with oseltamivir immediately. the humoral inflammation status, which had increased very rapidly to more than ae mg ⁄ dl within hours, was treated with the effective cotrimoxazol from the antibiogram. at the same time, the patient was heparinized. the following day the patient had no fever and was symptom-free. it was only through our early knowledge of what could develop pathophysiologically that we were in a position to make the right decision at the right time. every doctor treating outpatients can follow this procedure if he is familiar with the pathophysiology of the disease and has the available tests on hand: virus rapid test, additional laboratory parameters (leukopenia, iron), and the humoral inflammation status. the decisive factor, however, is the constant clinical alertness towards the course of every acute feverish cold with acute onset. the patient has to remain in the care of the attending physician, and the chosen treatment has to be administered and monitored. this means constant spo measurements and checking the humoral inflammation status every hours. if a clinical worsening occurs during monitoring, the treatment regime has to be changed immediately, which means the administration of an appropriate antibiotic. this outpatient care on the part of the doctor has to be available days a week so that no time will be lost. reports from the netherlands and denmark show that, with the help of this preventive strategy under the motto 'search and destroy,' the dangerous, fatal course of infections reported in germany with at least four deaths a day, can be avoided. however, the doctor has to be adequately remunerated for the elaborate amount of time this intensive outpatient care requires. with our strategy, we have moved from divergence to convergence in the care of our patients. we reported on our years of clinical experience with this approach at the antivirals congress in peking. our main message was early diagnosis and early treatment. we were able to demonstrate this in outpatients with seasonal influenza and h n ⁄ outpatients. our creed is: as much outpatient care as possible and as little hospitalization as possible. virological and autopsy findings in suspected and confirmed fatal cases of h n pandemic influenza in the czech republic -preliminary results influenza viruses cause substantial morbidity and mortality. pandemic influenza may have a serious impact on certain (mainly younger) age groups in comparison with seasonal flu. influenza is one of few viral infections capable of causing a pneumonia that is difficult to cure and ⁄ or leads to sudden death. the aim of this study was to analyze and compare virological and autopsy findings in patients who died with suspected or confirmed h n pandemic influenza virus infection. there were virologically confirmed cases of pandemic influenza and deaths in the czech republic during pandemic wave. more than influenza strains belonging to the new pandemic variant were isolated in the national influenza reference laboratory. postmortem biological samples were collected from any patient who died with suspected influenza infection to test for respiratory viruses. the samples were screened for h n pandemic influenza virus by real-time pcr (rt pcr), and when rt pcr positive, by virus isolation assay. no immunohistochemical staining for influenza antigen was done on the rna pcr positive cases. other important respiratory viruses such as respiratory syncytial virus, parainfluenza viruses, and adenoviruses were detected by virus isolation assay in a suitable cell culture. epidemiological analysis of postmortem histopathologic findings in the airway tissue was carried out in of fatal cases. virological findings were subsequently correlated with histological changes and available demographic and clinical data. statistical analysis was performed by t-test using spss software. sixty-one deaths ( males, females) were analyzed. the rna of the h n pandemic influenza virus was detected by pcr in cases, while cases remained negative. five respiratory syncytial viruses and two adenoviruses were detected in the influenza negative group. the mean age of confirmed h n pandemic influenza victims was ae years, age range - years and median ae years. the mean age of influenza negative victims was ae years, age range - years and median ae years. the % ci for the difference in the age between the two groups is ) ae ; ae . the test is statistically significant at the % level. the obtained significance (p = ae ) can be explained by the relatively small size of the study group. the most common postmortem histopathologic finding in the lung tissue of the h n pandemic influenza virus-positive victims was diffuse alveolar damage (often bilateral) and ⁄ or hyaline membrane formation, possibly with signs of respiratory distress syndrome (in , i.e., ae %, of autopsied patients). in the h n pandemic influenza virus negatives, the most common finding was pneumonia or bronchopneumonia with the detection of various bacterial species (in , i.e., ae % of autopsied patients). the cause might be either primary bacterial infection or superinfection following primary infection with influenza virus that remained undetected. the h n pandemic influenza victims were younger than the patients who died with suspected but undetected h n pandemic influenza. the majority of deaths were primarily linked to rapidly developing respiratory failure. this result supports the previous reports of severe respiratory outcomes in younger age groups that are typically linked to the spread of a pandemic strain of influenza. due to limited amount of pandemic vaccine, especially at the beginning of pandemic, it is advisable to assess experiences with antiviral treatment, mainly dosing, and way of antiviral administration. primers specific for each of the eight genes of pandemic h n ⁄ were adopted from assays as described previously to discriminate against seasonal human h n and h n viral segments (table ) . the primers were allowed to cross-react specifically with the sister clade viral segments of pandemic h n ⁄ . the method we employed in this study was a -step singleplex sybr green-based real-time rt-pcr. this approach helped lower the running cost of the assays and facilitated downstream molecular analyses (e.g., sequencing) by using screened cdna samples. viral rna was extracted from viral cultures or clinical samples as described , and was converted to cdna in a universal rt-pcr. each ll rt reaction containing ae ll of purified rna, ll of · firststrand buffer (invitrogen), u of superscript ii reverse transcriptase (invitrogen), ae lg of uni ( ¢-ag-caaaagcagg- ¢), ae mm of deoxynucleoside triphosphates and mm of dithiothreitol was incubated at °c for minutes, followed by °c for minutes for heat inactivation. for each segment-specific real-time pcr, the ll reaction contained ll of a -fold diluted cdna samples, ll of fast sybr green master mix (applied biosystems), and ae lm of the corresponding primer pair. the thermocycling conditions of all eight segment-specific pcrs were optimized as °c for seconds, followed by cycles of °c for seconds and °c for seconds, and all eight assays were performed simultaneously in a sequence detection system (applied biosystems). at the end of the amplification step, pcr products went through a melting curve analysis to determine the specificity of the assay ( - °c; temperature increment: ae °c ⁄ seconds). cdna of a ⁄ california ⁄ ⁄ virus was used as a positive control. robust and specific amplification was achieved in all eight segment-specific real-time rt-pcr reactions. pcr product for each segment of pandemic h n ⁄ yielded unique melting curve pattern with distinctive melting temperature (tm), which was not observed in negative and water controls ( figure ). reactions with tm value within sds of the mean tm were determined as positive. we evaluated the assays with a number of serologically confirmed human clinical samples. all pandemic h n ⁄ samples (n = ) were positive in all eight assays, while all seasonal samples (h n = ; h n = ) were negative in all assays, as expected ( figure and data not shown). these results showed that no reassortant of pandemic h n and seasonal viruses was present in the tested human isolates. we applied these assays to our on-going influenza virus surveillance program in swine. nasal and tracheal swab samples were collected at an abattoir in hong kong and cultured in madin darby canine kidney cells or embryonated eggs as described. positive viral cultures in hemagglutination assays were tested with the established segmentspecific real-time rt-pcr assays. among swine viral isolates collected from to september , of them were recognized as pandemic h n ⁄ in all eight segments. they were confirmed to be of pandemic h n ⁄ origin by subsequent full genome sequencing analyses, showing that there were interspecies transmissions of the virus from humans to pigs. , the remaining viruses had one to seven gene segments positive in the segment-specific real-time rt-pcrs. thirty of them were selected as representative samples for full genome sequencing analyses based on the genotyping data generated in our assays. they were swine h n or h n viruses with their gene segments derived from tr or eurasian avian-like swine lineages. it should be highlighted that all of their positive gene segments in our assays belonged to the sister groups of pandemic h n ⁄ . their melting curve patterns were very similar to those derived from segments of pandemic h n ⁄ , except for ha of tr lineage. our results successfully demonstrated the use of these segment-specific real-time rt-pcrs to recognize gene segments of contemporary tr (pb , pb , pa, ha, np, and ns) and ea (na and m) swine viruses. the ha-specific assay was able to discriminate pandemic h n ⁄ from other contemporary swine viruses in the same lineage. nevertheless, to confirm the identity and to examine all the genetic variations in the viruses of interest, full genome sequencing analyses were necessary. in this study, the biggest obstacles in primer design were sequence similarity and diversity of influenza viruses. we attempted to use degenerated primers, but they were highly non-specific. the finalized non-degenerated primers crossreacted with genes from pandemic h n ⁄ and its sister clade tr (pb , pb , pa, ha, np, and ns) and ea (na and m) swine viruses with some minor sequence mismatches. three avian (h n , h n , and h n ) and classical swine (h n ) were also tested with our assays. all of these animal viruses were negative, except for ns gene of the classical swine virus. our segment-specific real-time rt-pcr assays might be used in high throughput genotyping. they detected pandemic h n ⁄ viruses and acted as a preliminary screen-ing tool to select virus reassortants of interesting genotypes for further sequencing analyses. in fact, we identified a novel reassortant in january during the course of this study. this sw ⁄ hk ⁄ ⁄ has a previously unidentified viral gene combination as shown in figure . it was confirmed to be a reassortant between pandemic h n ⁄ and other swine viruses in full genome sequencing characterization. it has a pandemic h n -like n gene, an ea-like h , and the other six internal genes derived from tr swine viruses. , the eight established real-time rt-pcrs can rapidly reveal the gene-origins of influenza viruses. we are currently using these assays in influenza surveillance in humans and other animals. it is believed that similar strategy might be applied to detect and genotype other influenza viruses and possible reassortants in the future. pandemic influenza a ⁄ h n ⁄ infects millions of people around the world. a significant fraction of the world's population may also already have been exposed to the virus and, although asymptomatic, may be at least partially immune to the disease. a precise assessment of the number of people exposed to the influenza a ⁄ h n ⁄ virus is epidemiologically relevant. however, assays typically used to estimate antibody titers against a particular influenza strain, namely hi and neutralization, require use of the actual virus. this seriously limits broad implementation, particularly in regions where high biosafety facilities are unavailable. we developed an elisa method for the evaluation of presence of specific h n influenza virus-antibodies in serum samples. mouse anti-histidine tagged antibodies ( ll; lg ⁄ ml; abd serotec Ò , uk) in pbs (ph ae ) were dispensed into standard -well plates and incubated for - hour at room temperature. excess antibody was removed by at least two successive alternate washings with pbs-tween ae % and pbs. commercial blocking solution ( ll, superblock Ò t ; pierce Ò , usa) was added and incubated for at least hour at room temperature. after successive washing steps with pbs-tween ae %, non-glycosylated histidine-tagged recombinant protein ( ll; lg ⁄ ml) was added to each well. this protein consisted of the receptor-binding domain of the hemagglutinin of the influenza a ⁄ h n virus. , after hour incubation, wells were washed for at least two alternating minutes cycles with pbs-tween and pbs. a : dilution of the serum or plasma sample to be assayed ( ll) was added to each well and incubated at room temperature for hour. after repeated alternating minutes pbs-tween ae % and pbs washes, anti-human igg antibody solution ( ll ⁄ well; : dilution in pbs-tween ae %) marked with horse radish peroxidase (pierce Ò , usa) was added and incubated for hour at room temperature. after repeated alternate washes with pbs-tween ae % and pbs), substrate solution ( ll; -step ultra tmb-elisa; pierce Ò ) was added to each well. after incubation for minutes at room temperature in darkness, the enzymatic reaction was stopped by addition of m h so ( ll ⁄ well). yellow color produced by the enzymatic reaction was evaluated by absorbance at nm in a biotek Ò microplate reader (usa). blank assays using albumin in place of human sera established the elisa background signal, which was subtracted from sample absorbance signals: abs serum sample ¼ abs serum sample before correction À abs albumin sample : absorbance values were normalized based on the average signal of non-exposed subjects (uninfected subjects), and expressed as normalized absorbance (abs norm ): where abs serum ample is the sample absorbance signal, abs albumin sample is the albumin control absorbance signal, abs non exposed subjects is the average absorbance signal of non-exposed subject samples. for ferret serum samples, the same basic protocol was followed, with minor modifications. an anti-igg anti-ferret polyclonal antibody preparation was used at a dilution of : in pbs-tween ae %. a recombinant receptor-binding domain of the ha of the influenza a ⁄ h n ⁄ virus, expressed in escherichia coli strains, was used as the elisa antigen. this kda protein, designated here as ha - -rbd, contained amino acids - of the influenza a ⁄ mexico ⁄ indre ⁄ (h n ) hemagglutinin. a sequence coding for a series of six histidines at the n-terminus of the protein was included in the genetic construct to allow purification using immobilized metal affinity chromatography (imac) and attachment to assay surfaces treated with anti-histidine antibodies (or alternatively co + or ni + ). a panel of four samples (kindly provided by st. jude from ferrets exposed to different influenza strains, namely h n , h n swine, and h n , was also tested by the elisa method using : dilutions. protein ha - -rbd specifically and selectively recognizes antibodies from serum samples from convalescent h n ⁄ influenza subjects. dubois et al. demonstrated that this protein, produced in e. coli, folds properly into a -d structure practically indistinguishable from the analogous region in the ha of the influenza a ⁄ h n ⁄ virus. ha - -rbd preserves three of the conformational immunogenic epitopes (sa, sb, and cb) described for influenza a ⁄ h n hemagglutinins. the recombinant protein was used as the antigen, attached through histidine tags to microplate surfaces treated with anti-histidine antibodies to discriminate between serum samples from subjects exposed and non-exposed to influenza a ⁄ h n ⁄ . samples collected before the pandemic onset, and therefore presumed to exhibit low specific antibody titers against influenza a ⁄ h n ⁄ , were analyzed by elisa using the antigen ha - -rbd. the histogram of normalized absorbance values from this sample set displayed a normal behavior with a standard deviation of ae units. only ae , ae , and ae % of these samples exhibited normalized absorbance values higher than ae , ae , and ae , respectively. no sample from non-exposed individuals presented an absorbance value higher than ae . variability among samples from non-exposed subjects was much lower than in samples with high specific serum antibody titers from convalescent h n ⁄ patients. exposure to the h n ⁄ influenza virus with this elisa method can be predicted by absorbance values normalized to those of abs norm ¼ ðabs serum ample À abs albumin sample Þ=ðabs non exposed subjects À abs albumin sample Þ ð Þ serum from uninfected subjects. consequently, for reliable results, inclusion of samples from non-exposed subjects on every assay microplate is necessary. figure shows the analysis of human serum samples, including samples from convalescent patients with positive diagnosis by rt-pcr. three positive (dark gray bars) and two negative controls (light gray bars) were included in the same microplate. all serum samples corresponding to convalescent subjects exhibited absorbance values ae - ae times higher than negative samples ( figure ). normalized absorbance values above ae suggested exposure to the virus, although, a more conservative threshold value of ae units is proposed for discrimination between exposed and non-exposed subjects. the elisa method described here yields adequate reproducibility and a high signal ⁄ noise ratio within determinations in the same microplate and among different microplates. using a normalized absorbance value of ae , the method was able to discriminate samples from convalescent patients, preferably after the third week of infection, and at least up to the twentyfourth week of exposure. assay sensibility was further validated against results from hi assays. a previously reported study showed that all members in a pool of fourteen samples diagnosed as positive by hi exhibited normalized absorbance values higher than ae , and % of them exhibited normalized absorbance values higher than ae . in general, high hi titers (> ) were correlated with normalized absorbance values higher than ae . figure a shows results using the ha-rbd elisa method and the hi assay on a pool of seventeen known positive serum samples corresponding to convalescent h n ⁄ patients. all samples determined as positive by hi ( samples) were also positive by elisa. while sensitivity of the hi assay was ⁄ = ae %, the elisa method recognized all samples correctly as positive ( % sensitivity) when a threshold of ae or ae was used. figure b shows that sera from ferrets infected with other influenza strains (h n , h n swine, and h n ) showed no cross-reactivity when analyzed by elisa. in summary, the ha-rbd elisa method presented here consistently distinguished influenza a ⁄ h n ⁄ infected and non-infected individuals, particularly after the third week of infection ⁄ exposure. since no actual viral particles are required, this assay can be readily implemented in any basic laboratory. in addition, should sufficient vaccine be unavailable, this elisa could determine the level of specific antibodies against the virus and presumably the extent of partial protection in a subject. therefore, the elisa protocol might allow better administration of vaccination programs during pandemic or seasonal influenza outbreaks. in april , a novel h n influenza virus emerged in north america and caused the first influenza pandemic of the st century. [ ] [ ] [ ] [ ] the pandemic h n (pdmh n ) has a unique gene constellation that was not previously identified in any species or elsewhere. it is genetically related to the triple reassortant swine h n influenza viruses currently circulating in north america, with the exception of the neuraminidase (na) and matrix (m) genes, which are derived from a eurasian swine influenza virus. swine h n influenza viruses were first isolated in and continued to circulate in north america with very little antigenic changes (classical swine h n ) until . since , however, the antigenic make up of swine h viruses has shown increased diversity due to multiple reassortment events and the introduction of h n genes from human influenza viruses. currently, four swine h clusters (a, b, c, d) are found endemic in the north american swine population. , these swine h viruses show substantial antigenic drift compared to the classical swine h viruses. cluster d swine h is derived from current human h viruses, and there is a substantial antigenic divergence between classical swine h and human seasonal h viruses. epidemiological evidence shows a two-way transmission of influenza viruses between swine and humans, and such events lead to the emergence of the pdmh n virus. , , phylogenetic analysis have suggested that possible ancestors of the eight genes of pdmh n were circulating in the swine population for at least years prior to the emergence of the pdmh n virus in humans, although the pdmh n virus itself was not isolated from pigs until after the pandemic. interestingly, pdmh n infections have been reported not only in humans and pigs, but also in other animal species such as turkeys, cats, ferrets, cheetahs, and dogs. [ ] [ ] [ ] after the first report of pdmh n infection in swine in canada, other countries, including argentina, australia, singapore, northern ireland, finland, iceland, england, united states, japan, and china reported outbreaks of pdmh n in swine as well. , [ ] [ ] [ ] the ample geographic range of pdmh n outbreaks in swine, its apparent broad host range, and the possibility of two-way transmission between swine and humans poses a tremendous challenge for controlling the virus. therefore, to differentiate pdmh n from other h strains, particularly in swine and human populations, is an important issue to ascertain the magnitude of the disease caused by the pdmh n . in this study, we developed an elisa assay to discriminate pdmh n strains from other swine and human h viruses. madin-darby canine kidney (mdck) cells (atcc, manassas, va, usa) were maintained in modified eagle's medium (mem) containing % fbs. a ⁄ california ⁄ ⁄ ⁄ h n virus (ca ⁄ ) was kindly provided by the centers for disease control and prevention (cdc), atlanta, georgia. other viruses are listed in table . viruses were propagated in mdck cells and stored at ) °c until use. viruses were titrated by the reed and muench method to determine the median tissue culture infectious dose (tcid ). three monoclonal antibodies ( b , h , and f ) against ha of pandemic h n were prepared in our laboratory following previously described methods (shao and perez et al., unpublished). purification and labeling of mabs mab b , h and f were purified on a protein g-sepharose affinity column (upstate biotechnology, lake placid, ny, usa). biotinylation of the detection antibody in the elisa was performed using sulfo-nhs-lc-biotin (sulfosuccinimidyl- -(biotinamido)hexanoate; pierce, rockford, il, usa) according to the manufacturer's instructions. purified h and f were selected as the capture antibody, and biotin-conjugated b was selected as the detection antibody, and hrp-conjugated streptavidin (abcom, cambridge, ma, usa) was developed using the tmb substrate system (kpl, gaithersburg, md, usa). in brief, the mixture of the purified h and f ( ae and ae lg ⁄ ml respectively, in carbonate ⁄ bicarbonate buffer, ph ae ) was coated to -well plates (test well, t) for h at °c. at the same time, a control antibody was coated to -well plates (control well, c). after blocking the plates with % (w ⁄ v) non-fat milk in pbs for hour at °c, the samples were diluted in extract buffer ( %tween- , ae %bsa in pbs) and added to the wells ( ll ⁄ well, each sample was table . specificity assay of the sandwich elisa result (t ⁄ c) added to four wells-two for t wells and two for c wellsand the mixture was incubated at °c for hour. after four washes, ll biotin-conjugated b ( ae lg ⁄ ml) in dilution buffer ( ae % bsa in pbs) was added to the wells and the mixture was incubated for h at °c. following three washes, ll diluted hrp-conjugated streptavidin ( ae ng ⁄ ml) in dilution buffer was added to the plates. after incubation for h at °c, the plates were washed five times, and the binding developed using the tmb substrate system for minutes. the ratio of the average od value of the t wells to that of the c wells (t ⁄ c) of individual samples was calculated. t ⁄ c values > ae were considered positive in the sandwich elisa. we developed three monoclonal antibodies, b , h , and f , against a prototypical pdmh n strain, a ⁄ california ⁄ ⁄ (h n ) (ca ⁄ ). these monoclonals were used to develop a rapid sandwich elisa for specific diagnosis of pdmh n strains. purified h and f were used as capture antibodies, whereas the biotin-conjugated b was used as detection antibody. the sandwich elisa showed strong reaction with different pdmh n strains as described in in order to evaluate if the sandwich elisa could distinguish the pdmh n from other swine h clusters (a, b, c, d), swine influenza strains spanning these clusters were tested. these viruses were first diluted : in extract buffer, and then added to the coated plates. as shown in table , the t ⁄ c ratios of these viruses were < ae , and therefore showed negative elisa result. likewise, testing of human seasonal virus strains a ⁄ brisbane ⁄ ⁄ (h n ), a ⁄ malaya ⁄ ⁄ (h n ), a ⁄ wsn ⁄ (h n ), and a ⁄ brisbane ⁄ ⁄ (h n ) also showed negative elisa results. furthermore, the sandwich elisa showed no cross reaction with avian influenza viruses, including strains of the h , h , h , h , h , h , h , h , h , h , and h subtypes. more recently, the mutation d g in the ha of some pdmh n strains has been associated with exacerbated disease and altered receptor binding. [ ] [ ] [ ] [ ] [ ] to evaluate if such mutant could be detected in our sandwich elisa, we tested a mutant of a ⁄ netherland ⁄ ⁄ (h n ) carrying the d g mutation (engineered by reverse genetics). as described in table , our elisa could still capture the d g mutant virus and showed a positive reaction, which highlights the specificity of our assay for pdmh n strains, even those with mutations. to evaluate the sensitivity of the elisa, we used the serially diluted pdmh n viruses to determine the limit of detection (lod). as shown in table , in our elisa the highest positive dilutions of nl ⁄ and ca ⁄ were : and : , respectively. the lod of the sandwich elisa by tcid was ae · and ae · tcid ⁄ ml, for nl ⁄ and ca ⁄ , respectively. it is important to note that the t ⁄ c ratio from nl ⁄ and ca ⁄ viruses showed clearly a dose dependent effect, while the t ⁄ c ratio of a ⁄ swine ⁄ iowa ⁄ (h n ) did not show the same dependence and was always < ae , corroborating the high specificity of the sandwich elisa for pdmh n strains. although we did not compare our elisa with other current commercial rapid influenza detection kits, the lod of our elisa assay is similar to other commercial kits that detect human seasonal influenza virus. comparison of the sandwich elisa with the ''gold standard'' -virus isolation in order to further evaluate the feasibility of the application of the elisa to clinical samples, nasal wash samples ae · ^ )( ae ) )( ae ) )( ae ) )( ae ) )( ae ) )( ae ) )( ae ) )( ae ) -from ferrets, of those previously infected with ca ⁄ and shown positive by virus isolation, were tested. the samples were diluted : in extract buffer and then tested using the sandwich elisa. result showed out of positive samples by virus isolation were positive also by the sandwich elisa (sensitivity ae %). the samples tested that were negative by virus isolation were also negative in the elisa, indicating % specificity for our assay. these results show not only that our elisa has high compatibility with the virus culture method, but also indicates this application can be used for clinical samples. although real time rt-pcr targeting the ha gene has been used for specific diagnosis of pdmh n with high sensitivity, [ ] [ ] [ ] [ ] [ ] [ ] it is a method that requires manipulation of the sample to extract viral rna, and it is prone to crosscontamination during the pcr steps. in this study, we described a convenient sandwich elisa based on three mabs developed against the pdmh n strain. the elisa not only shows high specificity for pdmh n strain, but also shows great sensitivity. the elisa could distinguish pdmh n strains from human seasonal h and h viruses and, more importantly, from other swine h viruses. we must note that current rapid diagnostic tests cannot be used to differentiate pdmh n from swine or human h viruses. it is also worth noting that the sensitivity of commercial rapid antigen-based diagnostic tests for detecting pdmh n is lower than that for human seasonal influenza viruses. , a study by kok et al. showed that sensitivity of the current rapid antigenic tests for pdmh n is only ae %, whereas that for seasonal influenza a is ae %. chen et al. developed a dot-elisa and increased the sensitivity for influenza rapid antigen detection. however, the dot-elisa developed by chen cannot distinguish among subtypes. the lod of our elisa is between ae · to ae · tcid ⁄ ml, comparable to the lod of rapid diagnostic tests for human seasonal influenza viruses. compared to the ''gold standard''-virus isolation-our sandwich elisa showed ae % sensitivity using ferret nasal washes. our results highlight the potential application of our sandwich elisa for the specific diagnosis of pdmh n viruses. the timely and reliable laboratory evidences are vital factors for field epidemiologists trying to control outbreaks of infectious diseases and for the practicing clinicians to properly manage disease cases. therefore, analysis of new detection methods in comparison to the routine ''classical'' methods is essential to select new methods to be introduced into health service practices, especially in developing countries. in this study we have compared rt-rt-pcr detection of influenza viruses and direct fluorescent-antibody assay using r-mix hybrid cells (a &mv lu) with the ''classical'' cell culture methods in developing country settings. in this study, we analyzed nasopharyngeal swabs col- the detection of influenza h , h , b, and pandemic influenza (h )pdm virus-specific nucleic acids was performed by rt-rt-pcr in abi fast real time pcr system using primers recommended by cdc, usa, and super-scriptÔ iii one-step rt-pcr and platinum Ò taq dna polymerase kits (invitrogen). the cycling protocol was: minutes at °c, minutes at °c, and cycles of seconds at °c, seconds at °c. rapid detection of influenza infected cells has been performed by dfa using the infected hybrid cells of r-mix within hours after inoculation, according to the manufacturers instruction (diagnostic hybrids, inc., usa). the isolation of influenza viruses was performed on mdck cell culture by the protocol recommended by cdc, usa. we detected ( ae %) influenza virus-specific nucleic acid fragments from all tested samples by rt-rt-pcr. among the positive samples, there were ae % a(h n ), ae % a(h n ), ae % influenza b, and ae % a(h n )pdm with different distributions by time series in different age-groups. inoculation of the cell lines by rt-rt-pcr positive samples selected randomly has detected influenza virus in ae % ( ⁄ ) on mdck cell culture and % ( ⁄ ) on r-mix hybrid cell culture with varying distribution for different strains. in other words, mdck cell culture technique was better for isolation for pandemic influenza viruses and dfa using r-mix hybrid cell culture technique for detection of seasonal influenza viruses (table ) . average times needed for the final results for different methods were: hours for rt-rt-pcr, hours for dfa on r-mix and days for mdck cell culture with two passages at least. the peak of the seasonal influenza a virus detection occurred in the - th weeks of , however the pandemic influenza detection peak was observed in the - th weeks of ( figure ). the outbreaks by seasonal influenza viruses was observed mostly among the children of - years of age, and pandemic influenza virus outbreak was observed mostly in the adults of - years of age. the results of this study indicate that rt-rt-pcr is the most suitable method for decision makers in epidemiological and clinical settings by sensitivity and timeliness. the final results show that r-mix dfa requires times longer, and by mdck cell culturing, times longer periods, than by rtrt-pcr. mdck cell culture technique has a higher isolation of pandemic influenza viruses, and r-mix dfa has a greater detection rate of seasonal influenza viruses by our results. according to our study, with rtrt-pcr, the isolation of positive samples by tissue culture of influenza a viruses was % and influenza b viruses was ae %, which is lower than in similar spanish study. however our study illustrates similar results with a canadian study where the sensitivity of dfa method and tissue culture technique was shown to be lower than rtrt-pcr sensitivity. as recorded by a study of american researchers, r-mix hybrid and conventional cell culture techniques have had similar sensitivity, which does not match the results of our study. however, the results of our study match with the results of italian and american scientists , where the r-mix hybrid method for seasonal influenza viruses is higher than mdck cell culture technique. background: viral kinetics is increasingly used to study influenza infectiousness. the choice of the study design, i.e. when and how many times nasal samples are to be collected in individuals depending on the sample size, is crucial to efficiently estimate the viral kinetics (vk) parameters. material and methods: we performed a model based optimal design analysis in order to determine the minimal number of nasal samples needed to be collected per subject and when to collect them in order to correctly estimate the vk parameters. the model used was a non linear mixed effect model developed with data collected from patients sampled nine times in days (initial design - samples collected), and we used d-optimization for design identification. we also computed the minimal number of participants necessary. results: considering that % of the influenza-like illness cases are not due to volunteer challenge studies have been used since the 's to provide data on virus shedding from the respiratory tract during influenza infection. recently, vk was studied in naturally acquired influenza infection. , these data are invaluable to describe the natural history of influenza-infection and to compute natural history parameters such as the latent period, generation time, or the duration of infectiousness. [ ] [ ] [ ] [ ] however, among the studies used in a meta-analysis about viral shedding kinetics, the designs varied greatly from one to another. these differences led to variable amount of available information concerning the vk. the lack of adequate sampling leads to imprecise estimates. on the other hand, intensive sampling or over-sampling, while associated with highly informative data, may lead to unnecessary discomfort for the patient and cost to the investigator. optimal design is increasingly used to conceive studies and provides cost-efficient designs. here we propose an optimised design to model vk in the case of influenza infection. we defined the number of participants, the number of samples to collect and their allocations. this design allows, at a minimum cost and discomfort, accurate vk curves and allows the natural history parameters to be well described. model a vk population model was proposed for influenza infection. this model describes with eight parameters the relations between free virus, uninfected target epithelial cells, infected epithelial cells, and early immune response. this model was built on a dataset of volunteers from which nasal samples were collected once a day over days. we call this dataset the ''original dataset''. three parameters, the induction of the early immune response, the virus production rate, and the virus clearance, did not show inter-individual variability and were precisely estimated (relative standard error below %). we considered them as fixed in this research work. five parameters were hence considered here: b the infection rate, d the infected cell mortality rate, w the effect of early immune response on virus production rate and v init the initial value of virus titre. in order to correctly estimate these parameters it is crucial to determine a design to collect informative data. optimal designs maximise the amount of information provided by the study. it involves the determination of the number and allocation of sample times per subject as well as the number of participants. d-optimization is based on the maximization of the determinant of the fisher information matrix and thus minimizes the variance of the parameters. we used the fedorov-wynn algorithm implemented in pfim . to maximize this determinant, which implies to pre-define a set of possible sample times. with the hypothesis that the inoculation occurred at : am, we chose three possible hours ( : , : , and : ) for each day with respect of the sleep-time. to validate the design, we simulated datasets of volunteers with the optimised design obtained. we then estimated the population parameters using monolix . for each of the datasets. we compared the estimated parameters obtained with the simulated datasets to the parameters used to build the optimal design. we computed the relative bias as: with n: number of successful estimations among the simulated datasets. h i : parameter value obtained with the ith dataset. h: parameter value obtained with the original dataset. we also compared the observed rse from these simulations with the rse predicted by pfim and the rse obtained with the original dataset. the rse is proportional to ffiffiffi n p , where n is the population size. we can hence deduce the smallest number of participants necessary to obtain rse below %. where rse predicted is the highest predicted rse (here rse for w) with participants and n predicted = and rse min is equal to ae . considering that % of the influenza-like illness cases are not due to influenza virus, the total number of participants should be multiplied by ae . we found that the best design was when all the participants are sampled five times: three times during the second day post-inoculation at : , : , and : hours and twice on the third day post-inoculation at : and : ( figure ). the comparison of the relative bias and rse predicted by pfim and those obtained after simulation and re-estimation of the parameters are shown in figure . v init and d in a lesser extent present bias. fixed effect parameters are precisely estimated and accordingly to pfim except for v init . we found that participants shedding virus or participants with ili symptoms are necessary if % of them are not infected with influenza virus. we propose an optimised design to accurately study the vk of influenza virus with the minimal number of samples. this design is well balanced between the amount of necessary information and the precision of estimation. we found that samples are necessary to precisely fit the vk curves, which is five times less than the number of samples collected in the original study. ??? the samples should be collected during the second and third days after inoculation. yet we showed in a previous work that the incubation period lasted ae days. ??? hence, the optimised sample times correspond to the two-first days of symptoms and this design could be applied to naturally acquired infections studies in which the inoculation time is unknown. an advantage of this design is its practicality and convenience. all samples are collected during the daytime and after the onset of symptoms. it can thus be used for studies with naturally acquired infections. the design was validated with several criteria concerning the accuracy of the estimation with the optimised design. the parameters estimates were generally satisfactory. the parameter describing the effect of the early immune response on the virus production rate was, however, less precisely estimated (predicted rse = %), and the initial value of the viral titre was very different of the one obtained with the original dataset (bias v init on figure ). this is probably due to the fact that it was measured at day post inoculation, and that the inter-individual variability is much higher than at day . furthermore, d (the infected cell mortality rate) seems also to be biased. this may be due to the fact that three parameters were fixed. the model used was developed from experimentally inoculated healthy volunteers with low serum haemagglutinin antibody titre and with virus inoculation time at : am. the applicability of the design to naturally acquired infection would depend on the pathogenicity of the virus as well as pre-existing immunity and the relevance of challenge method to natural influenza acquisition. our design could be directly used to accurately study vk during influenza infections and would reduce the discomfort of patients and the cost of the experimentation. usefulness of a self-blown nasal discharge specimen for use with immunochromatography based influenza rapid antigen test introduction influenza rapid antigen tests (irat) have become very popular and are widely used for confirming suspected clinical diagnosis of influenza in japan. most of the currently used irat that are based on immunochromatography (ic), nasopharyngeal swab, nasopharyngeal aspiration, and throat swab have been approved as specimens for japanese national health insurance purposes. but the specimen collection by these methods gives patients considerable discomfort, and sometimes appropriate specimens cannot be obtained due to patient resistance, especially by children. in the present studies, self-blown nasal discharge was used as the specimen for an irat, and the results were compared with the results of viral isolation and an identical kit primed with nasopharyngeal swab specimens for seasonal influenza viruses and pandemic (h n ) virus. patients who visited any of the clinics that belong to the influenza study group of the japan physicians association in the - and the - influenza seasons with influenza-like illnesses exhibiting findings were registered after providing informed consent. a square plastic sheet of · cm was handed to the patient. nasal discharge was collected by blowing the nose into the plastic sheet as a specimen for irat, i.e. self-blown specimen. two nasopharyngeal swab specimens were also obtained at the same time for irat and virus isolation. self-blown specimens were obtained successfully by ( ae %) of consecutive outpatients in the - season, as seen in table the sensitivity and specificity of various influenza rapid antigen tests have been reported in various settings. [ ] [ ] [ ] [ ] direct comparison of the results is difficult because of differences in patient or influenza virus, characteristics such as age, study designs, and other features. in this study of the - influenza season, the sensitivity, specificity, and accuracy of the ic kit primed with nasopharyngeal swab specimens were ae %, ae %, and ae %, respectively. these results were quite comparable to our results of the - season, in which the overall results of other ic kits were ae %, ae %, and ae %, respectively, indicating that the ic kit used is quite reliable. the sensitivity, specificity, and accuracy of an ic kit will vary by the method of specimen collection. in general, virus titer is considered to be highest with nasopharyngeal aspiration, lower with nasopharyngeal swabs, and lowest with throat swabs. practically, nasopharyngeal swab is the most popular. the sensitivity, specificity, and accuracy of the ic kit with self-blown discharge specimens compared well with those of an identical ic kit primed with nasopharyngeal swab specimens. for self-blown specimens, sensitivity and specificity were ae % and ae % for influenza a, ae % and ae % for influenza b, % and ae % for pandemic (h n ) . self-blown specimens display sensitivity, specificity, and accuracy comparable to that of conventional nasopharyngeal swab specimens. there was no significant difference in sensitivity, specificity, or accuracy between self-blown specimens and nasopharyngeal swab for influenza a, influenza b, and pandemic (h n ) . these results suggest that selfblown specimens are as useful as nasal cavity swab specimens for the diagnosis of influenza in the clinical settings. nasal discharge, obviously, cannot be collected from infants incapable of blowing their own nose or patients who do not develop a nasal discharge. in this study, self-blown specimens were obtained from ae % of the patients. the rate of successful collection was over % in the age groups of - and - years. these rates would seem to be sufficient for clinical use. the procedure of self-blown specimen collection using a plastic sheet is easy and causes no pain or discomfort. it seems to be more acceptable and safe than the other methods, especially for children. furthermore, this procedure reduces the risk of influenza transmission from patients to the medical staff members involved in sample collection. self-blown sample collection may be superior to other sample collection methods in these respects. we previously reported an inverse correlation between the amount of virus in a specimen and the time to a positive reaction. in this study, there was no significant difference in the mean time to a positive between self-blown self-blown specimens enough to be examined were obtained from consecutive outpatients, and specimens showed a tendency to be obtained large amount from children rather than the aged. there were no statistically significant differences between the ic kit results primed with self-blown discharge and nasopharyngeal swab specimens for influenza a, influenza b and pandemic (h n ) . and nasal swab specimens, suggesting that the self-blown specimens contained sufficient viral antigen for the ic kits. the influence of the presence or absence of nasal congestion on the results of the kit was assessed. the sensitivity of selfblown specimens from patients with nasal congestion was significantly lower than that from patients without nasal congestion. it is possible that insufficient capability to blow the nose due to nasal congestion might tend to lead to false negatives. the observation that the time to positive is longer for patients with nasal congestion than for patients without nasal congestion is concordant. application of self-blown specimen collection only to appropriate patients would increase the sensitivity, which would be important in a clinical setting. we tested only two commercial antigen detection kit, the quick vue rapid sp influ kit and quicknaviÔ-flu (denka-seiken co., ltd). the resulting sensitivity, specificity, and accuracy of the ic kit primed with self-blown specimens were considered adequate for clinical use. to confirm the usefulness of self-blown nasal discharge specimens, further investigation is necessary using other kits and in different settings. the usefulness of a self-blown nasal discharge specimen for an influenza rapid antigen test based on immunochroma-tography was evaluated in the - and - influenza season. results suggest that self-blown nasal discharge specimens are useful as specimens for influenza rapid antigen tests based on immunochromatography for not only seasonal influenza viruses, but also pandemic (h n ) virus. the specimen collection by the patients themselves will reduce the burden of other collection methods and the risk of infection to the medical staff. in april , a mixed-origin h n influenza virus was recognized as a new causative agent of influenza-like illnesses (ili) in humans. since its emergence, the virus has spread rapidly throughout the world and caused a pandemic. most commercial rapid antigen tests (rat) can detect influenza a or b viruses, but cannot specifically distinguish pandemic (h n ) virus with seasonal influenza. recent studies have indicated that the poor performance of the rat approach and nonspecific detec-tion of the pandemic (h n ) virus was the main obstacle to their widespread use in private clinics. , with the need for a new rapid kit with reasonable sensitivity and specificity for pandemic (h n ) virus, we developed a new rat kit in collaboration with company, standard diagnostics, inc., (yongin-si, gyonggi, korea). monoclonal antibody (mab) against haemagglutinin (ha) of the pandemic (h n ) virus was developed using korean isolate and applied to the new kit with the mab to seasonal influenza virus. we examined the detection limit of the kit using the serial dilution of korean pandemic virus isolate (a ⁄ korea ⁄ ⁄ ). during december , clinical specimens from patients with ili were collected at sentinel clinics of six provinces in korea. the specimens were tested by the new rat, and the results were compared with those of real-time reverse transcription polymerase chain reaction (rrt-pcr) by us cdc and virus isolation in mdck cell culture to determine the sensitivity and specificity for the diagnosis of pandemic (h n ) . the detection limit of the new kit against ha of a ⁄ korea ⁄ ⁄ virus was confirmed to be pfu ⁄ ml. by contrast, the detection limit against the np protein was pfu. however, when the kit was applied to clinical specimens, no difference between the two targets was found. using rrt-pcr and viral culture as the references, the performance of the ridt is shown in table . among specimens, were tested positive by rrt-pcr and were tested positive by viral culture. among the rrt-pcr confirmed cases, were positive, and among the viral culture confirmed cases, were positive with the new rat. using rrt-pcr as the reference standard, the overall sensitivity of rat was ae % ( % confidence interval (ci): ae - ae %) and specificity was ae % (ci: ae - ae %). with viral culture as the reference, the rat sensitivity and specificity was ae % (ci: ae - ae %) and ae % (ci: ae - ae %), respectively. when analyzed by the regions tested, the sensitivity ranged between ae % and ae % for rrt-pcr and between ae % and ae % for viral culture as a reference. among patients who had a record of their symptom onset and sample collection date, ( ae %) visited the clinic on the day of symptom onset, and ( ae %) visited day later. when the rat performance was evaluated by day of onset, the sensitivity was lower at three or more days after the onset of symptoms; however, the sensitivity was highest at days after onset and reasonable on the day of onset or at day after ( table ). we found that this new rat had reasonable sensitivity and high specificity compared with rrt-pcr and viral culture for detecting the pandemic (h n ) virus. in one recent study, the sensitivity and specificity of the new rat kit was % and %, respectively, and the ha protein for pandemic (h n ) was detected more sensitively than the np protein for influenza a virus. the sensitivity and specificity of our new rat were lower than those of that study. we found that the test performance varied depending on the clinics in which the tests were performed, and this might be attributable to the persons who collected the specimens. although the clinicians were trained well for *ci, confidence interval. **ppv, positive predictive value. ***npv, negative predictive value. collecting specimens, there might be some differences in performance. the new rat kit could detect pandemic (h n ) virus specifically. although the sensitivity was lower than those of rrt-pcr and virus culture, and negative rat results should be confirmed with more sensitive methods, this kit could be useful in sentinel clinics if used with caution. determination of infectious virus titres is central to many experiments designed to study the biology of influenza virus. assays based on the measurements of viral components, whether viral protein or nucleic acid, does not differentiate infectious virus from non-infectious or defective viral particles, which may have no infectivity or biological *three hundred and forty samples with a known date of onset and sample collection were analyzed. ª blackwell publishing ltd, influenza and other respiratory viruses, (suppl. ), - activity. therefore the ''gold standard'' of virus measurement requires bioassays that examine the ability of viral particles to replicate and further infect other cells. titration on madin-darby canine kidney (mdck) cells in a well plate format is commonly used to measure influenza virus titre. this method is labour intensive, subjective in their read out of cytopathic effect, and takes several days to obtain a result. microneutralization tests that quantitate neutralizing antibody titres and assays of drugs for antiviral activity also require well based assays of residual virus infectivity. therefore, technologies that improve on the titration of infectious virus will be of great benefit. this study utilized the xcelligence system (roche applied science), which adopts microelectronic biosensor technology to monitor dynamic, real-time label free and non-invasive analysis of cellular events. the system measures electronic impedance using an array of microelectrodes located at the bottom of each culture well (e-plate ). adherent cells are attached to the sensor surface of electrode arrays, and changes in impedance can be detected and recorded. the xcelligence system can monitor cell events induced by viral infection, such as changes in cell number, adhesion, viability, morphology, and motility. measured electrode impedance is expressed as dimensionless cell index and is graphically represented using software to show the phenotypic changes of a cell population over time. the aim of this study is to demonstrate that using this platform to measure real-time cell index has potential to circumvent many of the limitations of the currently established procedures of end point titration of virus infectivity and for microneutralization assays. madin-darby canine kidney cells were propagated in growth medium consisting of minimum eagle's medium (invitrogen) supplemented with % fetal bovine serum (invitrogen), ae mg ⁄ l penicillin (invitrogen), and mg ⁄ l streptomycin (invitrogen), with incubation at °c in a % co humidified atmosphere. influenza a ⁄ hong kong ⁄ ⁄ (h n ), a seasonal influenza virus from a patient who suffered from a mild febrile illness, was propagated in mdck cells maintained in virus medium consisting of minimum eagle's medium (invitrogen) supplemented with ae mg ⁄ l penicillin (invitrogen), mg ⁄ l streptomycin (invitrogen), and mg ⁄ l np-tosyl-l-phenylalaninechloromethyl ketone-treated trypsin (sigma, st louis, mo, usa), with incubation at °c in a % co humidified atmosphere. virus stocks were aliquoted and stored at °c until use, and the % tissue culture infectious dose (tcid ) of the virus stock was determined by titration in mdck cells according to standard procedures, and the tcid of the stock virus was calculated by the method of reed and muench. to perform a microneutralization assay, mdck cells seeded at a density of cells ⁄ well in an e-plate was removed from the xcelligence system after approximately hour; growth medium was then removed, cells washed, and replaced with ll virus-medium. a human serum, which is known to contain high titre antibody against the h n virus was heat inactivated for min at °c, and twofold serial dilutions were performed in virus medium. the diluted serum was mixed with an equal volume of virus medium containing influenza virus at tcid ⁄ ll. after incubation for h at °c in a % co humidified atmosphere, ll of virus-antibody mixture was added to the mdck cells to give each well an equivalent virus dose of tcid . a back titration of the virus challenge dose was performed, and a cell control (free of virus) was performed in quadruplicates. after incubation at room temperature for minutes, the e-plate was then placed back onto the xcelligence system in the incubator and maintain at °c with % co , and the cell index values were measured every minutes for at least a further hour. the same procedures were performed with cells seeded in conventional well cell culture plates for parallel comparison with the currently used standard method. in this case, cells were examined for cytopathic effect under an inverted microscope after days of infection and the lowest virus dilution, which protected the cells from viral induced cytopathic effect taken as the neutralizing end point. after hour of seeding mdck cells at cells ⁄ well, standard microneutralization assay for influenza virus was performed. integral to this assay, a serial titration of the input virus at ae log increments was carried out. wells infected with the undiluted virus ( tcid ⁄ well), the cell index commenced dropping at a steeper gradient than the no-virus cell control after approximately hour of infection ( figure ). this drop in cell index continues at a consistent slope until it flattened out when approaching zero cell index. this steep decrease in cell index with constant gradient was also observed for virus dilutions up to and including log ( -folds), and the profile shifted with increased time in proportion to the dilution made to the virus. virus dilutions beyond log have cell index profiles similar to the no virus input control, and this corresponds to the absence of cytopathic effect as determined by microscopic observation at hour after infection. hence, there was a correlation between the amount of virus used for infection, the onset of the influenza virus-mediated cytopathic effect, and the steep decline in cell index. a human serum with known microneutralization antibody titre to h n virus was used in this study to investigate the real time cell index changes that occur during the assay ( figure ). using influenza virus treated with serum dilutions up to and including a dilution of : , the cell index profile remained essentially the same as the no virus cell control, which correlates with the lack of cytopathic effects under microscopic observation at hour of infection. at a serum dilution of : , the steep decrease in cell index, which is characteristic of cellular cytopathic effect induced by the virus, became evident at around hour post infection, and this was reduced to hour when serum dilution of : was used. in contrast, for the virus -no antibody control, the onset time for this steep decrease in cell index occurs at approximately hour. for both serum dilutions of : and : , full cytopathic effect was observed microscopically at hour of infection. from microscopic observation of cytopathic effect, according to the current standard procedures, the neutralizing titre of the human serum used in this study is at : as it is the last dilution of the serum that prevented cytopathic effect from being detected. an essential part of the microneutralization assay is to confirm the titre of the input virus (normally tcid ⁄well) by performing a titration assay with decreasing serial dilutions of the virus. under normal procedures, cells are examined microscopically after hour of infection for sign of cytopathic effects. in the case of mdck cells, the cytopathic effect is cell death, which is indicative of the presence of live influenza virus infecting and replicating in the cells. therefore, the titre of the virus is taken as the last dilution in which cytopathic effect is present. parallel realtime cell index measurements demonstrated that for wells with cytopathic effects, the profile exhibits a steep gradient linear decrease in cell index after infection with the virus, which can be termed the ''cpe plunge.'' the time in which the cpe plunge became evident appears to be inversely proportional to the amount of virus, therefore the opportunity exists to utilize this aspect to calculate or compare quantitatively different virus concentrations. for unequivocal assignment of cytopathic effect, it normally requires - days after infecting the cells, with days after infection being the standard time to read virus titration and microneutralization assays. using the real-time cell index monitoring, it is found that apparent cytopathic effect can only be observed microscopically when the cell index has dropped to near zero. as the time of onset of the ''cpe plunge'' becomes evident many hours prior to observable cytopathic effect, it is possible that the time to results can be drastically reduced after some formulation of the method. we compared the current standard method in perfoming a microneutralization assay with one utilizing the real-time cell index measurement to investigate whether this approach is able to offer better performance over the existing one. the current standard neutralization assay is the microscopic observation of antibody mediated protection from virus cytopathic effect in mdck cells. this study showed that this may also be achieved by examining the profile generated from the real-time measurements of the cell index. using real-time cell index monitoring, it is possible to detect inhibitory activity at higher dilutions of the anti-serum than can be detected by the standard microscopic observation of cytopathic effect. therefore, the realtime cell index monitoring could potentially be developed to be a more sensitive method for measuring anti-viral activity. as drug resistant strains of influenza a viruses including the pandemic h n are being reported, the real-time cell based monitoring system may also have the potential to be developed for use as a diagnostic platform for drug resistance assays. this study suggests that real-time cell index monitoring has the potential to substantially reduce human resources in reading results, as well as reducing time-to-result of these assays from days to two. the saving could be substantial for work involving bio-hazard level ⁄ pathogens such as h n viruses as personnel working with these organisms are require to be highly trained and experienced. in addition, the reduction in transferring plates to and from the microscope in reading cytopathic effect will substantially reduce the possibility of accidents from occurring. furthermore, the system provides objective digital data to an otherwise subjective assay method, which can improve standardization, data exchange, and hence collaboration between different laboratories. with more detailed validation and development, real-time cell index monitoring could transform the way we study and diagnose infection with pathogens such as influenza viruses. the emergence of a novel h n influenza a virus of swine origin, the pandemic a(h n ) , with transmissibility from human to human in april posed pandemic con-cern and required modifications to laboratory testing protocols. a new protocol for universal detection of influenza a and b viruses and simultaneous subtyping of influenza a (h n ) virus, composed of two-one-step rt-pcrs, fast set infa ⁄ infb and fast set h n v (relab, italy), was evaluated and compared to the reference protocol recommended by who. fast set infa ⁄ infb was able to detect influenza a and b viruses circulating between and belonging to different subtypes and lineages, and no cross reactions were observed by either fast set infa ⁄ infb or fast set h n v. the who assay was found to have a slightly lower end-point detection limit ( ) dilution) in comparison to the new protocol ( ) ). specificity of the assays was % as assessed on a panel of stored clinical samples including adenovirus, respiratory syncytial virus, metapneumovirus, parainfluenza virus, s. pneumoniae, n. meningitidis, h. influenza, and human influenza viruses. the new assay panel allows the detection, typing, and subtyping of influenza viruses as requested for diagnostic and surveillance purposes. the high sensitivity of the protocol is coupled with capacity to detect viruses presenting significant heterogeneity by fast set infa ⁄ infb and with high discriminatory ability by fast set h n v. a rapid and sensitive assay for the detection of influenza virus in clinical samples from subjects with ili or low respiratory tract infections is a fundamental tool for epidemiological and virological surveillance, management of hospitalized patients, and control of virus nosocomial transmission. the emergence, in april , of a novel h n influenza a virus of swine origin, the pandemic (a(h n ) ), with transmissibility from human to human poses pandemic concern and required modifications to the laboratory testing protocols. molecular diagnosis of influenza is generally achieved through a twophase process: a screening phase for the detection of virus, and the subsequent strain characterization performed by either sub-type-specific rt-pcr or entire ⁄ partial genome sequencing. during a pandemic, simultaneous implementation of both the detection of influenza a and b influenza viruses and identification of the new subtype is useful for clinical and epidemiological reasons. here, we describe a new protocol including two-one-step rt-pcrs, fast set infa ⁄ infb and fast set h n v (relab, italy) that allows universal detection of all influenza a viruses and, simultaneously, all subtypes that are influenza a(h n ) . specificity and clinical sensitivity of the two-one-step rt-pcrs (fast set infa ⁄ infb and fast set h n v; relab, italy) were evaluated by testing selected specimens, including: • fifty samples collected from nasopharyngeal swabs representative of influenza viruses, belonging to differ-ent subtypes and lineages, and other respiratory viruses and bacteria circulating in italy between and . • six purified a(h n ), a(h n ), and a(h n ) strains, kindly supplied by alan hay, who influenza centre, london, uk. • two hundred-fifty influenza positive samples selected according to type, subtype, clade and viral concentration from > specimens received by the liguria influenza reference laboratory between january st and december st, . since , nasopharyngeal swabs sampled from patients suspected of having contracted the influenza virus have been collected in viral transport medium, and upon arrival into the laboratory, the samples were divided in ‡ aliquots. those not immediately processed were stored frozen at ) °c. stored samples were used for this evaluation, and all specimens were re-extracted for the study. samples collected between and included specimens positive for: no seasonal a(h n ) have been detected since january st, . furthermore, weak positive sample using fast set infa ⁄ infb, but negative at block pcr and typing ⁄ subtyping assays was tested. the analytical sensitivity of the test under investigation was determined testing ten-fold serial dilutions of seasonal influenza a(h n ), seasonal influenza a(h n ), new pandemic influenza a(h n ) , and b cell culture-grown viruses. the intra-assay reproducibility was measured by testing the same a(h n ) positive sample times in the same experiment, while the inter-assay reproducibility was confirmed by testing the same samples in independent experiments. to evaluate the performance of the protocol, all samples were tested using a block pcr confirmation test (seeplex Ò rv ace detection), and all specimens collected between january st and december st, and dilutions were also assayed using the recommended who ⁄ cdc protocol of real-time rtpcr for influenza a(h n ). typing and sub typing were performed using the who protocol and ⁄ or sequencing. viral rna was extracted from swabs using the qiaamp viral rna mini kit (qiagen) according to the manufacturer's protocol. fast set infa ⁄ infb and fast set h n v are two multiplex one-step real time pcr assays developed and evaluated by the liguria regional reference centre for diagnosis and surveillance of influenza in collaboration with relab diagnostics. both assays contain primers and a dual-labelled hydrolysis probe that targets two regions of the matrix gene (table ) . amplification conditions were as follows: reverse-transcription °c for minutes, denaturation °c for minutes, then cycles of °c for seconds, °c for seconds. the entire amplification process extended for minutes. an internal control real-time assay was also incorporated in order to detect pcr inhibition, failed extraction ⁄ pcr and technical error. the cdc realtime rtpcr (rrtpcr) protocol for detection and characterization of swine influenza includes a panel of oligonucleotide primers and dual-labelled hydrolysis (taqman Ò ) probes to be used in real-time rtpcr assays for the in vitro qualitative detection and characterization of swine influenza viruses in respiratory specimens and viral cultures. this protocol recommends three primer-and-probe sets: infa, amplifying a conserved region of the matrix gene from all influenza a viruses; sw infa, designed to specifically detect the nucleoprotein (np) gene segment from all swine influenza viruses and sw h , designed to specifically detect the hemagglutinin gene segment from a(h n ) . the seeplex Ò rv ace detection for auto-capil-lary electrophoresis is a multiplex block rt-pcr that applies dpoÔ (dual priming oligonucleotide) technology and is designed to detect major respiratory viruses, respiratory rna (influenza a and b virus, parainfluenza virus type , and , respiratory syncytial virus a and b, rhinovirus a ⁄ b, coronavirus oc and e ⁄ nl ) viruses and dna (adenovirus) virus, from patients' samples including nasopharyngeal aspirates, nasopharyngeal swabs and bronchoalveolar lavage. conventional viral culture was performed inoculating ae ml of each specimen into mdck-siat seeded into -well plates for influenza isolation. virus detection was performed by the hemagglutination test using ae % guinea pig red blood cells (rbc). specificity and clinical sensitivity results of the new protocol are reported in table . fast set infa ⁄ infb was able to detect influenza a and b virus circulating between and belonging to different subtypes and lineages, and no cross-reactions were observed by either fast set infa ⁄ infb or fast set h n v. among specimens collected between january st and december st, , all fast set infa ⁄ infb and fast set h n v high titre positive samples resulted positive using the who ⁄ cdc assay and showing reactivity using infa and sw infa primer-andprobe sets. among low titre a(h n ) positive samples at fast set infa ⁄ infb, ( ae %) were not detected by the who ⁄ cdc assay, but were positive using seeplex Ò rv . the who ⁄ cdc sw h primer-and-probe set works in ae % ( ⁄ ) and ae % ( ⁄ ) of high and low titre a(h n ) positive samples, respectively. all a(h n ) strains collected during and initially detected by fast set infa ⁄ infb were confirmed after rna re-extraction by seeplex Ò rv and who ⁄ cdc assay showing reactivity using the infa primer-and-probe set. all infa ⁄ infb were confirmed after rna re-extraction by seeplex Ò rv . one influenza a case identified by the who ⁄ cdc kit (infa primer-and-probe set, ct values: ae , sw infa primerand-probe set: negative) and new protocol (a primer-andprobe set, ct values: ae , a(h n ) primer-and-probe set, ct values: ae ) was not detected by either seeplex Ò rv or by who subtyping protocol and ⁄ or sequencing, suggesting a very low viral load or unspecific results by real time assays. the analysis of serial dilutions of cell culturegrown a(h n ) showed that the detection limit of fast set infa ⁄ infb, fast set h n v, and seeplex Ò rv was identical ( ) ) and log lower than that using the who ⁄ cdc protocol ( ) ). a similar analysis with respect to a(h n ) and a(h n ) strains indicated that fast set infa ⁄ infb sensitivity ( ) and ) , respectively) was log lower than that showed by seeplex Ò rv ( ) and ) , respectively). in comparison with the new protocol, the who ⁄ cdc assays, considering infa primer-and-probe set, was found to have a slightly lower end-point detection, detecting the ) a(h n ) and a(h n ) dilution. also in detecting influenza b virus, fast set infa ⁄ infb sensitivity ( ) and ) , respectively) was log lower than that showed by seeplex Ò rv and the who ⁄ cdc protocol. data on intra-assay and inter-assay precision, measured as cv% of ct showed that the dispersion indices observed had values of less than %. since samples were detected using the new protocol that resulted negative using the who ⁄ cdc assays. the unfortunately low quantity of low titre a(h n ) samples collected during did not allow us to highlight differences between assays fast set infa ⁄ infb, and fast set h n v positivity was always confirmed by seeplex Ò rv , which demonstrated high sensitivity, showing a detection limit comparable or lower when compared with those observed using the who ⁄ cdc assays. the high analytical sensitivity of seeplex Ò rv is reported by kim who observed a detection limit of copies per reaction for each type ⁄ subtype of influenza viruses. the high sensitivity of the new protocol is coupled with its capacity to detect viruses presenting a significant heterogeneity by fast set infa ⁄ infb and high discriminatory ability by fast set h n v. fast set infa ⁄ infb was able to identify representative influenza viruses of circulating strains during the last decade belonging to different subtypes, lineages, and clusters, and fast set h n v primerand-probe set reacted selectively with a(h n ) target. a recent report demonstrated that the sw infa assay is not specific to a(h n ) and is able to detect both human and avian (h n ) influenza a viruses and so there is the potential for misidentification. high titre (ct ae and ae at fast set infa ⁄ infb) a(h n ) viruses did not react with fast set h n v primer-and-probe set (data not shown). available human a(h n ) sequences are similar within the h n v primer-and-probe regions, but having - mismatches in the forward primer and, more notably, two of the mismatches occurred within nucleotides of the end, an important determinant for primer specificity. in conclusion, this protocol can be a powerful tool in the diagnostic laboratory setting for specific simultaneous analysis of several samples in minimal time, showing enhanced sensitivity in detecting influenza viruses, and high discriminatory ability in identifying the new pandemic a(h n ) . a university-corporate partnership to enhance vaccination rates among the elderly: an example of a corporate public health care delivery public health campaigns usually rely on governmental infrastructure and finance for vaccine implementation programs. however, there are many financial and physical barriers which preclude widespread and effective vaccine administration, especially among the elderly. on an international scale, both government agencies and citizen groups have a vested interest in searching for more resourceful methods of attaining significant immunization levels (> % of the population). in fact, it seems to have become both a grassroots civic and governmental goal, especially among developing countries. we implemented the unique strategy of enlisting the assistance of a privately-owned food market chain to address the public health issue of mass vaccination for the elderly. in this context, publix pharmacy and the university of south florida (usf) recently developed both a handbook and a training program to facilitate the administration of vaccinations. between and , the publix-usf partnership resulted in administration of over thirty thousand influenza a (h n ) vaccinations, % of which were given to adults over years of age. consequently, vaccine administration costs were decreased by using corporate resources and bypassing overly strained municipal resources. this unique university-corporate partnership successfully delivered h n vaccine to a vulnerable cross-section of society at a lower cost and with minimal side effects and morbidity. it may be safely projected that university-corporate partnerships could result in an effective method for rendering a vital service to an aging and especially vulnerable segment of the population. government policy and funding are the foundation of immunization programs on an international scale. for example, in the united states, governmental programs account for over % of the monetary outlay used for immunization. until , the global alliance for vaccines and immunizations (gavi) acted as a catalyst for implementing vaccine and immunization programs in each targeted country. under the auspices of gavi-collaborations between governments, charitable organizations, and multinational health agencies (such as uncief and the who)-many countries have increased their spending for vaccination programs. however, development of financially sustainable immunization programs geared toward reaching the majority of the population are still at a nascent level of evolution. the development of more innovative and costeffective approaches has become imperative in order to reach a greater number of vaccination candidates. administering the influenza vaccine only to the subpopulation of over year olds would save an estimated quality-adjusted life years in a cohort of approximately half the world's population. widespread public vaccination programs are made more complex by the continuing development of newer vaccines, concomitant specialized administration costs, and the logistical challenge of conveying recipients to vaccination points of service. , in spite of the increasing complexity of mass vaccination, cost-benefit analyses clearly favor annual influenza vaccination in the elderly population on an international scale. , recently, in , influenza vaccine administration was reported to reach between % and % of the elderly population, which denotes varying degrees of success within each particular country. , however, there was also a report of a uniform plateau effect at around % of the population, beyond which additional vaccination coverage was difficult to achieve. physical limitations to vaccination seem to be more insurmountable for the elderly. unfortunately, this is the population segment which could experience the most significant vaccination-associated mortality reduction. we employed the unique strategy of involving the resources of publix supermarkets, a corporate food market chain, to address the public health issue of widespread vaccination for the elderly. we took advantage of recent changes in the florida statutes, which expanded the scope of pharmacists' practice to include administration of vaccines. subsequently, publix pharmacy and the university of south florida (usf) developed a handbook and training program to facilitate and enhance vaccine administration by publix pharmacists. by using proprietary pharmacists and more practical supply storage, we were able to decrease the costs of vaccine administration. the consumer was charged $ for administration costs plus the cost of the injection itself, regardless of insurance or eligibility for governmental subsidy. although patients were initially self-selected, they were ultimately excluded if they had demonstrated prior adverse effects to influenza vaccinations or to any of the components of such vaccinations. between and , the publix-usf partnership vaccinated people against influenza a (h n ), of which were florida residents. the age range was - years old with a median age of years old. seventysix percent of the participants were over years old (see figure ). within the population surveyed, the reported side effects of the vaccine in this study were not serious, but included: vertigo, cold sweats, chills, vomiting, syncope, rash, nausea, stomach pain, elevated blood pressure, injection site reaction, inflamed bursa, and bilateral thigh discomfort. participants from all socioeconomic classes were vaccinated. an income-by-zip code analysis revealed % of those vaccinated resided in zip code areas where the average household income was <$ per year. of those remaining, % had an average income of $ -$ per year, and % had an income of >$ per year. each person vaccinated was charged ten dollars for administration costs. this represents a decrease in the administration costs ranging from one dollar to ten dollars saved per vaccine. , conclusion this unique university-corporate partnership successfully delivered h n vaccine to a high-risk population with decreased vaccine administration costs. the influenza vaccine is well-tolerated, with minimal side effects when patients who have a history of adverse reactions are excluded. we can postulate that university-corporate partnerships may indeed be effective at reaching the aging population which is a challenge in most communities. this delivery model may prove to be another tool for improving the efficiency of mass immunization by facilitating accessibility, which results in wider coverage. this model also enhances delivery of healthcare by decreasing costs of immunization regardless of whether the payer is a government, insurance company, or self-pay consumer. the gavi initiative stressed three goals for accomplishing sustainability and independence in immunization programs. the goals were to: (i) mobilize additional resources from governmental and non-governmental sources; (ii) improve program efficiency to minimize additional administration resources needed; and (iii) increase the reliability of funding. empowering privately owned corporations within the community, such as food markets or pharmacies, to administer vaccines mobilizes additional resources to readily achieve the first goal of gavi. mobilizing resources of non-healthcare, corporate vaccination locations enhances accessibility due to travel convenience. in our study, participants came from all socioeconomic classes, suggesting that ease of access is independently hindering mass vaccination, and that people of all incomes are more likely engaged when access issues are eliminated. the second and third goals were also accomplished by recruiting a corporation's resources for vaccine administration (refrigeration, storage, and employees). this minimizes the money spent from vaccine program funds to support the infrastructure of immunizations, thus improving financial efficiency and sustainability. financial efficiency implies that money is spent to safely reach as large a portion of the population as possible. by using corporate storage facilities instead of paying for independent facilities, money can be spent elsewhere. more vaccines can be purchased and more money can be spent on media communications to encourage vaccination. sustainability requires the ability to fund annual vaccination programs which reach % of the population or greater. key to the control of pandemic influenza are surveillance systems that raise alarms rapidly and sensitively. in addition, they must minimise false alarms during a normal influenza season. we develop a method that uses historical syndromic influenza data from the existing surveillance system 'servis' monitoring seasonal ili activities in scotland. we develop an algorithm based on wcr of reported ili cases to generate an alarm for pandemic influenza. wcr is defined as the ratio of the number of reported cases in a week to the number of cases reported in the previous week. from the seasonal influenza data from scottish health boards, we estimate the joint probability distribution ( figure ) we compare our method, based on our simulation study, to the mov-avg cusum and ili rate threshold methods and find it to be more sensitive and rapid. the wcr method detects pandemics in larger fraction of total runs within the same early weeks of pandemic starting than does any of the other two methods ( figure ). as shown in the table, for % pandemic case reporting rate and detection specificity of %, our method is % sensitive and has mdt of weeks, while the mov-avg cusum and ili rate threshold methods are, respectively, % and % sensitive with mdt of weeks. at % specificity, our method remains % sensitive with mdt of weeks. although the threshold method maintains its sensitivity of % with mdt of weeks, sensitivity of mov-avg cusum declines to % with increased mdt of weeks. for a two-fold decrease in the case reporting rate ( ae %) and % specificity, the wcr and threshold methods, respectively, have mdt of and weeks with both having sensitivity close to %, while the mov-avg cusum method can only manage sensitivity of % with mdt of weeks. the first cases of the pandemic were reported in scotland in the th week of the season. the wcr algorithm as well as the mov-avg cusum method detects the pandemic weeks later in week . the ili threshold method detects it week later in week . both the wcr and mov-avg cusum methods therefore outperform the ili threshold method by week in the retrospective detection of the pandemic in scotland. while computationally and statistically very simple to implement, the wcr method is capable of raising alarms rapidly and sensitively for influenza pandemics against a background of seasonal influenza. although the algorithm has been developed using the servis data, it has the capacity to be used at large scale and for different disease systems where buying some early extra time is critical. more generally, we suggest that a combination of different statistical methods should be employed in generating alarms for infectious disease outbreaks. different detection methods would provide cross-checks on one another, boosting confidence in the outputs of the surveillance system as a whole. real-time evidence being created worldwide will greatly contribute to the full understanding of influenza pandemics. here we report the real-time epidemiology and virology findings of the influenza a(h n ) pandemics in mongolia. the epidemiological and virological data collected through isss of nic, nccd, mongolia (real-time information on registered ili cases and virological laboratory results are available from the weekly updates in the nic, mongolia website: http://www.flu.mn/eng/index.php?option=com_ content&task=category&sectionid= &id= &itemid= ) were used for analysis in relation to the previous seasonal influenza activities in the country. influenza viruses were detected in naso-pharyngeal samples from ili patients by rt-rt-pcr with applied biosystems fast real time pcr system , using primers and instructions supplied by cdc, usa. influenza viruses were isolated by inoculation of rt-rt-pcr-positive samples of mdck cell culture according to the standard protocol. ten representative strains of a(h n )pdm viruses were selected for sequencing of different gene segments, namely: a ⁄ ula- , and a ⁄ dundgovi ⁄ ⁄ . sequencing of influenza virus gene segments was performed in applied biosystems xl genetic analyzer using primers and instructions supplied by cdc, usa, and bioinformatic analysis was performed with abi ⁄ seqscape v. . and mega programs. the pandemic alert in mongolia was announced by the government on april , , just after the who announcement of the pandemic alert phase, and planned containment measures were intensified. despite intensive surveillance, no a(h n )pdm virus was detected in mongolia until the beginning of october . around suspected cases, mostly arriving from the a(h n )pdm epidemic countries, tested zero by rt-rt-pcr for a(h n )pdm virus. the first a(h n )pdm case detected by the routine surveillance system in ulaanbaatar city, the capital of mongolia, was confirmed by rt-rt-pcr on october , ( st week of ). the reported ili cases escalated rapidly, reached the peak in the - th week of , and gradually decreased thereafter ( figure ). week of . however, the registered ili cases increased again from the th week of , and peaked at the - th weeks of . the viruses isolated during this nd peak were influenza b strains ( figure and table ). for the genetic characterization of the mongolian pandemic isolates, gene segments i (pb ), gene segments ii (pb ), gene segments iii (pa), gene segments iv (ha), gene segments v (np), gene segments vi (na), gene segments vii (m), and gene segments viii (ns) of the representative a(h n )pdm mongolian strains were sequenced, and all sequences have been deposited in the genbank (accession numbers: cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy , cy ). all genes of mongolian strains were possessing ae - ae % similarity with the genbank deposited gene sequences of the original pandemic strain a ⁄ california ⁄ (h n ). the who declared the pandemic alert phase (phase iv) on april , , and was prompted to announce the pandemic phase (phase v) two days later. after days, the who declared the beginning of the pandemic peak period (phase vi) on june , . however, in mongolia, the pandemic alert period continued for days. mongolia was free of the pandemic virus during the whole first wave of the pandemics in the northern hemisphere. with the confirmation of the st influenza a(h n )pdm case on october , in ulaanbaatar, mongolia entered into the pandemic phase (phase v), and after just weeks, the registered ili cases peaked, confirming mongolia shifted into the pandemic peak period (phase vi), which i i i v i i v i v v v i i i i iii iv v vi vii viii worldwide by who in mongolia coincided with the nd wave of pandemics in many countries of the northern hemisphere (see, picture and table ). despite the relatively milder clinical manifestations, the disease burden for the health service was enormous, while the morbidity per population at the peak period was - times higher above the upper tolerant limit, and - times higher above the seasonal influenza outbreaks. in contrast to the seasonal influenza outbreaks where over % of the registered ili cases have been in the age group under , it has been observed that over % of the registered cases in this pandemic peak period were in the age group of - . on january , , we regarded the pandemic had entered into the post-peak period (phase vii) when the registered ili cases became lower than the upper tolerant limit, during which time mongolia experienced an influenza b outbreak. on may , we determined that mongolia entered the post-pandemic period (phase viii) as the influenza virus isolations were almost stopped, and after no pandemic virus detected for months. who announced pandemic vii and viii phases much later. , this first ever real-time laboratory confirmed influenza pandemics in mongolia and confirmed some variations of pandemic spread in different parts of the world. the comparison of deduced amino-acid sequence changes have shown that the mongolian strains belong to the clade , according to the classification of a(h n )pdm influenza strains suggested by m. nelson, which has circulated worldwide since july . this is also evidence that the st wave of the pandemics did not hit mongolia. the who public health research agenda for influenza is aimed to support the development of evidence needed to strengthen public health guidance and actions essential for limiting the impact of influenza on individuals and populations. each stream-specific group reviewed and discussed the proposed organization, content, rationale, and global health importance of their designated research stream. specific research recommendations were made for topics within each stream: background: a syndromic surveillance system using nonclassical data sources for detection and monitoring evolution of flu and flu-like illness (ili) in djibouti is reported here as part of the preliminary report of djibouti who-copanflu international study (wcis)**. methodology: clinical reports, over-the-counter drug sales, lab diagnosis report, and health communication trends were obtained for an integrated statistical analysis. results: transition to winter is concomitant with upsurge of ili cases and ili drug sales. in addition, more rural folks manage ili infections on self medicament than through clinical consultancy. inefficient and vague data collections were observed. a successful implementation of wcis will create a platform upon which challenges faced in djibouti health department in routine surveillance will be addressed to achieve a near-real time surveillance of flu pandemic. conclusion: innovations, prompt reporting, and instituting open source syndromic surveillance system software's in resource limited environment like djibouti will enhance early detection and evolution monitoring of pandemic flu. the spanish flu in ⁄ infected and killed millions of people, and threatened to wipe humanity off the face of planet. however, the recent scenarios of influenza h n ( ) pandemics' worldwide occurrence fell short of most scientific prediction on its magnitude and intensity. this dampened their confidence; they cannot state precisely as to when, how, where, and which of the spanish flu-like pandemic will occur in the future. in support of scientific community and governments, the who hasn't gone to slumber, but is reminding its member states to up their post pandemic surveillance and monitoring of influenza virus in circulation for advance preparedness in case of an outbreak. despite all uncertainty around the pandemic flu h n , there remains a common knowledge and understanding that this flu has shown a great potential to evolve and cause huge morbidity and mortality. although its future magnitude may be unpredictable, its recurring events have severe consequences on human health and the economic well being of everyone. and therefore, advance planning and preparedness is critical in protecting any population in the future, especially those located in resource limited environment without universal health cover and generous disaster emergency funds. . two collapsed sets of a weekly and monthly mean data (of four years period) were clustered in five categories of ili cases, drug sales, lab results, vaccine consumption, and health promotion. this was followed by a descriptive statistics analysis of cumulative weekly and monthly data to establish presence or absence of trend. time series analysis was not done due to data limitation. copanflu program: as at the time of going to press, the cohort study is at the household recruitment and inclusion phase and the study covers the djibouti city. it is in our intention to use the cohort study findings to validate or improve the niph ministry of health djibouti ili surveillance effort for better preparedness. clinical service: % of all health facilities are in djibouti city. of the ae % ( ) of the population that seeks medical care on influenza and influenza like illness each year, ae % ( ) and ae % ( ) of them are attended to at the city's public and private clinics, respectively ( figure ). the rest are attended from the regional health centers. the majority of ili incidence sharply rise with the onset of the winter season (october to april), affecting mostly the middle age group ( - years). pharmaco-surveillance: % ( ) of total prescriptions were antipyretic and antiflu drugs, ae % ( ) of which were consumed by peripheral regions, the non dji- lab diagnostics: the annual ili lab diagnosis was negligible ae % ( ), which can be attributed to less equipped virology laboratories to warrant routine service utility. documented cases were from previous bouts of avian influenza that had a human incidence from and . with support of egypt-based naval army medical research unit three (namru ), clinicians were motivated to sample all ili patients and submit to collaborating international reference influenza lab in cairo, egypt. vaccination: influenza vaccinations were undocumented, but at least ae % ( ) of population sought the service (for yellow fever and meningitis) as mandatory travel advisory or as childhood immunization need. at the time of going to the press, there were at least vaccine doses of h n ( ) virus donations yet to be administered. health promotion and hygiene: print and audiovisual risk communication remained favorite means of reaching out to urban dwellers ( ae %). while to the rural and nomadic population, person to person communications was the preferable means. to increasing public awareness that will encourage reporting of ili cases and entrench risk aversion health behavior that limits flu spread, who-copanflu international study djibouti has incorporated basic training on ili infection and personal hygiene by interviewers during household inclusion. improving national epidemic surveillance capacity and response under new international health regulation is important for any nation, including djibouti. our finding indicates the winter season predisposes one to ili infections; they therefore opt for medical services or self medication depending on their capability and ⁄ or understanding. in djibouti, almost no city dwellers favors self medication over clinical consultation, suggesting the presence of inhibitory factors like distance from the health centers and the cost of accessing consultancy. common in the absence of universal primary health care setting, it therefore calls for active innovativeness in outbreak detection, disease reporting, and preventive medicine on the part of health authority so as to achieve good population health. in respond to these, niph has turned resource limitation to a motivation instead and is working towards institutionalizing a near-real-time syndromic surveillance system as a core functional unit. it capitalizes on three major aspects within its reach: prompt accurate data generation for analysis, ehesp wcic-study input, and information technology use. prompt accurate data generation for analysis: data used in our analysis suffered from un-timeliness (weekly instead of daily basis), incompleteness (vague over-counter drug sales records), entry errors (incidence case reports), and poor collection format (most of data collection forms). use of satellite handset phones for regional health centers and mobile phones for city sentinel clinics will reduce unnecessary data delivery delays. in addition, creating awareness to data entry personnel on the importance of careful and completeness of entries is important, as is the need to reformat data collection forms to capture exact aspects of surveillance needs for relevant executable analysis. besides alerting for immediate impending epidemics, these data can also be adopted for projective predictive modeling of annual epidemics, including that for influenza. ehesp wcic-study input: djibouti wcic-study is complementary to the existing syndromic surveillance system, but with emphasis on flu and flu-like illness. various innovations as suggested above are used in seeking to overcome the prevailing challenges. while every attempt is made to realize its (wcic-study) objective and for global comparison, lessons learned from successful implementation will form a platform for future refined syndromic surveillance protocol as equally reported elsewhere in asian countries. , information technology: national institute of public health djibouti has an informatics department with sufficient working pcs and personnel to execute efficient data collection and management for epidemiological analysis. however, licensing cost of near-real time syndromic surveillance software is prohibitive, but the open access software with capacity to generate custom graphs, maps, plots, and temporal-spatial analysis output for specific syndromes should make implementation a lot easier. such output for conditions like flu (or gastroenteritis) will be essential to cause prompt response of the local public health office and international partners in saving lives and suffering of djibouti people. pandemic flu surveillance and preparedness requires multifaceted, interdisciplinary, and international approach whose efficiency and efficacy can only be refined over time. building on the health care system's swot for preparedness, the ehesp wcic-study promises to refine surveillance system operation and knowledge on individual's risk determinants to swine flu (h n ) virus infection at the household level in djibouti. these efforts are ultimately creating available control options at the time of need (pandemic occurrence), and at the same time exploring investment in quality data profiling and information technology, which will include syndrome surveillance software systems like essence, ewors, or other open sourced ones. the antibody efficacy -which compares the illness frequency between those with and those without a protective level of pre-epidemic hi antibodies ( ‡ : ) -has been proposed ; however, this index has rarely been used due to practical difficulties in confirming the strain-spe-cific disease corresponding to each of the vaccine-induced antibodies. we followed elderly individuals residing in a nursing home, whose serum specimens were obtained before and after undergoing trivalent influenza vaccination, in ⁄ influenza season (medium-scale mixed [a ⁄ h n and b] epidemic in study area, and a ⁄ h n was circulating at the nursing home). the serum antibody titre to each strain of influenza virus was measured by the hi method, using the same antigens as those in the vaccine. all participants' body temperatures, respiratory symptoms, other general symptoms, hospitalization, discharge, and death were recorded daily from november to april in a prospective manner. when the participants suffered any influenzalike symptoms, such as sudden fever ‡ ae °c, throat swabs were collected and tested using a rapid diagnosis kit for influenza, which utilizes an immunochromatographic method. the adjusted odds ratios (or adj ) for febrile illness and kit diagnosed influenza were evaluated using multiple logistic regression models adjusting for possible confounders (i.e., age, sex, coexisting conditions, and vaccine strains). after vaccination, the proportion of subjects achieving an hi antibody titre ‡ : (seroprotection level) were ae % ( ae - ae %) for a ⁄ h n , ae % ( ae - ae %) for a ⁄ h n , and ae % ( ae - ae %) for b. during the follow-up period, the a ⁄ h n strain was isolated therein, and subjects experienced sudden-onset fever ( ‡ ae °c), and eight subjects were positive for rapid diagnosis kit. patients with a seroprotection level of the hi antibody titre ( ‡ : ) had lower incidences of febrile illness (or adj , ae ; % ci, ae - ae ) and rapid kit diagnosed influenza (or adj , ae ; % ci, ae - ae ) than those with a lower titre. thus antibody efficacy ( ) or adj ) against fever related to a ⁄ h n and kit diagnosed influenza were both estimated to be %. although statistical significance was not detected due to limited sample size, these results lend support for the usefulness of antibody efficacy. some data presented within this manuscript was also published in hara et al. asia via a regional network from which epidemics in the temperate regions were seeded. the virus isolates obtained from nasopharyngeal swab specimens from outpatients were typed and subtyped by the hemagglutination (ha) inhibition assay. the emergence of a ⁄ fujian ⁄ ⁄ coincided with higher levels of influenza-like illness in korea than what is typically seen at the peak of a normal season. most of the intermediates and fujian-like strains were isolated from asian countries, and the mutational events associated with the fujian strains took place in asia. closely dated phylogeny from december , to august , showed that the antigenic evolution of the h n fujian strains had periods of rapid antigenic changes, equivalent to amino acid changes per year ( figure ). the fujian-like influenza strains were disseminated with rapid sequence variation across the antigenic sites of the ha domain. the antigenic evolution of the fujian strains was initiated by exceptionally rapid antigenic change that occurred in asia, which was then followed by relatively modest changes. some of the data presented in this manuscript was previously published in kang et al. we compared reactivity to the novel virus strain using haemagglutination inhibition (hi) assays performed on discarded plasma specimens left over from routine testing. samples were taken from healthy adult blood donors (> years) before and after the ph n influenza epidemic that occurred during the southern hemisphere winter of , and again prior to onset of the southern hemisphere influenza season. reactivity to the novel h n strain of influenza was relatively uncommon among the healthy adult population during the first australian winter wave, rising from a baseline of % to %. a further increase in the seropositive proportion from % to % was observed over the summer months, most likely attributable to immunisation. this level of immunity appears to have been sufficient to constrain the winter epidemic. together with a final serum collection, planned for late , these data will aid evaluation of the extent and severity of disease in this 'second wave' of ph n . assessment of the extent of disease due to novel influenza a(h n ) virus (ph n ) during the winter outbreaks in australia was made difficult by the generally mild nature of disease. the epidemic was experienced in a staggered fashion around the country, reflecting the considerable geographical distances between state and territory capital cities ( figure ). differences in the intensity of case-finding during the evolving pandemic response and between jurisdictions hindered comparisons of disease burden in distinct geographical regions. rates of reported hospitalisations and deaths appeared fairly similar across states but, without a consistent exposure denominator, assessment of relative severity was difficult. we conducted a national serosurvey of antibody to ph n using residual plasma from healthy blood donors collected before and after the epidemic to estimate ph n exposure. here we report the findings of that first collection, together with new data on seroprevalence of ph n antibody in specimens gathered in march-april . these latter samples were collected prior to onset of seasonal influenza activity to assess the impact of a national ph n vaccine program conducted in spring ⁄ summer ⁄ on the proportion of individuals with antibody titres deemed protective. findings informed estimates of population susceptibility to ph n prior to the influenza season and provided a baseline for a subsequent serosurvey that will be collected at the end of to assess the extent of exposure during the 'second wave.' tralian red cross blood service (the blood service) for dengue fever surveillance studies. these samples were used to provide a baseline estimate of prevalence of cross-reactive antibody to ph n in the australian population. discarded plasma specimens, taken for virologic testing from healthy adult blood service donors, were prospectively collected at two additional timepoints for measurement of antibody to ph n . collection periods were as follows: approximately plasma samples were randomly selected from donors in each of brisbane, hobart, melbourne, newcastle, perth, sydney, and townsville on each occasion. up to specimens were identified in each of the following age strata: - , - , - , - , - , and > years. at the last collection timepoint, there was deliberate over-sampling of the oldest and youngest age strata in which approximately specimens were collected (i.e., up to specimens per site). in accordance with the provisions of the national health and medical research council's national statement on ethical conduct in human research, individual consent was not required for use of these specimens, given the granting of institutional approval by the blood service human research ethics committee. reactivity of plasma against ph n was measured in haemagglutination inhibition (hi) assays using turkey red blood cells (rbc). egg-grown a ⁄ california ⁄ ⁄ virus was purified by sucrose gradient, concentrated and inactivated with b-propiolactone, to create an influenza zonal pool preparation (a gift from csl limited). plasma samples were pretreated with receptor destroying enzyme ii (denka seiken co. ltd), : (volume ⁄ volume) and tested as previously described. following hour incubation, ll % (volume ⁄ volume) of rbc was added to each well. hi was read after minutes. any samples that bound to the rbc in the absence of virus were adsorbed with rbc for hour and reassayed. samples in which background activity could not be eliminated by these means were excluded from the analysis. titres were expressed as the reciprocal of the highest dilution of plasma where haemagglutination was prevented. a panel of control sera and plasma samples was included in all assays. it comprised paired ferret sera pre-and postinfection with the pandemic virus or seasonal influenza a(h n ), a(h n ), or influenza b viruses and paired human plasma and sera collected from donors before april or after known infection with the pandemic virus or after immunisation with the australian monovalent pandemic vaccine. all assays were performed by the who collaborating centre for reference and research on influenza. for each of the three study timepoints and within each age group, the proportion of seropositive individuals (hi titres ‡ ) was calculated, with exact (clopper-pearson) confidence intervals. the contribution of individual variables (age, gender) and location to seropositive status was assessed in separate multivariate logistic regression models developed to assess the post-pandemic and pre-influenza season collections. all statistical analyses were conducted in stata . locations of specimen collection are shown in figure , together with the number of samples tested from each centre. samples with high background hi titres or discrepancies between assays were excluded at each timepoint as follows: at baseline, from the post-pandemic collection, and in early . pared with baseline was % overall, rising from % to % (table ). the only jurisdictions in which seropositive proportions were higher in october ⁄ november than in the baseline collection were hobart [ % ( % ci ae , ae )], perth [ % ( ae , ae )], and sydney [ % ( ae , ae )]. in the multivariate regression model, the only jurisdiction in which exposure appeared somewhat higher than the reference population of brisbane was hobart [or ae ( % ci ae , ae ), p = ae ]. a marked age effect on antibody status was observed at this timepoint, with an increase in the proportion of seropositive individuals in relation to the baseline collection only noted for those aged between and years (table ) . according to the multivariate model, the youngest and oldest cohorts had similar titres, with all other groups showing significantly lower seropositive proportions than the reference population of - years [e.g. - years or ae ( % ci ae , ae , p < ae )]. an overall increase in the seropositive proportion from % to % was observed between october and april , distributed throughout all jurisdictions ( ( , ) ]. antibody titres prior to the influenza season rose in all age groups, but remained significantly lower among [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] year olds than in the youngest age cohort (table ) . adjusted ors for the seropositive proportion in the multivariate model in these age groups were: - years [or ae ( % ci ae , ae )]; - years [or ae ( ae , ae )]. the relatively low titres observed in these groups reflected small incremental increases in the seropositive proportion across each of the time points studied, suggestive of both low rates of infection and vaccination. the rise in immunity observed across the population was most likely attributable to immunisation in the majority, given the absence of observed outbreaks and very few notified cases of ph n during the period between the two plasma collections. this study suggests that, while adult exposure to ph n during the southern hemisphere winter was uncommon at around %, vaccine uptake in the australian population over the period november -may was in the order of %. this latter estimate is in keeping with recently published figures for adult ph n vaccine coverage from a national immunisation survey conducted by the australian institute of health and welfare. in that survey, vaccine coverage was significantly higher in tasmania than in other states, but mostly in those over years of age, possibly in a subgroup whose health status may have differed from that of the donor population. no allowance has been made in this analysis for likely waning of natural or vaccine induced immunity, possibly resulting in lower estimates of natural and ⁄ or vaccine exposure than may have occurred over the period. regardless of such intervening processes, the seropositive proportion among australian adults at the start of the winter season appeared likely to be sufficient to constrain transmission of infection in the age groups tested. this assertion has been borne out in practice, with only modest levels of influenza reported during the late and protracted season. a final serum collection is planned for the end of the influenza season in australia from which to assess the level of exposure in relation to the baseline observed here. the need for epidemiologic studies such as this has been highlighted by groups such as the european centre for disease control to aid evaluation of the extent and severity of the 'second wave,' known to be variable from historical reports of past pandemics in disparate populations. in - , the first wave of the swine-origin novel h n flu (h n ) pandemic swept across the world, including japan. to examine the epidemiological nature of this novel infectious disease among school children within and among small regional communities, we have carried out a complete survey on the incidence of h n among school children using absentee reports provided by school health teachers in two small administrative districts (population: about in total) in japan. we then examined the epidemiological diversity on the inci-dence of h n within and among small regional communities. we investigated seventeen elementary and ten junior high schools in moroyama-town and sakado-city located in the central part of saitama prefecture. populations are: all ages, and ; elementary schools, and ; junior high schools, and , respectively. the number of school children in each school ranges from to . the surveillance system was built on an apache-and mysql-based web server using html, php, and java-script. school health teachers enter information on children absenteeism due to school infectious diseases via web browsers at each school infirmary on a daily basis. in addition to the trend graphs shown on the web browser, detailed analyses were reported to the schools and local educational boards weekly. the basic reproduction number (r ) of h n was estimated according to becker. agentbased modeling and simulations were also performed using a multi-paradigm simulator anylogic version . (xj technologies, st. petersburg, russia). by the end of march , cumulative incidence (ci) of h n among school children in moroyama and sakado reached % and %, respectively. the overall r among school children in this area was ae . vaccination rate of children in this area during the surveillance period was reported to be very low (< %). there was no considerable difference between the epidemic curves in this neighboring town and city. on the other hand, in the individual schools, the cis as of the end of march scattered from % to % ( figure ) even though the schools are closely located. to examine the cause of this diversity, we built an agent-based community model consisted of the same numbers of agents as those of children in the actual schools and people in moroyama and sakado to simulate the infection. the ratio of probability of infection in schools and the remaining places were assumed to be : or : . using a heuristic optimization scheme, we estimated the parameters for the simulations to give the overall ci of % (the ci as of the end of march ). we then performed simulations repeatedly. the cis obtained with the repetitive simulations with the assumption of higher probability of infection in schools scattered from % to %, indicating that the cis of the small population communities may vary considerably, even though all the agents were assumed to have the same susceptibility to infection at the beginning, and the other conditions were the same. the policies for surveillance ⁄ analyses ⁄ prevention of communicable diseases in local communities have generally been decided on governmental-and ⁄ or each local administrative district-basis (populations: several hundred thousands to several millions) in japan. we found the considerable variations in the cis of h n for children among much smaller areas, i.e., the school districts (populations: all ages, several thousands; school children, several hundreds). we thus conclude that the granularity of surveillance ⁄ analyses ⁄ prevention should be finer than in the past to achieve the most effective policies against influenza and similar communicable diseases in the local communities. the cause of this diversity can be explained in part by the stochastic nature of infection transmission processes in the small populations shown by the agent-based simulations. we have already conducted a complete questionnaire survey for the school children and their parents to clarify the relevance of the other issues including differences in environmental factors, preventive policies (e.g., vaccination, school closures), etc., in each school. the detailed analyses will be reported elsewhere. a www-based surveillance system for transmission of infectious diseases among school children within and among small regional communities. j epidemiol ; (s ):s . this study confirms previous findings that age, pandemic influenza vaccination, and history of ili are associated with elevated post-seasonal gmt. this study also shows that seasonal influenza vaccination may have contributed to an increase of the hai titer, especially in the elderly. further analyses in this cohort are needed to confirm and explain these first results. the follow-up of subjects involved in the copanflu-france cohort will provide data to study the risk factors for infection by the influenza virus. the first cases of the a ⁄ h n v pandemic influenza were reported in mexico and the united states in april . given the context of this new influenza virus and considering the likelihood of its pandemic spread, the cohorts for pandemic influenza (copanflu) international consortium was created in order to study individual and collective determinants of pandemic a ⁄ h n v influenza across different countries by setting up prospective cohorts of households, followed during years. this study relies on the first available data from the copanflu-france project, which is part of the copanflu international consortium. we studied factors associated with elevated haemagglutination antibody titers against a/h n v at entry in the copanflu-france cohort. we focused in this primary analysis on the association between the titers and influenza vaccination (seasonal or pandemic) across age groups. the copanflu-france cohort was set up in fall . inclusions began on december , and ended on july , . households were sampled using a random telephonic design (mitofsky-waksberg method) in a stratified geographical sampling scheme, aimed at including a sample of subjects representative of french general population. all household members were eligible to the cohort, without any age limit. the inclusion of a household required the participation of all members: the refusal of one or more member(s) prevented the inclusion of other members. the protocol was approved by a research ethics committee and written informed consent was obtained for all subjects. this study requires several visits to the households by nurses who collect written data with questionnaires and biological samples. during the inclusion visits, nurses collected from all subjects detailed data regarding medical history, including vaccination and preventive measures against influenza. blood samples were collected at entry and centralized. a standard hai technique was adapted to the detection and quantification of antibodies to the a ⁄ h n v virus. the titration endpoint was the highest dilution that exhibited complete inhibition of haemagglutination in two independent readings. the lowest read dilution was ⁄ . geometric mean titers were calculated for hai assays with the use of generalized estimating equations for interval-censored data, , taking into account a within-household correlation. multivariate models were derived from this method to identify factors associated with elevated gmts. we defined the ''gmt ratio'' (gmtr) as the multiplicative factor applied to the gmt in presence of an explanatory variable. for qualitative explanatory variables, a gmtr of n means a predicted n-fold higher gmt for subjects exposed to the considered factor compared to others. for continuous explanatory variable, the same interpretation applies to a unit difference. the following variables were included in the multivariate models: age, history of pandemic or seasonal influenza vaccination, and history of ili. age was categorized in three groups: - years (reference group), - years and over years. the definition of ili was that used by the cdc : fever ‡ ae °c and cough and ⁄ or sore throat without another known cause. history of ili was defined as an ili reported by the subject between september , (beginning of the influenza epidemic in france) and the date of inclusion. this preliminary analysis included subjects belonging to households. results reported hereafter do not account for missing data. participating households were sized - subjects, mean size = ae . in comparison, the mean size of french households is ae according to the latest national census. the median age of subjects at entry was ae years [iqr: ae ; ae ] versus ae [ ae ; ae ] for french population. the proportion of subjects reporting a history of ili since the beginning of the epidemic varied from ae % for subjects over years to ae % for subjects below years (table ) . vaccination with the pandemic strain was the highest in subjects below ( %) whereas vaccination with the seasonal strain was the highest in subjects over ( ae %). detailed data regarding vaccination is given in table . this study confirms previous findings that age, pandemic influenza vaccination, and history of ili are associated with elevated post-seasonal gmt. [ ] [ ] [ ] [ ] [ ] [ ] among non-vaccinated subjects, elevated gmt in the elderly may be the result of exposure to similar viruses in early life, whereas children and young adults with elevated gmt are likely to have been infected by the a ⁄ h n v virus. [ ] [ ] [ ] [ ] interestingly, a significant drop in the hai titer is observed during the months following vaccination with the pandemic strain. this study also shows that seasonal influenza vaccination may have contributed to an increase of the hai titer, especially in the elderly. the reason for this association is not obvious: although we cannot discard the hypothesis of a higher incidence of a ⁄ h n v infections in seasonal vaccine recipients, as described by several other studies, - the main explanation may be a cross-reaction between pandemic and seasonal strains. , , further analyses in this cohort are needed to confirm and explain these first results. the follow-up of subjects involved in the copanflu-france cohort will provide data to study the risk factors for infection by the influenza virus. in april , the cdc alerted about the appearance of a new strain of ia h n with unknown virulence. infants under years old had higher risks of hospitalization, complications, and rate of death for sari. materials and methods: a cross-sectional study was executed from may to december in . the sources were: mandatory reporting form of the province surveillance system, databases of the hospital management information system, clinical pictures reviews, and telephone daily medical reports. inclusion criteria: children under years old with diagnostic of ili or sari and confirmed cases with epidemiological nexus or laboratory confirmation (rrt-pcr, ifi). the age specific mortality rates were calculated with an estimated population for the province according to the national statistics and census institution. results: the ili rate in infants under years old was ae ⁄ people ( % ci - ) being higher in infants of years old ( ⁄ people of years ( % ci - ) ( table ) . infants had less risk of getting sick in relation to the rest of the population (rr ae [ % ci ae - ae ]) (p < ae ). the chance of sari in infants was ae ( % ci ae - ae ) compared to the rest of the population. the lethality rate was higher in infants under year old ( ⁄ people [ ⁄ ]). discussion: the evidence suggests that the infants under years old had lower risk of getting sick than the rest of the population, but had higher risk of sari if they had some past illness. the highest lethality rate was presented in infants under year old. non-medical interventions had an important role in the epidemic containment for not having a specific vaccination available. as this age group had high risks of hospitalization, it would be advisable to prioritize their vaccination. in april , the cdc alerted about the appearance of a new strain of ia h n with unknown dissemination and virulence. in june, the world health organization declared the pandemic. , the ili often presents an unspecific clinical picture in infants under years old, from mild symptoms to sari, especially in the newborn babies. infants under years old have higher risks of hospitalization, complications, and rate of death for sari. , on may th, argentina declared the first imported case of ia h n , and by the end of the month, it announced the viral circulation in the country. the epidemiological surveillance system of the province arranged that all the patients with influenza diagnosis made by a doctor must be reported. from april th to november th, suspected cases of ili in the province of tucumán were reported. the ili rate was ⁄ people, and ia h n comprised ⁄ people. the lethal rate of sari ia h n was ae ⁄ people ( ⁄ ). the objective of this research was to determine the epidemiological characteristics of the pandemic ia h n in infants under years old in the province of tucumán between may and december in . the province of tucumán is placed in the center of the northwest of the republic of argentina. it has a population of inhabitants of which are infants under years old. the crude birth rate for was ae &. the infant mortality rate was ae &. respiratory pathologies in infants under years old were the third cause of death in the province ( %). the public health system of the province is composed by three sectors: public, private, and welfare. with health facilities as a total, the average of available beds is & per inhabitants and & per neonates. a cross-sectional study was executed from may to december in in the province of tucumán, argentina. the following sources were used: mandatory reporting form of the surveillance system of the province filled by a doctor, databases of the hospital management information system, clinical pictures reviews, and telephone daily medical reports (patients with sari). inclusion criteria: • suspected case of ili: sudden appearance of fever higher than °c, cough, or sore throat. it may or may not be accompanied by asthenia, myalgia or prostration, nausea or vomiting, rhinorrhea, conjunctivitis, adenopathy, or diarrhea. ) were used for the analysis. the odds rations, risk ratio and % confidence interval were calculated to compare ambulatory with hospitalized patients, confirmed and dismissed, < years old and the rest of the population. it was considered significant a rate of p < ae . the age specific mortality rates were calculated with an estimated population for the province according to the national statistics and census institution. the epidemiological surveillance system of the province received ili reports, ae % ( ⁄ ) were infants under years old. twenty seven percent were dismissed ( ⁄ ), and % ( ⁄ ) of suspected cases were confirmed. the first ia h n case was a child of years from the province of buenos aires, in th epidemiological week, and the last suspected case was reported in october , ( figure ). the ili rate in infants under years old was ae ⁄ people ( % ci - ), being higher in infants of years old ( ⁄ people of years, [ %ci - ]). the higher ili rates in confirmed the pandemic of ia h n ( ) was detected for the first time in the province of tucumán. the evidence suggests that infants under years old had lower risk of getting sick than the rest of the population (protective factor), but had higher risk of sari if they had some past illness. the highest lethality rate was presented in infants under year old. towns with the highest demographic density had superior proportion of cases. non-medical interventions had an important role in the epidemic containment for not having a specific vaccination available. as this age group had high risks of hospitalization, it would be advisable to prioritize their vaccination. outbreak of h n influenza - : behavior of influenza h n in school children in the province of tucumá n, argentina criteria: patients treated with antiviral medication for prophylaxis, respiratory pathologies which did not justify specific medication, and incomplete forms. results: from all notifications, were cases of ili in the group aged - years old; % were males. the incidence rate in this group was ae per thousands of inhabitants. the % of laboratory samples were influenza a h n , % were confirmed as unspecific influenza, and % were dismissed. the school aged children group had a high risks of getting sick (r.r. ae [ % c.i. ae - ae ]), especially males. it appeared that school aged children had a protective factor for presenting sari (or ae [ % c.i. ae - ae ], p < ae ). the lethality rate in this group was ae ⁄ thousands. headaches, myalgia, coryza, and sore throat were very common and significantly different (p < ae ) than the rest of the population. it was reported a decrease in the ew coinciding with winter holidays (ew ). the epidemic curve was different in males compared to females during the winter holidays. discussion: school aged children got sick more than the rest of the population, although they presented less proportions of sari. however, comorbidities were decisive in order to present sari or death. the epidemic curve was different in males compared to females. through its analysis, the beneficial effect of school closure was observed, as long as children meet the recommendation to stay home. in april , different countries reported cases of influenza a h n ; mexico reported a high mortality rate associates with this disease. the world health organization (who) declared the phase influenza pandemic alert on june . several reports from different countries describe the behavior of the pandemic in school aged children. this group plays an important role in the transmission of influenza. in germany, during the summer peak, pandemic hardly spread within this group. this might be explained by the timing of the summer school holidays, which started between ew and . since mid october, after the autumn holidays, the school-aged children began to be more affected, and the proportion increased from % in the initiation period to ae % in the acceleration period. in australia, % of h n cases were school aged children ( - years), with a median age of years ( % of cases were aged - years and, and % between - years). in canada, the infection rate was highest in this group. in chile, the incidence rate was ⁄ inhabitants, although in general they had mild desease. school closure can operate as a proactive measure, aimed at reducing transmission in the school and spread into the wider community, or reactive, when the high levels of absenteeism among students and staff make it impractical to continue classes. the main health benefit of proactive school closure comes from slowing down the spread of an outbreak within a given area and, thus, flattening the peak of infections. this benefit becomes especially important when the number of people requiring medical care threatens to saturate health care capacity. it has its greatest benefits when schools are closed very early in an outbreak, before % of the population falls ill. school closure can reduce the demand for health care by an estimated - % at the peak of the pandemic under ideal conditions, but too late in the course of a community-wide outbreak, the resulting reduction in transmission is likely to be very limited. policies for school closure need to include measures that limit contact among students when they are not in school. tucumán is placed in northwest argentina and has a total area of km . the population ( census, projection ) was inhabitants; of wich were - years old. the health system of the province is composed of sectors: public, private, and welfare. it has a total of health facilities with internement available and an average of & inhabitants. influenza-like illness (ili) has seasonal and endemic behavior in this province, as evidenced by past records from the national health surveillance system and influenza sentinel surveillance unit of the province. an increase of ili was reported in , with a peak in the ew . the objectives were: general objective to describe the behavior of the influenza a h n epidemic in school aged children from the province of tucumán, argentina. specific objectives • to explore the response to preventive measures by school aged population. • to assess the effect of the suspension of classes in this group. • to estimate the magnitude and severity of the disease. • to observe the effect of co-morbidities in this group. a cross-sectional study was executed from may to december . data were gathered through mandatory reporting forms, wich were collected from all public and private health centers. inclusion criteria: patients with compatible symptoms with influenza a; school aged children - years old. exclusion criteria: patients treated with antiv- iral medication as prophylaxis, respiratory pathologies which did not justify specific antiviral medication, and incomplete forms. • suspected case of ili: cases considered by clinical criteria (fever higher than °c, cough or sore throat. it may or may not be accompanied by asthenia, myalgia or prostration, nauseas or vomiting, rhinorrhea, conjunctivitis, adenopathy, or diarrhea). • confirmed case: person with positive laboratory results for influenza a h n or unspecificed influenza a (by laboratory results through rrt-pcr or immunofluorescence techniques). • dismissed case: by negative or different laboratory results, or different clinical evolution. • comorbidities: chronic illnesses like arterial hypertension, diabetes, asthma, recurrent obstructive bronchial syndrome (robs), smoking, chronic obstructive pulmonary disease (copd), immunosuppression, hiv ⁄ aids, cancer, nephropathy, obesity; pregnancy was also considered. data were analyzed using epi software (epi infoÔ cdc, atlanta, eeuu). rates were calculated and rr was estimated with their respective confidence interval (ci). population data were taken from national census projections. an estimation based on the same census was used for the group between and years old. to observe the effects of other co-variables, the or and their ci were calculated. logistic regression was used to evaluate the influence of the comorbidities. x was used to compare proportions. respiratory samples (nasopharyngeal and faryngeal swabs) were obtained. they were analyzed at influenza sentinel surveillance unit of tucumán, and ⁄ or sent to national reference laboratory dr. c. malbrán (rt-pcr). from all notifications ( ), were cases of ili in the group aged between and years old, % ( ⁄ ) of which were males. the incidence rate was ae , and it differed according to the sexes: ae males and ae females per thousands of inhabitants (p < ae ). of all laboratory samples ( ) % were confirmed as influenza h n , % were confirmed as unspecificied influenza, and % were dismissed. the remaining percentage corresponded to the isolation of other viruses (parainfluenza, respiratory syncytial virus, and adenovirus). the school aged group had higher risk of getting sick, in relation to the rest of the population (rr ae [ % ci ae - ae ]), especially males (rr ae ) compared with females (rr ae ). the highest attack rate was observed in the capital of tucumán ( ⁄ inhabitants). according to the rest of the population, it looked like being school aged children meant a protective factor for presenting sari (severe acute respiratory infection) (or ae [ % ci ae - ae ], p < ae ). the lethality rate was ae ⁄ thousand. the risk of dying was low compared to other ages. persons with comorbidities had significantly higher risk of presenting sari (or ae [ % ci ae - ae ], p < ae ) and of dying (or ae [ % ci ae - ae ], p < ae ). respiratory comorbidities were the most fre- quent: asthma ae % ( ⁄ ) and % rors ( ⁄ ). the symptoms headaches, myalgia, coryza, and sore throat were very common and significantly different (p < ae ) than the rest of the population. if we compared the group aged - years with - years old, the epidemic curve of the first group showed a decrease in the ew , coinciding with winter holidays (ew ) (figure ). there was a slight increase in the tendency when classes began, but it showed a clear declination afterwards. the analysis of rates in school aged children by ew showed a reduction of ae % in males and ae % in females (p < ae ) at ew . however, after the first week of winter holidays, the curve in males had a significant increased to ae % compared to ew , reaching the highest weekly rate of the epidemic ( ⁄ inhabitants). the reopening of classes coincided with a significant decrease of the rate ( ae %), from to ae ⁄ inhabitants in ew (p < ae ). in females, the school closure coincided with a plateau-shaped curve, and the reopening with a significant decrease of ae % of the rate, from ae to ae in ew ( figure ). the school children got sick a lot more than the rest of the population, although they presented less proportions of sari. however, comorbidities were determined in order to present sari or death. symptoms like headache, myalgia, coryza, and sore throat were considered more conducting for the definition of cases in this population in tucumán. the epidemic curve was different in males compared to females during the winter holidays. the beneficial effect of school closure was observed as long as persons met the recommendations. the difference between males compared to females during winter holidays could mean that women would have carried out social distance recommendations much better, for example, remained at home. the significant reduction after the opening of classes is a factor to be considered as an effective intervention in the declining stage of the curve. here, we report pdmh n infection attack rate (iar) during the first wave of the pandemic. we used our iar estimates to infer the severity of the pandemic strain, including the age-specific proportion of infections that led to laboratory confirmation, hospitalization, intensive care unit (icu) admission, and death. [ ] [ ] [ ] [ ] part of these results are now available in ref. subjects of a community study, - years old between november and october , we conducted a cohort study of pediatric seasonal influenza vaccination and household transmission of influenza. one hundred fifty-one children aged - were recruited and provided baseline sera in november and december . between september and december a further children aged - were recruited and provided baseline sera for the second phase of the study. for this serologic survey, we tested the sera collected before the first wave and the sera collected after the first pandemic wave. written informed consent was obtained from all participants. parental consent was obtained for participants aged or younger, and children between the ages of and gave written assent. all study protocols were approved by the institutional review board of the university of hong kong ⁄ hospital authority hong kong west cluster. age-stratified data on virologically confirmed outpatient consultations, hospitalizations, icu admissions, and deaths associated with pdmh n from april to november were provided by the hong kong hospital authority (the e-flu database). since may , patients admitted with acute respiratory illnesses routinely underwent laboratory testing for pdmh n virus by molecular methods. sera were tested for antibody responses to a ⁄ california ⁄ ⁄ by viral microneutralization (mn). most individuals infected with influenza develop antibody titers ‡ : by viral microneutralization after recovery. we defined the pdmh n seroprevalence rate as the proportion of individuals who had antibody titers ‡ : . while mn antibody titers of ‡ are not by themselves conclusive evidence for pdmh n infection, we have assumed that the increase in cross-sectional seroprevalence between the pre-and post-first wave time periods are evidence of recent pdmhn infection. the iar was defined as the proportion of individuals infected by pdmh n during the first wave. the case-confirmation rate (ccr), case-hospitalization rate (chr), case-icu-admission rate (cir), and case-fatality rate (cfr) were defined as the proportion of pdmh n infections that led to laboratory-confirmation, hospitalization, icu admission, and death. due to containment efforts until june , all laboratory-confirmed cases were required to be hospitalized for isolation regardless of disease severity. as such, only surveillance data from june onwards were used to estimate severity measures. we estimated the iar as the difference between the prefirst-wave and post-first-wave seroprevalence rate. we used the estimated iar as the denominator for calculating the ccr, chr, cir, and cfr. we used an age-structured sir model with age classes ( - , - , - , - , and ‡ ) to describe the transmission dynamics of pdmh n in hong kong between june and november . we assumed that the mean generation time was ae days. using the age-structured transmission model, we estimated the following transmission parameters from the serial cross-sectional serologic and hospitalization data: (i) r o , the basic reproductive number; (ii) p and p , the reduction in within-age-group transmission for - and - years old during summer vacation (compared to school days during september-december ); (iii) d r , the average time for neutralization antibodies titer to reach ‡ : after recovering from infection; (iv) h a , the age-specific relative susceptibility with - years old adults as the reference group. we assumed non-informative priors for all parameters and used monte carlo markov chain methods to obtain posterior distributions of the parameters. sources of specimens: [ ] pediatric cohort study ( - april virological surveillance data suggested that the first wave of pdmh n in hong kong occurred from august to october . most of the laboratory-confirmed infections in this first wave occurred in individuals aged below years old accounting for > % of the lab-confirmed cases and hospitalizations, % of icu admissions, and % of deaths. taking into account a delay of - weeks for antibody titers to appear during convalescence, we found that these virological surveillance data were consistent with our serial cross-sectional seroprevalence data, which indicated a sharp rise in seroprevalence among the - years old from september to november and a plateau thereafter (data not shown). among individuals aged - years, the seroprevalence rates were similar across time between pediatric outpatient subjects and pediatric cohort study subjects (data not shown). similarly, for older age groups, the seroprevalence rates were largely similar between blood donor subjects and hospital outpatient subjects (except for the - years old in november-december). this provided some evidence that despite biases in our convenience sampling scheme, the resulting serologic data provided a reasonably representative description of seroprevalence in the community. the estimated pre-and post-first-wave seroprevalence rates and the corresponding iar estimates are shown in table . the severity estimates (ccr, chr, cir, and cfr) are shown in table . in summary, we estimated the iar was ae % among - years old, ae % among - years old, ae % among - years old, ae % among - years old, ae % among - years old, and ae % among - years old. overall, we estimated a population-weighted iar of ae % ( - %) among individuals aged - years through the first wave in hong kong. ccr were around ae - ae % among the - years old. chr were around ae - ae % among the - years old. cir increased from ae ( ae - ae ) per infections in - years old to ( ae - ) per infections in - years old. cfr followed a similar trend with ae ( ae - ae ) death per infections in - years old to ae ( ae - ) deaths per infections in - years old. compared to children aged - , adults aged - were ae and times more likely to be admitted to icu and die if infected. the best-fit age-structured transmission model gave the following parameter estimates: . the basic reproductive number was ae ( %ci, ae - ae ). . it took an average of ( - ) days for recovered individuals to develop neutralization antibody titer ‡ : . table . estimated age-specific proportions of individuals with pdmh n infections that were laboratory-confirmed, were hospitalized, were admitted to icu, and died. case-icu and case-fatality rates are expressed as number of episodes per infections . compared to - years old, - years old children and - teenagers were ae ( ae - ae ) and ae ( ae - ) times more susceptible to pdmh n infection, respectively. . compared to - years old, - years old older adults and - years old elderly were only ae ( ae - ae ) and ae ( ae - ae ) times as susceptible as the - years old, respectively. . compared to the school period during september-december , summer vacation reduced within-agegroup transmission by % ( - %) among - years old, but only % ( - %) among - years old. using computer simulations, we estimated that if preexisting seroprevalence is zero, real-time serologic monitoring with about specimens per week would allow accurate estimates of iar and severity as soon as the true iar has reached % (data not shown). we estimated that during the first wave in hong kong, ae % of school-age children and ae % of individuals aged - were infected by pdmh n . a serologic survey in england found similar iars in london and the west midlands. both studies highlight the importance of including serologic surveys in pandemic surveillance. the geographically compact and well-mixed population in the urban environment of hong kong permits some degree of confidence in the validity of our iar and severity estimates. the completeness of the pdmh n surveillance system, welldefined population denominator, and our large-scale serologic survey provide accurate numerators and denominators for the severity measures. we based severity estimates for pdmh n on the iar as the denominator. in most previous studies of pdmh n severity, the denominator was clinical illness attack rate, which depends on the probability of symptoms as well as medical care seeking behavior of the population. , our estimated cirs and cfrs are broadly consistent with presanis et al.'s 'approach ' severity estimates, but around - times lower than their 'approach ' estimates. our estimates of chr are - times higher than their approach estimates of symptomatic chr. however, the hospitalization-death ratio was ⁄ = as of november in hong kong, but ⁄ = as of june in new york, suggesting that the clinical threshold for admission in terms of disease severity at presentation may have been lower in hong kong. our study has a number of limitations. first, we have used antibody titers of ‡ : by viral microneutralization as an indicator of recent infection, correcting for pre-existing seroprevalence levels, but this may lead to underestima-tion of the iar if some infections led to antibody titers < : , or if some individuals with baseline titers ‡ : were infected. second, our estimates of the iar would be biased upwards if infection with other circulating influenza viruses led to cross-reactive antibody responses resulting in antibody titers ‡ : . however between august and october , % of influenza a viruses detected in hong kong were pdmh n , and only % of isolated viruses were seasonal h n viruses. third, a minority of severe illnesses associated with pdmh n infection might not be identified by molecular detection methods, for example if admission occurred after viral shedding from the primary infection has ceased, in which case we may have underestimated the disease burden of pdmh n . finally, our analyses are primarily based on seroprevalence among blood donors to the hong kong red cross, who may not be representative of the whole population. we do not have detailed data on donors to compare their risk of infection with the general population, but we did observe very similar seroprevalence rates across the three groups of subjects in our study, i.e., blood donors, hospital outpatients and participants in a community cohort (data not shown). in conclusion, around ae % of the population aged - and half of all school-age children in hong kong were infected during the first wave of pandemic h n . compared to school-children aged - , older adults aged - , though less likely to acquire infection, had ae and times higher risk of icu-admission and death if infected. thus, although the iar of pdmh n is similar to that of a seasonal epidemic, the apparently low morbidity and mortality of pandemic influenza (h n ) appears to be due to low infection rates in older adults who had a much greater risk of severe illness if infected. the reasons why older adults appear relatively resistant to pdmh n infection even though they appear to lack neutralizing antibody remains unclear. if antigenic drift or other adaptation of the pdmh n virus allows these older age groups to be infected more efficiently, the morbidity and mortality of subsequent waves of the pandemic could yet become substantial. and the national institute of allergy and infectious diseases, national institutes of health (contract no. hhsn c; adb no. n -ai- ). the funding bodies had no role in study design, data collection and analysis, preparation of the manuscript, or the decision to publish. bjc reports receiving research funding from medimmune inc., a manufacturer of influenza vaccines. the authors report no other conflicts of interest. some data presented in this manuscript were previously published in wu et al. it is well known that a primary goal of vaccination is to generate immunological memory against the targeted antigen to prevent disease in a vaccinated person. this ensures an accelerated immune response in the event of future contact with the pathogenic agent, such as a virus. therefore, it is very important to develop criteria for the assessment of vaccine immunogenicity by measuring both t and b memory cell levels from the vaccinated host. in contrast to inactivated influenza vaccines, live attenuated influenza vaccines (laivs) have been shown to provide primarily cellular and local immune responses. - to date, however, the hemagglutination-inhibition (hai) test (i.e. detection of serum antibodies) remains the method widely accepted for evaluation of an influenza vaccine's immunogenicity. improved understanding of the role of cellular and mucosal immunity and their contribution to protecting against severe illness caused by influenza infection has emphasized the need to reconsider methodologies used to evaluate the immunogenic impact of various influenza vaccines. such new assays need to include methods to measure local antibodies and virus-specific lymphocytes, especially in the case of live attenuated influenza vaccines, because of their potential to induce such broad-based immune responses. the aim of this study was to assess the ability of new russian pandemic laivs a ⁄ ⁄ duck ⁄ potsdam ⁄ ⁄ (h n ) ('ultragrivak,' registered ae ae ) and a ⁄ ⁄ california ⁄ ⁄ (h n ) ('influvir,' registered ae ae ) to induce memory t-cells in naïve human subjects and to compare results to levels of hai antibodies from each subject. a ⁄ ⁄ duck ⁄ potsdam ⁄ ⁄ (h n ) laiv was generated by : genetic reassortment of low-pathogenic avian influenza virus a ⁄ duck ⁄ potsdam ⁄ - (h n ) and master donor strain a ⁄ leningrad ⁄ ⁄ ⁄ (h n ). , the vaccine strain contains ha gene from avian virus, as well as na and internal genes from the master donor virus. a ⁄ ⁄ california ⁄ ⁄ (h n ) laiv was generated by classical ( : ) reassortment of a ⁄ california ⁄ ⁄ (h n ) with the master donor virus. the vaccine strain contains ha and na genes from a 'wild-type' h n strain and internal genes from the master donor virus. participants were aged to years and were without contra-indication of laiv vaccination. immunogenicity of a ⁄ ⁄ duck ⁄ potsdam ⁄ ⁄ (h n ) laiv was assessed in ten vaccinated persons and ten volunteers inoculated with a placebo (sterile physiological saline solution). immunogenicity of a ⁄ ⁄ california ⁄ ⁄ (h n ) laiv was estimated in vaccinated volunteers and nine volunteers inoculated with placebo. viruses or placebo were administered intranasally twice with an interval period of days at a dosage of ae ml per nostril for each vaccination. physical examination, venous blood and nasal swab samples were collected at four time points during the study: (i) before vaccination (day ); (ii) days after first vaccination (day ); (iii) days after the second vaccination (day ); and (iv) weeks after the second vaccination (day ). serum hai antibodies were measured by standard hai assay using % human red blood cells. test antigens for the assay were a ⁄ ⁄ duck ⁄ potsdam ⁄ ⁄ (h n ) or a ⁄ ⁄ california ⁄ ⁄ (h n ) to match the appropriate vaccine antigen. local iga antibodies in nasal swabs were evaluated by elisa using whole purified a ⁄ ⁄ duck ⁄ potsdam ⁄ ⁄ (h n ) or a ⁄ ⁄ california ⁄ ⁄ (h n ) viruses at hau per ae ml for absorption to elisa plates. endpoint elisa titers were expressed as the highest dilution of sera that gave an optical density (od) greater than twice the mean od of six negative controls in the same assay. percentages of virus-specific cd + cd + ifn-c + and cd + cd + ifn-c + peripheral blood memory cells were determined using a flow cytometry iccs assay performed by the published method. pbmcs were prepared with standard histopaque- gradient centrifugation from heparinized whole blood. wilcoxon matched pair test, mann-whitney u test and the students t-test were used for statistical data analysis. prior to the first vaccination (day ), gmts of hai antibodies to a ⁄ ⁄ duck ⁄ potsdam ⁄ ⁄ (h n ) and a ⁄ ⁄ california ⁄ ⁄ (h n ) laivs were ⁄ ae and ⁄ ae , respectively. in addition, gmts of siga against these specific antigens from nasal swabs were ⁄ ae and ⁄ ae , respectively. no hai antibody titers greater than : were observed prior to vaccination. background levels of virusspecific t-cells varied significantly within groups. mean levels of virus-specific cd + ifnc + cells were ae % to a ⁄ ⁄ duck ⁄ potsdam ⁄ ⁄ (h n ) and ae % to a ⁄ ⁄ california ⁄ ⁄ (h n ). for cd + ifnc + cells, initial levels were ae % and ae %, respectively. thus, background levels of virus-specific antibodies were low, but prior vaccination or virus exposure in some volunteers produced some pre-existing levels of t cells, thus they were not absolutely immunologically naïve in this sense. preexistence of h n -crossreactive antibodies and t-cells has been observed previously. [ ] [ ] [ ] effect of vaccination antibody immune responses both influenza a (h n ) and influenza a (h n ) laivs stimulated production of serum hai antibodies and local iga antibodies in nasal swabs. following the first vaccination with influenza a ⁄ ⁄ duck ⁄ potsdam ⁄ ⁄ (h n ) laiv, % percent of volunteers exhibited seroconversion of hai antibodies; after the second vaccination, % of volunteers exhibited seroconversion. after the first vaccination, a % conversion rate of siga was observed; after the second vaccination, % showed conversions in levels of siga. the first vaccination with a ⁄ ⁄ california ⁄ ⁄ (h n ) laiv showed ae % of hai antibodies seroconversions vaccination, and % seroconversion after second vaccination. for local siga, those results were ae % and ae % following the first and second inoculation, respectively. figure summarizes cellular immune responses observed in the vaccinated versus the placebo group. after the influenza a (h n ) laiv inoculation, significant differences in both cd and cd ifnc-producing t-cells were observed at day after the second vaccination (d ). these data indicate that healthy young people who never received such avian influenza vaccines and were not exposed to h n wild-type viruses were able to respond to the live attenuated h n influenza vaccine. after the first influenza a (h n ) laiv vaccination, reliable increases were observed in cd + cells only. after the second vaccination, increases in both cd + and cd + fold changes were significantly higher in vaccinated volunteers compared to the placebo group. it is noteworthy that cellular immune responses (cd + and cd + cells) were more marked in the a ⁄ ⁄ california ⁄ ⁄ (h n ). considering the long-term circulation of h -subtype viruses among humans in contrast to the novelty of h viruses, such a result would be expected. similar data were also observed following vaccination with the h n laiv. after first vaccination, the percent of people with notable increases in virus-specific cd + and cd + t-cells was % and % to h n and % and % to h n , respectively. after the second vaccination, these results were % and % to h n and % and % to h n , respectively. importantly, a significant number of vaccinated volunteers without remarkable increases ( ‡ -fold) in hai antibodies had notable increases in cd + and ⁄ or cd + memory cells. the percent of people with notable increases in virus-specific t cells after the second vaccination among hai()) volunteers was % and % to h n and h n , respectively. these results indicate that laivs were able to induce broadly responsive, key antiviral immune responses that would not have been detected by the hai assay alone. thus, it can be deduced that hai data alone fails to reveal important broad and specific immune responses to laiv. consequently, the hai test alone is not suitable for assessment of laiv immunogenicity. furthermore, vaccination with h n laiv was able to induce cross-reactive memory t-cells to a seasonal vaccine strain, a ⁄ ⁄ solomon islands ⁄ ⁄ (h n ) ( table ) . reliable increases to a (h n ) were observed in up to % of volunteers. there was an inverse dependence between levels of memory t cells before and after vaccination. authors are thankful to path for the financial support of these studies. we are also thankful to jessica d'amico and dr. rick bright for their editorial review. options for the control of influenza vii background: increased susceptibility of older populations to secondary bacterial pneumonia-like infections following influenza infection has been well documented. recent evidence in mouse models suggests that this increased risk from secondary bacterial infection occurs through a desensitization of the innate immune response. this recent finding, however, does not account for potential differences in immune responsiveness due to age. materials and methods: to address this parameter, we used three age groups (aged, adult, and young mice) to evaluate the role of age in influenza-mediated vulnerability to secondary bacterial challenge with pseudomonas aeruginosa. all mice were evaluated for multiple parameters including: (i) survival; (ii) lung bacterial load; (iii) total lung protein content; (iv) immune cell infiltration; (v) cytokine ⁄ chemokine expression; and (vi) toll-like receptor (tlr) rna expression profiles. results: prior challenge with influenza contributed to aberrant cytokine ⁄ chemokine profiles and increased lung cellular infiltrate in response to secondary bacterial infection across all age groups, supporting a critical role for influenza infection in the alteration of immune responses to other pathogens. also similar to human influenza, these changes were exacerbated by age in mice as demonstrated by increased bacterial load, mortality, and total lung protein content (an indicator of lung damage) after p. aeruginosa challenge. conclusions: these data support a potential role for virus-mediated and age-mediated alteration of innate immune effectors in the pathogenesis of influenza and the increased susceptibility of influenza virus infected mice to secondary bacterial infection. the understanding of the complex interaction of host and pathogen -and the role of age -in human influenza is critical in the development of novel therapeutics and improved vaccine approaches for influenza. our results support further examination of influenza-mediated alterations in innate immune responses in aged and non-aged animals to allow elucidation of the molecular mechanisms of influenza pathogenesis in humans. there is considerable evidence in the clinical literature to support the role of influenza infections with an enhanced risk for secondary bacterial pneumonias. [ ] [ ] [ ] given the increased pneumonia-related morbidity and mortality in both the young and elderly populations, there is rationale for gaining a deeper understanding as to the systemic changes in the pulmonary microenvironment. although there are some recent reports that account for some of the molecular mechanisms at work in this disease process, there is a paucity of experimental evidence that considers the potential effects of age. developmental changes in the immune system that occur in the aged environment have been well documented with regard to senescence of the adaptive immunity, global changes in myeloid cell function, and the establishment of a general pro-inflammatory state. , the aim of this work was to provide evidence for the contribution of the aged immune environment to the pathology of influenza mediated secondary bacterial infections. animals used in this study were housed under conditions approved by tulane university's institutional animal use and care committee. female balb ⁄ c mice used in these studies were divided into three age groups: aged ( months old), adult ( months old), and young ( months old). each age group was subdivided into two groups: influenza infected and naïve (control). mice were infected by the intranasal route with · pfu of mouse-adapted influenza a ⁄ pr ⁄ ⁄ . clinical disease was measured by body weight changes over a week period post influenza challenge, and recovery was determined as return to pre-infection weight. all mice were subsequently challenged intransally with · cfu pseudomonas aeruginosa strain pao . twenty-four hours post-pseudomonas challenge, bal with sterile pbs was performed on all mice in all groups. total rna from the cellular fraction was pooled from three experimental animals from each group. tlr mrna was detected by qrt-pcr, where expression levels were determined as relative to b-actin mrna levels. cdna was synthesized from total cellular rna from bal samples using iscript cdna synthesis kit (biorad). pcr reactions were composed of ae lg cdna forward and reverse primers according to optimized conditions and ae ll of · syber green icycler supermix (biorad), in a total vol-ume of ll and were run using a biorad icycler utilizing melting point determination. primers and concentrations used in this study included: mus_tlr f: tgctttcct-gctggagattt- nm, mus_tlr r: tgtaacgcaac agcttcagg- nm, mus_tlr f: atatgcgcttcaa tccgttc- nm, mus_tlr r: caggagcatactggt gctga- nm, mus_tlr f: ggcagcaggtggaattg tat- nm, mus_tlr r: aggccccagagttttgttc t- nm, mus_tlr f: ctggggacccagtatgctaa- nm, mus_tlr r: acagccgaagttccaagaga- nm, mus_tlr f: ggagctctgtccttgagtgg- nm, mus_tlr r: caaggcatgtcctaggtggt- nm, mus_ b-actinf: agccatgtacgtagccatcc- nm, mus_b-actinr: ctctcagctgtggtggtgaa- nm. as a measure of protein leakage into the alveolar space, total protein content in each bal was measured by bca assay of each supernatant fraction according to manufacturer's instructions (pierce). cytokine and chemokines levels were measured by multiplexed bead array (bioplex, biorad). immune cell characterization of bal was estimated by flow cytometry. lymphocyte populations were gated by forward versus side scatter and characterized as b cells (f ⁄ ) , cd + ) or t cells (cd b ) , cd + ). the myeloid population that is composed of macrophages, neutrophils, dendritic cells, and natural killer cells was enumerated by gating all but those found in the lymphocyte gate using forward versus side scatter plots. flow cytometry data was analyzed using flojo software (treestar). statistical analysis, where appropriate, was performed using a two-way analysis of variance (age versus influenza infection status) supported by bonferonni's correction for multiple comparisons. a recent finding by didierlaurent, et al., described an influenza mediated desensitization of tlr function as a primary contributor to an increase in bacterial burden when challenged after resolution of the primary influenza infection. this finding, however, was obtained using animals that were - weeks of age, where our study included two cohorts of older mice ( months and months). using whole protein content of the bal as an estimate of protein leakage into the lumen of the lung, we found elevated protein content in aged mice as compared to young and adult mice. in aged mice, a slightly lower total lung protein when comparing influenza infected to protein in the bal from influenza naïve mice challenged with p. aeruginosa (table ) . supporting previously published studies showing a generalized pro-inflammatory cytokine environment in the aged immune system, we provide evidence for significantly (p = ae ) and an increase in ifnc (p = ae ) was detected. the decrease in gm-csf correlates well with a previous report that gm-csf is less prevalent in influenza resolved animals (table ). we also report a noticeable change in the immune cell populations with respect to b-cells, cd + t-cells, and the myeloid cell populations. there is a trend of increased prevalence in cd t-cells in the post-influenza environment across all ages. b-cell numbers also trend toward increase in influenza treated animals in young and adult animals; however, there is a noticeable decrease in the bcells in aged animals. across all age groups, there is a general decrease in frequency of cells that would normally make up the myeloid cellular fraction of the bal (macrophages, neutrophils, dendritic cells, and natural killer cells) ( table ). our study also shows, as cited by others, that toll-like receptor (tlr) gene expression in the post-influenza environment is decreased in cells found in the bal after both influenza and pseudomonas infection. our data support the previous finding of a reduced expression of tlr mrna in influenza-cleared mice when we measured tlr , , , and . only tlr showed differences with respect to age with young mice showing little or no detectable change in tlr mrna expression. our results show an increase in the expression across all tlrs examined in the aged mice group (table ) irrespective of influenza infection status. these data support earlier studies performed with adult mice that showed reduced tlr mrna expression in the post-influenza environment. this study also expands the current understanding of the potential role of age in influenza mediated bacterial infection-induced mortality. the impact of these alterations in the immune microenvironment across age groups and infection status is highlighted by the ability of bacterially challenged animals to clear infection. assessment of bacterial load in the lungs of p. aeruginosa challenged mice indicated a difference in young and adult mice if previously infected with influenza virus. in aged mice, both influenza challenged and influenza-naïve mice had higher bacterial loads and less variability when comparing within the age group, supporting the risk of age alone in susceptibility to bacterial pneumonia (table , figure ). taken together, these data support the potential role for both virus-mediated and age-mediated alteration of innate immune effectors in the pathogenesis of influenza and increased the susceptibility to secondary bacterial infection that results from influenza infection in mice. these findings highlight distinct differences in the immune environment between age groups and thus reveal necessity for further examination as to the mechanisms of immunity across age with respect to current infection status. garnering a clearer understanding as to the complex interaction of host and pathogen with respect to age in influenza infections is central to the development of increased efficacy in vaccine and therapeutic strategies. prospective estimation of the effective reproduction background pandemic influenza a (h n ) virus (ph n ) emerged in early and rapidly spread to every continent. an urgent priority for international and national public health authorities was to estimate the transmissibility of the pandemic strain for situational awareness and to permit calibration of mitigation strategies. the basic reproductive number, r , is defined as the average number of secondary cases that index case generates in a completely susceptible population, and is a common measure of transmissibility. however, it is difficult to estimate r without an understanding of the degree of any pre-existing immunity in the population. the effective reproductive number, r, is defined as the average number of secondary cases that index case generates, and can be estimated over time (i.e. r t ). wallinga and teunis described a method to estimate r t based on illness onset dates of the cases while assuming that all secondary cases would have been detected, and cauchemez et al. extended the method to permit prospective estimation by adjusting for secondary cases that have not yet experienced illness onset at the time of analysis. we describe how the method can further be extended to account for reporting delays, allowing true real-time estimation of r t during an epidemic, and we illustrate the methodology on notifications of ph n and associated hospitalizations in hong kong. we obtained data on all laboratory-confirmed ph n infections ('cases') reported between may and november , to the hospital authority and center for health protection in hong kong collated in the eflu database. a subset of the cases was hospitalised. the database also included information on age, sex, illness onset date, laboratory confirmation date, and contact history (for the early cases). laboratory-confirmed ph n infection was a notifiable condition throughout our study period. we extended existing methods for estimating r t over time to allow for reporting delays between illness onset and notification, and between illness onset, notification, and hospitalisation for those cases that were hospitalised, where the reporting delay distribution were estimated empirically from the data. we further extended the methodology to allow for imported cases (infected outside hong kong) contributing to the estimation of r t as infectors but not infectees. we used multiple imputation to allow for missing data on some symptom onset dates to make best use of all available data. we used a serial interval with mean (standard deviation) of ae ( ae ) days, and in sensitivity analyses, we used serial intervals with mean ae days and ae days. statistical analyses were performed in r version . . (r development core team, vienna, austria). in late april following the who global alert, hong kong initiated containment protocols to attempt to delay local transmission of ph n for as long as possible. these measures included screening at ports, airports, and border crossings, and enhanced surveillance for people with influenza-like illness, particularly for those who had recently returned from abroad. laboratory testing capacity was substantial due to heavy investment in local infrastructure following previous experiences with avian influenza a ⁄ h n in and severe acute respiratory syndrome in . laboratory-confirmed ph n cases were isolated until recovery, and their close contacts were placed under quarantine for days. imported cases were identified sporadically through may and early june . the first case of ph n not traceable to importation (i.e. a local case) was identified on june and triggered a change to mitigation phase measures. some containment measures, including isolation of cases, were continued until the end of june to allow a soft transition between containment and mitigation phases. as an immediate measure to try to reduce community transmission of ph n , all childcare centres, kindergartens, and primary schools were proactively closed for days (subsequently extended for another - days to summer vacation in early july). any secondary schools in which one or more confirmed ph n case was identified were reactively closed for days. on june the government opened eight designated flu clinics across the territory to provide free medical consultation for outpatients with influenza-like illness and free laboratory testing for ph n . these clinics resumed regular chronic disease services in mid-august, and laboratory testing and antiviral treatment was restricted to high risk groups in september. the various interventions are highlighted in figure (a), superimposed on the epidemic curve of laboratory-confirmed ph n cases and ph n -associated hospitalizations. around % of the cases were hospitalised, and this proportion increased somewhat towards the end of the epidemic. figure (b) shows the estimates of r t based on laboratory-confirmed ph n cases. the estimated r t peaked at ae on june , and fell below between june and july (which was within the school closure period). r t fluctuated between ae and ae through the school summer vacations in july and august, it subsequently increased to around ae - ae after schools reopened in september until the epidemic peaked in late september, and then fluctuated below as the epidemic declined. the trends in r t based on h n -associated hospitalizations were similar, although with wider confidence intervals due to the smaller number of events ( figure c ). the extension of the methods to allow for reporting delays avoided substantial bias in realtime estimates of r during the epidemic for the most recent days, and closely tracked the final estimates of r t . our results suggest that ph n may have had slightly lower transmissibility in hong kong than elsewhere. for example, estimates of r t were around ae - ae in new zealand and australia. lower transmissibility in hong kong has been associated with school closures in june and july followed by summer vacations from july through august. furthermore, in hong kong the influenza virus usually does not circulate after august, and therefore seasonality could also be a cause for the lower r t . on the other hand, the interventions applied during the mitigation phase, such as the widespread use of antiviral treatment in hong kong and the pre-existing immunity in the ageing population in hong kong, may also be associated with lower transmissibility. there are some limitations to our work. first, we only used aggregated data, and we did not consider the heterogeneity among the cases in terms of sex and age or other factors. therefore our estimates can only provide a snapshot of the overall trend, but limited information for any specific subset of population. secondly, we did not consider the possibility that cases might be infected in hong kong and exported to other countries, which could lead to slight underestimation of the transmissibility. one has to be careful in translating the estimated r t to the effectiveness of any specific interventions, as interventions may not be the only factor influencing the transmissibility; for example, a depletion of the susceptible population during an epidemic can also be a factor for the decline in r t . in conclusion, real-time monitoring of the effective reproduction number is feasible and can provide useful information to public health authorities for situational awareness and planning. in affected regions, laboratory capacity was typically focused on more severe cases, and changes in laboratory testing and notification rates meant that that case counts may not necessarily reflect the underlying epidemic. a useful alternative to case-based surveillance is surveillance of the subset of severe infections, for example hospital admissions, or icu admissions, and our results show that it was feasible to monitor ph n -associated admissions in real-time to estimate transmissibility. influenza antigenic cartography projects influenza antigens into a two or three dimensional map based on immunological datasets, such as hemagglutination inhibition and microneutralization assays. a robust antigenic cartography can facilitate influenza vaccine strain selection since the antigenic map can simplify data interpretation through intuitive antigenic map. however, antigenic cartography construction is not trivial due to the challenging features embedded in the immunological data, such as data incom-pleteness, high noises, and low reactors. to overcome these challenges, we developed a computational method, temporal matrix completion-multidimensional scaling (mc-mds), by adapting the low rank mc concept from the movie recommendation system in netflix and the mds method from geographic cartography construction. the application on h n and pandemic h n influenza a viruses demonstrates that temporal mc-mds is effective and efficient in constructing influenza antigenic cartography. the web sever is available at http://sysbio.cvm. msstate.edu/antigenmap. as a segmented, negative stranded rna virus, influenza virus is notorious for rapid mutations and reassortments. the mutations on the surface glycoproteins (ha and na) of influenza viruses are called antigenic drifts, and these antigenic drift events allow the virus to evade the accumulating immunity from previous infection or vaccination and lead to seasonal influenza epidemics. a reassortment event with a novel influenza antigen may result in antigenic shift and cause influenza pandemic. for instance, the h n pandemic virus is a reassortant with a swine origin ha antigen. vaccination is the primary option for reducing the effect of influenza, and identification of the right vaccine strains is the key to development of an effective vaccination program. the antigenicity of an optimal vaccine strain should match that of the epidemic strain. in influenza surveillance program, the influenza antigenic variants are generally identified by the immunological tests, such as hemagglutination inhibition (hi) assay, microneutralization (mn) assay, or elisa. these immunological assays measure the antigenic diversity between influenza viruses by comparing the reaction titers among the test antigens and reference antisera. however, data interpretation of the data from these assays is not trivial due to the embedded challenges such as data incompleteness, high noises, and low reactors. by mimicking geographic cartography, influenza antigenic cartography projects influenza antigens into a two or three dimensional map using immunological datasets. antigenic cartography can simplify the data interpretation, and thus, facilitate influenza antigenic variant identification. recently, we developed a novel computational method, temporal matrix completion-multidimensional scaling (mc-mds), in antigenic cartography construction. in this paper, we described the details of temporal mc-mds, especially the original concepts introduced in this method, and how they can achieve the robustness in antigenic cartography construction. our method included two integrative steps: it first reconstructs the hi matrices using low rank mc method, and then generates antigenic cartography using mds with a temporal regularization. the mc concept was adapted from the movie recommendation system in netflix and the cartography concept from geographic cartography. in , netflix, an online dvd and blu-ray disc rentalby-mail and video streaming company, held a -year netflix prize contest (http://www.netflixprize.com/) on computational methods for improving its recommendation system. in its recommendation system, netflix collected the rating data from the individuals. based on his or her renting history and the ratings in the systems (e.g., from evaluators and other renters), netflix recommendation system suggests certain movies to a renter. apparently, no individuals would be feasible to provide ratings for all of the movies, as it will take hundreds of years for a single person to rate over movies available from netflix. thus, the resulting rating data is an incomplete matrix, and it can be as sparse as less as %. the challenge in netflix recommendation system is a classic mc problem. [ ] [ ] [ ] [ ] [ ] as the inspiration of netflix prize contest, many efficient low rank mc algorithms were developed, for instance, opt-space, svt, cf, bellkor, pf, and fwls. eventually, the team bellkor's pragmatic chaos won this contest. their methods combines nonlinear probe blending and linear quiz blending to come up with a predictor bigchaos. matrix completion estimates the unobserved values based on the observed values. the users can refill the missing data without repeating the experiments. furthermore, mc will help reduce the noises in the data, for instance, those biases by different individuals performing experiments. in influenza antigenic characterization, hi assay is a commonly used assay for antigenic analysis, since hi assay is relatively economic and easy to perform. however, hi is labor intensive, and it is almost impossible for any individual lab to complete the hi assays for all pairs of antigens and antisera during influenza surveillance. in addition, both testing antigens and the reference antisera are dynamic. for instance, in seasonal influenza surveillance, generally only contemporary antisera are used in experiments. thus, we will have to integrate multiple hi tables in order to evaluate the overall antigenic changes for influenza vaccine strain selection. the resulting hi tables will be incomplete, and the observed entries in the integrated hi data can be as less as %. the completion of this matrix can be formulated as a typical mc. briefly, given the combination of hi matrix with m antigens and n antisera, the hi matrix can be represented as m m·n = (m ij ) m·n , where m ij denotes the hi values from the reaction between testing antigen i and antiserum j. the low rank mc assumes that both antigen and antiserum can be embedded into a low rank space. to be specific, the low rank mc method is to seek matrix u m·r , v n·r and a diagonal matrix r r·r , where m = u m·r r r·r (v n·r ) t . in order to achieve this goal, the optimization formulation has been employed, which can be represent as following, where e denotes the observed entries in hi matrix and g(x) is a regularization function. the eqn ( ) is the standard format of a low rank mc formulation. the geographic cartography is a common technique to display the cities and their geographic distances in a map. this cartography can be generated using mds based on a geographic distance matrix. figure (a) shows the antigenic cartography generated using a distance matrix with seven cities, and figure (b) is a map for comparison. as an analog of geographic cartography, the influenza antigenic cartography maps the influenza antigens into a two or three dimensional map based on the distance matrix generated using immunological data. this incomplete matrix can be filled through mc algorithm discussed in section mc and netflix. low reactors, non-random date incompleteness, and temporal model generally, three types of data are present in a combined hi matrix: high reactor, low reactor, and missing values. among these three data types, high reactors are the most reliable data points. the low reactors are those values present in the hi matrix as ''equal to or less than a threshold h'', where h can be , , , or . low reactors have similar values in the affinity dataset but could be from different binding settings. these low reactors are present due to the detection limits of biotechnology, and they are not reliable. both these missing values and low reactors make it very difficult to analyze and interpret antigenic correlations amongst tested antigens and reference antigens. to our best knowledge, none of the existing mc method can handle the threshold values. in addition, the non-random incompleteness of influenza immunological datasets generates an additional challenge in traditional mc methods, which are based on the assumption that the observed values are randomly distributed among the matrix. in a typical combined antigenic hi data, most of the off-diagonal entries are missing values or low reactor values. in order to overcome the above issues, we incorporated a regularization function into the eqn ( ), where this indicator function is only valid for those entries with low reactor values. an alternating gradient decent method is applied to solve the optimization problem in eqn ( ) . in addition, a temporal mds method is proposed to project the antigens into a or dimensional map. x where d ij is the average distance between virus i and virus j, t i is the isolation year of virus i, d ij is the distance between virus i and virus j in cartography, d ac i is the distance between virus a and center of group i, and d c i c j is the distance between the centers of group i and group j. all the parameters are tuned by cross validation. we named this method as temporal mc-mds. by applying temporal mc-mds method in an h n dataset, low reactors. figure (a) is a three-dimensional influenza antigenic map based on this data by using mc-mds method. the reported clusters (hk , en , vi , tx , bk , si , be , be , wu , sy , and fu ) were displayed in the core of a spiral s-shape, and bk and be are located at the turning point of this s-shape. however, the antigenic distances between some viruses are incorrect. for example, the distance between hk and fu in the projection is ae units, which is close to the distance between hk and bk ( ae units). the main reason leading to those inaccurate distances is the unique distribution of hi datasets described in section . . in comparison, with the temporal model, not only the viruses in clusters have been clearly separated, but also the antigenic distances between each cluster are proportional to their isolation time interval. in this updated cartography ( figure b ), the antigenic distance between hk and fu is ae units, where the distance between hk and fu is ae units. this result suggested that the temporal information is critical for antigenic cartography construction for immunological datasets spanning a long time period. the hi data from seasonal influenza surveillance belong to this category. for seasonal influenza virus ⁄ pandemic influenza viruses within a short time span, the temporal model is probably not necessary, as there is lack of long-term immunological pressure present in the population. figure (c) is an antigenic cartography generated using a hi dataset with h n influenza viruses spanning from april of to june of . this map demonstrates that there is lack of antigenic drifts during the first wave of this pandemic influenza as all of these viruses are mixed altogether. our limited studies on h and h avian influenza viruses suggested the temporal model is not needed for avian influenza viruses. however, extensive studies are required to investigate whether there is any special data structure present in this type of data. in this study, we described in details the concepts and applications of new computational method, temporal mc-mds for influenza antigenic cartography construction. we formulate the influenza cartography as two integrative steps: low rank mc problem from the concept of netflix movie recommendation system and mds from geographic cartography construction. in order to handle two additional challenges, including low reactor and non random distribution of antigenic data, a temporal model is incorporated into mc-mds as temporal mc-mds. our applications demonstrated that temporal mc-mds is effective in constructing influenza antigenic cartography. the three dimensional antigenic cartography for a ⁄ h n seasonal influenza virus without temporal model, and the antigenic clusters were defined in ref. [ ] ; (b) the three dimensional antigenic cartography for a ⁄ h n seasonal influenza virus with temporal model; (c) the two dimensional antigenic cartography for a ⁄ h n pandemic influenza without temporal model, and these viruses were labeled in shape by the corresponding month for them to be detected. one grid is corresponding to a twofold change in hemagglutination inhibition experiment. the mechanisms driving the three waves of infection and mortality in the uk in - are uncertain. although the circulation of three distinct viruses could have generated three waves of infection, the virological evidence required to prove or disprove this hypothesis is lacking. social distancing, an alternate mechanism for generating fluctuations in the effective susceptible pool and therefore explaining multiple waves of infection, , was not generally imposed in the uk as it was in the us and australia. we are therefore motivated to explore the possible role of continual population-level changes in the average protective response against the circulating virus in generating a multi-wave pandemic, within a biologically motivated deterministic model for influenza transmission. the nature and duration of protection against further infection following recovery from influenza is uncertain and depends on the mode and tempo of viral evolution, as well as the response of the cellular and humoral arms of the adaptive immune system. for a given seasonal ⁄ pandemic strain, memory b-cells may generate a specific antibody response in a portion of the adult ⁄ elderly population, depending on the exposure to related antigenic sub-types. however neutralising antibodies are unlikely to be a widespread immunological response to a novel (pandemic) strain. memory t-cells which recognise conserved internal viral proteins may be a more common mechanism for protection; the generation of very high levels of cytotoxic cd + t-cells potentially facilitates rapid viral clearance, , and lower levels of cd + t-cells perhaps provide partial protection. in this work we explore key drivers of multi-wave pandemics within phenomenological models that incorporate different immune response mechanisms building on existing models , incorporating the role of evolving population-level protection in multi-wave pandemics. we use weekly reports of influenza mortality rates for five administrative units in the uk (blackburn, leicester, newcastle, manchester and wigan) where records from block censuses instigated by local medical officers to record the cumulative incidence of reported symptoms in each wave in a sample of or more households are also available. the symptom reporting data allows us to estimate the case fatality rate and thus use the mortality time series to constrain our transmission model. furthermore, the incidence of individuals reporting symptoms in multiple waves provides information about the acquisition and loss of immunity. we extract the death rate and symptomatic (re)infection rates predicted by our model prevalence for a given set of parameters and estimate a likelihood-based on a comparison to all the death and cumulative reported incidence data assuming a negative binomial error distribution. we utilise monte carlo markov chain (mcmc) methods with parallel tempering algorithms to maximise this likelihood and obtain parameter estimates. parallel tempering -which concurrently searches for maximal likelihood parameter solutions on a set of scaled likelihood surfaces -allows for relatively rapid exploration of the parameter space. we use bayesian information criteria (combined with qualitative assessment of biological plausibility) to aid model selection. we have implemented a deterministic compartmental transmission model, which allows for a variety of phenomenological modes of protection against the pandemic virus. to facilitate this, we stratify the population into two groups; the 'experienced' population (stratum ) who have had been exposed to an influenza virus and the 'naive' population (stratum ) who have not. in each stratum, i hosts may be classified as either susceptible s i , exposed e i and e i , having (recovered from) a symptomatic i i (r i ), or asymptomatic a i (ra i ) infection. note that the states tq i , tq i , e i , t i , and t i are included so that the hosts move between the key epidemiological states with a peaked (rather than exponential) distribution of waiting times. hosts in the experienced stratum may exhibit reduced susceptibility, infectiousness, and symptomatic proportion compared to naive hosts, parameterised by e i , e s , and e a , respectively; however note that depending on the model parameters, there may be fully susceptible hosts within the experienced stratum. in addition, we assume homogeneous population mixing and a constant basic reproduction number r with the force of infection: modulated by a sinusoidal seasonal term with amplitude b with phase chosen to maximise transmission in the winter season. here n is the total population size, and x e is the initial fraction in the experienced strata. the proportion of symptomatic cases a and the case fatality rate l are permitted to vary from wave to wave (and given indices , or accordingly). the transmission dynamics is described by the following set of coupled ordinary differential equations. where s in, = p utq i and s in, = in order to divert recovered infectious hosts from the naive stratum into the experienced stratum. the probabilities of gaining permanent protection are q = q and q = . the latent exposed period is fixed to be c = ⁄ ae days, and the rate of recovery is parameterised by m = ⁄ t inf , where t inf is the infectious period. hosts with prior sterilising protection begin in q and move into s at rate u q = ⁄ t wq . recovered hosts (r i ) migrate back to s at a rate u = ⁄ t w . the state p contains hosts with permanent protection. the modes of protection captured in this model are: i. permanent prior protection (beginning in state p ), ii. waning prior protection (beginning in state q ), iii. permanent acquired protection with probability q (moving into state p ), iv. waning acquired protection with probability ) q, and, v. partial prior protection (beginning in state s ) resulting in reduced infectiousness (e i ), susceptibility (e s ), and symptomatic proportion (e a ). in the context of this model, 'permanent' protection refers to protection which lasts for the duration of the epidemic. here we explore the results of parameter fitting to two models which differ in the nature of the assumed pre-existing protection in the community at the beginning of the pandemic. protection hypothesis assumes that the prior protection is sterilising but temporary, whilst protection hypothesis assumes that the prior protection is partial but permanent and may act on susceptibility, infectiousness, and ⁄ or asymptomatic proportion. each model allows waning acquired protection and for a proportion q of the experienced population to gain permanent protection following infection. fitted parameters common to each model are t inf , b , q, t w , a, l and the proportion beginning in p x i . prior protection hypothesis : sterilising, waning prior protection we fix x e = and fit for q (t = ) ⁄ n and t wq so that protective modes i, ii, iii, and iv are enabled ( figure ). it is important to note that due to the slow convergence of the mcmc chains, we cannot guarantee that our parameter estimates correspond to the global minimum. furthermore, parameter estimates can only be meaningfully interpreted for good fits to the data. due to the prediction of a fourth (unobserved) wave for the model fit to blackburn, we do not report these parameter estimates here. the fits to the leicester data are generated with the parameter set r = ae , a = ae , a = ae , a = ae , t w = ae years, t wq = ae years, we fix q (t = ) ⁄ n = and fit for x e , e a , e i , and e s so that protective modes i, iii, iv, and v are enabled (figure ) . the parameters corresponding to the fit in figure for leicester are r = ae , a = ae , a = ae , a = ae , t w = ae years, p (t = ) ⁄ n = ae , s (t = ) ⁄ n = ae , b = ae , t inf = ae days, q = ae , e a = ae , e i = ae , and e s = ae . our model with protection hypothesis -which, similarly to the model discussed in ref. [ ] , assumes that a sub-population has waning sterilising prior protection -is able to generate multiple waves of infection via the continual replenishment of s from an initially large proportion (over %) of hosts with prior protection in q combined with the waning of acquired immunity in around % of cases on a time-scale of months. disease severity as measured by symptomatic proportion increases from % in the first wave to above % for the second and third waves. over a quarter of the population are initially permanently immune, and a large r value of ae drives transmission in the remaining population. protection hypothesis -which assumes that prior protection offers partial susceptibility and ⁄ or reduced infectiousness or symptomatic disease -performs slightly more poorly; the fit to the leicester data has an inferior likelihood (although the mortality data only likelihood is a little larger), despite the higher dimensionality of the model. nevertheless, the model fit still mirrors many characteristics of the data, particularly for leicester. we note that for this model, a is very near the lower limit, corresponding to ubiquitous exposure in the first wave. in this scenario, refuelling of the susceptible pool to generate secondary and tertiary waves is still possible due to a shorter waning time of acquired protection (well within months) and a lower probability of gaining permanent protection following infection, when compared with the parameter estimate for hypothesis . the parameter estimates suggest that approximately % of the population initially experiences reduced disease severity (e a $ ae ), but similar susceptibility and infectiousness. a larger value for r $ ae is required to drive transmission despite low numbers beginning in p , due to the large number of hosts who acquire temporary or permanent immunity early on in the pandemic. it is clear that, at least mathematically and perhaps biologically, there are multiple possibilities for the structure of population-level protection which are compatible with the generation of multiple pandemic waves. however, whilst the models considered here are able to explain the observed mortality and reinfection data for some patterns of infection and mortality (e.g. leicester), they are not consistently able to reproduce a pandemic which dies out after three waves across the connected populations we are studying (e.g. for blackburn). it is challenging to construct a deterministic model for the spread of disease within multiple locations in the uk in , which assumes homogeneous mixing without modulation of the transmission rate by social distancing. an improved model working with these assumptions likely requires a richer structure for the host protection response than the structures we have explored thus far. we are currently seeking improved fits to the data by implementing a number of biologically defensible exten-sions to our model, including incremental immunity whereby t w increases by a factor v after each exposure to the pandemic flu, and incremental loss of prior protection whereby a increases as hosts lose their sterilising prior protection. it is important to note that the mechanism(s) generating differences in the pandemic experience recorded in geographically connected locations is an open question; true differences in demography, varying degrees of reactive social distancing, inhomogeneities in the circulation (or circulation history, i.e. prior immunity) of viral strains, stochastic variations, and ⁄ or unique socio-cultural ⁄ behavioural conditions may all contribute to this effect. the h n experience in australia and elsewhere highlighted the difficulties faced by public health authorities in diagnosing infections and delivering antiviral agents (e.g. oseltamivir) as treatment for cases and prophylaxis for contacts in a timely manner. consequently, forecasts from mathematical models of the possible benefits of widespread antiviral interventions were largely unmet. we summarise results from a recently developed model that includes realworld constraints, such as finite diagnostic and antiviral distribution capacities. we find that use of antiviral agents might be capable of containing or substantially mitigating an epidemic in only a small proportion of epidemic scenarios given australia's existing public health capacities. we then introduce a statistical model that, based on just three characteristics of a hypothetical outbreak [(i) the basic reproduction number, (ii) the reduction in infectiousness of cases governments and public health agencies worldwide, spurred by outbreaks of sars and h n , have developed preparedness strategies to mitigate the impact of emerging infectious diseases, including pandemic influenza. pandemic response plans are presently being revised in light of the h n experience. [ ] [ ] [ ] many developed countries amassed large stockpiles of neuraminidase inhibitors (nais) with the expectation that they could be used to not only treat the most severely ill, but curb transmission in the community. without relevant field experience indicating how nais should be distributed, mathematical and computational modelling has been used to inform optimal deployment policy in a pandemic scenario. - models of population transmission were used to infer likely effects on epidemic dynamics, using data from human and animal studies of experimental infection and nai efficacy trials. in the australian (and wider) context, models indicated the potential for substantial benefit at the population level if nais were distributed in a liberal manner, targeting close contacts of indentified cases. furthermore, results indicated that use of limited nai resources in this way may improve the impact of case treatment due to the effects on epidemic dynamics. however, these models did not take into account logistic and other real-world constraints, such as finite diagnostic and antiviral distribution capacities, which were identified as limiting factors during the australian h n pandemic response. [ ] [ ] [ ] in particular, if using positive pcr diagnosis as a 'decision to treat' test, delays to confirmation of diagnosis, particularly once total laboratory capacity was exceeded, prevented timely delivery of nais to both cases and contacts of cases. in previous work, we have extended our existing models to examine how diagnostic strategies [e.g. using pcr confirmation versus syndromic influenza-like illness (ili) presentation as a decision to treat], diagnostic-capacity, and nai distribution capacity each impact on the ability to deliver an effective intervention. the model uses case severity (the proportion of infections deemed severe) to determine the overall presentation proportion, and so the ability to identify individuals eligible for nai treatment and contact prophylaxis. figure (a) shows a key result from the model. for each curve shown, we simulated thousands of epidemics, sam-pling across plausible ranges of parameters describing virus, population, and intervention characteristics using a latin hypercube sampling (lhs) approach. without intervention, the proportion of the population infected either symptomatically or subclinically by the end of the epidemic is around %. if a syndromic strategy (ili presentation) is used to determine provision of nais as treatment and prophylaxis, excessive distribution of drug to individuals who are not infected with influenza occurs early in the epidemic. early stockpile expiry accounts for a marginal impact of the antiviral intervention on the final outbreak size, in the order of a few percent. the second strategy modelled (pcr ⁄ syndromic) is one where pcr confirmation of diagnosis is required early in the epidemic to make treatment decisions until such time as laboratory capacity is exceeded. from this point, individuals are treated on the basis of symptoms alone -during an epidemic phase in which a substantial proportion of ili presentations will be attributable to influenza. under this strategy, the intervention is able to control the outbreak in approximately % of the simulated epidemics given the 'base case' constraints on diagnosis and delivery assumed in the model. the results highlight that a successful antiviral intervention requires a highly sensitive diagnostic strategy in the initial stages of the epidemic and comprehensive distribution of post-exposure prophylaxis. a pcr ⁄ syndromic strategy for decision to treat and provide contacts with prophylaxis is thus optimal. the surface in figure (b) shows the percentage of simulation runs for the pcr ⁄ syndromic strategy that have a final population attack rate of < % (a substantial reduction from the no intervention case of approximately %) as a function of pcr capacity and nai daily distribution capacity. as indicated by the arrow, the estimated australian pcr laboratory capacity appears to be sufficient, while significant benefits for the public health outcome may be achieved if logistical delivery constraints for nai distribution can be ameliorated. however, the probability that such an interventioneven with substantial increases in pcr and nai distribution capacity -would successfully mitigate an epidemic is low ( - %), and consequently it is difficult to universally recommend an antiviral intervention. in this study, we introduce a statistical model that predicts whether or not an nai distribution strategy based on a pcr ⁄ syndromic antiviral distribution policy will be successful in mitigating an epidemic. we thereby provide proof-of-principle for the design of a decision support tool that may be used by public health policy makers during an epidemic when faced with formulation of context specific nai distribution policy. synthetic data of hypothetical outbreaks and interventions were generated using the lhs simulations developed in ref. [ ] . we selected a random sample of outbreaks from a total of simulated epidemics ( % of model simulations). using these data, we identified independent model parameters that were most highly rank-correlated with the final attack rate. these parameters were included in a logistic regression model to assess their ability to predict whether an influenza epidemic would be successfully mitigated by an antiviral intervention (ar < %). model predictions were then validated against the full simulated dataset. full details of the simulation model, its structure, parameterisation and parameter distributions are available in ref. [ ] . use of the lhs simulation approach, and the method of model analysis and evaluation was similar to that previously described. matlab a (mathworks, natick, ma, usa) was used for the analysis and statistical model fitting. table shows results from our logistic regression model. key parameters sufficient to predict whether or not an outbreak may be controlled by the deployment of av agents are: . r , the basic reproductive number of the outbreak (assigned values between ae and ae for this example). as the value of r increases, the epidemic progresses more rapidly and is more difficult to control, explaining the negative correlation coefficient. . e t , the relative infectiousness of treated individuals (assigned values between ae and ae ). higher values for this parameter indicate only modest drug effects on transmission, explaining the negative correlation coefficient. . g, the proportion of infections that are severe (assigned values between ae and ae ), and which in turn determines the presenting proportion (derived values between ae and ae ). as the presenting proportion increases, the ability to identify and treat cases and deliver prophylaxis to contacts also rises, increasing the impact of the antiviral intervention. the roc curve ( -specificity versus sensitivity, not shown) for the logistic regression model specified in table has an area under the curve of ae , demonstrating that the model predicts the success of an antiviral intervention extremely well. for example, with a sensitivity of % we still have a specificity of approximately %. evaluation of the pandemic response has emphasised the need for early informed decision-making to implement proportionate disease control measures. our model identifies a low probability of successful epidemic mitigation using targeted antivirals alone (figure and ref. ), in distinction to results from models that fail to account for the diagnosis and delivery constraints inherent in any public health response. the decision support tool (table ) highlights key epidemic characteristics that are predictive of a high likelihood of effective mitigation. the reproduction number was one of the earliest parameters estimated from early outbreak data during the h n outbreak. , our findings reinforce the importance of characterising epidemic severity as early and as accurately as possible, in order to inform a proportionate pandemic response. critically, a typically mild pandemic (low g), such as that experienced in , is predictably difficult to contain using a targeted antiviral strategy due to the low proportion of infectious cases that present to health authorities. the relative infectiousness of treated individuals, e t , is strongly negatively correlated with successful mitigation, perhaps a surprising result given the model's underlying assumption (based on available epidemiological and human clinical trials data) that e t lies in the range [ ae , ]. that is, nais provided as treatment have a maximum impact of just a % reduction in infectiousness. however, our previous results show a strong synergistic effect of treatment when overlayed on a contact prophylaxis strategy, explaining the observation here that e t is critical in determining likely success of an intervention. despite the limited impact of treatment at the individual-level, the model outcomes are highly sensitive to the value of the relative infectiousness of treated cases. it follows that determination of e t is important for predicting the population-level outcome of a control effort. a 'small' reduction (of the order approximately %) may be extremely valuable in terms of success of a public health control strategy, and so should not be discounted. using a mathematical model which takes into account some of the key logistic constraints that are inherent to healthcare responses, we have derived a logistic regression model for estimating the probability that an antiviral intervention based on liberal distribution of nais as treatment and prophylaxis could successfully mitigate an influenza epidemic. the model demonstrates an excellent degree of accuracy when applied to synthetic data. the choice of parameters for the regression model was restricted to those that were both highly correlated with the success of the intervention and hopefully feasible to measure during the early stages of an emerging epidemic. the model could therefore be a useful near real-time decision support tool for public health policy in the face of an influenza epidemic, although further validation on a range of synthetic data (and real-world data where available) is required. influenza to seasonal flu status to avoid overstretching the demands on healthcare services. a great deal of information has emerged as the result of the pandemic response exercises conducted by affected countries. however, uncertainties remain regarding the effectiveness of intervention measures, as well as the feasibility and the timing of their implementation. mathematical and computational models [ ] [ ] [ ] have been used to project the outcomes of influenza outbreaks under various scenarios and epidemiological hypotheses. motivated by the events of and public health measures adopted by the taiwan cdc, we use a stochastic, individual-based simulation model to study the spatio-temporal transmission characteristics of the h n virus, so as to quantitatively assess the effects of early intervention strategies. our stochastic disease simulation model builds upon a highly connected network of individuals interacting with each other via social contact groups. to represent the daily interactions of approximately million people living in taiwan, we constructed a computer-generated mock population based on national demographic and employment statistics (to derive daily commute patterns) from the taiwan census (http://www.stat.gov.tw/). each individual is created with a set of attributes, including age, sex, residence, family structure, and social standing (employment status, etc.). based on their attributes and the time of day, each individual is assigned to miscellaneous contact groups, where the potential of interactions between any two individuals resulting in flu virus transmission occurs. such epidemiological properties are defined by empirically parameterized attributes such as basic reproduction number r , transmission probability, contact probability and associated probability distributions outlining the disease's natural history. additionally, intervention measures are implemented as scheduled events that could alter control parameters during the course of a simulation run. the targeted basic reproduction number (r ) in all our simulations is ae , following the suggested range by who of ae - ae . as the latent ⁄ incubation and infectious periods for h n have not yet been reliably ascertained, we adopt the natural history of the and pandemic influenza viruses. , here, the latent period ranged from to days, with a median value of ae days. the infectious periods begin day prior to symptom onset and can continue for - days, with a median value of ae days. twothirds of the infected individuals will develop clinical symptoms, and the asymptomatic cases will have half the infectious strength. the efficacy of antiviral drugs (oseltamivir) and vaccines are based on these studies. , for the source region of the infected cases, we use the north american continent (canada, mexico and united states) with an estimated total population of and an average hours of flight time to taiwan. the average daily passenger number is based on the annual statistical report on tourism, tourism bureau, taiwan (http://admin.taiwan.net.tw/english/statistics/year.asp? relno= ). each simulation lasts days and starts with a baseline simulation of r % ae h n pdm outbreak at the source region. the outbreak was adjusted to approximate clinical attack rate (car) in the united states, april -march , . we estimate the daily number of imported cases according to average daily passenger numbers and their probability of holding a disease status. we then apply airport exit ⁄ entry screening per corresponding success rates, by subtracting the number of identified symptomatic cases. we also consider latently infected passengers with inflight disease progression, by fitting a gamma distribution to the cumulative distribution of time to onset data with hours average flight-time, as presented by pitman et al. the daily imported cases are seeded according to the traveling patterns of foreign tourists and residents returning home. from the disease's natural history, we derive that roughly % of the infected travelers present no symptoms; the percentage increases if most symptomatic individuals elect not to travel in their condition, or are stopped by airport screening. we use the official epidemic data provided by the taiwan cdc to calibrate the simulation model and perform regression analysis on scenario parameters. this data is a close estimation of the weekly new clinical cases of h n pdm patients. it consists of weekly opd (outpatient department) icd- code (influenza) tallies collected by the bureau of national health insurance, taiwanadjusted to exclude seasonal flu patients and to account for uninsured patients. we formulate our scenario settings according to events in taiwan, and establish settings to approximate the actual events. with domestic events and intervention schedules fixed in time, the start date determines the simulation outcomes and the data range for selected indicators, such as the mean car, the epidemic peak, and several significant dates for the incoming index case events. we plot the taiwan weekly h n opd cases alongside the weekly new clinical cases from our simulation results in figure . our simulations not only capture the epidemic trend, but also pick out the most likely date, may , for identifying the first symptomatic case at airport screening based on practical assumptions. we further analyze the effectiveness of various mitigation measures with february , as the empirical start date for h n pdm in north america. the simulation result confirms that by the time we identified the first symptomatic case at the border screening, infected cases had already made their way to the public. by our calculation, roughly four such cases had passed in each of our scenario settings, with the first case happening as early as weeks before detection. figure also highlights the importance of the timing for the implementation of mitigation measures; for example, a -day-delay of the identical intervention plan results in nearly an additional % of the population being infected. therefore, the rule of thumb for healthcare officials is to implement intervention measures as early as possible. in our study, we have ignored the possibility of inflight transmission and any false positive results by airport screening procedures. to assess the effectiveness of each mitigation strategy of interest and their combinations, we take the calibrated simulation model and perform simulation realizations for groups of scenarios containing only those intended mitigation measures, and analyze the averaged results. for example, in the airport exit screening policy only scenario, the first imported symptomatic case can be delayed up to months, and the epidemic peak can be delayed up to days. as the data suggests, the exit screening policy alone has very little impact on car. combining various screening success rates for both exit and entry screening allows us to quantitatively assess their beneficial ramifications on the epidemic. for example, there is very little additional benefit between % and % suc-cess rates for entry screening policies when exit screening policies are adequate, as the enhanced border screening only delayed the epidemic peak by day, and reduced car by < ae %. base on this result, the government should not attempt to exhaust all its resources in securing the border during a pandemic event, because the return of such a policy will be disappointing. instead, a response plan with a shifting focus on health resource allocation and the capacity of adjusting intervention strategies in line with the developing epidemic will be most effective. based on the same principle, we perform experiments with assorted scenarios, including relaxing entry screening policies after identifying the first imported symptomatic case, mass vaccination based on the actual vaccination schedule of h n pdm in taiwan, and altering the start dates of the vaccination schedule. our results show that with a reasonable reduction in the airport entry screening success rate, we conserve valuable healthcare resources, but loose a few days for the strategic planning and preparation of subsequent response measures. in other simulation scenarios, a national vaccination campaign has very little impact on the outcome, due to the late start of the vaccination schedule. we then explore the effect of a national vaccination campaign with various starting dates. the simulation results are illustrated in figure , where the benefit of an early start date for mass vaccination is clearly demonstrated. considering a scenario with an % airport exit screening success rate, % airport entry screening success rate and % symptomatic case tracing success rate, the combined intervention strategy results in: a % reduction in car if the vaccination campaign starts in mid-november; % reduction if the campaign starts in mid-october; % reduction if the campaign starts in mid-september; and % reduction if the campaign starts in mid-august. in retrospect, the taiwanese government's response to h n pdm proved to be effective. first and foremost, it initiated enhanced border monitoring and on-board quarantine inspection as soon as the threat of a flu pandemic became clear. at the same time, the domestic preparations towards h n pdm were escalated, such as antiviral drug stockpiling and distribution, and vaccine acquisition. as the h n cases increased worldwide, various revised plans were adopted and implemented; such as the shift from labor-extensive on-board quarantine inspection to the notifiable infectious disease reporting system and realtime outbreak and disease surveillance system in order to effectively track down symptomatic and exposed passengers, apply prophylaxis treatment and mandatory in-home quarantine. as a result, all h n pdm related statistics are well below the international average. in modern society, countries rely heavily on the global economy for their own prosperity. shutting down the border for any length of time is not only costly, but could have disastrous economic effects that linger long after the event is over. moreover, with nearly % of the infected passengers presenting no symptoms whatsoever, they are not detectable by any port authority's screening procedures, and the importation of the novel flu virus is therefore inevitable. many studies conclude that entry screening is unlikely to be effective in preventing or delaying the importation of influenza, and has negligible impact on the course of subsequent epidemic. however, these studies are based on the assumption that effective exit screening is in place. our study shows that as the exit screening success rate decreases, the sensitivity of the entry screening policy becomes more pronounced. with the same methodology, we can also study the effects of varying the length of flight time, or the disease's incubation time. lastly, the benefit of entry screening is even more crucial for a small island country such as taiwan, since all incoming traffic must go through the port authority where entry screening can be enforced. in england and wales, three waves of the pandemic struck in summer, autumn, and winter seasons of - . although the proportion of people reporting symptoms was often greater in the first wave, - a puzzling feature was the much higher mortality in the second wave, in which . % of the population died, compared with . % in the out-of-season first wave and . % in the third wave. an obvious hypothesis to explain the changes in mortality from wave to wave would be that the virus mutated to higher virulence after the (lower mortality) first wave. although pandemic virus reconstituted from the high mortality waves has proven to have high virulence in animals, it has not been possible to recover virus from the first wave in for comparative purposes. indeed it is questionable whether virulence mutation(s) occurring between wave and wave could have spread to so many different populations in the time-frames observed. furthermore, in all three pandemic waves, there was the same agedistribution of mortality, with more deaths occurring amongst younger adults than older adults. [ ] [ ] [ ] this 'pandemic signature', arguably due to immune protection of older adults who were exposed to a similar virus in the years before , , suggests that the - viruses were at least immunologically similar in all three waves. a second hypothesis would be that the higher case fatality in the later waves was due to higher rates of complicating bacterial pneumonia, to increased transmission of influenza virus in the cooler months of the year, or to other seasonal effects. we have considered a third (immunological) hypothesis to explain the greatly increased mortality in waves and . the underlying idea is that the mortality rate in the first wave was lower than in later waves because most persons were protected by prior immunity in the first wave, and that the mortality was higher in later waves because of waning of that short-lived immunity. this hypothesis builds on our earlier modelling papers suggesting that even before the first wave in , military, school, and urban populations in england and wales apparently had (short-lived) immune protection, presumably induced by recent prior exposure to seasonal influenza. [ ] [ ] [ ] we suggest that this short-lived strain-transcending protection was in addition to the longer-lasting immunity, presumably induced by exposures to a similar virus circulating prior to , that arguably reduced pandemic mortality for older adults in - . , cumulative mortality rates attributed to pandemic influenza were available for each of the three waves in - for populations in england and wales. we have built immunological models to potentially explain the variation in mortality rates across waves and populations. to show proof of principle, we have fitted these models to mortality data from a randomly selected sub-set of twenty populations. our key assumption was that the risk of a fatal infection would be limited to persons with inadequate immunity who were being exposed to the pandemic virus for the first time. persons who were exposed and who survived an earlier wave were assumed to be protected against death in a later wave. model a and assumptions (see figure ) before the first wave, we assumed that people could be fully susceptible (s ), or partially protected (q ), or fully protected (p) by prior immunity which was not necessarily specific for the new virus. we assumed that exposure to the new pandemic virus would be fatal (m) in a proportion h of fully susceptible persons who were actually exposed (e) in the relevant wave. for those surviving that first exposure, it was assumed that they would be permanently protected against death in later waves by an immune assumed that viral exposure and multiplication would induce an immune response specific for the pandemic virus that would protect them against death in that wave and in subsequent waves. in contrast, for persons with strong prior immune protection, p, the virus would not be able to multiply to induce pandemic-specific immune protection. between waves, it is assumed that due to the waning of non-specific prior immunity, persons in the p state can move to the q state, and persons in the q state can move to an s state before the next wave. the proportion (e) of susceptible persons exposed to productive infection in each population was estimated by applying the following version of the final size equation to the proportion susceptible (s & q) in each wave, for each population: note: in both figures and , we have omitted the flows out of the q and e states that removed persons from the risk of death. parameters: s = proportion fully susceptible to infection and death before wave ; q = proportion susceptible to immunising infection, but not to death from exposure in wave ; p = proportion temporarily protected against both immunising infection and death from exposure in wave ; n = proportion even more protected against both immunising infection and death from exposure in wave (model b only); r = basic reproduction number (the average number of secondary cases for each primary case) in a fully susceptible population; f = proportion moving from q to s between waves; g = proportion moving from p to q between waves; d = proportion moving from n to p between waves (model b); h = proportion of e that actually move to m and die. model a could provide a very good fit for the summer, autumn, and winter waves of the - pandemic (results not shown). however, because of the replenishment of the pool of susceptible persons over time, model a also predicted a fourth wave of influenza in the spring season of . as no such wave was seen, and as we could not find parameters values for model a that did not predict a fourth wave, we must regard model a as inadequate. model b was similar to model a, but with an additional stage of prior immunity (n), which could wane to p. model b allowed us to not only fit the three observed waves, but also to fit the imputed data (zero cases) corresponding to the absent fourth wave. following earlier work, , we used a bayesian approach with markov chain monte carlo (mcmc) procedures to estimate model parameters, and we used hyper-parameters to allow for parameter variation between populations. the initial conditions were specified by the parameters: p , q , s and n . from these and the other parameters, it was possible to simulate the behaviour of model a over three waves, and of model b over four waves, and to estimate the expected numbers dying in each wave in each population. we calculated the log likelihood of the observed numbers of deaths given the parameter estimates, and we used mcmc simulation to generate the posterior distributions of parameters. although we obtained an excellent fit between observed and expected numbers of deaths in each of the three waves for the populations for model a, we could not find parameter values for model a that would fit the three observed waves without giving rise to a fourth wave in the spring of . accordingly, in the modified model b, we allowed for an additional stage of prior immunity (figure ) , and we fitted the model to the same data, plus imputed data corresponding to 'the absent fourth wave'. we obtained a very good fit to the three observed waves and the absent fourth wave in each population. the % credibility intervals for parameter estimates, derived from the posterior distributions of the hyper-parameters were: h = . - . , s = . - . , q = . - . ; n = . (fixed); p = ) s ) q ) n ; f = . - . ; g = . - . ; d = . - . and r = . - . . this analysis had allowed all parameters to vary from population to population under the constraints of the hyper-parameters. however, several of the biologically determined parameters might be expected to be more constant from population to population, whereas those dependent on mixing history and other social characteristics which vary more widely from population to population. to test this possibility, we fixed the mean values for the more biological parameters (f = . ; d = . ; g = . ) and estimated the % credibility intervals for the others as: h = . - . ; s = . - . , q = . - . ; and as before n = . (fixed); in a subsequent paper we will be able to provide more details of the method, the robustness of the assumptions, and the results from fitting to many more populations. this short report suggests that the observed patterns of mortality in england and wales over the three waves of the - influenza pandemic , can be explained by an immunological model. in particular, the lower mortality in wave one can be explained by the assumption of protective immunity antedating the first wave, arguably induced by prior exposure to seasonal influenza. , the much greater mortality in wave two can be explained by the waning, between wave one and wave two, of that short-lived and less-specific immune protection. the somewhat lesser mortality in wave three and the 'absent fourth wave' can be explained in terms of the progressive acquisition of immunity specific to the pandemic virus. the credibility estimates for parameters are of potential interest. for example, r estimates of . - . across different populations are consistent with our earlier findings. , if all persons had been susceptible, such r values imply that the virus would have infected most people in all populations. however, even in the first wave, the proportion susceptible, s + q , was < % in all populations, so that a considerable number of persons escaped productive infection in that wave; as their immunity waned, they became susceptible to infection in the later waves. it is likely that the variation in r between populations is due to different rates of population mixing. estimates for h indicate that between % and % of infections in the most susceptible persons were fatal; the higher values of h could reflect higher rates of secondary bacterial infection in the most socially disadvantaged and overcrowded populations. although we have shown the plausibility of an immunological explanation for wave to wave changes in pandemic mortality, we cannot assume that our particular model is even approximately correct. nor can we exclude the possibility that the higher mortality in the later pandemic waves in - was because of genetic change in the virus in later waves, or because of changing rates of secondary bacterial infection or seasonal effects. nevertheless, there is growing evidence that the population spread of pandemic influenza, whether in - , or in , , can be constrained by significant prior immunity, even for viruses that are ostensibly novel. previous reports, reviewed in ref. [ , ] , support the idea of strain-transcending immune protection, which can wane over periods of a few months. this form of protection, probably induced by recent exposure to seasonal influenza, may not be mediated by hi or neutralizing antibody. in contrast, strain-specific immunity, most often mediated by hi or neutralizing antibodies can be so long-lasting that after several decades it will still provide significant protection against any closely-related virus that re-appears in the population. it has not escaped our notice that although attack-rates in the h n pandemic were low in many countries, with generally mild symptoms, the virus did cause lifethreatening illness in a small proportion of younger affected persons. it seems likely that those who were most severely affected in were doubly unlucky: they had missed out on seasonal influenza infection or vaccination in the preceding season(s), and they were born too late to have been protected by the closely-related viruses that are thought to have circulated before . during the early phases of the influenza pandemic in italy, real-time modeling analysis were conducted in order to estimate the impact of the pandemic. in order to evaluate the results obtained by the model we compared simulated epidemics to the estimated number of influenza-like illness (ili) collected by the italian sentinel surveillance system (influnet), showing a good agreement with the timing of the observed epidemic. by assuming in the model mitigation measures implemented in italy, the peak was expected on week ( % ci: , ). results were consistent with the influnet data showing that the peak in italy was reached in week . these predictions have proved to be a valuable support for public health policy makers for planning interventions for mitigating the spread of the pandemic. mathematical models have recently become a useful tool to analyse disease dynamics of pandemic influenza virus can-didates. [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] as of april , after the pandemic threat emerged worldwide, it was crucial for policy makers to have early predictions on the possible spread of the pandemic influenza virus in order to support, with quantitative insight into epidemic, policy decisions. thus, after the first pandemic alert was announced by the world health organization (who) in late april , a national crisis management committee headed by the minister of health was established in italy in order to provide weekly advice to the italian ministry of health. real-time analyses using an individual based model were undertaken. the transmission model was previously used for evaluating the effectiveness of the control measures adopted in the national pandemic preparedness plan and for assessing the age-prioritized distribution of antiviral doses during an influenza pandemic. to parameterize the transmission model, we used data derived from the national surveillance system until june and estimates of key epidemiological parameters as available at that time. in order to provide a preliminary assessment of the model predictions performed during the early stages of the epidemic, we compare model predictions with surveillance data of influenza-like illness (ili) available since august . after the first pandemic alert was announced by the who in late april , a national active surveillance system for the pandemic influenza was set up from april to july . however, over the period from april to october , surveillance systems, laboratory testing, and diagnostic strategies have varied considerably in italy. since end of july , following who recommendations, the focus of surveillance activities has changed in reporting requirements, as active case-finding became unsustainable and unnecessary. for this reason, the ministry of health (ministry of health, available in italian at the website: http://www.normativasanitaria.it) requested regional health authorities to report the weekly aggregated ili cases according to a new case definition (sudden onset of acute respiratory symptoms and fever > °c plus at least one of the following systemic symptoms: headache, malaise, chills, sweats, fatigue; plus at least one of the following respiratory symptoms: cough, sore throat, nasal obstruction). by october , following the increasing number of cases, the sentinel influenza surveillance system (influ-net available at: http://www.flu.iss.it) became the official surveillance system for ili cases in italy (ministry of health, available in italian at the website: http://www. normativasanitaria.it). since , influnet is routinely based on a nation-wide, voluntary sentinel network of sentinel community based physicians in the regions and autonomous provinces of the country. incidence rates are, therefore, not based on consultations, but on the served population of each reporting physician each week. influ-net usually consists of an average of (range - ) general practitioners (including physicians and pediatricians) per year, covering about ae - % of the general population, (representative for age, geographic distribution, and urbanization level) reporting ili cases (according with a specific case definition). italian influnet surveillance system is part of the european influenza surveillance scheme (eiss). a stochastic, spatially explicit, individual-based simulation model was used. individuals are explicitly represented and can transmit the infection to household members, to school ⁄ work colleagues, and in the general population (where the force of infection is assumed to depend explicitly on the geographic distance). the national transmission model was coupled with a global homogeneous mixing susceptible-exposed-infectious-removed (seir) model accounting for the worldwide epidemic, which is used for determining the number of cases imported over time. regarding the epidemiological assumptions (e.g., length and shape of the infectivity period, which lead to an effective generation time of ae days), this study is consistent with refs [ , , , ] , but for the proportion of symptomatic individuals, which is assumed to be ae %. the basic reproductive number of the national transmission model was set to ae , according to the early estimates as obtained during the initial phase of the epidemic in mexico in a community setting. , we initialized our simulations through the global homogeneous mixing model in such a way that imported cases were generated until june . this gives a reliable way for fixing the time in the simulations and thus determining the timing of school closure and vaccination in the simulations. the model accounts for school closure for both summer and christmas holidays: we assumed that in these periods contacts among students decrease, while contacts in the general community increase, as in ref. [ ] . we also considered scenarios accounting for partial immunity in the population. in order to investigate the effects of recommendations of the ministry of health (confirmed cases coming from affected areas were isolated for - days, either in hospital or at home) established in the early phase of the pandemic (april-july ), we assumed that a fraction of the imported symptomatic cases were isolated on the first day after the symptoms onset. this recommendation was in place until july . we also assumed, according to the italian school calendar, that schools were closed from june to september for the summer holidays, and from december to january for christmas holidays. the effects of prolonged school closure were also investigated. when considering vaccination, we assumed weeks for the logistical distribution of doses of pandemic vaccine. since at the time of simulation specific recommendations regarding the administration of a single dose of pandemic vaccine from ema were not available yet, we considered the administration of vaccine doses month apart). the pandemic vaccine was considered effective after the administration of the second dose with a vaccine efficacy of %. we assumed the vaccine to be administered by priority, vaccinating first the target population accounting for essential services workers (including health care workers and blood donors), pregnant women at the second or third trimester, and at risk patients (with chronic underlying conditions) younger than years old. the vaccination coverage was assumed %. regarding antiviral treatment and prophylaxis, recommendations of the ministry of health in the initial phase of the epidemic were to administer antivirals to all confirmed cases and to their close contacts. we assumed that the surveillance system would be able to detect % of symptomatic cases. after july , recommendations changed and antiviral treatment was considered only for cases with severe complications and in case of local clusters. since it was difficult to establish the proportion of treated cases, we considered different scenarios: antiviral treatment from % to % of the symptomatic cases. consistently with ref. [ ] , both treatment and prophylaxis were assumed to start day after the clinical onset of symptoms in the index case. treatment was assumed to reduce infectiousness by %, whereas antiviral prophylaxis was assumed to reduce susceptibility to infection by %, infectiousness by %, and the occurrence of symptomatic disease by %. as of july , approximately confirmed cases have been reported to the italian surveillance system for pandemic influenza. during july, the sudden increase of ili confirmed cases suggests for sustained autochthonous transmission in italy. by analyzing the number of ili cases reported to the surveillance during the weeks from to , we found that the exponential growth rate was ae ⁄ week and thus we estimated the national reproductive number to be r = ae . this estimate of the basic reproductive number supports the choice of the value adopted in the model simulations (r = ae ). in the absence of intervention measures, the predicted cumulative attack rate was ae % ( % ci: ae , ae ), and the peak was expected on week ( % ci: , ) with a peak day incidence of ae % ( % ci: ae %, ae %). by assuming case isolation, antiviral treatment, and prophylaxis to % of symptomatic cases until july , the peak was expected on week ( % ci: , ). when considering ae % of natural immunity in the population aged more than years, the peak was expected week later than in the previous scenario, i.e., on week ( % ci: , ). to validate the model, we compared model predictions (which are based only on the available information on the early phases of the epidemic) with ili data (figure ). based on model predictions, we estimated the underreporting factor of influnet ranging from ae to ae , considering different scenarios. by aligning the simulations with the ili data adjusted by the underreporting factor, we can observe that almost all the points in the increasing phase of the epidemic lie within the % ci of the model results (both considering or not natural immunity). the decay phase of the simulated epidemics shows a small delay with respect to the ili data. when introducing single and combined mitigation measures, such as case isolation, antiviral treatment, prophylaxis, and vaccination in the model, results showed that even a low proportion of symptomatic cases treated with antiviral drugs could have led to a relevant reduction in the epidemic size (table ) . we simulated the planned italian vaccination strategy (begun on october ), obtaining a limited but not negligible reduction in the attack rate with respect to the scenarios accounting only for antiviral treatment. moreover, the effect of vaccination would be higher if coupled with antiviral treatment; vaccination would have no effect on delaying the peak incidence. model predictions produced in italy during the early phase of the pandemic influenza are in excellent agreement with italian surveillance data on the beginning of the epidemic (when case isolation, antiviral treatment of index cases, and antiviral prophylaxis to close contacts were implemented by the italian regional public health authorities) and are basically consistent with the influ- net data during the course of the epidemic. the model has been useful for predicting the timing of the epidemic, while it has overestimated the impact of the influenza pandemic for adult and elderly individuals. however, the disalignment is probably due to the model parameterization. based on literature values, , we assumed a similar fraction of cases in the different social contexts considered in the model (namely ⁄ in households, ⁄ in schools ⁄ workplaces, and ⁄ in the general community), since analysis on the relative transmissibility of the virus was not carried out for any country yet. we were also able to estimate an underreporting factor for the influnet data in the range ae - ae . if we focus our attention on the reporting factor computed by considering the total number of cases (instead of symptomatic cases), the resulting value lies in the range - ae %, which is in excellent agreement with the range estimated in ref. [ ] on previous a ⁄ h n influenza seasons, namely ae %- ae %. moreover, based on our results showing that vaccinating % of the italian population was more than adequate to mitigate the pandemic, the ministry of health decided to stockpile a limited number of vaccines. we have also shown that starting the vaccination program in october (or later) could have had only a limited effect on reducing the impact of the epidemic, although it may have been useful to prevent a possible second wave and to protect essential workers and at-risk patients. finally, our results have shown that antiviral treatment would have been the most efficient strategy to reduce the impact of the influenza pandemic, even with a limited antiviral stockpile. a population-wide passive immunotherapy program in this paper, we assume that convalescent plasma (cp) is efficacious in treating severe cases of pandemic influenza. under this premise, we test the hypothesis that a population-wide passive immunotherapy program that collects plasma from a small percentage of convalescent individuals can harvest sufficient cp to treat a substantial percentage of severe cases during the first wave of the pandemic. the proposed program involves recruiting adults (individuals age - years) to donate blood if they have experienced influenza-like symptoms more than weeks ago (to account for the time needed for neutralizing antibodies to build up). the blood samples would be screened for infectious diseases (including hiv, hbv, hcv, htlv, and syphilis, etc., as in routine blood donation screening) and neutralizing antibodies against the pandemic virus. donors whose blood samples are free of known infectious agents and contain a sufficiently high titer of neutralizing antibodies would then be invited to donate plasma by plasmapheresis or routine whole blood donation. qualified donors with higher titers may be given higher priority for plasma donation. in this paper, we use the demographic and logistical parameters of hong kong as a case study. see figure for a schematic of the proposed passive immunotherapy program. we examine the following questions regarding the logistical feasibility and potential benefits of the proposed passive immunotherapy program: (i) what percentage of convalescent individuals (donor percentage) is needed in order for the program to significantly reduce pandemic mortality? (ii) how many severe cases can be offered passive immunotherapy? (iii) what are the ratelimiting factors in the supply of passive immunotherapy? (iv) what are the epidemiologic and logistical factors that determine the demand-supply balance of passive immunotherapy? a more detailed presentation of our results is now available in ref. [ ] . transmission and natural history model for pandemic influenza we use an age-structured disease transmission model to simulate the spread of pandemic influenza. the natural history model is similar to that used by basta et al. , the most important parameter in characterizing the growth of an epidemic is the basic reproductive number r , which is defined as the average number of secondary cases generated by a typically infectious individual in a completely susceptible population. we consider values of r between ae and , which is consistent with recent estimates. , [ ] [ ] [ ] logistical model for the passive immunotherapy program we assume that q d (%) of to year-old individuals who have recovered from symptomatic infections of pandemic influenza donate their blood for screening t r = days after cessation of symptoms. follow-ups of convalescent individuals infected with h n pdm in an ongoing clinical trial of passive immunotherapy suggested that neutralizing antibodies level reaches maximal level around - days after recovery and stays at that level for months after. we assume that q s (%) of these donors are qualified for plasma donation of which q r (%) are recurrent donors who return to donate plasma every t w = days. screening involves both detection of infectious agents and neutralizing antibodies against the pandemic virus. the latter is the rate-limiting step because neutralization tests of pandemic viruses can only be done in a bsl setting. we assume that five bsl -trained technicians are available to test the blood specimens, each running viral neutralization tests in days. therefore, the capacity and turnaround time of blood screening are u s = and t s = days, respectively. hong kong currently has nine plasmapheresis machines which allow a maximal throughput of plasma donations per day (assuming -hour daily operation with each donation taking minutes). therefore, the capacity and turnaround time of plasmapheresis are u p = and t p = ⁄ days, respectively. collected cp are ready for use in transfusion after final quality check, which takes t q = days. we assume that r t plasma donations are required to treat one severe case on average. the expert panel of the abovementioned study of passive immunotherapy for h n pdm in hong kong suggested that r t < . we assume that p h (%) of symptomatic cases will be severe cases for whom passive immunotherapy is suitable. although p h will be smaller than the case-hospitalization rate (passive immunotherapy may not be suitable for some hospitalized cases), we assume that the two have similar ranges and consider p h ranging from ae % to %. because each severe case requires r t plasma donations on average, demand for cp is simply r t p h times the number of symptomatic cases. therefore, r t p h can be regarded as a single parameter, which we refer to as the lumped demand parameter. we define the outcome as the percentage of severe cases that can be offered passive immunotherapy by the proposed program during the first wave of the local epidemic. we refer to this outcome as treatment coverage and denote it by q. we consider the base case scenarios assuming q r = % and q s = %. in general, the treatment coverage q increases sharply as the basic reproductive number r and the lumped demand parameter r t p h decrease (figure a ). in particular, when r is large and r t p h is small, q is very sensitive to r t p h , but insensitive to r . similarly, when r and r t p h are small, q is very sensitive to both. with a donor percentage of q d = %, the proposed program can supply passive immunotherapy to more than % of severe cases (q > %) if r < ae and r t p h < ae %, but < % if r > ae and r t p h > ae %. in general, the treatment coverage q increases sharply as the donor percentage q d rises from %, but with rapidly decreasing marginal increase ( figure b ). when r < ae and r t p h < ae %, q > % even if q d is as low as %, which is comparable to the current average blood donation rate of ae donations per population in developed countries. when q d is > %, q becomes largely insensitive to further increase in q d in most scenarios. the treatment coverage q for q d = % is more than % that for q d = % across all values of r and r t p h considered in the base case. therefore, increasing the donor percentage q d beyond % has a relatively small impact on cp supply. this is because increasing q d can boost supply only when plasmapheresis is not yet the supply bottleneck. for the same reason, once the donor percentage q d has reached %, the treatment coverage q is insensitive to further increase in q d even when the plasmapheresis and screening capacity are doubled ( figure b , lower panel). we conduct an extensive multivariate sensitivity analysis to test the robustness of our base case observations against uncertainties in parameter values. we generate epidemic scenarios by randomly selecting parameter values from their plausible ranges using latin-hypercube sampling. although there are numerous model parameters, the treatment coverage q is mainly determined by three lumped parameters: (i) r t p h , which indicates the magnitude of demand; (ii) q s q d , which indicates the magnitude of supply; (iii) the initial growth rate of the epidemic r (results not shown). while the dependence of q on r t p h and q s q d is readily comprehensible, it is not obvious a priori that q depends on the natural history and transmission dynamics of the disease via only the initial epidemic growth rate. when the plasmapheresis and screening capacity are very large, the supply-demand dynamics is further simplified: the treatment coverage q depends on lumped demand parameter r t p h and the lumped supply parameter q s q d only via their ratio. finally, q becomes insensitive to q s q d when the latter increases beyond - %, which is consistent with our base case observations. our results suggest that with plasmapheresis capacity similar to that in hong kong, the proposed passive immunotherapy program can supply cp transfusion to treat - % of severe cases in a moderate pandemic (basic reproductive number r < ae , lumped demand parameter r t p h < ae %) when the donor percentage is - %. increasing the donor percentage beyond % has little additional benefit because cp supply is constrained by the capacity of plasmapheresis during most stages of the epidemic. increasing plasmapheresis capacity could significantly boost cp supply, especially when there is a substantial pool of recurrent donors to alleviate the dependence of cp supply on donor percentage. in an ongoing clinical trial of passive immunotherapy for h n pdm virus infection in hong kong, % of convales- cent individuals agreed to donate their plasma for the study. therefore, the donor percentage required by the proposed passive immunotherapy program ( - %) is likely to be feasible. in view of the logistical feasibility of such program, we recommend that further clinical studies are conducted to evaluate the safety and efficacy of passive immunotherapy as a treatment for severe cases of pandemic influenza virus infection. our study is based on the premise that cp will be efficacious in reducing morbidity and mortality associated with pandemic influenza. in theory, the polyclonal nature of neutralizing antibodies in cp would lower the probability of an escape mutant emerging in treated patients. further, besides providing neutralizing antibodies against the pandemic virus, cp also might carry antibodies to other bacterial pathogens, which might decrease the severity of coexisting bacterial infections. as such, cp not only might reduce the case fatality rate but might also increase the recovery rate and shorten duration of hospitalization of severe cases. the proposed passive immunotherapy program can thus significantly reduce the burden on the healthcare system, especially the intensive care unit, which will likely be stressed, if not overloaded, at the peak of an influenza pandemic wave, hence benefiting the general public and not only those receiving passive immunotherapy. although the hypothesized efficacy of cp has yet to be proven in clinical trials, our modeling results show that a public health system similar to that in hong kong has the capacity to support a population-wide passive immunotherapy program that can supply cp treatment to a substantial percentage of the severe cases in a moderately severe pandemic. we estimate that compared to other developed countries, hong kong has a relatively low plasmapheresis capacity. our conclusions regarding donor percentage needed and rate-limiting factors remain valid for plasmapheresis capacity ranging from % to % of what we have assumed in the base case (results not shown). our conclusions are robust against uncertainties in the natural history and transmission dynamics of pandemic influenza. our sensitivity analysis shows that the outcome depends on these epidemiological characteristics only via the initial growth rate of the epidemic. as such, our results are applicable not only to pandemic influenza, but also to other emerging infectious diseases for which the time-scales of disease transmission and antibody response are similar to that for influenza virus. the three determinants of treatment coverage (the initial epidemic growth rate, the lumped demand parameter r t p h , and the lumped supply parameter q d q s ) are all readily measurable in real-time during an epidemic. therefore, our methods and results can be used as a general reference for estimating the treatment coverage of the proposed passive immunotherapy program for a given plasmapheresis capacity. background highly pathogenic h n virus continues to pose a serious threat to human health and appears to have the capacity to cause severe disease in previously healthy young children and adults. at present, antiviral therapy by oseltamivir remains the mainstay for managing h n patients. while early treatment improves survival, approximately % of patients treated within days of illness still succumb to the disease. in addition to the role of viral replication, there is good evidence that the host proinflammatory responses contributes to h n pathogenesis. this suggests that both antiviral and immune-modulatory drugs may have a role in therapy. we previously demonstrated that cyclooxygenase (cox- ) plays a regulatory role in h n hyperinduced pro-inflammatory responses, and its inhibitor has potent effects at modulating this host response. now we demonstrate that, in addition to its immune-modulatory effect, a selective cox- inhibitor, ns- has a direct antiviral effect against h n infection. materials and methods human primary monocytederived macrophages or alveolar epithelial cells (a ) were pre-treated with ns- or drug-vehicle for hour before h n virus infection. h n viruses at multipicity of infection (moi) of was used to infect the cells. following virus adsorption for mins, the virus inoculum was removed, and the cells were washed and incubated in corresponding medium with ns- or drug-vehicle as controls for , , , , and hours post-infection. cells were harvested for rna isolation at hours post-infection to study viral matrix (m) gene expression. supernatants were collected for % tissue culture infection dose (tcid ) assay to determine the virus titers at , , , and hours after h n infection. results ns- was found to suppress virus gene transcription and infectious virus yield in h n -infected human cells. conclusion we demonstrate that a selective cox- inhibitor, ns- , shows an inhibitory effect on h n viral replication in addition to its immune-modulatory effect that could counter the detrimental effects of excessive proinflammatory cytokine production. the findings suggest that selective cox- inhibitors may be a therapeutic target for treating h n disease in combination with appropriate antiviral therapy. the emergence and spread of the highly pathogenic avain influenza viruses (h n ) in poultry and wild birds with repeated zoonotic transmission to humans has raised pandemic concern. at the time of writing, human cases have been reported with fatalities, an overall case fatality rate of around % (cumulative number of confirmed human cases of avian influenza a ⁄ (h n ) reported to world health organization updated to october ). our previous data demonstrated that cox- was markedly up-regulated in h n -infected primary human macrophages, and that it played a regulatory role in the h n hyperinduced host pro-inflammatory responses. such cytokine dysregulation is proposed to be a major contributor to the pathogenesis of h n disease in humans. with the use of selective cox- inhibitors, we found that the h n -hyperinduced cytokine response was significantly suppressed by the drug in a dose-dependent manner. selective cox- inhibitor is a form of a non-steroidal anti-inflammatory drug that selectively targets cox- , and it is an inducible enzyme responsible for inflammatory process and immune response. here, we report a novel finding of a direct antiviral effect of a selective cox- inhibitor, ns- , against h n infection in human primary macrophages and alveolar epithelial cells. taken together with our previous findings that suggest an immuno-modulatory effect that can modulate virus driven cytokine dysregula-tion, these findings highlight a role for cox- and its downstream signaling as potential novel targets for adjunctive therapy of severe viral pneumonia, such as that caused by h n . such therapy may be combined with conventional antiviral drugs. the h n virus used was a ⁄ vietnam ⁄ ⁄ ( ⁄ ) (h n ), a virus from a patient with h n disease in vietnam during . the viruses were grown and titrated in madin-darby canine kidney cells cells as described elsewhere. virus infectivity was expressed as tcid . all experiments were performed in a biosafety level facility. monocyte-derived macrophages: peripheral-blood leucocytes were separated from buffy coats of healthy blood donors (provided by the hong kong red cross blood transfusion service) by centrifugation on a ficoll-paque density gradient (pharmacia biotech) and purified by adherence as reported previously. the research protocol was approved by the ethics committee of the university of hong kong. macrophages were seeded onto tissue culture plates in rpmi medium supplemented with % heat-inactivated autologous plasma. the cells were allowed to differentiate for days in vitro before use in the infectious experiments. alveolar epithelial cells: a cells were obtained from atcc and maintained in culture using dulbecco's modified eagle medium supplemented with % fetal calf serum, . mg ⁄ l penicillin, and mg ⁄ l streptomycin. differentiated macrophages or a cells were pre-treated with a selective cox- inhibitor, ns- (cayman), at concentrations as indicated or drug-vehicle for hour before infection. cells were infected with h n viruses at moi of . following virus adsorption for min, the virus inoculum was removed, the cells were washed and incubated in corresponding medium with ns- or drug-vehicle as controls throughout the experiments. cells were harvested for rna isolation at hours post-infection to study viral m gene expression. supernatants were collected for tcid assay to determine the virus titers at , , , and hours after h n infection. total rna was isolated using the rneasy mini kit (qiagen) according to the manufacturer's instructions. the cdna was synthesized from mrna with poly(dt) primers and superscript iii reverse transcriptase (invitrogen). transcript expression was monitored by real-time pcr using power sybr Ò green pcr master mix kit (applied biosystems) with specific primers. the fluorescence signals were measured using the real-time pcr system (applied biosystems). the specificity of the sybr Ò green pcr signal was confirmed by melting curve analysis. the threshold cycle (ct) was defined as the fractional cycle number at which the fluorescence reached times the standard deviation of the base-line (from cycle to ). the ratio change in target gene relative to the b-actin control gene was determined by the )ddct method as described elsewhere. ns- reduced the viral m gene expression in h n infected human macrophages in a dose-dependent manner ( figure ) . similarly, production of infectious virus yield in h n infected macrophages was found to be suppressed in the presence of ns- at lm compared to vehicletreated cells (figure a) . a comparable effect of ns- was observed in h n -infected human alveolar epithelial cells ( figure b ). we have previously demonstrated that cox- expression was dramatically upregulated following h n infection in human macrophages in vitro and in epithelial cells of lung tissue samples obtained from autopsy of patients who died of h n disease. this suggests that cox- may be an important host factor involved in h n pathogenesis and also provide a possible explanation on why h n virus replication is susceptible to a selective cox- inhibitor. cox- was previously reported to play an important role in the pathogenesis of other influenza a viruses. an in vivo study has highlighted the importance of cox- in h n - infected mice. findings showed that infection induced less severe illness and reduced mortality in cox- knock-out mice than in wild-type mice. on the other hand, cox- knock-out mice had enhanced inflammation and earlier appearance of proinflammatory cytokines in the bal fluid, whereas the inflammatory and cytokine responses were dampened in cox- knock-out mice. these data suggests that cox- and cox- may lead to opposite totally contrasting effects on influenza h n infected mice. cox- deficiency is detrimental, whereas cox- deficiency is beneficial to the host during influenza viral infection. therefore in the present study, instead of blocking cox enzymes in general as reported by others, we have chosen ns- that selectively block cox- but preserve cox- activity and showed that this drug significantly reduced h n virus replication in a dose-dependent manner. taken together with our previous report suggesting its immuno-modulatory effects, we believe that selective cox- inhibitors and cox- signaling pathways deserve investigation as a promising approach for targeting therapy in h n diseases. however, a few reports have suggested the importance of cox- in the late stage of inflammation for the resulution of inflammation, [ ] [ ] [ ] and this raises concern whether inhibition of cox- may be harmful in treating diseases related to dysregulation of host inflammatory response such as acute lung injury, which is a leading cause of death in h n patients. we previously looked at the autopsy samples of lung tissues from h n patients and found that cox- expression was markedly up-regulated compared with that from persons who died of non-respiratory causes. moreover, data also demonstrated that pro-inflammatory cytokines, such as tnf-a, was markedly elevated in the h n infected lung autopsies. taken together, with the histo-pathological findings, which showed predominant features of exudative inflammatory phase in autopsy lung samples from h n patients, , we may therefore speculate that people who had fatal h n infection died during acute inflammation phase, and before the resolution could occur, especially for the cases with a short disease duration (< - days). in conclusion, the roles of cox- in both pro-inflammation and pro-resolution phases deserves detailed investi-gation. the timing of selective cox- inhibitor therapy in h n infected patients may be extremely critical. therefore a time-dependent study using selective cox- inhibitors on h n -infected animal models will be particularly important in order to address the effectiveness of this drug in treating h n disease. avian antibodies to combat potential h n pandemic and seasonal influenza highly pathogenic avian influenza a virus (hpaiv) strain a ⁄ h n with unprecedented spread through much of asia and parts of europe in poultry remains a serious threat to human health. passive immunization (transfer of protective immunoglobulins) offers an alternative and ⁄ or additional strategy to prevent and cure influenza. here, we report that virus-specific immunoglobulin y (igy) isolated from eggs of immunized hens provide protection in mice against lethal h n virus infection by neutralization of the viruses in the lungs upon intranasal administration. importantly, chicken eggs obtained from randomly selected supermarkets and farms in vietnam, where mass poultry vaccination against a ⁄ h n is mandatory, contain high levels of igy specific for a ⁄ h n virus. when administered before or after the infection, igy prevented and significantly reduced replication and spread of hpaiv h n and related h n strains. thus, the consumable eggs readily available in markets of countries that impose poultry vaccination against a ⁄ h n could offer an enormous source of valuable biological material that provides protection against a ⁄ h n virus with pandemic potential. the approach could be used to control seasonal influenza. since , hpaiv of the h n subtype has resulted in more than cases of laboratory-confirmed human infection in countries with a death rate of more than % (http://www.who.int/csr/disease/avian_influenza/). h n influenza virus remains a global threat because of its continued transmission among domestic poultry and wild birds. passive immunization (the transfer of antigen-specific antibodies (abs) to a previously non-immune recipient host) offers an alternative and ⁄ or additional countermeasure against influenza. development of human monoclonal antibodies (mabs) against h n influenza haemagglutinin (ha) using epstein-barr virus (ebv) immortalization of b cells isolated from patients infected with h n , phage display, humanized mabs, and human recombinant abs has been attempted. chickens produce a unique immunoglobulin molecule called igy that is functionally equivalent to mammalian igg. igy is found in the sera of chickens and is passed from hens to the embryo via the egg yolk. egg igy has been used to prevent bacterial and viral infections (see review ) of the gastrointestinal tract and recently for protection against pseudomonas aeruginosa infection of the respiratory tract of patients with cystic fibrosis (cf). the epidemic of hpaiv h n virus has resulted in serious economic losses to the poultry industry, mostly in southeast asia. therefore, many countries including china, indonesia, thailand, and vietnam have introduced mass vaccination of poultry with h n virus vaccines that controls the h n epidemic to some extent. chickens immunized with recombinant h and ⁄ or inactivated h n reassortant vaccines produced a high level of virus-specific serum antibodies (abs) and were protected from h n virus challenge. theoretically, these abs could be found in egg yolk and separated for use in humans to prevent and cure h n hpaiv infection and disease, respectively. here, we examined the possibility that igy isolated from consumable eggs available in supermarkets in vietnam, where mandatory h n vaccination has been implemented, provide prophylaxis and therapy of hpaiv h n infection in mice. six-to -week-old female balb ⁄ canncrl (h- d) mice (charles river and jackson laboratory) and hy-line . igy abs were extracted from egg yolks as previously described. the % egg infectious dose (eid ) was determined by serial titration of virus stock in eggs, and eid ⁄ ml values were calculated according to the method of reed and muench. human virus stocks were grown in mdck cells as described previously , with viral titers determined by standard plaque assay. the % tissue culture infectious dose (tcid ) of virus was determined by titration in mdck cells. the standard elisa was performed for detection of anti-igy in the sera of igy-immunized mice. fifty percent lethal dose (ld ) titers were determined by inoculating groups of eight mice i.n. with serial -fold dilutions of virus as previously described. for infection, ketamine-anesthetized mice were inoculated intranasally with a lethal dose with pfu ( · ld ) of a ⁄ pr ⁄ ⁄ (h n ) virus as previously described, · ld of vn ⁄ (h n ) or · ld a ⁄ aquatic bird ⁄ korea ⁄ w ⁄ (h n ) resuspended in ll pbs per animal. ketamine-anesthetized mice were treated intranasally with ll of igy before or after infection. mice were observed for weight loss and mortality. subsets of animals were scarified for virus titre. we found comparable hai titers in the sera and egg yolks obtained from a farm in vietnam that was participating in a national mass vaccination program. furthermore we found % of eggs purchased in randomly selected supermarkets in hanoi, vietnam containing h -specific igy. the hai and vn titers of pooled egg yolk igy are comparable with those of sera obtained from hens selected randomly from the farm that underwent supervised h n vaccination. in contrast, igy separated from eggs purchased in korean markets where poultry are not vaccinated against avian influenza h n has no detectable h -specific hai or vn activity. we first treated naïve mice intranasally with h n -specific igy before infection with hpaiv h n strain, a ⁄ vietnam ⁄ ⁄ , isolated from a fatal case. such treated mice displayed mild weight loss and recovered completely by the end of the first week after inoculation ( figure a ). when animals were treated once with h n specific igy after h n inoculation they exhibited minimal weight loss during the first week after inoculation, and virus titers in the lungs were substantial reduced at day after infection; however, % of treated mice succumbed to infection during the second week after inoculation ( figure b) . it is possible that not all the hpaiv a ⁄ h n viruses were neutralized upon the single treatment with igy, and escaping viruses can spread systemically to organs outside of the lungs. these viruses may reappear in lung tissue later when specific igy is absent. indeed, vn ⁄ virus injected intravenously or into the brain can spread to the lungs. to circumvent the virus escape, we administered multiple treatments with h n specific igy after the infection. as a result, all infected mice recovered completely by the second week post-infection ( figure c) , and virus titers in the lungs were substantially reduced to the level that seen in protected mice that received single prior-infection treatment ( figure d) . similarly, the protective efficacy of h n -specific igy was observed in mice infected with lethal dose of mouseadapted avian influenza virus strain a ⁄ aquatic bird ⁄ korea ⁄ w ⁄ (h n ). this virus shares . % nucleotide sequence homology with ha (h ) but has different na (n ) from the one used for mass immunization in vietnam (reassortant avian h n influenza virus a ⁄ goose ⁄ gd ⁄ -derived, strain re- ). the results indicate that h n -specific igy isolated from eggs purchased in markets have preventive and therapeutic effects against infection with hpaiv h n and the related strain h n . the findings suggest that while a single treatment with igy prior to lethal infection was sufficient to protect the animals from the infection, multiple treatment is required for complete therapeutic effect after infection with hpaiv such as vn ⁄ strain. we further examined the protective efficacy of igy isolated from eggs laid by hens immunized in the laboratory with heat-inactivated human influenza a ⁄ h n virus, a ⁄ pr ⁄ ⁄ . we found substantial levels of hai and vn abs in the sera and yolks derived from immunized hens. when naïve mice were administered intranasally with such anti-pr ⁄ igy at - hours before or after infection with lethal dose of pr ⁄ virus, they were protected from the infection or lethal disease, respectively. the virus titers in the lungs of a ⁄ pr specific igy-treated mice at day after infection were also significantly lower than those seen in untreated mice or mice receiving normal igy. intranasal administration is the most effective route as compared to oral or peritoneal or intravenous administration for protection against lethal challenge, and the presence of virus-specific igy in bronchoalveolar lavage (bal) is required for the protection. the results provide a proof-of-concept that intranasal administration of virus-specific igy prevents influenza virus infection and cures the disease. the concept could be applied to control influenza outbreaks including seasonal and pandemic influenza. the protection was correlated with hai and vn activities of the igy and reduced virus titers in the lungs after treatments, suggesting that the protection is mediated by vn. we asked if administration of igy in the respiratory tract induces anti-igy ab response in mice. if this is the case, the next question is whether pre-existing anti-igy abs block igy-mediated protection. indeed, significant levels of anti-igy were observed in animals that received single or multiple administration of igy. when igy-immune mice were treated with virus-specific igy before or after lethal challenge, the results were identical to those obtained from treated naive mice, indicating that pre-existing anti-igy abs do not interfere with the protection mediated by virus-specific igy. consistently, incubation with anti-igy serum did not interfere with hai and vn activity of the virus-specific igy, indicating that anti-igy abs do not block virus binding by virus-specific igy (figure ). the finding suggests that the igy treatment could be applied to persons who have developed anti-igy during the individuals' life, and such treatment strategy could be repeated if multiple treatment is required and ⁄ or necessary later on to protect infections with other pathogens. the approach using specific igy for prevention and therapy of hpaiv h n infection offers a practical alternative to immunotherapy using convalescent plasma and an additional therapeutic option to antiviral drugs since widespread drug resistance has been recently reported among influenza virus strains. igy is relatively stable. we found no change in protective activity after at least months storage at °c, and lyophilization does not affect the activity, making production of igy practical. the use of igy immunotherapy has many advantages, since igy does not activate the human complement system or human fc-receptors, which all are well-known cell activators and mediators of inflammation. we chose the water dilution method for preparation of igy. the method is simple, efficient and does not require any toxic compounds or any additives. such igy preparations by this method have been used in other human study. , eggs are normal dietary components, so there is minimal risk of toxic side effects, except for those with egg allergy. thus, our study demonstrated that influenza virus-specific igy can be used in passive immunization that provides great help for immunocompromised patients and elderly who have weaken immune response to influenza vaccines. importantly, the consumable eggs readily available in the markets of countries that impose mandatory h n vaccination offer an enormous source of valuable, affordable, and safe biological material for prevention and protection against potential h n pandemic influenza. parts of the information and data presented in this manuscript were previously published in http://www.plosone.org/ article/info:doi% f . % fjournal.pone. . the polyphenol rich plant extract cystus is highly introduction the ⁄ h n influenza a virus pandemic clearly demonstrates that influenza is still a major risk for the public health. although the pandemic swine origin influenza a virus (soiv) caused only mild symptoms, the control of the outbreak still remains difficult. even as vaccine is available against this virus, the possibility of reassortment between the pandemic and a seasonal or avian a ⁄ h n influenza virus strain is indeed a frightening, but a likely event. this reassortant strain might be able to transmit easily between humans causing fatal infections, and the current soiv vaccine might no longer be sufficient to protect against the reassorted virus. in such a case, we can only rely on effective antiviral drugs. today, neuraminidaseinhibitors, such as oseltamivir, represent the most common clinically approved medication against influenza a viruses. unfortunately, the frequency of reports describing the appearance of drug-resistant seasonal h n and also h n influenza a viruses dramatically increased in the recent past. [ ] [ ] [ ] [ ] drug resistance to the known antivirals highlights the urgent need for alternative antiviral compounds with novel defense mechanisms. recently, we have reported that a polyphenol rich plant extract, cystus , which showed antiviral activity against influenza a viruses in cell culture and in mice. , moreover, the antiviral activity of cy-stus against seasonal influenza virus and common colds was also demonstrated in humans. however, the efficiency of cystus against soiv and a ⁄ h n isolates was unknown so far. therefore, we investigated cy-stus effectiveness against the pandemic strain and seven natural influenza a ⁄ h n isolates detected in several avian species during ⁄ avian influenza outbreak. additionally, the potency of the most common neuraminidase inhibitor oseltamivir was also investigated against these isolates. here, we show that cystus treatment was effective in in vitro studies against soiv and a ⁄ h n influenza virus. viruses avian h n isolates were originally obtained from the bavarian health and food safety authority, oberschleissheim, germany. the soiv a ⁄ hamburg ⁄ ⁄ was obtained from the robert-koch-institut, berlin, germany. all h n viruses were further propagated in embryonated chicken eggs or mdck ii (h n v) cells at the friedrich-loeffler-institut, tübingen, germany. for the cytopathological effect (cpe) inhibition screening, in accordance with sidwell, mdck ii cells were infected with different viruses at moi of ae . virus-infected cells were then treated with antiviral compounds cystus from ae to lg ⁄ ml or oseltamivir from ae nm to mm. after incubation for hours at °c and % co , cells were fixed, and viable cells were stained with crystal violet. after extraction of crystal violet from viable cells with % methanol, the extinction was measured with an elisa reader. immediately before infection, mdck ii cells ( · cells ⁄ well) were washed with pbs and subsequently incubated with virus diluted in pbs ⁄ ba ( ae % ba) mm mgcl , ae mm cacl , penicillin and streptomycin to a multiplicity of infection (moi) of ae for minutes at °c. cystus was added in a concentration of lg ⁄ ml directly to the virus-stock and on the cell monolayer simultaneously with the infection. after minutes incubation period, the inoculums were aspirated and cells were incubated with either mem or mem containing lm oseltamivir. at indicated time points, supernatants were collected. infectious particles (plaque titers) in the supernatants were assessed by a plaque assay under avicel as described previously. in order to investigate the antiviral potential of cy-stus , ec values based on the inhibition of the cpe on mdck ii cells were determined for cystus and in addition for oseltamivir. the ec values for cystus ranged from ae to ae lg ⁄ ml. cystus demonstrated the highest sensitivity against the soiv, sn and mb isolates with ec values below lg ⁄ ml. compared to these virus strains, cystus showed a slightly increased ec value for gsb ( ae lg ⁄ ml). in contrast the ec values for bb and bb were notably elevated ( ae and ae lg ⁄ ml). thus, the weakest antiviral effect of cystus was observed against these two isolates. the ec values evaluated for oseltamivir ranged from ae to ae lm ( table ), indicating that bb ( ae ) and gsb ( ae lm) can be considered resistant against oseltamivir. to confirm these results we investigated the ability of cystus to block virus replication as published before. as a control, virus infected cells were treated with oseltamivir as described earlier. in the absence of the drugs all influenza strains showed similar growth properties (figure , black squares) . first progeny viruses were detectable between and hours post infection (figure , black squares) . treatment with cystus resulted in reduction of virus titers of all influenza virus strains (fig. a-h, open triangles) . surprisingly, oseltamivir failed to inhibit the replication of two h n influenza virus strains (gsb and bb ), supporting the data of ec values ( figure d+h , grey rhombes). we assessed the antiviral activity of cystus against the newly emerged soiv and seven avian h n influenza viruses. cystus showed efficient antiviral activity against the pandemic h n v strain and was effective to a wide range of h n viruses. furthermore, cystus demonstrated a broader and more efficient antiviral potential than oseltamivir. cystus treatment leads to a stronger reduction of progeny virus titers, and more importantly, cystus was effective against all tested viruses, while oseltamivir was unresponsive against two of seven a ⁄ h n viruses. even though the pandemic strain in general is still sensitive to oseltamivir treatment, there are increasing numbers of reports of emerging resistant variants. the treatment with cystus does not result in the emergence of viral drug resistance since the mode of action is an unspecific physical binding of the virus particle that is also beneficial to reduce opportunistic bacterial infections. , , cystus is an extract from a special variety of the plant cistus incanus, and it is very rich in polymeric polyphenols. it is well known that polyphenols exhibit protein-binding capacity. however, cystus exhibited no neuraminidase inhibiting activity. therefore, ingredients of cystus may act in a rather unspecific physical manner by interfering with the viral hemagglutinin at the surface of the virus particle as demonstrated before. while this prevents binding of the virion to cellular receptors, it does not block accessibility and action of the viral neuraminidase. since, infections with influenza a viruses are still a major health burden and the options for control and treatment of the disease are limited, plant extracts such as cystus should be considered as a new candidate drug for a save prophylactic and therapeutic use against influenza viruses. attenuation of respiratory immune responses by antiviral neuraminidase inhibitor treatment and boost of mucosal immunoglobulin a response by co-administration of immuno-modulator clarithromycin in paediatric influenza the antiviral neuraminidase inhibitor osv and zanamivir are widely used treatment options for influenza infection and are being stockpiled in many countries. although mucosal immunity is the frontline of defense against pathogens, the effects of neuraminidase inhibitor treatment on airway mucosal immunity have not been reported. the suppression of viral rna replication and viral antigenic production by these drugs may result in a limited immune response against influenza virus. macrolides, such as cam and azithromycin, have anti-inflammatory and immunomodulatory properties that are separate from their antibacterial effects. [ ] [ ] [ ] this study examined the impact of osv treatment on immune responses in the airway mucosa and plasma in mice infected with iav and pediatric influenza patients. we also assessed the immuno-modulatory effects of cam in influenza patients who were treated with or without osv. female ae -week-old weanling balb ⁄ c mice were nasally inoculated with pfu of iav ⁄ pr ⁄ h n at day . immediately after infection, mice were given lg of osv orally or vehicle at -hours intervals for days. the levels of virus-specific siga in nws and bronchoalveolar fluids (balf) and igg in plasma were measured by elisa as reported previously. a retrospective clinical study was conducted. for the study, children with acute influenza were recruited and grouped according to the treatment received: days treatment with osv (n = ), cam (n = ), osv + cam (n = ), and untreated (n = ). since parents in japan are well aware of the adverse effects of osv especially the neuropsychiatric complications, the decision on whether to administer osv or not and to prescribe cam was made by the parents and the attending paediatricians, based on their anti-viral and immuno-modulatory activity. , comparisons were made of the levels of siga against iav ⁄ h n and iav ⁄ h n , total siga, in nws and disease symptoms before and after treatment. anti-ha siga and total siga in nws of patients were determined from the standard regression curves with human iga of known concentration in a human iga quantitation kit (bethy laboratories). because an affinity purified human anti-ha-specific siga standard of each influenza a subtype is not available, the relative value of anti-haspecific siga amount was expressed as unit (u). one unit was defined as the amount of one lg of human iga detected in the assay system as reported previously. the concentrations of siga in individual nws were normalized by the levels of total siga (lg ⁄ ml). oseltamivir suppresses viral rna replication and viral antigenic protein production. to investigate the influence of daily treatment with osv on ha-specific mucosal and systemic immune responses, we analyzed ha-specific siga levels in nws and balf as well as igg levels in plasma at days and post-infection in mice treated orally with osv or methylcellulose (mc) as vehicle. the osv treated mice showed lower antibody responses in nws and balf than control mice treated with mc solution (table ) . significantly reduced ha-specific siga responses were particularly noted in the osv group at day , the period of maximal mucosal siga induction. the airway secretions and plasma from mice at day did not contain detectable levels of ha-specific antibodies. these findings were supported by other data whereby mice treated with osv displayed significantly lower numbers of ha-specific iga antibody-forming cells (afcs) in the nasal lamina propria, mediastinal lymph nodes, and lungs compared with mc-treated mice. these results clearly indicate that oral administration of osv downregulates ha-specific siga responses in mucosa. on the other hand, there were no significant differences in the elevated levels of ha-specific plasma iga and igg antibodies or the increased numbers of ha-specific iga and igg afcs in the spleen between osv-and mc-treated mice. taken together, these results implicated the oral administration of osv in a suppressed induction of haspecific siga responses in respiratory lymphoid tissues, although systemic ha-specific antibody responses were not significantly affected by osv. since cam up-regulates il- , a mucosal adjuvant cytokine in the airways, and promotes the induction of siga and igg in the airway fluids of mice infected with iav, , we assessed the impact of treatment with osv and ⁄ or cam on the levels of anti-influenza siga in nws and clinical status of influenza patients. the concentration ratio of table . anti-ha-specific siga to total siga in nws was expressed as titer: anti-ha-specific siga (u ⁄ mg) ⁄ total siga (lg ⁄ mg) · . figure shows changes in the anti-ha(h n ) siga ratio (titer) and fold of increase in siga titer in each patient during the -days' treatment for the four different treatment groups. it is noteworthy that, upon admission to the hospital, the siga titers were < in % of patients. during the days of treatment, rapid increases in the titers were observed in almost all patients in cam, osv + cam, and no treatment groups. in contrast, in the osv group, the anti-ha-specific siga titers remained unchanged or decreased in the majority of patients. the finding of significant low induction of anti-viral siga in the osv group was supported by the results of animal experiments. however, the addition of cam to osv augmented siga production and restored mucosal siga levels; % of patients treated with osv + cam showed > -fold increase in the titers during treatment. these observations suggest that cam stimulated the local mucosal immunoresponse in the nasopharyngeal region of patients treated with osv. the prevalence of disease manifestations was also analyzed. among the symptoms listed, a significant decrease in the prevalence of cough was recorded between the no treatment group and the osv + cam group and between the osv group and the osv + cam group (**p < ae ), despite the limited number of patients in each group. the duration of the febrile period was significantly shorter in the osv and osv + cam groups than the no treatment group. however, no significant difference was observed between the osv group and osv + cam group. it has been reported that osv does not affect the cellular immune responses, such as cytotoxic t lymphocytes and natural killer cells. however, the effects of osv on mucosal immunity have not been studied so far. the present study showed that osv treatment of mice infected with iav induced insufficient protective mucosal siga responses in the respiratory tract, although treated mice showed the similar levels of systemic igg and iga antibody responses in plasma to those in mice treated with vehicle (table ) . the observed effect of osv on mucosal immunity was probably due to a suppression of viral replication and viral antigen production in the mucosal layer. these observations in mice are further supported by our clinical reports of siga in nws and balf of osv treated influenza patients. the membered-and membered-ring macrolides have been found to possess a wide range of anti-inflammatory and immuno-modulatory properties, , and to be effective in the treatment of respiratory syncytia and iav infection. , the efficacy of low doses administered on the long term against pathogens that are insensitive to macrolides indicates a mode of action that is separate from their antibacterial activity. , , , in the present study, we evaluated the immunomodulatory effects of cam on mucosal immune responses in pediatric influenza. a decrease in the proportion of total siga that was anti-ha-specific siga during treatment was observed in . % of patients in the osv group (those represented by the dotted lines and closed diamonds in figure ), whereas an increase in the proportion was observed in most patients of the other groups (except for one patient of the untreated group). despite the low or unchanged induction of anti-ha-specific siga in the majority of osv-treated patients, the additional use of cam with osv boosted the mucosal immune response and restored local mucosal siga levels. we are currently engaged in detailed immunological studies of the effects of cam and osv on the levels of mediators controlling iga class switching in nws of influenza patients and airway secretion of mice infected with iav. further studies should clarify the boost mechanisms of cam and the suppression mechanisms of osv in iga class switching. our findings suggest the risk of re-infection in patients showing a low mucosal response following osv treatment and cam effectively boosts the siga production for protection of re-infection. to date there is an urgent need to develop new antivirals against influenza. most of the molecules reported target influenza proteins that acquire rapid mutations of resistance. the development of new molecules that have a broad antiviral activity and are not subjected to influenza mutation is of particular interest. our laboratory and others recently showed that proteases can participate to the innate immune response in the airways through the activation of a family of receptors called par. in particular, through the release of interferon, par agonists curbed viral replication significantly in infected cells. in this study, since erk activation is crucial for virus replication, we investigated whether par could inhibit virus replication through inhibition of the erk pathway. results showed that while influenza a infection alone or par stimulation alone induced erk activation, par stimulation does not inhibit erk activation in influenza infected cells. thus, par agonists may be a potential new drug against influenza viruses that could be used in combination with other anti flu therapy such as the inhibition of the erk pathway. respiratory tract-resident proteases are key players during influenza virus type a infection. , in addition to their direct activating effect on surface viral proteins, lung mucosal proteases can regulate cellular processes by their ability to signal through protease-activated receptors (pars). after cleavage of the receptor by proteases, the new aminoterminal sequence of par binds and activates the receptor internally. these receptors are highly expressed at epithelial surfaces, in particular in the lung, where human influenza virus replicate in vivo. pars are thus directly exposed to proteases present in the airways. among the four different pars, par acts as an antiviral through an interferondependent pathway. , thus, agonists of par are potential new drugs against a broad range of influenza viruses, which is in accordance with the broad antiviral action of interferon. however, the signalling pathway induced by par agonists in influenza a infected cells has still to be investigated. in this manuscript, we showed that influenza infection or activation of par induced erk activation, a crucial step for efficient virus replication. , however, par agonists do not impaired erk activation in influenza a virus infected cells. since the pathway of par protection is likely to be erk-independent, the use of anti erk molecules in combination with par agonists maybe of potential interest in future anti-influenza therapy. influenza viruses a ⁄ wsn ⁄ (h n ) (a kind gift from nadia naffakh) was used in the present study. mdck (madin-darby canine kidney) and the human alveolar type ii a cell were obtained from atcc and grown as previously described. for western blot analysis, the following antibodies were used: monoclonal antibody for phospho-erk ⁄ (t ⁄ y ) and for erk ⁄ antibodies from cell signaling technology (beverly, ma), horseradish peroxydase (hrp)-coupled rabbit polyclonal antibodies against mouse or rabbit igg from paris (compiègne, france). a cells were infected with iav at an moi of in emem medium, as previously described. , at various time points post infection, cells were collected and proteins were analysed as previously described. , par stimulation was performed at °c in emem medium as previously described. after infection and ⁄ or stimulation, cells were lysed in ice-cold lysis buffer. lysates were centrifuged at g for min, and total proteins of the supernatants were analyzed by western blot analysis as previously described. , results since activation of the erk pathway is essential for efficient influenza replication, we first investigated the kinetics of erk activation after influenza infection in human a alveolar epithelial cells. for this purpose, a cells were infected with influenza viruses at a moi of at different time point post-infection, and activation of erk ⁄ pathway was assessed by western blot analysis using an anti-erk antibody. results showed that erk was phosphorylated after influenza infection in a time course depen-dent manner when compared to uninfected cells. in contrast, erk phosphorylation was not observed with heatinactivated viruses, suggesting that productive infection is needed for erk activation ( figure a ). antibodies against erk ⁄ were used as controls. since erk is activated after influenza infection, we then tested whether activation of par in uninfected cells also leads to activation of this pathway. for this purpose, a cells were stimulated with the selective human (h) or mouse (m) par agonist or a control peptide for the indicated time ( figure b ). when exposed to the par agonists and compared to controltreated cells, erk phosphorylation increased over the time course of stimulation. thus, influenza infection or stimulation of par without infection in a cells induced activation of the erk pathway at different time point post-infection. since influenza infection and par stimulation induced erk activation, we then investigated whether par could inhibit erk activation in influenza infected a cells. results in figure showed that in influenza infected cells, par activation for ten minutes does not inhibit erk activation after influenza infection. thus, erk activation is not inhibited by par activation in influenza stimulated cells. in this manuscript, we studied the activation of the erk pathway after par stimulation and or influenza infection. particularly interesting is the fact that either influenza infection or par stimulation alone induce erk phosphorylation in a epithelial cells, while erk activation is not inhibited in a infected cells compared to uninfected ones after par stimulation. proteases are key factor in the pathogenicity of influenza viruses. in addition to the cleavage of ha, necessary for iav replication, extracellular proteases also play a role in the modulation of the immune system against influenza viruses through the activation of pars. particularly par , activated by extracellular trypsin-like proteases, could inhibit virus replication through the release of interferon, , thus, strengthening the immune system via agonist peptides and providing new therapeutic potential against a broad range of influenza strains. in addition, targeting the host instead of the virus could provide a way to escape from virus resistance. thus, a better understanding of how virus escapes from immune surveillance may provide new therapeutic strategies to block iav. in addition, combinations of drugs that block virus replication via different pathways are of interest. the non classical molecules hla-g maybe an interesting new target as we recently showed that it is upregulated after influenza infection, and it is a well known immunotolerant molecule. indeed, it inhibits the innate immune response as well as the adaptive immune response. , also, as previously suggested, the erk signal transduction cascade is also of potential interest since it is crucial for virus replication and particularly influenza replication. , as shown here, it is unlikely that par protection occurs through an erkdependent pathway. thus strengthening the immune response with par agonists and blocking nuclear retention of the viral ribonucleoprotein complexes with inhibitors of the mek ⁄ erk pathway may be alternative combinatory approaches for influenza therapy. in addition, since those potential drugs target the host instead of the virus, this could help in the design of new antivirals molecules more resilient to iav mutations and thus to virus resistance. the initial waves of the first influenza pandemic of the st century have passed. in june , vaccine companies estimated they could produce in months almost . billion doses of pandemic vaccine. instead, they actually produced only million doses, of which % were non adjuvanted preparations. had these doses been produced with adjuvants (i.e., . lg instead of lg ha per dose), an additional billion doses could have been made available. yet there was public opposition to adjuvants in many countries, especially by regulatory officials in the united states. misperceptions about the safety of both adjuvanted and nonadjuvanted vaccines were widespread. added to this, shortfalls in vaccine production, delays in vaccine delivery, and the ''mildness'' of the pandemic itself meant that only a few countries achieved reasonable levels of vaccine coverage. millions of doses went unused and had to be destroyed. supplies of antiviral agents were even more limited. thus, despite the best efforts of influenza scientists, health officials, and companies, more than % of the world's people did not have timely access to affordable supplies of vaccines and antiviral agents. instead, they had to rely on th century public health ''technologies.'' given current understanding of biology in the early st century, they should have had -and probably could have had -something better. this report reviews evidence for an alternative approach to serious and pandemic influenza that could be used in all countries with basic health care systems. instead of confronting the influenza virus with vaccines and antiviral agents, it suggests that we might be able to modify the host response to influenza virus infection by using anti-inflammatory and immunomodulatory agents. this idea was introduced several years ago and has been reviewed in several publications. [ ] [ ] [ ] [ ] [ ] [ ] the central importance of the host response in the pandemic, young adults had high mortality rates. ever since, influenza virologists have sought to answer the question ''why did young adults die?'' by defining the molecular characteristics of the virus that were responsible for its virulence. in doing so, they have overlooked a crucial piece of clinical evidence from the pandemic: compared with young adults, children were infected more frequently with the same virus, yet they seldom died. consequently, the more important question is ''why did children live?'' this can only be explained by recognizing that children must have had a different host response to the influenza virus than adults. physicians have long recognized that for several other medical conditions, both infectious (e.g., pneumococcal bacteremia) and non-infectious (e.g., multiple trauma), children have a more benign clinical course than adults. , a corollary of this observation is that secondary bacterial pneumonia, although commonly found in young adults in , could not have been the primary cause of death. children must have had the same or higher rates of nasopharyngeal colonization with the same bacteria that were associated with pneumonia deaths in adults, yet children seldom died of secondary bacterial pneumonia. if young adults died with secondary bacterial pneumonia, underlying host factors must have made them more susceptible. few people who die of influenza do so during the first few days of illness when pro-inflammatory cytokine levels are high. instead, like patients with sepsis, they usually die in the second week, when anti-inflammatory cytokines and immunosuppression dominate. , , influenza deaths occur more frequently in older persons with cardiopulmonary conditions, diabetes, and renal disease, but as seen in the h n pandemic, they also occur in younger adults with obesity, asthma, and in women who are pregnant. regardless of age, people with all of these conditions share one characteristic in common: they have chronic low-grade inflammation. in effect, their ''innate immune rheostats'' have been set at different, and perhaps more precarious, levels that make them more vulnerable to influenza-related complications. laboratory studies of influenza virus infection confirm the importance of the host response. in several studies in mice in which the host response has been modified (e.g., cytokine knockout), survival has been improved without increasing virus replication in the lung. in fact, severe disease can be induced without any influenza virus replication. for example, fatal acute lung injury has been induced in mice by inactivated (not live) h n virus. in this model, antiviral agents would be useless; only the host response could be responsible for disease. these observations raise the following question: could the host response be modified so patients with severe seasonal and pandemic influenza might have a better chance of surviving? influenza is associated with acute coronary syndromes, and influenza vaccination and statins reduce their occurrence. these associations led to the suggestion in that statins might be used to treat pandemic influenza. other agents that might also be effective include ppara and pparc agonists (fibrates and glitazones, respectively) and ampk agonists (e.g., metformin). , these agents have been studied in laboratory models of inflammation, sepsis, acute lung injury, ischemia ⁄ reperfusion injury, energy metabolism, mitochondrial function, and programmed cell death. the results of these studies cannot be reviewed in detail here, but the major findings for cell signaling are summarized in the table . unfortunately, the results of experimental studies are not always clear cut. for example, in one study of influenza virus infected mice, il- was necessary for containing infection, but in another study il- appeared to be harmful. nonetheless, overall understand-ing of cell signaling pathways in influenza virus infections and the actions of statins, glitazones, fibrates, and ampk agonists strongly suggest that these agents could benefit patients with severe influenza. laboratory studies in mice infected with pr (h n ) h n and pandemic h n viruses show that resveratrol, fibrates, glitazones, and ampk agonists reduce mortality by - %, often when treatment is started - days following infection. - (resveratrol is a polyphenol found in red wine. it shares with these other agents many of the same cell signaling effects.) in h n -infected mice, treatment with celecoxib and mesalazine, together with zanamivir, showed better protection than zanamivir alone. remarkably, these immunomodulatory agents have not increased virus replication. even more remarkable, in another model of a highly inflammatory and frequently fatal conditionhepatic ischemia ⁄ reperfusion injury -glitazone treatment ''rolled back'' the host response of ''young adult'' mice ( - weeks old) to that of ''children'' ( - weeks old). this unique study suggests that immunomodulatory treatment might roll back the damaging and sometimes fatal host response of young adults with influenza to the more benign and rarely fatal response of children. several, but not all, observational studies have shown that outpatient statins decrease hospital admissions and mortality due to community-acquired pneumonia. for influenza itself, preliminary evidence presented in october suggests that immunomodulatory treatment of influ- table . cell signaling targets that might be affected by immunomodulatory treatment of severe seasonal and pandemic influenza* down regulate pro-inflammatory cytokines (e.g., nf-kappab, tnfa, il- , il- ) up regulate anti-inflammatory cytokines (il- , tgfb) up regulate pro-resolution factors (lipoxin a , resolvin e ) up regulate ho- and decrease tlr signaling by pamps and damps up regulate enos, downregulate inos, restore inos ⁄ enos balance and stabilize cardiovascular function decrease formation of reactive oxygen species and decrease oxidative stress improve mitochondrial function and restore mitochondrial biogenesis decrease tissue factor and its associated pro-thrombotic state stabilize the actin cytoskeleton in endothelial cells and intracellular adherins junctions, and thereby increase pulmonary barrier integrity and decrease vascular leak differentially modify caspase activation and apoptosis in epithelial and endothelial cells, macrophages, neutrophils and lymphocytes in the lung and other organs increase the bcl- ⁄ bax ratio in influenza virus-infected cells and prevent the apoptosis necessary for virus replication. *see references , , , for details. nf-kappab, nuclear factor kappab; tnfa, tumor necrosis factor alpha; tgfb, transforming growth factor beta; ho- , heme oxygenase - ; tlr, toll-like receptor; pamp, pathogen-associated molecular pattern; damp, damage associated molecular pattern; enos, endothelial nitric oxide synthase; inos, inducible nitric oxide synthase. enza patients with severe illness could be beneficial. in a study of almost patients hospitalized with laboratoryconfirmed seasonal influenza, inpatient statin treatment reduced hospital mortality by %. in these patients, the cell signaling effects of statin treatment, summarized in the table , probably acted to reduce pulmonary infiltrates, maintain oxygenation, stabilize myocardial contractility and the peripheral circulation, reverse immunosuppression, restore mitochondrial biogenesis, and prevent multi-organ failure. achieving these clinical effects led to a decrease in mortality. because of the molecular cross-talk between statins, fibrates, glitazones, and ampk agonists, , similar clinical benefits might be expected from other members of this ''family'' of immunomodulatory agents. simvastatin, pioglitazone, and metformin are produced as inexpensive generics in developing countries. they are used throughout the world in the daily treatment of millions of patients with cardiovascular diseases and diabetes. global supplies are huge. because most people with influenza recover without specific treatment (this was true in ), not all patients would require immunomodulatory agents. instead, only those at risk of ards, multi-organ failure, and death would need to be treated. importantly, the cost of treatment for an individual patient would be less than $ . (d.s. fedson, unpublished observations). moreover, unlike vaccines they could be used on the first pandemic day. thus far, influenza scientists and the institutions that support their work (e.g., nih and cdc, national health agencies in many countries, the bill and melinda gates foundation, the welcome trust, and the world health organization) have shown little interest in immunomodulatory treatment. nonetheless, when more than % of the world's people have no access to influenza vaccines and antiviral agents, their physicians must have access to an effective ''option,'' especially one that might be lifesaving. research on immunomodulatory agents for influenza must involve investigators in many fields outside influenza science -those with expertise in the molecular and cell biology of inflammation, immunity, sepsis, cardiopulmonary diseases, endocrinology and metabolism, ischemia ⁄ reperfusion injury, mitochondrial function, and cell death. laboratory studies needed to identify promising treatment agents would probably cost $ - million (d.s. the results of these studies would inform clinical trials that critical care physicians are already eager to undertake. , this work will be especially important for people in developing countries where critical care capacity is extremely limited and not likely to improve. like critical care physicians, influenza scientists too must recognize that they cannot afford not to undertake research to determine whether generic immunomodulatory agents might be useful in managing severe seasonal and pandemic influenza. the nf-kappab-inhibitor sc efficiently blocks h n influenza virus propagation in vitro and in vivo without the tendency to induce resistant virus variants introduction influenza is still one of the major plagues worldwide. the appearance of highly pathogenic avian influenza (hpai) h n viruses in humans and the emergence of resistant h n variants against neuraminidase inhibitors highlight the need for new and amply available antiviral drugs. we and others have demonstrated that influenza virus misuses the cellular ikk ⁄ nf-kappab signalling pathway for efficient replication, suggesting that this module may be a suitable target for antiviral intervention. here, we show that the novel nf-kappab inhibitor sc efficiently blocks replication of influenza a viruses, including avian and human a ⁄ h n isolates in vitro in concentrations that do not affect cell viability or metabolism. in a mouse infection model with hpai a ⁄ h n and a ⁄ h n viruses, we were able to demonstrate reduced clinical symptoms and survival of sc treated mice. moreover, influenza virus was reduced in the lung of drug-treated animals. besides this direct antiviral effect, the drug also suppresses h n -induced overproduction of cytokines and chemokines in the lung, suggesting that it might prevent hypercytokinemia we hypothesise to be associated with pathogenesis after infections with highly pathogenic influenza viruses, such as the a ⁄ h n strains. thus, a sc -based drug may serve as a broadly active nontoxic anti-influenza agent. to assess the number of infectious particles (plaque titers) in organs a plaque assay using avicel Ò was performed in -well plates as described by mastrosovich and colleagues. virus-infected cells were immunostained by incubating for hour with a monoclonal antibody specific for the influenza a virus nucleoprotein (serotec) followed by minutes incubation with peroxidase-labeled anti-mouse antibody (dianova) and minutes incubation with true blueÔ peroxidase substrate (kpl). stained plates were scanned on a flat bed scanner and the data were acquired using microsoft Ò paint software. the virus titer is given as the logarithm to the basis of the mean value. the detection limit for this test was < ae log pfu ⁄ ml. organs of infected and control mice were homogenized and incubated over night in ml trizol Ò reagent (invitrogen) at °c. total rna isolation was performed as specified by the manufacturer (invitrogen). rna was solubilised in ll rnase free water and diluted to a working concentration of ng rna ⁄ ll. reverse transcription real-time pcr was performed using quantifastÔ sybr Ò green rt-pcr kit and quantitect primer assays (qiagen) . all samples were normalized to gapdh and fold expression analyzed relative to uninfected controls. ct values were obtained with the smartcycler Ò (cepheid). to answer the question whether the nf-kappab inhibitor sc shows antiviral properties against influenza virus, h n infected mdck cells were treated with different concentrations of the inhibitor (figure ). already treatment with nm of sc led to a reduction of viral cpe of more than %. almost % protection of cells was achieved when cells were treated with lm sc . the results indicated that sc has antiviral properties at concentrations ranging from to nm. we next tested whether sc would also be effective in the mouse model of influenza virus infection. when h n mice were treated i.v. once daily for days with mg ⁄ kg sc , survival rate of the animals increased significantly (p < ae ). the same results were found when h n influenza virus infected mice were treated i.p. with mg ⁄ kg sc (data not shown). moreover, sc treatment was not only effective when the inhibitor was given prior to h n influenza virus infection, but also in a therapeutic setup when sc was applied to the animals days after infection (data not shown). since influenza virus infected mice showed increased survival after lethal infection, we next questioned whether the amount of influenza virus was reduced in the lung. therefore, we performed quantitative real-time (qrt) pcr to detect viral mrna. mice were treated with either sc or the solvent, and hour later the lungs were prepared to perform qrt-pcr. as shown in figure a the amount of viral mrna was reduced by % in sc treated mice compared to solvent treated controls, indicating that sc leads to a reduced expression of h n specific mrna in the lung of infected mice. since infection of mice with h n leads to hypercytekinemia, we also investigated the expression of cytokines in sc treated mice. as shown in figure b the amount of il- specific mrna was drastically reduced in sc treated mice compared to solvent treated controls. moreover, also the expression of ip- was altered in sc treated h n influenza virus infected mice. here, roughly % reduction of specific mrna was detectable ( figure c ). thus, sc leads to a reduced transcription of il- and ip- in h n infected mice. there is an urgent need for new concepts to develop antiviral drugs against influenza virus. targeting cellular factors is a promising but challenging approach, and the concerns about side effects are obvious. however, it should be considered that drugs targeting viral factors, such as amantadine or oseltamivir, also exhibit a wide range of side effects in patients. thus, drug safety has to be rigorously tested in clinical trials regardless whether a drug targets a cellular or a viral factor. moreover, resistance against human h n influenza viruses and highly pathogenic avian h n virus strains to oseltamivir and amantadine have been reported. in that respect, the strategy to target cellular factors , might be one way to ensure that new drugs against influenza virus will be useful and effective for a long time without causing the development of resistant virus variants. we were able to demonstrate that the nfkappab inhibitor sc is able to reduce influenza virus activity in cell culture. moreover, the compound was also effective against highly pathogenic avian influenza viruses of the h n and h n subtypes in the mouse model. next to the reduction of virus sc was also able to reduce h n -induced overproduction of cytokines and chemokines in the lung in the lung of mice after infection with h n . most importantly, the drug did not show any tendency to induce resistant virus variants (data not shown). thus, a sc based drug may serve as a broadly active non-toxic antiinfluenza agent. [ ] [ ] [ ] [ ] [ ] in hong kong, the first confirmed case was a tourist from mexico reported on may , . the local government made its first attempt to contain the spread of h n in the local community by closing the metropark hotel where that tourist was staying, and quarantining guests and staff for days. following identification of the first local case around weeks later on june , , the government closed all kindergartens and primary schools from june until early july. fever clinics were also opened, the alarm levels in hospitals were raised to the highest, and a public education campaign was implemented. previous studies of the community responses to severe acute respiratory syndrome (sars) and human-to-human h n avian flu identified the importance of understanding the background perceptions of risk and psychological impact on the community. [ ] [ ] [ ] [ ] [ ] in this study we investigated the psychological and behavioral responses of the general local community throughout the first wave of ph n , and we also examined the factors associated with greater use of preventive measures. a total of surveys were conducted between april and november , covering the entire first wave of the ph n pandemic. computer generated random-household telephone numbers from all land-based local telephone numbers covering over % of hong kong households were used to recruit a total of local adults. one cantonese-speaking adult (age ‡ ) was invited for interview in each selected household on the basis of a kish grid. the survey instrument was based on previous experience in sars and avian influenza projects. information, including knowledge on modes of transmission, psychological responses to pandemic influenza, preventive behaviors, attitudes towards the new vaccines and socio-demographics, was collected. informed consent was obtained prior to the interview. ethics approval was obtained from the institutional review board of the university of hong kong. descriptive statistics were weighted by sex and age based on the reference population data provided by the hong kong government census and statistics department. multivariable logistic regression analyses were used to examine the association between the use of preventive measures and knowledge, perceptions and behaviors, sociodemographic characteristics, and psychological responses to pandemic influenza. multiple imputation was used to cope with a small proportion of missing data and make the best use of all available data. statistical analyses were conducted in r version . . (r development core team, vienna, austria). twelve thousand and nine hundred and sixty-five local adults were recruited throughout the study period, with a total of telephone calls being made; the response rate among eligible participants was . %. hong kong entered the containment phase after the world health organization (who) announced a global alert, and policies including border screening, tracing, and quarantine of doi: . /j. - . . .x www.influenzajournal.com suspected cases were implemented. hong kong transitioned to the mitigation phase on june , when the first local case was reported. the chronology of these and other events plus the epidemic curve of laboratory-confirmed ph n cases are shown in figure (a) . the anxiety scores and risk perception of the respondents are shown in figure (b,c) . anxiety, measured by the state trait anxiety inventory, remained steady throughout the study period. in response to the announcement made by who and the unknown nature of the new virus, a higher proportion of the respondents expressed worry (more, much more, or extremely more worried than normal) if developed ili and perceived ph n severity (same, more, or much more serious than sars) initially in early may . fewer respondents reported worry if they developed ili as the pandemic proceeded, with a slight perturbation around the first deaths in july and a steady decline to . %, while perceived severity of ph n declined more dramatically after an early high. perceived risks of infection of respondents (absolute susceptibility) and risk relative to others (relative susceptibility) were also investigated and found to remain relatively stable throughout the first wave, with no indication of an increase during the period of peak ph n activity in september (figure c) . as the first wave of ph n progressed, knowledge on modes of transmission did not improve. on the contrary, later in the epidemic increasing proportions of respondents reported oral-fecal and cold weather as modes of transmission of ph n . around - % of the respondents did not recognize direct and indirect contact or touching infected persons and contaminated objects as transmission routes for ph n throughout the first wave ( figure d ). higher proportions of respondents avoided crowded places and rescheduled travel plans in the second half of june when local kindergartens and primary schools were closed and the first ph n -associated deaths were announced. social distancing measures such as avoiding crowded places and rescheduling travel plans remained stable with slightly decreasing trends thereafter. the use of hygiene measures and other social distancing strategies was relatively stable with slightly decreasing trends during the study period ( figure ). female sex and older age were generally associated with greater reported use of hand hygiene measures, home disinfection, avoidance of crowded places, and rescheduling of travel plans. female sex was also positively correlated with use of face masks and cough etiquette. we found a negative correlation between anxiety and use of all hand hygiene measures and cough etiquette, but a positive correlation between anxiety and use of home disinfection and (c) proportion of the respondents reporting higher worry if developed flu-like symptoms (more, much more, or extremely worried), higher perceived seriousness of h n compared to sars (much more or more severe), higher probability to contract h n over the next month (certain, much more, or more likely), higher probability to contract h n over the next month compared to others outside family (certain, much more, or more likely). (d) proportion of the respondents identifying possible modes of transmission as the actual modes of transmission of h n . social distancing measures. other significant factors contributing to greater use of preventive measures were worry and knowledge. greater worry was associated with higher probability of home disinfection, social distancing measures, and use of face masks. knowledge that h n could be spread by indirect contact was associated all the investigated preventive measures, and knowledge that h n could be spread by droplets was associated with cough etiquette, but not face masks. there were no consistent trends between all the investigated preventive measures and absolute and relative susceptibility. community transmission emerged in hong kong in mid-june , and prior to emergence of community transmission, perceived risk and perceived severity were high. as ph n spread in hong kong, risk perception declined, even at the same time as incidence was increasing. anxiety was low throughout, at around . on the -point scale, compared to a maximum of . during sars on the same scale. anxiety has been showed to be positively correlated to personal hygiene measures and social distancing in previous studies; , however, we found a negative correlation between anxiety and use of all hand hygiene measures, cough etiquette, and face masks, and a positive correlation between anxiety and home disinfection. the differences in findings may be due to the fact that our anxiety measure was not specific to h n , and the score could be affected by other factors including economics. unlike hygiene measures, higher anxiety level, greater worry, and higher risk of perception were all associated with more social distancing. , , , social distancing is the most direct strategy in avoiding infection from other people, and it is commonly observed in an outbreak that the general public avoids crowded places, travelling to other countries, and social gatherings, , but the economic impact could be substantial. as community incidence of h n peaked, we did not observe any increase in use of preventive measures (figure ) . we found that face mask use peaked at the early stage of the pandemic, while hand hygiene remained fairly constant, and the knowledge on the modes of transmission of ph n did not improve over time. the lack of substantial change in preventive measures or knowledge about the modes of ph n transmission in the general population suggests that community mitigation measures played little role in mitigating the impact of ph n in hong kong. on the other hand, knowledge that ph n could be spread by indirect contact was associated with all of the preventive measures studied. consistent with reports during the sars period, , this study also showed that females and those of older age were more likely than others to use hygiene measures, avoid crowded places, and reschedule travel plans. this study has some limitations. first, this was a crosssectional study that was carried out at different time points, rather than a longitudinal study following the same individuals over time, and so the inferences on changes in behavior may need to be interpreted more cautiously. second, we recruited samples from all land-based local telephone numbers that cover % of hong kong households, but the response rate was not high enough to guarantee a representative sample, and this could be a source of selection bias. third, the responses were self-reported, and this may lead to social desirability bias in estimating knowledge, attitudes, and preventive behaviors. fourth, since the hong kong population has previously gone through unique experiences from sars in and avian flu in , our results may not be comparable to other countries or settings. in conclusion, this study revealed that the ph n pandemic failed to generate an increase use of preventive measures in the local community. there was no association between anxiety level and the events of the pandemic. with a relatively low mortality and morbidity rates compared to sars, ph n was not a matter of concern in the hong kong community. the lack of substantial change in the use of preventive measures and improvement in knowledge on the modes of transmission of ph n suggested that public health campaigns during the pandemic may not have had substantial effects on the general public. london is a major tourist destination, the seat of government and finance in the uk, and in will host much of the olympic and paralympic games. along with the rest of the global community, in and early london faced the challenges of responding to the first pandemic of the st century. at the time, nhs in london was composed of organisations, including the london ambulance service, acute hospitals, mental health and primary care trusts, and the strategic health authority. while london's nhs is well practiced at responding to large, big bang incidents, the influenza a ⁄ h n v pandemic was a rising tide event that lasted many months. significant preparatory work had been undertaken prior to april , which meant that the nhs in london was ready to respond. nhs london (the strategic health authority for london) led the response in partnership with local managers in all nhs organisations. the first uk cases of influenza a ⁄ h n v were reported in scotland on april, with the first in london on april. cases continued to increase, and the first wave peaked in london in july. cases reduced over the school summer holidays, but increased again when children returned to school at the start of september, and a second, smaller wave occurred. it is essential that the nhs learns from the ⁄ influenza a ⁄ h n v pandemic to ensure it is prepared for future challenges. nhs london provided a standardised debriefing pack to all nhs organisations in the region to identify, capture, and learn lessons. each debrief event involved health and inter-agency partners to ensure all viewpoints were considered and brought together in a single local report. all local reports were compiled in an over-arching document, which brings together common themes to inform ongoing preparedness in the region. the debrief process identified a number of common themes, such as the need for clear and appropriate communication, the importance of working with partners, and the benefits of strong and early leadership. however, differences between and within organisations were also highlighted; for example, some wanted more freedom for local decision making, whereas others would have preferred more stringently applied central direction. the following paragraphs considers individual areas assessed in the debrief process. command and control was in the main effective, with clear direction delivered from the national centre through nhs london to local nhs organisations. effective leadership is essential; the identification of senior local individuals to lead the response with teams of people to support them was critical. appropriate use of technology to communicate messages and coordinate command and control processes greatly aided the response. this included the development of the nhs london noon brief, a daily digest and associated web portal, and regular teleconferencing. key points are: • operational management at all levels must be considered in pandemic planning. • appointing an executive lead in each organisation was invaluable in the response. • pandemic flu planning for london must continue to be regionally led. communication is an essential component of the response to any incident. it must be clear, timely, and accurate. in the main, communication was excellent and met these criteria. one of the most challenging aspects was when messages from partner organisations differed, which occasionally led to confusion, unnecessary work, or frustration. the use of technology greatly aided communication across the region and supported the response; this included secure web sites, bluetooth, and text messaging etc. key points are: • regular internal communications and staff briefings are critical in the response to emergencies. • regular teleconferencing should be incorporated into future plans. • organisations should consider proactive and innovative methods for communicating during emergencies. robust partnership working was an essential component of pandemic preparedness work; however in the event, the a ⁄ h n v pandemic had little impact on sectors in london other than health. resilient communication networks between organisations, a common understanding, and the ability to make decisions were essential to the response at local level. ipcs proved an excellent mechanism to maintain local working relationships and resolve problems. clarity on the seniority of those attending these meetings and whether multi-site organisations such as mental health trusts should attend every ipc should be considered on a local and regional basis. key points are: • pandemic planning must remain part of inter-agency working. • social care resilience and planning must be embedded and integrated in health planning. 'vulnerable groups' is a universal term that covers a large and fluid group of individuals with different needs. ensuring access to healthcare during the pandemic for those who became vulnerable due to the situation, or those identified as such prior to the event, was the role of the pct in partnership with the local authorities. work continues to ensure that communication with vulnerable people is appropriate and timely in all incidents, and that organisations work together to achieve this. key points are: • planning to support the breadth of vulnerable people must continue. • pandemic preparedness for the prison sector should be further developed. • red ⁄ amber ⁄ green ratings for assessing vulnerabilities of mental health service users in an emergency should be further developed across the region. correct and appropriate usage of ppe is an essential component of reducing influenza spread, particularly in healthcare settings. london's nhs had been working towards developing local stockpiles of ppe when the pandemic commenced; however, there was little in place. the unanticipated national stockpile, while providing ppe to all organisations, was accompanied with some challenges in that it was often unfamiliar stock. key points are: • work around local stockpiling of non-standard consumables should continue. • regular training and fit testing of respirators should be embedded in all organisations. antiviral treatment was a core component of the response to influenza a ⁄ h n v, and was provided free of charge from a national stockpile. npfs reduced pressure on frontline nhs services once it was activated; however, there were concerns that patients could 'cheat' the system and obtain the drugs prior their clinical need. information about storage requirements of countermeasures must be clearly explained when they are delivered to frontline services, and the potential for recall into national stockpiles should be planned for. key points are: • regular exercising of local mass countermeasures centres and antiviral collection points (acps) should continue. • the use of community pharmacies as acps should be further considered in the capital. pandemic influenza vaccine uptake by healthcare workers was better than usual seasonal influenza uptake in the majority of nhs organisations, but could have been even better. this was largely due to the second pandemic wave not being as significant as expected, lack of clarity around when the vaccine would be delivered, and limited amounts being available initially. • gp-led and mass vaccination models for pandemic vaccination should be considered in local plans. • local lessons from the pandemic vaccination campaign should be applied to seasonal flu vaccination. the ability to maintain or increase capacity in response to a surge in demand, no matter what the cause, must be planned for. any of a number of situations could result in reduced staff or more patients, such as industrial action, transport disruption, disease outbreak, major incident, or poor weather. the work undertaken during planning for and responding to the pandemic will stand organisations in good stead for future disruptions. the importance of robust business continuity planning locally cannot be overlooked, as this is a key component of maintaining and increasing capacity. key points are: • local gp 'buddy schemes' should be encouraged for response to extreme pressure events. • organisations should regularly run staff skills audits so as to be aware of their overall capability for managing emergencies. • less emphasis should be placed on the use of retired staff when planning service continuity. reporting is a necessary but onerous task, and is often one of the most time-demanding parts of any incident response. it is also the aspect least likely to be tested through exercising. nhs london worked with organisations to endeavour to reduce reporting pressures, but much of this was dictated by central government. it is essential that future reporting requirements are proportional, informative, and realistic. while recognising it is not possible to predict the detail of information that may be requested, some broad assumptions can be made. key points are: • organisations should consider how they would collect and collate data from disparate parts of their organisation, rather than focussing on the detail of what that might be. • national and regional planning should consider the need for information and how this is balanced with the demand this places on organisations. • the introduction of the concept of a daily dashboard to identify areas of pressure should be incorporated into pandemic flu planning. the winter and pandemic influenza resilience assurance process undertaken in autumn was a useful process to inform planning for the first winter when the pandemic virus would be circulating in the uk. this consisted of a regional inter-agency exercise and a comprehensive review of the winter and pandemic plans of all nhs organisations in london. • regular assurance of pandemic flu preparedness should be maintained. • future resilience assurance processes should be undertaken in a timely and measured manner. • local organisations should continue to undertake regular pandemic flu exercises. the recovery period is as important as the response, but often receives minimal attention and has the potential to suffer as staff return to their normal jobs. one of the aspects that was not anticipated during the pandemic was the amount of stock (ppe, antivirals, and vaccine consumables) that would be recalled into national stockpiles. this proved particularly challenging for pcts who had to coordinate the process across their local areas. key points are: • the recovery period of an emergency must be given the same status and importance as the response. • future pandemic flu planning must include the recovery of national stockpiles of equipment and medicines. it is essential the lessons from the ⁄ influenza a ⁄ h n v pandemic are learnt and embedded into business-as-usual and emergency response processes in preparation for the next pandemic and other incidents. even though the a ⁄ h n v pandemic was generally milder than previous pandemics, it still presented challenges to the nhs in london. the biggest challenge that remains is to ensure that the public and nhs staff are aware that a more virulent virus could cause significantly more illness, death, and disruption, and that we must maintain our preparedness should this happen. the influenza a ⁄ h n v pandemic has been a major stimulus to business continuity planning and emergency preparedness across health in london, and many of the experiences during the pandemic proved invaluable in the unusually severe weather in early . it is important that this impetus and focus is maintained. changes to the nhs landscape in london will be considered in ongoing pandemic and emergency preparedness to ensure we remain as well prepared as possible for future events, particularly as london approaches the olympic and paralympic games. one of the major lessons learnt from all global pandemic events is that better preparedness of national health systems to deal with influenza viruses could make a significant difference. the way national health systems operate during inter-pandemic and the pandemic alert periods and the methods they use to address potential threats posed by zoonotic viruses with pandemic potential, as well as sea-sonal influenza epidemics, can clearly indicate whether the countries have enough capacities to respond adequately to unexpected influenza outbreaks. these public health decisions to ensure the maximum of efficiency require a robust scientific knowledge base. the who public health research agenda for influenza developed by the global influenza programme (gip) in cooperation with international influenza experts identified specific research topics and their importance in meeting stream-specific breakout discussion groups during the global consultation meeting included representatives of researchers and public health professionals. funding organizations were invited to observe the process with no direct participation in the deliberations. the methods used to design the research roadmap for an influenza pandemic scenario are closely related to the process of development of the final document of who public health research agenda for influenza. during a pandemic scenario, the group prioritized topics and questions relating to rapid action and response. five to key public health needs associated with a pandemic scenario have been identified for each of the research agenda streams: five priority public health topics were identified for a pandemic scenario as follows: • examination of host range and transmission dynamics of animal influenza viruses to guide surveillance, control strategies, and risk communication. • enhanced surveillance in animals and humans to monitor virus evolution: o early detection of novel reassortants or changes in genotype and ⁄ or phenotype related to virulence. o development of epidemiological and laboratory diagnostic tools and capacity building to optimize case finding. o develop a framework for surveillance in animals that address ethical, legal, and social barriers to intra-pandemic surveillance and reporting. • deconstruct the origins of the pandemic virus to identify factors that permitted efficient human transmission. • develop strategies to limit economic, social, and cultural disincentives of animal-based interventions to reduce intra-and inter-species transmission. • operational research to optimize risk communication in the early phases of the pandemic linked to animal husbandry and food safety. stream : limiting the spread of pandemic, zoonotic and seasonal epidemic influenza ten priority research topics were identified for both pandemic and inter-pandemic scenario as follows: transmissibility of influenza across the progression of infection and spectrum of disease: • relative contributions of the different modes of transmission for influenza. five priority public health topics were identified for a pandemic scenario as follows: • identification of groups at higher risk of infection and severe disease outcome through enhanced surveillance. • understanding disease severity and identification of predictors of severe outcomes. • investigation of vaccine effectiveness, especially in high risk groups in diverse geographic areas. • establishment ⁄ enhancement of pharmacovigilance, particularly for adverse events among at-risk groups. • optimization of strategies for rapid and targeted vaccine deployment. • rapid assessment to optimize acceptance of pandemic vaccine. six priority public health topics were identified for a pandemic scenario as follows: • collaboration and coordinated sharing of data, protocols, regulatory, and other implementation strategies and databases from different countries on all aspects of patient management and outcome to accelerate improvements in patient care. • development of best practices in patient management in different settings, including checklists and algorithms for clinical care and treatment, prognostic parameters, and tests to predict potential for the development of severe disease. • rapid, reliable, simple, low-cost point-of-care diagnostic tools for influenza. • best use of current antiviral drugs and optimal formulations in different target populations, such as parenteral and other routes of administration for severe infections. • use of combination therapies, including use of adjunctive therapies (e.g., use of convalescent serum and immunomodulators). • role of ongoing viral replication, host responses, and the effect of co-infections in the pathogenesis of severe disease. modern tools for early detection and monitoring of disease the group on surveillance tools concluded that the agreed topics of interest were equally applicable during a pandemic or inter-pandemic period: • studies to appraise and adapt modern technologies for early detection of influenza outbreaks in surveillance at the human-animal interface. • develop, integrate, and evaluate innovative approaches for influenza surveillance and monitoring with other existing disease monitoring systems. • study efficient mechanisms on sharing data, clinical specimens, and viruses with consideration for local, ethical, legal, and research perspectives. • examine the timeliness and quality of data required for early detection from local to national and global levels for the respective stakeholders. five priority public health topics were identified for a pandemic scenario as follows: • identify environmental determinants of seasonal variation in influenza transmissibility in tropical and temperate regions. • estimate the transmission risk associated with types of contacts by comparing measured contact patterns with outbreak data. • incorporation of validated models of behavioral responses to risk and control measures in virus transmission. • development and implementation of novel technology for real-time sero-surveillance during a pandemic. • develop experimental and theoretical framework to assess host adaptation to study host receptor, antigenicity, and virulence. modern tools for strategic communication three priority public health topics were identified for a pandemic scenario as follows: • evaluate tools to more rapidly and accurately assess and monitor knowledge, attitudes, beliefs, and practices in different population groups to guide future communication efforts; develop tools and methods to more rapidly and accurately assess and monitor knowledge, attitudes, beliefs, and practices in different population groups, and thereby, guide future communication efforts. for communicating in different cultural settings, which engage and empower individuals and communities to practice and promote appropriate risk reduction measures. implementation of the identified research priorities is expected to underpin public health decision making at all levels with proven knowledge that will help to save large numbers of lives, reduce health costs and economic loss, and mitigate potential social disruption. complemented by an analogous research roadmap for a pandemic influenza scenario, the research recommendations for an interpandemic period represent a framework to provide evidence to guide public health policies on influenza control. one of the major lessons learnt from all global pandemic events is that better preparedness of national health systems to deal with influenza viruses could make a significant difference. these public health decisions to ensure the maximum of efficiency require a robust scientific knowledge base. the who public health research agenda for influenza developed by the global influenza programme (gip) in cooperation with international influenza experts identified specific research topics and their importance in meeting public health needs for inter-pandemic periods according to its five key research streams: • stream . reducing the risk of emergence of pandemic influenza. • stream . limiting the spread of pandemic, zoonotic, and seasonal epidemic influenza. • stream . minimizing the impact of pandemic, zoonotic, and seasonal epidemic influenza. • stream . optimizing the treatment of patients. • stream . promoting the development and application of modern public health tools. stream-specific breakout discussion groups during the global consultation meeting included representatives of researchers and public health professionals. funding organizations were invited to observe the process with no direct participation in the deliberations. the methods used to design the research roadmap for an influenza inter-pandemic scenario are closely related to the process of development of the final document of who public health research agenda for influenza. during an inter-pandemic phase, a more comprehensive approach was applied to establish research topics and prioritizing a range of questions that will build a solid foundation to guide research activities to support public health decision making. five to ten key public health needs associated with an inter-pandemic scenario have been identified for each of the research agenda streams: stream : limiting the spread of pandemic, zoonotic, and seasonal epidemic influenza ten priority research topics were identified for both pandemic and inter-pandemic scenario as follows: . transmissibility of influenza across the progression of infection and spectrum of disease . relative contributions of the different modes of transmission for influenza . biological, behavioral, and social host factors that influence the risk of transmission and infection . patterns, drivers, and mechanisms affecting the seasonality of transmission . viral and population factors that influence transmission and spread of different influenza types, subtypes, and strains . strategies to reduce the transmission of influenza in community, household, and health care settings, especially in less-resourced areas . impact and cost effectiveness of social measures, such as school closures, and the role of surveillance in assessing timing of these interventions . impact, effectiveness, and cost effectiveness of individual measures, such as isolation and quarantine . role of vaccination in limiting the spread of influenza and strategies for its use . impact of antiviral treatment and prophylaxis in reducing transmission of influenza stream : minimizing the impact of pandemic, zoonotic, and seasonal epidemic influenza . identify higher risk groups and severe disease through surveillance; disease severity and identification of predictors of severe outcomes . evaluate vaccination preventable disease burden and the potential impact of immunization programs through vaccine demonstration projects . enhancement of the properties of existing vaccines, including duration and breadth of protection, safety, immunogenicity, and dosesparing . development of new vaccines and vaccine platforms, especially suitable for under-resourced country settings . study the effectiveness of vaccine strategies to reduce disease burden in children and other high risk groups in a wide range of settings . improved uptake and acceptability of vaccines for both seasonal and pandemic influenza seven priority public health topics were identified for an inter-pandemic seasonal influenza scenario as follows: inter-pandemic seasonal influenza scenario . research on the burden of severe disease with a focus on regionalspecific factors, such as the burden of tb and hiv and optimization of pandemic and management . development of new antiviral strategies and validation of surrogate endpoints which may aid in advancing understanding of disease progression . further clinical evaluation of current antiviral drugs, particularly in populations at risk . integration of seasonal influenza with pandemic preparedness; strengthen surveillance, health care systems, capacity, and preparedness planning . improving diagnostics (e.g., multiplex assays for viruses and bacteria), including antiviral resistance testing at point-of-care . dissemination of best practices, situation analysis, preparation for next epidemic (e.g., establish protocols for rotating stockpiles of antiviral drugs) . increased attention to basic science research such as studying immunomodulatory drugs five priority public health topics were identified for an inter-pandemic zoonotic influenza scenario as follows: inter-pandemic zoonotic influenza . antiviral susceptibility of circulating zoonotic viruses (e.g., h , h , h influenza viruses) . reassortment between zoonotic and human influenza viruses and the potential for inter sub-type spread of antiviral resistance and virulence modern tools for early detection and monitoring of disease the group focusing on surveillance tools concluded that the agreed topics of interest were equally applicable during both pandemic and inter-pandemic period: . identify modern technologies for early detection of influenza outbreaks as well as their application in surveillance at the human-animal interface . develop and evaluate innovative approaches for influenza surveillance and monitoring with other existing disease monitoring systems . studies to address challenges on data, clinical specimens, and viruses sharing with consideration for local, ethical, legal, and research perspectives . examine the timeliness and quality of data required for early detection from local to regional, national, and global levels role of modeling in public health decision making five priority public health topics were identified for an inter-pandemic seasonal influenza scenario as follows: . integration of genetic and epidemiological data to understand spatiotemporal spread to forecasts evolution for vaccine strain selection and to anticipate likely burden of disease . quantifying the relative contributions of different modes of transmission of human influenza and developing mechanistic modeling of transmission processes . research using data-capture technologies to characterize human contact and mobility patterns at local, regional, and global scales, and their correlation with transmission risk . integration of genetic, antigenic, and epidemiological analyses to optimize surveillance for newly emerging pathogens at the animal ⁄ human interface . identifying and quantifying human and environmental ecological, behavioral, and demographic determinants of the risk of cross-species transmission and pandemic emergence modern tools for strategic communication four priority public health topics were identified for an inter-pandemic seasonal influenza scenario as follows: . review of evidence and experience related to health crisis communication from fields to organize knowledge and support evidencebased practice in strategic communication . identify and develop tools to rapidly and accurately monitor knowledge, attitudes, and practices in different population groups and guide future communication efforts . identify and develop communication tools and approaches for cultural settings and communities to practice and promote appropriate risk reduction measures . understand the potential ethical, social, economic, and political communication in crisis and develop strategies to work within constraints while maximizing opportunities complemented by an analogous research roadmap for a pandemic influenza scenario, the research topic recommendations for an inter-pandemic period represent an important outcome of joint international efforts by who, academicians, and public health experts. implementation of the identified research priorities is expected to underpin public health decision-making at all levels with proven knowledge that will help to save large numbers of lives, reduce health costs, and economic loss and mitigate potential social disruption over a medium-tolong term period. the impacts of school resumption on the incidence of pandemic (h n ) in school students introduction school closure is one non-pharmaceutical intervention that is often suggested in pandemic preparedness plans, and it was widely implemented in pandemic (h n ) to reduce transmission amongst school students. however, from past epidemiological studies, the effect of school closure in reducing respiratory disease transmission was inconclusive. given this public health intervention causes major disruption to the education system and potentially raises childcare issues to working parents, evaluating its effect in the recent pandemic is necessary to improve future pandemic planning. in hong kong, since school closure was implemented early in the pandemic and closure was effectively continued with the commencement of summer holiday, the lack of incidence data in the absence of school closure makes it difficult to analyse its effect directly. this has prompted us to analyse the situation indirectly from the angle of school resumption after summer holiday. in hong kong, public health surveillance on pandemic (h n ) was effective from th april- th september : healthcare professionals were advised to report suspected cases of infection to centre for health protection, department of health, hksar, for further laboratorial confirmation. demographics of reported cases were subsequently recorded into a computerised system (the ''e-flu'' database). following institutional approval, a dataset of all confirmed cases diagnosed from may to september was obtained, which included the age, gender, confirmation date, and notification date of each report. all cases were classified into four defined socio-economic classes by age: pre-schoolers ( - ), school students ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) , adults ( - ), and retirees ( ‡ ). assuming cases had contracted infection on the earlier date between confirmation and notification, daily incidence in each age class was counted for epidemic curve construction. upon observing an unusual rise in the epidemic curve of school students when school season resumed in september, interrupted time series analysis (also known as intervention analysis) was applied to obtain the statistical significance of this observation. the analysis was applied to the incidence in school students from th july to th september , which covered the period from the start of summer holiday to the end of the th week of new school season. incidence in school students before summer holiday was deliberately dropped since not all schools were closed when the school closure policy was effective: all primary schools were closed proactively, whereas secondary schools were individually closed on a reactive basis if students were identified to have contracted the infection. school activity was formulated as a step function, which takes value from st september onwards (st = : t < st september, st = otherwise). a range of times series models were fitted by the maximum likelihood method and aic (akakine information criterion) was used to select the one with best fit. all computations were performed in sas version . . a total of ( ae %) pre-schoolers, ( ae %) school students, ( ae %) adults, and ( ae %) retirees were diagnosed with the infection in the surveillance period. the epidemic curves of preschoolers, school students, and adults showed a steady rise from th june onwards when local transmission of pandemic influenza was identified. an upsurge in the epidemic curve of school students can be observed in early september, coinciding with the commencement of the new school year (figure ) . interrupted time series analysis on the epidemic curve of school students returned an arima( , , ) model with equations: where st, yt, yt denote school activity, predicted and actual incidence in school students on day t, respectively. standard error and significance for model constants were: ae (se = ae , p = ae ), ae (se = ae , p = ae ). in short, the model can be interpreted as: the number of infected school students rose by ae per day on average during the entire study period, with a sharp increase by ae coming into effect when the new school year began. time series analysis showed, at the marginally significance level, that daily incidence in school students had a major increase when school season resumed. on the assumption that the increase was not caused by any change in health seeking behaviour, this result suggests that school resumption had facilitated transmission amongst school students. on the basis that school activity significantly increases incidence of pandemic influenza in school students, this study suggests closures of schools in the early phase of pandemic (h n ) and subsequently in the summer holiday probably had a major effect in mitigating transmission amongst school students. youngsters were postulated to be major vector for transmission in pandemic (h n ) . if this were true, it would be reasonable to expect the epidemic curves of the other age classes to show a similar upsurge when one is observed in school students. the absence of such observation in the epidemic curve of hong kong suggests school students were mostly disseminating the virus amongst themselves, but not to the other age groups. in november , gip convened the first global consultation on a public health research agenda for influenza to identify key research topics in each of the five main streams of public health research. during this meeting, the scientific working group (swg) of the sub-stream in ''modern tools for risk communication'' identified the requirements in research during influenza pandemics and inter-pandemic periods to provide clear, credible, and appropriate messages which meet the needs of diverse communities. the swg suggested that who hold a follow-up workshop to assess the use of modern tools related to strategic and risk communication and to further promote research in these areas. communication'' in may . one of the main objectives of the meeting was to generate a roadmap of public health research priorities related to strategic and risk communication. the research roadmap was developed by the group of invited experts on the basis of an analysis of available evidence and experience on public health and health crisis communication from relevant disciplines across global regions, as well as critical assessment of existing communication methods related to influenza control in different cultural, social, and ethnic settings. the workshop consisted of a series of presentations by experts in relation to experiences and lessons learned about communication during the sars, h n epidemic, and h n pandemic. there were also a series of group discussions on identifying research needs for pandemic and interpandemic periods in order to strengthen the research agenda. the expert group identified important public health needs in relation to communication during pandemics as well as in the inter-pandemic times. the main topics of discussion centered on communicating issues of influenza virus transmission, the use of influenza vaccines safety and efficacy, and use of antivirals as well as definition of the severity of the pandemic and the phase changes. in this context a number of research areas were identified, which can be broadly classified into four areas: understanding of communication principles and mechanisms is associated with an array of research topics covering different subject areas. one of the key questions here relates to the link between communication and ''behaviour change'' models and their application and appropriateness for different settings. the expert group defined the term ''behaviour change'' in this context as the modification of behaviour towards better health practices that are supported by clinical and scientific evidence for personal protection against infectious diseases and other adverse health risks. research topics related to these models require understanding and differentiating information and ''behaviour change'' needs of different audience segments, such as stakeholder mapping, target audience analysis, research into behaviour motivation, social norms, and the cultural, religious, social, legal, and political barriers and enablers of particular behaviors that are beneficial in influenza control. this research area also includes the analysis of media consumption among different audiences, role models, including ways to analyse how rumours and misinformation are spread, and ways to provide evidence-based information correctly. other important areas of investigation embrace methods to communicate uncertainty, learning how to build trust while communicating about a pandemic, and understanding what needs to be done before, during, and after a pandemic in order to create the best environment for influenza pandemic communication. critical key audiences identified for more intensive analysis were health workers, religious, public health, and societal (political and community) leaders. • investigation of the role of different communication channels and communication formats for different target audiences in a pandemic, particularly for groups that are ''hard-to-reach.'' • determining effects of perceptions related to pandemic influenza (severity, susceptibility, response efficacy, self efficacy, perceived social norms) on protective behaviours in different groups. • understanding audience in terms of their knowledge, preventive activities, and reasons why engaged ⁄ not engaged. • developing mechanisms to synergies between risk communication and behavior oriented approaches in the pandemic and inter-pandemic phases. • determining social, economic, cultural, and religious factors which support behaviours to limit spread and minimize impact in different settings. • identification of the key predictors ⁄ factors that influence people's behavior among different groups and populations vis-à -vis pandemic flu behaviors. • identification of elements that contribute to trust among populations and in different settings (country, public, professional, community), particularly where trust was previously compromised. • understanding psychology of different groups regarding their response to uncertainty, and finding the best way to communicate uncertainty. the research questions in this section relate to the planning, development, and evaluation of tools that can be quickly accessed and used in a pandemic situation. these may include communication materials and channels; the setting up of key stakeholder and champion communication networks; research protocols that are ready for rapid assessment during a pandemic or new communication tools. the use and understanding of terminology and language by both lay and professional groups and communities in planning for and ⁄ or reacting to a pandemic are important areas of research. acute examples, such as the naming of the viruses or the use of the word ''pandemic,'' illustrate this need well. the research focus of this area is to look at lessons learned from the a(h n ) pandemic and to document and evaluate case studies, both looking at best practices, challenges, and barriers that were experienced. different communication strategies need to be evaluated and models to be built not only in terms of reach, but also in terms of impact on thinking, emotional response, and behavioural modification. a key question was how to prepare communication for a pandemic and how can the pandemic communication contribute to longer term ''behavioural change.'' mathematical modelling on gauging outcomes of such ''behaviour change'' would provide strategic approaches in risk communication. this section aims to answer the question whether the modeling, mapping, and scenario planning are actually useful in the pandemic situation. the expert group agreed that the research on the above issues should use a variety of methods and engage a number of disciplines. this would include literature reviews, case studies, trials, ethnographic studies, modelling, surveys, network analysis, as well as any other useful methodology. in an inter-pandemic situation for actual behaviour under pandemic conditions. • study the synergies and develop priority research topics on strategic ⁄ risk communication for influenza under inter-pandemic situations that includes zoonotic and seasonal infections. the who public health research agenda for influenza initiated and facilitated a multi-disciplinary discussion for communication during pandemic and inter-pandemic situations. it focused on both theoretical and practical issues to improve practice and ensure the health of the public for influenza. critical areas for research were identified to build evidence in this field. it was recognized that there are extensive bodies of knowledge in a number of disciplines, , such as health promotion, behavioural psychology, social sciences, social and behaviour change communication, social marketing, and communication for development relating to these questions, and that these should be explored. outcomes of these research activities are expected to widen the evidence base which will support developing communication strategies for influenza by countries, institutions, and individuals and will, consequently, help to improve public health world-wide. abstract background: cytokine dysregulation contributes to the unusual severity of h n (reviewed in ). previously, we demonstrated that interferon regulatory factor (irf ) and p map kinase (p ) signaling pathways separately contribute to the induction of pro-inflammatory cytokines and chemokines in h n -infected cells. here we investigate the role of innate sensing receptors in the induction of these cytokines and chemokines in response to h n and seasonal h n infection. materials and methods: human macrophages derived from peripheral blood monocytes were infected with h n ( ⁄ ) or seasonal h n ( ⁄ ) viruses. the role of innate sensing receptors in cytokine and chemokine induction by h n virus was investigated using transient knock-down of these receptors with sirnas. the expression of innate sensing receptors in infected cells, and as a result of paracrine activation (by virus free supernatants of infected cells) of adjacent uninfected cells were also monitored by real-time pcr and ⁄ or western blotting. the involvement of janus kinase (jak) signaling pathways in these autocrine ⁄ paracrine cascades was investigated using a jak inhibitor. results: we previously showed that tnf-alpha, ifn-beta, and ifn-lambda are the key mediators directly induced by the h n virus in primary human macrophages with other cytokines and chemokines being induced as part of a secondary autocrine and paracrine cascade. here we demonstrated that retinoicacid-inducible gene i (rig-i) rather than toll-like receptor (tlr ) plays the predominant role in h n -induced cytokines and chemokines in human macrophages via the regulation of irf and nf-kb nuclear translocation. in addition to the effects on virus infected cells, paracrine interactions between macrophages and alveolar epithelial cells contributed to cytokine cascades via modulation of jak signaling and by the upregulation of sensing receptors. conclusions: h n directly induced tnf-alpha and ifnbeta mainly via rig-i signaling, and the subsequent activa-tion and nuclear translocation of irf and nf-kb in human macrophages. in addition to the effects on cytokine signaling, the innate immune sensing regulators themselves were also up-regulated by h n infection, much more so than by seasonal influenza infection, via jak signaling. the up-regulation of innate sensing receptors was not limited to the infected cells, but was also found in adjacent uninfected cells through paracrine feedback mechanisms. this may lead to broadened and amplified cytokine signals within the microenvironment of the infected lung. a more precise understanding of the signaling pathways triggered by h n virus leading to cytokine induction may provide novel options for the design of therapeutic strategies for severe human h n influenza and also for treating other causes of acute respiratory disease syndrome. human h n infection is associated with a mortality rate of more than %. the basis for the unusual severity of h n disease has not been fully explained. cytokine dysregulation has been suggested to contribute to the disease severity of h n (reviewed in ). however, signaling pathways involved in the cytokine induction by h n virus are not fully understood. previously, we demonstrated that irf and p map kinase (p ) are separate signaling pathways which contribute to the induction of pro-inflammatory cytokines and chemokines in h n -infected cells. rig-i and melanoma differentiation-associated gene (mda ) are important cytosolic sensors of nucleic acid of pathogens, while tlr and tlr also recognize nucleic acid species of pathogens, but they are localized at the endosomal membrane. rig-i was found to be responsible for the recognition of influenza a virus infection, and the transfection of vrnps induces ifn-beta expression. while many studies have shown the role of rig-i in the induction of ifn-beta by influenza virus infection, the majority of these studies used either immortalized cell lines or mouse embryonic fibroblasts. there is a lack of data on the role of these innate sensing receptors in highly pathogenic avian influenza h n infection in primary human cells in vitro, which are more physiologically relevant. furthermore, there is little data on the autocrine and paracrine up-regulation of these innate immune sensors following virus infection. human macrophages were obtained from peripheral blood monocytes by adhesion and differentiation in vitro for days in rpmi medium supplemented with % autologous plasma. the cells were infected with h n ( ⁄ ) or seasonal h n ( ⁄ ) viruses at a moi of ae . a cells were obtained from atcc and cultured in mem medium supplemented with % fcs and % penicillin and streptomycin. the role of innate sensing receptors in cytokine induction by h n and h n viruses was investigated using transient knock down of these receptors with sirnas in human macrophages as previously described using specific sirnas purchased from qiagen. immunofluorescence staining assay of irf and nf-jb was employed to detect the nuclear translocation of these transcription factors after h n infection. rabbit polyclonal antibodies against human irf and and nf-kb were obtained from santa cruz biotechnology. goat anti-rabbit igg antibody conjugated with alexa fluor was a product of molecular probes. for investigation of paracrine effects on rig-i and tlr expression, culture supernatants collected from mock, ⁄ or ⁄ infected human macrophages were used to treat uninfected cells. the supernatants were first passed through a filter with -kda cut-off. virus particles as well as molecules with a molecular weight higher than kda were retained and removed, while the filtrate was collected for treatment of uninfected cells. the expression of innate sensing receptors in infected cells and in adjacent uninfected cells following paracrine activation by virus free supernatants of infected cells was monitored by real-time pcr. the involvement of jak signaling pathways in these paracrine cascades was investigated using a jak inhibitor (calbiochem). we previously showed that tnf-alpha, ifn-beta, and ifnlambda are the key mediators directly induced by the h n virus in primary human macrophages with others being induced as part of a secondary autocrine and paracrine cascade. in this study, we demonstrate that knockdown of rig-i or tlr led to the reduction of ifn-beta and tnf-alpha in human macrophages by both ⁄ (h n ) and ⁄ (h n ) infection. as shown in figure a , ⁄ virus induced higher level of ifn-beta mrna expression than ⁄ infection. cells transfected with rig-i or tlr sirna significantly reduced the expression of ifn-beta after ⁄ infection, by % and %, respectively. rig-i silencing also significantly reduced the ifn-beta expression in ⁄ infected cells by %. in contrast, silencing of mda or tlr did not suppress the induction of ifn-beta by either ⁄ or ⁄ infection; in fact, there was a slight ( %) increase of ifn-beta in cells transfected with mda sirna. based on these results we conclude that while both rig-i and tlr contribute to h n -induced interferon-beta induction in human macrophages, rig-i plays the dominant role. in order to investigate the relationship between these innate sensing receptors and the activation of transcription factors irf and nf-jb, we next measured the nuclear translocation of irf and nf-jb in cells with rig-i or tlr silencing after h n infection. immunofluorescence staining assay on irf and nf-jb was performed and the number of cells with nuclear translocation was quantitated. the percentages of cells with nuclear translocation were plotted in figure b . we demonstrated that rig-i knockdown led to a significant reduction of irf nuclear translocation after ⁄ infection, whereas the nuclear translocation of nf-jb after ⁄ infection was significantly suppressed by rig-i or tlr silencing. these results suggest that the involvement of rig-i and tlr in the cytokine induction by ⁄ was via the regulation of irf and nf-jb nuclear translocation. since rig-i and tlr are important in influenza a virus-induced cytokine expression, we next explored the expression of these innate receptors in neighboring uninfected human macrophages by treating the uninfected macrophages with the filtered culture supernatants collected from mock, ⁄ , or ⁄ infected macrophages. as shown in figure a , ⁄ supernatant differentially induced the mrna expression of rig-i, mda , and tlr compared to ⁄ supernatant treated human macrophages. the induction of rig-i was higher than the induction of mda and tlr . in the presence of lm of jak inhibitor, the up-regulation of all three innate sensing receptors was significantly reduced showing their induction was dependent on jak activity. human lung epithelial a cells were also treated with the supernatants collected from macrophages infected with mock, ⁄ , or ⁄ virus. differential induction of rig-i, mda and tlr by ⁄ supernatant compared to ⁄ supernatant treated cells was observed (figure b) . ⁄ supernatant dramatically induced all three innate sensing receptors, while ⁄ supernatant only marginally induced rig-i and mda , but not tlr . as in human macrophages, treatment with lm of jak inhibitor caused a significant suppression of ⁄ supernatantinduced rig-i, mda , and tlr expression in a cells. these results, taken together with the direct effects on virus infected cells, suggest that paracrine interactions between macrophages and alveolar epithelial cells contributed to cytokine cascades via modulation of jak signaling and by the up-regulation of innate sensing receptors. h n directly induced ifn-beta ( figure ) and tnf-alpha (data not shown) mainly via rig-i signaling and the consequent activation and nuclear translocation of irf and nf-kb in human macrophages. these results were consistent with a previous study using beas- b cells showing the essential role of rig-i in ifn-beta reporter activity by h n influenza virus infection. while tlr also played a role in induction of ifn-beta and the activation of irf and nf-kb, it plays a less important role compared to rig-i. the reduction of irf and nf-kb activation was also confirmed with the study by le goffic showing differential regulation of irf and nf-kb by rig-i and nf-kb can also be regulated by tlr . in addition to the direct role of rig-i and tlr in sensing and signaling the presence of influenza virus, the innate immune sensing regulators were themselves also highly upregulated in both infected (data not shown) and adjacent uninfected cells by influenza virus infection. compared with seasonal h n virus, the h n viruses had a much more dramatic effect on inducing innate sensing receptors via jak signaling pathways activated by autocrine and paracrine mediators. the up-regulation of rig-i, mda , and tlr was markedly induced by virus free culture supernatants from h n -infected macrophages, while supernatant from ⁄ -infected cells induced the expression of these receptors only to a lesser degree. the soluble mediators in the virus infected cell supernatant caused paracrine upregulation of rig-i, mda , and tlr in uninfected macrophages as well as human lung epithelial cells. these effects may lead to broadened and amplified cytokine signals within the microenvironment of the infected lung. taken together these results provide, at least, part of the explanation on the hyper-induction of cytokines in h n infection. a more precise identification of the signaling pathways triggered by h n virus leading to cytokine induction may provide novel options for the design of therapeutic strategies for severe human h n influenza and also for treating other causes of acute respiratory disease syndrome. we generated mutants of y (h n ) and a ⁄ duck ⁄ hokkaido ⁄ vac generation and characterization of mutant viruses rgy sub (h n ), rgvac sub (h n ), and rgvac ins (h n ), which have a serial basic amino acid residues at their ha cleavage sites were generated by site-directedmutagenesis and reverse genetics. rgy sub (h n ) and rgvac ins (h n ) required trypsin to replicate in mdck cells, and showed similar levels of growth to their parental viruses (table ) . chickens intravenously inoculated with rgy sub (h n ) or rgvac ins (h n ) did not show any signs of disease. rgvac sub (h n ) replicated in mdck cells without exogenous trypsin, and one of the eight chickens inoculated with the virus showed slight depression at day post-infection. the h and h mutant viruses were serially passaged in the air sacs of chicks to assess their ability to acquire pathogenicity. plaque formation in mdck cells and pathogenicity in -day-old chicks and -week-old chickens are shown in table . rgy sub (h n ) replicated in mdck cells in the absence of trypsin and killed all of the chicks after six consecutive passages. two of the eight-four-weekold chickens inoculated intravenously with rgy sub-p (h n ) died within days. eventually, over % of the chickens intravenously infected with rgy sub-p (h n ) died by days post inoculation, and its pathogenicity was comparable to that of hpaivs. rgvac sub-p (h n ) was pathogenic to both chicks and -week-old chickens, and mortality increased after one more passage. rgvac ins-p (h n ) replicated in mdck cells in the absence of trypsin, killed all of the chicks, and caused % mortality among -week-old chickens. the lethal effect of rgvac ins-p (h n ) on chickens increased with one additional passage in the air sacs of chicks, as in the case of rgvac sub (h n ). to examine whether the pathogenicity of each virus via the natural route of infection correlated with that by intravenous infection or not, three -week-old chickens were challenged intranasally with the viruses at an eid of ae and observed for clinical signs until day post-infection (data not shown). all chickens inoculated with rgy sub-p (h n ) or its parental viruses survived without showing any clinical signs, and serum antibody responses were detected in the hi test. on the other hand, rgvac sub-p (h n ) and rgvac ins-p (h n ) were pathogenic as in the intravenous experiment, killing two of three chickens by day post-inoculation. one of three chickens were not infected with rgvac sub-p (h n ) or rgvac ins-p (h n ) via intranasal route (data not shown), indicating these p viruses had not been completely adapted to the host. to investigate the possibility of these p viruses to acquire further pathogenicity for chicken, rgvac sub-p (h n ) and rgvac ins-p (h n ) were obtained from the brain homogenates of the chickens that died on days post intranasal inoculation with the p viruses. although mortality rate of chickens inoculated with the p viruses was equal to that with p viruses, enhancement of pathogenicity was observed in intranasal inoculation study; all of the chickens inoculated with rgvac sub-p (h n ) were infected, and time to death was shortened to - days post inoculation in chickens with rgvac ins-p (h n ) (data not shown). to investigate whether tissue tropism of the viruses was involved in their pathogenicity, we determined viral titers in the tissue and blood samples from -week-old chickens intranasally inoculated with each virus on days post infection ( table ) . rgy (h n ) and rgvac (h n ) were scarcely recovered from the samples, and the mutant strains before passage showed broader tissue tropism than the parental viruses. none of the chickens inoculated with rgy sub-p (h n ) showed any signs of disease, and viruses were recovered from each of the samples except the brain and the blood. one chicken inoculated with rgvac sub-p (h n ) showed clinical signs such as depression, and viruses were recovered from virtually all of its organs and blood samples. two of three chickens inoculated with rgvac ins-p (h n ) showed disease signs, and one died days post inoculation. the viruses were recovered from almost all samples of the two chickens showing signs of disease. p viruses were efficiently replicated in systemic organs of the chickens as compared with p viruses. throughout the study, the viruses were recovered from the brains of all of the chickens showing clinical signs. here, we demonstrated that the h influenza virus acquired intravenous pathogenicity after a pair of di-basic amino acid residues was introduced into the cleavage site of the ha and passaged in chicks. rgy sub-p (h n ) killed % of chickens infected intravenously, and its pathogenicity was comparable to that of hpaivs (table ) . however, chickens intranasally inoculated with rgy sub-p (h n ) did not show any clinical signs of disease (data not shown). these results are consistent with a previous study in chickens that found some h influenza viruses did not show intranasal pathogenicity although their intravenous pathogenicity index was over ae , classified as hpaiv according to the definition by european union. ohuchi et al. reported that the insertion of additional basic amino acids into the h ha cleavage site resulted in intracellular proteolytic cleavage. other groups reported that h and h has tolerated amino acid mutations into their cleavage sites, and the viruses with the mutated has replicated in mdck and ⁄ or qt cells in the absence of trypsin. , the results in the present study is in agreement with these, namely, cleavage-based activation by a ubiquitous protease is not restricted to the h and h has. the intranasal pathogenicity of the h and h mutants were different (data not shown), although these viruses similarly replicated in mdck cells in the absence of trypsin and killed chickens by intravenous inoculation ( table ) . the viruses were recovered from the brain and the blood of some chickens infected with rgvac mutants (h n ), and morbidity was closely associated with viral titers in the brain (table ) . on the other hand, no viruses were recovered from the brain of chickens infected with rgy mutants (h n ), explaining why rgy sub-p (h n ) did not show intranasal pathogenicity. all the viruses passaged in the air sacs of chicks killed chicken embryos by hours post allantoic inoculation (data not shown). rgvac sub-p (h n ) and rgvac ins-p (h n ) were more pathogenic to chicken embryos than rgy sub-p (h n ); the allantoic fluid obtained from the embryonated eggs inoculated with the h viruses passaged in air sacs was turbid. it has been reported that infection of a highly pathogenic h virus were strictly confined to endotherial cells in chicken embryos or chickens. , therefore, it is suggested that endotheliotropism differed between the h and h viruses passaged in air sacs and affected their intranasal pathogenicity. taken together, it is assumed that rgvac sub-p (h n ) and rgvac ins-p (h n ) showed marked intranasal pathogenicity with high levels of viremia caused by replication in vascular endothelial cells, leading to invasion of the brain. in the intravenous experiment, rgy sub-p (h n ) easily reached systemic organs, including the brain hematogenously, replicated through the cleavage of ha by a ubiquitous protease, and then exerted its pathogenicity. further study including a pathological analysis is currently underway to test this hypothesis. for all hpai viruses of subtypes h and h known to date, the cleavage of ha occurs at the c-terminal r residue in the consensus multibasic motifs, such as r-x-k ⁄ r-r with r at position p and k-k ⁄ r-k ⁄ t-r with k at p , and leads to a systemic infection. early studies demonstrated that the ubiquitously expressed furin and pcs are activating proteases of hpai viruses. furin and pcs cleave the consensus multi-basic motif r-x-k ⁄ r ⁄ x-r with r at position p . however, replacement of p r by k and a nonbasic amino acid significantly suppresses the processing activities of furin and pcs. most of the type ii transmembrane serine protease identified so far recognize a single r at position p , but the newly isolated mspl and its transcript variant tmprss preferentially recognize paired basic residue, particularly r and k at position p , at the cleavage site. [ ] [ ] [ ] thus, mspl and tmprss can activate various bioactive polypeptides with multibasic residue motifs, including fusogenic viral envelope glycoproteins. the present study was designed to characterize the proteolytic processing of the hpai virus ha by mspl and tmprss in comparison with furin. hpai virus a ⁄ crow ⁄ kyoto ⁄ ⁄ (h n ) was isolated from embryonated eggs inoculated with tracheal homogenates from dead crows. then, the mutant ha sequence was constructed by changing r residue to k residue (n'-rkkr-c' to n'-kkkr-c') at the ha cleavage site by sitedirected mutagenic pcr as described. we used human cell line ecv , which expresses mspl and tmprss at levels below detection, and established the cells stably expressing mspl and tmprss , such as ecv -mspl and ecv -tmprss . to determine the cleavage specificities of mspl ⁄ tmprss and furin, peptides ( lg each) were incubated with ae mu mspl ⁄ tmprss for hour and furin for hours at °c, respectively. after incubation, the samples were separated by reverse-phasehigh-performance liquid chromatography (rp-hplc) with the use of a c column. the elution samples were then identified by amino acid sequence analysis and by maldi-tof-ms. we analyzed the cleavability of -residue synthetic peptides derived from ha cleavage sites of hpai strains, such as a ⁄ chick ⁄ penn ⁄ ⁄ (h n ) and a ⁄ fpv ⁄ rostock ⁄ (h n ), and low pathogenic strain a ⁄ aich ⁄ ⁄ (h n ). after incubation with human mspl or human furin, the digested samples were separated by rp-hplc, and peptide fragments were characterized by mass-spectrometry and protein sequencing. in contrast to the low cleavage efficiencies of the h ha peptide with a single r at the cleavage site ( figure a) , both the h ha peptide with the k-k-k-r motif ( figure b ) and the h ha peptide with the r-k-k-r motif ( figure c) were fully processed at the correct positions by mspl within hour. in the case of h ha peptide with multiple basic residues, mspl cleaved two carboxyl-terminal sides of r in the cleavage site sequence of n'-k-k-rfl-k-k-rfl-g-c', while furin cleaved only at a single site of r with r at position p , n'-k-k-r-k-k-rfl-g-c' in the presence of mm cacl . these cleavage site specificities of furin were consistent with that reported for the h ha peptide of hpai virus a ⁄ hong kong ⁄ ⁄ (h n ) with r-k-k-r motif. however, the h ha peptide with k at position p ( figure b) was hardly cleaved by furin under the same experimental conditions. tmprss showed similar results (data not shown). these findings suggest that mspl and tmprss cover diverse cleavage specificities, including non-susceptible specificity to furin. full length recombinant ha of hpai virus with kkkr cleavage motif was converted to mature ha subunits with membrane-fused giant cell formation in mspl or tmprss transfectant cells. in addition, this conversion was suppressed by bowman-birk trypsin inhibitor, a membrane non-permeable highmolecular mass inhibitor against mspl ⁄ tmprss . to test for the generation of infective virus, the conditioned media of -day culture of ecv -wt and ecv -mspl cells infected with wt and mutant hpai h n viruses were inoculated into newly prepared cells and cultured for hours. although spreading of wt virus infection with ha cleavage motif of r-k-k-r was detected from the conditioned medium of both ecv -wt and ecv -mspl cells, that of mutant virus with ha cleavage motif of k-k-k-r was only detected from the condition medium of ecv -mspl cells. these results strongly suggest that the expression of mspl, but not furin, potentiates multicycles of hpai virus with k-k-k-r ha cleavage motif. seasonal human influenza a virus has have consensus monobasic cleavage site sequence, n'-q ⁄ e-x-rfl-g-c', and all hpai virus has have two types of cleavage site sequences with multiple basic amino acids, n'-r-k ⁄ r-k ⁄ r ⁄ x-rfl-g-c' with r at position p in a large number of hpai viruses and n'-k-k ⁄ r-k ⁄ t-rfl-g-c' with k at position p in a small number of hpai viruses. figure shows furin efficiently cleaved synthetic hpai a ⁄ hong kong ⁄ ⁄ (h n ) ha cleavage site peptide with the r-k-k-r motif, but hardly cleaved the hpai virus a ⁄ chick ⁄ penn ⁄ ⁄ ha cleavage site peptide with the k-k-k-r motif. furthermore, cleavage of the full-length ha of hpai virus with r-k-k-r motif was detected, but cleavage of hpai virus ha with k-k-k-r motif was hardly detected in ecv -wt cells containing furin ( figure ). these substrate specificities of furin suggest that proteases other than furin and pc ⁄ play a role in the processing of has of hpai virus with k-k ⁄ r-k ⁄ t-r cleavage motif. mspl and tmprss show unique cleavage site specificities of the double basic residues at the cleavage site, and r or k at position p greatly enhanced the efficiency, which none of the other ttsps have shown similar substrate specificities so far. furthermore, infectious and multicycle viral replication along with ha processing was also noted in genetically modified mutant recombinant live hpai virus a ⁄ crow ⁄ kyoto ⁄ ⁄ (h n ) with k-k-k-r cleavage motif in ecv -mspl cells (figure ) . these results were supported by the data of two cleaved peptides by mspl in figure c . these findings suggest that mspl has diverse cleavage specificities and may cleave ha at least two sites, although multiplicity of the mutant hpai virus was observed under the conditions. these results also suggest that mspl and tmprss in the membrane might potently activate the ha membrane fusion activity of hpai viruses and promote their spread. highly pathogenic avian influenza viruses replicate in various organs in birds, and the ha processing proteases might be widely distributed in these organs. indeed, tmprss and mspl are ubiquitously expressed in almost all human organs tested and are highly expressed in lungs, leukocytes, pancreas, spleen, and placenta. , in addition, mspl and tmprss are strictly localized in the plasma membranes, suggesting that proteolytic activation of hpai virus ha occurs not only through the trans-golgi network by furin and pc ⁄ , but also on the cell surface by mspl and tmprss . the pb -f protein, which is translated from the + reading frame of the pb gene segment, has been linked to the pathogenesis of both primary viral and secondary bacterial infections in a mouse model. - a mitochondrial targeting sequence is located in the c-terminal portion of the pb -f open reading frame, and expression of full length pb -f has been associated with mitochondrial targeting and apoptosis in a monocyte dependent manner. , it has been theorized that enhanced virulence could result from mitochondrial disruption with subsequent cell death mediated by pb -f . , a suggested second function of the pb -f protein is that it enhances immunopathology by triggering the inflammatory response. , in earlier studies from our group, the pro-inflammatory phenotype was markedly upregulated when the pb -f from the pandemic strain was expressed, arguing that this protein may be an important virulence factor for highly pathogenic pandemic viruses. , in this report we analyze the pb -f protein's contribution to pathogenesis in a mouse model, examining both inflammation and cell death. pb -f proteins from a variety of epidemiologically important iav strains including all pandemic strains from the th century, a highly pathogenic avian influenza virus of the h n subtype, and representative seasonal strains were utilized to determine the relevance to pandemic disease. we demonstrate that macrophage mediated immunopathology, but not apoptosis, are relevant functions of pb -f proteins from past or potential pandemic influenza viruses. using the predicted amino acid sequences of the pb -f proteins from pr , a ⁄ brevig mission ⁄ ⁄ , ⁄ singapore ⁄ ⁄ , a ⁄ hong kong ⁄ ⁄ , a ⁄ wuhan ⁄ ⁄ , and a ⁄ vietnam ⁄ ⁄ , peptides from the c-terminal end were synthesized as described. an additional n-terminal peptide was synthesized from the pr sequence as a positive control (mgqeqdtpwilstghistqk) as described. a panel of viruses were reverse engineered as described , and included laboratory strain pr , a virus unable to express pb -f (dpb -f ⁄ pr ), or expressing the pb -f of the pandemic strain ( pb -f ⁄ pr ) or the truncated h n strain (beij pb -f ⁄ pr ). , in addition, : reassortants encoding pb gene segments from a *current address: department of immunology and microbiology, university of melbourne, melbourne, vic., australia. highly pathogenic avian influenza of the h n subtype (h n pb ⁄ pr ), or from a human h n strain (h n pb ⁄ pr ) were utilized along with their isogenic deletion mutants for pb -f (h n dpb -f ⁄ pr and h n dpb -f ⁄ pr ). cell lines and cell death assays raw . cells were grown under conditions as described. cells were infected with one multiplicity of infection (moi) of virus for - hours, or exposed to lm (final concentration) of peptides derived from the c-terminal portion of pb -f for hour. cells from the supernatant and monolayers were harvested, washed, and stained with annexin (apc) and propidium iodide (pi) (becton dickinson, san jose, ca, usa), then analysed for cell death as described. six-to eight week old female balb ⁄ cj mice (jackson laboratory, bar harbor, me, usa) were maintained in a biosafety level facility in the animal resource center and procedures approved by the animal care and use committee at sjcrh. infectious agents and peptides were diluted in sterile pbs and administered intranasally to anesthetized mice (n = - ) in a volume of ll ( ll per nare) and monitored for overt signs of illness and weight loss daily. following euthanasia by co inhalation, the trachea was exposed and cannulated with a gauge plastic catheter (bd insyte; becton dickinson, sandy, ut, usa). bronchoalveolar lavage fluid (balf) was collected, red blood cell depleted, and cellular content analyzed via flow cytometry as described. one way analysis of variance (anova) was used for multiple comparisons of cell death and cellularity of balf. a p-value of < ae was considered significant for these comparisons. graphpad prism version . for windows (graphpad software, san diego, ca, usa) was utilized for all statistical analyses. to assess the contribution of pb -f to inflammation, we utilized a panel of previously described reverse engineered viruses in the mouse infection model. , the effect of pb -f expression was observed clearly in the inflammatory infiltrate in response to infection in the lungs. deleting pb -f from pr or expression of the c-terminally truncated beij pb -f had a significantly reduced influx of macrophages ( figure a) . expression of the pb -f caused similar inflammatory effects as the pr virus. disruption of pb -f expression the virus containing the h n pb gene segment in a pr background also significantly decreased the inflammatory response compared to the virus maintaining the ability to express full length pb -f ( figure a) . however, no differences were seen that could be attributed to the h n derived pb -f . the lungs of mice infected with the panel of pb -f variant viruses were examined at hours. pathologic changes typical of pr viral infection were observed in all lungs. these typical findings included perivascular inflammation, airway necrosis, hemorrhage, and deposition of cellular debris (figure ). in the lungs of mice infected with pr or pb -f ⁄ pr , however, significantly more perivascular cuffing was noted, with a prominent increase in numbers of macrophages (figure a, c) . the overall number of inflammatory cells throughout the lungs, including both airways and alveoli, was quantitatively greater in these mice than in mice infected with dpb -f ⁄ pr or beij pb -f ⁄ pr ( figure b, d) . as the function and influence of pb -f protein on normal viral function is not currently understood, and given the abrogation of enhanced inflammation induced by the truncated pb -f beij ⁄ pr virus, we sought to elucidate whether the c-terminal domain of pb -f could alone induce this inflammatory response. mice were exposed to a panel of peptides and were euthanized hours later for collection of balf. significant influxes of macrophages into the balf were seen following exposure to c-terminal pb -f peptides derived from pr , the pandemic strains from (h n ), (h n ), and (h n ), and the h n virus compared to controls ( figure b) . similar effects were not seen with the peptide derived from a more recent h n strain, a ⁄ wuhan ⁄ ⁄ . when peptide exposed mice were followed for morbidity for days, peptides proven to induce a heightened inflammatory response correlated strongly with overt clinical signs of illness (data not shown). thus, the ability to cause lung inflammation appears to be a property of pb -f proteins of viruses containing pb gene segments reassorted directly from the avian reservoir. the pb -f protein may contribute to virulence by rendering the host cellular immune response ineffective through inducing apoptosis. we sought to determine whether this was an epidemiologically important function for combating the host immune response to infection by testing the ability of pb -f proteins from several different iav strains to cause cell death. we therefore infected raw . cells with the panel of recombinant viruses at an moi of for - hours. as has been demonstrated previously, , , pr virus induces significant cell death compared to uninfected controls ( figure c ). when raw . cells were infected with pr virus, necrotic death peaked hours after infection. viruses lacking the c-terminal portion of pb -f , including the dpb -f ⁄ pr and the beij pb -f ⁄ pr were unable to cause cell death ( figure c ). in addition, expression of the pb -f also did not cause significant increases in cell death over controls. expression of pb -f or deletion of pb -f in either an h n or h n pb gene segment background similarly did not alter the cell death phenotype. to examine additional strains for which we did not have isogenic virus pairs, we next exposed the balbcj mouse derived macrophage cell line raw . to the panel of pb -f peptides derived from pr , the pandemic strains from (h n ), (h n ) and (h n ), and the h n for hours. cell death in raw . cells was caused only by the peptides derived from the laboratory strain pr and the peptide derived from the pandemic strain ( figure d ). viability was not affected by exposure of raw . to peptides derived from other virus strains. we conclude from these data that the mechanism by which pb -f contributes to the pathogenicity of pandemic influenza is unlikely to be through its reported ability to cause cell death. these data presented here demonstrate that the lung inflammatory response is enhanced by the influenza a virus pb -f protein in a mouse model. this inflammatory response was characterized by increased cellular infiltration of macrophages into the interstitial and alveolar spaces of the lungs, as well as enhanced perivascular inflammation, airway necrosis, hemorrhage, and deposition of cellular debris. this augmentation was shown to be induced by pb -f proteins only from those strains contributing to the formation of all pandemic strains of the th century and from the currently circulating, highly virulent h n strains that constitute an imminent pandemic threat. the iav h n strains circulating in humans since around code for a truncated pb -f . these viruses may lack the cterminal residues responsible for the inflammatory effects demonstrated in this publication. additionally, recently circulating h n strains, in contrast to their pandemic forbear from , have lost the capacity to cause pb -f mediated inflammation through mutation of the c-terminus of this protein. in a novel h n iav emerged from an animal reservoir and caused a human pandemic. disease burden from this strain has been considered mild in contrast to the three pandemics of the th century. the reasons for this disparity in pathogenesis are unclear. an examination of the origins of the three th century pandemics shows that only the hemagglutinin (ha) and pb gene segments were reassorted directly from the avian reservoir in every case, suggesting gene products of one or both of these may be important. the ha surface glycoprotein provided the antigenic novelty required for the each virus to achieve pandemic status. however, the significance of inclusion of a novel pb gene segment in each of the th century pandemics is not yet understood. we show here that the pb -f of these pandemic strains contributes to virulence through induction of inflammatory responses. thus pb -f may serve as a marker of the pathogenicity of pandemic strains. since the h n strain codes a truncated pb -f of only predicted amino acids, the lack of pb -f mediated inflammation may account in part for its relatively lower virulence. , of the panel of pb -f proteins studied, only that from the laboratory strain pr was capable of rendering responding host-immune cells ineffective by induction of cell death. we therefore hypothesize that molecular signatures specific to induction of apoptosis may have been lost through genetic mutation of the pb -f gene throughout the evolution of the iavs. our findings suggest that this apoptotic function is unlikely to be important for the virulence of any of the known pandemics. rather, the inflammatory phenotype appears to be the dominant contribution of pb -f to pandemic disease. influenza virus-cytokine-protease cycles are principal mechanisms of multi-organ failure in severe influenza and therapeutic approaches introduction influenza a virus is the most common infectious pathogen in humans, causing significant morbidity and mortality, particularly in infants and the elderly. mof with severe edema is observed in the advanced stage of influenza pneumonia. however, the relationships amongst factors that induce vascular hyper-permeability in severe influenza remain unclear. it is reported that significant increases in levels of pro-inflammatory cytokine levels, such as tnf-a, il- , and il- b, affect host survival both positively and negatively. the inflammatory response affects cell adhesion, permeability, apoptosis, and mitochondrial reactive oxygen species, potentially resulting in vascular dysfunction and mof. in addition, iav infection up-regulates several cellular proteases including ectopic trypsin and mmp- . up-regulated ectopic trypsin mediates the post-translational proteolytic cleavage of viral envelope hemagglutinin (ha), which is crucial for viral entry and replication and the subsequent tissue damage in various organs. the aim of the this study was to define the pathogenic impact of cytokine storm in iav infection and the molecular mechanisms by which pro-inflammatory cytokines and proteases cause vascular dysfunction in animal model. weanling female mice aged weeks (c bl ⁄ crslc) were infected with iav ⁄ wsn ⁄ ( pfu) with and without treatment of pdtc ( . mg ⁄ kg), nac ( mg ⁄ kg), and ndga ( mg ⁄ kg). these inhibitors were administrated once daily for days after infection. the levels of cytokines in tissue homogenates were measured by elisa kits. the effect of inhibitors on viral replications was determined by real-time pcr. gelatin zymography and western blotting were conducted as reported previously. host cellular responses in the airway after iav infection figure shows schematic view of typical biological responses in the airway of mice after iav infection. an initial response before viral proliferation is significant increases in pro-inflammatory cytokine levels. immediately after cytokine inductions, there is a marked up-regulation of ectopic trypsin along with an increase in virus titer in the airway, lung, and brain. ectopic trypsin mediates the post-translational proteolytic cleavage of iav ha, which is crucial for viral entry and replication and the subsequent tissue damage in various organs. we also found that iav infection markedly induces mmp- and matrix degradation. just after the peak of viral proliferation, the innate and adaptive immune responses of protective immunity are induced for defense and recovery, or oppositely on rare occasions, mof with vascular hyper-permeability is started into the advanced stage of influenza. the levels of tnf-a and il- in the lungs were increased persistently for days after iav wsn infection, and that of il- b peaked at days - post-infection (figure a ). since these cytokine responses are associated with activation of nf-jb and ap- , we treated mice once daily for days with anti-oxidant inhibitors: pdtc and nac against nf-jb activation, and ndga against ap- activation. pdtc and ndga significantly suppressed the up-regulation of tnf-a and il- b (p < . ), and nac suppressed tnf-a (p < . ), and il- (p < . ) at day post-infection. gelatin zymography showed up-regulation of ectopic trypsin and mmp- in mice lung, brain, and heart during infection for days ( figure b ). trypsin and mmp- induction was inhibited by treatment with pdtc, nac, and ndga, probably via blockade of nf-jb and ap- binding in the promoter region of the genes. viral rna replication in various organs at day post-infection was suppressed by more than one order of magnitude by pdtc, nac, and ndga ( figure c ). suppression of viral multiplication and induction of cellular factors by pdtc, nac, and ndga, significantly improved the survival of mice at day post-infection, the late stage of infection ( figure d ). to elucidate the mechanisms underlying brain vascular dysfunction of influenza-associated encephalopathy, changes in the levels of tight-junction proteins, intracellular zonula occludens- (zo- ) and transmembrane occludin, and the matrix protein laminin, were analyzed by western blotting. marked reductions in the expression levels of tight-junction constituents were detected at day post-infection, which were partly rescued by pdtc, nac, or ndga (figure e ). no other tight-junction protein, claudin- or matrix fibronectin and type iv collagen, were affected. the present study reports several new observations: (i) proinflammatory cytokines, tnf-a, il- b, and il- , when up-regulated by iav infection, induce trypsin and mmp- expression in various organs in mice; (ii) inhibitors of nf-jb and ap- effectively suppress the up-regulation of proinflammatory cytokines, trypsin, and mmp- and improve survival rates of infected mice. based on these results, we propose the 'influenza virus-cytokine-protease cycle' hypothesis as one of the mechanisms of vascular dysfunction in mof with cytokine storm in severe influenza and influenza-associated encephalopathy. the significance of pro-inflammatory hyper-cytokinemia, or 'cytokine storm,' in the pathogenesis of iav infection remains unclear. on the positive effects, cytokines promote lymphocyte activation and infiltration at the sites of infection and exert direct antiviral effects. however, on the negative effects of excess cytokines, the hyper inflammatory process evoked by viral infection may become harmful through intracellular activation of nf-jb, ap- , and the janus kinase-signal transducers and activators of transcription signaling pathways. , [ ] [ ] [ ] the in vivo experiments presented here showed that nf-jb and ap- inhibitors markedly suppress the expression of cytokines, trypsin, mmp- , and viral replication, resulting in a significant increase in the survival of infected mice. furthermore, cytokines interact with mitochondria to increase the production of reactive oxygen species, resulting in the production ⁄ activation of vasodilatory mediators such as nitric oxide and bradykinin, and subsequent endothelial dysfunction and edema in various organs. the molecular mechanisms underlying tight-junction disruption in endothelial cells and vascular hyper-permeability following the 'cytokine storm' remain unclear. tnfa up-regulation alters the cellular redox state, reduces the expression of four complex i subunits by increasing mitochondrial o ) production and depleting atp synthesis, decreases oxygen consumption thereby resulting in mitochondrial damage, , and increases [ca + ] i atp depletion dissociates zo- from the actin cytoskeleton and thereby increases junctional permeability. endothelial dysfunction induced by 'influenza virus-cytokine-protease cycle' in the early stage of severe influenza may further affect various circulating factors, coagulation factors and complement systems, and vascular interacting cells, such as neutrophils, macrophages and lymphocytes. mof is the final outcome of metabolic and mitochondrial fuel disorder, immunosuppression, endocrine disorder, and tissue injury followed by endothelial dysfunction in many organs. another key pathway of acute lung injury in the highly pathogenic avian influenza virus h n and acute respiratory syndrome-corona virus infection reported recently involves oxidative stress and formation of oxidized phospholipids, which induce lung injury via toll-like receptor signaling pathway. in addition to these data, up-regulated trypsin and pro-inflammatory cytokines may also affect tissue destruction and immunosuppression in the late stage of iav infection. further studies are required on the role of the 'influenza virus-cytokine-protease cycle' in the pathogenesis of mof, particularly in the late stage of viral infection. though influenza a virus replication kinetics and host responses have been previously studied in umbilical vein endothelial cell or transformed endothelial cell lines, the tropism of influenza a virus including h n and pandemic h n pdm for primary human lung microvascular endothelial cell has not been well defined. in this study we employed primary human lung microvascular endothelial cells, which are more physiologically relevant for understanding pathogenesis of influenza in the lung as to obtain a better understanding of the links of endothelial cell infection to systematic virus dissemination and multiple organ involvement in severe human influenza. supernatants of cells infected at moi of two were collected for cytokine protein assays, and total rna was extracted for gene expression analysis using qpcr. we found that seasonal influenza h n and h n viruses initiated viral gene transcription and viral protein expres- sion, but did not produce infectious progeny, while the highly pathogenic avian influenza h n and the pandemic influenza h n pdm virus could replicate even with the absence of exogenous protease (figure ) . furthermore, when compared to seasonal h n and h n , the h n virus was a more potent inducer of cytokine and chemokine including ifn-b, mcp- , rantes, ip- (figure ) , and il- , in virus infected endothelial cells, whereas h n pdm induced intermediate levels of cytokine and chemokine. avian influenza h n and pandemic h n pdm virus (but not the seasonal h n and h n virus) can productively replicate in human lung microvascular endothelial cells. this is likely to be of relevant to pathogenesis and provides a possible explanation for the extra-pulmonary infection seen in animal infection models. this extra-pulmonary spread may support the previous speculation and anecdotal evidence that h n and h n pdm virus can infect the gastrointestinal tract through the virus dissemination from the infected respiratory tract as the first target cells for influenza infection. [ ] [ ] [ ] in addition, the release of proinflammatory cytokine and chemokine induced by influenza h n and h n pdm virus infection in lung microvascular endothelial cells may be important contributors to the pathogenesis of severe human influenza disease leading to endothelial cell dysfunction that contributes to severe pulmonary disease symptoms. during its replication, influenza virus utilizes the host cellular machinery for many aspects of its life cycle. characterization of such virus-host protein-protein interactions is a must to identify determinants of pathogenesis. the m ion channel protein plays a crucial role during the entry and late stages of the viral life cycle where its c-terminal domain, well conserved among influenza a viruses, is accessible to cellular machinery after fusion with endosomal membrane and during its trafficking along the secretory pathway prior to assembly and budding. the aim of the study is to identify cellular interactants of m that play important regulatory roles during influenza infection. to identify cellular partners of m we performed a genome-wide yeast-two-hybrid (y h) screening approach using the cytosolic domain of m as bait and a human placenta random primed cdna library as prey and tested more than million interactions. from the y h screening, an interesting interaction with the human annexin a (anxa ) protein, a member of annexin family proteins that binds to phospholipds in a ca + -dependent manner, was identified. co-immunopre-cipitation of myc-tagged anxa and viral m proteins coexpressed in hek t cells after transfection and infection confirmed the direct interaction between anxa and m . we further investigated whether this interaction had any functional significance with regards to influenza life cycle. using a rna interference strategy to silence the anxa gene in human lung epithelial a cells, we observed increased progeny virus titers either in a single or multiple viral growth kinetics study, suggesting a negative regulatory role for anax during viral infection (figure ). a novel interaction between m and anxa was identified. more functional studies are in progress to define precisely the potential negative regulatory role of this interaction during viral infection. a systematic dissection of the viral life cycle will be performed to identify the step(s) affected by the anxa cellular factor using specific assays such as real-time quantitative rt-pcr in a single or multiple viral growth kinetics study, cell transduction with ha-and m -pseudotyped lentiviral particles, virion attachment and internalization assay, immunofluorescence staining of np protein as a marker of viral ribonucleoproteins localization, viral polymerase activity measurement, and viral budding observation by electron microscopy. rna extraction was achieved by qiagen biorobot ez prior to respiratory multiplex pcr analysis. what remained of the extracted material of each specimen was stored by refrigeration at °c. electronic patient records were searched for parameters, such as c-reactive protein (crp), white cell count (wcc), length of admission in days, and patient co-morbidities. patients were divided into three groups according to clinical severity: mild, moderate, and severe. the 'mild' group comprised of those admitted for three days or fewer, or not admitted at all. the 'moderate' group comprised those who required admission to hospital for more than days as a result of swine flu, but who did not require admission to an intensive care unit (itu). the 'severe' group comprised those who had required itu admission. invitrogen ' · reaction mix': ae mm of each dntp + mm magnesium sulphate. primer ⁄ probe mix recipe applied biosystems fast real-time pcr system, 'respiratory multiplex' program. well content ll; thermocycler initial stage ae °c for minutes, then °c for minutes. subsequent cycles of ae °c for seconds followed by °c for seconds for cycles. sequence detection software version . (applied biosystems). of clinical isolates analyzed, all samples produced amplification of pdh material; produced amplification of both swine flu and pdh material. human male dna (lot no. at ng ⁄ l, applied biosystems) at concentration calculated at ae cells ⁄ ll was diluted from ) to ) , yielding mean average ct values of respectively ae , ae , ae , and ae . plotting log of cell number versus ct gave a y = mx + c line from which ct could be interpolated into cell numbers. for swine flu quantification, a sample of swine flu ct ae was diluted through ) to ) . it must be noted that due to variability in resultant swine flu ct values, repetitions at these dilutions were done using an rna carrier ( lg ⁄ l, qiagen; cat no. ) in place of rnasefree water. the ) concentration was positive in nine out of assays; this fraction was used in the calculation described by simmonds to obtain a copy number of targets per reaction by the equation copy value = )ln(f), where f is decimal fraction of failure rate. here, f = ⁄ = ae ; )ln ae = ae copies. a control curve was generated with ct values of ae , ae , ae , and ae giving copy values of , ae , ae , and ae , respectively. using excel (microsoft office, ), these control series were adapted into formulae to convert swine flu and pdh ct values into copy numbers of these elements per reaction. simple division derived a value for swine flu copy per pdh copy, but this was chosen to be expressed as swine flu copy number per human cells. this will be referred to as the 'c' value. forty-two patients had known clinical details; average age was ae , female to male ratio : , and average admission length of days. of the mild group (n = ), nine cases were not admitted to hospital. of the remainder, the mean average admission length was ae days. mean average c value for all samples was ae · , with a standard deviation of ae · ; geometric mean was ae , and median average was ae . log(mean average c value) is shown for each severity group and for identified risk factors in the 'mild' severity group (figures a, b respectively) . in each case variation was too great to yield statistical significance. figure shows the range of c values observed in the 'moderate' severity group. > - · ; < - · > - · ; < - · > - · ; < - · > - · ; < - · > - · ; < - · > - · ; < - · > - · ; < - · > - · ; < - · > - · ; < - · > · ; < · > · ; < · > · ; < · > · ; < · > · ; < · > · ; < · in a study by duchamp et al., no significant correlation was observed between viral ct value and presence or absence of cardiaorespiratory disease, myalgia, digestive symptoms, or upper or lower respiratory tract infection (although a trend was observed towards patients presenting with signs of upper respiratory tract infection). to our knowledge, no other study has used a dual pcr for analysis of respiratory virus concentrations, and no study has attempted to correlate biochemical markers with respiratory virus concentration. the data exhibited a spectrum of c values, from values < · ) to over · . the three severity group standard deviations all overlapped with each other, preventing statistical significance. analysis of co-morbidities showed a high mean average c value when asthma was present ( ae · ), but again this was associated with an excessive standard deviation. whereas the median average c value in the presence of asthma was higher than the overall average c value ( ae versus ae ), it was significantly lower than the median c value when no co-morbidity was documented ( ae ). there are multiple caveats that may be the cause of such variety of c values obtained. the duration between initial rna extraction and study pcr had a range of to days, with mean average delay of days. the degradation of viral rna is an important contributor to assay variance and failure; rna degradation in clinical samples has been studied. [ ] [ ] [ ] degradation of human dna in clinical samples may have occurred. several studies have chartered degradation of stored human dna. , with regards to sampling, the clinical collection of throat swabs is naturally variable according to the method of the collector. a small number of bronchoalveolar lavage samples were analyzed, yet did not amplify, presumably due to rna degradation. the upper respiratory tract may be only a physical stepping stone for the virus, and take no further role in pathogenesis of severe disease (although undoubtedly is crucial for transmission). interestingly, a ferret study of pathogenesis observed that swine flu yields from the upper respiratory tract were greater than those given by ordinary seasonal h n , with consequently increased shedding. the review by mansfield cites significant findings regarding influenza pathogenesis, including the predilection of h n strains for type ii pneumocyte cells and alveolar macrophages. it also highlights the limitation of knowledge through dearth of human autopsy studies; an exception is the recognition of haematophagocytic syndrome in severe cases. it is known that specific immunoglobulin is effective against establishment of infection in the upper respiratory tract, whereas specific cytotoxic t lymphocytes (ctls) are necessary for clearance of the virus from the lower respiratory tract. it is also suggestive that a gap of two whole days transpires between initial infection and instigation of a specific immune response. it is plausible that in the healthy individual, virus progression is confounded by efficient natural mucosal immunity, in part through good secretory immunoglobulin levels. airway inflammation associated with asthma exacerbation is known to increase both risk of respiratory viral infection and poorer outcome. it is unproven but likely that the local inflammatory processes give rise to increased virion burdens in the upper airways; however, the same effect is conceivable for epithelial cell turnover. there will likely be variance within each clinical category due to patient circumstances and clinicians' judgment of required admission. unfortunately, the duration of symptoms prior to swab collection was often omitted in the clinical notes. finally, stratification of patient group by receipt of antiviral treatment was not studied. no correlations were observed with c values and crp, wcc or admission length. trends were observed towards higher c values in 'mild' cases, but without statistical significance. the relative small study size, coupled with the intrinsic variability of the parameters studied, warrants larger, better controlled, prospective studies to elucidate clinical use of the c value for influenza illness prediction and management. in mid-april a novel variant of a(h n ) influenza virus began to spread rapidly throughout the world, causing the first pandemic of the st century. the majority of the cases associated with this new virus show to be mild, but severe and fatal cases have been reported. molecular markers associated with severity have already been identified, as is the case of the mutation d g. resistant viruses to antiviral drugs have also been identified, highlighting the importance of rapid determination of the antiviral drug profile. global a(h n ) genetic characterization, molecular evolution dynamics, antiviral susceptibility profiles, and inference of public health implications require nation and region wide systematic analysis of circulating virus. the objective of this ongoing research study was, primarily, to thoroughly characterize the genetic profile and evolution of the emergent influenza a(h n ) virus circulating in portugal and its phenotypic expression on antiviral drugs susceptibility. the cases considered in this study were obtained from the community and from two collaborating hospitals in lisbon -a reference hospital for adults (hospital de curry cabral) and a reference hospital for children (hospital dona estefânia). the cdc real-time pcr protocol, recommended by world health organization (who), was the method used to confirmed all influenza a(h n ) cases. from a total of a(h n ) positive cases diagnosed and confirmed, were selected for this study, taking in consideration that they should cover the period of epidemic activity in portugal and include cases from persons belonging to risk groups and cases associated with more severe clinical features. ninety-six a(h n ) strains were isolated in mdck-siat cells, from combined naso-oropharyngeal swabs. for the evaluation of the genetic profile of a(h n ) virus circulating in portugal, of the isolates were characterized by genetic analysis of the ha, na, and mp genes. the remaining five gene segments (pb , pb , pa, ns, and np) were also sequenced for six of this isolates. briefly, sequencing was performed according to the protocol developed by cdc and recommended by who, using bigdye terminator v. . technology. nucleotide sequences were determined in a dna automatic sequencer abi prism xl genetic analyzer. for each genomic segment, genetic analysis was performed with lasergene v. . software (dnastar inc, usa) using an average of - overlapping readings, including sense and antisense, for precise nucleotide and amino acid sequence determination. genetic mutation and phylogenetic analysis were performed by neighbor-joining method, using mega . software, against published sequences from the vaccine strain (a ⁄ california ⁄ ⁄ ) and from selected a(h n ) strains available on gisaid epiflu database. all mutations were identified with reference to the vaccine strain genome sequence. antiviral drug susceptibility profile of a(h n ) influenza virus circulating in portugal was evaluated both phenotypically and genotypically for nais and genotypically for amantadine. phenotypic evaluation to nais, oseltamivir and zanamivir, was performed for all isolates by ic determination through munana fluorescence assays. genotypic evaluation was performed by searching for mutations associated with resistance to nais in all na gene sequences. amantadine susceptibility profile was performed for all isolates by searching on m sequence for the molecular markers associated with resistance to this antiviral drug (l f ⁄ i; v a ⁄ d; a t; s n; g e). genetic characterisation of the ha subunit of ha reveals point mutations in different strains. all analysed strains present p s and i v mutations, which distinguish them from the vaccine strain ( figure a ). thirty-three of the sequenced strains group in the s t branch. this mutation is referred in the literature as being associated with the putative antigenic site ca. most of these strains ( ) further subgroup in the d e branch, this mutation being associated with one loop of the receptor-binding site. from the early to the late epidemic period, an increased circulation of virus carrying the mutation s t was observed. this is in agreement with the association between this mutation and an enhanced viral fitness that is described in the literature. additional mutations were also observed in a small number of virus, of which we highlight: regarding the genetic characterisation of na, the majority of strains analysed ( of ) presents the mutations n d and v i ( figure b) . as mutation s t in ha gene, these two na mutations are described in the literature as associated with enhanced viral fitness. the few strains not carrying these mutations have circulated in the beginning of the epidemic period. fifteen of the analysed strains further subgroup in y h branch. additionally, mutation i v was identified in two strains. for the remaining gene segments available for the six analysed strains, the observations include: (i) no previously described virulence markers in pb , pb -f , and ns were detected; (ii) pb -f protein is present in the truncated form of amino acids; (iii) the presence of mutations i v and l q in ns and v i in np; (iv) the described association of mutation i v in ns and v i in np genes with viral fitness. phenotypic evaluation of nais susceptibility revealed the existence of three minor and two major outliers to oseltamivir ( figure ). the two minor outliers exhibited a reduction of approximately twofold in the susceptibility to this antiviral drug, comparing to the baseline level, while the reduction exhibited by the two major outliers was of approximately three-and fourfold. regarding zanamivir, two minor outliers were identified with a reduction of approximately twofold in the susceptibility, compared to the baseline level. these two minor outliers (a ⁄ portugal ⁄ ⁄ and a ⁄ portugal ⁄ ⁄ ) correspond to the two major outliers identified for oseltamivir. genetic analysis revealed the presence of the mutation i v in the na sequence of these two strains. the contribution of this mutation for the profile of reduced susceptibility identified for both nais is not known, but a mutation in the same na position (i r) has been referred to as being associated with a reduction in nais susceptibility. full genome sequence analysis of these strains shows that both strains also present the v i mutation in pb gene. however, no association of this mutation with antiviral drug susceptibility is referred in the literature. concerning genetic evaluation of susceptibility to amantadine, all analysed strains present a serine in position , which is a molecular marker of resistance to m inhibitors. these preliminary results allow us to discuss several points. however, the additional data that is being obtained through this ongoing study will be essential for a more complete analysis. for example, more information is needed to determine if the mutations found alter the biology and the fitness of the virus or if there are associated with an increased prevalence of the virus. the majority of the mutations identified in ha subunit have been detected in a(h n ) strains distributed throughout the epidemic curve, not evidencing a specific evolutionary trend. this is in agreement with the genetic and antigenic homogeneity that has being described for a(h n ) virus. the occurrence of mutations in the position of the ha subunit of a(h n ) virus have been described. however, more studies are needed to clarify the outcome of these mutations, as for example in patients with severe complications. it could also be relevant to investigate the presence of single and mixed variants in viruses and in clinical specimens and the possibility of these mutations affecting the binding specificity. regarding the susceptibility of a(h n ) pandemic viruses to antiviral drugs, all analysed strains were found to be resistant to amantadine. this resistant profile was not unexpected since the mp gene from this new variant had originated in the eurasian swine lineage, which is characterised by being resistant to this antiviral drug. the majority of the a(h n ) strains analysed revealed to be susceptible to both nais, with only five strains exhibiting a profile of reduced susceptibility, three to oseltamivir and two to both nais. for these last two, the presence of the i v mutation in the na sequence could explain the reduction observed, but a more complete analysis is needed to confirm this. the french national pandemic plan includes an early containment phase followed by a limitation phase. the efficacy of such a plan depends on pre-existing surveillance and laboratory networks. the grog community surveillance network and the hospital lab networks organized by the two french nics carried out the virological monitor- the efficacy of such plan depends on pre-existing influenza surveillance and laboratory networks. in france, the community surveillance is carried through the grog surveillance network. in addition, surveillance is also carried out in hospitals by the renal network. this renal network is divided in two sub-networks: the so-called h -labs network, activated during the containment phase and the extended renal lab network activated in the limitation phase. the h -labs have bsl- facilities that can be used for diagnosis purposes. as part of the national influenza surveillance system led by the french institute for public health surveillance (invs), the grog community surveillance network and the lab networks linked to the two french nics carried out the virological monitoring of the a(h n ) pandemic from the early containment phase up until the end of the pandemic phase. during the containment phase, all suspected cases were hospitalized and declared to invs. each patient was tested on the same day by specific virological diagnosis. hospital admission was not mandatory during the limitation phase, (i) the clustered cases were monitored to study transmission chains, and (ii) the circulation of the virus in the community was monitored through grog swabs collected by practitioners. the nics organized the influenza surveillance to fulfill several objectives according to the epidemiological situation. first, rt-pcr tools (influenza a m gene rt-pcr and a(h n ) specific h and n genes rt-pcrs) were developped and distributed to the lab networks on the th of may . from the early phase, the nics and the h -lab network analyzed all the samples collected from hospitalized and community patients. during the early phase of the limitation phase, an increasing number of labs were performing the specific assays. when the pandemic wave started, all hospital labs could do the testing. results were centralised by nic and reported on a weekly basis. in addition, nics carried out the monitoring of antiviral resistance emergence (na pyrosequencing, specific h y rt-pcr, and phenotypic assays), and real-time surveillance of genetic changes involved in virus adaptation (pb ) virulence factors or antigenic variations (ha). this sequencing was carried out by the pf sequencing platform of the institut pasteur. the first imported a(h n ) influenza cases were observed from the th of april . a limited number of cases have been reported in may. local transmission could be detected end of may. clusters were observed in schools in june and in summer camps during summer. as opposed to the epidemiology of the a(h n ) virus in other european countries, no summer wave was observed in france. only a limited number of sporadic cases were reported up until october. early september, a significant number of cases presenting with influenza-like illness was reported (figure ). the virological investigation of these cases showed high prevalence of rhinovirus infection. this circulation of rhinovirus was a counfounding factor of the pandemic. the pandemic wave lasted weeks between mid-october and the end of december (week to week , figure ). the pandemic wave started week - in the ile-de-france area, and only week - in the rest of france. the peak was recorded week ( figure ). the impact of the pandemic was mainly observed in the - years group of age. overall, severe cases have been admitted to the hospital, and deaths have been recorded by the end of the pandemic wave. the major impact was observed in the - years group of age ( % of deaths recorded). amongst the severe cases and the deceased cases, % and % of cases had no risk factor, respectively. these specimens, were positives for h n , representing ae % of total influenza virus detections. only nine brisbane-like h n , brisbane-like h n , and eight b viruses have been detected in the same period of time. the weekly positive rate ranged from % to %. phylogenetic and antigenic analyses of the viruses collected during the pandemic wave did not show any emerging genetic or antigenic variants (figure a,b) . eight patients, all among cases presenting with severe illness, were infected by a virus harbouring the d g mutation in the ha. amongst the virus tested for antiviral susceptibility or screened for the h y mutation by or specific rt-pcr, only oseltamivir-resistant viruses related to the na h y mutation have been detected. one of these cases also had an i r mutation associated to a reduced sensitivity to zanamivir. all but one resistant virus were detected in treated immunocompromised patients. overall, eight patients presented a virus with the d g mutation in the ha. all these patients had a severe infection; one of these had also a h y mutation in the na asociated to oseltamivir resistance. the pandemic started by the end of april . although the first cases recorded were as early as the th of april, the epidemic wave associated with a widespread spread of the virus was only recorded in october. the french population did not have to face a summer wave, as observed in north america and in numerous european countries. , it is difficult to speculate the reasons for the lack of summer wave; the specimens collected were negative for influenza. moreover, during september, it was anticipated that school openings would be the trigger for the beginning of the pandemic wave. as a matter of fact, a significant increase of influenza-like syndromes were observed at that time, but the virological investigation carried out by the laboratories showed thta is was related to a very large epidemic of rhinovirus. the epidemic circulation of other respiratory viruses can be counfounding factors for the surveillance of the influenza epidemic clinical when the survellance is only based on collection of clinical information. the starting of the pandemic wave was heterogeneous in france. the ilede-france region (paris and its suburbean area), where the population is dense, experienced an early start as compared to the rest of france. however, once the pandemic started in the rest of the county, the epidemic curves were quite similar. the peak was reached at identical times, although it may have been delayed in some remote places in france. overall, we estimate that % of the french population consulted for an ili presentation. the impact was mainly observed in the - years groupe of. however, this age groupe represented only a limited number of severe cases and deaths. on the other hand, the - years groupe of age, where the prevalence was not high, was the age group where the majority of severe cases and deaths was recorded ( % and %, respectively). this data is consistent with the observational data reported by numerous other countries. according to the profile of hospitalized cases, a(h n ) was more aggressive than seasonal viruses. the number of admission to the hospital was ten-fold that observed during a normal influenza epidemic. even if the mortality was limited ( cases), the age distribution of the deceased patients was different as compared to seasonal influenza ( % mortality in < years of age). the lack of recordeable excess mortality has been interpreted to be the consequence of a very mild pandemic, milder than some seasonal epidemics. however, the median age of the fatal cases was much younger than those observed during the seasonal flu, leading to a mis-interpretation of the real impact of the pandemic. when the impact is measurered in loss of years of life, the impact of this pandemic is larger than seen with seasonal influenza, and is quite comparable to these of the two last pandemics. the pandemic preparadness of numerous countries, the develoment of new intensive care techniques and equipment, and the large use of antivirals have reduced the overall impact of this pandemic. these are new factors that should be taken into account when evaluating the real impact of the h n virus. the virological monitoring of the pandemic was achieved by the community-based and hospital-based sea- sonal influenza networks, reminding the importance of maintining such networks. the diagnosis of influenza in most of the patients was carried out by molecular techniques. it has been clearly stated from the beginning of the pandemic that near-patient tests were lacking of susceptibility and could not be used for patient management. the distribution of a set of validated and comprehensive techniques by the two nic was very helpfull for the monitoring of the pandemic and the patients. however, this diagnostic procedure change should not preclude maintaining virus isolation that is necessary for whole genome analysis, monitoring of antigenic changes, and phenotypic testing for antiviral testing. some of the mutants that have been recorded, including viruses with antiviral resistance phenotype or genotype, could be analysed from grown virus strains. it is striking that despite a large antiviral usage, only a limited number of isolates had mutations associated to resistance. however, the frequent isolation of such resistant virus was observed in immunocompromised patients that presented severe infections and long virus shedding. the impact of the pandemic is still under evaluation. sero-epidemiological analysis will be performed to asses for the real attack rate of the pandemic virus. as in other countries, it has been recorded that asymptomatic infections could be observed frequently. it is quite unlikely that the impact of the pandemic was reduced by the vaccination campaign, although this vaccination started on the th of november, just when the pandemic started in france. it is estimated that millions received the vaccination. pandemic strains of the influenza virus sporadically emerge, deviating from the regular endemic strains of seasonal influenza. in april , a novel pandemic influenza virus a ⁄ h n emerged, swiftly spreading across the world. immediately, domestic and international public health agencies were forced to develop containment and mitiga-tion strategies in response to the pandemic. however, the dynamics and transmission patterns of this novel virus are yet to be fully understood. simultaneously, seasonal strains of influenza (a ⁄ h n , a ⁄ h n , and b) continued to circulate in many nations. both pandemic and seasonal variants of influenza are responsible for significant morbidity and mortality. to characterize the dynamics of this disease and the variation within strains, a more detailed understanding of the patterns in viral shedding during natural infection is required. the majority of data on the patterns of viral shedding during influenza infection are a result of volunteer challenge studies. in these studies, volunteers are commonly screened for pre-existing immunity against the challenge strain and are of a certain demographic and age. information on the patterns of viral shedding in natural influenza infections, pandemic or seasonal, is limited but should provide greater generalizability. we describe the trends of viral shedding and clinical illness in community acquired cases of pandemic and seasonal strains of influenza. in , a community-based study was conducted to analyse the effectiveness of non-pharmaceutical interventions to prevent the spread of influenza in households. in , a similar community-based study was initiated to collect comparative data from individuals infected with seasonal and pandemic influenza. both studies were conducted with very similar protocols, involving households in total. the specimens and symptom data required for this study all arise from secondary infections ascertained in these two community-based studies. the recruitment process in both studies was essentially identical. index cases were first recruited from their healthcare provider if they presented with influenza-like illness (ili). this individual would be included in the follow-up if he ⁄ she tested positive for influenza virus infection by rapid antigen test (quickvue) and was the first person in his ⁄ her household that showed signs of ili in the previous weeks. follow-up consisted of three home visits that spanned approximately - days. at each home visit, nasal and throat swab (nts) specimens were collected from all household members, regardless of the presence or absence of symptoms. symptoms were recorded in daily symptom diaries provided for every household member, and digital thermometers were provided to record daily tympanic temperature. the symptoms recorded were fever ‡ ae °c, headache, myalgia, cough, sore throat, runny nose, and phlegm. influenza virus infection and subtype was identified by reverse transcription polymerase chain reaction (rt-pcr) on the nts specimens. viral shedding was quantified from the same specimens by rt-pcr to determine viral loads, as well as by quantitative viral dilutions to determine median tissue culture infectious dose (tcid ). the details concerning laboratory methods have been described in a previous study. all analyses in this study focus exclusively on secondary cases; these are household contacts of recruited index cases who acquire influenza virus infection following the initial home visit. index cases generally presented with a certain threshold of illness severity requiring medical attention, whereas infections among household contacts can vary from asymptomatic to severe representing naturally acquired influenza infections. these secondary cases must be negative for influenza for their first nts specimen, and subsequently tested positive. we analysed mean viral loads measured by rt-pcr and quantitative culture by plotting by day since acute respiratory illness (ari) onset according to strain of influenza (pandemic a ⁄ h n , seasonal a ⁄ h n , seasonal a ⁄ h n , and seasonal b). ari is the reference time point, because the day of infection is unknown and is defined as the presence of ‡ of the symptoms mentioned above. average symptom scores were also plotted according to ari onset and grouped into upper respiratory symptoms (sore throat and runny nose), lower respiratory symptoms (cough and phlegm), and systemic signs and symptoms (fever ‡ ae °c, headache, and myalgia). mean daily tympanic temperatures were also plotted since date of ari onset and according to strain of influenza virus. all analyses were conducted using r software (version . . ; r development core team). a total of households and individuals were followed-up in the two studies. of household con-tacts tested by rt-pcr, were found to be influenza positive. among these influenza infections, ( ae %) were asymptomatic (rt-pcr positive plus symptoms recorded), were subclinical (rt-pcr positive plus symptom recorded), and presented with an onset of ari during the follow-up period. from the cases with ari onset, seven pandemic a ⁄ h n , seasonal a ⁄ h n , seasonal a ⁄ h n , and seasonal b influenza virus infections were identified. the age distribution among secondary cases was observed to be largely comparable across the four strains of interest (table ). there were a lower proportion of males who acquired pandemic a ⁄ h n compared to the seasonal strains of the virus. cough was the most commonly reported symptoms during follow-up in cases of pandemic a ⁄ h n and seasonal b, whereas runny nose was most common in seasonal a ⁄ h n and a ⁄ h n cases. cumulatively, fever ( ‡ ae °c) was reported in approximately half ( %) of the secondary cases. patterns of viral shedding were analysed in a subset of influenza positive individuals who recorded an onset of ari in their symptoms diaries (figure ). household contacts that were asymptomatic, subclinical, or did not have an ari onset were excluded from the analysis. viral shedding in all three influenza a strains were recorded to occur on the day of ari onset or day post-ari onset. follow- ing the peak, measured levels of viral shedding declined steadily to undetectable levels over - days. the trend of viral shedding in influenza b infected individuals rose days before ari onset, fluctuated for around days before eventually resolving. the patterns of viral shedding over time measured by quantitative viral culture were generally similar to the patterns measured by rt-pcr. the patterns of symptoms and signs were comparable in the four strains of influenza included in this study, peaking on the day or day post-ari onset, and gradually declining over a period of - days. in all strains, systemic symptoms and signs were observed to resolved faster than upper and lower respiratory symptoms. the trend of tympanic temperature in each influenza strain was comparable to the respective symptom pattern. patterns of viral shedding observed in influenza a strain infections (pandemic a ⁄ h n , seasonal a ⁄ h n , and seasonal a ⁄ h n ) were broadly similar. the pattern differed from the observed pattern of viral shedding in seasonal influenza b infections. the majority of viral shedding in influenza a strains occurred at and near ari onset, whereas there were variable amounts of viral shedding preand post-ari onset for those with influenza b. the biological reason for this difference is yet to be clarified. these differences are consistently observed regardless of laboratory method used to quantify the viral loads. it was observed that viral shedding measured by tcid resolved more quickly than when measured by rt-pcr, suggesting that rt-pcr is more sensitive, but it could be detecting inactivated fragments of rna instead of active virus. the trends observed for the seasonal strains of influenza in this study were similar to those reported in literature. the patterns of symptoms and signs as well as tympanic temperature in the four different strains of interest in this study were found to be comparable. these patterns closely resemble the patterns of viral shedding observed in the influenza a virus strains, but not in the influenza b virus strain. the trends of viral shedding, symptom scores, and tympanic temperature for pandemic a ⁄ h n were similar to trends observed for seasonal a ⁄ h n and seasonal a ⁄ h n infections, suggesting that the dynamics of these viruses are largely the same. the clinical course of infection with pandemic a ⁄ h n influenza virus appeared to be similar to the seasonal b influenza virus, but the patterns of viral shedding over time diverges. in general, our results suggest that the dynamics of the pandemic a ⁄ h n virus were similar to the seasonal a ⁄ h n and a ⁄ h n viruses, and clinically similar to the seasonal b virus. this study faced sample size limitations; very few cases of pandemic a ⁄ h n were detected and the secondary attack rate in general was low, though a total of households were followed up. this lack of power led to the inability to analyse the differences between adult and children and other characteristics that could be correlated with amount of viral shedding. there are also biases that must be factored in during recruitment. the eligibility criteria of only healthy households could select for households with higher innate immunity. on the other hand, recruitment at health care providers can be biased towards index cases that had more severe illness that required medical attention. the strength of the study is the broad generalizability of the results due to the strict classification of secondary cases. the infections reported in this study were all community-based and should represent true natural infections. pandemic potency of the influenza virus is largely determined by its transmissibility. the first objective of this study was to model the transmission of influenza h n and h n viruses. at present, vaccination with laiv has been used as a widespread, effective public health measure for influenza prophylaxis. some unsubstantiated concerns have been raised about a potential possibility of reassortment of circulating influenza viruses with laiv viruses following vaccination with laiv. thus, another objective of this study was to assess the probability of pig-to-pig transmission of cold-adapted viruses and their potential reassortment with wt influenza strains. female albino guinea pigs weighing - g were inoculated intranasally with eid of virus without anaesthesia. transmission studies were then performed hours after inoculation. inoculated animals were housed at % relative humidity and °c in the same cage with noninfected guinea pigs or in cages placed m away from non-infected pigs. virus replication was determined by virus isolation in hen eggs and by pcr. sera were collected at and days post inoculation. seroconversions were assessed by routine hai test. genome composition of reassortants was monitored by rflp analysis. capacity of the viruses to grow at optimum, low, and elevated temperatures (ca ⁄ ts phenotype) was evaluated, and virus growth properties were observed following virus titration in hen eggs. when infected pigs were co-caged with non-infected (naïve) individuals, vn , indo ⁄ , a ⁄ california ⁄ ⁄ , and nibrg- were isolated in %, % ae %, and % of contact animals, respectively. serological confirmation of virus transmission was higher than virological data ( %, %, %, and %, respectively). in addition, it was shown that when pigs inoculated with a ⁄ california ⁄ ⁄ were co-caged with animals inoculated with nibrg- , they got infected with both viruses ( table ) . the ability of direct transmission of cold-adapted viruses was also investigated. data show that the a ⁄ ⁄ california ⁄ ⁄ laiv candidate was detected in the upper respiratory tract of ae % vaccinated pigs. the mdv was identified in % of infected animals. however, neither group of contact pigs, co-housed with the vaccinate pigs, had evidence of infection with cold-adapted viruses. in addition, none of the contact pigs had any evidence of seroconversion to the coldadapted viruses as determined by hai assay. it was also most interesting to note that pig-to-pig transmission of the highly transmittable nibrg- reassortant virus was not seen when pigs, vaccinated with mdv, were co-caged with animals infected with nibrg- virus (table ) . this strongly implies a form of interference or protection from transmissibility that was provided by the cold-adapted virus. the results show that nibrg- and indo ⁄ viruses were able to spread between cages over the m distance ( % and % naïve animals were successfully infected, respectively). a ⁄ california ⁄ ⁄ influenza and vn viruses did not transmit between infected and non-infected guinea pigs housed in separated cages (table ) . pigs with confirmed a ⁄ california ⁄ ⁄ virus replication were also infected with nibrg- virus if h n -and h n -infected animals were separated by a space. thus, influenza virus transmission from h n -to h n -infected pigs has been shown, but the reverse pattern did not occur. transmission of nibrg- or a ⁄ california ⁄ ⁄ viruses was not observed when contact pigs were first vaccinated with the mdv and housed at a m distance ( table ) . it was also shown that efficiency of transmission of nibrg- was much higher than of other studied h n viruses; it can be transmitted between naïve guinea pigs separated from infected animals at a distance of - m (data not shown). five reassortants were isolated from animals which were infected with a ⁄ california ⁄ ⁄ virus and co-caged with pigs inoculated with nibrg- . two reassortants possessed different combinations of pr , nibrg- , and a ⁄ california ⁄ ⁄ genes and demonstrated the non-ca ⁄ non-ts phenotype typical of wt viruses. unexpectedly, two other reassortants inherited ha gene from nibrg- , na gene from a ⁄ california ⁄ ⁄ , and other genes from pr became ca and ts. : non-ts reassortant inherited pa gene from pr and seven other genes from a ⁄ california ⁄ ⁄ , gained ca properties. in spite of aforesaid experimental data, we cannot exclude the theoretical possibility of simultaneous infection of human host with cold-adapted and wt influenza viruses. to better understand possible consequences of such a reassortment event, we co-infected guinea pigs with a mixture of mdv and nibrg- viruses. nasal washes were collected and cloned by limited dilutions in hen eggs in the presence or absence of immune serum to the mdv. cloning of nasal washes without antiserum led to isolation of over clones, which were all identical to the mdv (data not shown). when nasal washes were cloned in the presence of antiserum, only nine clones were isolated. genome composition analysis showed that all isolates were triple reassortants, which had inherited pb and na genes from mdv, pa gene from pr , and ha gene from nibrg- . the origin of the other gene segments (pb , np, m, ns) in the genome of guinea pig-derived reassortants varied. reassuringly, all reassortants generated in vivo had the phenotype typical of the mdv. the severity of influenza outbreaks is partly determined by efficient spreading of the causative virus strain between human hosts. however, little is known about mechanisms underlying influenza virus transmission in humans. guinea pigs have been shown to be a suitable model for influenza transmission studies. our in vivo study showed that influenza a viruses vary in their transmissibility. nib-rg- and indo ⁄ viruses were able to transmit to naïve animals caged distantly from infected animals. in contrast, cold-adapted viruses, the same as those used for licensed laivs, showed no signs of transmission from one guinea pig to another. our study also provided evidence of a lower level of transmissibility of the novel pandemic h n virus compared to the nibrg- and indo ⁄ h n strains evaluated. benefits of vaccination with laiv to aid in the control of influenza outbreaks are acknowledged by the who. in our study, the mdv inoculated into guinea pigs appeared to interfere with and even offer protection from transmission of the highly transmissible nibrg- virus. the ability to immunize with the laiv and subsequently block the spread of a homologous h n subtype and a heterologous h n subtype influenza virus between guinea pigs has been shown. interference between cold-adapted and wildtype influenza virus infection was the most likely explanation for the data observed in our study. the mdv inoculated into guinea pigs might in some way interfere with transmission of highly transmissible influenza viruses. it is believed by some that widespread use of laiv could increase the potential risk of reassortment of the vaccine strain with circulating influenza viruses immediately following vaccination. however, it was shown that any such potential reassortments would most likely lead to yet attenuated viruses. our in vivo studies have shown that introduction of mdv genes into the genome of nib-rg- virus led to the generation of triple reassortants inherited pb and na genes of mdv and ha gene of h n virus. all isolates possessed phenotypical markers associated with attenuation of mdv. our data suggest that even if a reassortment event of such rare occurrence between a laiv strain and a circulating virus were to occur, it would most likely lead to a reassortant that would retain highly attenuated phenotypic properties of the vaccine strain. our data strongly support the safety of laivs, especially those developed against highly transmissible h n and h n pandemic influenza viruses. this information builds upon databases that have clearly shown the low likelihood of transmitting an laiv, as well as the high likelihood of any field reassortment of laiv with a circulating influenza virus to retain important properties of the cold-adapted, temperature-sensitive vaccine master composition. very interestingly, we also present data that show the potential of a laiv to prevent the transmission of highly infectious influenza viruses, perhaps identifying a broader role for laiv in the overall scheme of influenza virus prophylactic use. background: schlieren imaging is a non-invasive, real-time airflow visualization technique that relies on differences in air temperatures (and the resulting changes in the refractive index) to allow exhaled human airflows to be seen clearly against the background of more-stationary, ambient air. recently, this technique, well-known to engineers, has been applied to better understand and characterize airflow behaviors associated with everyday, as well as healthcarerelated, human respiratory activities. materials and methods: as a surrogate marker for the behavior of airborne infectious agents, schlieren imaging was used to visualize the airflow patterns produced by adult human volunteers of different ages while coughing with and without the wearing of standard surgical and n masks. results: the cough plumes were generally similar in shape and range for all the adult volunteers used in this study. although both the surgical and n masks decelerated and blocked some of the forward momentum of the coughed airflows, much of the cough plume was redirected and escaped around the top, bottom, and side edges of the masks to merge with the volunteer's natural, verticallymoving thermal plume. conclusions: schlieren imaging is a safe technique for visualizing exhaled airflows from human volunteers without the need for potentially-irritant or toxic particle tracers. findings from these schlieren imaging experiments will assist the development of more effective aerosol infection control guidelines in healthcare premises where patients infected with potentially airborne infectious agents (e.g., influenza and tuberculosis) are present. these infectious agents may be transmitted to healthcare workers, other patients, and their visitors by way of exhaled airflows. with the recent influenza pandemic , and the ongoing concerns about human cases of avian influenza h n infections, there is now a very real concern about the potential for the aerosol transmission of respiratory pathogens. such concerns amongst staff and patients in healthcare environments have led to a greater emphasis on the understanding and control of infectious airflows. , previous visualization techniques have used potentially-toxic or irritant gas or particulate tracers with hazardous laser light sources that have precluded the use of human volunteers as subjects. instead, various forms of lung models that simulate human respiratory patterns with such particulate tracers have been used. , schlieren imaging is a technique familiar to engineers and offers a non-invasive (i.e., no tracer required) airflow visualization method that depends only on differences in the refractive index of the warmer, human-exhaled air and the cooler ambient air. the use of a simple incandescent or light-emitting diode (i.e., non-laser) light source is safe and allows human volunteers to be used as experimental subjects, where their exhaled airflows are then observed using a large, precise spherical or parabolic telescopic mirror and a camera, and are recorded for later analysis and presentation. [ ] [ ] [ ] the analysis of these patterns of 'real-life' human airflows will be useful in optimizing aerosol infection control guidelines, which aim to reduce the transmission of airborne infectious agents to other healthcare personnel, patients, or their visitors. the images and analysis presented here have all been obtained from the large m diameter parabolic mirror (figure ) situated at the gas dynamics laboratory of penn state (directed by gary s. settles). this large schlie-ren imaging system has been in use for over years to obtain high quality schlieren images for various engineering applications. it has only recently been applied to clinically-relevant imaging. the objective of this paper is to augment and expand upon the details of the methods and results presented in an earlier study using this same schlieren imaging system. the aim of this series of studies is to visualize and capture a series of airflow images produced by coughing from adult human volunteers of different ages ( - years old). these included males (three of years, one of years of age) and females (one of years, one of - years, and one of - years of age). each volunteer was tested with and without wearing either a standard surgical mask or n mask. more specifically, the aim was to visualize the extent and direction of leakage around the mask whilst each subject was coughing. penn state institutional approval for experiments involving human subjects was also obtained. each volunteer was asked to stand approximately m in front of the schlieren mirror, facing across the surface of the mirror on one side, and to cough several times as the real-time, color image and video footage was recorded by the operator (using a nikon d camera; nikon inc. melville, ny, usa). this process was repeated whilst each volunteer was wearing a standard surgical mask then an n mask (supplied by mÔ, st paul, mn, usa). some of the schlieren images obtained from some of these volunteers have been published previously: for a -year old male, the year-old female and a -year old male, and the - year-old female. this article completes this series of schlieren images obtained from these experiments by including the images recorded for the older, year-old man. generally, it was found that the shape of the cough plumes (shown in the figure as darker shadows emanating from the subject's mouth) produced by adult humans of different ages was relatively similar. cough plumes are roughly conical in shape and very turbulent, usually passing beyond the extent of the m mirror (figure a) . a previous detailed study of one of these images measured a maximum airflow velocity of m ⁄ second for an adult cough. similarly, the effects of wearing surgical and n masks can be generalized across different ages. wearing a surgical mask allows leakage of the coughed air from the sides, top, and bottom of the mask ( figure b ). there is also some leakage through the mask, as indicated by the darker patches of air directly in front of the mask ( figure b, c) . the useful effect of the mask appears to be a deceleration and redirection of this coughed (and potentially infectious) air into the natural, upward-rising human thermal plume, which captures it and carries it upwards where it is diluted and less likely to transmit infection to others. the effects of the n mask are similar (i.e., deceleration and redirection), yet due to its tighter (mask-fitted) face seal, more of the coughed air appears to penetrate the front of the mask ( figure c ). this penetrating air is, however, also decelerated sufficiently to allow the wearer's natural thermal plume to carry it upwards. , discussion from these series of schlieren images presented in this and other related studies, [ ] [ ] [ ] it is clear that schlieren imaging offers a safe, non-invasive, real-time technique to visualize human exhaled airflows for all age groups. it is apparent that, at least where airflow patterns are an acceptable surrogate marker for airborne transmission risks, there are beneficial effects of wearing either type of mask, even when the mask fit is relatively poor. this is often the case when n -style masks are purchased and used by the general public -in contrast to the situation with healthcare workers, who are often accurately fit-tested for this type of mask. the immediate significance of this can be seen when masks are bought by parents for their children. often, these will not be of pediatric size and the mask-fit will be loose. children are well-known to be major sources of infection in the community because of their relatively poor immunity to many types of infectious agents due to their young age and, therefore, limited past-exposure history. these images allow infection control teams to literally see how far and how fast potentially-infectious human exhaled airflows can travel from an individual. this may have significant implications for guidance on the wearing of masks for infected staff and patients, on ward bed-spacing, as well as for the types of masks to be used in different situations. the important practical potential lies in the non-intrusive visualization of airflows associated with human volunteers, to assist in heightening the awareness amongst healthcare workers of the risks and potential for the airborne transmission of infectious agents, as well as the development of more effective aerosol infection control policies. schlieren images can be analysed more quantitatively, e.g., with the 'schlieren-piv' technique, , though this additional quantitative data is probably more of research interest than being of immediate practical use to everyday hospital infection control teams. these are the subtypes that we have studied. clearly, the question arises as to whether the changes in antigenicity are coupled with changes in germicide susceptibility. we have employed a modified log-reduction method in a cell culture system employing mdck cells in serum-free ex-cellÔ medium supplemented with trypsin. microscopic examination of cpe was the marker for infectivity together with plaque assay. we confirmed antiviral potency by using specific subtype influenza identification subtype technology, quidel quickvue Ò influenza a + b test. the log inactivation and percent inactivation by bac after a second contact time for the h , h , and h pandemic strains are as follows: a ⁄ swine ⁄ iowa ⁄ ⁄ h n , ae log ⁄ ae %; a ⁄ swine ⁄ cal ⁄ h n , ae logs ⁄ ae %; a ⁄ j ⁄ ⁄ h n , logs ⁄ ae %; and a ⁄ hong kong ⁄ h n , ae logs ⁄ ae % (table ). comparable results of antiviral efficacy are obtained with the tcid and plaque assays against all subtypes studied. when performing the plaque assay the sensitivity of virus recovery was better in the vessel with a larger surface area and overall recovery was in agreement with the potency determined by tcid assay. in our plaque assay, we inoculated a ⁄ hong kong ⁄ ⁄ virus dilutions into two different vessels with hours adsorption time: -well plate and t- flask, ml inoculum per replicate. virus titers obtained were: ae · pfu ⁄ ml from -well plate and ae · pfu ⁄ ml from t- flask ( table ). the discrepancy on virus potency can possibly be explained as: the binding of virus to host cell occurs only when virus gets a chance to interact with the cell on the monolayer during adsorption time. the percentage of virus population in the inoculum that has the opportunity to bind to the cell mainly depends on the surface area where this interaction takes place. therefore, in our experiment the plaque assay in the t- flask gave higher virus recovery ae versus ae · pfu ⁄ ml. the increased virus recovery can translate into better sensitivity of the test system for disinfectant and antiviral agents. the potency of the virus used in this study was determined by tcid was · tcid ⁄ ml. rapid diagnostic testing for influenza (quickvue Ò influenza a + b test, quidel) for aj versus bac was studied. the presence of influenza viral nucleoprotein a determined by quickvue kit correlated % with the viral infection based on by cpe in viral culture. interestingly, the inactivation of viral nucleoprotein was able to be revealed with diagnostic kit in the dilutions of virus ⁄ bac reaction mixture, which possessed prominent cytotoxic effect for the host cells in viral culture system. this type of molecular testing method is useful for interpreting antiviral efficacy against a background of cytotoxicity. these experiments are intended for the sponsor to substantiate to us fda that their antiviral substances are safe and effective. the data shows that the three hemagglutinin subtypes were highly susceptible to the quaternary ammonium compound in the short term in vitro experiment. the appearance of novel subtypes in the future can be met with the assurance that disinfectant and ⁄ or antiseptic resistance will be unlikely. certainly, from the above data, although genetic reassortment of human and swine viruses may modulate influenza pathogenesis and limit existing vaccine benefit, it is not likely be a factor in control of viruses on environmental surfaces by benzalkonium-type disinfectant ⁄ cleaning agents in community or health care environments. table . comparison of viral titer obtained in different vessels using quantal tcid and plaque assay methods plaque assay tcid assay t- ( cm ) -well plate ( cm ) tcid ⁄ ml tcid ⁄ ml ae · pfu ⁄ ml ae · pfu ⁄ ml · ae · options for the control of influenza vii outbreak influenza in aged care facilities (acfs) is associated with an increased risk of poor health outcomes among residents, including death. in this paper we share our experience of managing an outbreak of viral respiratory infection in an acf very early in the influenza pandemic and also describe some of the emerging issues relating to crossreacting antibodies to the pandemic (h n ) influenza virus in the very elderly. the outbreak investigation was conducted as part of an urgent public health intervention initiated by the new south wales (nsw) department of health during the early stages of the first southern hemisphere wave of the pandemic. nose and throat swabs for nucleic acid testing (nat) plus acute and convalescent serum samples ( weeks apart) were collected from all the residents of an acf where an influenza-like illness (ili) outbreak occurred. the investigation revealed dual outbreaks of pandemic (h n ) influenza and rhinovirus infection. out of residents, three had laboratory confirmed influenza [two with pandemic (h n ) ], and had rhinovirus infection on nat. testing of acute sera collected from every subject found elevated ( ‡ : ) pandemic (h n ) hai antibody in % ( ⁄ ) subjects aged years or more (born before and median age years; geometric mean titre-gmt ae ) compared with none of the residents aged under years (born after and median age years; gmt ae , p = ae ). the acf was closed to visi-tors for days. the symptomatic residents received treatment-dose oseltamivir, and all other residents were given oseltamivir prophylaxis. more than one virus may be circulating in an acf with an ili outbreak at any one time in winter. a significant proportion of elderly residents had pre-existing cross reacting antibody to the pandemic (h n ) , which may explain the minimal clinical impact of pandemic (h n ) in this elderly population. influenza is one of the leading causes of infectious death in elderly people, principally due to co-morbidities and declining immune competence with age. it is the most important agent in outbreaks of respiratory illness. influenza in aged care facilities (acfs) is associated with an increased risk of poor health outcomes among residents, including death. the clinical presentation of influenza in residents of acfs can be subtle, with a blunted febrile response and a non-specific decline in mental and functional status. residents commonly have underlying diseases that can be exacerbated by influenza infection, and in addition, they are at higher risk of serious influenza-related complications than community dwelling elderly people. people aged over years are also at higher risk of influenza-related death, and more than % of annual influenza-related mortality is usually confined to this high risk group. in australia, influenza and pneumonia have sub-stantial health impacts; recorded as being the underlying causes of death for persons in . since the world health organization declared an influenza pandemic in june , australia has suffered one of the highest rates of confirmed infection during the first southern hemisphere wave. by late october there were reported deaths due to pandemic influenza in australia, and to date there have been about deaths reported worldwide. although disproportionately far fewer elderly people developed clinical influenza during the current pandemic than occurs with seasonal influenza, their case-fatality rate remained substantial. early in the pandemic (june ), we investigated a suspected pandemic influenza outbreak in a rural acf in the state of nsw, australia. the epidemiology (including virulence and clinical outcome in the elderly) of the pandemic (h n ) virus was mostly unknown at the time of investigation, and as time passed, this investigation provided clarity on some important issues of the influenza epidemiology in the elderly population. in this paper we share our experience of managing a dual outbreak of viral respiratory infections early in the pandemic, and also describe some of the emerging issues relating to the cross-reacting antibodies to pandemic influenza in the very elderly. the outbreak investigation was conducted as part of urgent public health intervention initiated by the nsw department of heath in conjunction with the local public health unit, the national centre for immunisation research and surveillance (ncirs), and the institute of clinical pathology and medical research (a who national influenza centre). to determine the extent and cause of the outbreak, a public health research doctor (gk) was dispatched from sydney over a weekend to assist with outbreak investigation and control. on june th , the greater southern public health unit surveillance officer (bd) received a report of a possible pandemic (h n ) outbreak in a local acf. on investigation, it was discovered that days earlier a year old female resident had become generally unwell, but without specific symptoms of influenza like illness (ili). soon after, nine of the co-residents (but no staff) had developed symptoms suggestive of influenza. one other resident had returned from a melbourne (victoria) hospital (where pandemic (h n ) was known to be circulating) the previous week after surgery, but did not have ili symptoms. on june th, the symptomatic residents had nasal swabs taken by the local doctor for influenza [including pandemic (h n ) ] nucleic acid testing (nat). there was rising concern due to reports of widespread pandemic (h n ) influenza in a local army camp just over the border in nearby victoria, where pandemic (h n ) influenza was known to be circulating widely. on june th, the year old lady proved nat positive for pandemic (h n ) , but none of the other samples were pandemic (h n ) nat positive. concern arose that there might be an outbreak of pandemic (h n ) in the facility, and that some of the swabs from other residents might be false negatives. between and june, after consent was obtained, directly or through next of kin in demented residents, all submitted to venipuncture for serology, successfully, and the other as yet un-swabbed residents were swabbed. basic demographic data were collected from every resident with clinical information on co-morbidities and current medication use. convalescent blood samples were collected after weeks on th july from of the residents. swabs were sent to icpmr where nat for influenza a [including pandemic (h n ) ] and b was performed. the acute and convalescent serum samples were tested later (in december ), using haemagglutination inhibition assay (hai) to detect pandemic (h n ) antibody. , interventions the acf was closed to visitors from th until th june. treatment of the positive case and the nine symptomatic residents, with twice daily oseltamivir, was begun on saturday june th, and all other residents were started on once daily oseltamivir prophylaxis. the facility manager and local general practitioner (gp) monitored patient health on a daily basis, and none had to stop oseltamivir due to adverse events. one resident with ili who was known to have moderately impaired renal function was given once daily rather than twice daily oseltamivir treatment. the age range of the residents was - years with a median of years. all residents had underlying medical conditions, e.g., chronic cardiac and respiratory diseases ( table ) testing of acute sera collected from every subject found elevated ( ‡ : ) cross-reacting hai antibody to the pandemic (h n ) in % ( ⁄ ) of subjects aged years or more (born before and median age years; geometric mean titre-gmt ae ). however, the hai titre was consistently < : and significantly lower (gmt ae , p = ae ) in the residents aged under years (range - years, median years) (figure ). the index case (nat positive) did not show a significant raise in hai level in convalescence (going from to ). the pandemic (h n ) case that was determined by serology was pandemic (h n ) nat negative. to our surprise, seven of the other asymptomatic residents had rhinovirus detected on extended nat (reported on june th), despite being asymptomatic at time of swabbing and remaining so. the original nine influenza nat negative samples were then tested and three of these were also nat positive for rhinovirus; in total, ten proved nat positive for rhinovirus ( ae %). the serologically confirmed pandemic (h n ) case was also positive for rhinovirus infection. of interest was that only one resident had a documented fever. this investigation illustrates some of the difficulties in managing and investigating possible influenza outbreaks in real time in the context of an influenza pandemic. finding a nat positive case of pandemic (h n ) influenza among many other symptomatic cases raised the possibility (although not the probability) that pandemic (h n ) was the cause of the outbreak. rhinovirus infection, however, was confirmed by nat in ten residents. this outbreak illustrates that more than one virus (in this case and perhaps ) may be circulating in an acf at any one time in winter. in ili outbreaks in acfs, broad laboratory testing is recommended; nat is the most sensitive method of detecting influenza or other viruses in respiratory tract samples. studies have found that the pandemic (h n ) haemagglutinin (ha) gene is more closely related phylogenetically to the h n virus and classical swine influenza a ⁄ h n viruses than more recent seasonal human influenza a ⁄ h n viruses. it is antigenically similar to the h n pandemic virus in terms of the immunodominant antibody response to haemagglutinin. [ ] [ ] [ ] it is likely that individuals alive during the emergence and initial persistence of the pandemic virus would have higher levels of cross-reacting hai antibodies to the pandemic (h n ) , which would contribute towards better clinical protection. in our investigation, % of the residents born before (aged years or above in ) had pre-existing cross-reacting hai antibody to the pandemic (h n ) . in elderly populations, severe illness may be associated with organisms typically considered to be mild, such as rhinovirus. however, studies have shown that nursing home residents may be susceptible to outbreaks of rhinovirus that may cause mild to severe respiratory illness, particularly in those with a history of lung disease. one rhinovirus outbreak in a nursing home in the usa caused fatalities. another outbreak showed residents with underlying lung disease are more likely to have longer infection, require antibiotics, develop bronchospasm, and have difficulty breathing; two residents with underlying lung disease required emergency treatment and one died. a previous influenza outbreak in a nsw aged care facility in caused significant mortality and morbidity. that outbreak resulted in hospital admissions and six deaths. in our investigation we have found that % of the residents had chronic lung disease and % had chronic cardiac conditions both considered as high risk for severe complications of both rhinovirus and influenza infection. however, there were no hospitalisations or deaths in our outbreak investigation. indeed only one resident developed fever, indicating that non-specific signs of illness (such as in our index case) may be the only, or early, indication of an ili. our own experience with managing other ili outbreaks has also taught us that staff of acfs may not be vigilant enough to detect fevers. in this outbreak, the nursing home staff, local gp, public health unit and the outbreak investigation team and supporting laboratory staff acted quickly and in a coordinated way. pre-existing cross-reacting antibody in the very elderly (aged ‡ years) probably helped to limit the spread of the pandemic virus (compared to the circulation of rhinovirus) within the acf. exposure to the pandemic (or a close variant occurring before ) appears to be responsible for a high hai titre in the very elderly, which contributed towards better clinical protection. however, wider testing early on would have alerted us more quickly to the main cause of the outbreak. treatment and prophylactic use of oseltamivir may also have contributed to halting the spread of pandemic (h n ) and also to symptom relief. pandemic (h n ) influenza virus (ah pdm) has spread worldwide since march . in a paper of ah pdm, % of infected individuals have experienced gastrointestinal symptoms such as diarrhea and vomiting, which is higher than that of seasonal influenza. however, little is known whether viable virus shed from stool and replication of viruses are ongoing in the gastrointestinal tract. , viral load and isolation of ah pdm in cell culture in stool samples has been reported. stool specimens were collected from patients suspected to have pandemic (h n ) infection from november through may . virus isolation was conducted in cell culture by using madin-darby canine kidney (mdck) cells and taqman based rt-pcr from % (w ⁄ v) stool suspension in phosphate-buffered saline. taqman based rt-pcr was conducted by using primers, probes, and positive controls provided by niid (national institute of infectious diseases of japan). to confirm presence of ah pdm viral rna, lamp (loop-mediated isothermal amplification) was used as supplemental testing. of patients, one child (case ) submitted one nasal swab and four stool samples, another one nasal swab and two stool samples, and the other one stool sample. informed consent was obtained. strand specific rt-nested pcr was performed for only case by using only one primer at the rt reaction and also assayed neu aca - gal and neu aca - gal binding specificity about isolated strain derived from nasal swab and stool. receptor binding specificity was performed using a solid-phase binding assay with the sialylglycopolymers (poly a-l-glutamic acid backbones containing neu aca - galb - glcnacb-pap or neu aca - galb - glcnacb-pap bond as described. ) nucleotide sequences of the ha gene of ah pdm viruses isolated from stool sample and nasal swab were analysed. in order to exclude the possibility of contamination, the stool samples and nasal swabs were subjected to virus isolation separately. after getting the results on the nucleotide sequence, we also confirmed no strain harboring identical sequence was isolated in our laboratory before and after the day of sample collection. ah pdm viral rna was detected in nine ( %) of the subjects from stool samples. among nine subjects, one case (case no. ) was positive for viral isolation. case , a healthy -year-old girl, experienced fever and abdominal pain, and the others had gastrointestinal symptoms without upper respiratory symptoms. in case , influenza a virus was diagnosed by rapid antigen test on the day of symptom onset. viable ah pdm virus was isolated from the stool sample and nasal swab on the second day from onset using mdck cells (table ). viral load decreased gradually after symptom onset. however, viral shedding was still present days after symptom onset. positive stranded rna was detected days after symptom onset from the stool specimen ( figure ). above two ah pdm strains (isolated from nasal swab and stool specimen) bound exclusively to human type receptor, neu aca - gal. sequence analysis demonstrated that isolated virus from stool samples was identical with that from nasal swabs in comparison of ha gene ( bp). ah pdm influenza virus was isolated from the stool and nasal swab samples in the same patient simultaneously by using mdck cells. our results suggests the detection of viral rna and viable ah pdm influenza virus from stool samples may serve as a potential mode of transmission and has important implications in understanding the context of ah pdm influenza virus. strategies to prevent transmission of influenza include use of respirators. ffp and n respirators are certified to fil-ter at least % of particles ( ae lm in diameter), and many guidelines have recommended that healthcare workers wear respirators in certain healthcare settings to protect against infection from patients with pandemic influenza. [ ] [ ] [ ] we have developed a proprietary acid-polymer formulation to coat a standard ffp respirator with an antiviral layer. we aimed to test this coated respirator for antiviral efficacy against a range of influenza viruses. a series of tests compared the antiviral efficacy of coated and uncoated respirators in conditions designed to simulate real-life exposure to influenza by varying the route of inoculation, contact time, temperature, humidity, moisture, and contaminating substances. we also investigated whether infectious viruses could be transferred from contaminated respirator surfaces to gloves. we tested human, swine, and avian influenza viruses, including influenza a and b viruses. influenza a subtypes were the a ⁄ h n pandemic strain, seasonal h n , h n , h n , h n , and h n . in each test, suspensions of influenza viruses were prepared to - log tcid ⁄ ml in mem. in some tests, organic contaminants (yeast, bsa, and mucin) were added. one set of respirators was maintained at °c and % relative humidity for hours before the viral challenge, and repeatedly sprayed with he-pes buffer to simulate respiratory secretions. for each test, three coated (glaxosmithkline actiprotect) and three uncoated (sperian willson easy fit) ffp respirator samples were inoculated with ae ml of a viral suspension, which was applied with a pipette, sprayed, or aerosolised to create airborne droplets. after minute at room temperature (on a shaker), the respirator samples were assayed for the presence of infectious viruses using standard methods. in one test, after a minute contact time of the respirator with the virus, nitrile gloves were applied with light pressure to the outer surface of inoculated respirator samples and then assayed after minute. samples were put into test medium (mem, supplemented with antibiotics [penicillin, gentamycin, or streptomycin] and amphotericin b or l-glutamine). the supernatants were vortexed, extracted, and used to prepare serial -fold dilutions in mem. each dilution was used to inoculate four wells of rmk cells in a multi-well plate, and these cultures were incubated and scored over days for cytopathic effects, cytotoxicity, and viability. (some tests substituted mdck cells; others used inoculated embryonated chick eggs.) all tests included negative cell controls, cytotoxicity controls, and neutralisation controls. the spearman-karber formula was used to calculate viral loads as tcid or eid . antiviral efficacy was calculated from the difference between the geometric mean loads of influenza virus on the coated and uncoated respirators after minute of exposure. the viral loads applied to respirators in these experiments ranged from ae to ae log tcid , and were therefore high in comparison with respiratory secretions from infected patients at the peak of influenza symptoms (range - log tcid ). tables - show that the average viral loads detected on uncoated ffp respirator samples remained high in all conditions tested, ranging from ae to ae log tcid (or ae - ae log eid ). in contrast, the average viral load on coated respirators after minute of exposure ranged from below the limits of detection to £ ae log tcid ( ae log eid ). therefore, the relative antiviral efficacy of the coating ranged from ‡ ae to ae log . table shows that the relative antiviral efficacy of the coated mask remained high in simulated-use conditions such as organic contaminants and repeated saturation at high temperature and humidity. in the experiment to test transfer of viruses from respirators, the gloves applied to regular uncoated inoculated respirators had a viral load of ae log eid (table ) . by contrast, no viruses were detected on either the coated respirators or the gloves applied to them. the relative reduction in contamination was therefore ‡ ae log . ‡ ae log viral load with organic contaminants* ae ae ae log viral load after heat, moisture, and simulated secretions** ae ae ae log viral load transferred to glove** ae £ ae ‡ ae log eid *influenza subtype was a ⁄ h n , and strain was vnh n -pr ⁄ cdc-rg. **influenza subtype was a ⁄ h n , and the strain was hong kong ⁄ ⁄ . results are mean log tcid , unless specified otherwise. results are mean log tcid , unless specified otherwise, based on an infectivity assay in triplicate. limits of detection varied. * pandemic strains. **results are mean log eid , based on a haemagglutinin assay in duplicate. options for the control of influenza vii ª blackwell publishing ltd, influenza and other respiratory viruses, (suppl. ), - strategies to prevent transmission of influenza include use of respirators, and many guidelines have recommended that healthcare workers wear respirators in certain healthcare settings for protection against pandemic influenza. - ffp respirators are certified in europe to filter at least % of nacl particles ( ae lm in diameter), and ffp and ffp respirators must filter at least % and % of these particles, respectively. influenza a viruses are typically ae lm, and can be carried in aerosolised droplets smaller than lm in diameter, which can disperse widely, remain airborne for hours, and be inhaled deeply into the respiratory tract. we have developed an acid-polymer formulation to coat the outer layer of a standard ffp respirator, in order to provide antiviral activity on the outer surface. we compared this coated respirator against standard ffp , ffp , and ffp respirators for filtration of aerosolised influenza viruses. the aim was to simulate protection against infectious viruses in droplets released when infected people cough and sneeze, and during aerosol-generating procedures in healthcare settings. the first assay compared three samples of coated ffp respirators (glaxosmithkline actiprotect) with three ffp controls (sperian willson easy fit). for each test, suspensions of influenza a (h n ) at ae log tcid ⁄ ml in ae · minimum essential medium (mem) were aerosolised with a nebulizer. the airborne droplets were introduced into a sterile chamber upstream of a respirator sample for minutes, at a flow rate of ae l ⁄ minute. constant airflow was maintained for another minutes after exposure to the virus. then the collection dish in the downstream sieve sampler (anderson) was assayed for infectious viruses using standard techniques. briefly, serial dilutions of the collection medium (mem with % fbs, % gelatine, and % hepes, supplemented with antibiotics and amphotericin b) in mem + trypsin were used to inoculate madin-darby canine kidney epithelial (mdck) cells in quadruplicate in a multi-well plate. these cultures were then incubated and scored over - days for cytopathic effects, cytotoxicity, and viability. negative cell controls and cytotoxicity and neutralisation controls were also performed. the spearman-karber formula was used to calculate tcid . the second assay compared five samples of coated respirators with five ffp controls ( m ) and five ffp controls ( m ). a suspension of influenza a (h n ), at ae tcid ⁄ ml, was nebulized for minute and seconds into the aerosol chamber, at a flow rate of ae l ⁄ minute, followed by constant airflow for minutes after exposure to the virus. then the collection medium in the downstream chamber (as before, with % nahco ) was assayed as described above. initial viral loads in the first and second assays were ae and ae log tcid , respectively, and were therefore high in comparison with respiratory secretions from infected patients at the peak of their influenza symptoms (range - log t-cid ). table shows that the average viral load that passed through the uncoated ffp respirators in the first assay was ae log tcid . the average viral load that passed through the coated respirators was ae log tcid . therefore, for active filtration of viruses, the relative efficacy of the respirator with antiviral coating was ae log greater than the uncoated respirator. for surface inactivation, the relative antiviral efficacy of the coated respirator was ae log . in the second study, table shows that the average viral load that passed through the uncoated ffp respirators was ae log tcid . in contrast, ae log tcid passed through the coated ffp respirators. by comparison with the viral load when no respirator was present ( ae log tcid ), the ffp respirators reduced the viral load by ae log , and the coated ffp by ae log . therefore, for active filtration of viruses, the respirators with antiviral coating reduced the viral load by ae log more than the ffp respirators. in this second study, the average viral load that passed through the uncoated ffp respirators was also ae log tcid . by comparison with the viral load when no respirator was present ( ae log tcid ), the ffp respirators reduced the viral load by ae log . therefore, for active filtration of viruses, the respirators with antiviral coating reduced the viral load passing through the mask by ae log more than the ffp respirators. table also shows that the coated respirators reduced the infectious viruses remaining on the mask surfaces by ae log more than the ffp respirators, and ae log more than the ffp respirators. even with a very high viral challenge, the coated respirators prevented passage of at least an additional ae log infectious viruses, compared with uncoated respirators. large numbers of infectious virions passed through all uncoated respirators tested. ffp respirators were no more effective than ffp respirators at blocking airborne influenza viruses. based on these in-vitro results, respirators with the antiviral coating could be expected to provide more protection than standard respirators from the risk of inhaling influenza viruses. strategies to prevent transmission of influenza include use of respiratory protection. ffp and n respirators are certified to filter at least % of nacl particles ( ae lm in diameter), and many guidelines have recommended that healthcare workers wear these respirators in certain healthcare settings to protect against infection from patients with pandemic influenza. , we have developed a proprietary acid-polymer formulation, designed to coat a standard respirator and inactivate influenza viruses on contact. we tested this coated respirator for cytotoxicity, skin irritation, and sensitisation potential. the antiviral coating was also tested for stability and leaching under extreme environmental conditions, such as physical abrasion and simulated breathing at different temperatures, levels of humidity and co , and saturation with contaminants. eight coated respirators were tested at standard relative humidity ( % rh) for hours, and one at elevated humidity ( % rh) for hours. four coated masks were treated with synthetic blood or oral secretions, and then tested at % rh for hour. the sample respirators were sealed onto a mannequin head inside an airtight chamber, and air at °c and ppm co was pumped through the masks by a cyclic breathing machine at l ⁄ minute. a mm glass-fibre filter was placed behind the respirator, over the mannequin's mouth opening. at the end of all tests, these filters were eluted and analysed using high-performance liquid chromatography (hplc). standard in vitro methods were used to assess the cytotoxicity of the coated polyester and uncoated polypropylene layers of the respirator (glaxosmithkline actiprotect). samples were extracted in minimum essential medium (mem), supplemented with serum, penicillin, streptomycin, amphotericin b, and l-glutamine, at °c for hours. triplicate monolayers of mouse fibroblast cells (l- ) were dosed with each extract (including a reagent control and negative and positive controls), and incubated at °c in % co for hours. after hours of incubation with samples or controls, the monolayers of mouse fibroblast cells were examined microscopically for abnormal cell morphology or cellular degeneration. samples of the coated respirator (comprising four polypropylene layers bonded to the coated polyester outer layer) were applied under occlusive patch conditions to the skin of adults. controls, including individual layers, were applied in the same way. in a separate patch test, samples of the coated polyester outer layer and controls were applied under the same conditions to adults. after hours, test patches and controls were removed. sites were then scored for itching, erythema, oedema, epidermal damage, and papular response after and hours. the patches were applied three times a week for weeks. to evaluate sensitisation, test patches were applied - days later for hours at different sites to the original samples. after this challenge, skin was assessed and graded for sensitisation potential after and hours. table shows that no residues of the antiviral coating or degradation products were detected in the air that had passed through any of the eight respirators. cytotoxicity tests showed that the coated respirator material caused % cell lysis or toxicity, classified as slight reactivity (grade ), and that uncoated material caused no cell lysis or toxicity (grade ) ( table ) . results for positive and negative controls were severe reactivity and no reaction, respectively. from the results of the two human repeat-insult patch tests, neither the coated or uncoated layers nor the fullthickness respirator fabric caused irritation (including itching, erythema, edema, vesiculation, epidermal damage, papules, or reactions beyond the patch site) or sensitisation in any of the adult volunteers at any of the time points. based on these results, in conjunction with published data on acute and repeat-dose toxicity, mutagenicity, local irritation, dermal sensitisation, and inhalation safety for all components of the antiviral coating, the potential topical or inhalation exposure to the coated antiviral respirator does not pose a safety risk. the antiviral coating is durable and stable, and stays on the outer surface of the respirator, even in extreme environmental conditions. the coated respirator is non-irritating and non-sensitising. therefore, this respirator is considered to be well-tolerated and safe for its intended use. ies were funded by gsk consumer healthcare, and gsk investigators were involved in all stages of the study conduct and analysis. knowing how influenza virus is transmitted at home and in school is the key to preventing its spread. at the previous two meetings of this conference, , we introduced our study of household transmission of seasonal influenza and reported our conclusion that protracted survival of the virus even after treatment increases household transmission, and is a major factor in the transmission of the virus to infants. on the other hand, during the recent pandemic, many schoolchildren developed serious respiratory tract disorders, which again highlights the significance of schoolbased transmission of the disease. in this study, we compared transmission of a new influenza strain at home and in school with that of seasonal influenza and proposed countermeasures. the for the analysis of school-based transmission, the epidemic status of seasonal influenza in children at six elementary schools over the past two seasons ( - and - seasons) was compared with that of pdmh in children at two primary schools. using observational data of school-based transmission, we also constructed a model for influenza transmission , and evaluated the effects of factors that could affect influenza transmission (e.g., antibody prevalence, transmission rate, non-infectious latent period, infectious latent period, school closure) through the use of simulations. in this study, a diagnosis of influenza was confirmed by rapid influenza antigen detection kit. we previously reported the high sensitivity of the kits, - not only for seasonal influenza, but also for h n pandemic compared to virus isolation and pcr. serum antibody was not investigated. most of the index patients were treated with oseltamivir or zanamivir, and patients were treated with amatadine. no treatment was done for patients. no nai therapy was done as prophylaxis within the family. the incidence of households with an initial case patient who subsequently infected another member of the household was ae % ( of households) for seasonal influenza or ae % ( of households) for pdmh . thus, the household incidence of pdmh was lower than that of seasonal influenza. in addition, the percentage of family members in households who were infected by initial case patients (household transmission rate) was ae % ( of individuals) for seasonal influenza or ae % ( of individuals) for pdmh . thus, the household transmission rate was also lower for pdmh than that for seasonal influenza. effect of family size on household incidence and household transmission rate an analysis of the effect of family size on household incidence showed that, in families consisting of - individuals, the incidence of seasonal influenza in order of increasing family size was ae %, ae %, ae %, ae %, ae %, and ae %, respectively, and the incidence of pdmh was ae %, ae %, ae %, ae %, ae %, and ae %, respectively, indicating that household incidence tends to increase with increasing family size. in contrast, no definite relationship was noted between household transmission rate and family size. transmission rates for seasonal influenza in order of increasing family size were ae %, ae %, ae %, ae %, ae %, and ae %, respectively, or ae %, ae %, ae %, ae %, ae %, and ae %, respectively, for pdmh (shown in table ). effect of age cohort of initial case patient in household on household incidence and household transmission rate an analysis of the effect of the age cohort of the initial case patient in the household on household incidence and transmission rate showed that the household incidence of seasonal influenza in c , c , c , and c was ae % ( of households), ae % ( of households), ae % ( of households), ae % ( of households), and for m and f was ae % ( of households) and ae % ( of households), respectively. therefore, household incidence was the highest in c , followed by the parents. when the initial case patient was a child, the household incidence increased with decreasing patient age. in contrast, the household incidence of pdmh in c , c , c , and c was ae % ( of households), ae % ( of households), ae % ( of households), ae % ( of households), and for m and f was ae % ( of households) and ae % ( of households), respectively. therefore, household incidence was higher when the initial case patient was a parent, rather than a child. the household transmission rates for seasonal influenza from c to f were ae %, ae %, ae %, ae %, ae %, and ae %, respectively. therefore, as for household incidence, the highest rate ( ae %) was observed in c . the corresponding household transmission rates for pdmh were ae %, ae %, ae %, ae %, ae %, and ae %, respectively, with the highest transmission rates observed for infections from parents (shown in table ). if the rate of individuals with a secondary infection transmitted from the initial case patient in a household is presented as a percentage of the total number of affected individuals, the rates for seasonal influenza and pdmh were ae % ( of individuals) and ae % ( of individuals), respectively. therefore, the rate of individuals with a secondary infection was lower for pdmh than that for seasonal influenza. by age cohort, the corresponding rates of individuals for seasonal influenza in c , c , c , and c were ae % ( of individuals), ae % ( of individuals), ae % ( of individuals), ae % ( of individuals), and for m and f was ae % ( of individuals) and ae % ( of individuals), respectively. for pdmh , the corresponding rates in c , c , c , and c were ae % ( of individuals), ae % ( of individuals), ae % ( of individuals), ae % ( of individuals), and for m and f was ae % ( of individuals) and ae % ( of individuals), respectively. these findings indicate that, especially in the case of pdmh , most secondary infections in parents tend to be transmitted from another household member. the mean annual prevalence of seasonal influenza and the new influenza strain at the elementary schools for the two seasons was ae % and ae %, respectively, whereas the prevalence determined days after appearance of the first case in school was ae % and ae %, respectively. in the recent season at the same elementary schools, however, the prevalence was a high ae %. since the prevalence at days after the appearance of the first case in school was already ae %, these data show that the influenza virus spread quickly throughout the schools. at the schools with high transmission rates in the early period of the pandemic, new infections were confirmed even days after the school closure action was taken. these findings indicate that pdmh , the current influenza virus, has a long latent period during which it becomes infectious and spreads from infected individuals to numerous others in their vicinity. we constructed a model for influenza transmission in schools and estimated the time course of changes in the number of expected cases and the expected prevalence during the season. in this model, school children were divided into six groups depending on the stage of infection: uninfected period with no immunity, non-infectious latent period, infectious latent period, onset, post-onset infectious period, and immune period. it was assumed that schoolbased transmission occurred during the infectious latent period prior to onset and that no infections occurred during the post-onset infectious period because children were absent from school. due to the long latent period of pdmh , the distribution of the non-infectious latent period of pdmh was established as (day , day , day , day ) = ( %, %, %, %) and the distribution of the infectious period as (day , day , day ) = ( %, %, %). when simulations were performed under these conditions using the model for school-based transmission of influenza in which children from classes with an outbreak were kept at home for days, the time course of changes in the number of affected individuals actually observed and the time course of changes in the number of expected cases were determined. the expected prevalence under these conditions was %. to evaluate the effect of school closure, simulations were performed based on the assumption that children from affected classes were not kept at home for days. it was shown that there was an increase in the expected number of cases during the days corresponding to the period of actual school closure and that the expected prevalence increased to %. based on these findings, it was concluded that keeping children home from classes with an outbreak is an effective means of controlling the transmission of influenza in schools (shown in figure ). if the transmissibility of pdmh virus at home is estimated based on the speed of transmission and the degree to which pdmh is prevalent in schools, it would be expected that the household transmission of pdmh is also higher than that of seasonal influenza. in fact, the opposite is the case. this paradox can be explained in two ways. . the number of children aged or more and parents with pdmh influenza as a percentage of the total number of affected individuals is lower than those with seasonal influenza ( ae % versus ae %). further, although the number of parents with a secondary infection was high at home, the percentage of the total number of individuals with pdmh was a low ae % ( of individuals), compared to that for seasonal influenza ( ae % [ of individuals]). in other words, adults are less susceptible to pdmh infections and there was a correspondingly small number of affected individuals. therefore, it was considered that the transmission rate at home was lower than that at school for this reason. . the percentage of households with more than one affected individual within the same family was higher for pdmh at ae % ( of households) than for seasonal influenza at ae % ( of households). in the patients secondarily infected with pdmh , ae % of them showed symptoms of infection days or more after the onset in the first patient, suggesting that they were not infected at home, and the actual household transmission was ae % ( of households). therefore, although the prevalence was higher for pdmh , it seems that household transmission was lower because households with an affected individual implemented satisfactory control measures against infection. seasonal influenza differs greatly from pdmh influenza in its transmissibility at home and in school. in the household transmission of pdmh influenza, both the household incidence and household transmission rate of pdmh were low compared to those for seasonal influenza. although transmission of seasonal influenza from infants to parents was marked, in the case of pdmh , the reverse was true with transmission from parents to children being predomi-nant. it should be noted that household transmission in mothers was common in all eight seasons, suggesting the need to reconsider control measures against infection when nursing unwell family members. in the case of school-based transmission, pdmh was more prevalent than seasonal influenza, indicating that the virus spread quickly throughout the schools. this difference was attributed to the long infectious latent period when pdmh rapidly became rampant in the schools. an analysis of school-based transmission using a model for influenza transmission showed that, when % of the student population is infected, schools should be closed for five consecutive days in order to minimize the spread of the disease. the effectiveness of seasonal influenza vaccine in preventing pandemic and seasonal influenza infection: a randomized controlled trial introduction household transmission has been estimated to account for one-third of all influenza transmission, , and children are at high risk of spreading the disease. with reference to previous evidence, - some vaccine deployment strategies target children to prevent them from infection and transmitting influenza. nevertheless, few studies evaluated the effectiveness of vaccinating children in reducing household transmission. , during - , a pilot randomized controlled trial was conducted to investigate such effect by studying households with school age children randomized to receive trivalent inactivated seasonal influenza vaccine (tiv). the monovalent vaccine against pandemic influenza a (h n ) (ph n ) had yet been available until the end of the first wave. various conclusions have been made as to whether seasonal influenza vaccine might possibly protect against ph n . [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] we report findings on the effectiveness of tiv against ph n observed in our cohort. households were screened if they expressed interest after receiving invitation letters distributed via their children's school or an existing pediatric cohort study. to be eligible, the household had to include at least one child aged - years who was not allergic or hypersensitive to any of the tiv components. children known to have immunosuppressive conditions or other contraindications against tiv were also excluded. written consent and assent were obtained from participants aged above years and those aged - years, respectively. proxy written consent was obtained from legal guardians or parents for participants younger than years. ethical approval was obtained from the institutional review board of the university of hong kong. consented households were allocated to the tiv and placebo group (in ratio : ) according a code generated by block randomization with random block sizes of , , and . an independent nurse prepared . one child (study subjects) from each household in the tiv group received a single dose of tiv with one child from each household in the placebo group receiving a single dose of saline placebo. parents and legal guardians were asked to report any adverse reactions days following vaccination. all participants, study nurses, and other research staff were blinded to the allocation and administration of vaccine or placebo. the vaccine allocation sequence was only disclosed to the investigators at completion of the study. serum specimens were collected from subjects shortly before (november-december ), one month after vaccination (december -january ), and after the winter (april ) and summer influenza seasons (august-october ). serum specimens were obtained from household contacts at baseline and after the winter and summer influenza seasons. all household members recorded any fever ‡ . °c, chills, headache, sore throat, cough, presence of phlegm, coryza, or myalgia daily on a symptom diary. they were also invited to report to the study hotline immediately if they experienced at least of the above signs or symptoms. as a response, the study nurse would visit the households with any sick members and collect nose and throat swab from all household members. the households were also telephoned monthly or increased to fortnightly during influenza seasons to monitor for signs and symptoms and remind them to report to the hotline. supermarket or book vouchers (for children) were given to the households including us$ for each serum specimen collected, us$ . for each home visit, and us$ for completion of the study. serologically-indicated influenza infection was the primary outcome of this study. it was define as a ‡ fold rise in antibody titer within each influenza season. other study outcomes included rt-pcr confirmed influenza virus infection, acute respiratory illness (ari) (two of any of the above listed signs or symptoms), and influenza-like illness (ili) (fever ‡ . °c with cough or sore throat). antibody titers against the vaccine strains were obtained by testing each serum specimens by haemagluttination inhibition (hai). viral microneutralization (vn) using standard methods was found to be more sensitive than hai in detecting antibody response against a ⁄ california ⁄ ⁄ (h n ) in another study conducted by our group and was, therefore, used in this study. the sera was initially diluted at ⁄ and further tested in serial doubling dilutions. nose and throat swabs were tested by reverse transcription polymerase chain reaction (rt-pcr) for influenza a and b viruses. technical details of the laboratory methods have been reported elsewhere. , fisher's exact test and chi-squared tests were used to compare count data including occurrence of side effects, laboratory confirmed, and clinically defined influenza infections. wilcoxon signed-rank test were used to compare the serum antibody titers between groups. exact binomial method or the wald approximation was used to estimate % confidence intervals where appropriate. all analyses were carried out in r version . . (r development core team, vienna, austria). twenty-five primary and secondary schools in the district of the study clinic were invited to participate. to parents of three schools that agreed to take part and another study cohort, invitation letters were sent and households were enrolled. personal referrals were made from these parents to enroll additional households. among enrolled households, subject with history of epileptic seizure was assessed to be contra-indicated against receiving the vaccine. blood taking failed in another subject, and both of them withdrew from the study. eleven households did not complete the study. table shows subject and household contacts of the tiv and placebo group were similar in demographics and prior influenza vaccination history. antibody titers before vaccination were comparable between groups (data not shown). most study subjects who received tiv showed antibody titer ‡ against the vaccine strains month after receiving tiv, and the proportion was significantly higher than those who received placebo (a ⁄ h n % in tiv versus % in placebo group, p < . ; a ⁄ h n % versus %, p < . ; b % versus %, p = . ). none of the study subjects had antibody titer ‡ against ph n following receipt of seasonal tiv. no serious adverse reactions were reported, and only pain at injection sites was slightly higher in tiv group (data not shown). subjects who received tiv had lower rates of serologically confirmed seasonal influenza a(h n ) ( % versus %, p = . ), a(h n ) ( % versus %, p = . ) and b infection ( % versus %, p = . , although the differences were not statistically significant (table ) . study subjects had higher rate of serologically confirmed ph n infection ( % versus %, p = . ), yet it was not statistically significant. after adjusting for potential cross reactive antibody response, % of subjects in tiv versus % in placebo groups showed ph n infection confirmed by either serology or rt-pcr (p = . ). little differences were observed for rt-pcr confirmed infection, ari, and ili in results combining the winter and summer influenza seasons. during winter season when seasonal influenza predominated, study subjects who had received tiv showed a lower tendency to develop ili ( % versus %, p = . ) or ari ( % versus %, p = . ). an opposite tendency was seen (ili % versus %, p = . ; ari % versus %, p = . ) during summer when ph n predominated. however, these differences were not statistically significant. rates of ili in subjects infected with ph n did not differ statistical significantly between subject who received tiv and placebo ( % versus %, p = . ). the study was not powered to detect indirect benefits to household contacts of vaccines resulting from reduced household transmission. attack rates were found to be similar between household contacts of subjects received tiv and placebo (data not shown). to examine potential factors that might affect risk of laboratory confirmed ph n infection, a multivariable logistic regression model was fitted to study all subjects and their household contacts. younger participants aged below years were found to have a higher risk (< years or = . , % ci . , . ; - years or = . , % ci . , . , > or = . ). after adjusting for age, sex, and date of study completion, receipt of tiv for the - influenza season was not found to affect risk of ph n infection. however, participants who had laboratory confirmed seasonal influenza infection during the study period had % lower risk of ph n infection (infected with seasonal influenza or = . , % ci . , . ; not infected with seasonal influenza or = . ). as (see table s for winter and summer results separately). influenza-like illness (ili) defined as temperature ‡ . °c plus cough or sore throat; acute respiratory illness (ari) defined at least any two of fever ‡ . °c, chills, headache, sore throat, cough, presence of phlegm, nasal congestion, runny nose, muscle or joint pain. limited by the sample size, we were not able to differentiate between the protective effect of seasonal a(h n ) and a(h n ) infection against ph n . other details of the results from the study were published elsewhere. discussion a non-significantly higher rate of ph n infection was observed in study subjects who received tiv compared to placebo. results from a multivariable logistic regression suggested that such a pattern might be explained by more common seasonal influenza infection in placebo group prior to the pandemic, protecting the placebo group against ph n . seasonal influenza infection within - months observed in our study might have conferred better cross protection than tiv against ph n . this resembles similar previous findings on cross protection between influenza infections in human and animal studies. [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] however, the same phenomenon has not been observed in some studies on seasonal influenza vaccine against ph n . , , [ ] [ ] [ ] apart from differences in study design and vaccine used, we speculate that a short time interval between ph n and most recent seasonal influenza peak activities might be crucial for the phenomenon. hong kong is a subtropical area where the pandemic was preceded immediately by summer seasonal influenza circulation and a few months apart from the winter - influenza peak. if cross protection from seasonal influenza lasts for only a short period, it might have waned below partial cross protection from tiv over time from last seasonal influenza infection. the current study is limited by a small sample size, and further studies are required to confirm our hypothesis. while tiv is only effective against matching strains, a universal influenza vaccine could provide better protection against the ever evolving influenza viruses. introduction immunisation of healthy, as well as high risk, children has been the focus of much recent attention both in prevention of seasonal influenza and during the h n pandemic. detailed information on reactogenicity, particularly for newer vaccine formulations that include adjuvants, is limited. we recently reported results of a head-to-head comparison of two h n pandemic influenza vaccines in children in the uk. here we present new, detailed analyses of reactogenicity data from that study, which has important potential implications for future paediatric influenza vaccine development and use. we compared the safety, reactogenicity, and immunogenicity of two h n influenza vaccines, one as b (tocopherol based oil in water emulsion) adjuvanted egg culture derived split virion, the other non-adjuvanted cell culture derived whole virion, given as two dose schedules days apart, in a randomised, open label trial as previously reported. the study was age stratified ( months to under years & - years) to ensure adequate data in young children. age appropriate safety data (simplified for under year olds) were collected for days after each vaccine dose and serum was collected at enrolment & days after the second dose. nine hundred-thirty seven children received vaccines as per-protocol. when comparing the two vaccines, grade ( ‡ mm) local reactions were seen more frequently following the adjuvanted than the non-adjuvanted vaccine in both age groups, after both vaccine doses. in children over years old, ae % versus ae %, p < ae , after dose one; ae % versus ae %, p = ae , after dose two, in children under years old, ae % versus ae %, p = ae , after dose one (non significant, ns); ae % versus ae %, p < ae after dose two. fever ‡ °c (axillary measurement) was seen more frequently following the second dose of the adjuvanted vaccine compared to the non-adjuvanted vaccine in < year olds ( ae % versus ae %; p < ae ). looking specifically at the adjuvanted vaccine in under year olds, comparing the second dose with the first, there were significantly higher rates of fever ‡ °c (axillary measurement) ( ae % versus ae %, p < ae ), local grade ( ‡ mm) reactions ( ae % versus ae %, p = ae ), pain ( ae % versus ae , p = ae ), use of analgesia or antipyretic medication ( ae % versus ae %, p < ae ), and decreased activity ( ae % versus ae %, p < ae ). the adjuvanted vaccine was significantly more immunogenic, most notably in the younger children. in < year olds, haemagglutination inhibition (hi) seroconversion rates were ae % versus ae %, p < ae . among all general and local reactions measured, only the maximum temperature measured during the days after the second dose of the adjuvanted vaccine showed a significant (positive) association with post vaccination hi titres. for each °c rise in temperature there was a % increase in titre (p < ae ). these reactogenicity data demonstrate a step towards the future possibility of one-dose influenza immunisation programmes for young children associated with low rates of fever and other reactions. the occurrence of fever following adjuvanted vaccine, seen particularly after a second dose in younger children, was quantitatively associated with enhanced antibody titres. this association was not seen with unadjuvanted vaccine. this apparent difference between the relatedness of the pyrogenic and immunogenic effects of the two vaccines merits further investigation. novel adjuvants appear to have the potential to overcome the relatively poor immunogenicity previously experienced with inactivated influenza vaccines in infants and young children. however, careful adjustment may be needed to optimise the balance between high protection and acceptable reaction rates. tries causing sporadic human infections. vaccination has been used as an effective public health tool for influenza prophylaxis. the goal of this study was to evaluate live attenuated influenza vaccine (laiv) vaccine candidates for subtypes h and h . the attenuated phenotype of h and h laiv candidates has been proven in experiments in ovo and in vivo. in randomized clinical trials among adult volunteers, no significant adverse reactions attributable to the live vaccine occurred. our results indicate that pandemic laiv candidates were well tolerated and elicited serum, local, and cellular immune responses. the emergence and spread of highly pathogenic avian influenza h n viruses in avian populations and concurrent infections in humans since has prompted efforts to develop vaccines for use in the event of an influenza pandemic. in , the world faced a new h n pandemic. immunization with inactivated or live vaccines is the primary measure for preventing influenza. laivs appear to be safe and efficacious, and might possibly provide broader immune responses than inactivated vaccines. our study evaluated laiv pandemic candidates as part of the global influenza pandemic preparation project outlined by the who. capacity of the viruses to grow at optimum, low, and elevated temperatures (ca ⁄ ts phenotype) was evaluated by routine technique in embryonated hen eggs. laiv and placebo were supplied by microgen (irkutsk, russia). the monovalent laiv was produced from the pandemic vaccine candidates and formulated to contain and ae eid per dose ( ae ml) of a ⁄ ⁄ california ⁄ ⁄ and a ⁄ ⁄ duck ⁄ potsdam ⁄ ⁄ , respectively. the vaccine or placebo was administered intranasally with a single-use dosing nasal sprayer. two doses were given at an interval of days. one hundred-ninety healthy adults aged - years were randomly divided into groups to receive either pandemic vaccine candidates ( ) or placebo ( ) . subjects were informed about purposes and methods of the study and potential risks associated with participation. all participants had an hai antibody titer of £ : to a ⁄ california ⁄ ⁄ (h n ) pandemic virus. in all there were and vaccines and and participants who received placebo, and were further tested for immune responses to h n or h n pandemic vaccine, respectively. another participants vaccinated with h n laiv were children between to years old. before the children were vaccinated, their parents were advised about study and their consent was required before any child was enrolled. on the advice of the national ethics committee, we did not include a placebo group in this study. individuals were not enrolled if they had an acute illness or fever at the beginning of the study or a history of egg allergy. immune responses of subjects were assessed by routine hai test (evaluation of serum igg antibodies), elisa (evaluation of iga antibodies eluted from the nasal swabs into steril pbs), and cytokine flow cytometry assay (evaluation of virus-specific cd + cd + ifnc + and cd + cd + ifnc + peripheral blood mononuclear cells). the results of phenotypic analysis in ovo showed that pandemic vaccine candidates retained the cold adapted-temperature sensitive (ca ⁄ ts) phenotype, typical of the coldadapted parental mdv. in contrast and as expected, a ⁄ california ⁄ ⁄ and a ⁄ duck ⁄ potsdam ⁄ - parental strains had the non-ts ⁄ non-ca phenotype typical of wt viruses. the h n pandemic vaccine candidate demonstrated an attenuated phenotype in mice and in java macaques and did not infect chickens. the vaccine attenuation study confirmed the attenuated phenotype of a a ⁄ ⁄ california ⁄ ⁄ pandemic laiv candidate in mouse, ferret, and guinea pig models. the phase i ⁄ ii randomized, controlled, double-blind clinical study safety evaluation of pandemic vaccine candidates in adults clinical examination of subjects who received two doses of pandemic vaccine candidates indicated that both vaccines were well tolerated. no fever reactions were observed after the first or second vaccination. after the first vaccination, ae % and ae % of reactogenicity events consisting of catarrhal symptoms, such as pharyngeal irritation or hyperemia, were observed for h n and h n vaccine candidates, respectively. after revaccination, subjects did not report local or systemic reactions. to determine whether a serological response occurred in the cohort of immunologically naïve subjects vaccinated with pandemic vaccine candidates, hai and elisa tests were used (table ) . post-vaccination geometrical mean titers (gmt) among subjects who received two doses of h n vaccine were significantly higher than pre-vaccination titers. the frequency of ‡ fold antibody rises was significantly higher ( ae %) after revaccination than after one dose ( ae %). the percentage of subjects with post-vaccination serum hai titers to h n ‡ : was ae % and for titers ‡ : , it was ae %. no seroconversions in the placebo group were detected. the virus-specific nasal iga antibody response to vaccination after two doses of the h n vaccine candidate demonstrated significant increases of ‡ fold rise iga antibodies ( %) compared to one dose. cumulative data of h n vaccination (all applied tests) showed % and % of conversions after the first and the second vaccination, respectively. increasing h n vaccine virus infectivity from ae to ae eid ⁄ dose lead to an enhancement of post-vaccination hai titers in vaccinees after the first vaccination to homologous h n antigen from ae % to ae % of ‡ fold antibody rises. values of post-vaccination serum hai antibody titers in subjects vaccinated with another pandemic vaccine candidate, a ⁄ ⁄ california ⁄ ⁄ , also proved to be rather low. after the primary vaccination, the percentage of subjects with hai protective antibody titers ‡ : were ae %. after revaccination, this parameter increased to ae %. four-fold increases in serum hai antibody titres were four-fold conversions after the first and the second vaccination was ae % and ae %, respectively. elisa antibodies in nasal swabs showed had an advantage in detecting induction of local iga as compared to serum hai antibodies. after revaccination four-fold serum hai antibody conversions were ae % vs. ae % of iga conversions in nasal swabs, respectively. taking into account cumulative data of h n vaccination (hai and elisa data), the obtained results were here and in the ae % and ae % of conversions after the first and the second vaccination, respectively. fourty-seven subjects were vaccinated with h n laiv, and who received a placebo were chosen for evaluation of cellular immune response by cytokine assays. after revaccination, the mean increases of both cd + and cd + memory cells were significantly higher in vaccinated subjects compared to the placebo group. interestingly, the same effect of vaccination was observed in vaccinees without detectable conversions of hai antibody titers. even after a single vaccination, the rate of subjects with significant increases of these cells in the blood was ae % (cd + ) and % (cd + ). after the revaccination, the percentage of subjects with significant increases in cd + and in cd + cells was ae %. immunogenicity of h n pandemic vaccine candidate in children hai antibody results among children aged to years proved to be significantly higher when compared to adult subjects: after the first vaccination, ae % of the children seroconverted; after revaccination, seroconversions reached ae % ( table ). the gmt rise to h n vaccine with primary vaccination was : ; after revaccination it increased to : . benefits of vaccination with laiv to aid in the control of influenza outbreaks are acknowledged by the who. many years of laiv seasonal trials have shown excellent tolerability and low reactogenicity. [ ] [ ] [ ] indeed, data showed that live influenza vaccines cause minimal systemic, local, and thermal reactions, generally from to %. a different situation was observed in the cohort of immunologically naïve volunteers vaccinated with pandemic vaccines. the rate of local reactions to a ⁄ ⁄ california ⁄ ⁄ and a ⁄ ⁄ duck ⁄ potsdam ⁄ ⁄ vaccine candidates increased to ae % and ae %, respectively. after revaccination no significant local and systemic reactions were observed. this confirms, indirectly, the development of a sufficiently high level of protection after the first vaccination with pandemic laiv. the most important criterion for assessing the quality of vaccines is their estimated safety, epidemic effectiveness, and immunogenicity. however, current regulatory documentation mandates that induction of serum antibodies, measured by hai, as the only criterion for a laiv immunogenicity evaluation. in addition to the standard hai assay, we determined serum (igg) and local (iga) antibodies in adult subjects vaccinated with an h n pandemic vaccine candidate. evaluation of overall results obtained in these additional serological tests, as well as those from the hai assay, showed an immune response to the vaccine in the majority of subjects ( ae % of ab seroconversions after the single vaccination and ae % after revaccination, respectively). these data show that methods used to routinely measure laiv immunogenicity should be revised to include a number of additional immunological methods such as igg and iga elisa, and cytokine assays consistent with the recently updated who recommendations on laiv monitoring. these clinical studies clearly demonstrated that pandemic laiv candidates are effective at generating pandemic specific influenza immunity. a key finding from this study is that it may be practical to give the vaccine as a single dose to both children and adults. evaluation of our laiv pandemic vaccine candidates was performed as part of the global influenza pandemic preparation project outlined by the who. it was considered that laiv could be produced in greater quantities and more rapidly than inactivated vaccines. together with the generation of herd immunity by laiv, this suggests that laiv implementation during the first wave of a pandemic may provide significant social, economic, and health benefits to the community. authors are thankful to path for the financial support of h n pandemic vaccine study. we are grateful for the the main evolutionary mechanism of influenza viruses during inter-pandemic period is the antigenic drift, but the epidemiological picture of circulating viruses is complicated by a high level of heterogeneity of strains, even though drift does not occur, due to co-circulation of drifted and old strains or to co-circulation of viruses belonging to the same type ⁄ subtype but with different antigenic patterns. [ ] [ ] [ ] [ ] [ ] [ ] lack of data exists on the impact of the wide heterogeneity of circulating strains on the seroprotection and on-field effectiveness of influenza vaccine: in particular, little is known about the ability of influenza vaccine to elicit an effective immune response against isolates with few amino acid mutations with respect to vaccine strains that represent the majority of circulating viruses. mf -adjuvanted vaccines, which are currently used for the prevention of seasonal influenza epidemics in elderly, are showed to confer higher seroprotection against homologous and drifted a(h n ) strains than non-adjuvanted vaccines. [ ] [ ] [ ] the broader immune response showed by mf -adjuvanted vaccine was measured using hi and nt assays against egg-grown drifted strains representing vaccine composition changes during the following seasons, but its ability to elicit a broader immune response against circulating viruses belonging to vaccine cluster and presenting amino acid mutations onto antigenic sites or against on-field isolates not-antigenically distant from vaccine strains has not yet been investigated. showing amino acid changes onto antigenic sites in position (n k), (n k), and (p s) with respect to a ⁄ california ⁄ ⁄ . in particular, a ⁄ genoa ⁄ ⁄ and a ⁄ genoa ⁄ ⁄ presents n d amino acid mutation detected in clade a ⁄ wyoming ⁄ ⁄ -like viruses. the ha sequences of a ⁄ genoa ⁄ ⁄ , a ⁄ genoa ⁄ ⁄ , genoa ⁄ ⁄ , a ⁄ genoa ⁄ ⁄ , and a ⁄ genoa ⁄ ⁄ fell within the clade represented by the ha of a ⁄ califor-nia ⁄ ⁄ ; among these isolates, a ⁄ genoa ⁄ ⁄ and a ⁄ genoa ⁄ ⁄ showed antigenic site sequences very close to that of the ⁄ vaccine strain, whereas ha sequences of a ⁄ genoa ⁄ ⁄ , a ⁄ genoa ⁄ ⁄ ⁄ and a ⁄ genoa ⁄ ⁄ posses amino changes onto antigenic site a(r k), c(g e) and d(r k), respectively. the ha sequences of more recent isolates fell within the clade represented by the ha of a ⁄ brisbane ⁄ ⁄ and characterized by the amino acid changes, relative to the ha of a a ⁄ california ⁄ ⁄ , g e and k i, with the exception of a ⁄ genoa ⁄ ⁄ , showing r g and l s amino acid changes present in viruses belonging to a ⁄ nepal ⁄ ⁄ clade. measure of genetic distance between vaccine and circulating strains was calculated as previously described by gupta. two blood samples were collected from each subject, just before and ± day post-vaccination. all sera were stored at ) °c. all samples were tested at the laboratory of health sciences department, university of genoa, by haemagglutination-inhibition (hi) and neutralization (nt) assays, performed following the who criteria and standardised method in our laboratory, respectively. [ ] [ ] [ ] guinea pig red blood cells were used for hi assay. all samples were assayed twice for hi and for nt. the obtained antibody titre was expressed as the reciprocal of the last sera haemagglutinating or inhibiting virus dilution. immunogenicity was determined by: geometric mean titre (gmt); mean-fold increase (mfi; ratio of post-to pre-vaccination titre); seroprotection rate (the percentage of subjects achieving an hi and nt titre ‡ iu); and seroconversion rate (percentage of subjects with a fourfold increase in hi or nt antibody titers, providing a minimal post vaccination titer of : ). post-vaccination gmt was reported as ratio, with the corresponding % confidence interval, of gmts after vaccination with mf -adjuvanted vaccine and with non-adjuvanted subunit vaccine. seroprotection and seroconversion rate % confidence interval was calculated using modified wald method. comparisons of seroconversion and seroprotection rates between subunit and mf -adjuvanted vaccine groups have been analyzed by fischer's exact test. the results were evaluated against the committee for medicinal products for human use (chmp) criteria for approval of influenza vaccines in the elderly, which require that at least one of the following criteria be met: mfi > ; seroprotection rate > %, or seroconversion rate > %. furthermore, hi titres were also transformed into binary logarithms, corrected for pre-vaccination status, as described by beyer et al. and were expressed as median titres, with the corresponding °- °i nter-quantile range. comparisons of corrected post-vaccination titers between subunit and mf -adjuvanted vaccine groups were analyzed by wilcoxon test. difference in immunogenicity profile between vaccine groups, expressed by ratio of different parameters, was correlated with genetic and antigenic distance between vaccine and viruses used in the study using spearman test. pre-vaccination titres were not significantly different between vaccine groups, for all strains (data not shown). post-vaccination gmt ratios between mf -adjuvanted and non-adjuvanted vaccine groups determined using hi and nt assays, with the corresponding % confidence interval, according to viral strain are shown in figure . both vaccines met chmp requirements for mfi (> ), seroconversion (> %), and seroprotection rate (> %) against a ⁄ wyoming ⁄ ⁄ -like, with the exception of a ⁄ genoa ⁄ ⁄ and a ⁄ california ⁄ ⁄ -like circulating viruses and against egg-grown a ⁄ wyoming ⁄ ⁄ , a ⁄ california ⁄ ⁄ , and a ⁄ wisconsin ⁄ ⁄ strains; the immune response against a ⁄ genoa ⁄ ⁄ met the requirements for mfi and seroprotection rate only in mf -adjuvanted vaccine group. requirements for mfi, seroconversion, and seroprotection rate against the a ⁄ brisbane ⁄ ⁄ -like virus a ⁄ genoa ⁄ ⁄ and the a ⁄ nepal ⁄ ⁄ -like genoa ⁄ ⁄ viruses and against egg-grown a ⁄ brisbane ⁄ ⁄ strain were reached only in subjects vaccinated with the mf adjuvanted vaccine. a similar pattern emerged from the analysis of mfi, seroconversion and seroprotection rates using nt assays. subjects vaccinated with the mf -adjuvanted vaccine showed significantly higher post-vaccination hi gmts against a ⁄ wyoming ⁄ ⁄ -like, a ⁄ california ⁄ ⁄ -like, a ⁄ nepal ⁄ ⁄ -like and a ⁄ brisbane ⁄ ⁄ like viruses, with the exception of a ⁄ genoa ⁄ ⁄ , and against egg-grown a ⁄ california ⁄ ⁄ , a ⁄ wisconsin ⁄ ⁄ , and a ⁄ brisbane ⁄ ⁄ strains, compared with individuals immunized with the non-adjuvanted vaccine ( figure ). the mf -adjuvanted vaccine also induced significantly higher seroconversion and seroprotection rates against following correction for pre-vaccination status, hi titres were significantly higher for the mf -adjuvanted vaccine group when evaluated against a ⁄ wyoming ⁄ ⁄ -like viruses, a ⁄ brisbane ⁄ ⁄ -like a ⁄ genoa ⁄ ⁄ , and a ⁄ nepal ⁄ ⁄ -like a ⁄ genoa ⁄ ⁄ strain ( figure ). pre-vaccination titre corrected response was higher in subjects vaccinated with mf adjuvanted vaccine also against egg-grown a ⁄ wyoming ⁄ ⁄ , a ⁄ california ⁄ ⁄ ⁄ , a ⁄ wisconsin ⁄ ⁄ , and a ⁄ brisbane ⁄ ⁄ . among viruses more closely related to a ⁄ california ⁄ ⁄ , subjects immunized with mf -adjuvanted vaccine showed a significantly higher corrected titres against a ⁄ genoa ⁄ ⁄ , a ⁄ genoa ⁄ ⁄ , and a ⁄ genoa ⁄ ⁄ strains compared with the non-adjuvanted vaccine ( figure ) . spearman test showed a clear correlation between the distances and the advantage offered by mf expressed by ratio between mfi, post-vaccination gmts, corrected post-vaccination median, seroconversion, and seroprotection rates calculated using hi test in the two vaccine groups. similarly, ratio between mfi, seroconversion, and seroprotection rates calculated with nt test correlated with the genetic and antigenic distance between vaccine and viruses used for the study. the ability of mf to enhance the immunogenicity and to elicit a broader immune response against drifted strains than non-adjuvanted vaccine is consistent with other findings reported during the last decade. [ ] [ ] [ ] in subjects vaccinated with the mf -adjuvanted vaccine containing a ⁄ california ⁄ ⁄ , the immune response, expressed by a number of parameters, such as crude and corrected postvaccination titers, seroconversion, and seroprotection rates calculated using hi and nt assays, is higher than that observed in individuals immunized with subunit vaccine when it is evaluated against a drifted strains, such as a ⁄ brisbane ⁄ ⁄ -like and a ⁄ nepal ⁄ ⁄ -like strains, and against egg-grown a ⁄ brisbane ⁄ ⁄ virus. for the first time in this study, the impact of heterogeneity of circulating strains antigenically close to the vaccine on the antibody response elicited by mf -and non-adiuvanted vaccines is evaluated. immune response against viruses isolated during the ⁄ season, that appear more phylogenetically close to ⁄ vaccine strain a ⁄ wyoming ⁄ ⁄ , was higher in subjects vaccinated with mf -adiuvanted vaccine as demonstrated by higher crude and corrected post-vaccination hi titres and higher postvaccination nt titres, with the exception of a ⁄ genoa ⁄ ⁄ , against whom the nt post-vaccination gmt is identical in mf and subunit vaccine groups. furthermore, hi seroconversion and seroprotection rates were higher in mf vaccine group when evaluated against a ⁄ genoa ⁄ ⁄ and a ⁄ genoa ⁄ ⁄ . as far as the immune response against a ⁄ california ⁄ ⁄ -like viruses, the small number of enrolled subjects did not allow appreciating differences using qualitative response indicators, but crude post-vaccination hi titres were higher in mf vaccine group for all the strains. interestingly, a ⁄ california ⁄ ⁄ -like viruses with at least one amino acid change onto antigenic sites, i.e. a ⁄ genoa ⁄ ⁄ , a ⁄ genoa ⁄ ⁄ , and a ⁄ genoa ⁄ ⁄ , showed a more marked difference in terms of response between the two vaccine groups. individuals immunized with mf -adiuvanted vaccine showed higher corrected post-vaccination hi titres and post-vaccination nt titres in comparison with subjects vaccinated with plain vaccine. these response indicators were similar in the two vaccine groups when the response was evaluated against a ⁄ genoa ⁄ ⁄ and a ⁄ genoa ⁄ ⁄ , which present no amino acid changes onto antigenic sites and identical hi titers respect with a ⁄ california ⁄ ⁄ at molecular and antigenic characterization, respectively. thus, the advantage offered by mf in terms of higher immunogenicity expressed by higher post-vaccination hi titres is observable also against viruses showing antigenic and molecular pattern undistinguishable from vaccine strain, but it became even more evident as the antigenic and molecular distance between vaccine and circulating strains grew. as emerged for a ⁄ genoa ⁄ ⁄ , a ⁄ genoa ⁄ ⁄ , and a ⁄ genoa ⁄ ⁄ , one amino acid was a sufficient change in antigenic sites for -fold decrease of hi titre against homologous vaccine strain to observe -fold higher post-vaccination nt titers (mf ⁄ subunit postvaccination gmt ratio range between ae and ae , figure ) and one-dilution higher corrected post-vaccination hi titers in mf vaccine group ( figure ) . finally, the correlation between the distance and the improvement offered by mf in terms of higher immunogenicity clearly emerged by spearman correlation analysis: it remains wellfounded both using a number of different response parameters obtained from hi and nt assays and calculating the distance by serological and genetic methods. outbreaks of h n pdm in pigs in commercial swine operations have been reported in several countries. in all incidents, epidemiological investigations have linked humans as the possible source of the infection to pigs. experimentally, it was established that the virus is pathogenic and transmits readily in pigs. the natural outbreaks of h n pdm and laboratory studies underscore the threat that the virus poses to the swine industry and highlight the need for developing effective control strategies. in the united states, a trivalent live attenuated influenza vaccine (flumistÒ) has been licensed for use in humans since . in swine medicine, however, temperature-sensitive laivs are not available. currently, only inactivated vaccines are available for pigs, but they provide limited protection against antigenically diverse influenza viruses. additionally, the use of inactivated vaccines has been associated with enhanced pneumonia when immunized pigs were challenged with divergent viruses. thus, the development of laivs has the potential to circumvent the drawbacks associated with commercial vaccines. with the aim of developing laiv temperature-sensitive influenza vaccines against the h n pdm virus, we have used reverse genetics to introduce attenuation markers in the polymerase genes of a swine-like tr h n influenza virus, a ⁄ turkey ⁄ ohio ⁄ ⁄ (h n ) (ty ⁄ ). we chose this isolate because it grows well in both eggs and cell culturebased substrates, displays a broad host range, and has internal genes similar to the h n pdm virus. safety and efficacy studies of the ty ⁄ att vaccine candidates in pigs demonstrated that this vaccine backbone is attenuated in swine and conferred sterilizing immunity upon an aggressive intratracheal challenge of pigs with the h n pandemic virus. thus, introduction of genetic signatures for att in the backbone of a swine-like tr influenza virus resulted in highly attenuated and efficacious live influenza vaccines with promising applications veterinary medicine. -t cells and mdck cells were maintained as previously described. a ⁄ turkey ⁄ ohio ⁄ ⁄ (h n ) (ty ⁄ ) has options for the control of influenza vii ª blackwell publishing ltd, influenza and other respiratory viruses, (suppl. ), - been previously described and it was kindly provided by yehia saif, ohio state university. a ⁄ california ⁄ ⁄ (h n ) (ca ⁄ ) was kindly provided by the centers for disease control and prevention (cdc). generation of recombinant viruses by reverse genetics (rg) was done using a previously described method. the genetic signatures for attenuation were introduced into the pb and pb genes of ty ⁄ . ny : ty ⁄ att is a : reassortant with the surface genes from the a ⁄ new york ⁄ ⁄ (h n ) virus and the ty ⁄ att internal genes. all viruses were amplified in mdck cells to produce viral stocks. twenty-five pigs were divided into five groups (n = ) and intranasally inoculated with tcid ⁄ animal of either h n : ty ⁄ att or with ny(h n ) : ty ⁄ att vaccines diluted in ml of mem. two other groups were similarly inoculated with h n : ty ⁄ wt and h n : ty ⁄ rg and served as controls, whereas a fifth group was mockvaccinated with pbs alone. clinical observations were performed as previously described. , efficacy of h n ty ⁄ att vaccine in pigs fourty pigs were divided in four groups (n = )( table ) . group was vaccinated with tcid ⁄ animal of ny(h n ) : ty ⁄ att through intranasal route, whereas group was vaccinated intramuscularly with ml of an adjuvanted uv-inactivated ca ⁄ vaccine (uvadj-ca ⁄ ). group , non-vaccinated and challenged (nv+ca ⁄ ), and group , non-vaccinated, mock-challenged (nv+mock), were also included. pigs were boosted two weeks later. fourteen days post boost (dpb), pigs from groups - were challenged intratracheally with ml of · tcid of ca ⁄ . following challenge, pigs were monitored using methods as previously described. all statistical analyses were performed using graphpad prism software version ae (graphpad software inc., san diego, ca). the differences were considered statistically significant at p < ae . the ty ⁄ att-based vaccines are attenuated in swine pigs inoculated with wt ty ⁄ viruses developed fever (> °c) that peaked hpi ( figure a) and shed large amounts of in nasal secretions ( figure b) . similarly, viral titers in bronchoalveolar lavage fluid (balf) collected at dpi ranged from to tcid ⁄ ml ( figure c ). at necropsy, the lungs from animals inoculated with these viruses had severe pneumonia ( figure d ). in contrast, none of the animals inoculated with h n or h n ty ⁄ att viruses developed clinical signs following vaccination, indicating that the ty ⁄ att viruses were safe for administration to pigs ( figure a) . correspondingly, there was - fold less virus shedding from the nose of pigs vaccinated with ty ⁄ att viruses as compared to unmodified ty ⁄ viruses. in general, ny(h n ) : ty ⁄ att -vaccinated pigs shed less virus than h n : ty ⁄ att inoculated pigs ( figure b ). in addition, viral titers in balf were significantly reduced (p < ae ) in ty ⁄ attvaccinated pigs as compared to ty ⁄ wt-infected pigs ( figure c ). although both vaccines caused mild gross and microscopic lesions in the lungs, the percentage of lung ae ± ae * ± * ± * ± * balf, bronchoalveolar lavage fluid, uvadj-ca ⁄ , uv-inactivated ca ⁄ vaccine; nv+ca ⁄ , non-vaccinated, challenged positive control group; nv+mock, non-vaccinated, non-challenged negative control group. *significantly different from nv+ca ⁄ control group at p < ae . geometric mean hi titer against ca ⁄ at the day of challenge. à percentage of macroscopic lung lesions given as mean score ± sem. § average viral titer (log ) measure as tcid per ml. -average viral titer (log ) in balf at dpc. involvement was not significantly different from mock-vaccinated pigs, corroborating the clinical findings that these vaccines are sufficiently attenuated in pigs ( figure d, e) . histopathologically, nasal turbinates and trachea obtained from pigs immunized with either vaccine were similar to control animals, as opposed to the wt-inoculated pigs ( figure e ). vaccination with h n ty ⁄ att-based vaccines provides sterilizing immunity against h n pdm in pigs the clinical performance in pigs of the h n vaccines is summarized in table . nv+ca ⁄ animals had macroscopic pneumonia, viral replication in balf and shedding in the nose. uvadj-ca ⁄ vaccine provided satisfactory protection, but this protection was not sterilizing. remarkably, animals vaccinated with ny(h n ) : ty ⁄ att had sterilizing immunity. in both vaccine groups there was a significant reduction (p < ae ) in the percentage of macroscopic lung pathology compared to the nv+ca ⁄ group. control pigs had neither significant macroscopic nor microscopic lesions in the lungs. hi antibody titers measured at the day of challenge in both vaccine groups were approximately the same (table ). in the present study, we developed for the first time, temperature-sensitive laiv for use in pigs. data from our safety studies showed that both the h n and h n ty ⁄ att vaccines were attenuated in pigs. although the ty ⁄ att vaccines were detected in balf samples, the level of viral replication was significantly reduced in comparison to unmodified virus and, more importantly, caused no overt clinical signs. a minimal amount of replication is likely beneficial for eliciting t-cell responses to internal genes that may provide heterologous cross-protection. one of the most challenging tasks in producing effective live attenuated vaccines is to achieve an adequate balance between safety and efficacy. by introducing the att modifications into the polymerase genes of a swine-like tr strain, this desirable balance was achieved. the vaccines were histopathologic scores of nasal turbinates, trachea and lungs at dpi. ny(h n ) : ty ⁄ att (a virus that carries the surface genes of a ⁄ new york ⁄ ⁄ (h n ) and ty ⁄ att internal genes). all h n viruses have their surface genes derived from ty ⁄ . values are shown as the mean ± sem. * p < ae ; **p < ae ; *** p < ae . options for the control of influenza vii ª blackwell publishing ltd, influenza and other respiratory viruses, (suppl. ), - attenuated in pigs and, more importantly, provided sterilizing immunity upon an aggressive challenge with pandemic h n as opposed to an experimental ca ⁄ inactivated vaccine, which elicited protective but not sterilizing immunity in all animals. in the face of influenza pandemics that have the ability to overcome the species barriers such as the h n , the supply of vaccines for use in agriculture could be jeopardized. our cell culture-based live att h n vaccines could be an attractive alternative for this possible pandemic vaccine shortage. because the ty ⁄ att live vaccines developed here are efficacious in swine, are easier to manufacture than inactivated vaccines, and do not require adjuvants, our study represents a major advance in vaccine development for the h n pandemic. in conclusion, our second generation of live att influenza vaccines based on modifications of the pb and pb genes of ty ⁄ retains its safety properties in vivo and can induce excellent protection against aggressive h n challenges in the swine host. influenza virus is one of the most important respiratory pathogens worldwide. , type a influenza causes an acute disease of the upper airways, and affects - million persons yearly. moreover, the threat of human influenza epidemic and pandemic has dramatically increased in recent years. vaccination is one of the crucial interventions for reducing the spread and impact of influenza. the generally used parenteral inactivated influenza vaccines induce mainly systemic antibody responses and only weak cell-mediated immunity and low levels if any mucosal immunity. on the other hand, intranasal immunization with live virus can induces a broad spectrum of both systemic and mucosal antibodies, and the immune response localized in the mucosa blocks the virus even during the first phase of infection. unfortunately, the use of live vaccines is always associated with a certain risk. the development of a crossprotective vaccine against potentially pandemic strains is an essential part of the strategy to control and prevent a pandemic outbreak. we induced intrasubtypic and intersubtypic cross-protection in balb ⁄ c mice by intratracheal (it) immunization with inactivated influenza viruses together with dead delipidated bacillus firmus (dbf) as an adjuvant. ten days after the nd immunization dose, the mice were infected with live influenza virus b ⁄ lee ⁄ lethal for mice (total infection dose corresponded to · ld ) or a⁄ pr ⁄ (total infection dose corresponded to ae - ld ). dbf adjuvant markedly increased both systemic and mucosal anti-viral antibody formation when applied together with inactivated influenza a or b viruses. protective significance was tested in vivo. mice were preimmunized with ) pbs (controls), ) dbf alone, ) virus alone, and ) vir-us+dbf. influenza b virus strains b ⁄ lee and b ⁄ yamanashi ⁄ ( years phylogenetically distant and antigenically substantially different, especially in terms of the main protective antigen -surface haemagglutinin) or two different influenza a subtypes -a ⁄ pr ⁄ (h n ) and a ⁄ california ⁄ (h n ) -were used (figures and ) . the mice were challenged with · ld of either b ⁄ lee ⁄ or a ⁄ pr ⁄ as appropriate. all controls died. the mice treated with dbf alone died with a delay or survived, which could be explained by stimulation of innate immunity. the animals immunized with virus alone were protected against homologous strains. adjuvant immunization was cross-protective: the mice immunized with a heterologous b strain (figure ) fell ill (pronounced body mass loss), but almost all survived and recovered. the mice immunized with a heterologous a subtype were excellently protected (negligible weight loss and zero mortality). intratracheal dbf ( lg per mouse) given to non-immunized mice hour before influenza infection eliminated the lethal effect in - % of infected animals depending on infection dose ( ae - ld ); in mice infected with lower than lethal doses ( ae ld ), weight loss was minimized or did not occur. the current mode of vaccination-induced immunity is mostly effective against a homologous strain of the virus used for vaccination. the attention is therefore focused on vaccines that are able to induce cross-protection and could be effective also in case of sudden appearance of a new virus variant. inactivated influenza viruses are known to be often insufficiently effective when used for mucosal immunization and for induction of cross-protection against drifted influenza viruses or novel subtypes. the drawback of vaccination with dead virus can be overcome by using a suitable adjuvant. mouse models were successfully immunized with vaccine containing inactivated virus in combination with cholera toxin or the escheria coli heat-labile toxin (lt). [ ] [ ] [ ] the use of cholera toxin in humans is precluded because of its high toxicity; a number of lt mutants that retain their adjuvant activity have been prepared; these mutants were likewise tested on the mouse model and should not cause any serious side effect in humans. for this reason, current studies aim at finding a suitable and safe mucosal and systemic immune response. dbf has been shown to be a very efficient adjuvant for mucosal immunization stimulating both innate and adaptive immunity. intratracheal immunization with inactivated influenza viruses and dbf as adjuvant induced efficient and even heterosubtypic cross-protection. dbf given hour before infection provided partial protection probably because of its strong stimulatory effect on the innate immunity. temperature-sensitive and cold-adapted candidates for live attenuated influenza vaccine with genomic composition of : based on highly pathogenic influenza a ⁄ h n viruses with pandemic potential were generated by the replacement of six internal genes from the influenza a ⁄ puerto rico ⁄ ⁄ (pr ) virus from pr -based rg-candidates for inactivated vaccine with appropriate internal genes of influenza a ⁄ leningrad ⁄ ⁄ ⁄ (h n ) master donor virus (mdv) for russian laiv by methods of classical reassortment. all attempts to capture avian n neuraminidase into the genome of the mdv laiv production were ineffective. : reassortants were not generated. step by step co-infection of triple reassortants (h n -h n -h n ) with h n mdv in some cases was the only possibility to generate influenza a ⁄ h n cold-adapted vaccine reassortants. difficulties in generating : reassortants could be explained by a substantial gene constellation in the genome of pr based h n reassortant viruses. strong coupling of pb ⁄ pr and avian n genes in a ⁄ h n -pr -rg reassortants was revealed. annually updated laiv strains are generated by classical reassortment of circulating influenza viruses with well characterized, attenuated, ts ⁄ ca mdvs. resulting attenuated reassortants inherit the relevant ha and na of wild type parental virus and six internal genes of the mdv. candidates for inactivated influenza vaccines based upon avian influenza viruses with pandemic potential are generally generated by reverse genetics methods. in these cases, like with laiv, vaccine strains are : reassortants which possess the modified ha and na from potentially pandemic virus and six internal genes from the pr virus. the pr virus is considered to be of low virulence, i.e. attenuated, for humans, yet offers properties of high seed virus growth for influenza vaccine production. the ha of avian h influenza viruses with pandemic potential is engineered to remove four basic amino acid codons from the cleavage site of ha, resulting in a virus that is considered attenuated for natural hosts and safe for people. the objective of this study was to safely generate vaccine candidates for a laiv using highly pathogenic avian influenza viruses by the replacement of six internal pr genes in the genome of candidates for inactivated vaccine subtype h n (a ⁄ h n -pr -rg) with internal genes of the laiv mdv by methods of classical reassortment. len -mdv and a ⁄ h n -pr -rg virus were co-infected in embryonated chicken eggs. five rounds of selective propagation were performed, three of which were at low temperature ( °c). the production and selection of reassortants were carried out in the presence of rabbit antiserum to len -mdv. cloning by endpoint dilution was performed in each of the last three passages. a virus sample in an open petri dish was rocked gently for sec while being irradiated with a ge watt germicidal lamp at a distance of cm from the dish. the residual infection titer was measured by titration in embryonated chicken eggs. genome composition of reassortant viruses was monitored by rflp analysis. in addition, capacity of reassortant viruses to grow at optimum, low, and elevated temperatures (ca ⁄ ts phenotype) for influenza viruses was determined by virus titration in chicken eggs. reassortment of the mdv with the vn-pr or indo-pr viruses either resulted in reassortants that contained six internal genes from len -mdv. however, all generated clones contained the na from the mdv. of ten such : reassortants based on vn-pr three reassortants had the pa gene from pr and one had ns gene from pr . : reassortants from the targeted h n composition were not generated. after repeated attempts, : temperature sensitive and cold adapted reassortants based on vn-pr and indo-pr viruses were obtained, but again, none had inherited the avian n neuraminidase (table ) . in contrast, nibrg- didn't reassort with the mdv at all. twelve unsucsessful attempts to develop : or : reassortants of nibrg- with mdv showed that the classical reassortment procedure (cloning by limited dilutions in the presence of anti-mdv serum, followed by co-infection of equal doses of two parental viruses in eggs and two selective passages at °c) did not work for this virus pair. to disharmonize the incredibly strong gene constellation of nibrg- , various modifications of the co-infection step were studied, such as: altering the nibrg- to mdv ratio (from : to : tions of anti-mdv serum alone or together with anti-pr serum. it was noted that even if the h n to mdv ratio was : , the clones obtained were presumably parental h n viruses without the transfer of any mdv-genes into genome of nibrg- . in all, clones were isolated, and of them were identical to nibrg- parental virus. in nine clones, only the pa gene from mdv was included, whereas in three clones only the 'cold' ns gene was included (data not shown). using uv inactivation of nibrg- prior co-infection was more encouraging. after the first round of co-infection of partially uv-inactivated nibrg- with mdv (at ratio : ), reassortants that inherited several internal genes of mdv were obtained in the context of the nibrg- background (b , c , c , d ) ( table ). some of them (c , c , d ) were chosen for the next round of co-infection. after the second round of co-infection, c , c , and d 'intermediate' reassortants with mdv (at ratio : or : ) : vaccine reassortants finally were obtained. live attenuated influenza vaccine is considered as one of the most promising pandemic vaccines. according to the who there is evidence that laiv might be more effective than inactivated vaccines. this study attempted the safe development of laiv for potential pandemic highly pathogenic avian a ⁄ h n viruses on the base of rg-reassortants for inactivated vaccine with modified h hemagglutinin and mdv for laiv. replacement of pr based internal genes into genome of vn-pr and indo-pr reassortants with appropriate genes of mdv was realized by the classical reassortment procedure. difficulties were encountered in obtaining : reassortants that contained both the ha and na from the wild type avian h n parental virus. in attempts to reassort the nibrg- with mdv, the classical reassortment procedure was unsuccessful. the challenge faced was to break an incredibly strong gene constellation of the nibrg- virus. partial uv-inactivation of nibrg- was encouraged in replacement of some pr internal genes with mdv genes in some cases avian-human reassortant viruses with gull h n and human influenza h n genes were difficult to generate, and reassortants with the desired genotype of six gull virus genes with human influenza a h and n genes were not isolated despite repeated attempts. the gull pb , np, and ns genes were not present in any of the gull-human h n reassortants generated. it is difficult to fully understand potential reasons for observed difficulties to reassort some avian viruses with human strains. unsuccessful attempts to develop : vaccine reassortants may be caused by an observed strong connection of pb and na genes in the genome of a ⁄ h n -pr -rg viruses. in our attempts, each reassortant that possessed avian n neuraminidase inheritied pb gene of pr as well. and vice versa, the 'cold' pb gene always appeared to be coupled with the n neuraminidase of the mdv. in some cases, step by step co-infection of triple reassortants (h n -h n -h n ) with h n mdv may be the only possibility to generate a cold-adapted vaccine reassortant. our studies demonstrate unique and significant challenges that are faced in the development of influenza vaccines for avian influenza viruses with pandemic potential. such challenges must be further studied to identify methodologies to allow for rapid development and response to emerging viruses in a crisis. it is imperative that these studies be continued and expanded to identify either mechanisms of such tight gene constellations in influenza viruses produced by rg-derived vaccine strains or inability some genes of human h n and avian h n viruses to cross. in addition, further studies to improve the efficiency of classical reassortment processes will be conducted. during the period from to , avian influenza outbreaks among humans have been registered in countries of asia, europe, and africa. morbidity and mortality of humans followed the global spread of avian influenza h n among wild and domestic birds, which caused great economic loss to the poultry industry in many regions including some highly developed countries. the global threat from avian influenza forced scientists to develop technologies for the production of a ⁄ h n human vaccine. the development of ai a ⁄ h n vaccines using strains isolated in kazakhstan and the organization of local production and creation of strategic stockpiles of effective vaccines is the an important issue for public health protection in the republic of kazakhstan. to address this, a scientific program 'influenza a ⁄ h n vaccine development for public health protection in kazakhstan' was approved and financed from to . in this article we give basic results of the development of a recombinant ai a ⁄ h n inactivated whole virion vaccine with aluminium hydroxide as adjuvant for public health protection in kazakhstan. [ ] [ ] [ ] the development of vaccine technology was conducted with the use of a ⁄ astanarg ⁄ : ⁄ (a ⁄ h n ) recombinant strain made of a ⁄ chicken ⁄ astana ⁄ ⁄ (h n ) and a ⁄ pr ⁄ ⁄ (h n ) strains by the reverse genetics. inactivation of virus containing allantoic fluid was carried out with the use of formalin in different concentrations. complete-ness of the virus inactivation was tested by -fold virus passaging in embryos. , purification and concentration of the inactivated viruscontaining allantoic fluid was conducted with the use of ultra filtration in tangential flow, which was followed by gel filtration. then we evaluated the content of total protein, hemagglutinin, and ovalbumin in purified and concentrated material. vaccine was composed of clarified and inactivated virus concentrate with the known ha dose containment, and ae % aluminum hydroxide was added in : proportions. composition components and quality control of finished vaccine was determined in the stages of semi-finished product and finished biopreparation. determination of quantitative ovalbumin content was conducted by elisa applying a strip test-system chicken egg ovalbumin elisa kit cat. n (alpha diagnostic international, usa). vaccine immunogenicity was evaluated by hai micro test in u-bottom -well plates produced by 'costar' (usa). vaccine apyrogenicity was evaluated after intravenous injection of the studied preparation to rabbits. , for confirmation of the results vaccine series were tested for bacterial endotoxins with the use of limulus amebocyte lysate produced by charles river laboratories, inc. usa. the vaccine toxicity was evaluated in white mice with body weight - gm and in rats with body weight - g both males and females according to glp principles. allergenic characteristics of the inactivated vaccine was determined in white outbred mice and guinea-pigs both males and females according to 'methodic guideline for evaluation of allergenic characteristics of pharmacological substances'. in the first series of experiments, we conducted work for obtaining influenza a(h n ) recombinant strain. bidirectional expression plasmid phw_b with full-length sequences of ha and na gene segments of the strain a ⁄ chicken ⁄ astana ⁄ ⁄ (h n ) isolated in kazakhstan were synthesized in geneart ag, (regensburg, germany). ha gene was modified by deleting the region encoding multiple basic amino acid rrrk motif in ha cleavage site. moreover, to prevent recovery of repeating basic amino acids motif due to polymerase slide, we inserted replacements g fi t and k fi t. thus the ha cleavage site consists of the following sequence ntpqgerrrkkrglfgai ntpqtetrglfgai. the basic amino acid motif of highly pathogenic strain a ⁄ chicken ⁄ astana ⁄ ⁄ (h n ) was replaced by the sequence tetr ⁄ glf, which is characteristic of low pathogenic strains of influenza h n . sequence of gene coding na in the strain a ⁄ chicken ⁄ astana ⁄ ⁄ (h n ) was cloned without modifications. the other segments pb , pb , pa, np, m and ns were obtained from influenza virus ivr- and synthesized and cloned in two-forked expression plasmid phw_b in geneart ag company, germany. the origin of genetic segments of vaccine strain a ⁄ astanarg ⁄ : ⁄ (h n ) is presented in table . vero cell culture ( passage) (who) was received from european cell culture collection (salisbury, wiltshire sp jg, great britain). the cell culture was grown in dmem ⁄ f medium with the addition of % of fetal bovine serum and mm l-glutamine. to obtain reassortant virus a ⁄ astana ⁄ ⁄ r- : , vero cells were infected with correlative plasmids by way of electroporation using nucleofector ii (amaxa) equipment. infected cells were placed in -well plates. after hour, dmem ⁄ f medium was changed into ml of opti-pro sfm (gibco) medium adding mm l-glutamine and lg ⁄ ml trypsin. two days after cytopathic effect appearance supernatant was collected and used for infection of spf-eggs. the virus a ⁄ astanarg ⁄ ⁄ - : was grown in chicken embryos, and then virus titer was determined in chicken embryos and madine-darby canine kidney (mdck) cell culture. the titer of two final a ⁄ astanarg ⁄ - : virus stocks was ae log eid ⁄ ml (chicken embryos); ae log tcid ⁄ ml (mdck cells); ha titer : . a ⁄ chicken ⁄ astana ⁄ ⁄ (h n ) virus contains motif of repeating basic amino acids in ha cleavage site. it is known that this sequence is the main determinant of ai virus pathogenicity. that is why this site was deleted in vaccine candidate strain. sequence results confirmed that influenza virus a ⁄ astanarg ⁄ ⁄ r- : strain ha gene sequence contains modified ha cleavage site and keeps mutations inserted for prevention of return to virus wild type. to confirm stability of modified ha gene sequence, five additional passages of recombinant strain a ⁄ astana rg ⁄ ⁄ - : were conducted in chicken embryos. sequencing and following phylogenetic analysis of the recombinant strain a ⁄ astana rg ⁄ ⁄ - : ha gene sequence proved the presence of modification in ha cleavage site. deletion of pathogenicity site of the obtained virus was confirmed by lethality test for chicken embryos, intravenous pathogenicity test in chicken, and in plaque-forming test with trypsin. pathogenicity test in chicken embryos showed that recombinant strain a ⁄ astanarg ⁄ - : is capable of growing up to high titers without causing embryos' death. a ⁄ astanarg ⁄ - : strain pathogenicity evaluation was conducted in - week-age white leghorns chicken, and this study proved that the strain a ⁄ astanarg ⁄ - : (h n ) is not virus pathogenicity inductor in chickens, which got intravenous injections of this virus (pathogenicity index is equal to ). h n strain ha cleavage site modification provides its cleavage capability only with tripsin-like proteases, which shows low level of pathogenicity. aiming at confirmation of ha cleavage site modification, we experimentally studied virus replication ability both with trypsin and without this enzyme. and we got the following results. in the plaque-forming test, a ⁄ astanarg ⁄ - : strain produced plaques in mdck cells only with trypsin, proving the trypsin-dependent phenotype characteristic of low pathogenic avian influenza viruses. to prove the ha subtype antigenic analyses of a ⁄ astana ⁄ ⁄ r- : strain was conducted by means of serological methods in hemagglutinin inghibition test with the use of postinfection antisera of rabbits and rats (influenza research institute swd rams), standard serum received from cdc, atlanta, usa. hai test proved that a ⁄ astana ⁄ ⁄ r- : strain belongs to h subtype. furthermore, toxicity of vaccine candidate strain was evaluated by way of subcutaneous injection of viral material to balb mice. the strain appeared to be non-toxic for white mice getting subcutaneous injection of ae ml of the preparation. the conducted research showed that according to all tested characteristics, a ⁄ astana ⁄ ⁄ r- : strain can be used for influenza a ⁄ h n inactivated vaccine production. according to its genetic characteristics, this strain belongs to the group of vaccine strains recommended by who for the development of influenza pre-pandemic inactivated vaccines. we determined basic cultivation parameters of the recombinant strain a ⁄ astanarg ⁄ - : in - day chicken embryos. the determined parameters are the following: infection dose, - eid ; cultivation period, hour; incubation temperature, °c. these cultivation parameters allow obtaining virus containing material with biological eid and hemagglutinating activity of ae - ae log eid ⁄ cm and : ha titre and even higher. in the next series of experiments, we conducted research on the determination of optimal sequence of technological stages of virus clarification, concentration, and inactivation in the order of vaccine production. samples of viral material were subjected to inactivation before and after clarification and concentration. the regimen of virus inactivation by formaldehyde with final concentration of ae %, period of inactivation of days, temperature of inactivation medium of - °c, ph of inactivation medium of - ae . on the basis of the conducted experiments we determined that the selected regimen of inactivation provides complete and irreversible inactivation of viral suspensions of the hpai strain irrespective of the kind of inactivated material. we did not observe reduction of ha activity in non-clarified viral suspensions. however, when we inactivated clarified and concentrated material, ha activity reduced by an order of magnitude. comparison of forms and sizes of virion structural elements in native (non-clarified) and formalin inactivated preparations did not reveal any significant differences. concentration of virus particles in the studied preparations was similar. the selected inactivation regimen provides obtaining completely avirulent viral suspension of the strain a ⁄ astanarg ⁄ - : , and it does not influence the structure of the virus. on the basis of the experiments results, we selected method of viral allantoic fluid inactivation without preliminary clarification. during further research, we tried to get highly clarified viral concentrate. this study resulted in the combined scheme, which includes clarification of inactivated viral allantoic fluid by low speed centrifugation at circulations per min for minutes, filtration through membrane filters with pore diameter of ae lm, ultrafilatration ⁄ diafiltration, gel filtration in b sepharose, and sterilization of viral suspension through membrane filters with pore diameter of ae lm. the experiments resulted in the development of production technology of embryonic inactivated vaccine based on recombinant strain a ⁄ astanarg ⁄ : ⁄ (h n ) contain-ing aluminium hydroxide as adjuvant. the developed influenza a ⁄ h n human vaccine has the trade name kazfluvacÒ. its composition components are presented in table . preclinical testing of the vaccine kazfluvacÒ was conducted according to the following parameters: general health condition of animals, change of body weight and temperature of immunised animals (for ferrets), presence of post vaccination antibodies response in sera, forming protective immune response against reassortant viruses of h subtype, study of acute and chronic toxicity of three experimental vaccine series in different doses and semi-finished vaccine product applying different ways of injection, study of allergic and immunotoxic characteristics of the vaccine, as well as study of pyrogenic reaction and analysis for bacterial endotoxins presence. [ ] [ ] [ ] [ ] preclinical tests of kazfluvacÒ vaccine safety showed that this vaccine does not have toxic effect on organisms of warm-blooded laboratory animals. double intramuscular injection of kazfluvacÒ vaccine in inoculative dose does not effect appearance, general health condition, behaviour of animals, their muscular strength and physical activity, does not have negative effect on biochemical parameters of blood and basic physical functions of animals organism, and does not cause pathomorphological changes. this shows the safety of the vaccine. local irritation action was not observed. the results of the vaccine allergic action study showed that the vaccine does not have allergic effect at the intravenous injection. the research also showed that the vaccine does not have negative effect on immune system of laboratory animals. research conducted on mice and ferrets showed high immunogenic activity of the vaccine at one-and two-dose regimen of injection. the research showed % of protective effect of kazfluvacÒ vaccine at two-dose injection regimen in ferrets infected by homological strain of influenza virus. the devised inactivated influenza a ⁄ h n vaccine kaz-fluvacÒ is a safe and immunogenic biopreparation that is not worse than the overseas analogues in its immunobiological characteristics. [ ] [ ] [ ] [ ] to date the whole-virion inactivated influenza a ⁄ h n vaccines of the producers such as omnivest (hungary), biken, denka seiken, kitasato institute, kaketsuken (japan), gsk biologicals (belgium), sinovac biotech (china) are registered. all of them are produced on the basis of chicken embryos and aluminum is used as an adjuvant. kazfluvacÒ differs from its analogues in the flowchart of the virus purification and concentration that makes possible to produce a safer preparation. , the results of the conducted research and preclinical testing allow starting work towards implementation of phase i preclinical tests on volunteers. it is planned to conduct a randomized blind placebo-controlled phase i study on double application of kazfluvacÒ vaccine in increasing doses. the preparation will be administered to volunteers aged - years for assessment of its safety and immunogenicity in doses of ae and ae lg of ha. when the world health organization (who) announced the sixth phase of a ⁄ h n v influenza pandemic, scientists all over the world started investigation to develop technology for production of prophylactic means against the disease. having taken into consideration the threat of a pandemic for kazakhstan, the ministry of education and science of the republic of kazakhstan launched the program ''monitoring, study, and development of diagnostic, prophylactic, and therapeutic means for influenza a ⁄ h n .'' this paper presents the experimental data obtained at the ribsp in the course of the studies towards the development of technology for production of an inactivated a ⁄ h n influenza vaccine, as well as the results of pre-clinical testing of the developed vaccine. the development of vaccine production technology was conducted with the use of who recommended vaccine strain nibrg- xp constructed by the method of reverse genetics in the national institute for biological standards and control (nibsc, great britain). the virus was inactivated with formalin at different final concentrations, and the extent of inactivation was evaluated via threefold virus passages in developing chicken embryos. the inactivated virus was purified and concentrated by the method of ultrafiltration in tangential flow followed by gel filtration. the purified and concentrated material was evaluated judging on the total protein, hemagglutinin (ha), and ovalbumin. the vaccine was prepared by pooling the purified and concentrated virus material with the certain weight content of ha and the work solution of aluminum hydroxide ( ae %) in the ratio : . the ovalbumin content was quantified in elisa with the use of the strip test system chicken egg ovalbumin elisa kit (cat. no. alpha diagnostic international, san antonio, texas, usa). weight content of the virus ha was determined according to sominina, burtseva. the content of the residual formaldehyde, aluminum (al + ) ions, and thiomersal in the vaccine was measured according to the operating instructions. the vaccine immunogenicity was assessed in the hemagglutination inhibition test, which was carried out as a microassay in -welled u-bottomed plates (''costar'', new york, usa). , apyrogenicity of the vaccine was assessed post intravenous administration of the tested preparation to rabbits. , to confirm the obtained results the vaccine batches were tested for bacterial endotoxins with use of the limulus amebocyte lysate (charles river laboratories, inc., wilmington, ma, usa). the toxicity of the vaccine was assayed in white mice weighing - g and in rats weighing - g (male and female) in compliance with the principles of good laboratory practice. allergenic properties of the inactivated vaccine were determined according to the ''operating instructions on assessment of allergenic properties of pharmaceutical substances'' in white outbred laboratory mice and guinea-pigs of both sexes. the first step in the course of developing technology for vaccine production was to determine the major conditions for influenza virus cultivation: usage of -days embryonated chicken eggs at the infectious dose within - eid , incubation temperature ( ± ae )°c, and duration of the incubation period hours. the established parameters for virus cultivation made it possible to produce virus-containing materials of infectious activity within ae - ae log eid ⁄ cm and hemagglutinating activity : and higher. in the subsequent experiments, an optimal method for virus inactivation was selected. on the basis of the experimental findings, the following conditions for inactivation of the native virus-containing material were elected: formalin of ae % final concentration as an inactivating agent; inactivation period of hours at temperature ( ± )°c. these conditions provide the complete inactivation of the virus (nibrg- xp strain) material, did not impact distinctly the structural organization of the virus, and did not reduce the antigenic activity. as it is well known, virus purification and concentration means very much in the development of technology for production of an inactivated whole-virion influenza vaccine. the investigation into optimization of the technological step of purification and concentration of the recombinant influenza virus nibrg- xp strain resulted in selection of an optimal pattern including such steps as clarification of the virus suspension by filtration through membranes with pore size ae lm, virus concentration by ultrafiltration in a tangential flow, dialysis filtration in a tangential flow, gel filtration on sepharose b, and sterilization of the viral suspension through membrane filters with pore size ae lm. the studies conducted by the ribsp specialists resulted in the development of technology for production of the first domestic whole-virion inactivated a ⁄ h n influenza vaccine with aluminum hydroxide as adjuvant and with the brand name refluvac Ò . the key processing characteristics of the whole-virion inactivated a ⁄ h n influenza vaccine vaccine refluvac Ò are shown in table . simultaneous with the performance of all process operations, the parameters such as sterility, inactivation extent, ph, vaccine specificity, total protein content, weight content of has, aluminum and formalin contents, content of thiomersal, and ovalbumin, pyrogenicity of the vaccine and its immunogenicity for mice, were optimized. the key qualitative characteristics of the designed influenza a ⁄ h n vaccine refluvac Ò are shown in table . before implementation of phase i clinical trials on volunteers, preclinical testing of three experimental batches of refluvac for immunogenic activity and safety was carried out. it was conducted in three laboratory bases of research institutions: the toxicology institute ⁄ federal medicobiological agency, russia (st petersburg), the research institute for biological safety problems (republic of kazakhstan), and the influenza research institute ⁄ north-western branch of the russian academy of medical sciences (st petersburg), with use of different animal models (mice, rats, chinchilla rabbits, guinea-pigs, ferrets). the results of the preclinical testing are as follows: • electron microscopy of the preparation has shown that the viral particles are well dispersed and do not aggregate. the portion of whole (intact) particles is over %, which is evidence of virion integrity; • assessment of polypeptide composition of the vaccine refluvac by electrophoresis in % polyacrylamide gel with sodium dodecyl sulfate has shown the vaccine to contain both surface antigens (ha, na) and highly purified inner virion proteins (np, m ) that are typespecific antigens, so the vaccine is a preparation of full immunological value; • judging on the parameters of acute and chronic toxicity for white mice and rats of both sexes, the vaccine is a non-toxic and safe preparation; • under conditions of a chronic experiment on white mice and rats, it was found that refluvac does not produce changes in behavior, somatic, or vegetative responses; • assay of hematological and biochemical blood characteristics of white mice and rats following vaccine administration did not reveal any significant differences as compared to the animals of the control group; • refluvac does not cause allergenic and immunotoxic impact; • the vaccine refluvac does not cause local irritative effect; • refluvac is apyrogenic for laboratory animals; • the pathomorphological and hystopathological analysis did not reveal any changes due to immunization in animal organs; • testing of immunogenic characteristics of the vaccine on mice and ferrets has shown formation of hemagglutinating antibodies in animals after single administration; • refluvac induces % protection in immunized ferrets at their challenge with the wild-type influenza virus a ⁄ california ⁄ ⁄ (h n v). the results of the performed preclinical testing have allowed concluding that refluvac, an inactivated whole-virion vaccine with aluminum hydroxide as adjuvant, is a safe and highly effective preparation against influenza a ⁄ h n v. the implemented study resulted in development of technology for production of the first domestic inactivated allantoic whole-virion influenza a ⁄ h n vaccine with aluminum hydroxide as an adjuvant under the brand name refluvac Ò based on the recombinant strain nibrg- xp. the devised pandemic vaccine meets who requirements as well as requirements concerning safety and immunogenicity of the national pharmacopeias of the republic of kazakhstan and russian federation. [ ] [ ] [ ] [ ] the devised technology for vaccine production differs from the previous technologies for production of allantoic whole-virion influenza a ⁄ h n vaccines in its processdependent parameters. presence of an adjuvant (aluminum hydroxide) increases significantly the vaccine immunogenicity and allows maximal reduction of the dose of the administered antigen that, in turn, results in diminished reactogenicity of the vaccine. aluminum hydroxide is an adjuvant that is most frequently used in clinical practice. to date the results of the double-centered randomized study of the europe-licensed vaccine fluval p [monovalent inactivated whole-virion influenza vaccine with aluminum phosphate based on strain a ⁄ california ⁄ ⁄ (h n ) nymc x- a (omninvest, pilisborosjeno, hungary)] that is similar to the refluvac preparation are published. the data of this research are an evidence of safety and high immunological effectiveness of the vaccine in dose lg ha at single administration both in adults and elderly persons. the results of the pre-clinical tests allow recommending carrying out phase clinical testing of the refluvac Ò vaccine for safety and immunogenicity. single immunization of volunteers with refluvac Ò in doses ae , ae , and ae lg of ha are planned. mid , respectively. the study results confirm that new h n laiv and h n laiv candidates are safe and immunogenic and confer protection from homologues influenza virus infection in mice. the recent emergence of a new pandemic h n virus and the threat of transmission of avian viruses to humans had stimulated research and development of live attenuated cold-adapted influenza vaccines against newly appeared influenza viruses. formulations of live attenuated influenza a vaccine (laiv) against pandemic influenza strains, including h n , h n , h n , and h n are currently being tested in preclinical and phase i clinical studies. the following paper describes the preclinical study of new h n and h n laiv candidates in mice. the study addressed the following three objectives: (i) to demonstrate that cold-adapted (ca) reassortant influenza a(h n ) and a(h n ) vaccine candidates are indistinguishable from the parental a ⁄ leningrad ⁄ ⁄ ⁄ (h n ) master donor strain (mds) virus with regard to replication efficiency in upper and lower respiratory tract of mice; (ii) to demonstrate the immunogenicity of different doses of cold-adapted (ca) reassortant influenza a(h n ) and a(h n ) vaccine candidates in mice; and (iii) to demonstrate the protective efficacy of cold-adapted (ca) reassortant influenza a(h n ) and a(h n ) vaccine candidates in mice against a homologous wild-type virus challenge. the a ⁄ ⁄ mallard ⁄ netherlands ⁄ ⁄ (h n ) reassortant containing the ha and na genes from a ⁄ mallard ⁄ netherlands ⁄ (h n ) and six other genes from mds, the a ⁄ ⁄ california ⁄ ⁄ (h n ) reassortant containing the ha and na genes from a ⁄ california ⁄ ⁄ (h n ) and six other genes from a ⁄ leningrad ⁄ ⁄ ⁄ (h n ) were generated by classical genetic reassortment in embryonated chicken eggs (ec). viruses were propagated in days old eggs ( °c, hours). fifty percent egg infectious dose (eid ) titers were determined by serial titration of viruses in eggs. titers were calculated by the method of reed and muench. female balb ⁄ c mice, - weeks of age were used in all experiments. mice were lightly anesthetized with ether and then inoculated intranasally (i.n.) with ll of infectious virus diluted in phosphate-buffered saline (pbs). mice were inoculated with mid ( % mouse infectious dose) of a ⁄ ⁄ california ⁄ ⁄ (h n ), a ⁄ ⁄ mallard ⁄ netherlands ⁄ ⁄ (h n ), and a ⁄ leningrad ⁄ ⁄ ⁄ (h n ) mds. viral loads were measured in respiratory and brain tissues collected at and days post-infection (dpi). tissue homogenates prepared using a disruptor and clarified supernatants were titrated on eggs at permissive temperature to determine infectious concentrations. groups of animals were inoculated with mid or mid of either h n laiv or h n laiv intranasally after collecting a pre-immunization blood sample. a second blood sample was collected at dpi. on the same day, the animals received a second intranasal inoculation with the same virus that was used for priming at dpi. to assess protection, all animals were infected dpi with either mid of a ⁄ california ⁄ ⁄ (h n ) or mid a ⁄ mallard ⁄ netherlands ⁄ (h n ) virus by the intranasal route. four animals from each group were euthanized at dpi, and the respiratory and systemic organs were harvested for virus titration. a forth blood sample was collected at dpi from the remaining animals. hi antibody titers were determined for individual serum samples collected on days , , , and . body weights were taken daily following challenge through day postchallenge. sera were tested for hi against homologous h n and h n viruses. the h n laiv, h n laiv and h n mds influenza viruses replicate in mice lungs at level ae - ae lgeid ⁄ ml at dpi (figure ). at dpi, replication of the viruses in the lungs decreased to ae - ae lgeid ⁄ ml (data not shown). in contrast, the wild-type virus a ⁄ mallard ⁄ netherlands ⁄ (h n ) demonstrated high level replication in lungs - ae lgeid ⁄ ml. the levels of replication of studied viruses in nasal turbinates were ae - ae lg eid ⁄ ml at dpi (figure ) , and ae - ae lgeid ⁄ ml at dpi (data not shown). there were no significant differences between the viruses in regard to replication in upper respiratory tract of mice. thus, it was shown that a ⁄ ⁄ mallard ⁄ netherlands ⁄ ⁄ (h n ) and a ⁄ ⁄ california ⁄ ⁄ (h n ) vaccine candidates was indistinguishable from parental a ⁄ leningrad ⁄ ⁄ ⁄ (h n ) in terms of replication in the lungs and noses of mice at and dpi. no virus was found in the brain tissue of immunized mice at and dpi (in undiluted samples tested). thus, it was shown that a ⁄ ⁄ mallard ⁄ netherlands ⁄ ⁄ (h n ), a ⁄ ⁄ cali-fornia ⁄ ⁄ (h n ) vaccine candidates are identical to a ⁄ leningrad ⁄ ⁄ ⁄ (h n ) in lacking neuroivasive capacity, and all three viruses similarly fail to replicate in the brain. it was shown that all immunized animals survived after challenge with wild-type a ⁄ mallard ⁄ netherlands ⁄ ⁄ (h n ) virus. the mice in vaccine groups showed no signs of morbidity. average weight changes were tracked from day to day in all study groups, but the changes did not exceed %. as shown in figure , the challenge virus actively replicated in respiratory tissue taken from mock immunized animals ( ae lgeid in the lung and ae lgeid in the nose), but failed to infect the brain and spleen. on the other hand, in both h n laiv vaccinated groups, all tested organs were free from presence of challenge virus. thus, immunization of mice with either mid or mid h n laiv protected the animals from the subsequent challenge infection with a homologous with wild-type h n virus. both h n and h n laiv candidates were found to be immunogenic. after one dose of mid of h n laiv, gmt of hi antibodies were ae . one dose of mid or mid h n laiv elicited hi antibody level with gmt of ae and ae , respectively. the second dose of h n laiv further stimulated serum hi antibody levels to gmt ae and ae , for mid or mid , respectively (data not shown). the mouse model is widely used to better understand the pathogenicity of avian influenza viruses for mammalian species, to be able to predict the pandemic potential of such viruses, and to develop improved methods for the prevention and control of the virus in a potential pandemic. a subset of the h viruses was evaluated for the ability to replicate and cause disease in balb ⁄ c mice following intranasal administration. h subtype viruses were able to infect mice without adaptation and manifested different levels of lethality and kinetics of replication. there is limited preclinical information available for laiv. thus, live monovalent vaccine against pandemic influenza virus h n (influvir) was tested for acute toxicity and its effect on the systems and organs of laboratory animals. according to toxicology and necroscopy results, the live monovalent influenza vaccine influvir, when applied intranasally, was safe and was well tolerated. in our current study we demonstrate that a(h n ) and a(h n ) laiv are indistinguishable from the parental mds virus with regards to replication kinetics in the upper and lower respiratory tract of mice. both h n and h n laiv candidates were immunogenic and protect mice against subsequent a challenge with the wild-type virus. live attenuated cold-adapted (ca) influenza vaccines are an effective means for the control of influenza, most likely due to their ability to induce both humoral and cellular immune responses. in our study we confirm that new h n laiv and h n laiv candidates are safe, immunogenic, and confer protection from influenza infection in mice. health organization (who) declared a pandemic by raising the worldwide pandemic alert level to phase . therefore, h n inactivated monovalent vaccine formulated with our proprietary oil-in-water emulsion based adjuvant was evaluated in ferrets for its potential to induce with low antigen dose efficient, robust, and rapid protective immunity against a wild type challenge virus (a ⁄ netherlands ⁄ ⁄ ). this adjuvant was also tested in ferrets in a h n avian influenza model for its ability to induce a cross-clade immunity and cross-protection. two independent studies (a&b) were carried out with male and female outbred ferrets (musleta putorius furo) in compliance with ''guide for the care and use of laboratory animals,'' ilar recommendations and aaalac standards. ferrets used in both studies were influenza seronegative by anti-nucleoprotein elisa and by hi assay against the pandemic and seasonal strains. in study a, four groups of seven ferrets aged approximately of months received one or two im vaccinations weeks apart of either af -adjuvanted ( ae lg of ha with af ) or unadjuvanted ( body weight loss was monitored as an indicator of disease and a mean body weight loss of % was recorded in the control group at day of necropsy. body weight loss was reduced to £ % and £ % in animals that had received and doses of either unadjuvanted or af -adjuvanted vaccine, respectively. viral lung titration showed high levels of virus replication ( ‡ ae tcid ⁄ g tissue) in the lungs of all control ferrets days after challenge. one or two administrations of unadjuvanted vaccine reduced lung viral load by and log , respectively. interestingly, ferrets that received either one or two doses of af -adjuvanted h n vaccine, showed significantly greater reduction of lung viral loads (> log ). no virus was detected in the lungs of ⁄ ( %) animals immunized with a single injection of the af -adjuvanted vaccine and in % of ferrets vaccinated twice. assessment of viral shedding from the upper respiratory tract showed that the af -adjuvanted a ⁄ h n monovalent vaccine was able to reduce the viral load in the nose and in the throat by ae and ae log , respectively, as compared to the control group. conversely, viral loads were only slightly reduced in the nose and mostly unchanged in the throat in ferrets immunized with either one or two doses of unadjuvanted a ⁄ h n monovalent vaccine. gross pathology and histology examinations revealed lung lesions consistent with influenza a ⁄ h n virus infec- however, a second dose of af -adjuvanted vaccine strongly increased hi and mn titers, which persisted for months (table ). antibody responses cross-reactive to heterologous clade . strain were elicited ferrets vaccinated with the af -adjuvanted clade . vaccine. hi antibody titers ‡ crossreactive to clade . and persistent up to d were observed in vaccinated animals. an inter-clade low crossreactive hi response to a clade strain was only detected in a few ferrets that had been vaccinated with the af -adjuvanted clade . . all af -adjuvanted clade . antigen vaccinated animals survived challenge either with the homologous or heterologous virus until euthanized day . after challenge, mean body temperature and mean body weights were monitored as indicators of disease. in the control ferrets, mean body temperature increased by - °c (depending on the challenge virus strain) h post challenge, with an accompanying mean body weight loss ranging from ae % to ae %. ferrets vaccinated with the af -adjuvanted clade . vaccine showed a lower and delayed fever compared to control ferrets that received the same viral challenge, whereas no significant differences were observed between vaccinated animals and their respective controls upon challenge with clade . or clade viruses. body weight loss was reduced in all vaccinated animals when compared to controls after challenge with either the homologous clade . strain or with one of the heterologous strains. lung virus titration showed high levels of virus replication in all control animals days after homologous challenge with the clade . virus. lung viral loads of all ferrets immunized with the af -adjuvanted clade . vaccine were reduced more than log . vaccination resulted in complete viral clearance from the lungs of % of animals assessed days after challenge. as compared to controls, a reduction of the mean viral load of about log was observed in ferrets vaccinated with the af -adjuvanted clade . vaccine after heterologous challenge with either the clade or clade virus. conversely, vaccination with af -adjuvanted clade . vaccine did not result in reduction of lung viral loads after challenge with the clade . heterologous virus strain. titration of pharyngeal swabs showed high levels of viral shedding in all control ferrets after challenge with clade . strain, whereas virus was not detected in any vaccinated animal. similarly, log reduction of viral shedding was seen in vaccinated versus control ferrets following clade heterologous challenge. lower reductions in viral shedding were observed after clade . challenge ( ae log ) and clade challenge ( ae log ). gross pathology and histology revealed lung lesions consistent with influenza a ⁄ h n virus infection all control animals challenged with the clade . , clade . or clade strains. mild to moderate lung lesions were observed in control animals following challenge with clade virus. macroscopic evaluation (percentage of affected lung parenchyma) and histopathological analysis (extent and severity of alveolitis, alveolar oedema and hemorrhage) showed that lung lesions were significantly reduced in af -adjuvanted clade . vaccinated animals after challenge with the homologous clade . virus strain as compared to controls. similarly, a reduction of the macroscopic and microscopic lung lesions was observed in vaccinated animals upon heterologous challenge with clade . and clade virus strains, whereas no differences were observed between control and vaccinated animals after challenge with clade virus. the results of these ferret challenge studies demonstrated that low doses of pandemic influenza vaccines formulated with an oil-in-water emulsion adjuvant, af , elicited strong antibody responses specific to the immunizing strain. importantly, these vaccines provided protection after homologous challenge with complete virus clearance in ferret lungs and reduced viral shedding from the upper respiratory tract suggesting an ability to reduce virus transmission. moreover, af -adjuvanted h n vaccine can provide cross-protection upon challenge with different h n clades by preventing mortality and reducing the viral burden in the lower and the upper respiratory tract. in conclusion, the results of these studies highlighted the ability of af -adjuvanted influenza vaccines to induce potent immune responses and full protection in ferrets against homologous challenge and suggested that protection may be mediated, at least in part, by antigenspecific humoral immunity. since , outbreaks of h n influenza virus infection in poultry have occurred in eurasian countries. phylogenetic and antigenic analysis of h n isolates revealed that there are three sublineages, consisting of g , g , and korean, among ha genes of the eurasian h n viruses. h n viruses do not cause severe disease in poultry, but co-infection of h n viruses with bacteria such as staphylococcus aureus, haemophilus paragallinarum, or attenuated coronavirus vaccine may exacerbate the disease. , h n viruses were isolated from domestic pigs in china and korea and from humans with febrile respiratory illness in hong kong in kong in , kong in , and it is, thus, postulated that in the present study, h virus strains were analyzed antigenically and phylogenetically to select a proper h n vaccine strain. inactivated whole virus particle vaccine was prepared, and its potency against h virus challenge was assessed in mice. viral rnas were extracted from the allantoic fluid of chicken embryos infected with viruses by using a commercial kit (trizol ls reagent; invitrogen, california, usa) and reverse-transcribed with the uni primer and m-mlv reverse transcriptase (invitrogen). the primers used for the ha gene amplification were h - f and h - r. for phylogenetic analysis, sequence data of the genes together with those from public database were analyzed by the neighbor-joining method. h influenza viruses were analyzed by hemagglutinationinhibition (hi) test. chicken hyperimmunized antisera against seven h viruses were prepared according to previous report. virus replication and pathogenicity against embryonated chicken eggs viruses were inoculated into -day-old embryonated chicken eggs and incubated for hours at °c. ha titers and % egg infectious dose (eid ) were measured every hours post-inoculation. pathogenicity of dk ⁄ hok ⁄ ⁄ against embryonated chicken eggs was evaluated by mean death time (mdt) as described previously. dk ⁄ hok ⁄ ⁄ was injected into the allantoic cavities of -day-old embryonated chicken eggs and propagated at °c for hours. the virus in the allantoic fluids ( ha) was purified by differential centrifugation and sedimentation through a sucrose gradient according to previous report. the concentration of protein was measured by od using ultrospec pro (amersham biosciences, tokyo, japan). the purified virus was inactivated with ae % formalin at °c for days. immunization of mice and challenge of immunized mice with hk ⁄ ⁄ four-week-old female balb ⁄ c mice were purchased from japan slc, inc. (shizuoka, japan). the mice were injected subcutaneously with , , ae , or ae lg proteins of inactivated dk ⁄ hok ⁄ ⁄ whole virus vaccine. two weeks later, the mice were boosted by subcutaneous injection with the same dose of the vaccine. control mice were injected with pbs. serum samples were tested by enzyme-linked immunosorbent assay (elisa) according to previous report. one week after the second vaccination, mice in each group were challenged intranasally with ll of ae eid of hk ⁄ ⁄ under anesthesia. on days postinfection, five mice in each group were sacrificed, and the lungs were separately homogenized to make a % (w ⁄ v) suspension with minimal essential medium (nissui, tokyo, japan). the virus titers of the supernatants of lung tissue homogenates were calculated in -day-old embryonated chicken eggs and expressed as the eid ⁄ gram of tissue. the other five mice in each group were monitored for body weight for days after challenge. the ha genes of h viruses were sequenced and analyzed by the neighbor-joining method. all of the h viruses were classified into the eurasian lineage ( figure ) . eleven, seven, and four strains were classified in the korean, g , and g sublineages, respectively. the h viruses of the korean and g sublineages were isolated from waterfowl, poultry, pigs, and humans in the east asian countries, and those of the g sublineage were isolated from poultry in the west asian countries. the cross-reactivity between these antisera and h n viruses were analyzed by hi test. the antisera against h viruses belonging to the korean sublineage were broadly cross-reacted to h viruses belonging to the g and g sublineages. h viruses belonging to the korean lineage were reacted to the antisera against h viruses belonging to the g and g sublineage compared with h viruses belonging to the other sublineage (data not shown). thus, it was suggested that h vaccine strain should be selected from the viruses of korean sublineage to prepare for the vaccine strain of h viruses. dk ⁄ hok ⁄ ⁄ replicated efficiently in -day-old embryonated chicken eggs (data not shown). pathogenicity of dk ⁄ hok ⁄ ⁄ against embryonated chicken eggs was determined by mdt. dk ⁄ hok ⁄ ⁄ was low pathogenic against embryonated chicken eggs (data not shown) and was selected as an h vaccine strain. to assess the potency of the vaccine against h virus infection, mice vaccinated subcutaneously with inactivated dk ⁄ hok ⁄ ⁄ were challenged intra-nasally with hk ⁄ ⁄ . immunogenicity of the inactivated vaccine was assessed by measuring the igg antibodies in mouse sera by elisa. antibody was detected in the group of mice injected lg protein after the first immunization and detected in the group of mice injected lg protein after the second immunization. thus, potency of the present inactivated whole virus vaccine was demonstrated in mice. next, to assess the protective immunity of the inactivated vaccine in mice, viral titers in the lungs was determined. the virus titers in the lungs were ae - ae eid ⁄ g in the groups of mice injected , and lg protein, and ae - ae eid ⁄ g in the other vaccinated groups. body weight reduction of mice were observed in the group of mice injected ae , ae lg protein, and control groups from dpi, and reached to % body weight loss from -to -day post-infection ( figure ). this result correlates with antibody titer in mouse sera and viral titers in the lungs. these results suggest that the test h inactivated whole vaccine confers prevent of weight loss and reduction of virus replication against h influenza virus infection in mice. recently, h n viruses of all of three sublineage have been isolated from wild birds and poultry in worldwide. h n viruses were isolated from pigs and humans in china and korea, suggesting that h n virus would be a potential for a pandemic influenza virus in human population. h n viruses were isolated from pigs in china and korea and were classified into the g and korean sublineage. in human cases, all h n virus isolated from humans in china was classified into the g sublineage. it was suggested that h n viruses isolated from pigs and humans vary in antigenicity of isolates between the korean, g , and g sublineages. therefore, it is important for the preparedness of influenza pandemic to develop h influenza virus vaccine, which could broadly cross-react to antisera of all sublineage viruses. so, we selected the vaccine candidate strain, dk ⁄ hok ⁄ ⁄ , which could broadly cross-react to antisera of all sublineage viruses, and which could replicate in this study, it was suggested that the test vaccine has potency to protect against challenge with h virus using mice for mammalian model. the challenge virus, hk ⁄ ⁄ , was isolated from human, replicates efficiently in mice, and shows pathogenicity in mice. the test vaccine inhibited viral replication and body weight loss in mice. whole inactivated vaccine produced protective immunity, supporting our approach of using whole virus particles for vaccine development. furthermore, whole particle virus vaccine could induce igg and mucosal iga levels after intranasal vaccination with whole particle vaccine. the present results may facilitate the studies of the vaccine for future pandemic caused by h influenza virus in humans. tants to attempt to improve growth. to determine whether wild type h n pdm grew better in the novartis mdck suspension cell line (mdck pf) than in eggs, isolations from h n pdm positive clinical samples were attempted in both substrates. the isolation rate of h n pdm viruses was higher in mdck pf cells ( %) ( ⁄ ) compared to allantoically inoculated eggs ( %) ( ⁄ ) . however the yields were lower than observed with seasonal viruses. little improvement in virus yield was seen with extra passaging or dilutions of h n pdm viruses isolated in mdck pf cells. with the emergence of the swine-origin pandemic h n (h n pdm) influenza in april , the need for efficient production of a suitable vaccine was a high priority. virus isolates were distributed by the who for the urgent development of suitable vaccine strains early in the pandemic. vaccine viruses can be grown in embryonated chicken eggs or in certified mammalian cells. , unfortunately wildtype h n pdm virus strains distributed by the who grew poorly in cell lines and eggs, requiring the generation of a series of conventional and reverse genetics derived reassortants to attempt to improve growth. from these reassortants, only the conventional egg derived reassortants nymc-x- a and nymc-x- (both based on one of the earliest known viruses a ⁄ california ⁄ ⁄ ) showed high enough growth and yield in eggs and cell culture to make them suitable for vaccine manufacture. these reassortants, while acceptable, still only gave haemagglutinin (ha) yields of approximately % that of seasonal h n reassortants. to determine if more recent wild type h n pdm viruses grew better in the novartis mdck suspension cell line (mdck pf), h n pdm positive clinical samples were cultured in mdck pf cells and also in embryonated hen's eggs. in addition, to improve virus yields from mdck pf isolates, extended passaging of three wild type h n pdm influenza viruses was performed using various virus dilutions at each passage level. the results were assessed using various serological and molecular biology techniques and compared to viruses isolated in eggs and conventional mdck cells. h n pdm viruses were received at the centre from who national influenza centres, who influenza collaborating centres and other regional laboratories and hospitals in australia, new zealand, and the asia ⁄ pacific region. viruses were received as original clinical specimens consisting of nasal swabs, throat swabs, nasopharyngeal aspirates, or nasal washes that had previously been shown to be h n pdm positive by real time rt-pcr. these specimens were then cultured in mdck pf cells with serum free medium containing trypzean (optaflu) and also independently inoculated into the allantoic cavity of day-old embryonated hen's eggs. virus cultures in mdck pf cells were sampled at and hour and evaluated by various means including ha titres. at hour, virus cultures were further passaged at varying dilutions ranging from ) to ) up to a total of passages. embryonated hen's eggs were incubated at °c for days and allantoic fluid was harvested and ha titres performed to determine whether a further passage was required in order to improve growth. the conventional reassortants were produced by a mixed infection of eggs or mdck pf cells with the wild type virus and a donor virus carrying the internal genes of the a ⁄ puerto rico ⁄ ⁄ virus. the reassortants were obtained by sequential passages using immuno-selective antisera against the surface antigen of the donor virus to remove virus populations carrying the ha and na protein of the donor strain. the reverse genetics viruses were rescued in vero cells using the plasmid system. both types of reassortants were generated and supplied by who collaborating centres and essential regulatory laboratories except the nvd-c- strain, which was produced by novartis. in this small study with recent h n pdm viruses, the isolation rate was higher in mdck pf cells ( %) ( ⁄ ) compared to allantoically inoculated eggs ( %) ( ⁄ ) . assessment of ha titres, however, showed higher ha titres in egg-isolated viruses compared to viruses isolated in mdck pf cells after two passages. egg generated or cell generated reassortant viruses gave higher ha titres compared to the homologous wild type viruses (table ) . no amino acid changes were observed in mdck pf isolated influenza viruses compared to original specimens or viruses isolated in conventional atcc derived mdck cells, unlike egg isolated viruses which showed a number of amino acid changes, many consistent with egg adaptation mutations (table ) . viruses isolated in mdck pf cells grouped phylogenetically with viruses isolated in conventional atcc derived mdck cells or viruses sequenced from original clinical samples, while egg isolated viruses grouped slightly differently (data not shown). as a result of the poor growth of h n pdm viruses in mdck pf cells, serial dilutions were performed over a number of passages ( figure ). based on the results obtained from the virus isolates, a ⁄ victoria ⁄ ⁄ , a ⁄ wellington ⁄ ⁄ , and a ⁄ darwin ⁄ ⁄ , a supplemental protocol was developed and used in the isolation of a ⁄ brisbane ⁄ ⁄ (figure ). only small differences in ha titer were seen between different dilutions, and copy number showed a similar trend to ha titer at each passage ( figure ). following the supplemental protocol for the isolation of a ⁄ brisbane ⁄ ⁄ results showed slightly higher ha titres with little variation between passages. the egg derived reassortants nymc-x- a and nymc-x- were also assessed for growth in mdck pf cells and were found to be superior by ha titer to other conventional reassortants (egg or cell derived), reverse genetics derived reassortants, or wild type viruses (table ) . two methods were used to determine the ratio of ha to other viral proteins: densiometric analysis using sds-page and reversed-phase hplc using a subtype specific standard. ha content in different vaccine seeds of influenza a subtypes demonstrated that the ha content per total virus protein from the nymc h n pdm reassortants was significantly different to the seasonal influenza a subtypes. for the seasonal h n the ratio of ha to p p p p p p p p p p p p p p p p n and m was ‡ %, for the h n the ratio of ha to n and m was £ %, while for the pandemic a ⁄ h n , the ratio of ha to n and m was much lower at £ % (data not shown). the results of this study has observed the growth of a series of - h n pdm viruses in vaccine suitable mdck pf cells to be generally lower than what has been seen with other seasonal influenza viruses. little improvement in virus yield was seen with extra passaging of h n pdm viruses isolated and passaged in mdck pf cells. passaging up to times in mdck pf cells using dilutions ranging from ) to ) resulted in supernatants with viral ha titres ranging from ha ⁄ ll to ha ⁄ ll. the isolation rate of h n pdm viruses was higher in mdck pf cells ( %) compared to allantoically inoculated (and passaged) eggs ( %), a trend also seen in previous work with seasonal influenza viruses. in contrast a study by hussain and colleagues found similar rates of isolation and replication of seasonal influenza viruses in mdck cells and eggs. the virus load as determined by matrix gene copy number showed a similar trend to ha titers. two of the isolates exhibited small rises and falls in ha titer during passaging, while a third, a ⁄ victoria ⁄ ⁄ gave consistently higher titers. interestingly this virus was unable to be isolated in eggs. the ha sequences of all strains were assessed at p , p , p , p , p and when available compared to the original clinical sample ha sequence. mdck pf-isolated viruses had few if any changes in their ha amino acid sequence, while the majority of egg isolates showed - amino acid changes compared to the clinical sample, with an egg adaption change (l i) evident in a number of them. the ha sequence of one of the better growing viruses, a ⁄ victoria ⁄ ⁄ , was found to have a g e change compared to the a ⁄ california ⁄ ⁄ reference virus. this change was also seen in the virus isolated in conventional, adherent mdck cells. these viruses with g e change when tested by hai have shown reduced reactivity with ferret antisera to a ⁄ california ⁄ ⁄ -like viruses, but normal reactivity with ferret antisera to h n pdm a ⁄ bayern ⁄ ⁄ -like viruses. despite this mutation all mdck pf derived viruses appeared to be a ⁄ california ⁄ ⁄ -like by hai. the h n pdm egg-derived reassortants (nymc x- a and nymc x- ) when grown in mdck pf cells were superior to wild type h n pdm viruses, reverse genetics derived reassortants, and other egg-derived reassortants. the yields of haemagglutinin from the nymc h n pdm reassortants were still below those seen with sea-sonal h n reassortants as was also seen in eggs. this trend has also been noted in other studies. in summary, attempts to improve growth and yield of the h n pdm wild types for mdck pf cells by extended passaging were not successful, and reassortants did not perform as well as seasonal h n reassortants have in the past. however, using higher dilutions for the passaging of h n pdm viruses in mdck pf cells did result in higher ha titres (a ⁄ brisbane ⁄ ⁄ ). further work is therefore required to generate pandemic h n seed viruses that grow well in a variety of cell culture and egg based vaccine production systems. the aim of this study is to evaluate antibody response to influenza virus neuraminidase (na) following immunization with live attenuated influenza vaccine (laiv). we adjusted the peroxidase-linked lectin micro-procedure previously reported by lambre, et al. ( ) to assay neuraminidase inhibition (ni) antibody in sera taken from immunized mice and from human subjects in a clinical trial. for the assay, we prepared the a(h n ) reassortant virus containing the na of a ⁄ california ⁄ ⁄ (h n ) and the hemagglutinin (ha) of a ⁄ equine ⁄ prague ⁄ ⁄ (h n ). in addition, we used an na-specific igg elisa assay to test sera from immunized mice and volunteers. in mice, one dose of laiv induced ni antibody of a geometric mean titer (gmt) of ae , compared to ae in the control group. gmt of ni from human subjects who received two doses of pandemic a(h n ) were significantly higher than pre-vaccination titers. in unvaccinated human subjects, na-specific cross-reactive antibodies to pandemic a(h n ) were detected more often than cross-reactive antibodies to ha. antibody response to influenza virus na contributes to the overall immune response to influenza and may provide partial protection against influenza infection and reduce severity of disease in the host. a number of preclinical studies using purified or recombinant na have shown that various two-dose vaccine regimens in mice may significantly reduce pulmonary virus titers following viral challenge. [ ] [ ] [ ] a plasmid dna-vaccine model demonstrated cross-reactive antibodies to human n in mice could provide partial protection against a lethal challenge against h n or recombinant pr bearing the avian n . immunogenicity of current influenza vaccines, including laivs, is measured primarily as a level of strain-specific hemagglutination inhibition (hi) antibodies. however, the who meeting on the role of na in inducing protective immunity against influenza infection ( ) specified a need to develop suitable assays for anti-na antibody detection to enhance influenza vaccine evaluation in preclinical and clinical studies. the aim of the current study was to evaluate anti-na antibodies to pandemic a(h n ) influenza virus following laiv immunization. the rn ⁄ -swine a(h n ) reassortant influenza virus containing the na of a ⁄ california ⁄ ⁄ (h n ) and the ha of a ⁄ equine ⁄ prague ⁄ ⁄ (h n ) generated by classical genetic reassortment in embryonated chicken eggs (ce). parental a ⁄ equine ⁄ prague ⁄ ⁄ (h n ) influenza virus was obtained from the center for disease control and prevention, atlanta, ga, usa. viruses were propagated in day old ce and purified by sedimentation out of the allantoic fluid, followed by ultracentrifugation on - % sucrose step gradient. for the mouse studies, week old cba mice were inoculated intranasally with one dose eid ⁄ ae ml of a ⁄ ⁄ california ⁄ ⁄ (h n ) vaccine strain or received ae ml pbs. blood samples were collected on day post inoculation. healthy young adults were immunized twice, or days apart in the fall with a ⁄ ⁄ california ⁄ ⁄ (h n ) laiv manufactured by microgen, irkutsk, russia. for the human studies, peripheral blood specimens were collected from volunteers before vaccination, days after the first vaccination, and days after the second dose of vaccine. sera from five subjects diagnosed with influenza a(h n ) were collected in december , to weeks post infection and kindly provided by e. vo ıtsekhovskaia from biotechnology laboratory, institute of influenza, rams. also, sera obtained in from unvaccinated vol-unteers were tested for presence of cross-reactive antibodies to a ⁄ california ⁄ ⁄ (h n ). sera were treated with a receptor-destroying enzyme from vibrio cholera (denka-seiken, tokyo, japan) and then were tested in duplicates for hemagglutination-inhibition (hi) h specific antibodies by standard procedures using a ⁄ ⁄ california ⁄ ⁄ (h n ) test antigen. the peroxidase-linked lectin micro-procedure previously reported by lambre, et al. was adjusted to assay ni antibody. briefly, -well plates (sarstedt, inc., nümbrecht, germany) were coated overnight with ll of lg ⁄ ml fetuin. the purified a(h n ) reassortant virus was diluted in pbs with % bsa and mm ca + to give a four times higher optical density at nm (od ) compared to control wells not containing virus. fifty-microliter volumes of serially diluted serum samples were incubated with an equal volume of prediluted virus for hour at °c. after incubation, the plates were washed and neuraminidase activity was measured by subsequently adding peroxidase-labeled lectin ( lg ⁄ ml; sigma, st. louis, mo, usa), incubating for hour at room temperature, washing the plates, and adding ll of peroxidase substrate (tmb). the reaction was stopped after minute by adding ll of n sulfuric acid. od values were measured at nm using the universal microplate reader (el x ; bio-tek instruments, inc., winooski, vt, usa). the ni titers were expressed as the reciprocal dilution that gave % od of positive control (virus, no serum control). in addition we used an igg elisa assay with ae lg ⁄ ml of purified na from a ⁄ california ⁄ ⁄ (h n ) to test sera from immunized mice and volunteers. data were analyzed with statistica software (version ae ) (statsoft, inc. tulsa, oklahoma, usa). geometric mean titers (gmt) were calculated and used to represent the antibody response. the comparisons were made within groups between pre-and postvaccinated titers (expressed as log ) after first and second vaccination using wilcoxon matched pairs test. to compare multiple independent groups we used a kruskal-wallis anova with subsequent multiple pairwise comparison based on kruskal-wallis' sums of ranks. a p-value of < ae was considered to be statistically significant. in mice, one dose of laiv induced antibody responses to both ha and na components of the a ⁄ california ⁄ ⁄ (h n ) influenza virus vaccine (table ) . geometric mean titers of ni antibody levels from vaccinated mice were ae and were significantly higher compared to those in unvaccinated control animals (p < ae ). elisa igg titers expressed as log were ae compared to ae in control group. there was good correlation between antibody rises obtained using ni or elisa tests (r = ae ). in a study during the fall of , % of examined unvaccinated subjects were negative to pandemic a(h n ) (hi titers £ : ). serum hi antibody titers to pandemic a(h n ) ‡ : were considered to be protective against *the postvaccination gmts of hi antibodies after revaccination were higher than respective prevaccination titers (p = ae ) **the postvaccination gmts of ni antibodies after revaccination were higher than respective prevaccination titers (p = ae ) serum hi and ni antibodies to a ⁄ california ⁄ ⁄ (h n ) after one or two doses of pandemic laiv were evaluated in subjects who had pre-vaccination hi titers £ : ( table ) . post-vaccination gmts of a(h n )-specific antibodies were significantly higher than pre-vaccination titers only among subjects who received two doses of laiv ( table ). the frequency of subjects with ‡ fourfold rises in hi antibody titers was higher after two doses ( ae %) compared to responses after one dose ( ae %) although the differences were not statistically significant ( table ). the highest antibody titers of hi and ni antibodies were achieved after natural infection (p < ae compared to all post-vaccination groups). all five subjects with confirmed influenza also had high levels of n -specific igg measured by elisa using purified na as the coating antigen (data not shown). influenza ha and na surface proteins are primary targets of neutralizing antibodies that provide protection against influenza infection. the correlation of strain-specific hi antibody titers ‡ : to protection of % of the subjects against influenza infection is based on a number of reports published in s. serum antibodies against viral na as result of influenza infection or vaccination also can neutralize the virus from infecting cells; however, little is known about protective levels of such antibodies. to evaluate ni antibodies directed against pandemic a(h n ) we used the reassortant a(h n ) influenza virus with mismatched ha to avoid non-specific inhibition. we demonstrated laiv immunization effectively increased levels of ni antibody, although in smaller amounts compared to influenza infection. our data suggest that an antibody to neuraminidase, resulting from an earlier infection of the circulating seasonal influenza a(h n ), evidently cross-reacted with the n of pandemic influenza virus, perhaps due to the previously reported % of conserved na epitopes in pandemic a(h n ). the peroxidase-linked lectin test using the reassortant a(h n ) influenza virus was shown to be a sensitive and time effective means of revealing homologous and cross-reactive anti-na antibodies after laiv immunization or influenza infection. this could be a useful method for influenza vaccine evaluation. significant levels of anti-na antibodies detected in peripheral serum from subjects infected with wildtype h n virus or with h n laiv. and the cross-antibody response to ph n . for calculation of geometric mean titer (gmt), a titer of < was assigned a value of . statistical significance was determined by paired t-test. cross-reactive antibody response to ph n in vaccinated populations of seasonal influenza virus table shows the antibody response to seasonal influenza viruses and ph n of participants. before vaccination, no or little antibody response to ph n had been detected in all age groups. vaccination with seasonal influenza vaccines resulted in seroresponse in over % of subjects, except children aged - years ( %) and subjects aged of - years ( %) vaccinated with - season influenza vaccine and adults aged ‡ years ( %) vaccinated with - season influenza vaccine. seroconversion was detected in over % of subjects of all ages. postvaccination to prevaccination gmt ratios for response to seasonal influenza viruses was more than ae -fold. in contrast, seroresponse to a ⁄ california ⁄ ⁄ after vaccination with - and - seasonal influenza vaccines were detected in only % and % of those aged - years, % of those aged - years, % and % of those aged - years, % and % of those aged ‡ years, respectively. seroconversion in all participants ranged from % to %, and postvaccination to prevaccination gmt ratios were < ae -fold. preexisting antibody response to ph n among subjects born before s in china according to a recent report, people who were born from to had a preexisting immunity to ph n . although only a very low level of cross-reactive antibody response to ph n had been observed among older subjects aged more than years old in china, we further analyzed these data by different age distribution of subjects, which can trace back to the previous infection that is genetically and antigenically more closely related to this new ph n influenza virus. the proportion of seroresponse to ph n with the titer of , , and (highest titer detected from participants of all ages in this study) and the value of gmt were analyzed according to the birth decade of subjects from . similarly, a peak of antibody response and the value of gmt occurred both in subjects born from to and sharply decreased afterward ( figure ). the seroresponse of subjects born in and before is significantly higher than subjects born afterward (p < ae ). similar to recent studies in some asia countries (guangxi province of china and singapore), limited antibody response to ph n had been detected in children and adults. , but, some other studies from european countries (finland, germany, the united kingdom) and the united states reported a high proportion of older individuals aged > years with pre-existing cross-reactive antibodies to ph n , which may possibly ba a result of previous exposure to antigenically related h n influenza viruses circulating in earlier decades or a lifetime of exposure to influenza a, which has resulted in broad heterosubtypic immunity among older individuals in those countries. previous infection and vaccination with a ⁄ new jersey ⁄ may also contribute to the high level of cross-reactive antibody response to ph n among adults older than years in the us. , the peak of the antibody response to ph n in subjects born between and , which is consistent with recent reports, may suggest the previous viral infections of spanish flu or closely related influenza viruses, which is before and little after the year of . recent antigenic report of new ph n viruses indicated that they are antigenically homogeneous among historical viruses, which are most similar to classical swine a(h n ) viruses. a number of reviews [ ] [ ] [ ] [ ] confirmed that the virus is the likely ancestor of all four of the human and swine h n and h n lineages, as well as the 'extinct' h n lineage. in , a(h n ) influenza viruses were first isolated from swine. they have been shown to be antigenically highly similar to the recently reconstructed human a(h n ) virus. the cellular responses may contribute to the sustaining and long term antibody response. probably, boosting by persisting antigenically related viruses in the early decades of the th century, may have contributed to the ability of these subjects to sustain memory b cells, and it is well established that a subset of plasma cells is long-lived, and these cells contribute to durable humoral immune responses, such as that observed after childhood smallpox vaccination. furthermore, t cells that recognize cross-reactive epitopes are preserved and might be enriched in the memory population; the course of each infection is influenced by the t-cell memory pool that has been laid down by a host's history of previous successive infections. our study indicated that wide transmission of this new virus or any antigenically close related influenza a(h n ) viruses may not have circulated among populations in china before the outbreak of ph n . our data also suggests the need for vaccination with ph n vaccine in all age groups. hypo-and agammaglobulinemia patients have an impaired immune system and are particularly susceptible to bacterial infections that are normally defended against by antibodies. therefore, patients routinely receive replacement therapy with immunoglobulins isolated from healthy blood donors. these patients are also prone to get viral infections, possibly due to defects in toll-like receptors and . because these patients lack an antigen specific humoral immune response, they are rarely vaccinated. the ability of hypogammaglobulinemic patients to produce a specific cell-mediated immune response upon vaccination has only been sparsely investigated. in contrast to local mucosal antibodies, vaccine-induced cell-mediated immunity is not believed to protect against pathogen entry per se, but may be sufficient to provide protection against severe disease and death following transmission of some microbes. , the aim of this pilot study was to investigate if influenza vaccination of hypogammaglobulinemic patients can induce an influenza-specific cell-mediated immune response. we therefore vaccinated hypogammaglobulinemic patients and healthy controls with pandemic h n virus vaccine and subsequently investigated the bcell and t-cell responses. the percentages of ifn-c, il- , and tnf-a cytokine producing cd + th -cells were determined, as these cytokines are important indicators of cell-mediated immunity. five a-or hypogammaglobulinemic patients were classified based on the freiburg classification : patient # is diagnosed with x-linked agammaglobulinemia, patient # and # are in group ia, patient # is in group ib and patient # is in group ii. the monovalent egg grown split virus vaccine adjuvanted with as was manufactured by glaxosmithkline (gsk), belgium. the vaccine strain was produced by reassortment between influenza a ⁄ california ⁄ ⁄ (h n ) and a ⁄ pr ⁄ ⁄ (h n ) to produce a ⁄ california ⁄ ⁄ -like virus (x a). the vaccine was mixed with adjuvant to contain ae lg haemagglutinin (ha) of a ⁄ california ⁄ ⁄ -like virus (h n ), squalene ( ae mg), dl-atocopherol ( ae mg), and polysorbate ( ae mg) per ml. healthy controls and hypogammaglobulinemia patients were vaccinated by intramuscular (im) injection. hypogammaglobulinemia patients received one or two vaccine doses days apart. the intention was to vaccinate the hypogammaglobulinemic patients with two doses of ae lg ha, but ae lg ha was inadvertently administered to the patients as the first dose. for patient # this was the second dose as he had received an initial dose of ae lg ha months prior to the study. patient # , # , and # received a second dose of ae lg ha. four healthy controls were immunised with one dose of ae lg ha according to norwegian national guidelines. peripheral blood mononuclear cells (pbmcs) were harvested and washed in pbs with % fbs. the pbmcs were resuspended in lymphocyte medium (rpmi with l-glutamine, ae mm non-essential amino acids, mm hepes ph ae , mm sodium pyruvate, iu ⁄ ml penicillin, lg ⁄ ml streptomycin, ae lg ⁄ ml fungizone and % fbs) prior to use in the enzyme-linked immunospot (elispot) and influenza-specific cd + t-cell assays. serum haemagglutination inhibition antibodies were tested by a standard method using ha units and ae % turkey erythrocytes. all samples were tested in duplicate and the test was repeated at least two times. titres < were assigned a value of for calculation purposes. for numeration of antibody-secreting cells (asc), an eli-spot assay was conducted as previously described with the following modifications. ninety-six well elispot plates were coated with lg ⁄ ml of a ⁄ california ⁄ ⁄ like (x a) h n virus diluted in pbs overnight at °c. after blocking with rpmi ( % fbs), pbmcs were added and incubated ( °c, % co ) for hour. secreted antibodies were detected with biotinylated goat anti-human igg, iga and igm specific antibody (southern biotech, birmingham, alabama, usa), incubated for hour at room temperature and developed with extravidin peroxidase and aec substrate. the numbers of spots were counted using an elispot reader (immunoscanÔ) and immunospot Ò software. the influenza-specific cd + th -cell response was measured by intracellular cytokine production of ifn-c, il- , and tnf-a. peripheral blood mononuclear cells ( per well) were incubated for hour ( °c, % co ) in ll lymphocyte medium containing lg ⁄ ml anti-cd , lg ⁄ ml anti-cd d, ae lg ⁄ ml monensin, lg ⁄ ml brefeldin a, (bd biosciences, franklin lakes, new jersey, usa), and the h n influenza split virus vaccine x a (either ae lg ⁄ ml or lg ⁄ ml ha). basal cytokine production was determined by incubating pbmcs in lymphocyte medium without influenza virus, and the percentage of cytokine positive cells without influenza stimulation were subtracted from influenza-stimulated cells. cells were stained for cd , cd , cd , ifn-c, il- , and tnf-a (bd biosciences) as previously described. finally, cells were resuspended in pbs containing % fbs and ae % sodium azide and analysed by bd facscanto flow cytometer ( - cells acquired). flowjo v ae ae (tree star, ashland, oregon, usa) was used for data analysis. five to six fold lower gmts were found in the patient group as compared to the healthy controls throughout the study ( figure a) . the lowest hi titres were obtained in patients # , # , and # , whilst patients # and # and all healthy controls fulfilled two of three european medicines agency committee for medicinal products for human use (chmp) seasonal influenza vaccine licensing criteria, by obtaining an hi titre > and a mean geometric increase of ae between pre-and post-vaccination. thus, the hi data indicate that two vaccine doses was sufficient to induce a protective hi antibody response in two out of five of the hypogammaglobulinemia patients tested in this study. the numbers of influenza-specific iga, igg, and igm asc were tested pre-vaccination and days post-vaccination with the h x a virus. few or no ascs were detected pre-vaccination (data not shown). at days post-vaccination the patient's iga, igg, and igm asc levels were significantly lower (p < ae ) compared to the healthy controls ( figure b) . but, the post-vaccination asc numbers in the patients were generally higher than at pre-vaccination stage ( - ascs). patient # had the highest iga and igg asc numbers, followed by patients # and # , whilst patient # and # had few or no asc's. these results confirm that the patients are indeed hypogammaglobulinemic and that some of the patients (# and # ) could be agammaglobulinemic in the context of producing influenza-specific antibodies. the asc levels of patients # , # , and # were lower than those of the healthy controls, but could possibly be adequate for reducing the severity of influenza disease. the influenza-specific th -cell response was evaluated by stimulating pbmcs with the influenza x a virus , , and days post-vaccination. stimulation of healthy control pbmcs with x a days after vaccination, induced ifn-c, il- , and tnf-a production by an average of ae %, ae %, and ae % cd + t-cells, respectively. patient # and # had higher responses than the healthy controls and stimulation with x a induced ae %, ae %, and ae % of t-cells from patient # to produce ifn-c, il- , and tnf-a, respectively (figure a) . the response of patient # was further boosted by a second vaccine dose, which resulted in ae %, ae %, and ae % cd t-cells producing ifn-c, il- , and tnf-a, respectively at day ( figure b ). these results show that the hypogammaglobulinemia patients studied here did not have a common impaired influenza-specific cd + th cytokine response. rather, there was a tendency towards increased responses, suggesting that the diminished antigen specific b-cell responses could induce a compensatory antigen specific th -cell response. the results from this pilot study suggest that some hypogammaglobulinemia patients may benefit from influenza vaccination. we found very different patient responses to influenza vaccination, but some of the patients (patient # and # ) did mount low influenza-specific asc responses. in addition, the vaccine-induced hi antibody titres above the protective level in patient # and # . these results are in accordance with previous publications, which described that polypeptide vaccines induce humoral responses in subgroups of common variable immunodeficiency patients. [ ] [ ] [ ] in this study, we also investigated cell-mediated immunity and found the percentages of homologous and cross-reactive influenza-specific cd + th -cells to be in the same range (for patient # , # , and # ) or higher (for patient # and # ) in the a-or hypogammaglobulinemic patients compared to the healthy controls. the higher response is probably due to the patients having received a vaccine dose of ae lg ha, whilst the controls received ae lg ha. in addition, the patients received a second booster dose, which influences the day and months responses. nonetheless, these results are the first to demonstrate that proliferation of pandemic influenza antigen specific th cells can be induced in hypogammaglobulinemic patients. in addition, vaccination induced influenza-specific asc's in some patients. the findings are promising and provide hope that hypogammaglobulineamic patients could be vaccinated against influenza and other diseases preventable by figure . peripheral blood mononuclear cells s from patients and healthy controls were isolated at day (a), (b), and day (c) and stimulated for hour with x a virus before staining and flow cytometric analysis. the figure shows the mean ± sd frequency of influenza-specific cd + cytokine producing cells (%) where the basal cytokine production from unstimulated cells has been subtracted. data for the hypogammaglobulinemia patients are additionally shown as a number for each patient. **significantly higher frequency of il- producing cd + t-cells in the patients compared to the healthy controls (students t-test p < ae ). titres are presented as the geometric mean titre ± % confidence interval. elispot data (b) are presented as the mean number of influenza-specific iga, igg, and igm ascs per peripheral blood mononuclear cells ± sem. data for the hypogammaglobulinemia patients are additionally presented by a number for each patient. *significantly higher numbers of ascs were detected in the healthy controls as compared with the hypogammaglobulinemia group (students t-test, p < ae ). vaccination. however, this hypothesis should be tested in larger clinical studies. the influenza virus undergoes antigenic evolution under intense immune selection pressure from herd immunity in humans through the process called antigenic drift and shift. , because of antigenic drift, yearly updating of vaccine strain is needed. a mismatch between the circulating strains and the vaccine strain in the subsequent season is often encountered, resulting in reduction of vaccine effectiveness and lack of protection from the circulating strain. in order to address this, a universal influenza vaccine based on a more conserved part of the influenza virus, which is not affected by antigenic change and that is conserved across all strains, remains the ultimate goal to afford cross-protection to drifted strains as well as to other subtypes of influenza which may arise from antigenic shift. , previous studies have investigated the potential of the m e. , m e has remained highly conserved since it was first isolated in . several studies have examined the use of m e as a vaccine component, using various approaches including proteins, peptides, dna vectors, and attenuated viral vectors. , [ ] [ ] [ ] [ ] [ ] [ ] although m e is a weak antigen, by linking the protein to a carrier hepatitis b virus core particle, protection against influenza has been achieved in mice particularly when administered with an adjuvant. some articles found that vaccination with m e coupled to hbc induces protective antibodies, whereas the contribution of t cells to protection was negligible. protection induced by vaccination with m e-hbc was weak overall and failed to prevent weight loss in vaccinated infected animals, and mice succumbed to high dose infection. we aimed to address the poor immunogenicity of m e-hbc by using igv as adjuvant. igv domain is common and conserved in the tim family. ligand binding sites of t cell immunoglobulin mucin (tim) located at igv domain. [ ] [ ] [ ] tim function is done by anti tim antibody which recognized the ligand binding sites of igv domain. tim family members share a common motif, including an igv domain. they are differentially expressed on th cells and th cells with the ability to regulate the immune system. , the igv domain of human b - is sufficient to co-stimulate t lymphocytes and induce cytokine secretion. soo hoo et al. vaccinated with tim- antibody and inactivated influenza and found enhanced vaccine-specific immune response. we report here for the first time the use of igv recombinant protein as adjuvant to immunize mice with influenza m e-hbc. results indicated that igv can induce the strong cellular immune response and cross reaction with different subtype influenza virus antigen. target igv may be used to develop the new method for vaccination strategies. expression and purification of recombinant igv protein rna was extracted from healthy human pbmc. one-step rt-pcr (qiagen, valencia, ca, usa) was done for the amplification igv gene. the pcr product was purified and cloned into pet a (novagen, madison, germany). the resultant construct pet a-igv has a histidine (his) tag ( his) at the n terminus. dna sequence of the insert was determined by sequencing. igv. recombinant protein was expressed in escherichia coli and was purified on a ni column (novagen). the purified protein was examined by sds-page and western blotting. six-eight weeks female balb ⁄ c mice (institute of zoology chinese academy of sciences, china) was used for the study. mice were immunized twice intradermally with ug m e-hbc (provided by cnic, china) combined with different doses of recombinant igv protein , , ug, respectively, or without igv as control. the area proximal to the tibialis anterior muscle was sterilized with % ethanol and different groups of mice were injected bilaterally with , , ug igv plus ug m e-hbc in ul phosphate buffer saline per mouse using a ml syringe with attached ⁄ ¢¢ g needle. the immunization was given at weeks intervals. four blood samples were obtained from every mouse: before immunization, after the first and second immunization, and after virus challenge by retro-orbital plexus puncture. after clotting and centrifugation, serum samples were collected and stored at ) °c prior to use for assays. mouse-adapted a ⁄ pr ⁄ ⁄ (h n ), a ⁄ brisbane ⁄ ⁄ (h n ), a ⁄ xinjiang ⁄ ⁄ (h n ), and a ⁄ guangzhou ⁄ ⁄ (h n ) were provided by chinese national influenza centre. nine to eleven days old embroynated specific pathogen free (spf) chicken eggs were inoculated with virus, and the eggs were incubated at °c for - days. the allantoic fluid was collected and purified by sucrose density gradient centrifugation, and the virus was inactivated by formaldehyde at °c overnight. to identify igg, igg , igg a against m e, elisa assays were used. in brief, -well (nunc, brunei, denmark) were coated with ul ⁄ well of m e recombinant protein (provided by gene lab of ivdc, xuanwu district, beijing, china) in carbonate buffer (ph ae ) overnight at °c. immediately before use, the coated plates were incubated with blocking solution ( % bsa in pbs) for h at °c and washed four times with pbs containing ae % tween (pbs-t). the serum samples were serially diluted and added in the plates. the detection color was developed by adding hrp-labeled goat anti-mouse igg, igg , or igg a ( figure ) . no cross-strain response was observed in the control group. the igv adjuvented groups show splenocytes stimulation with seasonal h n , h n , h n , and h n antigens. m e-hbc immunization without igv showed splenocyte stimulation, but the extent was lower than animals immunized in the presence of the igv adjuvent. these data suggested that igv had enhanced effect on priming against the conserved viral antigen matrix protein and generation cross-strain immune response. influenza is a respiratory disease causing epidemics every year. h n viruses and swine-origin h n have also infected humans in recent years. seasonal influenza vaccine cannot cope with significant antigenic drift or with the emergence of pandemic viruses of different subtypes not contained in the vaccine. the high extent of conservation of the m e makes it a promising immunogen. a vaccine based on coupling of the m e peptide to an appropriate carrier may provide a universal vaccine with effectiveness and safety. m e based vaccination induces protective antibodies not only in mice, but also in ferrets and monkeys. the carrier hepatitis b core as carrier with m e forms a virus like particle (vlp). vaccination with m e coupled to hbc induces protective antibody, whereas the contribution of t cell protection was negligible. protection induced by vaccination with m coupled to hbc was weak overall. in order to improve the vaccination effect of m e-hbc, new adjuvant igv was evaluated in combination with the m e-hbc. the tim molecules are a recently discovered class of proteins with the ability to regulate the immune system. crystal structures of the tim molecules has revealed a unique, conserved structure with ligand-binding sites in the igv domain. to determine the potential immunostimulatory molecular properties of igv, we have evaluated immune response of the igv in combination with m e-hbc vlp. previous papers reported that vlp immunized mice can induce the th and th immune response. different adjuvant combined vlp can produce biased immune response th ⁄ th mixed immune response, or th -preferred th ⁄ th profile. thus, the response following the use of igv as a new adjuvant combined with m e-hbc vlp needs to be evaluated. results indicated that igv combined groups showed th biased immune response and enhanced cross reactive t cell immune responses. this may show that igv immunized the mice and antiigv antibody can cross link the igv on t cells and enhance the cell figure . t cell proliferation assay. mice were immunized twice with , , , ug ⁄ ml igv plus m e-hbc, respectively, and naive group was immunized with pbs. three weeks after a boosting immunization, spleens were harvested from immunized and naive mice. different subtypes of inactivated virus antigen (a) h n , (b) h n , (c) h n , (d) h n were added and cocultured with different group splenocytes for h. quick cell proliferation assay kit was used to detect the cell proliferation. the - nm absorbance was read on a plate reader. data were showed were shown as mean values. the difference between naive group and different doses igv plus m e groups was determined using the student's t-test. all significance level is p < ae . response. we also evaluated the cross-protection produced by igv combined m e-hbc. we challenge with mouseadapted strain pr and prove the cross protection via reaction between the cells from the immunized animal and different subtypes of virus antigen. some subtypes of virus cannot infect the mice naturally, and therefore, virus challenge cannot be used to evaluate the effect. we co-cultured the t cells with inactivated antigen h , h , h , and h , and t cell proliferation was measured. results indicated that after immunization with igv plus m e-hbc, the t cells show cross-protection with other subtypes. this provides evidence that igv can enhance the cross protection across subtypes. the results of this study demonstrated that recombinant igv can be useful as an adjuvant and polarize the m e-hbc vlp immune response to a th profile. igv induced the m e-hbc vlp to induce t cell proliferation and cross-reactive responses to different influenza virus subtypes. this finding represents a new direction for the promotion of cell mediated immunity in m e based vaccine against influenza. a core european protocol, i-move, describing the methods to estimate influenza vaccine effectiveness (ive) was proposed by the european centre for disease prevention and control (ecdc) and epiconcept for the - season. it includes a case control method for pooled analysis based on a randomized ''systematic'' sample of swabs. , collection of swabs using a non randomized, i.e., ''ad hoc,'' sampling strategy, left at the appreciation of sentinel practitioners, provides a greater number of cases and con-trols for ive estimation more easily than using a systematic randomized sampling strategy. the french grog (groupes régionaux d'observation de la grippe) early warning network collects more than specimens yearly from cases of acute respiratory illness (ari), using both sampling methods. , during the circulation of pandemic influenza viruses in france, it gave an opportunity to compare ive estimates using systematic randomized versus non systematic ''ad hoc'' sampling. influenza vaccine effectiveness was estimated by a casecontrol methodology according to ecdc i-move protocol, using on the one hand a systematic random sampling, on the other hand ''ad hoc'' non random sampling. the study was proposed to primary care practitioners of the grog network ( general practitioners and pediatricians) trained to collect data and swabs. the study population was patients from the community of all ages consulting a grog practitioner for an influenza like illness (ili) and having a nasal or throat swab taken within an interval of < days after symptom onset. ili was defined according to the european union (eu) case definition as sudden onset of symptoms with at least one of the following four systemic symptoms: fever or feverishness, malaise, headache, myalgia; and at least one of the following three respiratory symptoms: cough, sore throat, shortness of breath. swabs were performed through usual surveillance. no ethical approval was needed, but an oral informed consent was requested. cases were excluded if they refused to participate in the study or if they were unable to give informed consent or to follow the interview in native language because of aphasia, reduced consciousness, or other reasons. an individual was considered as vaccinated against pandemic influenza if he or she reported having received a pandemic influenza vaccination during the current season, and if at least one vaccine dose occurred more than days before ili onset. the study period started with the initiation of active influenza surveillance by the grog network, i.e., days after the beginning of the influenza vaccination campaign, and finished at the end of the influenza period defined as the last week with at least one swab positive for influenza within the grog network. ''ad hoc'' sampling patients from which swabs were taken were selected by the grog practitioners during the study period. systematic random sampling during the same period, patients were selected at random as follows. an age-group - years (gps and pediatricians); - years (gps and pediatricians); - years (gps); years or more (gps) was assigned to each practitioner, who was requested to swab the first patient of the week presenting with an ili within the pre-assigned age-group. swabs were collected in appropriate transport medium (virocult Ò , viralpack Ò , utm copan Ò ) and sent by post to the laboratory in triple packaging following the international guidelines for the transport of infectious substances (category b, classification un ). laboratory confirmation of influenza was by rt-pcr to detect currently circulating influenza a (subtypes h , seasonal and pandemic h ) and b viruses. an influenza case was defined as an ili case with a respiratory sample positive for influenza during the study period. controls were cases of ili having a swab negative for influenza during the study period. the outcome of interest is laboratory confirmed influenza. confounding factors and effects modifiers identified during the i-move preliminary study were registered: risk factors, chronic diseases, severity of underlying conditions, smoking history, former vaccinations, and functional status. data on cases and controls were collected by the practitioners using a standardized questionnaire adapted from the i-move study. questionnaires were sent by the practitioners with the swab to the virology laboratory, and sent to the grog national coordination. data entry and validation were ensured by open rome through the vircases computing tool. validation steps included control of exhaustiveness of centralization of questionnaires, comparison of data entered by the labs and the national grog coordination, coherence control, and identification of missing data. analysis was done for the two sampling groups (systematic and ad hoc) on cases ⁄ controls following the european method proposed by epiconcept, using excel ª (microsoft corp. redmond, washington, usa) and stata ª . baseline characteristics of cases and controls in unmatched studies were compared using the chi-square test, fisher's exact test, or the mann-whitney test (depending on the nature of the variable and the sample size). the association between vaccination status and baseline characteristics was assessed for both case and control groups. the vaccine effectiveness was computed as ive = )or (odds ratio). an exact % confidence interval (ci) was computed around the point estimate. analysis was stratified according to age groups, time (month of onset), presence or absence of chronic disease, and previous influenza vaccination. effect modification was assessed comparing the or across the strata of the baseline characteristics. confounding factors were assessed by comparing crude and adjusted or for each baseline characteristic. a multivariable logistic regression analysis was conducted to control for negative and positive confounding factors using a complete case analysis (with records with missing data dropped) and using multiple imputation with chained equations. the complete model included age group, number of gp visits, onset week, seasonal vaccination, previous seasonal influenza vaccination, presence of chronic disease and associated hospitalizations in the previous months, gender, and smoking status. variables were tested for multi-colinearity. interactions were tested using the likelihood ratio test (or wald test) and included in the model if significant at % level. a model with fewer variables (age group, number of gp visit, onset week, and seasonal vaccination) was also tested. several models were applied to both the ''ad hoc'' and systematic sampling groups of cases and controls. as shown in table , whatever the analysis method used, the ''ad hoc'' sampling strategy led to a slightly lower estimate of ive. the ci were extended when data were missing and reduced when using multiple imputations with chained equations. however, from a statistical point of view, comparison of ''ad hoc'' versus systematic strategies is not straightforward, because ''ad hoc'' sampling is not randomized and does not allow comparisons with statistical tests using statistical distribution laws. there are more missing data with the ad hoc sampling method. this is mainly due to our validation procedure: in the case of missing data in the systematic sampling group, as required by the i-move study protocol, queries were sent to sentinel practitioners using mail and phone calls. this specific heavy workload is not usually performed during routine surveillance and has not been achieved for the ''ad hoc'' sampling group given the great number of cases and controls ( ). within the framework of the i-move study, several items were added to the grog's usual clinical form accompanying swabs (hospitalizations, number of gp visits, smoking status, help needed for bathing or walking). in - , gps explained that this added workload was not compatible with their daily additional workload due to the pandemic situation. therefore, many of them refused to fill these new items systematically and threatened to leave the network. we thus obtained that the ''i-move items'' would be filled in for the clinical forms linked to systematic sampling, but were not in a position to obtain that for ''ad hoc'' sampling. the weekly distribution of systematic swabbing is not similar to that of ad hoc swabbing. the percentage of ad hoc swabs was higher than systematic swabs during the pandemic wave (mid-november to end of december) during which time the percentage of swabs positive for influenza was also higher ( figure ). this could explain the higher rate of positive swabs within the ''ad hoc'' samples. the vaccination campaign was launched by the ministry of health on october , , and vaccination coverage increased during the surveillance period. in february, the vaccination coverage was ae % in patients swabbed in the systematic group ( ae % on imputed data) and ae % [ ae - ae ] in the ad hoc group ( ae % on imputed data). at the national level, vaccine coverage is estimated at ae %. due to the over-mediatisation of pandemic vaccination and to rumors about its poor effectiveness, overconsultation of vaccinated patients and over-swabbing of vaccinated patients in the ad hoc group are not surprising. age distribution is significantly different between our two samples (p < ae ): the rate of - years old is lower in the systematic sampling group ( ae %) than in the ad hoc sampling group ( ae %). this can be explained by the fact that for the systematic sampling procedure, each grog practitioner had to swab the first ili patient in his assigned age group, whereas for ''ad hoc'' sampling, every grog practitioner could swab any ili patient irrespective of age. given the emphasis by health authorities and media on the burden of pandemic influenza among children and teenagers, one can hypothesize that when they were able to, sentinel practitioners focused on these age groups. gps in the ad hoc sampling scheme seem to have been more likely to select cases and further, to select vaccinated cases. those patients may have consulted earlier with specific symptoms (strong headache being more prevalent among cases). over-swabbing of patients having these symptoms in the ad hoc group is likely. the - pandemic influenza season was markedly different from previous ones: vaccination rate increased during and mainly after the pandemic peak; behaviors were strongly modified by unusual media hype; clinical features and risk factors might be different. it will be necessary to see if similar results are observed during a regular influenza season during which the vaccination rate increases before the epidemic peak with usual messages about vaccination and usual clinical influenza features. influenza early warning networks can estimate ive, taking into account many covariates. from a stakeholders and patients point of view, during the - influenza pandemic wave, there were no major discrepancies between ive estimated with an ad hoc sampling strategy, based on sentinel practitioners instinct, and ive estimated with a systematic random sampling strategy whatever the multivariable analysis methodology. although from a statistical point of view, comparison of the two strategies is not readily feasible because of the non random nature of ad hoc sampling. this latter strategy seems to result in slightly lower ive estimates, which could potentially be attributed to sentinel practitioners swabbing behavior. the ability to avoid missing data is a key point to decide which sampling method must be adopted, because ci extent depends greatly on the proportion of missing data among covariates. to match ive evaluation to surveillance networks practicality, selection of only those data essential for the study endpoint and easily collected by sentinel practitioners is paramount. it will be necessary to determine if results similar to those observed during the - pandemic season are found during a regular influenza season. influenza a viruses are important pathogens which remain a major cause of morbidity and mortality worldwide, and large numbers of the human population are affected every year. the first influenza pandemic in this century broke out in humans in march , and it was declared to be pandemic by mid-june. as of august jul , the pandemic virus had caused more than deaths worldwide, according to the world health organization (http:// www.who.int/csr/don/ _ _ /en/index.html). the infection and spread of the pandemic influenza was reduced in part due to the use of vaccines. however, the lack of h n pdm vaccine early in the pandemic illustrates the need to improve vaccine production and to generate vaccines that induce stronger cross-protection. inactivated split vaccines or live attenuated influenza virus vaccines (laivs) against h n pdm viruses were approved for human use by the united states food and drug administration. both the inactivated vaccines and laivs are produced by creating reassortant viruses that generally contain six vrnas (pb , pb , pa, np, m, and ns) from a master donor strain, plus the two glycoprotein vrnas (ha and na) from a virus that antigenically matches the strain predicted to circulate in upcoming influenza season (e.g. a ⁄ ca ⁄ ⁄ ). the reference viruses containing inactivated split virus vaccines are produced in embryonated chicken eggs, and primarily result in the production of antibodies that recognize the viral glycoproteins. both of these vaccine approaches require significant lead time for vaccine production, and modern approaches to speed preparation of vaccines and improve their efficacy is a global priority. , the ns protein of influenza a virus is a multifunctional protein that plays important roles in virus replication and as potent type i ifn antagonist. , mutations and ⁄ or deletions in ns typically induce stronger ifn responses by the host; those in turn suppress the replication of influenza virus - and can enhance immune recognition. [ ] [ ] [ ] [ ] in this study, we created a panel of experimental h n pdm ns-laiv candidates that have different deletions in the ns vrna and analyzed the vaccine potential of each ns-laiv in mice and ferrets to identify the best candidate(s). wt h n pdm influenza a virus a ⁄ new york ⁄ ⁄ (ny ) was created by reverse-genetics directly from a human swab specimen collected in new york state in april . deletions were introduced into the ny ns plasmid to create three mutant ns segments: ns - , ns - , and nsd . nucleotides - (cdna of ns segment) and - were replaced by stop codons to generate ns - and ns - ; nucleotides - were deleted to generate nsd , whose open reading frames for ns and nep were maintained. recombinant viruses were generated by co-transfection of eight reverse-genetics plasmids carrying the cdna of each gene segment into t ⁄ mdck cocultured monolayer adapted from hoffmann et al. , mouse studies experiments were performed in a biosafety level laboratories approved by the u.s. centers for disease control and prevention and the u.s. department of agriculture, and were conducted under approved animal care and use protocols. groups of -week-old female balb ⁄ cj (jackson laboratory, bar harbor, me, usa) were anesthetized with isoflurane and inoculated intranasally with tcid of each recombinant virus in ll of pbs diluent, or pbs as controls. body weights and clinical symptoms of the mice were monitored daily for days. nine mice in each group were euthanized on , , and days post inoculation (dpi), and nasal washes and lungs were collected for virus titration by tcid assay in mdck cells. at dpi, mice per group were challenged intranasally with · tcid ( ld in -week-old mice) of a mouse-adapted variant of ny (a ⁄ ny ⁄ ⁄ -ma ) (accepted, journal of virology). disease symptoms and weights of the vaccinated mice were monitored for days, and four mice from each virus group were euthanized at and days post challenge. lungs were removed and homogenized for virus titration by tcid assay. the mice that became moribund or lost > % of their starting body weight were euthanized for humane reasons. male fitch ferrets (triple f farms, sayre, pa, usa), - months of age and serologically negative by hemagglutination inhibition (hi) assay for currently circulating influenza viruses were used in this study. groups of or ferrets were inoculated intranasally with ae tcid of one of the viruses: ny wt (n = ), ns - (n = ), ns - (n = ), or nsd (n = ). ferrets were monitored for clinical signs through dpi as previously described. nasal washes were collected on , , , and dpi and were titrated in mdck cells by tcid assay. serum was isolated from blood collected ae weeks after immunization and used for neutralization assays. the ferrets were challenged with pfu of a ⁄ mexico ⁄ ⁄ ae weeks postimmunization and monitored for clinical signs of disease through dpi. nasal washes were collected on , , , and dpi, and were titrated in mdck cells by plaque assay. using reverse genetics, we created three laiv candidates weight loss of wt virus inoculated mice became evident at dpi, and the mice did not recover until dpi (figure a) . in contrast, mice inoculated with any one of the vaccine candidates had no clinical signs of disease and continued to gain weight at the same rate as did the mock- inoculated mice ( figure a ). viral titers in the lungs of ns - , and ns - infected mice were $ -fold lower than titers from wt virus-infected mice at all the time points analyzed ( , , and dpi) ( figure b) . notably, the nsd laiv was cleared from the mouse lungs very rapidly, and the mean titers were $ -fold and -fold lower than the titers of the wt virus at and dpi, respectively ( figure b) . the vaccinated mice were challenged with a mouseadapted variant of ny (accepted, journal of virology) on dpi. no disease symptoms were observed in the mice immunized by any of the ns-laiv candidates or the wt control. in contrast, disease symptoms including ruffled fur, hunched posture, and weight loss were observed in the mock-immunized mice as early as days post challenge (dpc); the symptoms progressed to severe disease, and the animals showed dramatic weight loss, became moribund, and succumbed to infection by dpc (figure c ). high titers of virus ($ tcid ⁄ ml) were present in the mock-immunized mice at dpc and at dpc ( figure d ). in contrast, virus was not detected in the lungs of immunized mice ( figure d ). this challenge data demonstrates that all of the ns-laiv candidates, including the highly attenuated nsd , induced sterilizing immunity that protected mice from a lethal ny h n pdm variant. groups of ferrets were intranasally immunized with ae tcid of each vaccine candidate or the wt virus. the titer of viruses recovered from nasal washes ranged from ae to ae tcid ⁄ ml through day in the wt virusinfected group, while the ns-laivs showed various degrees of attenuation (figure a) . the viral titer of all of the ns-laivs is at least -fold lower than that of wt in the nasal wash collected at dpi. the ns - laiv was the least attenuated in ferrets, and its replication was similar to that observed in mice. relative to the wt virus, the ns - laiv showed -fold reduction in titer, and the nsd laiv was below the limit of detection (at least fold reduction) at dpi. sera from blood collected ae weeks after immunization was analyzed for the presence of neutralizing antibodies by micro-neutralization assays. the ns-laiv candidates all induced very strong neutralizing antibody responses ( - ) that were similar to the titer elicited by wt virus infection ( figure b ). the ferrets were challenged with pfu of a ⁄ mexico ⁄ ⁄ (h n pdm) ae weeks post immunization. little disease or weight loss were observed in the naïve ferrets, and the ferrets immunized by infection with wt virus or the ns-laiv candidates didn't show any disease symptoms or weight loss. in contrast to the high titer of virus detected in the naïve ferrets through dpc, the ns-laiv immunized ferrets had very low levels of a ⁄ mexico ⁄ ⁄ in their nasal washes at dpc ( figure c ). the ferrets immunized with the ny ns-laivs had $ -to -fold lower viral titers than did the naïve animals ( figure d ). in summary, the ns-laiv candidates dramatically inhibited initial replication of the h n pdm virus under stringent challenge conditions ( pfu), and that the vaccinated animals rapidly cleared the infection (to below the limit of detection, by dpc). our results demonstrate that all of the ns-laiv candidates are attenuated compared to the wt h n pdm virus, and the degree of attenuation is dependent on the specific ns mutation. ns - was the least attenuated and does not represent a good vaccine candidate; whereas, nsd and ns - were highly attenuated in both the mouse and ferret models. although they were markedly attenuated, they elicited strong neutralizing antibody responses and protected mice and ferrets from subsequent challenge. nsd has a subtle in-frame deletion ( nt) that affects both the ns (residues - ) and nep (residues - ), and is analogous to a naturally attenuated variant of a normally highly pathogenic h n virus (a ⁄ sw ⁄ fj ⁄ ). the analogous ns deletion in a ⁄ sw ⁄ fj ⁄ (residues - ) was shown to reduce binding to host cleavage and polyadenylation specificity factor (cpsf), reduce ns protein stability, and enhance the type i ifn response of this h n virus. our study indicates that deletion of these nt in the ns vrna of the h n pdm also stimulates the host ifn response, specifically, ifn-ß, ifn-k , ip , and mxa (data not shown). the role of the deletion of residues - from nep has not been elucidated, but the induction of ifn and isgs by nsd was similar to, or slightly lower than, their induction by ns- , suggesting that the nep mutation also has an attenuating effect that warrants future investigation. in summary, we have generated a panel of laivs directly from a swab specimen containing a new pandemic virus and analyzed their attenuation and immunogenicity in two animal models. our study demonstrates that nsd is a novel ns-laiv that could be used to create laivs for diverse influenza a viruses. this study also validates the use of ns-laiv candidates, which are not only highly attenuated, but they also elicit strong innate and adaptive immune responses, resulting in protection of mice from subsequent challenge with a lethal mouse-adapted variant of ny , and ferrets from challenge with a ⁄ mexico ⁄ ⁄ (h n pdm). currently, a total of approximately million doses of inactivated influenza vaccine are being produced worldwide each year. one of the limitations in vaccine production is poor growth of human isolates in embryonated chicken eggs. this is essential to develop high yield seed viruses for large scale production of influenza vaccines. influenza a vaccine production utilizes high yield reassortants carrying ha and na genes from a wild type (wt) strain with generally - internal genes from the a ⁄ pr ⁄ ⁄ (pr ) strain, an highly egg adapted high growth donor strain. influenza b vaccines, however, have been produced directly from wt strains, partly because no high yield donor analogous to pr has been identified. in recent years, reverse genetics has been used as an alternative means of developing high growth vaccine viruses. , since in this plasmid-based technology, a : reassortant (six internal genes from a donor strain and two surface antigen genes from wild type strain) can be directly rescued, reverse genetics-derived reassortant viruses were expected to grow as efficiently as those derived from classical reassortment. however, reverse genetics reassortants have not produced the expected high growth for several reasons: (i) the : configuration is not always the best for virus yield, (ii) there is no process included for positive selection of adaptive mutants from quasispecies, and (iii) cell-derived viruses are not readily adapted to grow efficiently in eggs. our laboratory at new york medical college has been preparing b reassortants for several years by classical reassortment using b ⁄ lee ⁄ as a donor. it has been possible to develop b reassortants, which produce higher virus yields than wt strains in eggs, and it was found that the np gene of b ⁄ lee ⁄ was important in producing high yield b reassortants. however, b ⁄ lee ⁄ is inconsistent in providing high yield properties to b reassortants. in this study, in an attempt to find an alternative donor, we investigated the usefulness of b ⁄ panama ⁄ ⁄ for developing high yield b reassortants. as a wt strain, b ⁄ brisbane ⁄ ⁄ was used, which is one of the recommended influenza b virus vaccine strains for the ⁄ and ⁄ seasons. we found that b ⁄ panama ⁄ ⁄ is a useful donor, and some of the resultant reassortants were considered as vaccine candidates. b reassortant viruses were prepared by the classical reassortment method described by kilbourne. the antiserum to b ⁄ panama ⁄ ⁄ hemagglutinin and neuraminidase (hana) was raised in this study by immunizing rabbits with hana isolated from b ⁄ panama ⁄ ⁄ ; purified igg was used for antibody selection. the yields of the reassortants and their corresponding parent viruses were assessed by hemagglutination assay. viral rna was extracted directly from the allantoic fluid and amplified by rt-pcr to produce cdna for analyzing the gene composition. restriction fragment length polymorphism (rflp) analyses were performed to determine the origin of each gene segment of the high yield reassortants. restriction enzyme sets for each gene segment are available upon request. in this study we investigated the usefulness of b ⁄ panama ⁄ ⁄ as a donor for transferring high yield phenotype. b ⁄ panama ⁄ is a yamagata lineage strain with high growth phenotype (ha titer: - ). b ⁄ panama ⁄ ⁄ itself was a recommended b virus vaccine strain for ⁄ - ⁄ seasons. as a wt virus, a victoria lineage strain, b ⁄ brisbane ⁄ ⁄ , was used, which is a recommended b virus vaccine strain for use in the ⁄ and ⁄ seasons. reassortants were prepared according to classical reassortment protocol. after co-infection of b ⁄ panama ⁄ ⁄ and b ⁄ brisbane ⁄ ⁄ , progeny viruses carrying surface antigens (ha and na) of the vaccine strain were negatively selected by anti-b ⁄ panama hana antibodies, followed by passages without antibodies for positive selection of eggadapted viruses and finally limited dilution cloning. nymc bx- , bx- b, bx- d, and r- a are representative of resultant reassortants, which have significantly higher ha titers than the wt strain. the complete gene compositions of these reassortants were determined by rt-pcr ⁄ rflp analyses. as shown in table , all of these reassortants contained the pb of b ⁄ panama ⁄ ⁄ . other genes of b ⁄ panama ⁄ ⁄ (np of bx- , m of bx- b, and pb of bx- d) may not be involved in the high virus yield, since no significant growth difference among these reassortants in eggs was found as assayed by hemagglutination test. accordingly, the pb of b ⁄ panama ⁄ ⁄ is considered to be the sole factor involved in the high yield phenotype donated to the vaccine strain. we previously found that the b ⁄ lee ⁄ np gene was important in producing high yield b reassortants. it was of interest to examine whether b ⁄ lee ⁄ np and b ⁄ panama pb could work together to produce even higher yields. to test this possibility, bx- b ( : reassortant: pb and m genes from b ⁄ panama and the rest of the genes from b ⁄ brisbane) was selected and further reassorted with b ⁄ lee ⁄ . despite some difficulty in removing the na gene of b ⁄ lee ⁄ (r- c, b, b in table ), by monitoring ha and na genes of resultant viruses after each antibody selection passage with anti b ⁄ lee ⁄ hana antibodies, we were able to isolate and clone a triple reassortant, nymc bx- , which contains the np gene from b ⁄ lee ⁄ and pb and m genes from b ⁄ panama; the remaining genes are from b ⁄ brisbane ⁄ ⁄ (table ). in comparison with bx- b, no significant growth enhancement (nor reduction) in eggs was found for bx- over that seen for bx- b. nevertheless, bx- stably produces high virus yield and has been utilized as a seed virus for influenza b vaccine production for the - season by one or more vaccine manufacturers. there are contradictory reports - about the usefulness of reassortment for high yield influenza b viruses. however, we have been preparing b reassortants for several years by classical reassortment using b ⁄ lee ⁄ as a donor, and have been able to generate higher virus yield than wt strains. in this study, we found that b ⁄ panama ⁄ ⁄ serves as an efficient donor in providing the high growth capacity to b ⁄ brisbane ⁄ ⁄ (a recommended vaccine virus of victoria lineage for ⁄ - ⁄ seasons), and that the pb of b ⁄ panama ⁄ ⁄ is associated with the high yield phenotype. this particular strain from yamagata lineage might be useful to prepare high yield reassortants for other victoria lineage vaccine viruses. we noticed in this study that there may be segment incompatibilities between b ⁄ panama ⁄ ⁄ and b ⁄ brisbane ⁄ ⁄ . as shown in table , the pa and ns genes of all the high yield reassortants examined are derived from wt, b ⁄ brisbane ⁄ ⁄ , not from the donor, b ⁄ panama ⁄ ⁄ . this indicates that in this reassortment, the pa and ns genes are not replaceable with that of the donor to obtain high yield viruses. this degree of incompatibility might be common in b reassortment, resulting in low donor ⁄ wt reassortants, such as : and even : reassortants that we obtained in this study. if this is the case, reverse genetics based on : configuration may not result in generating high yield b reassortants unless a variety of donor ⁄ wt combinations are designed. one can speculate that in influenza b viruses, the surface glycoproteins (ha and na) and some of the internal proteins are functionally more closely related than in influenza a virus, as was seen in that pa and ns genes of b ⁄ brisbane ⁄ ⁄ reassort together with the ha and na genes of the same parent (table ). in our recent study on a reassortment between b ⁄ lee ⁄ and b ⁄ panama ⁄ ⁄ , it appeared that ha shapes overall gene constellations of the resultant reassortants, namely the reassortants tend to have more internal genes from the same parent of ha, no matter which parent's ha is selected by antibodies against the surface antigens of the other parent (data not shown). because of success in influenza a virus reassortment with pr , it is generally believed that reassortant with : or : configuration is optimal for virus yield. this may be the case in most instances of influenza a reassortment, but is not necessarily so in b reassortment. as shown in this study, only a single donor gene is capable of improving the yield of vaccine strain by reassortment. influenza a ⁄ h n v has spread rapidly in all parts of the world in as a true pandemic. epidemic events in russia occurred during the last week of september starting from far east region (yuzhno-sakhalinsk). kaliningrad (the western most russian city) was the second starting point of the epidemic. during october the epidemic spread over the whole russian territory. in a short period the new virus started to change genetically as it began to adapt to human populations during this pandemic (http://www.who.int; http://www.euroflu.org). in the period from may to december , clinical samples (nasopharyngeal swabs and postmortem materials) of patients with influenza-like illness from different regions of russian federation were analyzed to confirm the diagnosis using real-time reverse transcription pcr (rrt-pcr). clinical nasopharyngeal swabs and bronchoalveolar lavage and post mortal fragments of trachea, lungs, bronchi, spleen from saint petersburg hospitals and basic laboratories of federal influenza center were included in this study. all specimens were taken from patients with influenza-like illness or viral pneumonia. specimens were tested by rrt-pcr according to cdc protocols, i.e. using superscript iii platinum one-step qrt-pcr system (invitrogen) with primers and probes for infa, h seasonal, and h sw (biosearch technologies). in addition, the test-systems 'amplisense influenza virus a ⁄ b-fl' and 'influenza virus a ⁄ h -swine-fl' for pcr-detection, typing and subtyping of influenza viruses were also used. these test-systems are produced by central institute of epidemiology, moscow, russia and recommended by russian ministry of health as tests for influenza diagnosis. sequencing was carried out on an abi prism -avant genetic analyzer (applied biosystems, usa) with bigdye terminator cycle sequencing kit. phylogenetic analysis was performed using programs vector nti . (invitrogen) and mega . (psu, usa) by maximum likelihood with the tim+i+g model for ha, and -hky+i+g model for na. evolutionary model was selected by akaike information criterion (aic) in model-test (posada, crandall, ). statistical reliability of tree branches was evaluated by bootstrap test ( replications). immunohistochemical study was performed using novalink antibodies to ha and np with novocastra visualization system. influenza virus a ⁄ h n v rna was detected in patients with severe form of influenza-like illness and fatal cases. out of pcr-confirmed flu recovered cases % were patients under years of age, % were aged - years, and % were older than years. mean age of recovered patients was ae years (from month to years). viral rna in postmortem materials was detected mostly in lung tissue ( % of specimens) and trachea fragments ( %), and less commonly in spleen ( %). mean age of the deceased with confirmed flu (h n v) infection was ae years with age ranging from months to years. in % of fatal cases, influenza was complicated by viral or secondary bacterial pneumonia. median time from the onset of illness until death was days. according to our data, % of patients died had diabetes, ae % were obese, and % were pregnant women in the nd or rd trimester. ha and np were detected by immunohistochemical assay in lung tissue of dead patients with confirmed influenza virus a ⁄ h n v infection. ha and np was revealed in the endothelium of different sized blood vessels (capillaries and arterioles). these influenza virus proteins were also detected in some tissue macrophages apart from epithelium and endothelium. the localization of the two proteins was different: ha is mostly localized in cell membrane and cytoplasm, and np -mostly in the nucleus. here we present data on molecular genetic characteristics of strains of pandemic virus, strains obtained from clinical specimens, and from post mortal ones isolated in the research institute of influenza. all the strains studied contain the s n substitution in m protein, which indicates resistance to the adamantane antivirals, and have no h y substitution in the neuraminidase, which indicates resistance to oseltamivir. the phylogenetic analysis showed that russian viruses were similar to influenza viruses a ⁄ texas ⁄ ⁄ and a ⁄ california ⁄ ⁄ (ha similarity ae %). all russian viruses could be divided in two clusters: the first one includes viruses similar to the reference strain a ⁄ california ⁄ ⁄ , and the second one, which is the majority of viruses analyzed includes strains with substitutions ha s t, na n d, v i, and ns i v (figure ). bootstrap support was . the isolates with ha s t substitution can be classified in one of the five minor genome variants of a ⁄ h n v viruses found in the united states and mexico in . several viruses had strain-specific substitutions in antigenic sites sb and ca and the mutation d g in ha receptor-binding site. the substitution of amino acid residue asp to gly at position of ha was found in eight of eleven isolates ( %) from postmortem lung and trachea samples and two of forty isolates ( %) from nasopharyngeal swabs of patients with severe course of the disease. appearance of amino acid substitutions in the ha receptor-binding site (d e and d g ⁄ e) could be associated with influenza virus passaging on eggs. five strains that contained g at position of ha were isolated from post mortal specimens on mdck cells in this study, thereby excluding the possibility of substitution appearance hence to virus adaptation on eggs. in order to reveal genome changes in a(h n )v, strains isolated on the territory of russian federation during the pandemic, full genome sequences from genbank, and research institute of influenza database were analyzed comparing two groups of viruses (isolated before and after sept ). nine amino acid changes observed predominantly in late pandemic strains were found. five of them (s p, s n, d g, v i, v i) reside in ha, two in na (i v, n k), two in pb (k n, t i), and one in pa (f l). towards the end of the epidemic the viral population had demonstrated statistically certain rise in number of strains containing mutations in four genes. difference between groups was statistically significant (chisquare test, p = ae ). if v > ae , than difference between early and late strains is statistically significant. additionally fisher's test determined whether 'early strains' and 'late strains' differ significantly in the proportion of 'no mutation event' and 'mutation event' attributed to them in each particular position. all calculations were performed in fisher_tk freeware by vladimir belyaev similar to calcfisher (haseeb, ) fully described here (http://www.jstatsoft.org/v /i /paper). we have selected positions with statistically significant amino acid changes in late strains (p-value ae ). according to full genome analysis of influenza virus a ⁄ h n v strains, seven clades were distinguished, but the divergence between representatives of different clades remained small. (figure ). besides the strain a ⁄ perth ⁄ ⁄ also contains substitution s f in the same ha antigenic site. according to data obtained, the epidemic in russia was caused only by influenza virus a ⁄ h n v. unlike the previous epidemic periods when most severe influenza cases were registered among the children under years and among elderly people aged over years, the first wave of pandemic due to influenza virus a (h n )v resulted in increased level of mortality mainly among the people aged - years. though all pandemic viruses showed comparative genetic homogeneity, some evolutionary trends could be outlined. for clarification of the exact pathogenic role of mutation d g in ha receptor binding site, further studies are necessary. full-genome analysis of influenza virus a ⁄ h n v strains circulating in the southern hemisphere in the new epidemic season revealed the phylogenetic subgroup distinguished by seven substitutions in inner proteins (pb , pb , np, ns ) and sa antigenic site of ha (n d). the changes revealed could be caused by adaptation of the virus to an immunized human population. nasal and throat swabs (placed in ml mem and frozen at ) °c until use for viral rna extraction and tissue culture inoculation) were collected from patients with febrile illness, i.e., > ae °c. samples were received from clinics in us embassies and us military laboratories located throughout the world since the initial who declaration of novel h n outbreaks as a global pandemic on june , . viral isolates were obtained from inoculating cultures of mdck cells with ae - ae ml viral suspensions collected in mem originated from patients after - days incubation. [ ] [ ] [ ] [ ] due to low viral titers in normal clinical samples, most of full viral genome sequences were derived from viral stocks obtained by tissue culturing passages (mdck, - times). viral rna was extracted from clarified supernatant fluid of nasal ⁄ throat swabs or mdck cultures using the 'charge-switch' rna extraction system based on the user manual protocol from the manufacturer (invitrogen inc., ca, usa). total rna was eluted into volume equal to original sample volume, i.e., ll starting viral supernatant used to yield final ll rna in molecular grade water (invotrogen inc.) and stored at ) °c until tested. generating ⁄ preparing overlapped cdnas for full genome coverage of novel h n viruses by multiple rt-pcr amplifications the first step in the high-throughput sequencing pipeline for full influenza genome sequences was to establish a robust rt-pcr amplification scheme consisting different rt-pcr primer pairs covering all rna segments to ensure % amplification coverage of full viral genomes of all the incoming targeted viruses (houng, hs. , submitted for publication). extracted viral rna ( ll), derived from mostly mdck culturing stock or clinical sample containing sufficient viral load (> infectious units per ml) was added to primer-free rt-pcr total master mixture ( ae ll) for each virus followed by adding primer pair ( ll, pmole ⁄ ll per primer). rt-pcr was then performed: rt reaction through two hold-steps ( °c, minutes and °c, minutes); cycling amplifications ( °c for seconds, °c for seconds, °c for ae minutes). specific cdna amplicons corresponding to each individual primer pair were routinely monitored and visualized by agarose gel electrophoresis. pooled cdna products ( - lg) from each viral rt-pcr amplification run were used as sequencing substrates according to the roche flx user manual and bulletins by incorporating adaptors containing individually multiplex identifier [mid]-key assigned to each individually pooled viral cdna. up to different mid-keyed viral cdna were further pooled together to be clonally amplified on capture beads in water-in-oil emulsion micro-reactors (em amplifications), and pyrosequenced using one of two regions of a · mm picotiterplate. for each individual viral genome containing multiple assemblies ( rna segments), we obtained sff file(s) containing raw sequencing reads from which nucleotide sequence data and phredlike quality scores were extracted. on average, ae - ae % of - million mid-key specific nucleotides were extracted and mapped for consensus genome sequences. roche gsmapper (v. . and . ) software was used to assemble all sequencing raw data and sff files into consensus sequences. new reference mapping projects were created to assemble each individually mid-keyed viral cdna into consensus viral sequences. one of the earliest h n genomes of california origin, a ⁄ california ⁄ ⁄ (h n ), deposited in genbank, was routinely employed as a reference genome sequence for most of gsmapper projects. the resultant consensus sequences obtained were further verified and validated through the ncbi annotation utility check and ultimately deposited to the ncbi influenza database, genbank. nucleotide sequences specific to each individual rna gene were aligned by the geneious pro . . software (http://www.geneious.com). trees were built based on the tamura-nei genetic distance model using the neighbor-joining method with no outgroup used via geneious pro . . . phylogenetic trees of the h n genomes were constructed by importing fasta files containing specific concatenated target sequences of pb , pb , pa, ha, np, na, mp, and ns from each individual virus into the geneous pro software and going through the sequence assembling and tree building steps. high-throughput pyrosequencing of pooled novel h n cdnas by roche flx system up to viral cdnas could be routinely sequenced to completion for different full viral genomes from a single roche flx picotiter plate by utilizing the combination of pico-titer plate's two distinct regions as well as different mid-keyed adaptors. the 'shotgun' sequencing approach employed in this study is a feasible method to viral isolates (n) sequence multiple pooled h n viral genomes. for each pyrosequencing experiment, approximately - passed key reads (single fragment per bead) were obtained that yielded readable nucleic acid sequences. among those close to a million passed key reads, only - passed key reads had an average sequencing read length of > bps, defined as 'long reads' ( bps · reads = total of million bases of nucleic acid sequences) that were used to assemble into influenza genome sequences. mathematically, - million bases of raw sequencing data from each single roche flx experiment would provide sufficient sequencing bases to cover full genome sequences with approximate - · of sequencing depth coverage of influenza a with average genome size of bps for the total of eight segmented rnas. so far, more than full h n genomes sampled worldwide have been successfully sequenced and deposited in the ncbi database by division of viral diseases, walter reed army institute of research (wrair). the bioinformatics derived from unique viral genome sequences generated from this study based on constant rt-pcr amplification scheme and identical roche pyrosequencing protocols provide a reliable data set in predicting the evolutionary patterns of pandemic viruses. wrair received clinical samples from us embassies and military personnel throughout the world since the initial who announcement of novel h n outbreaks. nearly equal distributions of sequenced viruses derived from three broadly categorized geographic regions, north america, central ⁄ south america, and asia ⁄ europe ⁄ africa (data not shown). besides the geographic distribution pattern of viral isolates, figure displays the viral isolation time lines of all the sequenced viruses reflecting two peaks that coincided with two waves of pandemic infections, early-mid summer and fall of . phylogenetic trees of the eight influenza a segments of all sequenced viruses were tentatively generated. it was found that the substitution frequencies per site for the ha, na, and ns genes are at much higher rate than the other five genes, pb , pb , pa, np, and mp genes (data not shown). the observed higher genetic variations for ha and na genes of h n are consistent with the historical genomic and epidemiological dynamics data of human influenza a revealing higher temporal fluctuations in ha and na genes. [ ] [ ] [ ] [ ] analysis of full influenza genomes containing concatenated eight complete rna segments revealed the existence of two distinctive genetic clades in circulation since the beginning of pandemic, as shown in fig-ure . it is noteworthy that all viruses of mexico and california origins (clade shown at the top of figure ) were isolated at the beginning of pandemic prior to the isolation of all other viruses belonging to the second genetic clade . , discussion during the past decade, the advance of dna sequencing technology, such as development of ngs, in making full viral genome sequences readily available have enabled study of far broader and more detailed aspects of evolutionary change for any new emergent infectious pathogen. the massive sequencing capacity of roche flx system allows simultaneously process and sequence millions of individual cdna molecules, in contrast to processing and sequencing individual cdna fragments by conventional sanger sequencing method. within a short period of few months since the beginning of the pandemics, wrair accomplished large number of representative h n full genomes of worldwide origins via roche flx system. sequencing data derived from this study illustrates a much higher genetic variation rate for ha and na genes of h n that is compatible to the higher temporal fluctuation rate for ha and na genes of seasonal influenza a derived from decades of intensive monitoring and comparison studies and analyses. [ ] [ ] [ ] [ ] following the mexican and us reported cases, confirmed outbreaks of swine h n rapidly proliferated and spread throughout europe, asia, africa, and south america, most probably via global airline travel. , it seemed that new cases in the us and most cases throughout the world had been clinically mild relative to the initial reported cases in mexico. [ ] [ ] [ ] [ ] here we demonstrate through the phylogenetic relationship of sequenced h n full genomes that the clinical isolates could be divided into two different clades of viruses, i.e., the clade genetic group contains only viruses isolated at the beginning (march ⁄ april , mexico and california) of pandemics and the rest of other viruses all belong to the nd genetic group, clade . thus, it's likely that the currently circulating h n of clade causing worldwide infections is genetically different from the initial h n isolates that caused the early infections in mexico and california. , introduction a pandemic influenza virus ( h n ) was recently introduced into the human population. the hemagglutinin (ha) gene of h n is derived from 'classical swine h n ' virus, which likely shares a common progenitor strain with the human h n virus that caused the pandemic in . since antigenic changes of influenza virus ha occur more slowly in swine than in humans, we hypothesized that h n might still retain an antigenic structure similar to that of h n or the early isolates of its descendants. in this study, we compared ha antigenic structures of h n and human h n viruses by a molecular modeling approach to demonstrate the existence of shared epi-topes for neutralizing antibodies. we found that has of h n and the h n virus shared a significant number of amino acid residues in known antigenic regions. from this observation, we hypothesize that the h n ha antigenic sites will be targeted by antibody-mediated selection pressure in humans in the near future. we further discuss possible directions of antigenic changes in the evolutionary process of h n . sequence data of ha genes modeller v was used for homology modeling of ha structures. after models of the ha trimer were generated, the model was chosen by a combination of the mod-eller objective function value and the discrete optimized protein energy statistical potential score. after addition of hydrogen atoms, the model was refined by energy minimization with the minimization protocols in the accelrys discovery studio . software package using a charmm force field. steepest descent followed by conjugate gradient minimizations was carried out until the root mean square gradient was less than or equal to ae kcal ⁄ mol ⁄ a. the generalized born implicit solvent model was used to model the effects of solvation. the ha model was finally evaluated by using procheck, whatcheck, and verify- d. custom-made programs were developed with the ruby language and used for investigating the numbers of potential n-glycosylation sites and candidate codons (cand ) in ha sequences. it is known that the h ha molecules have four distinct antigenic sites: sa, sb, ca, and cb. , as a result, these sites consist of the most variable amino acids in the ha molecule of the seasonal human h n viruses that have been subjected to antibody-mediated immune pressure since its emergence in , although it was absent in humans from to . to investigate the structures of these antigenic sites of h n , d structures of the ha molecules of sc , the recent seasonal human h n virus (br ), and h n (ca ) were constructed by a homology modeling approach, and compared by mapping all the amino acid residues that were distinct from those of sc ha (data not shown). we found that most of these antigenic sites of br ha predominantly contained altered amino acid residues if compared with sc . by contrast, amino acid residues at these positions were relatively conserved in ca ha when compared with sc ha. notably, the sa and sb sites, which contain many amino acids involved in neutralizing epitopes near the receptor binding pockets, remain almost intact ( table ), suggesting that antibodies raised by natural infection with sc or its antigenically related descendant viruses play a role in specific immunity against ca . these observations lead us to hypothesize that such antigenic sites involving the conserved amino acids will soon be targeted by antibody-mediated selection pressure in the human population. based on this hypothesis, we speculated that h n would undergo patterns of amino acid substitutions in ha similar to those seen in seasonal human h n viruses during its epidemic period (i.e. those that have been substituted since ) (figure ) . we then predicted possible amino acid substitutions of h n from the sequence similarity of the antigenic sites. for example, both sc and ca had an asn residue at position in the sa site. for sc , the residue at this position has altered from asn to lys since . combining these two facts, it seems reasonable to hypothesize that ca will also undergo an amino acid substitution from asn to lys at position in the future. interestingly, we found that some of the recent variants of the h n virus have indeed undergone substitutions identical to those predicted in figure . it is important to monitor whether such variants will be selected and survive in sustained circulation in humans. next, we analyzed the acquisition of potential n-glycosylation sites associated with antigenic changes. previously, we reported that cand sites, a set of three codons that require single nucleotide substitution to produce n-glycosylation sequons, were important motifs to rapidly acquire n-glycosylation sequons. therefore, we investigated the number and location of potential n-glycosylation sites and cand sites in h n ha. we found that ca also had a single n-glycosylation sequon at the same position in the globular head region of ha, and lacked the multiple n-glycosylations that have been observed in the antigenic changes of the human h n virus during the early epidemic of this virus. we also found that ca ha possessed three cand sites that were present at the same position in sc ha (positions of the first asn residue, , , and ). of these, the cand sites with positions at and had actually become potential n-glycosylation sites in human h n viruses. this result suggests the likelihood of additional n-glycosylation at these sites during future antigenic changes of h n ha. notably, some of the recent h n variants (as of march , ) have an additional n-glycosylation sequon at position , where the h n virus readily acquired an n-glycosylation site during its circulation. the present study suggests that the antigenic structure of h n ha is similar, at least in part, to that of the h n ha. the and h n has share unique three-codon motifs that are important to readily acquire n-glycosylation sequons in their globular head region. based on these similarities, we predicted possible amino acid substitutions that might be associated with future antigenic changes of h n , and confirmed that such substitutions occurred in some of the recent variants of this virus. the present study provides an insight into likely future antigenic changes in the evolutionary process of h n in the human population. influenza viruses are classified into three types, a, b, and c, based upon the antigenic properties of nucleoproteins and matrix proteins. influenza a virus infects a wide range of hosts, including human, bird, swine, equine, and marine mammal species, while influenza b and c are less pathogenic than influenza a and are mainly found in humans, although there is evidence that they can also infect other species. influenza a has evolved in association with its various hosts on different continents for extended periods of time. to survive as a successful pathogen, the influenza viruses have developed a number of mechanisms, including antigenic mutation and genome reassortment, to continuously evolve and evade the surveillance of the host immune systems. antigenic and genetic analyses have provided important insights into the molecular dynamics of influenza virus evolution. however, a comprehensive understanding of influenza viral genetic divergence and diversity remains lacking. neuraminidase (na) is a major surface glycoprotein of influenza a and b, but is absent in influenza c. it plays a key role in virus replication through removing sialic acids from the surface of the host cell and releasing newly formed virions. influenza a viral na genes are classified into nine subtypes (na -na ) based upon their antigenic properties, while na genes of influenza b are not classified into subtypes. furthermore, most na subtypes of influenza a have evolved into distinct lineages and sub-lineages, which correspond to specific hosts or geographical locations. in this study, we conducted large-scale analyses of influenza na sequences in order to infer their evolution and to identify lineages (or sub-lineages) of influenza a viruses. a total of na sequences that excluded laboratory recombinant sequences were downloaded from genbank. sequences were aligned with muscle and mafft. the alignments were adjusted manually using translatorx, based upon corresponding protein sequences. phylogenetic analyses were conducted using the maximum-likelihood (ml) method in raxml. a set of perl scripts were written by us to facilitate this computational analysis. lineages and sub-lineages were determined based on the topology of the ml trees. additional information such as hosts, geographical regions, and circulation years were also considered in the classification. we used the same lineage nomenclature as described in, but with the following modifications: a single digit is used to represent one of the nine subtypes and a letter is used to represent a lineage; a sub-lineage is also represented using a digit; a dot is used to separate a lineage and a sublineage. for example, a. means na subtype, lineage a, and sub-lineage . the time of most recent common ancestor (tmrca) was estimated using the bayesian mcmc method in beast. in all cases, we employed the gtr + u nucleotide substitution model, in which the first and second codon positions are allowed different rates relative to the third codon position. all data sets were analyzed under a relaxed molecular clock and the bayesian skyline population coalescent prior. the maximum clade credibility (mcc) tree across all plausible trees was computed from the beast trees using the treeannotator program, with the first % trees removed as burn-in. phylogenetic analysis based upon na sequences revealed two large groups corresponding to influenza a and b, respectively ( figure a ). within influenza a, two subgroups were found, one consisting of na , na , na , and na and the other consisting of the remaining five subtypes. subtype na was found to be a sister subtype of na , na being a sister subtype of na , and na a sister subtype of na . finally, each na subtype forms a distinct cluster, indicating its genetic uniqueness. influenza a and b viral na were estimated to have diverged around years ago ( figure b ). however, it had large % hpd values which ranged from years to years ago. the na subtypes of influenza a diverged from more than to several hundred years ago. the time of most recent common ancestor (tmrca) of each subtype of influenza a virus was generally recent and ranged from the calendar years to (figure b ). in addition, the tmrca for influenza b viral na was dated back to . a total of lineages were identified in influenza a (table ) . three lineages, a, b, and c, were identified for na based upon the tree topology. linage a originated from avian viruses and was further divided into sub-lineages: a. , a. , a. , a. , and a. . linage b consists of north american swine influenza viruses whereas c is a human lineage. two large lineages, a and b, were identified in na . lineage a is a human-specific lineage. interestingly, five major swine clades were observed within this lineage. lineage b is an avian-specific lineage, and consists of sub-lineages, b. , b. , and b. . three lineages were found in na . lineage a was found in north american avian, b in eurasian ⁄ oceanian avian, and c also in avian, but it does not show any geographical pattern. for na , na , and na , each was classified into lineages, one found in north american avian ( a, a, a) and the other in eurasian ⁄ oceanian avian ( b, b, b). three lineages identified respectively in na and na are north american avian ( a, a), equine ( b, b), and eurasian avian ( c, c). na was also found to have lineages: north american avian ( a), eurasian ⁄ oceanian avian i ( b), and eurassian ⁄ oceanian avian ii ( c), respectively. in this study, we conducted large-scale phylogeny and evolutionary analyses using influenza viral na sequences. the results showed that divergence between influenza a and b viruses occurred earlier than between any influenza a subtypes. this observation was consistent with previous findings based upon phylogenetic analysis of the ha gene, one of the most important genes related to host infection. within influenza a, two sub-groups were found, one consisting of na , , , and and the other consisting of the rest of five subtypes (na , , , , ) . this observation does not agree with the result described by liu et al., where na subtypes , , , , and formed one group and the remaining four subtypes (na , , , and ) formed the other group. this difference is apparently caused by the fact that an outgroup was not used in their phylogenetic analyses. in the present study, both influenza a and b viral na sequences were included in the analysis. high bootstrap values were obtained for major groups, indicating that the inferred evolutionary relationship should be highly reliable. classification and designation of the lineages and sublineages within the influenza a virus are essential for studies of viral evolution, ecology, and epidemiology. a total of lineages were identified within nine influenza a viral na subtypes and with the majority of the identified lineages found to be host or geographic specific or both. our results demonstrated a comprehensive view for the evolution of na genes and provided a framework for the inference of evolutionary history of pandemic viruses and for further exploring of viral circulations in multiple hosts. for example, the global pandemics of human h n in , h n in , the pandemic of human h n virus in , the crisis of h n hpai in hong kong in , and swine-origin h n influenza in , all can be mapped onto the lineages and sub-lineages identified in this study. such information will facilitate not only identification of known genetic origins but also early detection of novel influenza a viruses. influenza viruses constantly evolve to avoid the human immune pressure in the process of antigenic drift. through sequencing of viral genomes, the rates and direction of virus evolution can be observed. moreover, comparison of protein sequences allows us to determine amino acid substitutions that are related to immune pressure and antigenic drift. the creation of global influenza genetic databases, along with concurrent development of analytical tools, allows the comparison of multiple influenza virus strains. the main aim of this study was to perform antigenic and genetic comparison of pandemic influenza viruses (h n ) isolated during the - pandemic in ukraine and in other countries. nasopharyngeal swabs and autopsy materials collected from infected patients were received from the areas of ukraine. in addition, field isolates of influenza viruses from the ⁄ season and strain specific serum were used for identification by hemagglutinin inhibition assay. influenza viruses were identified and subtyped using real-time rt-pcr analyses using cdc primers and adopted protocols. sequencing was performed in two world health organization (who) influenza collaboration centers (centers for disease control and prevention, atlanta and national institute for medical research, london). hemagglutinin inhibition assay was conducted using chicken and guinea pig red blood cells following standard who protocols. the all ukrainian isolates of influenza viruses, which were isolated in ukraine during august-november , were identified as a ⁄ california the phylogenetic analyses confirmed the evolutionary relationship between ukrainian isolates and viruses from other countries, which were isolated during the first wave of the pandemic. high genetic and antigenic conservation of pandemic influenza viruses from ukraine and other countries also were demonstrated. considering that the emergence of the novel pandemic influenza strain occurred in countries of northern hemisphere during summer, it was very interesting and significant tracking the dynamics of genetic changes in influenza viruses, which were isolated at the beginning of epidemic and those isolated during the rise of the epidemic in ukraine. influenza a virus causes moderate to severe epidemics annually and catastrophic pandemics sporadically. due to the evasiveness of the influenza virus and the nature of its genome (eight single-stranded and negative-sense rna segments), it is essential to understand the evolution of this important pathogen. influenza virus evolves by two major mechanisms: mutation and reassortment. antigenic and genetic analyses have revealed partially the molecular dynamics of influenza virus evolution. , however, important questions, such as how many genotypes in the influenza a virus, remain unanswered. one of the major issues pertaining to this genotyping problem is how many lineages or sub-lineages can be determined for a subtype and according to what criteria. because of the unique structure of the influenza a viral genome, the computational genotyping methods developed for other viruses cannot be applied to the influenza virus. constructing phylogenetic trees is a powerful technique for the identification of evolutionary groupings (i.e., lineages ⁄ clades). however, for large trees, it is hard to determine how many lineages and the boundaries for each lineage. in this regard, multivariate analysis methods, such as multidimensional scaling (mds) and model-based hierarchical clustering, both taking advantage of dimension reduction and visualization, can complement conventional phylogenetic methods. hemagglutinin (ha), the fastest evolving segment, is recognized as the most important gene in the influenza virus that plays a key role in viral pathogenesis. however, we have only limited knowledge of lineages and sub-lineages occurring in the hemagglutinin (ha) gene of influenza a virus, although much effort has been made in assigning clades or sub-clades in highly pathogenic avian influenza (hpai) virus ha. in this study, both model-based hierarchical clustering and phylogenetic methods were used for sequence analysis. one objective for this study is to explore and develop a more accurate lineage approach for further comprehensive influenza lineage and genotype analyses. a total of hemagglutinin (ha) sequences (approximately nucleotides long), excluding laboratory recombinant sequences, were downloaded from genbank as of march, . sequences were aligned with muscle and mafft. the genetic distance matrix of all pairwise sequences was computed using the k p model under mega . . we then used the distance matrix as input to the cmdscale module in r . . for the mds analysis. the principle coordinates resulting from mds were used for the model-based hierarchical clustering analysis, again in r . . (the r foundation. available at: http://www.r-project.org/). the bayesian information criterion (bic) values were computed based upon ten different statistical data models -eii, vii, eei, evi, vei, vvi, eee, eev, vev, and vvv. the highest bic value was used to determine the number of clusters in the given sequence data. phylogenetic analysis was conducted using maximumlikelihood (ml) in raxml. raxml uses rapid algorithms for bootstrap and maximum likelihood searches and is considered one of the fastest and most accurate phylogeny programs for large-scale sequence analysis. all the analyses were conducted on the supercomputer cluster (holland computing center, http://hcc.unl.edu/main/index.php). the trees were visualized in figtree (version . . ) . lineages and sub-lineages were determined based on both the topology of the ml trees and model-based clustering results. additional information such as hosts, geographical regions, and circulation years were also considered in the classification. we used the same lineage nomenclature as described in, with the following modifications: lineage analysis was conducted for each ha subtype, which agrees with the convention of influenza virologists that ha subtypes were identified in influenza a virus; ha lineages are represented with digits and letters, where the digit(s) represent one of the subtypes and a letter represents a lineage; here, we present sub-lineages or sub-sub-lineages also in digits, with smaller numbers representing earlier lineages or sub-lineages within the same subtype (e.g., lineage occurs earlier than lineage ); the digit is used to indicate inclusion of ancestral viruses in a lineage (or sub-lineage); a dot is used to separate lineages, sub-lineages, and sub-sub-lineages. for example, a. ae means ha subtype, lineage a, and sub-lineage , and sub-sub-lineage . the sub-lineage level can be extended as necessary. the model-based clustering method corroborates commonly used phylogenetic methods in lineage and sub-lineage assignment. here we use the h subtype as an example to show the lineage and sub-lineage assignment. the bayesian information criterion (bic) reaches its maximum when the number of clusters for h equals , regardless of which mode we choose ( figure a ). therefore, based on bic, the optimal number of clusters for the h subtype is . as a result, a total of clusters based upon the vvv model were identified ( figure b) . a significant correlation was found in lineage assignments by the phylogenetic method and the model-based hierarchical clustering method ( figure b,c) . lineages a and b were identified for h , which correspond to north american avian and eurasian avian, respectively. lineage a was further divided into sub-lineages, a. , a. , where a. is the ancestral sub-lineage in a. based on both model-based hierarchical clustering and phylogenetic analyses, a total of distinct lineages were identified among subtypes, averaging out to be ae lineages per subtype ( table ). the majority of the identified lineages were found to be host or geographic specific or both. for example, three lineages, a, b, and c, were identified for ha . lineage a was further divided into two sub-lineages, a. and a. . the a. is swine-specific, whereas a. is a human pandemic h n sub-line- how to accurately identify an evolutionary lineage of influenza a viruses is challenging. one commonly used approach is molecular phylogeny, where phylogenetic trees are constructed, and the tree topology is used for lineage determination. here, we used a bayesian model-based clustering method, along with phylogenetic methods, to decide lineages and sub-lineages of influenza a viruses based upon sequence data. the results demonstrated that the modelbased clustering method corroborates phylogenetic methods and increases the accuracy of lineage assignment. one salient feature of this study is its large-scale analysis of all available influenza a hemagglutinin sequences. a total of distinct lineages and sub-lineages were classified; the majority of them were found to be host or geographic specific. this observation agrees largely with previous findings. we are conducting further analyses of other influenza a segments and expect to identify their lineages and create a comprehensive genotypes database for all influenza a viruses. such information will allow us to detect the genetic origin of newly found viruses, track their genetic changes, and identify potential genome reassortments. a hierarchical nomenclature system has been proposed and adopted for hpai ha clades and sub-clades by who influenza surveillance centers. wan et al. also proposed a hierarchical approach for influenza a viral genotypes system. the work presented here is one of the first steps towards the development of a nomenclature system for influenza a virus lineages (at the segment level) and genotypes (at the genome level). whether the naming system will be accepted and used by the influenza research community is more challenging than the lineage analysis itself. identification of the genetic origins of influenza a viruses will enhance our understanding the evolution and adaptation mechanisms of influenza viruses. the phylogenetic analysis is the traditional approach to identify the influenza progenitor. first, the nucleotide sequences are aligned using multiple sequence alignment methods, such as clustalw, muscle, and t-coffee. second, phylogenetic analysis is performed on these aligned sequences to infer their evolutionary relationship using neighbor-joining (nj), likelihood, or bayesian inference. bootstrap analyses or computation of posterior probability are usually applied to estimate the phylogenetic uncertainty. however, this phylogenetic analysis is time consuming due to intensive computations in multiple sequence alignments and phylogenetic inferences. it is difficult to perform an analysis using this method on a large dataset, for instance, with more than taxa, as is the common case for influenza studies. alternatively, blast is applied to identify the prototype genes in the database. blast determines a similarity by identifying initial short matches and starting local alignments. since influenza viral sequences have very high similarities, especially for most conserved regions, blast usually generates a large number of outputs, which will not be helpful for progenitor identification. since blast is a local sequence alignment, the results from blast may not reflect the global evolutionary information between the sequences. the blast scores cannot be used to define the evolutionary relations between viruses, especially in the context of the entire genetic pool. recently, we have developed a distance measurement method, complete composition vector (ccv), that can calculate genetic distance between influenza a viruses without performing multiple sequence alignments. , we also adapted the minimum spanning tree (mst) clustering algorithm for influenza reassortment identification. the application of this approach in the analyses of pb genes of influenza a virus showed that the integration of ccv and mst allows us to identify the potential progenitor genes rapidly and effectively. based on these results, here we develop a webserver called ipminer for influenza progenitor identification. ipminer can identify potential progenitors for a query sequence against all public influenza datasets within a few minutes. in order to improve the computing efficiency, distance matrices were pre-computed by ccv, and they include for ha (h to ), for na (n to n ), and one for each of the internal gene segments (pb , pb , pa, np, ns, and mp). these pre-computed matrices will be updated weekly. ipminer just needs to compute the query matrices for a query sequence and sequences in the database. the standalone ccv program is also available at http://sysbio.cvm.msstate.edu/ipminer. in order to identify the influenza progenitor genes, ipminer first integrates the query matrix and a corresponding pre-computed matrix into a full distance matrix, which is then clustered by mst clustering algorithm. we adapted the threshold we measured previously in mst, u + nr, where u is the average distance and r is the standard deviation of a cluster. as a result, mst will generate a hierarchical structure for the clusters. in each cluster, we will randomly select viruses or % of the cluster size if this cluster has more than viruses. ipminer will return the viruses with the smallest distances when the search reaches to the lowest level (the largest n) in this hierarchical structure. our analyses have shown that the level has generally yielded good results for influenza a viruses. to visualize the overall mst structure, ipminer applies multi-dimensional scaling (mds) method to project all the viruses in the genetic pool onto a two dimensional graph, and the precursor viruses are marked in different shapes ( figure ). the users can select other prototype viruses from the graph for further phylogenetic analyses. a single job with one query sequence takes < min. the genbank identifiers and associated genetic distances and sequence identities are displayed. the users can download the sequences for the identified precursor viruses as well as those from the prototypes viruses. in addition, for the users' convenience, ipminer generates a phylogenetic tree using nj method implemented in phylip to illustrate the phylogenetic relationship among the query sequence(s), the identified progenitors, and the selected prototypes viruses. the programs in this solution package are written in java. the shell scripts are written in korn shell script in order to achieve high performance. cascading style sheets (css) are used for a consistent look across the pages. this also enables to change the overall design just by replacing the css definition file. php has been used as server side scripting and is written in java. in order to achieve high performance for computing in a genomic scale, we apply hash function or a binary tree, which enables that the precursor identification has a time complexity of o(n). for single queries, the users can visualize the results online. for batch queries of multiple sequences, the results will be sent to the users by e-mail. ipminer has been tested on microsoft internet explorer, mozilla firefox, and safari. the users need javascript to obtain full function of ipminer server. the webserver is available at http://sysbio.cvm.msstate.edu/ipminer. in summary, ipminer webserver has three major computational features for influenza progenitor identification: (i) it calculates the genetic distances through ccv and identifies the viruses with the shortest ccv distances against the query virus to be the progenitor genes; (ii) it projects influenza viruses onto a two dimensional map, which illustrates the global relationship between the progenitor genes and other viruses in the genetic pool; and (iii) it performs phylogenetic analyses between the query virus, the identified progenitor genes, and other selected prototype viruses. ipminer provides a user friendly web service for influenza progenitor identification in real time. the gisaid initiative offers an alternative to current public-domain database models in response to growing needs of the global influenza community for the sharing of genetic sequence and associated epidemiological and clinical data of all influenza strains. gisaid's publicly accessible epifluÔ database is governed by a unique sharing mechanism that protects the rights of the submitter, while permitting ongoing research as well as the development of medical interventions, such as drugs and vaccines. for the gisaid initiative, the max planck institute for informatics (mpii) saarbrücken, germany, has developed a web portal that is accessible at http://www.gisaid.org featuring the gisaid epifluÔ database that offers a unique collection of nucleotide sequence and other relevant data on influenza viruses. the database is based on software by oracle and the dante Ò system by a systems gmbh, germany. extensive metadata are also collected for most isolates. the database provides features for searching, filtering specific datasets for download, and user friendly upload functionality. to uphold gisaid's unique sharing mechanism, all users must positively identify themselves. while access is free of charge, all users agree that they will not attach any restrictions on the data, but will acknowledge both the originator of the specimen and the submitter of the data, and seek to undertake to collaborate with the submitter. all uploaded sequence data are submitted to rigorous curation by the friedrich-loeffler-institute for animal health (fli), germany. the database has been live since september , . among its contributors are all five who collaborating centers for influenza who routinely contribute data in addition to using the epifluÔ database for their semiannual vaccine strain selection. to provide a complete picture of data, all data available in the public domain is routinely imported. as of october , , the rapidly growing gisaid dataset comprises nucleotide sequences (from isolates) with (from isolates) uniquely submitted to this database. software development is underway to continually extend the spectrum of available data analysis tools. the intergovernmental process of the nd world health assembly specifically mentions gisaid as a publicly available database for depositing virus sequence data. starting in , germany's federal ministry of food, agriculture and consumer protection will be the long-term host of the gisaid platform. the mpii will continue to develop the portal and database software and enable gisaid to act as a catalyst for the development of advanced bioinformatics software connected directly to the database. gisaid has become an indispensible resource for the international scientific community on influenza. the consortium will expand its activities and offers to catalyze research and development on a wide variety of issues pertaining to risk analysis, drug development, and therapy of influenza. options for the control of influenza vii ª blackwell publishing ltd, influenza and other respiratory viruses, (suppl. ), - the pandemic h n virus emerged in and spread rapidly throughout the world, principally affecting children and young adults. as this virus is new to the human population, it is important to determine if these influenza infections are more commonly associated with other respiratory pathogens compared to previously circulating influenza strains. co-infecting respiratory viruses may cause increased morbidity in individuals with pandemic h n , and may also be unwanted contaminants in influenza vaccines if original clinical samples containing these adventitious viruses are used to directly inoculate certified cell lines for vaccine production. to examine this issue, stored rna from original clinical samples (nasal swabs, nasal aspirates, throat swabs) from australian and new zealand subjects that were collected in that were positive for pandemic h n and samples collected in that were positive for seasonal influenza by real time pcr assay (using the cdc, usa kits), were subjected to a resplex ii -panel version . (qiagen) pathogen screen. the resplex ii assay detects common respiratory viruses, such as respiratory syncytial viruses (rsv a, b), influenza a and b viruses, parainfluenza viruses (piv - ), human metapneumo-viruses (hmpv), coxsackieviruses ⁄ echovirus (cvev), rhinoviruses (rhv), adenoviruses (adv b, e), coronaviruses (nl , hku , e, oc ), and bocaviruses. resplex ii uses a combination of multiplex rt-pcr, hybridization of pcr onto target specific beads followed by detection using luminex-xmap technology. original clinical samples were received at the center from who national influenza centers, who influenza collaborating centers, and other regional laboratories and hospitals from australia, new zealand, and the asia ⁄ pacific region. most samples were from australia and new zealand. these samples consisted of nasal swabs, nasopharyngeal swabs, nasal washes, throat washes, and throat swabs. all samples were stored at ) °c until rna was extracted. rna was extracted from ll of clinical sample using either the magnapure extraction system (roche, australia) or the qiaxtractor system (qiagen, australia) according to the manufacturer's recommendations with an elution volume of ll and stored at ) °c until used. a ll aliquot of rna was used to amplify the selected influenza virus gene using specific primers and probes as supplied by cdc (atlanta, usa) along with super-script iii platinum one-step rt-pcr reagents (invitrogen, australia). real time pcr detection was performed on a fast system with sds software (applied biosystems, ca, usa). a cut off of a cycle threshold (c t ) of or below was considered positive. resplex ii panel ver . detection the qiagen molecular differential detection (mdd) system was used, which combines qiaplex amplification (multiplex rt-pcr) with detection on the liquichip workstation (luminex's xmap microsphere based multiplexing system) and qiaplex mdd software according to the manufacturer's instructions. a low level cutoff was used ( ) to obtain maximum sensitivity. from the clinical specimens that were positive for influenza from by real time pcr, there were ( %) a(h n ) seasonal influenza viruses, ( ae %) a(h n ) viruses, ( %) b viruses, and ( ae %) viruses which were influenza a positive, but could not be typed. clinical samples from selected to study were all influenza a(h n ) pandemic positive by real time pcr. detection of influenza virus in respiratory samples was much lower with the resplex ii assay (using a low cut off of units) for pandemic influenza a virus ( ⁄ ; sensitivity ae %) and to a lesser extent for seasonal influenza a ( ⁄ ; sensitivity of ae %) and b viruses ( ⁄ ; sensitivity of ae %) when compared to real time pcr. there were relatively few co-infecting respiratory viruses with either pandemic h infections in ( ae %) or seasonal influenza infections in ( ae %) ( table ). the most common dual infection seen with pandemic h n viruses and seasonal b viruses was with cvev ( ⁄ ; and ⁄ ; , respectively) while for a(h ) viruses there were no dominant co-infecting viruses ( table ). in one case was detected with three respira- tory pathogens in the same sample, a year old female who had pandemic h n , cvev, and rhv, and in a seasonal influenza sample, one case with a triple infection was detected (bocavirus, piv and influenza b). the median age of subjects with co-infections was younger for both pandemic h n with a median age of years (range: months to years), compared to the full sample set which had a median age of years (range: months to years), while for the patients from with seasonal influenza viruses with co-infections they had a median age of ae years (range: months to years) compared to all samples which had a median age of years (range: months to years). there was good concordance in detecting influenza a and b in respiratory samples collected in between real time rt-pcr and the resplex ii system ( % versus > ae % for seasonal influenza a and b respectively). this data compares well with other studies such as li et al. who found that resplex ii had ae % sensitivity and % specificity for seasonal influenza a viruses and ae % sensitivity and % specificity for influenza b viruses. in contrast, the present study found only ae % sensitivity for the resplex ii detection of influenza a with the samples that were positive for pandemic h n by real time rt-pcr. a recent study by rebbapragada et al. also showed lower sensitivity for pandemic h n viruses in nasopharyngeal samples with the resplex ii system ( % sensitivity and % specificity) compared to other commercial platforms seeplex rvp ( % sensitivity and % specificity) and luminex rvp ( % sensitivity and % specificity). interestingly the latest version of the resplex system offered by qiagen the resplex ii plus panel ruo now has a separate target for the pandemic h n virus (mexico ). in terms of detection of other respiratory viruses such as piv- , piv- , rsv and hmpv, high sensitivities ( ae %, ae %, ae %, and %, respectively) and specificities ( ae - %) compared to taqman rt-pcr have been reported from testing of nasal wash and nasopharyngeal clinical samples. in both the seasonal influenza positive and the pandemic h n positive (by real time rt-pcr) clinical specimens, few other respiratory viruses were detected. only of the samples had another virus detectable and one had two other viruses, while in out had another virus and one had two other viruses detected from a total of influenza virus positive samples collected in each year. enteroviruses, coronaviruses, and parainfluenza viruses were most often found with both seasonal and pandemic infections. younger age appeared to be associated with co-infections with those subjects in with dual infections having a median age of only years compared to the study groups years; and similarly for , the median age for subjects with dual infections was only ae years compared to the study groups' median age of years. a study by chong et al. on nasopharyngeal swabs collected during - using resplex ii and luminex xtag rvp fast, they found dual respiratory virus infections in ⁄ ( ae %) of samples and only ( ae %) with triple respiratory viral infections; however, these were from cases with any combination of multiple respiratory viruses not necessarily influenza, although influenza positive cases were the most common respiratory virus detected ( ae % of all positive samples). given the low level and variety of viral co-infections along with both seasonal and pandemic influenza seen in this study, it is unlikely that influenza infections predispose subjects to particular respiratory viruses, but may still allow bacterial colonization, such as has been seen with severe and fatal cases with pandemic h n with various bacteria including streptococcus pneumoniae, streptococcus pyogenes, staphylococcus aureus, or haemophilus influenzae. , low levels of other respiratory viruses along with the finding that certain cell lines (like the mdck -cells used in this study) do not propagate a number of these viruses (e.g. rsv a and b, rhinoviruses, coronaviruses), but do propagate others (e.g. parainfluenza ) should make testing for unwanted viruses that might be co-isolated with influenza viruses more focused and hence easier to detect and eliminate this isolate for future vaccine production. global influenza surveillance is one of the most important approaches to combat spread of disease. current laboratory methods for characterizing influenza are time-consuming and labor-intensive, and few viral strains undergo full characterization. even fewer strains from domestic poultry and swine or from wild aquatic birds are wellcharacterized. these strains are important for global surveillance since they are thought to be the precursors to pandemic influenza strains. we have designed a highthroughput global bio laboratory to address these surveillance needs. the goal of this project was to develop highspeed and high-volume laboratory capabilities for extensive surveillance and rapid and accurate detection and analysis of influenza. the workflow consists of surveillance, sample transportation, laboratory testing, data management and analysis. five robotic systems have been designed for this laboratory: sample accessioning, biobanking, screening, viral culture, and sequencing. sample accessioning logs barcodes, centrifuges, and aliquots samples are then sent to biobanking. the robotic biobank stores samples at ) °c and reformats tubes for screening. the screening system extracts rna and confirms the presence and subtype of influenza. aliquots of positive samples are sent to the viral culturing system for scale-up. finally, cultured samples are extracted and sent to the sequencing system for full genome sequencing. the sample accessioning, sequencing, and biobanking systems have been built, delivered, and validation processes are currently being completed. robotic screening and culturing systems have been fully designed and are ready to be built. a biosafety level -enhanced containment laboratory was built to enable the flow of samples containing highly pathogenic avian influenza viruses. in full operation, this approach to surveillance is designed to enable the sequencing of up to full virus genomes per year, more than the total of all full influenza genomes sequenced to date. the design of a robotic laboratory for influenza surveillance presents unique challenges and opportunities. before a robotic system is built, each assay is worked out on the bench top, each movement of the plates and reagents is defined, and the laboratory information management system (lims) must be able to address each step of the process. alternate assays are conceived for processes that are not automation-friendly. waste streams, worker safety, and space constraints are considered. each possibility is taken to reduce processes that have the potential to aerosolize or cross-contaminate influenza samples. instruments must be found that fit the capabilities needed. detailed specifications for each of the robotic systems were written including all the parameters listed above. once the systems are built, a long validation process takes place where the processes and instruments in each system are adjusted to function together properly. finally, a validation study is performed to ensure that the system is able to produce useful data for influenza research. the entire process takes months from start to finish for each robotic system and requires complete cooperation from a diverse team of researchers. the accessioning system logs initial sample information with the lims system. samples arrive in barcoded cryotubes. the liquid handler brings all samples up to a common volume and clarifies samples by centrifugation. samples are then transferred from screw-cap sample vials into storage plates containing individually punchable storage tubes. each tube ( ae ml) is individually identifiable with a d barcode on the bottom. six archive aliquots are made, and tubes are individually weld-sealed for storage. tips for aspiration are fixed and undergo a high-pressure plasma process between each use to sterilize tips and destroy nucleic acids. samples are stored at ) °c. each module has a capacity of remp plates or $ samples. the automated freezer system can assemble requested samples as -well plates while samples remain frozen. the screening system uses magnetic bead extraction chemistry, real-time pcr, and a liquid handling system to extract samples, confirm and quantify the presence of influenza, and reformat extracted samples for input into the sequencing system. serotype of human influenza samples will be performed by real-time pcr. many samples will not have enough material for further analysis and will need to be scaled up. the culturing system combines incubators, a liquid handling platform, plate reader, and real-time pcr to culture, monitor growth, harvest, and quantify influenza. when the system is not being used for culture and scale-up, it can be used to assay previously cultured influenza samples for drug resistance. a challenge to sequencing large numbers of influenza samples is the manpower required for sample preparation. the sequencing system has the capacity to prepare up to samples for sequencing per year for sanger sequencing. sanger sequencing was chosen because it is well-established for influenza surveillance, and automation-friendly. the system is designed to work with multiple primer sets ( , , ) . robotic systems all report to the lims. each process completion, plate movement, and data point are entered and checked by an online, web-based lims. status updates, notification, reporting, and data analysis can be achieved without entering the bsl containment facility. routine data analysis such as determining whether a cultured sample is ready to be harvested will be performed by the lims. complex data analysis, while still requiring significant human input, will be made easier by the data-acquisition functions of the lims. the implementation of a high-throughput influenza surveillance laboratory will provide an influenza research and response capacity that far exceeds what is available today. with the addition of each new system, we add a new capability to the influenza community and new opportunities to foster partnerships and collaborations with government, foundations, businesses, and academic institutions. this laboratory will not only enable cutting edge research, but will also enable a more effective response of near real-time surveillance during a pandemic outbreak. pandemics of and were believed to arise from avian influenza viruses. the tropism of avian and human seasonal influenza viruses for the human lower respiratory tract deserves investigation. the target cell types that support replication of avian influenza a viruses in the human respiratory tract in the early stages of clinical infection have not well defined. in a previous autopsy studies of human h n disease, influenza a virus were found to infect alveolar epithelial cells and macrophages. in this study, viral infectivity and replication competence of human and high and low pathogenic avian influenza viruses were systematically investigated in the human conducting and lower respiratory tract using ex vivo organ cultures. we compared the replication kinetics of human seasonal influenza viruses (h n and h n ), low pathogenic avian influenza viruses (h n , h n ) with that of the highly pathogenic h n viruses isolated from human h n disease. a range of human seasonal influenza a viruses of subtypes h n and h n viruses were included in this study from to . two isolates of low pathogenic avian influenza a (lpai) (h n ) viruses from different virus lineages isolated from poultry in hong kong in , a low pathogenic influenza a (h n ) virus isolate from wild ducks in hong kong in , and two virus isolates of highly pathogenic avian influenza (hpai) a subtype h n were included. fragments of human bronchi and lung were cut into multiple - mm fragments within hours of collection and infected in parallel with influenza a viruses at a titer of tcid ⁄ ml and as control cultures were infected with ultraviolet light inactivated virus. these tissues fragments were infected for hours and washed twice with pbs and incubated for , , and h at °c. the bronchial tissue was cultured in an air-liquid interface using sponge. viral yield was assessed by titration in mdck cells. one part of the infected tissue were fixed in formalin and processed for immunohistochemistry for influenza antigen. other part of infected tissue was homogenized and underwent rna extraction, and the expression of influenza virus matrix gene was measured by quantitative rt-pcr. human bronchus ex vivo cultures supported human seasonal influenza virus to replicate efficiently. avian influenza h n virus replicated, although less efficiently than that of seasonal influenza viruses, whereas hpai h n did not productively replicate in ex vivo cultures of human bronchus. this is in agreement with our previous finding in the well-differentiated bronchial epithelial cells in vitro. on the other hand, human lung ex vivo cultures supported prominent productive replication of human seasonal influenza h n ( figure a ) and hpai h n ( figure f ) viruses. lpai, such as h n ( figure c -d) and h n ( figure e ), also replicated productively, but with a lower viral yield. surprisingly, the replication of human influenza h n viruses ( figure b ) across the last three decades was greatly inhibited. there are clear differences in viral tropism of human seasonal and avian influenza viruses for replication in the human bronchus and lung. hpai h n virus can infect and productively replicate in the lower lung, which may account for the severity of human h n disease, but not in the conducting airways. surprisingly, there are marked differences in the replication competence of seasonal influenza viruses in ex vivo lung tissues, with influenza h n viruses being able to replicate efficiently while h n viruses do not. this may be related to the more strict siaa - gal binding preference of h n viruses. on the other hand, the efficient replication of influenza h n viruses in the alveolar spaces indicates factors other than tissues tropism alone play a role in the differences in disease severity between human seasonal h n and avian h n virus infections. pre-mrnas of the influenza a virus m and ns genes are poorly spliced in virus-infected cells. by contrast, in influenza c virus-infected cells, the predominant transcript from the m gene is spliced mrna. the present study was performed to investigate the mechanism by which influenza c virus m gene-specific mrna (m mrna) is readily spliced. ribonuclease protection assays showed that the splicing of m mrna in infected cells was much higher than that in m gene-transfected cells, suggesting that viral protein(s) other than m gene-translational products facilitates the splicing of viral mrnas. the unspliced and spliced mrnas of the influenza c virus ns gene encode two nonstructural (ns) proteins, ns (c ⁄ ns ) and ns (c ⁄ ns ), respectively. the introduction of translational premature termination into the ns gene, which blocked the synthesis of c ⁄ ns and c ⁄ ns proteins, drastically reduced the splicing of ns mrna, raising the possibility that c ⁄ ns or c ⁄ ns enhances the splicing of viral mrnas. the splicing of influenza c virus m mrna was increased by co-expression of c ⁄ ns , whereas it was reduced by co-expression of influenza a virus ns protein (a ⁄ ns ). the splicing of influenza a virus m mrna was also increased by co-expression of c ⁄ ns , whereas it was inhibited by that of a ⁄ ns . these results suggest that influenza c virus ns , but not a ⁄ ns , can up-regulate the splicing of viral mrnas. pre-mrnas of the influenza a virus m and ns genes are poorly spliced in virus-infected cells. , the inefficient splicing of viral pre-mrnas can be understood partly by the fact that influenza a virus ns protein is associated with spliceosomes and inhibits pre-mrna splicing. , cis-acting sequences in the ns transcript also negatively regulate splicing. by contrast, in influenza c virus-infected cells, the predominant transcript from the m gene is spliced mrna. the present study was performed to investigate the mechanism by which influenza c virus m gene-specific mrna (m mrna) is readily spliced. the yamagata ⁄ ⁄ strain of influenza c virus was grown in the amniotic cavity of -day-old embryonated hen's eggs. cos- and t cells were cultured in dulbecco's modified eagle's medium containing % fetal calf serum. subconfluent monolayers of cos- cells were transfected with pme s containing influenza c virus m gene cdna using the lipofectamine procedure and then incubated at °c. total rna was extracted from both the transfected cells and cells infected with c ⁄ yamagata ⁄ ⁄ virus using the rneasy mini kit (qiagen). ribonuclease protection assay was performed using a ribonuclease protection assay kit rpa iii (ambion). briefly, a [ p]-labeled influenza c virus rna -specific rna probe (vrna sense) was synthesized by in vitro transcription and hybridized with the total rna at °c overnight. hybrids were digested with rnase a ( ae u) and rnase t ( u) at °c for minutes and then analyzed on a % polyacrylamide gel containing m urea. hmv-ii cells infected with c ⁄ yamagata ⁄ ⁄ and cos- cells transfected with pme s expressing influenza c virus ns were fixed with carbon tetrachloride at various times after infection and transfection, respectively. the cells were then stained by an indirect method using anti-gst ⁄ ns serum as the primary antibody and fluorescein isothiocyanate-conjugated goat anti-rabbit igg (seikagaku kogyo) as the secondary antibody. the splicing efficiency of influenza c virus m gene-specific mrna (m mrna) in infected cells was higher than that in m gene-transfected cells the ratio of m encoded by a spliced m mrna to cm encoded by an unspliced m mrna in influenza c virusinfected cells was about times larger than that in m gene-transfected cells. ribonuclease protection assays showed that the splicing of m mrna in infected cells was much higher than that in m gene-transfected cells (figure ). these data suggest that viral protein(s) other than m gene-translational products facilitates viral mrna splicing. the influenza c virus ns gene translational product may up-regulate the splicing of viral mrnas the unspliced and spliced mrnas of the influenza c virus ns gene encode two nonstructural (ns) proteins, ns (c ⁄ ns ) and ns (c ⁄ ns ), respectively. the introduction of translational premature termination into the ns gene, which blocked the synthesis of c ⁄ ns and c ⁄ ns proteins, drastically reduced the splicing of ns mrna, suggesting that c ⁄ ns or c ⁄ ns enhances viral mrna splicing. immunofluorescent staining showed that ns localized in the nucleus in the early phase of infection, and was distributed in both the nucleus and cytoplasm in the late phase of infection, raising the possibility that influenza c virus ns protein plays a role in viral mrna splicing that occurs in the nucleus. the splicing of influenza c virus m mrna was increased by co-expression of c ⁄ ns , whereas it was reduced by co-expression of influenza a virus ns protein (a ⁄ ns ) (figure a ). the splicing of influenza a virus m mrna was also increased by co-expression of c ⁄ ns , though it was inhibited by that of a ⁄ ns ( figure b ). these results suggest that influenza c virus ns , but not a ⁄ ns , can up-regulate the splicing of viral mrnas. in influenza a virus-infected cells, splicing is controlled so that the steady-state amount of spliced mrnas is only - % of that of unspliced mrnas. , the mechanisms by which influenza a virus ns pre-mrnas are poorly spliced have been investigated and the following confirmed. influenza a virus ns protein associates with spliceosomes and inhibits pre-mrna splicing. , two cis-acting sequences in the ns transcript (positions - in the intron and positions - in the ¢ exon region) inhibit splicing. by contrast, influenza c virus m gene-specific mrna (m mrna) is efficiently spliced in influenza c virus-infected cells. in this study, we examined the mechanism by which influenza c virus m mrna is efficiently spliced and the regulatory mechanism of the splicing of ns gene-specific mrna (ns mrna). the introduction of a translational pre-mature termination into the influenza c virus ns gene, thereby blocking the synthesis of influenza c virus ns (c ⁄ ns ) and ns (c ⁄ ns ) proteins, drastically reduced the splicing rate of ns mrna. we further examined whether c ⁄ ns potentially facilitates viral mrna splicing. the splicing rate of m mrna of influenza c virus was increased by co-expression with c ⁄ ns , whereas it was reduced by co-expression with influenza a virus ns protein (a ⁄ ns ) (figure a ). the splicing of influenza a virus m gene-specific mrna was also increased by co-expression with c ⁄ ns , though it was inhibited by co-expression with a ⁄ ns ( figure b ). these results suggest that influenza c virus ns can facilitate viral mrna splicing, but in no way inhibit it, which is in striking contrast to the inhibitory effect of influenza a virus ns on pre-mrna splicing. , the mechanism for splicing enhancement by c ⁄ ns also remains to be determined. we speculate that c ⁄ ns may interact with some host proteins involved in splicing, thereby leading to an up-regulation in splicing, or that c ⁄ ns may bind to pre-mrna, increasing its accessibility to the spliceosome. the spliced mrna of the influenza c virus m gene encodes the m protein, which plays an important role in virus formation and determines virion morphology. , therefore, it is speculated that the mechanism for efficient splicing of m mrna, which provides the m protein necessary for virus assembly in a redundant amount, has been maintained in the influenza c virus. by contrast, unspliced mrna from the influenza c virus m gene encodes the cm ion channel, which is permeable to chloride ions, and also has ph-modulating activity. although the role of the influenza c virus cm ion channel in virus replication remains to be determined, it is conceivable that the over-expression of the cm protein has a deleterious effect on virus replication since the fact that a high level of influenza a virus m protein expression inhibits the rate of intracellular transport of the influenza a virus ha protein and other integral membrane glycoproteins has been demonstrated. if this is the case, efficient splicing of m mrna may control the amount of cm synthesized to optimize virus replication. therefore, we speculate that efficient splicing of m mrna leads to a high level of m expression and the reduced expression of cm , thereby creating conditions that are optimal for virus replication. in this study, we provided evidence that c ⁄ ns facilitates the splicing of m mrna. furthermore, c ⁄ ns may regulate the splicing efficiency of its own ns mrna during infection, controlling the amount of c ⁄ ns and c ⁄ ns proteins in infected cells. c ⁄ ns plays an important role in the nuclear export of vrnp, and is also associated with vrnp in the later stages of infection in virus-infected cells and is incorporated into virions, suggesting that c ⁄ ns is involved, not only in the sorting of vrnp into the assembly site, but also in virus assembly. therefore, it is likely that there is a mechanism by which an appropriate amount of c ⁄ ns is provided during infection to accomplish these functions. in conclusion, c ⁄ ns , which enhances the splicing of viral mrna, may regulate both the expression level of m gene-derived m and cm proteins, and that of ns gene-derived ns and ns proteins, thereby leading to optimal virus replication. propagation of the human influenza viruses in embryonated hen's eggs always results in a selection of variants with amino acid substitutions in the hemagglutinin (ha) that affect viral receptor-binding characteristics (reviewed ). brookes et al. recently studied infection in pigs using the egg-grown virus that contained a mixture of the original a ⁄ california ⁄ ⁄ (h n pdm) and its two egg-adaptation mutants with single amino acid substitutions d g and q r ( and in h numbering system). only the original virus and the variant with g were detected in the directly inoculated animals, indicating that the variant with r failed to infect. only the original virus was detected in nasal secretions of contact infected pigs, suggesting that the d g mutant failed to transmit. in contrast, there was an apparent selection of the d g mutant in the lower respiratory tract samples from directly inoculated pigs. the d g substitution is of a special interest as it can emerge during virus replication in humans and was associated with severe and fatal cases of pandemic influenza in - - and . here we compared phenotypic properties of the original clinical isolate of h n pdm virus a ⁄ hamburg ⁄ ⁄ and its d g and d r mutants to explain observed effects of these mutations on virus replication in swine and to predict their potential effects on virus replication in humans. a ⁄ hamburg ⁄ ⁄ (ham) was isolated from clinical material by two passages in mdck cells. the virus was passaged twice in -day-old embryonated hen's eggs and plaqued in mdck cells. the plaques were amplified in mdck cells and the sequences of the viral ha were determined. the variants with single mutation d g and q r were aliquoted and designated ham-e and ham-e , respectively. the receptor-binding specificity of the viruses was assessed by assaying their binding to desialylated-resialylated peroxidase-labeled fetuin containing either a - -linked sialic acid ( - -fet) or a - -linked sialic acid ( - -fet). in brief, viruses adsorbed in the wells of -well eia micro plates were incubated with serial dilutions of - -fet or - -fet, and the amount of bound fetuin probe was quantified by peroxidase activity. the binding data were converted to scatchard plots (a ⁄ c versus a ), and the association constants of the virus-fetuin complexes were determined from the slopes of these plots. viral cell tropism and replication efficiency in human airway epithelium were studied using fully differentiated cultures of human tracheo-bronchial epithelial cells (htbe). , to determine cell tropism, cultures were infected at a moi , fixed hours after infection, and double immuno-stained for virus antigen and cilia of ciliated cells. infected cells were counted under the microscope ( · objective with oil immersion) in the epithelial segment that included - consecutive microscopic fields containing between % and % ciliated cells relative to the total number of superficial cells. percentages of infected ciliated cells and infected non-ciliated cells relative to the total number of infected cells were calculated. ten segments per culture were analyzed and the results were averaged. to compare growth kinetics of ham and ham-e, replicate htbe cultures were infected with plaque-forming units of the viruses followed by incubation at °c under airliquid interface conditions. at , , and hours postinfection, we added dmem to the apical compartments of the cultures and incubated for minutes at °c. the apical washes were harvested, stored at ) °c, and analyzed simultaneously for the presence of infectious virus by titration in mdck cells as described previously. the non-egg-adapted h n pdm virus ham, similarly to the seasonal human virus a ⁄ memphis ⁄ ⁄ (h n ), bound to - -fet ( figure a ) and did not show any significant binding to - -fet. this result contrasted with the binding of h n pdm viruses to several - -specific probes in carbohydrate microarray analysis. reduced avidity of virus interactions with soluble glycoprotein in solution as compared to its binding to the probe clustered on the microarray surface could account for these differences in the assay results. the d g mutant ham-e differed from the parent virus by its ability to bind to -fet and by its reduced binding to -fet. the q r mutant only bound to - -fet, although less strongly than did the avian virus a ⁄ duck ⁄ alberta ⁄ ⁄ (h n ). the viral cell tropism in htbe cultures ( figure b ) correlated with receptor specificity. ham and mem ⁄ showed a typical human-virus-like tropism , with preferential infection of non-ciliated cells (< % of infected cells were ciliated). the mutant with r and control duck virus displayed a typical avian-virus-like tropism (preferential infection of ciliated cells). the d g mutant displayed a cell tropism that was intermediate between those of human and avian viruses; in particular, this mutant infected significantly higher proportion of ciliated cells than ham and mem ⁄ . observed alteration of receptor specificity and cell tropism ( figure ) suggested that egg-derived mutations can affect replication of the h n pdm virus in human airway epithelium. to test this, we first compared the capacity of the viruses to initiate infection in htbe cultures. replicate cultures were infected with identical doses of the viruses, fixed hours post-infection, and immuno-stained for viral antigen. under these conditions, ham and ham-e infected comparable numbers of cells, whereas ham-e infected at least times less cells (data not shown). this result indicated that the mutation q r markedly impaired the ability of ham-e to infect human airway epithelial cultures. we next compared two other viruses ham and ham-e for their multi-cycle replication in htbe cultures and found that the original virus reached threefold higher peak titers hours post infection than did the d g mutant ( figure ). the d g mutation in h n pdm virus facilitates virus binding to - -linked receptors and alters viral cell tropism in human airway epithelium. these changes could account for increased replication of the d g mutant in the lower respiratory tract in humans - and pigs and correlation of this mutation with severe pulmonary disease. [ ] [ ] [ ] [ ] [ ] the d g mutant replicates less efficiently in human airway cultures than the original virus. this finding correlates with an apparent lack of transmission of variants with g in humans and pigs. egg-derived mutation q r abolishes virus binding to - -linked receptors and strongly decreases infection in cultures of human airway epithelium. this result agrees with poor infectivity of the q r mutant in pigs and highlights potential pitfalls of using egg-adapted viruses with this mutation for the preparation of live influenza vaccines. nin-esterase-fusion (hef), nucleoprotein (np), matrix (m ) protein, cm , and the non-structural proteins ns and ns . , cm is the second membrane protein of the virus and is encoded by rna segment (m gene). [ ] [ ] [ ] [ ] [ ] [ ] it is composed of three distinct domains: a -residue n-terminal extracellular domain, a -residue transmembrane domain, and a -residue cytoplasmic domain. , , it is abundantly expressed at the plasma membranes of infected cells and is incorporated in a small amount into virions. , cm forms disulphide-linked dimers and tetramers, and is posttranslationally modified by n-glycosylation, palmitoylation, and phosphorylation. [ ] [ ] [ ] analyses of a number of cm mutants revealed the positions of the amino acids involved in the posttranslational modifications. , evidence was obtained that the n-glycosylation was not required for either the formation of disulfide-linked multimers or transport to the cell surface, and that none of dimer-or tetramer-formation, palmitoylation or phosphorylation was essential to the transport of cm to the cell surface. in the present study, in order to investigate the effect of cm palmitoylation on influenza c virus replication, we generated a cm palmitoylation-deficient influenza c virus, in which a cysteine at residue of cm was mutated to alanine, and examined the viral growth and viral protein synthesis in infected cells. t and hmv-ii cells were maintained as described previously. , llc-mk cells were maintained at °c in minimal essential medium with % foetal bovine serum and % calf serum. monoclonal antibodies (mabs) against the hef, np, and m proteins of c ⁄ ann arbor ⁄ ⁄ (aa ⁄ ), and antisera against the aa ⁄ virion and the cm protein were prepared as described previously. , [ ] [ ] [ ] the seven pol i plasmids for the expression of viral rnas of aa ⁄ , and the nine plasmid dnas for the expression of the influenza c viral proteins were reported previously. , plasmid dna, ppoli ⁄ cm -acy(-), in which -tgt- of the m gene was replaced with -gct- , was constructed based on ppoli ⁄ m. to generate a recombinant wild-type (rwt) virus, the above-mentioned plasmids were transfected into t cells as described previously. to rescue a mutant virus, rcm -c a, a recombinant influenza c virus lacking a cm palmitoylation site, the plasmid ppoli ⁄ cm -acy(-), instead of ppoli ⁄ m, was transfected together with the other plas-mids. at hours posttransfection (p.t.), the respective culture medium of the transfected- t cells was inoculated into the amniotic cavity of -day-old embryonated chicken eggs, and a stock of the recombinant virus was prepared. the infectious titres of the stocked recombinant viruses and the supernatants of recombinant-infected hmv-ii cells were determined according to the procedure reported previously. radioimmunoprecipitation hmv-ii cells infected with recombinants were labeled with [ s]methionine or [ h]palmitic acid. cells were then disrupted and subjected to immunoprecipitation with the indicated antibodies. the immunoprecipitates obtained were then analysed by sds-page on ae % gels containing m urea, and processed for fluorography. flotation analysis was performed according to the procedure described previously. to examine whether the cm protein without palmitoylation is synthesized in rcm -c a-infected cells, hmv-ii cells infected with the recombinants were subjected to , and the lysates of the cells were immunoprecipitated with anti-cm serum and analysed by sds-page. as shown in figure , the cm protein was synthesized both in the rwt-and rcm -c a-infected cells, but no incorporation of [ h]palmitic acid into the cm proteins synthesized in the rcm -c ainfected cells was observed, indicating that cm in the rcm -c a-infected cells was not palmitoylated. the rwt or rcm -c a viruses were infected to hmv-ii cells at an m.o.i. of and incubated at °c for up to hours. the infectious titres (p.f.u. ⁄ ml) of rwt were approximately -to -fold higher than those of rcm -c a at - hours p.i. (data not shown), indicating that rwt grew more efficiently than did rcm -c a. thus palmitoylation of cm appears to have some effect on the generation of infectious virions in cultured cells. to investigate the reason(s) for the difference in growth kinetics between the two recombinants, we analysed viral proteins synthesized in the infected hmv-ii cells. pulsechase experiments of hmv-ii cells revealed no significant differences in the synthesis and maturation of the hef, np, m , and cm proteins between the rwt-and rcm -c a-infected cells (data not shown). the infected cells pulse-labeled and chased were respectively immunoprecipitated with anti-cm serum in the presence of mm iodoacetamide and analysed by sds-page in non-reducing condition. in both populations of infected cells, several bands corresponding to cm a-monomer, -dimer, and -tetramer, as well as cm b-dimer and -tetramer were detected (data not shown). these results demonstrate an absence of any significant differences between palmitoylation-deficient cm and authentic cm in terms of conformational maturation and transport in infected cells. membrane flotation analysis revealed that no significant differences in the kinetics of the hef, m , and cm proteins were observed between rwt-and rcm -c ainfected cells (data not shown). in contrast, a slight difference in np kinetics was observed. the pulse-labeled np proteins were recovered in the bottom fractions in both rwt-and rcm -c a-infected cells. in the chase experiment, the amount of membrane-associated np proteins in fractions and was % of the total np in the rwt-infected cells, which was higher than that ( %) in the rcm -c a-infected cells (data not shown). this finding may suggest that the affinity of the np protein, presumably representing the viral ribonucleoprotein (vrnp) complex, to the plasma membrane in the rcm -c ainfected cells is lower than that in rwt-infected cells, leading to the less efficient generation of infectious virions. since cm is structurally similar to m , an influenza a virus membrane protein known to be involved in infectious virus production, [ ] [ ] [ ] [ ] [ ] it is possible that the cytoplasmic tail of cm participates in the genome packaging through interaction with vrnp. in the present study, we showed that the affinity of np to the plasma membrane of rcm -c a-infected cells was slightly lower than that to the plasma membrane of rwt-infected cells. this observation may suggest that palmitoylation of cm is involved in the viral ribonucleoprotein (vrnp) incorporation, leading to efficient infectious virion generation. we hypothesize that palmitoylation contributes to proper regional structure formation in the cm cytoplasmic tail, which is competent to recruit vrnp efficiently into virions. alternatively, the cm cytoplasmic tail without palmitoylation is not likely to reach the proper conformation, resulting in reduced interaction with vrnp and less efficient generation of infectious progeny virions. the questions of if and how the m protein is involved in the interaction between the cm cytoplasmic tail and np remains to be clarified. we showed that cm synthesized in rcm -c ainfected cells was oligomerized and transported to the cell surface. this finding is consistent with the previous observation that palmitoylation is not required for the transport of cm to the cell surface in cm -expressing cos- cells. however, the use of reverse-genetics system has enabled us to conclude that the palmitoylation of cm is required for efficient infectious virus production. this suggests that the significance of the other posttranslational modifications of cm during virus replication can be clarified using recombinant viruses lacking the respective modification sites. sialic acid (sia) linked glycoproteins are the classical influenza receptors for influenza virus haemagglutinin to bind. the distribution of sia on cell surfaces is one of the determinants of host tropism, and understanding its expression on human cells and tissues is important for understanding influenza pathogenesis. previous research has shown the differences in apical versus basolateral infection and release of different influenza virus from polarized epithelial cells and correlated this with sialic acid distribution in the human respiratory tract. moreover, mass spectrometric analysis was recently employed to elucidate the glycans present in the tissue in a higher resolution in human lung. the objective of this study was to examine in detail the distribution of these sia-linked glycans at the cellular level by the use of confocal microscopy. human primary type i-like and type ii pneumocytes were isolated from human non-tumor lung tissue by tissue fragmentation, percoll density gradient centrifugation, and magnetic cell sorting. the cells were seeded on coverslips and maintained in small airway growth medium. when confluence was reached, cell monolayers were fixed with % paraformaldehyde. we used the plant lectins, sambucus nigra glutinin (sna) from roche which binds to siaa - gal, maackia amurensis agglutinin (maa)i and maaii from vector lab, which bind the siaa - gal linked glycans using vector red as fluorescent chromogen. the cells were counter-stained with dapi or with fitc-conjugated antibody against endoplasmic recticulum (protein disulfideisomerase, pdi). the cells were imaged with multi-photon excitation laser scanning microscopy using zeiss lsm. the optical cross-section pictures were reconstructed by zeiss lsm meta. we found that there was more binding of maai and ma-aii to type ii pneumocytes than type i-like pneumocytes and more overall binding of these lectins than binding of sna ( figure ). in keeping with results from other polarized cells there was more binding to the apical than basolateral aspect, thus, explaining the previously published data on apical versus basolateral infection. as sialic acid has been implicated in the targeting of proteins to the surface, the relative lack of sialic acid on the basolateral aspect can explain why there is little seasonal influenza virus dissemination to the systemic circulation in human infections. furthermore, though there was little binding of sna to the figure . primary human type i-like and type ii pneumocytes stained with lecins (red), pdi (green), and dapi (blue) and imaged captured with confocal microscope. apical or basolateral aspects of the pneumocytes, the experimental findings of infection by influenza h n virus that has a strict siaa - gal tropism suggests that there are siaa - gal glycans present, which are not readily bound by the lectin sna. the in vitro model of primary human type i-like and type ii pneumocytes system formed a polarized epithelium that has a similar lectin distribution to human alveoli in vivo which demonstrated that it is a physiologically relevant model to study the tropism and pathogenesis of influenza a virus. human disease caused by highly pathogenic avian influenza (hpai) h n virus is associated with fulminant viral pneumonia and mortality rates in excess of %. cytokine dysregulation is thought to contribute to its pathogenesis. , we previously found delayed onset of apoptosis in h n infected human macrophages and, therefore, a longer survival time of the target cells for prolonged virus replication and cytokine and chemokine secretion, which may contribute to the pathogenesis of h n disease in humans. as bronchial and alveolar epithelial cells are target cells of influenza virus because of their proximal physiological location and interaction with macrophages, we further investigated if the differential onset of apoptosis could be found in influenza h n and seasonal influenza h n infected human respiratory epithelia. we dissected the apoptotic pathways triggered by influenza virus infection. seasonal influenza h n virus (a ⁄ hk ⁄ ⁄ ), a low pathogenic avian influenza h n lineage isolated from poultry (a ⁄ quail ⁄ hk ⁄ g ⁄ ), and two virus isolates of hpai a subtype (a ⁄ hk ⁄ ⁄ and a ⁄ vn ⁄ ⁄ ) were included. primary human bronchial and alveolar epithelial cells were infected with influenza viruses at moi of and the cell monolayer was collected at , , and hours post infection for tunel assay, and supernatant were collected for ldh assay. fragments of human lung tissues were cut into multiple - mm fragments within hours of collection and infected with influenza a viruses at a titer of tcid ⁄ ml. these tissues fragments were infected for hours and incubated for hours at °c. one part of the infected tissue was fixed in formalin and processed for immunohistochemistry for influenza antigen, and the other part was homogenized and underwent rna extraction. apoptosis cdna superarray platform (sabioscience) was employed to conduct apoptosis pathway analysis. in bronchial epithelial cells, seasonal influenza h n virus induced a high percentage of apoptotic cells by tunel assay at , , and hours post infection with a peak of (figure ) . a similar observation of delayed onset of apoptosis was found in influenza h n and h n infected alveolar epithelial cells. besides, cdna array data of ex vivo infected human lung showed that both influenza h n and h n virus induced trail expression compared with mock-infected tissue (approximately folds) at hours post infection, but influenza h n virus infected lung induced significantly more trail ( folds compared to mock infected cells), albeit with a limited viral replication ( figure ). influenza h n virus infected lung also elicited more tnf-alpha and fasr transcription than either h n or h n . these observations can account for the greater apoptotic response in influenza h n virus infected lung. as little impact on the expression of intrinsic pathway components was observed, it seems that the apoptotic response to influenza virus infection in lung was mainly through the extrinsic pathways. no significant changes in the expression of anti-apoptotic protein gene was found, except for a moderate induction of birc by influenza h n virus, which may act to modulate the apoptotic response. the delayed onset of apoptosis by hpai h n and low pathogenic avian influenza h n virus infected respiratory epithelial cells may be a mechanism for the influenza viruses to have more prolonged replication within the human respiratory tract, and this may contribute to the pathogenesis of human disease. hemagglutination (ha) assay % crbc suspension was treated by mu a , -specific sialidase at °c for minutes. complete elimination of a , -receptor on sialidase-treated crbcs was confirmed by receptor staining and flow cytometry. ha assay of live viruses with % crbc or % sialidase-treated crbc were performed in bsl- facility. synthetic ¢sln-paa-biotin(pa ), ¢sln-paa-biotin(pa ), ¢sln-ln-paa-biotin(pa ) was provided by the scripps research institute (tsri). as described elsewhere with some modifications, generally, serial dilutions of sialyglycopolymers were coated in -well-flat-bottom polystryrene plates, and hau live virus ⁄ well were added. alternatively, the plates were precoated with lg ⁄ ml sialyglycopolymers, and then , , , , hau live virus ⁄ well influenza viruses were added. rabbit antisera against a ⁄ ah ⁄ ⁄ diluted in pbs containing % bsa was added into the wells. bound antibody was detected by use of hrp-conjugated anti-rabbit igg antibody and tetramethylbenzidine substrate solution. each sample was determined in duplicates and the absorbance read at nm. a total of h n virus strains were obtained from to . the name and passage history of influenza viruses used in the study are listed in table . as the same sequences of eight rna segments were detected in a ⁄ js ⁄ ⁄ and a ⁄ js ⁄ ⁄ , only a ⁄ js ⁄ ⁄ was tested here. three amantadine-resistant variants with m mutation of screening of receptor-binding preference by ha assay representative results from three sets of independent experiments are shown in table . complete ha with sialidasetreated crbcs, which were only with a , -receptors, was detected in human influenza virus (a ⁄ brisbane ⁄ ⁄ , h n ) and two human h n virus strains, a ⁄ gd ⁄ ⁄ and a ⁄ gx ⁄ ⁄ . high binding of a , oligosaccharides to h n viruses was detected ( figure a -c). and enhanced a , -binding preference was also detected in a ⁄ gd ⁄ ⁄ and a ⁄ gx ⁄ ⁄ . the a , -binding was dose dependent for sialyglycopolymers and virus titer. notably, as compared with a ⁄ gd ⁄ ⁄ of both short-and long-a , recognition, a ⁄ gx ⁄ ⁄ prefers to bind to long-a , six oligosaccharides at low viral titer ( figure b,c) . however, both of them showed strong affinity to short-and long-a , oligosaccharides at high viral loads ( figure d ). sialoside-, galactoside-, mannoside-and sulfo-os-binding are the four types of carbohydrate-binding properties of influenza virus. binding of influenza virus to the a , -or a , -linked sialylated glycans on cell surface is important for host range restriction, and the preference to a , of h n virus limited its efficient infection in human. here, dual receptor-binding preferences were detected in a ⁄ gd ⁄ ⁄ and a ⁄ gx ⁄ ⁄ , which are of clade ae ae . although there is no direct evidence supporting the occurrence of human-to-human transmission in these infection events or the association between viral virulence and receptor-binding switching, viral systemic disseminations are found in the both fatal cases (data not shown). furthermore, with the introduction of clade ae ae into the adjacent countries of china, the finding of h n virus with - binding in human should be of concern. though h n virus with human-type receptor-binding was isolated from one patient treated by oseltamivir and those viruses were with ha and ⁄ or na substitutions, whether the substitutions responsible for receptor specificity switching is pre-existed or selected in human host remains unknown. our finding that three mutant viruses bearing m mutations of a s, a t, and s n cloned from one isolate a ⁄ hb ⁄ ⁄ suggested it is likely that the resistant viruses emerged in the host environment. no variation was found in their ha and na sequence, and all of them show high affinity to a - -binding. our data suggest that the binding-specificity was not affected by the mutations on viral envelope protein m . with the adaptation from wild aquatic birds to domestic poultry or even in human host environment, influenza virus may possess broader carbohydrate-binding spectrum or topology conformation. , we demonstrated differential a , -binding property of two human h n viruses, a ⁄ gd ⁄ ⁄ and a ⁄ gx ⁄ ⁄ . though minor effect of short-a , -binding was detected in viruses a ⁄ gx ⁄ ⁄ at low virus titer, both were of high affinity to long-a , glycans, even at the low titer which are rich on apical side of human upper respiratory epithelia. notably, no evident binding preference switching was detected in the viruses isolated from the sporadic human infection cases at the early of in china (table ) . however, higher affinity to the long-a , glycans was observed in bj ⁄ ⁄ , gz ⁄ ⁄ , and xj ⁄ ⁄ (data not shown). the discrepancy from the findings obtained by sialidase-treated crbc maybe associated with a limited abundance of n-linked a - with long branches on crbc, as demonstrated in a recent study. therefore, glycan dose-dependent binding assay is valuable and should be applied in flu surveillance. the underlying cause of the tendency is unknown, and further research on receptor-binding specificity of h n viruses is required. influenza a viruses of migrating wild aquatic birds in north america towards improved influenza a virus surveillance in migrating birds european union council directive ⁄ ⁄ eec the neighbor-joining method: a new method for reconstructing phylogenetic trees confidence limits on phylogenies: an approach using the bootstrap prospects for inferring very large phylogenies by using the neighbor-joining method mega : molecular evolutionary genetics analysis (mega) software version . the influenza virus resource at the national center for biotechnology information characterization of low-pathogenic h subtype influenza viruses from eurasia: implications for the origin of highly pathogenic h n viruses h n virus outbreak in migratory waterfowl a ⁄ h and a ⁄ h influenza viruses: different lines of one precursor evolution and ecology of influenza a viruses evolutionary processes in influenza viruses: divergence, rapid evolution, and stasis antigenic and genetic conservation of h influenza virus in wild ducks biologic characterization of chicken-derived h n low pathogenic avian influenza viruses in chickens and ducks genetic and pathogenic characterization of h n avian influenza viruses isolated in taiwan between and experimental selection of virus derivatives with variations in virulence from a single low-pathogenicity h n avian influenza virus field isolate evolution and ecology of influenza a viruses is china an influenza epicenter genesis of a highly pathogenic and potentially pandemic h n influenza virus in eastern asia evolution and molecular epidemiology of h n influenza a viruses from quail in southern china establishment of influenza a virus (h n ) in minor poultry species in southern china h n influenza viruses: outbreaks and biological properties seroprevalance and identification of influenza a virus infection from migratory wild waterfowl in china avian flu: h n virus outbreak in migratory waterfowl migration of waterfowl in the east asian flyway and spatial relationship to hpai h n outbreaks avian influenza monitoring in migrating birds in taiwan during establishment of an h n influenza virus lineage in domestic ducks in southern china evolution and molecular epidemiology of h n influenza a viruses from quail in southern china the genesis and evolution of h n influenza viruses in poultry from southern china human infection with influenza h n human infection with an avian h n influenza a virus in hong kong in antigenic and genetic characterization of h n swine influenza in china cocirculation of avian h n and contemporary ''human'' h n influenza a viruses in pigs in southeastern china: potential for genetic reassortment? h n influenza a viruses from poultry in asia have human virus-like receptor specificity characterization of h subtype influenza viruses from the ducks of southern china: a candidate for the next influenza pandemic in humans? bioedit: a user-friendly biological sequence alignment editor and analysis program for window ⁄ ⁄ nt genetic algorithm approaches for the phylogenetic analysis of large biological sequence datasets under the maximum likelihood criterion phylogenetic analysis using parsimony (and other methods) . beta a novel genotype h n influenza virus possessing human h n internal genomes has been circulating in poultry in eastern china since characterization of h n influenza viruses isolated from vaccinated flocks in an integrated broiler chicken operation in eastern china during a year period characterization of avian h n influenza viruses from united arab emirates phylogenetic analysis of influenza a viruses of h haemagglutinin subtype h n subtype influenza a viruses in poultry in pakistan are closely related to the h n viruses responsible for human infection in hong kong diversified reassortants h n avian influenza viruses in chicken flocks in northern and eastern china genotypic evolution and antigenic drift of h n influenza viruses in china from the nucleoprotein as a possible major factor in determining host specificity of influenza h n viruses pigs as the ''mixing vessel'' for the creation of new pandemic influenza a viruses origins and evolutionary genomics of the swine-origin h n influenza a epidemic pandemic (h n ) outbreak on pig farm reassortment of pandemic h n ⁄ influenza a virus in swine from where did the 'swine-origin' influenza a virus (h n ) emerge? substitution of lysine at position in pb protein does not change virulence of the pandemic h n virus in mice evolution and ecology of influenza a viruses the origins of pandemic influenza -lessons from the virus characterization of the influenza virus polymerase genes origins and evolutionary genomics of the swine-origin h n influenza a epidemic emergence of a novel swine-origin influenza a (h n ) virus in humans antigenic and genetic characteristics of swine-origin a(h n ) influenza viruses circulating in humans genetic reassortment of avian, swine, and human influenza a viruses in american pigs detection of two antigenic subpopulations of a(h n ) influenza viruses from pigs: antigenic drift or interspecies transmission genetic relatedness of hemagglutinins of the h subtype of influenza a viruses isolated from swine and birds cases of swine influenza in humans: a review of the literature triple-reassortant swine influenza a (h ) in humans in the united states reassortment of pandemic h n ⁄ influenza a virus in swine ferrets as a transmission model for influenza: sequence changes in ha of type a (h n ) virus the ferret: an animal model to study influenza virus human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals medical management of influenza infection incidence of adamantane resistance among influenza a (h n ) viruses isolated worldwide from to : a cause for concern surveillance of resistance to adamantanes among influenza a(h n ) and a(h n ) viruses isolated worldwide peramivir emergency use authorization peramivir and its use in h n influenza cs- , a prodrug of the new neuraminidase inhibitor r- , shows long-acting antiinfluenza virus activity detection of influenza viruses resistant to neuraminidase inhibitors in global surveillance during the first years of their use surveillance of influenza isolates for susceptibility to neuraminidase inhibitors during the - influenza seasons surveillance for neuraminidase inhibitor resistance among human influenza a and b viruses circulating worldwide from oseltamivir-resistant influenza viruses a (h n ), norway, - influenza activity -united states and worldwide, - season emergence of resistance to oseltamivir among influenza a(h n ) viruses in europe oseltamivir-resistant influenza virus a (h n ), europe, - season widespread oseltamivir resistance in influenza a viruses (h n ), south africa and composition of the - influenza vaccine emergence of h y oseltamivir-resistant a(h n ) influenza viruses in japan during the - season pyrosequencing as a tool to detect molecular markers of resistance to neuraminidase inhibitors in seasonal influenza a viruses neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir host cell selection of influenza neuraminidase variants: implications for drug resistance monitoring in a(h n ) viruses neuraminidase receptor binding variants of human influenza a(h n ) viruses due to substitution of aspartic acid in the catalytic site -role in virus attachment? neuraminidase inhibitor susceptibility testing in human influenza viruses: a laboratory surveillance perspective update: drug susceptibility of swine-origin influenza a (h n ) viruses comprehensive assessment of pandemic influenza a (h n ) virus drug susceptibility in vitro detection of molecular markers of drug resistance in pandemic influenza a (h n ) viruses by pyrosequencing pandemic (h n ) and oseltamivir resistance in hematology/oncology patients fluview: a weekly influenza surveillance report prepared by the influenza division development of a sensitive chemiluminescent neuraminidase assay for the determination of influenza virus susceptibility to zanamivir evaluation of neuraminidase enzyme assays using different substrates to measure susceptibility of influenza virus clinical isolates to neuraminidase inhibitors: report of the neuraminidase inhibitor susceptibility network surveillance for neuraminidase inhibitor resistance among human influenza a and b viruses circulating worldwide from different neuraminidase inhibitor susceptibilities of human h n , h n , and h n influenza viruses isolated in germany from oseltamivir-and amantadine-resistant influenza viruses a (h n ) infections with oseltamivirresistant influenza a (h n ) virus in the united states isolation of oseltamivirresistant influenza a ⁄ h n virus of different origins in yokohama city, japan, during the - influenza season a two-year survey of the oseltamivir-resistant influenza a(h n ) virus in yamagata, japan and clinical effectiveness of oseltamivir and zanamivir oseltamivir-resistant influenza a pandemic (h n ) virus detection of an oseltamivir-resistant pandemic influenza a ⁄ h n virus in hong kong a novel small-molecule inhibitor of the avian influenza h n virus determined through computational screening against the neuraminidase aurintricarboxylic acid is a potent inhibitor of influenza a and b virus neuraminidases oseltamivir-resistant influenza a viruses are transmitted efficiently among guinea pigs by direct contact but not by aerosol oseltamivir is adequately absorbed following nasogastric administration to adult patients with severe h n influenza prevention and control of influenza influenza-associated hospitalizations in the united states mortality associated with influenza and respiratory syncytial virus in the united states severe respiratory disease concurrent with the circulation of h n influenza staphlococcus aureus pneumonia studies on influenza in the pandemic of - . ii. pulmonary complications of influenza bacterial pneumonia during the hong kong influenza epidemic of - streptococcus pneumonia diagnostic value of microscopic examination of gram-stained sputum and sputum cultures in patients with bacteremic pneumococcal pneumonia pneumonitis-associated hyperprocalcitoninemia clinical review : procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors procalcitonin in sepsis and systemic inflammation: a harmful biomarker and a therapeutic target procalcitonin in children with suspected novel influenza a (h n ) infection in vitro and in vivo calcitonin i gene expression in parenchymal cells: a novel product of human adipose tissue serum procalcitonin and c-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis respiratory syncytial virus infection in elderly and high-risk adults procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations simultaneous detection of chlamydophila pneumoniae and mycoplasma pneumoniae by use of molecular beacons in a duplex real-time pcr years influenza therapy with antivirals (zanamivir and oseltamivir), nd world summit of antivirals the art of viewing and influenza -its importance for diagnosis, rd european influenza conference emergence of a novel swine origin influenza a (h n ) virus in humans origins and evolutionary genomics of the swine-origin h n influenza a epidemic molecular detection of a novel human influenza (h n ) of pandemic potential by conventional and real-time quantitative rt-pcr assays pandemic influenza a(h n )v: human to pig transmission in norway? an investigation into human pandemic influenza virus (h n ) on an alberta swine farm pandemic (h n ) infection in swine herds implications of the emergence of a novel h influenza virus emergence of a novel swine-origin influenza a virus (s-oiv) h n virus in humans rapid detection of reassortment of pandemic h n ⁄ influenza virus rapid diagnosis of a coronavirus associated with severe acute respiratory syndrome (sars) universal primer set for the fulllength amplification of all influenza a viruses cocirculation of avian h n and contemporary ''human'' h n influenza a viruses in pigs in southeastern china: potential for genetic reassortment? hog in the limelight: swine flu's got new genes on reassortment of pandemic h n ⁄ influenza a virus in swine pediatric hospitalizations associated with pandemic influenza a (h n ) in argentina factors associated with death or hospitalization due to pandemic influenza a(h n ) infection in california mortality from pandemic a ⁄ h n influenza in england: public health surveillance study antigenic and genetic characteristics of swine-origin a(h n ) influenza viruses circulating in humans characterization of a newly emerged genetic cluster of h n and h n swine influenza virus in the united states experimental inoculation of pigs with pandemic h n virus and hi cross-reactivity with contemporary swine influenza virus antisera triple-reassortant swine influenza a (h ) in humans in the united states identification of human h n and human-swine reassortant h n and h n influenza a viruses among pigs in ontario genetic and pathobiologic characterization of pandemic h n influenza viruses from a naturally infected swine herd archive number pandemic (h n ) outbreak on pig farm reassortment of pandemic h n ⁄ influenza a virus in swine a simple method for estimating percent endpoints occurrence of haemagglutinin mutation d g in pandemic influenza a(h n ) infected patients in the west of scotland rrt-pcr) protocol for detection and characterization of swine influenza (version diagnostic hybrids, inc. readycells respiratory training r-mixÔ&d Ô dfa respiratory virus screening & id kit handbook centers for disease and control and prevention. influenza laboratory course comparison study of a real-time reverse transcription polymerase chain reaction assay with an enzyme immunoassay and shell vial culture for influenza a and b virus detection in adult patients comparison of a commercial qualitative real-time rt-pcr kit with direct immunofluorescence assay (dfa) and cell culture for detection of influenza a and b in children prospective comparison of r-mix shell vial system with direct antigen tests and conventional cell culture for respiratory virus detection optimized detection of respiratory viruses in nasopharyngeal secretions evaluation of r-mix freshcells in shell vials for detection of respiratory viruses time lines of infection and disease in human influenza: a review of volunteer challenge studies comparative epidemiology of pandemic and seasonal influenza a in households viral shedding and clinical illness in naturally acquired influenza virus infections population modeling of influenza a/h n virus kinetics and symptom dynamics sensitivity of influenza rapid diagnostic tests to h n and pandemic h n viruses clinical evaluation of an immunochromatography test kit, capilia flua,b, for rapid diagnosis of influenza time to positive reaction of influenza rapid diagnosis kit and its clinical significance the speed and reliability of the antigen detection kit capilia flu a, b when used in a clinical setting options for the control of influenza vi role of rapid immunochromatographic antigen testing in diagnosis of influenza a virus h n infection poor clinical sensitivity of rapid antigen test for influenza a pandemic (h n ) virus evaluation of new rapid antigen test for the detection of pandemic influenza a ⁄ h n virus application of real-time cell electronic sensing (rt-ces) technology to cell-based assays world health organization. pandemic (h n ) role of the laboratory in diagnosis of influenza during seasonal epidemics and potential pandemics rapid detection and identification of respiratory viruses using a dual priming oligonucleotide systembased multiplex pcr assay world health organization. influenza world health organization. cdc protocol of realtime rtpcr for influenza a (h n ) development of a reverse transcription-loop-mediated isothermal amplification assay for detection of pandemic (h n ) virus as a novel molecular method for diagnosis of pandemic influenza in resource-limited settings one-step real-time rt-pcr for pandemic influenza a virus (h n ) matrix gene detection in swine samples detection of pandemic influenza a ⁄ h n ⁄ virus by real-time reverse transcription polymerase chain reaction detection of influenza a(h n )v virus by real-time rt-pcr development of a real-time rt-pcr for the detection of swine-lineage influenza a (h n ) virus infections evaluation of multiple test methods for the detection of the novel influenza a (h n ) during the new york city outbreak design and clinical application of a molecular method for detection and typing of the influenza a ⁄ h n pdm virus confirmation of the first hong kong case of human infection by novel swine origin influenza a (h n ) virus diagnosed using ultrarapid, real-time reverse transcriptase pcr evaluation of four real-time pcr assays for detection of influenza a(h n )v viruses diagnostic assay recommended by the world health organization for swine origin influenza a (h n ) virus cross-reacts with h n influenza virus increasing immunization coverage the cost-effectiveness of influenza vaccination for people aged to years: an international model national seasonal influenza vaccination survey in europe seasonal influenza and vaccination coverage influenza vaccination coverage rates in five european countries during season ⁄ and trends over six consecutive seasons influenza in the elderly -a mini-review cost of vaccine administration among pediatric practices cost of universal influenza vaccination of children in pediatric practices surveillance report: respiratory infections strategies for mitigating an influenza pandemic methods for monitoring influenza surveillance data approaches to syndromic surveillance when data consist of small regional counts rrt-pcr) protocol for detection and characterization of swine influenza (version influenza virus strains circulating in mongolia in - swine influenza who ( ) influenza a(h n ) world now at the start of influenza pandemic general statement following the ninth meeting of the emergency committee who ( ) influenza updates us dept of defense global emerging infections surveillance è me recensement general de la population et l'habitat (rgph ), ministè re de l'economie des finances et de la planification ministry of health djibouti a survey of human cases of h n avian influenza report by who before international health regulation (ihr) electronic public health surveillance in developing settings statistical analyses in disease surveillance systems potential for a global dynamic of influenza a (h n ) infectious disease informatics: syndromic surveillance for public health and biodefense visualization techniques and graphical user interfaces in syndromic surveillance systems statistical inference for infectious diseases. risk-specific household and community transmission parameters evaluation of seasonal influenza vaccination effectiveness based on antibody efficacy among the institutionalized elderly in japan australian influenza surveillance summary report. canberra: australian government department of health and ageing australia's winter with the pandemic influenza a (h n ) virus seroprevalence of pandemic influenza a(h n ) virus in australian blood donors pandemic vaccination survey: summary results. cat. no. phe concepts and procedures for laboratory-based influenza surveillance. who collaborating centres for reference and research on influenza influenza a(h n ) seroconversion rates and risk factors among distinct adult cohorts in singapore ecdc. forward look risk assessment: likely scenarios for influenza in and the ⁄ influenza season in europe and the consequent work priorities. stockholm: european centre for disease prevention and control epidemiology of influenza -summary of influenza workshop iv sampling of populations: methods and applications comparison of influenza serological techniques by international collaborative study eliminating bias in the estimation of the geometric mean of hi titres reply to ''nauta jjp, eliminating bias in the estimation of the geometric mean of hi titers novel influenza a virus infections. case definition institut national de la statistique et des é tudes é conomiques. taille des mé nages dans l'union europé enne estimation de la population au er janvier par ré gion, dé partement, sexe et â ge sero-immunity and serologic response to pandemic influenza a (h n ) virus in hong kong pandemic influenza a(h n ) virus in scotland: geographically variable immunity in spring , following the winter outbreak high prevalence of antibodies to the pandemic influenza a(h n ) virus in the norwegian population following a major epidemic and a large vaccination campaign in autumn incidence of pandemic influenza a h n infection in england: a cross-sectional serological study prevalence of seroprotection against the pandemic (h n ) virus after the pandemic antibodies in residents of new south wales, australia, after the first pandemic wave in the southern hemisphere winter older age and a reduced likelihood of h n virus infection pre-existing antibody response against pandemic influenza h n viruses in taiwanese population cross-reactive antibody responses to the pandemic h n influenza virus seasonal influenza vaccine and increased risk of pandemic a ⁄ h n -related illness: first detection of the association in british columbia association between the - seasonal influenza vaccine and pandemic h n illness during spring-summer : four observational studies from canada does seasonal influenza vaccination increase the risk of illness with the a ⁄ h n pandemic virus seasonal h n influenza virus infection is associated with elevated pre-exposure antibody titers to the serum cross-reactive antibody response to a novel influenza a (h n ) virus after vaccination with seasonal influenza vaccine world now at the start of influenza pandemic rki working group pandemic. the first wave of pandemic influenza (h n ) in germany: from initiation to acceleration department of health and ageing. australian influenza surveillance canadian surveillance studies help to understand h n patterns influenza pandé mica a un añ o de la primera ola. ¿qué podemos decir ahora? revista chilena de infectología pandemic (h n ) briefing note options for the control of influenza vii managing and reducing uncertainty in an emerging influenza pandemic the severity of pandemic h n influenza in the united states assessing the severity of the novel influenza a ⁄ h n pandemic tecumseh study of illness. xiii. influenza infection and disease, - the infection attack rate and severity of pandemic influenza (h n ) in hong kong school closure and mitigation of pandemic (h n ) , hong kong comparative epidemiology of pandemic and seasonal influenza a in households incidence of pandemic influenza a h n infection in england: a cross-sectional serological study mortality from pandemic a ⁄ h n influenza in england: public health surveillance study monthly summary tables of influenza virus isolation different epidemic curves for severe acute respiratory syndrome reveal similar impacts of control measures estimating in real time the efficacy of measures to control emerging communicable diseases the effective reproduction number of pandemic influenza in hong kong: prospective estimation multiple imputation: a primer comparative epidemiology of pandemic and seasonal influenza a in households strategies for containing an emerging influenza pandemic in southeast asia estimation of the serial interval of influenza school closure and mitigation of pandemic (h n ) , hong kong estimating the reproduction number of the novel influenza a virus (h n ) in a southern hemisphere setting: preliminary estimate in new zealand early transmission characteristics of influenza a(h n )v in australia: victorian state methods for monitoring influenza surveillance data comparative estimation of the reproduction number for pandemic influenza from daily case notification data how to maintain surveillance for novel influenza a h n when there are too many cases to count a computational framework for influenza antigenic cartography mapping the antigenic and genetic evolution of influenza virus proc of kdd cup and workshop matrix factorization techniques for recommender systems exact matrix completion via convex optimization a singular value thresholding algorithm for matrix completion matrix completion from a few entries matrices with prescribed entries and eigenvalues combining predictions for accurate recommender systems the bellkor solution to the netflix grand. prize the pragmatic theory solution to the netix grand prize feature-weighted linear stacking technical report. of health and ageing (australia). the australian health management plan for pandemic influenza influenza pandemic contingency plan, version . world health organisation. pandemic influenza preparedness and response prophylaxis or treatment? optimal use of an antiviral stockpile during an influenza pandemic the response to novel influenza a (h n ) epidemic in taiwan and analysis of the initial confirmed cases mitigation strategies for pandemic influenza in the united states strategies for mitigating an influenza pandemic containing pandemic influenza at the source efficient simulation of the spatial transmission dynamics of influenza world health organization. mathematical modelling of the pandemic h n a mathematical model for the global spread of influenza pandemic potential of a strain of influenza a (h n ): early findings effectiveness of the - influenza vaccine among children months to years of age, with vs doses cdc estimates of h n influenza cases, hospitalizations and deaths in the united states accessed entry screening for severe acute respiratory syndrome (sars) or influenza: policy evaluation pandemic of influenza - america's forgotten pandemic. the influenza of influenza: a survey of the last years in the light of modern work on the virus of epidemic influenza understanding mortality in the - influenza pandemic in england and wales genomic analysis of increased host immune and cell death responses induced by influenza virus the age pattern of mortality in the - influenza pandemic: an attempted explanation based on data for england and wales protective immunity and susceptibility to infectious diseases: lessons from the influenza pandemic deaths from bacterial pneumonia during - influenza pandemic understanding influenza transmission, immunity and pandemic threats a biological model for influenza transmission: pandemic planning implications of asymptomatic infection and immunity prior immunity helps to explain wave-like behaviour of pandemic influenza in - influenza: accounting for prior immunity - influenza pandemic mortality in england and wales. colchester, essex: uk data archive [distributor] cross-reactive antibody responses to the pandemic h n influenza virus australia's winter with the pandemic influenza a (h n ) virus model predictions and evaluation of possible control strategies for the a ⁄ h n v influenza pandemic in italy the role of population heterogeneity and human mobility in the spread of pandemic influenza age-prioritized use of antivirals during an influenza pandemic mitigation measures for pandemic influenza in italy: an individual based model considering different scenarios strategies for containing an emerging influenza pandemic in southeast asia modeling targeted layered containment of an influenza pandemic in the united states reducing the impact of the next influenza pandemic using household-based public health interventions mitigation strategies for pandemic influenza in the united states effective, robust design of community mitigation for pandemic influenza: a sytematic examination of proposed us guidance containing pandemic influenza at the source strategies for mitigating an influenza pandemic new influenza a (h n ) virus: global epidemiological situation velluci l. enhanced epidemiological surveillance of influenza a(h n )v in italy changes in reporting requirements for pandemic (h n ) virus infection use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza guidance document: pandemic influenza preparedness and response situation updates -pandemic (h n ) pandemic potential of a strain of influenza a (h n ): early findings estimating the impact of school closure on influenza transmission from sentinel data preexisting immunity to pandemic (h n ) understanding the dynamics of seasonal influenza in italy: an analysis of disease incidence and population susceptibility what is the optimal therapy for patients with h n influenza meta-analysis: convalescent blood products for spanish influenza pneumonia: a future h n treatment? treatment with convalescent plasma for influenza a (h n ) infection prophylactic and therapeutic efficacy of human monoclonal antibodies against h n influenza logistical feasibility and potential benefits of a population-wide passive-immunotherapy program during an influenza pandemic strategies for pandemic and seasonal influenza vaccination of schoolchildren in the united states mitigation strategies for pandemic influenza in the united states pandemic potential of a strain of influenza a (h n ): early findings transmission potential of the new influenza a(h n ) virus and its age-specificity in japan the transmissibility and control of pandemic influenza a (h n ) virus effect of clinical and virological parameters on the level of neutralizing antibody against pandemic influenza a virus h n world health organization. facts on blood transfusion hyperinduction of cyclooxygenase- -mediated proinflammatory cascade: a mechanism for the pathogenesis of avian influenza h n infection the role of influenza virus gene constellation and viral morphology on cytokine induction, pathogenesis, and viral virulence induction of proinflammatory cytokines in human macrophages by influenza a (h n ) viruses: a mechanism for the unusual severity of human disease? analysis of relative gene expression data using real-time quantitative pcr and the acetylsalicylic acid (asa) blocks influenza virus propagation via its nf-kappab-inhibiting activity cyclooxygenase plays a pivotal role in the resolution of acute lung injury role of -deoxy delta( , ) prostaglandin j and nrf pathways in protection against acute lung injury resolution of inflammation in murine autoimmune arthritis is disrupted by cyclooxygenase- inhibition and restored by prostaglandin e -mediated lipoxin a production inhibition of cox- aggravates neutrophil migration and pneumocyte apoptosis in surfactantdepleted rat lungs re-emergence of fatal human influenza a subtype h n disease apoptosis and pathogenesis of avian influenza a (h n ) virus in humans h n infection of the respiratory tract and beyond: a molecular pathology study molecular biology, and pathogenesis of avian influenza a (h n ) infection in humans passive immunity in prevention and treatment of infectious diseases prophylactic and therapeutic efficacy of human monoclonal antibodies against h n influenza neutralizing human monoclonal antibody against h n influenza ha selected from a fab-phage display library passive immunoprophylaxis and therapy with humanized monoclonal antibody specific for influenza a h hemagglutinin in mice generation, characterization and epitope mapping of two neutralizing and protective human recombinant antibodies against influenza a h n viruses igy: clues to the origins of modern antibodies chicken antibodies: a clinical chemistry perspective oral immunotherapy with yolk antibodies to prevent infections in humans and animals good effect of igy against pseudomonas aeruginosa infections in cystic fibrosis patients avian influenza vaccines: a practical review in relation to their application in the field with a focus on the asian experience vaccination: a tool for the control of avian influenza immunoglobulins from egg yolk: isolation and purification a simple method of estimating fifty per cent endpoints characterization of the reconstructed spanish influenza pandemic virus detection of antibody to avian influenza a (h n ) virus in human serum by using a combination of serologic assays avian influenza (h n ) viruses isolated from humans in asia in exhibit increased virulence in mammals heterosubtypic immunity to influenza a virus infection requires a properly diversified antibody repertoire early control of h n influenza virus replication by the type i interferon response in mice successful treatment of avian influenza with convalescent plasma chicken antibodies: taking advantage of evolution -a review oral administration of specific yolk antibodies (igy) may prevent pseudomonas aeruginosa infections in patients with cystic fibrosis: a phase i feasibility study avian flu: isolation of drug-resistant h n virus reduced sensitivity of influenza a (h n ) to oseltamivir enzymatic properties of the neuraminidase of seasonal h n influenza viruses provide insights for the emergence of natural resistance to oseltamivir surveillance for neuraminidase inhibitor resistance among human influenza a and b viruses circulating worldwide from a polyphenol rich plant extract, cystus , exerts anti influenza virus activity in cell culture without toxic side effects or the tendency to induce viral resistance cystus , a polyphenol-rich plant extract, exerts anti-influenza virus activity in mice cistus incanus (cystus ) for treating patients with infection of the upper respiratory tract. a prospective, randomised, placebocontrolled clinical study in vitro and in vivo assay systems for study of influenza virus inhibitors new low-viscosity overlay medium for viral plaque assays antibacterial and antifungal activities of cistus incanus and c. monspeliensis leaf extracts flavan- -ols and proanthocyanidins from cistus incanus inhibition of the infectivity of influenza virus by tea polyphenols attenuation of inducible respiratory immune responses by oseltamivir treatment in mice infected with influenza a virus anti-inflammatory activity of macrolides: a new therapeutic potential? macrolide antibiotics as immunomodulatory medications: proposed mechanisms of action proteases essential for human influenza virus entry into cells and their inhibitors as potential therapeutic agents modified pulmonary surfactant is a potent adjuvant that stimulates the mucosal iga production in response to the influenza virus antigen boost of mucosal sectretory immunoglobulin a response by clarithromycin in paediatric influenza intranasal interleukin- is a powerful adjuvant for protective mucosal immunity immunological effects of the orally administered neuraminidase inhibitor oseltamivir in influenza virus-infected and uninfected mice clarithromycin in the treatment of rsv bronchitis: a double-blind, randomized placebo-controlled trial bird flu''), inflammation and anti-inflammatory ⁄ analgesic drugs clinical effects of low-dose long-term erythromycin chemotherapy on diffuse panbronchiolitis proteolytic activation of influenza viruses by serine proteases tmprss and hat from human airway epithelium proteolytic activation of the influenza virus hemagglutinin protease-activated receptors: new concepts in regulation of g protein-coupled receptor signaling and trafficking protective role for protease-activated receptor- against influenza virus pathogenesis via an ifn-gamma-dependent pathway agonists of proteinaseactivated receptor- enhance ifn-gamma-inducible effects on human monocytes: role in influenza a infection plasmacytoid dendritic cells migrate in afferent skin lymph annexin ii incorporated into influenza virus particles supports virus replication by converting plasminogen into plasmin plasminogen promotes influenza a virus replication through an annexin ii-dependent pathway in absence of neuraminidase costimulatory receptors in a teleost fish: typical cd , elusive ctla trypsin increases pseudorabies virus production through activation of the erk signalling pathway characterization of hla-g , -g , -g , and -g isoforms transfected in a human melanoma cell line immunosuppressive hla-g molecule is upregulated in alveolar epithelial cells after influenza a virus infection influenza virus propagation is impaired by inhibition of the raf ⁄ mek ⁄ erk signalling cascade influenza viruses and the nf-kappab signaling pathway -towards a novel concept of antiviral therapy the immunotolerance role of hla-g hla-g co-expression boosts the hla class i-mediated nk lysis inhibition hla-g inhibits the allogeneic proliferative response hla-g-mediated inhibition of antigen-specific cytotoxic t lymphocytes the world health organization. h n influenza vaccine task force pandemic influenza: a potential role for statins in treatment and prophylaxis commentary: from scarcity to abundance: pandemic vaccines and other agents for ''have not'' countries new technologies for meeting the global demand for pandemic vaccines confronting the next influenza pandemic with inexpensive generic agents: can it be done? was bacterial pneumonia the predominant cause of death in the - influenza pandemic? meeting the challenge of influenza pandemic preparedness in developing countries confronting the next influenza pandemic with antiinflammatory and immunomodulatory agents: why they are needed and how they might work molecular and cellular aspects of sepsis-induced immunosuppression immune homeostasis in the respiratory tract and its impact on heterologous infection identification of oxidative stress and toll-like receptor signaling as a key pathway of acute lung injury effector t cells control lung inflammation during acute influenza virus infection by producing il- a detrimental effect of interleukin- on protective pulmonary humoral immunity during primary influenza a virus infection inhibition of influenza a virus replication by resveratrol increased survival after gemfibrozil treatment of severe mouse influenza tnf ⁄ inos-producing dendritic cells are the necessary evil of lethal influenza virus infection peroxisome proliferator-activated receptor and amp-activated protein kinase agonists protect against lethal influenza virus challenge in mice acetylsalicylic acid (asa) blocks influenza virus propagation via its nf-kappab-inhibiting activity new low-viscosity overlay medium for viral plaque assays cyproquant-pcr: a real time rt-pcr technique for profiling human cytokines, based on external rna standards, readily automatable for clinical use role of hypercytokinemia in nf-kap-pab p deficient mice after h n influenza a virus infection developing new antiviral agents for influenza treatment: what does the future hold? influenza viruses and the nf-kappab signaling pathway -towards a novel concept of antiviral therapy rna viruses and the mitogenic raf ⁄ mek ⁄ erk signal transduction cascade world health organization writing group. non-pharmaceutical interventions for pandemic influenza, international measures effects of school closures, winter influenza season, hong kong entry screening to delay local transmission of pandemic influenza a (h n ) simple physical interventions such as hand washing and wearing masks can reduce spread of respiratory viruses hand hygiene and virus transmission demographic and attitudinal determinants of protective behaviours during a pandemic: a review perceptions related to human avian influenza and their associations with anticipated psychological and behavioral responses at the onset of outbreak in the hong kong chinese general population perceptions about status and modes of h n transmission and associations with immediate behavioral responses in the hong kong general population longitudinal assessment of community psychobehavioral responses during and after the outbreak of severe acute respiratory syndrome in hong kong public perceptions, anxiety, and behaviour change in relation to the swine flu outbreak: cross sectional telephone survey community psychological and behavioral responses through the first wave of the influenza a(h n ) pandemic in hong kong main tables of the population census. hong kong: government of the statistical analysis with missing data the impact of community psychological responses on outbreak control for severe acute respiratory syndrome in hong kong economic impact of sars: the case of hong kong sars-related perceptions in hong kong group members: stream -ilaria oie -world organisation for animal health, france; malik peiris us department of health and human services, usa; masato tashiro, national institute of infectious diseases, japan; marie-paule kieny , david wood . stream -tawee chotpitayasunondh world influenza centre at national institute for medical research philippe veltsos , cathy roth , gregory härtl options for the control of influenza vii who public health research agenda for influenza outbreak communication best practices for communicating with the public during an outbreak, doc who ⁄ cds ⁄ . . geneva: world health organization who outbreak communications guidelines, geneva: world health organization characterization of h subtype influenza viruses from the ducks of southern china: a candidate for the next influenza pandemic in humans? genetic conservation of hemagglutinin gene of h influenza virus in chicken population in mainland china continuing evolution of h influenza viruses in korean poultry evolution and molecular epidemiology of h n influenza a viruses from quail in southern china characterization of the pathogenicity of members of the newly established h n influenza virus lineages in asia sequence analysis of the hemagglutinin gene of h n korean avian influenza viruses and assessment of the pathogenic potential of isolate ms molecular characterization of h n influenza viruses: were they the donors of the ''internal'' genes of h n viruses in hong kong? h n influenza viruses possessing h n -like internal genomes continue to circulate in poultry in southeastern china role of infectious bronchitis live vaccine on pathogenicity of h n avian influenza virus manual of diagnostic tests and vaccines for terrestrial animals (mammals, birds and bees) an avian influenza virus of h subtype that is highly pathogenic for chickens, but lacks multiple basic amino acids at the haemagglutinin cleavage site human influenza virus hemagglutinin with high sensitivity to proteolytic activation insertion of a multibasic cleavage motif into the hemagglutinin of a low-pathogenic avian influenza h n virus induces a highly pathogenic phenotype acquisition of a polybasic hemagglutinin cleavage site by a low-pathogenic avian influenza virus is not sufficient for immediate transformation into a highly pathogenic strain pathology and virus distribution in chickens naturally infected with highly pathogenic avian influenza a virus (h n ) during the outbreak in the netherlands implication of the proprotein convertases furin, pc and pc in the cleavage of surface glycoproteins of hong kong, ebola and respiratory syncytial viruses: a comparative analysis with fluorogenic peptides substrate cleavage analysis of furin and related proprotein convertases. a comparative study cloning and expression of novel mosaic serine proteases with and without a transmembrane domain from human lung host envelope glycoprotein processing proteases are indispensable for entry into human cells by seasonal and highly pathogenic avian influenza viruses world health organization ⁄ oie ⁄ fao h n evolution working group. toward a unified nomenclature system for highly pathogenic avian influenza virus (h n ) novel type ii transmembrane serine proteases, mspl and tmprss , proteolytically activate membrane fusion activity of hemagglutinin of highly pathogenic avian influenza viruses and induce their multicycle replication is virulence of h n influenza viruses in chickens associated with loss of carbohydrate from the hemagglutinin? targeted infection of endothelial cells by avian influenza virus a ⁄ fpv ⁄ rostock ⁄ (h n ) in chicken embryos detection of circulating asian h n viruses by a newly established monoclonal antibody a novel influenza a virus mitochondrial protein that induces cell death influenza a virus pb -f protein contributes to viral pathogenesis in mice expression of the influenza a virus pb -f enhances the pathogenesis of viral and secondary bacterial pneumonia the influenza a virus pb -f protein targets the inner mitochondrial membrane via a predicted basic amphipathic helix that disrupts mitochondrial function influenza virus pb -f protein induces cell death through mitochondrial ant and vdac a single mutation in the pb -f of h n (hk ⁄ ) and influenza a viruses contributes to increased virulence the effects of influenza a virus pb -f protein on polymerase activity are strain specific and do not impact pathogenesis eight-plasmid system for rapid generation of influenza virus vaccines pb -f proteins from h n and century pandemic influenza viruses cause immunopathology pneumonia and respiratory failure from swine-origin influenza a (h n ) in mexico emergence of a novel swine-origin influenza a (h n ) virus in humans dating the emergence of pandemic influenza viruses in vitro and in vivo characterization of new swine-origin h n influenza viruses emergence of a novel swine-origin influenza a virus (s-oiv) h n virus in humans influenza: emergence and control systemic cytokine responses in patients with influenza-associated encephalopathy inflammatory cytokines in vascular dysfunction and vascular disease identification of trypsin i as a candidate for influenza a virus and sendai virus envelope glycoprotein processing protease in rat brain mechanisms of matrix metalloprotease- upregulation and tissue destruction in various organs in influenza a virus infection activation of influenza a viruses by trypsin treatment host envelope glycoprotein processing proteases are indispensable for entry into human cells by seasonal and highly pathogenic avian influenza viruses dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation influenza virus-cytokine-protease cycle in the pathogenesis of vascular hyperpermeability in severe influenza molecular pathogenesis of influenza a virus infection and virus-induced regulation of cytokine gene expression active nf-jb signaling is a prerequisite for influenza virus infection nf-jb and virus infection: who controls whom tnf-induced mitochondrial damage: a link between mitochondrial complex i activity and left ventricular dysfunction acute encephalopathy associated with influenza and other viral infections molecular structure and assembly of the tight junction identification of oxidative stress and toll-like receptor signaling as a key pathway of acute lung injury human influenza virus infection and apoptosis induction in human vascular endothelial cells fatal outcome of human influenza a (h n ) is associated with high viral load and hypercytokinemia h n infection of the respiratory tract and beyond: a molecular pathology study fatal avian influenza a (h n ) in a child presenting with diarrhea followed by coma influenza virus m protein mediates escrt-independent membrane scission the protein-protein interaction map of helicobacter pylori development of a real-time rt-pcr for the detection of swine-lineage influenza a (h n ) virus infections long-term storage and recovery of buccal cell dna from treated cards pandemic a(h n ) influenza virus detection by real time rt-pcr: is viral quantification useful? the effect of storage at different temperatures on the stability of hepatitis c virus rna in plasma samples impact of various handling and storage conditions on quantitative detection of hepatitis c virus rna blood storage at degrees c-factors involved in dna yield and quality effects of prolonged storage of whole plasma or isolated plasma dna on the results of circulating dna quantification assays pathogenesis and transmission of swine-origin a(h n ) influenza virus in ferrets viral tropism and the pathogenesis of influenza in the mammalian host influenza: pathogenesis and host defense cutting edge: stealth influenza virus replication precedes the initiation of adaptive immunity genetic and antiviral drug susceptibility profiles of pandemic a(h n )v influenza virus circulating in portugal observed association between the ha mutation d g in the pandemic influenza a(h n ) virus and severe clinical outcome world health organization. sequencing primers and protocol antiviral drug profile of seasonal influenza viruses circulating in portugal from predicting the antigenic structure of the pandemic (h n ) influenza virus hemagglutinin genomic signature and mutation trend analysis of pandemic (h n ) influenza a virus weekly update on oseltamivir resistance to influenza a (h n ) viruses pandemic a(h n ) influenza virus detection by real-time rt-pcr: is viral quantification useful? virulence associated substitution d g in hemagglutinin of pandemic influenza a(h n ) virus affects receptor binding the first wave of pandemic influenza (h n ) in germany: from initiation to acceleration new york city swine flu investigation team, et al. the severity of pandemic h n influenza in the united states from rhinovirus delayed the circulation of the pandemic influenza a(h n ) virus in france dynamics and impact of the a(h n ) epidemic in metropolitan france clinical aspects of pandemic influenza a(h n ) virus infection preliminary estimates of mortality and years of life lost associated with the a ⁄ h n pandemic in the us and comparison with past influenza seasons oseltamivir resistance in adult oncology and hematology patients infected with pandemic (h n ) virus household transmission of the pandemic a ⁄ h n influenza virus: elevated laboratoryconfirmed secondary attack nrates and evidence of assymptomatic infections time lines of infection and disease in human influenza: a review of volunteer challenge studies facemasks and hand hygiene to prevent influenza transmission in households comparative epidemiology of pandemic and seasonal influenza a in households viral shedding and clinical illness in naturally acquired influenza virus infections r: a language and environment for statistical computing the guinea pig as a transmission model for human influenza viruses in the control of epidemic and pandemic influenza - blocking interhost transmission of influenza virus by vaccination in the guinea pig model phenotypic properties resulting from directed gene segment reassortment between wild-type a ⁄ sydney ⁄ ⁄ influenza virus and the live attenuated vaccine strain emergence of a novel swine-origin influenza a (h n ) virus in humans pneumonia and respiratory failure from swine-origin influenza a (h n ) in mexico cumulative number of confirmed human cases of avian influenza a ⁄ (h n ) reported to who factors involved in the aerosol transmission of infection and control of ventilation in healthcare premises airborne transmission of disease in hospitals noninvasive positive-pressure ventilation: an experimental model to assess air and particle dispersion airflow and droplet spreading around oxygen masks: a simulation model for infection control research coughing and aerosols. images in clinical medicine antimicrobial products registered for use against influenza a virus on hard surfaces. office of pesticide programs u.s. environmental protection agency antimicrobials division the genesis of a pandemic influenza virus influenza in the elderly -a mini review control of influenza in the long term care facility: a review of established approaches and newer options a study of the impact of influenza on the functional status of frail older people influenza in long-term care facilities: preventable, detectable, treatable mortality associated with influenza and respiratory syncytial virus in the united states causes of death australia : leading causes of death australian government department of heath and ageing. pandemic (h n ) update bulletins for pandemic (h n ) update bulletins for world health organization. pandemic (h n ) -update factors associated with death or hospitalization due to pandemic influenza a (h n ) infection in california influenza a (h n ) antibodies in residents of new south wales, australia, after the first pandemic wave in the southern hemisphere winter qualification of the hemagglutination inhibition assay in support of pandemic influenza vaccine licensure managing outbreaks of viral respiratory infection in aged care facilities -challenges and difficulties during the first pandemic wave laboratory diagnosis of influenza virus infection antigenic and genetic characteristics of swine-origin a(h n ) influenza viruses circulating in humans incidence of pandemic influenza a h n infection in england: a cross-sectional serological study cross-reactive antibody responses to the pandemic h n influenza virus in vitro and in vivo characterization of new swine-origin h n influenza viruses cross-reacting antibodies against pandemic influenza a (h n ) virus in elderly australians rhinovirus outbreak in a long term care facility for elderly persons associated with unusually high mortality a rhinovirus outbreak among residents of a long term care facility lessons from a respiratory illness outbreak in an aged-care facility detection and isolation of pandemic (h n ) influenza virus infection among pediatric patients reporting diarrhea and influenza-like illness significance of seasonal influenza viruses in the stool of pediatric patients viral load in patients infected with pandemic h n influenza a virus haemagglutinin mutations responsible for the binding of h n influenza a viruses to human-type receptors biedermann e references world health organization writing group. nonpharmaceutical interventions for pandemic influenza, international measures avian influenza, including influenza a (h n ), in humans: who interim infection control guideline for health care facilities inactivation of influenza a viruses in the environment and modes of transmission: a critical review quantitative method for evaluating virucidal activity of biocides used on hard surfaces nonpharmaceutical interventions for pandemic influenza, international measures avian influenza, including influenza a (h n ), in humans: who interim infection control guideline for health care facilities inactivation of influenza a viruses in the environment and modes of transmission: a critical review distribution of airborne influenza virus and respiratory syncytial virus in an urgent care medical clinic characterisation of stability, cytotoxicity, and skin sensitisation and irritation for respirators with antiviral coating nonpharmaceutical interventions for pandemic influenza, international measures avian influenza, including influenza a (h n ), in humans: who interim infection control guideline for health care facilities c cf/ /infectioncontrol.pdf international organization for standardization. : biological evaluation of medical devices, part : tests for cytotoxicity: in vitro methods effects of antiviral drugs on viral detection in influenza patients and on the sequential infection to their family members. serial examination by quick diagnosis (capiria) and virus culture intrafamilial transmission of influenza a and b analysis of infectious diseases data stochastic models for analysis of household transmission data: examining human-made transmission experiments factors influencing the effectiveness of oseltamivir and amantadine for the treatment of influenza. a japanese study of the multi-center study of the ⁄ influenza season clinical evaluation of an immunochromatography test kit, capilia flua, b for rapid diagnosis of influenza usefulness of a self-blown nasal discharge specimen for use with immunochromatography based influenza rapid antigen test. options for control of influenza vii ; abstract book. options for the control of influenza vii strategies for containing an emerging influenza pandemic in southeast asia flute, a publicly available stochastic influenza epidemic simulation model the japanese experience with vaccinating schoolchildren against influenza mass vaccination of schoolchildren against influenza and its impact on the influenza-associated mortality rate among children in japan effect of vaccination of a school-age population upon the course of an a -hong kong influenza epidemic herd immunity in adults against influenza-related illnesses with use of the trivalent-live attenuated influenza vaccine (caiv-t) in children the effect of mass influenza immunization in children on the morbidity of the unvaccinated elderly effect of influenza vaccination of children on infection rates in hutterite communities: a randomized trial efficacy of live attenuated and inactivated influenza vaccines in schoolchildren and their unvaccinated contacts in novgorod, russia effectiveness of influenza vaccination of day care children in reducing influenza-related morbidity among household contacts effectiveness of schoolbased influenza vaccination strategies for pandemic and seasonal influenza vaccination of schoolchildren in the united states strategy for distribution of influenza vaccine to high-risk groups and children estimating the impact of childhood influenza vaccination programmes in england and wales population-wide benefits of routine vaccination of children against influenza prevention and control of seasonal influenza with vaccines: recommendations of the advisory committee on immunization practices (acip) protective efficacy of seasonal influenza vaccination against seasonal and pandemic influenza virus infection during in hong kong partial protection of seasonal trivalent inactivated vaccine against novel pandemic influenza a ⁄ h n : case-control study in mexico city association between the - seasonal influenza vaccine and pandemic h n illness during spring-summer : four observational studies from canada cross-reactive antibody responses to the pandemic h n influenza virus effectiveness of - trivalent influenza vaccine against pandemic influenza a (h n ) -united states seasonal influenza vaccine and protection against pandemic (h n ) -associated illness among us military personnel interim analysis of pandemic influenza (h n ) in australia: surveillance trends, age of infection and effectiveness of seasonal vaccination pandemic (h n ) risk for nurses after trivalent vaccination infection and death from influenza a h n virus in mexico: a retrospective analysis birth weight, infant growth, and childhood body mass index: hong kong's children of birth cohort comparative epidemiology of pandemic and seasonal influenza a in households facemasks and hand hygiene to prevent influenza transmission in households: a cluster randomized trial partial protection against challenge with the highly pathogenic h n influenza virus isolated in japan in chickens infected with the h n influenza virus prior h n influenza infection and susceptibility of cleveland family study participants during the h n pandemic of : an experiment of nature transmission of pandemic h n influenza virus and impact of prior exposure to seasonal strains or interferon treatment prior infection with an h n swine influenza virus partially protects pigs against a low pathogenic h n avian influenza virus protection against a european h n swine influenza virus in pigs previously infected with h n and ⁄ or h n subtypes infection of mice with a human influenza a ⁄ h n virus induces protective immunity against lethal infection with influenza a ⁄ h n virus evidence of a cross-protective immune response to influenza a in the cotton rat model heterosubtypic immunity to influenza a virus: where do we stand? safety and immunogenicity of as b adjuvanted split virion versus non-adjuvanted whole virion h n influenza vaccine in uk children aged months- years: open label, randomised, parallel group, multicentre study options for live attenuated influenza vaccines (laiv) in the control of epidemic and pandemic influenza - pilot studies on recombinant cold-adapted live type a and b influenza virus vaccines development of cold-adapted recombinant live, attenuated influenza vaccines in usa and ussr clinical and epidemiological evaluation of a live, cold-adapted influenza vaccine for - -year-olds revised requirements for influenza vaccine (live) global pandemic influenza action plan to increase vaccine supply characteristics of human influenza a ⁄ h n , a ⁄ h n and b viruses isolated characteristics of human influenza a ⁄ h n , a ⁄ h n and b viruses isolated characteristics of human influenza a ⁄ h n , a ⁄ h n and b viruses isolated characteristics of human influenza a ⁄ h n , a ⁄ h n and b viruses isolated dynamics of antigenic and genetic changes in the hemagglutinins of influenza a ⁄ h n viruses of three consecutive seasons molecular epidemiology of a ⁄ h n and a ⁄ h n influenza virus during a single epidemic season in the united states an mf -adjuvanted inactivated influenza vaccine containing a ⁄ panama ⁄ (h n ) induced broader serological protection against heterovariant influenza virus strain a ⁄ fujian ⁄ than a subunit and a split influenza vaccine response of influenza vaccines against heterovariant influenza virus strains in adults with chronic diseases cross-protection by mf tmadjuvanted influenza vaccine: neutralizing and hemagglutinationinhibiting antibody activity against a (h n ) drifted influenza viruses quantifying influenza vaccine efficacy and antigenic distance detection of antibody to avian influenza a (h n ) virus in human serum by using a combination of serologic assays world health organization global influenza programme. who manual on animal influenza diagnosis and surveillance antigenic characterization of influenza b virus with a new microneutralisation assay: comparison to haemagglutination and sequence analysis seroprotection rate, meanfold increase, seroconversion rate: which parameter adequately expresses seroresponse to influenza vaccination? the adjuvanted influenza vaccines with novel adjuvants: experience with the mf -adjuvanted vaccine experimental inoculation of pigs with pandemic h n virus and hi cross-reactivity with contemporary swine influenza virus antisera current status of live attenuated influenza vaccine in the united states for seasonal and pandemic influenza failure of protection and enhanced pneumonia with a us h n swine influenza virus in pigs vaccinated with an inactivated classical swine h n vaccine isolation and characterization of h n influenza a virus from turkeys a new generation of modified live-attenuated avian influenza viruses using a two-strategy combination as potential vaccine candidates a dna transfection system for generation of influenza a virus from eight plasmids efficacy of inactivated swine influenza virus vaccines against the a ⁄ h n influenza virus in pigs mortality associated with influenza and respiratory syncytial virus on the united states realities and enigma of human viral influenza: pathogenesis, epidemiology and control immune response after adjuvant mucosal immunization of mice with inactivated influenza virus stimulation of protective and cross-protective imunity against influenza b virus after adjuvant mucosal immunization of mice protective and cross-protective mucosal immunization of mice by influenza virus type a with bacterial adjuvant synergistic action of cholera toxin b subunit (and escherichia coli heat-labile toxin b subunit) and a trace amount of cholera whole toxin as an adjuvant for nasal influenza vaccine effects of intanasal administration of chlera toxine (or escherichia coli heat-labila enterotoxin b subunits)supplemented with a trace amount of the holotoxin on the brain the adjuvants mf and lt-k enhance the mucosal and systemic immunogenicity of subunit influenza vaccine administrated intranasaly in mice generation of influenza vaccine strains by genetic reassortment a description of the process of seasonal and h n influenza vaccine virus selection and development pcr restriction analysis if genome composition and stability of cold-adapted reassortants live influenza vaccines options for live attenuated influenza vaccines (laiv) in the control of epidemic and pandemic influenza - characterization of an influenza a h n reassortant as a candidate for live-attenuated and inactivated vaccines against highly pathogenic h n viruses with pandemic potential are there alternative avian influenza viruses for generation of stable attenuated avian-human influenza a reassortant viruses? organization of production, quality control and provision of the republic of kazakhstan with the a ⁄ h n vaccine development of diagnostics and vaccines against influenza a ⁄ h n and a ⁄ h n is the basis for biological safety and protection of population in kazakhstan maior results of developing a technology for production of a pandemic influenza a ⁄ h n vaccine» abstract book ''options for the control of influenza vii abstract book international scientific conference of students, graduates and young scientists ''lomonosov isolation of influenza viruses in cell cultures and chicken embryos and their identification development of quality and safety control methods of the inactivated vaccine based on the strain a ⁄ astanarg ⁄ : ⁄ (h n control methods of medical immunobiological preparations injected to humans. guidelines, muk . / . . - (adopted by goskomsanepidnadzor rf ob scientific center for expertise of medical products, moscow. russian national pharmacopeia. ist edn the guidance for pre-clinical testing of pharmaceutical substances for safety and effectiveness (regulations of good laboratory practice in the russian federation -glp). manual on experimental (pre-clinical) assay of new pharmaceutical substances. moscow: ministry of public health ⁄ department of quality, effectiveness and safety control of medicines ⁄ scientific center of expert examination and national control of medicines ⁄ pharmacological national committee manual on experimental (pre-clinical) assay of new pharmaceutical substances. moscow: medline status of the development of influenza a ⁄ h n vaccines in the world and in russia approval of instruction for preclinical testing of pharmacological and medical substances in the repubilic of kazakhstan preclinical testing of new medical immunobiological substances. basic principles. moscow: ussr ministry of health order and methods of control of vaccine immunobiological safety. general methodic principles. moscow: ussr ministry of health planning and performance of clinical study of medicines federal pharmaceutical substances law. # -fz russian federation national standard. good clinical practice. # -st order of the minister of health of russian federation # signed . . . rules for clinical practice in russian federation a single-dose influenza a (h n ) vaccine safe and immunogenic in adult and elderly patients: an approach to pandemic vaccine development cross-reactive immunity to clade strains of influenza virus a subtype h n induced in adults and elderly patients by fluval, a prototype pandemic influenza virus vaccine derived by reverse genetics, formulated with a phosphate adjuvant, and directed to clade strains develop of domestic vaccinal and diagnostic preparations for influenza a ⁄ h n and a ⁄ h n as a basic principle of biological safety and security for the population of kazakhstan guidelines: ''isolation of influenza viruses in cell cultures and chicken embryos and their identification''. moscow: a-print validation of control methods for chemical and physicochemical characteristics of mibp quality: organization the guidance for pre-clinical testing of pharmaceutical substances for safety and effectiveness (regulations of good laboratory practice in the russian federation -glp). manual on experimental (pre-clinical) assay of new pharmaceutical substances. moscow: ministry of public health ⁄ department of quality, effectiveness and safety control of guidance on assessment of allergenic characteristics of pharmaceutical substances on adoption of the instructions for performance of pre-clinical assays and tests of pharmaceutical substances and medicines in the republic of kazakhstan national pharmacopoeia of the republic of kazakhstan planning and performance of clinical study of medicines federal law on medicines no. -aii dated national standard of the russian federation ''proper clinical practice'' no. -st guidance on clinical practice in the russian federation'' (in russian) aluminum hydroxide adjuvants activate caspase- and induce il- beta and il- release safety and immunogenicity of a pandemic influenza a h n vaccine when administered alone or simultaneously with the seasonal influenza vaccine for the - influenza season: a multicentre, randomised controlled trial current status of live attenuated influenza vaccine in the united states for seasonal and pandemic influenza a simple method of estimation fifty per cent endpoints use of animal models to understand the pandemic potential of highly pathogenic avian influenza viruses evaluation of replication and pathogenicity of avian influenza a h subtype viruses in a mouse model results of preclinical studies of live monovalent influenza vaccine influvir swine influenza a (h n ) infection in two children -southern california comparison of rna hybridization, hemagglutination assay, titration of infectious virus and immunofluorescence as methods for monitoring influenza virus replication in vitro concepts and procedures for laboratory-based influenza surveillance. us department of health and human services and pan-american health organization detection of antibody to avian influenza a (h n ) virus in human serum by using a combination of serologic assays fda ⁄ nih ⁄ who public workshop on immune correlates of protection against influenza a viruses in support of pandemic vaccine development coinfection of avian influenza virus (h n subtype) with infectious bronchitis live vaccine co-infection of staphylococcus aureus or haemophilus paragallinarum exacerbates h n influenza a virus infection in chickens human infection with an avian h n influenza a virus in hong kong in avian-to-human transmission of h n subtype influenza a viruses: relationship between h n and h n human isolates human infection with influenza h n universal primer set for the full-length amplification of all influenza a viruses phylogenetic analysis of hemagglutinin and neuraminidase genes of h n viruses isolated from migratory ducks the neighbor-joining method: a new method for reconstructing phylogenetic trees application of a microtechnique to viral serological investigations biological activity of monoclonal antibodies to operationally defined antigenic regions on the hemagglutinin molecule of a ⁄ seal ⁄ massachusetts ⁄ ⁄ (h n ) influenza virus development of vaccine strains of h and h influenza viruses isolation of ortho-and paramyxoviruses from feral birds in hokkaido head-to-head comparison of four nonadjuvanted inactivated cell culture-derived influenza vaccines: effect of comparison, spatial organization and immunization route on the immunogenicity in a murine challenge model evaluation of growth, genetic, and antigenic characteristics of pandemic h n viruses isolated and passaged in qualified mdck suspension cells a (h n ) influenza virus pandemic: a review influenza vaccine: from surveillance through production to protection trivalent mdck cell culture-derived influenza vaccine optaflu (novartis vaccines) validation of the safety of mdck cells as a substrate for the production of a cell-derived influenza vaccine genetic composition of a high-yielding influenza a virus recombinant: a vaccine strain against ''swine'' influenza rescue of influenza a virus from recombinant dna of health, public health service. concepts and procedures for laboratory based influenza surveillance a rapid method for immunotitration of influenza viruses using flow cytometry generation of live attenuated novel influenza a ⁄ california ⁄ ⁄ (h n ) vaccines with high yield in embryonated chicken eggs haemagglutinin quantification and identification of influenza a&b strains propagated in per.c cells: a novel rp-hplc method comparison of egg and high yielding mdck cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: in vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissive cells effect of neuraminidase antibody on hong kong influenza infection-permissive immunization with influenza virus neuraminidase prevents weight loss in infected mice protection of mice with recombinant influenza virus neuraminidase cross-reactive neuraminidase antibodies afford partial protection against h n in mice and are present in unexposed humans note for guidance on harmonization of requirements for influenza vaccines who meeting on the role of neuraminidase in inducing protective immunity against influenza infection who manual on animal influenza diagnosis and surveillance [electronic resource] ⁄ world health organization, department of communicable disease surveillance and response measurement of anti-influenza neuraminidase antibody using a peroxidase-linked lectin and microtitre plates coated with natural substrates detection of antibody to avian influenza a(h n ) virus in human serum by using a combination of serologic assays large trials confirm immunogenicity of h n vaccines pre-existing immunity against swine-origin h n influenza viruses in the general human population yuelong shu references novel swine-origin influenza a (h n ) virus investigation team. emergence of a novel swine-origin influenza a (h n ) virus in humans serum crossreactive antibody response to a novel influenza a (h n ) virus after vaccination with seasonal influenza vaccine detection of antibody to avian influenza a (h n ) virus in human serum by using a combination of serologic assays concepts and procedures for laboratory-based influenza surveillance manual on animal influenza diagnosis note for guidance on harmonization of requirements for influenza vaccines (cpmp ⁄ bwp ⁄ ⁄ ). european agency for the evaluation of medicinal products cross-reactive antibody responses to the pandemic h n influenza virus serologic survey of pandemic (h n ) virus influenza a(h n ) seroconversion rates and risk factors among distinct adult cohorts in singapore swine influenza a outbreak reflections on the swine flu vaccination program the flu and other influenza pandemics: ''over there'' and back again evidence of an absence: the genetic origins of the pandemic influenza virus the influenza virus: a killer comes into view antigenic and genetic characteristics of swine-origin a(h n ) influenza viruses circulating in humans pathogenesis and immunogenicity of influenza viruses with genes from the pandemic virus lifetime of plasma cells in the bone marrow humoral immunity due to long-lived plasma cells no one is naive: the significance of heterologous t-cell immunity infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over years signaling by toll-like receptors and requires bruton's tyrosine kinase antiviral cytotoxic t-cell memory by vaccination with recombinant listeria monocytogenes cell-mediated immune response of human lymphocytes to influenza a ⁄ ussr (h n ) virus infection severe deficiency of switched memory b cells (cd (+)igm(-)igd(-)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease an early humoral immune response in peripheral blood following parenteral inactivated influenza vaccination multifunctional th cells define a correlate of vaccine-mediated protection against leishmania major note for guidance on harmonization of requirements for influenza vaccines (cpmp ⁄ bwp ⁄ ⁄ ) active vaccination in patients with common variable immunodeficiency (cvid) serum bactericidal antibody response to serogroup c polysaccharide meningococcal vaccination in children with primary antibody deficiencies specific anti-influenza virus antibody production in vitro by lymphocytes from a subset of patients with hypogammaglobulinemia shu a a state key laboratory for infectious disease control and prevention, national institute for viral disease control and prevention, chinese center for disease control and prevention, beijing, china. b state key laboratory for molecular virology and genetic engineering, national institute for viral disease control and prevention roles of adjuvant igv combined with influenza m e based virus like particle in the immune response and cross protection usa) ae h at °c. tetramethylbenzidine (tmb) was applied, and the optical den epidemiology and pathogenesis of influenza epidemiology and virology of influenza illness influenza vaccine: the challenge of antigenic drift evolving strategies for the prevention of influenza infection: potential for multistrains targeting a ''universal human influenza'' a vaccine universal influenza a vaccine: optimization of m -based constructs the epitope recognized by a monoclonal antibody in influenza a virus m protein is immunogenic and confers immune protection high-epitope density in a single recombinant protein molecule of the extracellular domain of influenza a virus m protein significantly enhances protective immunity pre-clinical study of influenza virus a m peptide conjugate vaccines in mice, ferrets, and rhesus monkeys induction of influenza type a virus-specific resistance by immunization of mice with a synthetic multiple antigenic peptide vaccine that contains ectodomains of matrix protein a universal influenza a vaccine based on the extracellular domain of the m protein protective immunity against influenza a virus induced by immunization with dna plasmid containing influenza m gene protection against influenza virus challenged by topical application of influenza dna vaccine influenza a vaccine based on the extracellular domain of m : weak protection mediated via antibody-dependent nk cell activity t cell immunoglobulin mucin- crystal structure reveals a novel ligand binding surface structures of t cell immunoglobulin mucin protein show a metal-ion-dependent ligand binding site where phosphatidylserine binds structures of t cell immunoglobulin mucin receptors and reveal mechanisms for regulation of immune responses by the tim receptor family the tim gene family: emerging roles in immunity and disease th -specific cell surface protein tim- regulates macrophage activation and severity of and autoimmune disease identification of a surface glycoprotein on african green monkey kidney cells as a receptor for hepatitis a virus the igv domain of human b - (cd ) is sufficient to co-stimulate t lymphocytes and induce cytokine secretion vaccination with cell immunoglobulin mucin- antibodies and inactivated influenza enhances vaccine-specific lymphocyte proliferation, interferon-r production and cross-strain reactivity incorporation of membrane-anchored flagellin into influenza virus-like particles enhances the breadth of immune response virus-like particle induces protective immunity against homologous and heterologous strains of influenza virus site accessed on st study designs for timely estimation of influenza vaccine effectiveness using european sentinel practitioner networks a new influenza surveillance system in france: the ile-de-france ''grog''. . principles and methodology site accessed on st i-move'' towards monitoring seasonal and pandemic influenza vaccine effectiveness: lessons learnt from a pilot multi-centric case-control study in europe population and risk group uptake of h n influenza vaccine in mainland france - : results of a national vaccination campaign of global health and emerging pathogens ns deletions convert the -h n pandemic virus into a live attenuated vaccine. influenza and other respiratory viruses the influenza virus enigma vaccine production capacity for seasonal and pandemic (h n ) influenza interferon-induced isg conjugation inhibits influenza a virus gene expression and replication in human cells the multifunctional ns protein of influenza a viruses influenza a and b viruses expressing altered ns proteins: a vaccine approach multiple anti-interferon actions of the influenza a virus ns protein the ns protein of a human influenza virus inhibits type i interferon production and the induction of antiviral responses in primary human dendritic and respiratory epithelial cells immunization with live attenuated influenza viruses that express altered ns proteins results in potent and protective memory cd + t-cell responses plasmacytoid dendritic cells delineate immunogenicity of influenza vaccine subtypes regulation of adaptive immunity by the innate immune system the influenza virus ns protein: inhibitor of innate and adaptive immunity single-reaction genomic amplification accelerates sequencing and vaccine production for classical and swine origin human influenza a viruses unidirectional rna polymerase i-polymerase ii transcription system for the generation of influenza a virus from eight plasmids avian influenza (h n ) viruses isolated from humans in asia in exhibit increased virulence in mammals transmission and pathogenesis of swine-origin a(h n ) influenza viruses in ferrets and mice a naturally occurring deletion in its ns gene contributes to the attenuation of an h n swine influenza virus in chickens future influenza vaccines and use of genetic recombinants eight-plasmid system for rapid generation of influenza virus vaccines rescue of influenza b virus from eight plasmid high yield reassortants of influenza type b viruses np gene obtained from high yield donor. options for control of influenza vi. abstract # summary of status of development and availability of b ⁄ brisbane ⁄ ⁄ -like candidate vaccine viruses and potency testing reagent reassortants of influenza b viruses for use in vaccines: an evaluation preparation of influenza b virus recombinant strains genetic and phenotypic analysis of reassortants of high growth and low growth strains of influenza b virues pandemic influenza in russia: detection and molecular references evolutionary pattern of pandemic influenza (h n ) virus in the late phases of the pandemic antigenic and genetic characteristics of swine-origin a(h n ) influenza viruses circulating in humans effects of egg adaptation on the receptor-binding properties of human influenza a and b viruses the early diversification of influenza a ⁄ h n pdm update on influenza a (h n ) monovalent vaccines clinical and epidemiologic characteristics of early cases of influenza a pandemic options for the control of influenza vii virus infection, people's republic of china genome evolution of novel influenza a (h n ) viruses in humans introduction and transmission of pandemic influenza a (h n ) virus -kenya emergence of a novel swine-origin influenza a (h n ) virus in humans first season of h n influenza origins and evolutionary genomics of the swine-origin h n influenza a epidemic modeling gene sequences over time in h n influenza a virus populations differentiation of two distinct clusters among currently circulating influenza a(h n )v viruses conversion of mdck cell line to suspension culture by transfecting with human siat e gene and its application for influenza virus production trivalent mdck cell culture-derived influenza vaccine optaflu (novartis vaccines) use of mdck cells for production of live attenuated influenza vaccine flow cytometric monitoring of influenza a virus infection in mdck cells during vaccine production cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences seroprevalence following the second wave of pandemic molecular evolution of human influenza a viruses in a local area during eight influenza epidemics from evaluation of hemagglutinin subtype swine influenza viruses from the united states the early molecular epidemiology of the swine-origin a ⁄ h n human influenza pandemic the genomic and epidemiological dynamics of human influenza a virus reconstructing the initial global spread of a human influenza pandemic: a bayesian spatial-temporal model for the global spread of h n pdm mild form of h n influenza infection detected by active surveillance: implications for infection control the pandemic (h n ) swine influenza virus is mild compared to the pandemic (h n ) virus because of a prolineto-serine substitution in the receptor-binding site of its hemagglutinin -a hypothesis pathogenesis and transmission of swine-origin a(h n ) influenza virus in ferrets investigation of the first cases of human-to-human infection with the new swine-origin influenza a (h n ) virus in canada antigenic and genetic characteristics of swine-origin a(h n ) influenza viruses circulating in humans molecular evolution of hemagglutinin genes of h n swine and human influenza a viruses antigenic structure of influenza virus haemagglutinin defined by hybridoma antibodies the predicted antigenicity of the haemagglutinin of the spanish influenza pandemic suggests an avian origin genetically destined potentials for nlinked glycosylation of influenza virus hemagglutinin global patterns of influenza a virus in wild birds antigenic and genetic characteristics of swine-origin a (h n ) influenza viruses circulating in humans translatorx: multiple alignment of nucleotide sequences guided by amino acid translations raxml-iii: a fast program for maximum likelihood-based inference of large phylogenetic trees flugenome: a web tool for genotyping influenza a virus beast: bayesian evolutionary analysis by sampling trees origin and evolution of influenza virus hemagglutinin genes panorama phylogenetic diversity and distribution of type a influenza virus early alterations of the receptor-binding properties of h , h , and h avian influenza virus hemagglutinins after their introduction into mammals human influenza a h n virus related to a highly pathogenic avian influenza virus origin and evolutionary genomics of the swine-origin h n influenza a epidemic keywords novel influenza viruses, oseltamivir resistance phylogenetic analyses of pandemic influenza viruses textbook of influenza mapping the antigenic and genetic evolution of influenza virus cdc protocol of realtime rt-pcr for swine influenza a(h n ) revision the hemagglutination and hemagglutination ingibitions test. who collaborating center for surveillance molecular evolutionary genetics analysis (mega) software version . pandemic influenza: an inconvenient mutation large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution origin and evolutionary genomics of the swine-origin h n influenza a epidemic antigenic and genetic characteristics of swine-origin a (h n ) influenza viruses circulating in humans genetic subtyping using cluster analysis panorama phylogenetic diversity and distribution of type a influenza virus continuing progress towards a unified nomenclature for the highly pathogenic h n avian influenza viruses: divergence of clade . viruses the influenza virus resource at the national center for biotechnology information muscle: multiple sequence alignment with high accuracy and high throughput multiple alignment of dna sequences with mafft raxml-iii: a fast program for maximum likelihood-based inference of large phylogenetic trees flugenome: a web tool for genotyping influenza a virus evolution of influenza viral neuraminidase (na) genes revealed by large-scale sequence analysis. proceedings of the options for the control of influenza vii a quantitative genotype algorithm reflecting h n avian influenza niches xiu-feng wan a a department of basic sciences complete composition vector, influenza a virus, minimum spanning tree, phylogeny, progenitor ipminer: a progenitor gene identifier for influenza a virus avian-to-human transmission of the pb gene of influenza a viruses in the and pandemics triple-reassortant swine influenza a (h ) in humans in the united states clustal w: improving the sensitivity of progressive multiple sequence alignment through sequence weighing, positionspecific gap penalties and weight matrix choice muscle: multiple sequence alignment with high accuracy and high throughput coffee: an objective function for multiple sequence alignments the neighbour-joining method: a new method for reconstructing phylogenetic trees mrbayes: bayesian inference of phylogenetic trees basic local alignment search tool a quantitative genotype algorithm reflecting h n avian influenza niches computational identification of reassortments in avian influenza viruses ubiquitous reassortments in influenza a viruses phylip -phylogeny inference package (version . ) pandemic influenza in russia: isolation, antigenic produced in our laboratory. normal equine serum was purchased from sigma (usa) comparative data on the development of influenza pandemic in russia and in the other european countries (in russian). materials of the ii annual all-russian congress on infectious diseases isolation on . . and deposition in the state virus collection of the first strain a ⁄ moscow ⁄ ⁄ (h n )swl, similar to the swine virus a(h n ) from the first patient diagnosed in moscow isolation of influenza viruses in cell cultures and in chicken embryos and their identification. methods guidance (in russian) molecular genetic characterization of the strains of pandemic influenza a(h n )v isolated on the territory of russian federation in (in russian). materials of the ii annual all-russian congress on infectious diseases genetic and antigenic analyses of influenza a (h n ) viruses, - sialic acid receptor detection in the human respiratory tract: evidence for widespread distribution of potential binding sites for human and avian influenza viruses pandemic influenza a(h n ) virus mutations reported to be associated with severe disease antigenic and genetic characteristics of swine-origin a(h n ) influenza viruses circulating in humans barr b,c a novartis vaccines and diagnostics gmbh, marburg, germany. b who collaborating centre for reference and research on influenza co-infecting viruses in pandemic h n and seasonal influenza positive human respiratory samples emergence of a novel swine-origin influenza a (h n ) virus in humans simultaneous detection and high-throughput identification of a panel of rna viruses causing respiratory tract infections comparison of multiple commercial assays for the detection of swine-origin influenza a (h n ) virus (soiv) evidence from multiplex molecular assays for complex multipathogen interactions in acute respiratory infections performance comparison of res-plex ii and xtag rvp fast for detecting respiratory viruses clinical virology symposium communityacquired respiratory co-infection (carc) in critically ill patients infected with pandemic influenza a (h n ) virus infection bacterial co-infections in lung tissue specimens from fatal cases of pandemic influenza a (h n ) -united states a quantitative risk assessment of exposure to adventitious agents in a cell culture-derived subunit influenza vaccine john's hopkins bloomberg school of public health design of an automated laboratory for high-throughput influenza surveillance human influenza surveillance: the demand to expand influenza: an emerging disease avian-to-human transmission of the pb gene of influenza a viruses in the and pandemics proinflammatory cytokine responses induced by influenza a (h n ) viruses in primary human alveolar and bronchial epithelial cells induction of proinflammatory cytokines in human macrophages by influenza a (h n ) viruses: a mechanism for the unusual severity of human disease? influenza h n and h n virus replication and innate immune responses in bronchial epithelial cells are influenced by the state of differentiation mapping of the two overlapping genes for polypepetides ns and ns on rna segment of influenza virus genome sequences of mrnas derived from genome rna segment of influenza virus: collinear and interrupted mrnas code for overlapping proteins influenza virus ns protein inhibits pre-mrna splicing and blocks mrna nucleocytoplasmic transport the influenza virus ns protein: a novel inhibitor of pre-mrna splicing identification of cis-acting intron and exon regions in influenza virus ns mrna that inhibit splicing and cause the formation of aberrantly sedimenting presplicing complexes identification of a second protein encoded by influenza c virus rna segment influenza c virus ns protein upregulates the splicing of viral mrnas identification of an amino acid residue on influenza c virus m protein responsible for formation of the cord-like structures of the virus a mutation on influenza c virus m protein affects virion morphology by altering the membrane affinity of the protein detection of ion channel activity in xenopus laevis oocytes expressing influenza c virus cm protein evidence that the cm protein of influenza c virus can modify the ph of the exocytic pathway of transfected cells the ion channel activity of the influenza virus m protein affects transport through the golgi apparatus intracellular localization of influenza c virus ns protein (nep) in infected cells and its incorporation into virions receptor specificity, host range and pathogenicity of influenza viruses replication, pathogenesis and transmission of pandemic (h n ) virus in non-immune pigs world health organization. preliminary review of d g amino acid substitution in the haemagglutinin of pandemic influenza a (h n ) viruses observed association between the ha mutation d g in the pandemic influenza a(h n ) virus and severe clinical outcome quasispecies of the d g substitution in the hemagglutinin of pandemic influenza a(h n ) virus from patients with severe disease in hong kong a possible association of fatal pneumonia with mutations of pandemic influenza a ⁄ h n sw virus in the receptor-binding site of the ha subunit severe outcome of influenza a ⁄ h n ⁄ v infection associated with g ⁄ n polymorphisms in the haemagglutinin: a multicenter study influenza pandemic caused by highly conserved viruses with two receptor-binding variants overexpression of the alpha- , -sialyltransferase in mdck cells increases influenza virus sensitivity to neuraminidase inhibitors human and avian influenza viruses target different cell types in cultures of human airway epithelium avian-virus-like receptor specificity of the hemagglutinin impedes influenza virus replication in cultures of human airway epithelium receptor-binding specificity of pandemic influenza a (h n ) virus determined by carbohydrate microarray fields virology. philadelphia, pa: lippincott williams & wilkins the molecular virology and reverse genetics of influenza c virus identification of a second protein encoded by influenza c virus rna segment identification of a amino acid protein encoded by rna segment of influenza c virus influenza c virus cm protein is produced from a amino acid protein (p ) by signal peptidase cleavage a mutation on influenza c virus m protein affects virion morphology by altering the membrane affinity of the protein influenza c virus cm integral membrane glycoprotein is produced from a polypeptide precursor by cleavage of an internal signal sequence evidence that the matrix protein of influenza c virus is coded for by a spliced mrna functional properties of the virus ion channels the cm protein of influenza c virus is an oligomeric integral membrane glycoprotein structurally analogous to influenza a virus m and influenza b virus nb proteins characterization of a second protein (cm ) encoded by rna segment of influenza c virus phosphorylation of influenza c virus cm protein the sites for fatty acylation, phosphorylation and intermolecular disulphide bond formation of influenza c virus cm protein identification of an amino acid residue on influenza c virus m protein responsible for formation of the cord-like structures of the virus a human melanoma cell line highly susceptible to influenza c virus antigenic characterization of the nucleoprotein and matrix protein of influenza c virus with monoclonal antibodies construction of an antigenic map of the haemagglutinin-esterase protein of influenza c virus the synthesis of polypeptides in influenza c virus-infected cells new low-viscosity overlay medium for viral plaque assays the influenza virus m protein cytoplasmic tail interacts with the m protein and influences virus assembly at the site of virus budding the cytoplasmic tail of the influenza a virus m protein plays a role in viral assembly the influenza a virus m cytoplasmic tail is required for infectious virus production and efficient genome packaging distinct domains of the influenza a virus m protein cytoplasmic tail mediate binding to the m protein and facilitate infectious virus production influenza virus m ion channel protein is necessary for filamentous virion formation influenza h n virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells das inhibits h n influenza virus infection of human lung tissues receptor binding specificity of recent human h n influenza viruses differential onset of apoptosis in avian influenza h n and seasonal h n virus infected human bronchial and alveolar epithelial cells: an in vitro and ex vivo study human influenza virus a ⁄ hongkong ⁄ ⁄ (h n ) infection induction of proinflammatory cytokines in human macrophages by influenza a (h n ) viruses: a mechanism for the unusual severity of human disease? proinflammatory cytokine responses induced by influenza a (h n ) viruses in primary human alveolar and bronchial epithelial cells differential onset of apoptosis in influenza a virus h n -and h n -infected human blood macrophages avian flu: influenza virus receptors in the human airway haemagglutinin mutations responsible for the binding of h n influenza a viruses to humantype receptors an avian influenza h n virus that binds to a human-type receptor evolution of highly pathogenic h n avian influenza viruses in vietnam between evolutionary dynamics and emergence of panzootic h n influenza viruses writing committee of the second world health organization consultation on clinical aspects of human infection with avian influenza a (h n ) virus recent avian h n viruses exhibit increased propensity for acquiring human receptor specificity a simple screening assay for receptor switching of avian influenza viruses glycan topology determines human adaptation of avian h n virus hemagglutinin h n chicken influenza viruses display a high binding affinity for neu acalpha - galbeta - ( -hso )glcnac-containing receptors a strain of human influenza a virus binds to extended but not short gangliosides as assayed by thin-layer chromatography overlay search for additional influenza virus to cell interactions avian flu: isolation of drug-resistant h n virus the surface glycoproteins of h influenza viruses isolated from humans, chickens, and wild aquatic birds have distinguishable properties this study was supported by the li ka shing foundation, the national institutes of health (niaid contract hhsn c), and the area of excellence scheme of the university grants committee (grant aoe ⁄ m- ⁄ ) of the hong kong sar government. this work was supported by the national institute of allergy and infectious diseases (niaid) contract hhsn c, the li ka shing foundation, and we thank all french and vietnamese field staff involved in the data collection in viet nam for their enthusiasm and support and we are grateful to the pig farmers participating in the study for their cooperation and patience. this study was a part of the gripavi project and was funded by the french ministry of foreign affairs. this research was supported in part by the national institute of allergy and infectious diseases (niaid) contract hhsn c and the area of excellence scheme of the university grants commission (grant aoe ⁄ m- ⁄ ) of the hong kong sar government. we acknowledge the food and environmental hygiene department of hong kong for facilitating the study. this work was supported by the national institute of allergy and infectious diseases (niaid) contract hhsn c, the li ka shing foundation, and the area of excellence scheme of the university grants committee (grant aoe ⁄ m- ⁄ ) of the hong kong sar government. we gratefully acknowledge our colleagues from iiii, shantou university and skleid, hku for their excellent technical assistance. the study was supported by the rfcid commissioned study (lab# ) from research fund secretariat, food and health bureau, hong kong sar; area of excellence scheme of the university grants committee (grant aoe ⁄ m- ⁄ ), hong kong sar; and by niaid contract (sjceirs, hhsn c), nih, usa.ferrets in all groups inoculated with a ⁄ turkey ⁄ ⁄ virus survived the infection and were observed once daily for days. below lower limit of detection (< ae log eid ⁄ ml).statistical cutoff of ic values for nai susceptibility, determined by x ae + iqr. outliers with ic above this cutoff and > times the mean ic for each drug were characterized as extreme outliers; those with known drug-resistance mutations such as h y were classified as resistant and analyzed separately. h wildtype, oseltamivir-susceptible isolates. h y variants, oseltamivir-resistant virus isolates. iqr, interquartile ranges; nai, neuraminidase inhibitors. we wish to thank our collaborators in the who global influenza surveillance network and united states public health laboratories for the submission of virus isolates and clinical specimens. we also thank our colleagues from the virus reference team and the influenza sequence activity, influenza division, cdc, for their valuable technical assis-the findings and conclusions of this report are those of the authors and do not necessarily represent the views of the centers for disease control and prevention (cdc). we are indebted to yonas araya, theresa wolter, and ivan gomez-osorio for their excellent laboratory techniques and animal handling assistance. we would like to thank andrea ferrero for her laboratory managerial skills. this research was possible through funding by the cdc-hhs grant ( u ci ), niaid-nih grant, (r ai ), csrees-usda grant ( - ), and niaid-nih contract (hhsn c). we thank c bazzoli for advice. this work was supported by a grant from the european union fp project flu-modcont (no. ). we thank staff at seoul, incheon, daejeon, gwangju, gangwon, and jeonbuk provincial research institute of health and environments for their laboratory testing. additionally, we would like to acknowledge the contributions of participating sentinel doctors for evaluating the new rat kit. this study was supported by a grant from the korea cdc. we thank roche applied science for providing the materials and equipment for this evaluation. this research was supported in part by the national institute of allergy and infectious diseases (niaid) contract hhsn c and the area of excellence scheme of the university grants committee (grant aoe ⁄ m- ⁄ ) of the hong kong sar government. the authors would like express their sincere thanks to cdc, usa for supporting the routine surveillance of ili in we would like to acknowledge the australian red cross blood service (the blood service) and the australian government, which fully fund the blood service for the provision of blood products and services to the australian community. we also wish to thank the donors and staff of the blood service, who have assisted in provision of specimens for testing in this protocol, as well as the staff at the who we are grateful to liping long for her assistance in map generation. this project was supported by nih niaid rc ai . cz is supported partially by canadian nserc postdoc fellowship. the authors thank the national investigation team based at the national institute of health (istituto superiore di sanita'), italy (in particular antonino bella, maria cristina rota, stefania salmaso) for providing their support in data collection, and the european union this study was supported in part by a grant-in-aid ( ) and the special coordination funds for promoting science and technology of ministry of education, science, sports and culture of japan. this study was supported in part by a grant-in-aid from the ministry of education, science, and culture of japan ( ) and the special coordination funds for promoting science and technology of mext of japan. the work described here was supported by phs grant ai- (jam) and alsac. we thank all authors for their participation in data gathering and analysis, and in writing this manuscript. the studies were funded by gsk consumer healthcare, and gsk investigators were involved in all stages of the study conduct and analysis. py, po, dw and kb are employees of glaxosmithkline. this study was funded by glaxosmithkline. we thank all authors for their participation in data gathering and analysis, and in writing this manuscript. the studies were funded by gsk consumer healthcare, and gsk investigators were involved in all stages of the study conduct and analysis. this study was funded by glaxosmithkline. we thank all authors for their participation in data gathering and analysis, and in writing this manuscript. the stud- authors are thankful to path for the financial support of this research. we would like to acknowledge jessica d'amico and dr. rick bright of path for their editorial review. this study was supported by path. the authors would like to thank rick bright, jessica d'amico, and vadim tsvetnitsky for editing assistance. the we thank dr. m. enami (kanazawa university) for generously providing plasmids containing cdnas to influenza a virus m and ns genes. we also gratefully thank dr. r. sho (department of public health, yamagata university faculty of medicine) for statistical analysis. some data shown in this study have also been presented in the reference paper. this work was supported in part by a grant-in-aid for scientific research from the ministry of education, culture, sports, science, and technology, japan, takeda science foundation, terumo life science foundation, and a grant-in-aid from the global coe program of the japan society for the promotion of science. we thank markus eickmann for his help in isolation and initial characterization of a ⁄ hamburg ⁄ ⁄ and for providing antisera against h n pdm. this study was supported by the european union fp global a(h n ) genetic characterization, molecular evolution dynamics, antiviral susceptibility profiles, and inference of public health implications require nation and region wide systematic analysis of circulating virus. in this study we analysed the genetic and antiviral drug susceptibility profiles of pandemic a(h n ) influenza virus circulating in portugal. genetic profile analysis was performed in isolates to the hemagglutinin (ha), neuraminidase (na) and mp genes, and in six of these isolates the pb , pb , pa, np and ns genes were also analysed. antiviral drug susceptibility profile was analysed for isolates, phenotypically and genotypically to neuraminidase inhibitors (nai) and genotypically to amantadine. the point mutations identified in ha, na, and mp genes of different strains do not seem to evidence an evolutionary trend. this is in agreement with the genetic and antigenic homogeneity that has being described for a(h n ) virus. all analysed strains were found to be resistant to amantadine, and five of these strains exhibited a reduced susceptibility profile to nai, three only for oseltamivir and two for both inhibitors. introduction: the dynamics of pandemic influenza a ⁄ h n compared to seasonal strains of influenza is not clearly understood. it is important to understand the patterns of viral shedding and symptoms over time in community-based infections.materials and methods: household infections were followed-up in two large community-based studies. patterns of viral shedding, symptoms and signs, and tympanic temperature were plotted over time and grouped according to strain for analysis.results: the patterns of viral shedding, symptoms and signs, and tympanic temperature in three influenza a strains (pandemic a ⁄ h n , seasonal a ⁄ h n , and seasonal a ⁄ h n ) were comparable. peak viral shedding occurred close to the onset of symptoms and resolved after - days. patterns of viral shedding in influenza b virus infections differed.discussion: the patterns of viral shedding and clinical course of pandemic influenza a ⁄ h n infections were broadly similar to seasonal influenza a ⁄ h n and a ⁄ h n . only the clinical course of seasonal influenza b infections was similar to pandemic influenza a ⁄ h n . the dynamics of pandemic influenza a ⁄ h n were observed to be largely alike to the dynamics of seasonal influenza a ⁄ h n and a ⁄ h n . the coated respirators inactivated a broad range of influenza strains within minute, including the pandemic strain and human, swine, and avian influenza viruses. antiviral effectiveness was not reduced by hot, humid conditions or repeated saturation, which might occur during prolonged use of respirators. in contrast, infectious virions were detected on the surfaces of all uncoated ffp respirators, and could be transferred to glove surfaces during handling of contaminated masks. growth of the viruses was monitored by ha titer using turkey red blood cells, by quantitative real time rt-pcr (qrt-pcr) to detect the influenza a matrix gene, and also by flow cytometry to detect virus positive cells using monoclonal antibodies (imagen influenza virus a and b). , matrix gene copy number was determined using qrt-pcr and analysed using the sequence detection software on a fast system sds (applied biosystems, california, usa). further characterisation was performed through sequence analysis and the ha inhibition (hai) assay. sequence analysis was performed using dnastar and all sequences obtained were compared with the sequence of either the original clinical specimen if available or the conventional atcc derived mdck cell isolate. the hai assay was used to characterize the viruses against a panel of known standard reference viruses and their homologous ferret antiserum.options for the control of influenza vii abstract background: we measured the cross-reactive antibody response to pandemic h n in children and adults before and after vaccination with [ ] [ ] [ ] [ ] influenza season vaccines as part of the rapid public health response to the emergence of ph n and to provide evidence for ph n vaccination policy development in mainland china. materials and methods: archived serum specimens from previous vaccine studies were detected by hemagglutination inhibition assay. results: limited crossreactive antibody response to ph n had been detected among participants of all age groups before and after they had been vaccinated with - , - influenza seasonal vaccines. vaccination with seasonal influenza viruses resulted in limited seroconversion to ph n in all age groups, compared with - % of seroconversion to seasonal influenza viruses. but similar to recent studies, a peak of cross-reactive antibody response to ph n was observed in % and % of participants born from to before and after vaccination. conclusions: in order to protect our populations in china, our study strongly suggests vaccination with ph n is required in all age groups and that older populations born before may be associated with a lower infection rate of ph n . on april and april , , cases of ph n were identified in specimens obtained from two epidemiologically unlinked patients in the united states and soon thereafter in texas and mexico. since that time, the virus has spread across the globe. assessment of cross-reactive antibody response to the ph n after vaccination with sea-sonal influenza vaccine was first reported from us centers of disease control and prevention (us cdc). according to their results, the seasonal influenza vaccines provided little or no protection against the ph n , but some degree of preexisting immunity to the virus existed, especially among adults aged ‡ years. in this study, using archived serum samples from previous vaccine studies, we measure the level of cross-reactive antibody response to ph n in children and adults vaccinated intramuscularly with trivalent inactivated vaccine developed for the northern hemi- serum specimens were collected and provided by provincial centers for disease control and prevention of china as a public health response to the emergence of ph n exempt from human-subjects review. a total of serum samples were collected from xinjiang uygur autonomous region, yunnan, and shandong provinces. all the serum specimens were grouped by the age of subjects ( - , - , - , ‡ years) and by different influenza seasons.hemagglutination inhibition assay was performed according to standard procedures in this study. [ ] [ ] [ ] as with h n components of the vaccine, the seasonal influenza viruses used in this study were a ⁄ solomon islands ⁄ ⁄ and a ⁄ brisbane ⁄ ⁄ . the ph n influenza virus used in this study was a ⁄ california ⁄ ⁄ provided by us cdc. all the viruses were propagated in specific pathogenfree embryonated chicken eggs and inactivated by & paraformaldehyde. the criteria recommended by the european agency for the evaluation of medical product was applied for the assessment of seasonal influenza vaccine gmt, geometric mean titer; hi, hemagglutination inhibition. three weeks after boosting immunization, spleens were harvested from immunized and control mice. splenocytes were prepared by lymphocyte separation media (ez-sepÔ, shen zhen, china). the cells were washed and resuspended in complete rpmi- containing fetal bovine serum (hyclone, logan, ut, usa), glutamax, um b-me. splenocytes were cultured in vitro in the presence of inactivated h n , h n , h n , and h n influenza virus antigen for h. quick cell proliferation assay kit (biovision, san francisco, ca, usa) was used to detect the cell proliferation. the - nm absorbance was read on a plate reader. all experiments have been repeated at least three times.results are presented as mean standard error of the mean (sem). comparison of the data was performed using the student's t-test. significance was defined as a p value of < ae . to evaluate the adjuvant effect of recombinant igv, the anti m e antibody subclasses was measured. igg and igg a were detected after the first and second immunization ( table ). the ratio of igg a ⁄ igg was calculated. immunization with only m e-hbc showed a lower igg a ⁄ igg ratio < ae . igv combined with m e-hbc led to a high igg a ⁄ igg ratio of up to - after first and second immunization. these igg subclass distributions indicated that igv can induce a th immune response. to determine whether the splenocytes were stimulated in vitro with different subtypes of inactivated influenza antigen after the igv plus m e-hbc antigen immunization, h n , h n , h n , h n inactivated antigen was used table . the serum igg, igg , igg a, and igg a ⁄ igg ratio were measured by elisa after first and second immunization. m e were coated on the wells plate overnight, and serial dilution sera of day , , after first and second immunization were added , ae , , , , ug ⁄ ml of igg, igg , igg a purified antibody were also added for obtaining the standard curve. hrp-labeled goat anti-mouse igg, igg , or igg a was then added, washed, and the optical density was read at nm. the results were showed at mean ± sem. day after first immunization days after second immunizationoptions for the control of influenza vii the french grog (groupes régionaux d'observation de la grippe) early warning network collects more than specimens yearly from cases of acute respiratory illness (ari), using two sampling methods: systematic randomized and non systematic ''ad hoc'' sampling. although vaccines against influenza a virus are the most effective method by which to combat infection, it is clear that their production needs to be accelerated and their efficacy improved. a panel of recombinant live attenuated human influenza a vaccines (laivs), including ns - , ns - , nsd , were generated by rationally engineering mutations directly into the genome of a pandemic-h n virus. the vaccine potential of each laiv was determined through analysis of attenuation, immunogenicity, and their ability to protect mice and ferrets. the data indicate that the novel nsd -laiv was ideally attenuated and elicited strong protective immunity. this study also shows that attenuating mutations can be rapidly engineered into the genomes of emerging ⁄ circulating influenza a viruses in order to produce laivs. the influenza virus exhibits complicated evolutionary dynamics due to multiple reasons, such as diverse hosts, high mutation rates, and rapid replications. in this study, large-scale analyses of influenza neuraminidase (na) sequences revealed influenza a and b na genes diverged first around years ago, and subsequently the na subtypes of influenza a emerged around years ago. all nine na subtypes of influenza a were genetically distinct from each other, with a total of lineages identified. in addition, five and three sub-lineages were further identified in lineage a of na and lineage b of na , respectively. the majority of lineages and sub-lineages were found to be host or geographic specific. this study provides not only a better understanding of influenza na evolution, but also a database of lineages and sub-lineages that can be used for early detection of novel genetic changes for improved influenza surveillance. although phylogenetic approaches are commonly used and often found to be powerful, how to accurately identify lineages or sub-lineages of a gene segment of the influenza a virus remains a challenging issue. in this study, we address this issue by analyzing hemagglutinin (ha) sequences using a combination of statistical and phylogenetic methods. following a hierarchical nomenclature system that uses a letter to represent a lineage and a digit for a sub-lineage, we identified distinct lineages and sub-lineages in all ha subtypes through large-scale analyses of influenza a hemagglutinin sequences. the majority of the lineages or sub-lineages were host or geographic specific or both. further analysis of other segments will allow us to construct a comprehensive database for influenza a lineages and genotypes, facilitating early detection of new viral strains and genome reassortments and hence improve influenza surveillance. identification of the genetic origin of influenza a viruses will facilitate understanding of the genomic dynamics, evolutionary pathway, and viral fitness of influenza a viruses. the exponential increases of influenza sequences have expanded the coverage of influenza genetic pool, thus potentially reducing the biases for influenza progenitor identification. however, these large amounts of data generate a great challenge in progenitor identification. clinical (nasopharyngeal swabs) and post-mortem materials (fragments of trachea, bronchi, lungs, spleen) were obtained from clinics and ⁄ or out-patients from st. petersburg and from base virological laboratories (bvls) of the research institute of influenza in different regions of the country, which cover approximately ⁄ of the territory of russia. the informed consent for the bio-materials collection and studies was obtained from research subjects or from their relatives in cases of post-mortem materials. isolation of viruses was carried out in the mdck cell culture (cdc, atlanta, ga, usa) and in -day-old chicken embryos (e). isolation was done according the standard internationally accepted methods. the reaction of hemagglutination (ha) and the inhibition of hemagglutination (hai) were performed according the who recommended standard method. for the identification of epidemic isolates, we used the hyperimmune diagnostic bovine or ovine antisera annually obtained from the who reference center (cdc). for a detailed antigenic analysis we used the hyperimmune rat antisera against epidemic and reference influenza strains during the period from july , up to april , , we have obtained swabs from clinics and out-patients in st. petersburg and swabs from the bvls. in this period, rather high incidence of lethality from pneumonia was observed, which developed on the background of the pandemic flu h n v. thus, we received from bvls postmortem materials from deceased patients which manifested pcr+ influenza h n v-specific rna. all materials were tested for a possibility of isolation of influenza virus h n v both in eggs and in mdck cells. pcr-negative materials were discarded. we isolated strains of pandemic influenza from the materials collected in st. petersburg and region, which comprised ae % of the total number of analyzed samples. at the same time, we did not isolate any other sub-types of influenza in the season - except the pandemic flu. from the swabs purchased from bvls, strains were isolated, which compose ae % of the pcr+ samples, and strains from the post-mortem materials ( ae % of the pcr+ samples).altogether in the season - , we isolated, retrieved, and analyzed in hai influenza strains. ae % of them were pandemic strains a(h n )v, and only ae % influenza b viruses. these data together with the epidemiologic data and the results of pcr-diagnostic provide evidence in favor of nearly mono-etiological character of epidemic season - in russia for pandemic influenza a(h n )v.though the isolation of pandemic viruses was fulfilled in two traditional model systems, in the case of pandemic virus, we could observe the tendency of preferential multiplication in embryos compared to mdck, especially in cases of post-mortem material for which chicken embryos are the preferential system of isolation.h n v viruses, which were isolated and passaged in mdck, even with significant ha titers, quickly lost their ha activity provided they were kept at + °c. moreover, some other tested cell lines proved to be practically nonsensitive to the pandemic viruses h n v. we used hai reaction for the typing and antigenic characterization of isolated viruses. in the course of isolation of viruses in the reported period, we produced rat polyclonal antisera to the strains a ⁄ california ⁄ ⁄ and a ⁄ st. petersburg ⁄ ⁄ (h n )v and the antisera to the strains a ⁄ new jersey ⁄ ⁄ -the virus isolated during the epidemic in the united states and also of the swine origin -and to the 'swine' strains a ⁄ sw ⁄ ⁄ and a ⁄ iowa ⁄ ⁄ . the hai results of representative strains are given in figure . table shows that the isolated strains were homogenous in their antigenic properties and interacted with the diagnostic antiserum cdc for a(h n )v and also with the antisera to the strains a ⁄ california ⁄ ⁄ and a ⁄ st. petersburg ⁄ ⁄ up to - ⁄ homologous titer. viruses that were isolated from post-mortem materials did not differ by their antigenic characteristics from those isolated from swabs of live patients. only two strains could be attributed to the drift-variants of the strain a ⁄ california ⁄ ⁄ because they reacted with the appropriate antiserum up to ⁄ homologous titer; these strains were a ⁄ pskov ⁄ ⁄ and a ⁄ belgorod ⁄ ⁄ . it is interesting that the isolated strains reacted with the antisera to the strains a ⁄ new jersey ⁄ ⁄ and a ⁄ sw ⁄ ⁄ to ⁄ - ⁄ , and some particular strains even to ⁄ homologous titer. it is even more interesting that some pandemic isolates reacted with the antiserum to the strain iowa isolated in up to ⁄ - ⁄ homologous titer. despite of the fact that since the outbreak of 'swine flu' in the usa in new jersey years had gone (and for the strain iowa this period is nearly years) the ha of these viruses and of the pandemic influenza share some common antigenic determinants as was shown in hai.one more interesting feature of a considerable part of isolated strains is their capability to react with high titers with normal equine serum heated to and to °c, while all the strains of swine origin isolated earlier were inhibitor-resistant ( figure ). russian isolates of divided, in this respect, in two clear and approximately equal in number groups: one of them is similar to the reference strain amino acid substitutions, among them more than were disclosed in antigenic sites, so the degree of similarity to this strain is %. a new site of glycosylation was also discovered in the position of ha. essential distinctions of the aminoacid sequence of ha and antigenic properties of the h n v strains as compared with actual circulating and vaccine strains is one of the factors that determine the pandemic potential of this new influenza virus.according to the literature, the mutation in the ha gene d g could cause a broadening of the spectrum of receptor specificity of influenza virus by the acquisition of the capacity to bind both the residues a( fi ) and a( fi ) of the sialic acid of cellular receptors. both types of receptors are present at the human respiratory tract, but in different parts of it, and they exist in different proportions. according to the data of the european center of disease control and prevention (ecdc), the varieties g of the h n v virus were isolated in countries from subjects deceased of influenza or who suffered a severe form of illness, as well as from those who sustained only a light course of influenza. concerning the strains isolated in rii, this mutation was discovered in nine cases: four were isolated from live patients and five from post-mortem materials. thus, there are no convincing data at present that could prove a causal relationship of the given substitution and the aggravation of a disease course. this is in accordance with previous observations. concerning the resistance of studied strains to the widely used antiviral preparations, it was shown that all tested strains possessed the substitution s n in the m protein that determine the resistance to adamantanes. there was no substitution in the position of neuraminidase (na), which determines the resistance to oseltamivir (h y). these substitutions are the characteristic indices of the eurasian lineage of swine influenza viruses. thus all studied russian h n v isolates were resistant to adamantanes (rimantadine) and sensitive to oseltamivir. respiratory clinical samples taken in and that tested positive by real time reverse transcription (rt)-pcr for seasonal influenza viruses (a and b) and pandemic h n respectively were assessed for other respiratory viruses using the resplex ii panel ver . system distributed by qiagen. results showed that co-infections with another respiratory viruses were relatively rare, with a small number of samples having another co-infecting virus present, very few samples having two other viruses detectable in their samples, and none with further viruses. this low number of co-infecting viruses and the ability of certain cell lines not to support infection with particular viruses may make primary isolation of influenza viruses in cell lines easier than might have been thought previously. cm is the second membrane protein of influenza c virus and is posttranslationally modified by phosphorylation, palmitoylation, n-glycosylation, and dimer ⁄ tetramer formation. in the present study, we generated rcm -c a, a recombinant influenza c virus lacking cm palmitoylation site, and examined viral growth and viral protein synthesis in the recombinant-infected cells. the rcm -c a virus grew less efficiently than did the wild-type virus. membrane flotation analysis of the infected cells revealed that less np was recovered in the plasma membrane fractions of the rcm -c a-infected cells than that in the wild-type virus-infected cells, suggesting that palmitoylation of cm is involved in the affinity of the ribonucleoprotein complex to the plasma membrane, leading to the efficient generation of infectious viruses. influenza c virus has seven single-stranded rna segments of negative polarity, encoding pb , pb , p , haemaggluti- both the a , linkage and its topology on target cells were critical for human adaptation of influenza a viruses. the binding preference of avian flu virus h n ha to the a , -linked sialylated glycans is considered the major factor that limited its efficient infection in human. currently, the switch in binding-specificity of human h n viruses from a , to a , -glycans did naturally occur, and limited humanto-human transmission was found. to monitor their potential adaptation in the human population, receptor-binding specificity surveillance was made in china. here, the binding specificity of human h n virus strains isolated from to was demonstrated. dual binding preference to a , and a , -glycans were found in a ⁄ guangdong ⁄ ⁄ and a ⁄ guangxi ⁄ ⁄ . furthermore, both of them showed a high affinity to the long-branched a , -glycans, which predominate on the upper respiratory epithelial in human. our data suggests that the existence of h n virus with binding specificity to humans should be of concern.introduction via envelope glycoprotein hemagglutinin (ha), influenza viruses bind to cell-surface glycosylated oligosaccharides terminated by sialic acids (sa) where their linkage is celland species-specific. differential receptor binding preference is a host barrier for influenza virus transmission. although most h n viruses have low affinity to neu aca , gal (human-type) receptor, recent findings suggested that the adaptation of h n virus to human by mutations in the receptor-binding site (rbs) do indeed happen and resulted in enhanced affinity to human-type receptor. [ ] [ ] [ ] in contrast to its putative precursor, a ⁄ gs ⁄ gd ⁄ ⁄ , diverse genotypes were presented in currently circulating h n virus, accelerating evolution and widespread occurrence. , to date, distinct phylogenetic clades ( - ) were identified based on h n ha, and the confirmed human infections were caused by clade , , ae , ae , ae , and . in china, human h n disease was mostly caused by clade ae ae , which was identified in isolates from confirmed patients from provinces since . clade and clade ae are responsible for the case in and , respectively. two current cases of and were due to clade ae ae . now information on receptor property has been documented in some h n viruses of clade , ae , and ae . [ ] [ ] [ ] little is known about h n virus of clade ae ae , particularly from human.recently, a , -specific sialidase-treated red blood cell (rbc) agglutination assay was developed and used for receptor specificity screening of h n virus. , the a , or a , -binding preference can be distinguished by the change of hemagglutination titer reacted with rbcs and enzymatic rbcs. since fine receptor specificity existed in h n viruses, , the glycan array including sulfated-, fucosylated-, linear sialosides, di-sialosides, or direct binding assay with synthetic polyacrylamide (paa)-based sialylglycopolymers was also recommended for the receptor-specificity surveillance on h n viruses. furthermore, the long-branched a , sialylated glycans were currently identified to predominate on the upper respiratory epithelial in human and the recognition of this topology, ¢sln-ln is the key determinant for the human-adaptation of influenza a virus. here, we analyzed the receptor-binding specificity of human h n viruses isolated in china from to . since , a total of h n infection cases were confirmed in china from provinces. the pharyngeal swabs and lower airway aspirations from the patients were collected within days after disease onset, maintained in viral-transport medium, and tested within hours.options for the control of influenza vii key: cord- -axr qu authors: rolland, john s. title: covid‐ pandemic: applying a multi‐systemic lens date: - - journal: fam process doi: . /famp. sha: doc_id: cord_uid: axr qu the covid‐ pandemic has a pervasive effect on all aspects of family life. we can distinguish the collective societal and community effects of the global pandemic and the risk and disease impact for individuals and families. this paper draws on rolland’s family systems illness (fsi) model to describe some of the unique challenges through a multi‐systemic lens. highlighting the pattern of psychosocial issues of covid‐ over time, discussion emphasizes the evolving interplay of larger systems public health pandemic challenges and mitigation strategies with individual and family processes. the paper addresses issues of coping with myriad covid‐ uncertainties in the initial crisis wave and evolving phases of the pandemic in the context of individual and family development, pre‐existing illness or disability, and racial and socioeconomic disparities. the discussion offers recommendations for timely family oriented consultation and psychoeducation, and for healthcare clinician self‐care. the novel coronavirus- pandemic presents unique challenges for individuals and families. with the current lack of an effective treatment or a preventive vaccine, all aspects of life are affected (luttik et al, ) . stringent mitigation efforts, such as social distancing, household quarantine, facemasks, vigilant hand washing, and avoidance of public gatherings and transportation were instituted in the united states in march and are likely to continue in some form for the foreseeable future. the covid- pandemic has unmasked the stark reality and profound health and economic consequences of glaring socio-economic and healthcare disparities. risks for morbidity and mortality vary enormously by social location, in particular, race, social class, gender, age, ability, and geographic location (cdc, ; price-haywood et al, ) . with infection, the course, and recovery or fatality. with a pandemic individuals and families are continually dealing with developments at all levels. it is useful to inquire about and frame adaptation in those terms. most people focus on their local situation and risks in their daily lives, job, family, and social network -getting food, medicine, and other needs. this discussion will highlight the individual and family experience. also, this paper is written in the midst of the pandemic when some of the emerging issues, such as if and when of second or third waves/spikes of cases, the timing of a vaccine or economic recovery, and the ultimate scale of emerging mental health and psychosocial impact remain uncertain (amsalem, dixon, & neria, ; wanga et al, ) . how can we organize this complex covid- landscape in a manner helpful to families and clinical practice? the family systems-illness (fsi) model (rolland, ; ; ) provides a useful framework for assessment and treatment with families dealing with a range of serious and chronic illness and disability, including infectious disease. (see rolland [ ] for useful resources, practice guidelines and case examples). the fsi model is grounded in a strengths-orientation, viewing family relationships as a potential resource and emphasizing possibilities for resilience and growth (walsh, ) . seeing the family as the interactive focal point, this approach attends to the systemic interaction between an illness and family that evolves over time. the goodness of "fit" between the psychosocial demands of a particular condition over time and the family style of functioning and resources is a prime determinant of successful versus dysfunctional coping and adaptation. the fsi model focuses on three dimensions of experience: ) a psychosocial typology of this article is protected by copyright. all rights reserved chronic conditions; ) major time phases in their evolution; and ) key family system components. in addition to communication processes and organizational/structural patterns, particular emphasis includes: family and individual life course development in relation to the time phases of a disorder; multigenerational legacies related to illness and loss; and belief systems (including influences of culture, ethnicity, race, spirituality, and gender) (figure ). place figure about here covid- is a novel coronavirus infectious disease. to create a normative context for the pandemic experience, families can benefit from a psychosocial map as they navigate overwhelming challenges. first, the psychosocial map offers an understanding of covid- in systems terms, which explicates the expected (or uncertain) pattern of practical and emotional demands of this disease over the course of the pandemic. second, such maps are helpful for families in understanding systemic processes. in the fsi model, illness patterning can vary in terms of type of: ) onset (acute or gradual) ) course (resolves versus progressive, constant, relapsing) ) outcome (non-fatal to fatal) ) type and degree of disability or complications ) level of uncertainty about its trajectory. some diseases have clear-cut predictable patterns; such as als, which is gradual onset, progressive, disabling, and fatal. by contrast, covid- manifests in a variety of unpredictable ways. for most, it is not a chronic illness, but for some it has long-term health consequences. for some, it is fatal. despite significant risk differences related to social location, age, and health status, anyone can be infected and then can transmit covid- ; anyone may develop a severe case and may die. unlike other infectious diseases that run their course in known timeframes or are seasonal and/or regional, currently there is no known endpoint to the covid- pandemic. this uncertainty and indeterminate timeframe are particularly taxing in a cumulative way -pandemic fatigue. further, data is accumulating that recovery can be protracted and result in long-term medical complications - this article is protected by copyright. all rights reserved cardiovascular, pulmonary, and neuropsychiatric are among the most common (long et al, ; varatharaj et al, ) . in the united states, six in ten adults have a chronic illness (nccdphp, ) , which medically heightens their risk of getting covid- and increases the risk, to varying degrees, of a severe case and mortality. one in four adults have a chronic disability. the pandemic magnifies longstanding prejudices toward those with disability, stigmatizing and treating them as inferior. many in the disability community fear that their lives would be expendable in circumstances of a shortage of adequate covid- testing, icu beds, respirators, and response resources. ageism contributes to attitudes that older persons are expendable. compared with younger and disease-free individuals, older adults and those with preexisting chronic conditions must grapple with higher risk of complications and deciding their acceptable social risk as covid- restrictions are relaxed. individuals and families with an already chronically ill or disability-challenged member may be far less able to absorb the added caregiving burdens if either an affected member or a primary caregiver develops covid- . uncertainties and unknowns abound with covid- . perhaps the most challenging are the facts that transmission is invisible and many individuals that carry the disease, maybe even most, are asymptomatic, yet contagious. these disease characteristics heighten the experience of living with risk and anticipatory loss (rolland, ; ) . for example, the ambiguity of being at risk versus an asymptomatic carrier would increase fears of transmitting covid- to an older or chronically ill at risk family member. the importance of viral load (the concentration of virus in saliva) in covid- severity is established, but the length of exposure and the level of viral load needed for infection to occur are still ambiguous. further, the incubation period, although on average five days, can vary from two to fourteen days. technically, this means that if someone wants to visit an individual at higher risk beyond the socially distanced visit they should consider self-quarantine for fourteen days beforehand. for many families this is not feasible or realistic. now the discussion is about safe "social pods" visiting with others who are practicing safe protections. this article is protected by copyright. all rights reserved ) unpredictable course. some who are infected seem fine then progress rapidly to a lifethreatening state (see the case description below). some appear to be improving and then take a turn for the worse. this necessitates ongoing monitoring and vigilance by family members for a protracted period. ) uncertainty regarding long-term complications (e.g. cardiac, respiratory, cns). recovery has proven slow and ongoing complications may occur, even in those who were asymptomatic. this puts the affected member and family members into a protracted period of limbo. they don't know what will be the eventual new normal. key questions for families include: "what caregiving and role functions may need longer-term reevaluation?" and "what additional economic strains would this create?" larger collective public health uncertainties include: ) who has been infected? who has immunity and for how long? antibody status and degree and length of time of protection from antibodies are not yet well understood (robbiani, et al ) . ) how long until an effective and widely available vaccine emerges or until herd immunity (roughly % of total population has developed antibodies) negate the impact of the disease? despite some horrific initial spikes, such as new york city, the proportion of individuals that have been infected with covid- in these hot spots is only % of the population. ) incidence and fatality trends can improve in one region, but then spike in another region. a second or third wave of resurgence is very likely, unless widespread readily accessible testing and contact tracing are implemented, and the public adheres to ongoing and shifting precautions. as of july , we are seeing the dire consequence of too rapid state-level relaxation of restrictions and resulting widespread disregard of key precautions (e.g. mask usage). ) without strong national leadership, regulations, and guidelines, regional improvements and surges can occur independently. from a public health standpoint, often divergent and sometimes politically motivated state-based regulations are epidemiologically nonsensical. locally, individuals and their families lack clear, consistent information and guidelines. this chaotic process is both medically dangerous and psychologically exhausting. this article is protected by copyright. all rights reserved these myriad individual and population level uncertainties have significant impact on and implications for families. as this is written in july , the cumulative mental and physical health consequences of this "pressure cooker" existence are just beginning to emerge (killgore et al, ; wanga et al, ) . living well with illness uncertainties and threatened loss (rolland, ; ) entails acknowledging the possibility of loss, sustaining hope, and building flexibility into planning that can accommodate changing circumstances. similar to living with chronic illness, the metaphor that living with the uncertainties of the pandemic is a marathon not a sprint is apt and clinically useful. systemic racism has a profound impact on covid- susceptibility. july cdc data reveals that latinx and african-americans are three times as likely to become infected with covid- as their white neighbors throughout urban and rural regions of the united states and across all age groups. and, they are twice as likely to die from the disease as white people. native american people also experience similar disparities. lower income families, disproportionately african-american, latinx, and immigrant, rely on income from members working in job conditions at high risk of infection. crowded multigenerational living conditions makes social distancing difficult in households (cdc, ). living with racial residential segregation, at a distance from healthcare facilities and grocery stores, makes it harder to get needed care or garner supplies for stay-at-home precautions. lower income families' livelihoods require leaving home and taking public transportation daily to work in the service sector, factories, and/or other crowded conditions, where personal safety is often compromised for the sake of a paycheck needed for family survival. these families live with the daily fear that covid- will be brought into the home from work settings and travel to and from work. the ability of most whitecollar desk jobs to be accomplished remotely has provided double protection -preventing covid- infection and keeping one's job. this is a huge advantage over jobs requiring physical presence. dr. anthony fauci, the director of the national institute for allergy and infectious diseases, stated at a us congressional hearing (june , ) that the coronavirus has been a "double whammy" for african-americans, because they are more likely to be exposed to the disease by way of their employment in jobs that cannot be done remotely. second, they are more vulnerable to severe illness this article is protected by copyright. all rights reserved from the coronavirus because they have higher rates of underlying conditions like diabetes, high blood pressure, obesity and chronic lung disease (bolin & kurtz, ; cunningham et al, ) . these individuals often lack health insurance or are under-insured, and lack access to adequate basic health care, including paid family and medical leave (bartel et al, ) . this leaves them and their families extremely vulnerable to severe illness and economic ruin if covid- strikes. almost twothirds of us bankruptcies are linked to illness and unaffordable medical bills (himmelstein et al, ). the need for an "improved medicare for all" national healthcare system could never be more urgent. covid- is a risk to all family members and prevention requires an understanding of mitigation strategies within the household and in the community. this necessitates ongoing effective communication amongst family members of all ages. children coping with chronic illnesses, such as diabetes or asthma, need to learn about their illness and aspects of self-management from an early age. the covid- pandemic warrants the same mindset, although here healthy children (and adults) may be introduced for the first time to a "new reality" of personal disease risk. it is valuable to inquire whether anyone is protected in or excluded from such discussions (e.g. children; or aged, frail, or vulnerable family members) and why. adults may feel reticent to share with children given the uncertain nature of covid- , but communicating age-appropriate information about the disease supports psychological wellbeing for the child and the family (dalton, rapa, & stein, ) . the pandemic may reveal sharp differences between partners regarding beliefs about appropriate safety restrictions for children or each other (grose, ) . couples need to discuss these differences, which may warrant additional input from primary care providers. individual family members may process the same covid- information through very different historical, cultural, and political ideological filters, leading to conflicting views. it's crucial to understand beliefs about what can cause or prevent covid- and personal risk perception. research has repeatedly shown that the perception of risk is a more powerful behavioral motivator than actual risk (ferrer & klein, ) . given covid- 's highly transmissible nature, perceptions of relative invulnerability and disregarding precautions can put all family members at risk. teenagers this article is protected by copyright. all rights reserved and young adults often ignore social distancing and mask use out of a belief in personal invulnerability. it can be enormously helpful for families to hold regular family "meetings" to review daily life together during the pandemic and make any needed adjustments. where possible, tele-technology can enhance such pragmatic discussions by facilitating inclusion of family members living at a distance and separated by pandemic precautions. families at higher risk benefit from proactive discussions or consultations about role function flexibility and other potential extended family, community, or healthcare provider resources. this might include adult children (and their parent(s) conferring about shared responsibilities to protect an elder or tend to them if covid- strikes. another example is proactive discussions among parents and with their teenage children about any misguided sense of invulnerability. disagreements about appropriate safety precautions can occur among family members, between neighboring families, between states, and sadly often divide along political party lines. we need one data-driven and unified national public health mandate on precautions and adequate testing, which is separated from politicians and divergent political agendas. this would save countless lives. it must be well funded across socio-economic and minority group strata. compared to other countries strategies over time, us failings at a national level are increasingly and blatantly clear. a unified message would greatly help galvanize state, community, and family level buy-in and cohesion. although most contemporary couples and families strive toward flexible and equitable gender role relations, the influence of culturally based gender norms persist for caregiving roles. as a health crisis, covid- heightens the tendency to expect women to absorb the bulk of child and elder care and attend to the practical and emotional needs of an ill member. it is crucial to explore family expectations about caregiving roles. encourage flexibility and a shift from defining one female member as the caregiver to that of a collaborative caregiving team (walsh, ) . with the geographic dispersion of many families, members may need to accept not seeing loved ones for an indeterminate period. elders, especially those that are frail and chronically ill, this article is protected by copyright. all rights reserved consider that they may not see members living at a distance again. adult children and grandchildren might not see an older parent again. this possibility always is present, yet, is heightened with the pandemic. families can harness this fact to appreciate each other more fully, express caring, and use it as an opportunity to repair and heal relationship wounds. similar to many people living with the uncertainties of a life-threatening illness, the pandemic can stimulate a sense of urgency for family members to deal with unresolved relational issues. whether living near or far, adult sons and daughters have to weigh under what circumstances they would visit their elder parents. if their parents contract covid- or develop a different health crisis, would they accept the risk of seeing them and providing caregiving, thereby putting themselves and their own children at risk. conversely, adult children often fear bringing the infection to their older parents, who are at higher risk. these are profoundly difficult questions, warranting proactive family discussion and consultation with healthcare providers. adult children need to discuss these issues within their own nuclear family. a spouse or partner may have different views about acceptable risk as well as their own aging parents or kin to consider. as the pandemic continues to evolve, these discussions will need to be revisited -relating to new covid- data and to changing family circumstances, such as life cycle transitions or altered economic and health status. those living alone, especially seniors, are at increased mental health risk for anxiety, depression, even suicide during the pandemic (aronson, ) . they can experience despair that meaningful social contact and purpose will no longer occur within the timeframe of their remaining years. they typically lack the support and companionship provided by a spouse, partner, or sibling, for instance. other family members carry additional concerns about the vulnerability of an isolated member. social media and tele-technology options (e.g. zoom, facetime, skype) have provided ways for family members and friends to remain more connected. many families have actually had this option for several years, but are now discovering its utility for the first time. geographically dispersed members can gather for a weekly zoom meeting. grandparents can have a play date with grandchildren. despite the two-dimensional shortcomings and oft heard complaint that it's not the same as in-person, this technology enables clinicians to more easily convene family members for this article is protected by copyright. all rights reserved health and mental healthcare consultations and therapy. however, lower income families often lack the computer resources to avail themselves of this technology, adding another layer of disparity. long-term care facilities (ltcf) are a major challenge for safety during the pandemic. june data revealed that in most states a staggering - % of covid- related deaths occur in ltcf (d'adamo, yoshikawa, & ouslander, ). families may need to evaluate the relative safety of leaving a family member in a ltcf or bringing them to live with them. data shows that persons with cognitive impairment are four times more likely to die of covid- in a ltcf than other residents (cdc, ). lack of judgment, impulsiveness, and confusion with dementia all interfere with risk reduction behavior. those with dementia or intellectual disabilities may be particularly distraught and not comprehend why family members are not able to visit. a family caregiving for an elder with advancing alzheimer's disease, that is becoming unmanageable at home, may have to make a wrenching decision between their own limits and personally caring for a loved one. consultation with involved primary care, specialist, and family behavioral health providers can guide and support family decision-making. fortunately, use of technology through video conferencing allows persons who are hospitalized or in ltcf and their loved ones to sustain vital contact. this is especially important in situations of advanced chronic illness or covid- where death may ensue without loved ones physically present again. applying the fsi model time phases can help us understand two levels: ) the course of the covid- pandemic; and ) the experience living with personal covid- risk and infection over time. this section discusses the evolving challenges at both levels for individuals and families (rolland, ) . despite the uncertainty of the future pandemic unfolding, we can diagram a timeline for each level (figures & ) . the pandemic level phases (figure ) are intended to clarify psychosocial challenges over time rather than emphasize covid- biological or public health incidence and prevalence. core psychosocial themes in the evolving course of the covid- pandemic can be conceptualized into this article is protected by copyright. all rights reserved three broad phases. the initial crisis phase is characterized by a wave of cases with varying course, indeterminate length, and potential spikes. for some countries this initial phase/wave subsided within a few months. in the united states, as of july , with a rising spread of cases and regional spiking, it is unclear when the initial wave will end. in the next phase, a second wave is predicted with the potential for one or more following waves. in the final phase, the course of the pandemic spread diminishes as herd immunity is reached, with or without a vaccine. the pattern of the initial crisis wave has varied considerably in different regions. figure illustrates several general patterns in the initial crisis wave and recurrent wave(s). place figure about here with the current pandemic, the initial crisis phase involves adaptation to the societal risk for everyone. depending on social location, the entire population was presented with the medical risks of covid- as well as mitigation and prevention measures. families needed to reorganize family life, including roles and routines, and communicate about practical and emotional challenges of living with the pandemic. acknowledging risk is needed while maintaining hope. it is vital that families see the covid- pandemic as a shared challenge in "we" terms both at a community and family level. because this is a novel virus, our understanding of medical risks has been evolving as new and more population level data emerges. this changing landscape has been complicated by multiple scientific and political voices with different priorities and agendas. health care experts and policymakers often vehemently disagree about whether to prioritize disease prevention or immediate economic recovery strategies. the lack of a unified message in the face of a life-threatening illness is akin to multiple and divergent medical opinions that can leave families bewildered and frightened, often leading to opposing and conflicted viewpoints about what is needed. this pattern increases the likelihood that dysfunctional family patterns will emerge or pre-existing ones will be exacerbated. the economic consequences of the pandemic, stark witnessing and worsening of racial and socio-economic disparities, and the need for covid- -related health precautions are all simultaneously important. yet, immediate priorities, such as continued vigilant covid- illness prevention and back-to-work imperatives in the face of massive unemployment has collided both at accepted article the macro societal level and among family members. the relative weighing of these different risks and options can vary enormously depending on social location. more affluent families can prioritize covid- risk management because of a more secure economic base. most working and middle class families, who live with economic strains, cannot afford to prioritize health unless protected economically by continued government subsidies. with persistence of the initial wave many individuals and families have shifted from a crisis reactive mode to a longer-haul mind-set. where the initial wave has subsided, others may hold onto hope that there will be no second wave. whenever this psychosocial transition occurs, it involves fuller acceptance of the ongoing nature of the pandemic and living with covid- uncertainty/risk and threatened loss. it is a period when families may consider modifying precautions and reorganizing to adapt to a more protracted coping with the pandemic. the emotional strain of living with covid- risk can feel heightened as they experience the realities of living with an ongoing pandemic. as discussed below, the enormous variation in timing and unfolding of covid- new case trajectories locally, regionally, and nationally adds ambiguity to when this transition is salient for a particular family or community. as with the initial crisis phase/wave, one can conceptualize a more indeterminate length recurrent wave phase in the covid- pandemic. this is distinct from an infected individual living with a chronic phase of covid- . covid- is not the only threat to health and wellbeing. as aronson ( ) notes, the challenge for individuals and a society, is that two contradictory realities are simultaneously true. our approach to pandemic containment works, but our approach causes suffering, eroding physical and mental health, and causing economic dislocations. this affects everyone, but especially individuals with pre-existing chronic illness, disability, in later life, and/or subject to socio-economic and racial disparities. the key is to sustain daily structure and meaningful purpose. digital technology facilitates roles for elders, for instance, in connecting with grandchildren, volunteering to help the less advantaged, or political activism. increasingly with covid- , many families struggle with the ongoing challenges of being this article is protected by copyright. all rights reserved confined at close range for extended and open-ended time. in the united states, many parents needed to negotiate more flexible childrearing roles to accommodate having their children home / without going to school, having after school activities, and depending on usual daycare. with special needs children (e.g. autism, cerebral palsy, intellectual disability) or adults (e.g. serious mental disorders, acquired brain injury), families are managing alone without the usual specialized supportive and educational services. communities are exploring innovative ways to provide in-person education and specialized services. also, increased substance use and family violence are emerging as the pandemic continues (bradbury-jones & isham, ). primary care based health and mental health clinicians can touch base periodically with families at known risk and provide some measure of prevention and early intervention. different geographic regions vary in their approach to transition (re-entry) from the initial crisis phase/wave to a more protracted phase for living with ongoing covid- risk. state-by-state stages of re-entry are akin to recovery and rehabilitation from an illness, where "vital signs" are monitored to guide timing of graduation to the next stage of recovery or retreat to a previous one. these larger system rules and recommendations inform and guide families. it is essential for families to discuss this step-wise transition as newer longer-haul covid- guidelines become available. families need to consider how these guidelines fit with their own beliefs and priorities. distinctions for members at different ages (e.g. children, elders) warrant discussion. again, consultation with a healthcare provider can offer clearer guidance, for instance with decisions about a college student or young adult losing a job and returning home to live with parents. with the covid- pandemic, relative risk may wax and wane with the alternation of periods of "flattening the curve" and decline in new cases with periods of resurgence, higher risk, and the need to resume more intensive case suppression/mitigation public health measures. like relapsing illnesses, communities and families need to maintain some measure of vigilance and preparedness for both, not knowing "if" and "when" a resurgence/flare-up may occur (rolland, ) . unlike a condition that is always symptomatically present, here families are strained both by the potential fluctuation of transition between covid- quiescent and resurgence periods and the ongoing uncertainty of when a spike may occur. good spirits in resuming more normal routines may be dashed by a new wave of cases. hunkering-down again after a period of greater freedom can be this article is protected by copyright. all rights reserved discouraging and anxiety provoking. the psychological shift between these two ways of living is a particularly taxing feature for this pandemic as it is for relapsing chronic illnesses. this fluctuating pattern may exact a huge psychological toll over time. public health media and primary care based psychoeducation supplemented by offering periodic individual or family mental health consultation and brief treatment can be beneficial. when living with personal risk and actual infection, shown in figure , we can identify three phases: ) at risk, ) acute infection, which can be symptomatic (possibly fatal) or asymptomatic, and ) a long-term phase that can lead to recovery, may involve complications/chronicity, or can be fatal. living at risk has been integrated into earlier discussion. place figure about here if a family member becomes ill with covid- , especially an elder, precautions often require isolation and self-care without direct caregiving support from family members. in severe life threatening situations that require hospitalization, family members are restricted from direct contact with the ill member. and, if the member dies in a hospital or skilled care facility, it is typically without loved ones present. the inability to be there physically for the dying member's final hours, say goodbye, or have a traditional funeral and burial service can burden family members with myriad complex feelings, such as guilt and anger, that complicate grief reactions. in one recent case, bill, who is and in good health, with the covid- disease, the long-term phase for affected individuals and their families is influenced by an emerging wide range of complications and may be marked by constancy, progression, or episodic change. it is "the longer haul," involving day-to-day living with a potentially chronic condition and associated disruptions in lives and livelihood. salient family issues include: ( ) pacing and avoiding burnout; ( ) minimizing relationship imbalances between the affected individual and other family members; ( ) maximizing autonomy and preserving or redefining individual and family developmental goals within the constraints of covid- ; and ( ) sustaining connectedness in the face of threatened loss (rolland, ; ) . all major life course milestones and nodal events are impacted (rolland, ; ) . covid- risk has put a threatening cloud on the horizon of any event where family, friends, and community networks would gather. this includes: weddings, graduations, funerals and memorial services, family this article is protected by copyright. all rights reserved reunions, annual holiday or vacation traditions, and regular gatherings of community groups or religious congregations. improvisation and creative adapting of events and rituals are key responses fostering family and community resilience (imber-black, ). by example, one of our center trainees' wedding plans were modified to include only ten individuals present for the actual ceremony in their backyard, while other family and friends joined the ceremony via zoom. this adaptive response allowed family members, who live at a distance to join the celebration. while there are a number of important individual and family developmental phases, this discussion will highlight several especially salient ones. those over and/or with a chronic illness (e.g. heart disease, diabetes, obesity, respiratory conditions, immune system compromise) are at much higher risk with more stringent and ongoing restrictions. many families have organized to protect elders and members with chronic conditions, such as limit entering their home or having close range contact. the lack of physical contact, such as hugging, is particularly difficult, contributing to feelings of isolation and disconnection (killgore et al, ) . with all older clients and those with chronic illness, it is important for clinicians to encourage them to have updated advance directives, a health care proxy, and wills. with life-threatening conditions, like covid- , that can involve rapid progression, unresponsive state, or leave cognitive impairment, there is added incentive for preventive or early frank conversations. knowing family members' wishes concerning heroic medical efforts and life support can benefit everyone. despite the short-run challenge of having end-of-life discussions, it is important to keep in mind that many of the most wrenching end-of-life experiences for families occur when the wishes of a dying member are unknown or have been disregarded. since family members are typically not allowed to be present in the hospital with covid- , it is particularly important that a health care proxy has been designated and identified to the healthcare team (rolland, emanuel, & torke, ) . the proxy can be proactive regarding limits of heroic measures or other important cultural and religious preferences. and, the healthcare team benefits in knowing whom to contact in dire circumstances, where urgent life and death decisions may be necessary. this article is protected by copyright. all rights reserved with colleges managing remotely on-line and unemployment staggering among younger adults, future plans are impacted and some put indefinitely on hold. for financial reasons, many young adults are returning home to live with their families-of-origin concurrent with increased economic hardships at home. covid- anxieties, pandemic fatigue, and evolving public health restrictions; along with economic and co-habiting stresses can easily lead to or heighten family tensions. regular family "check-in" meetings can help manage these inevitable strains. covid- and its economic fallout are causing young adults to encounter huge uncertainties about future hopes and dreams. this may be a significant undercurrent strain for adolescents, young adults, and their parents that can benefit from open discussion. it is worthwhile to ask individuals and family members about prior illness or life crisis/adversity experiences that they can draw on when facing the covid- pandemic. areas of vulnerability and resilience are important to identify. for instance, a family history of an untimely illness or death by infection, the succumbing of a robust family member, or a family member suffering alone, can signify particular sensitivity in the context of covid- . a past experience of enduring well prolonged adversity (e.g. poverty) or an illness with high risk and uncertainty (e.g. heart disease) can inspire resilience in the face of covid- . as the covid- pandemic continues, the enormous toll on frontline healthcare workers is emerging as exhaustion, anxiety, depression, insomnia, trauma, and suicide (schechter, et al, ; wong, et al, ) . this toll profoundly and severely impacts their own family relationships. at times, the relentless and largely untreatable nature of covid- confronts the core identity of healthcare professionals to save and cure patients. although healthcare providers often make decisions amid uncertainty, "we typically focus on the patient's risk, not our own. in an infectious disease epidemic, our calculus must incorporate our own exposure risk -and how exposure would limit our ability to care for future patients" (rosenbaum, ) . the sense of helplessness and witnessing waves of death is deeply and cumulatively disturbing, and can lead to a sense of failure and moral injury (griffin et al, ) . this has been compounded by restrictions barring patients' family members' physical this article is protected by copyright. all rights reserved presence to provide comfort as their loved one's life is threatened and often in their final hours. this leaves clinicians aware that they may be the last person that the covid- patient interacts with. as one anesthesiologist put it, "i could be the last person some of these patients ever see, or the last voice they hear. a lot of people will never come off the ventilator. that's the reality of this virus. i force myself to think about that for a few seconds each time i walk into the icu to do an intubation" (saslow, ) . working with illness and loss typically stimulates concerns related to our own and our loved ones' physical vulnerability and mortality. this is especially true with covid- , where we are all at risk. a we-they mindset is impossible. there is an enormous need for debriefing with colleagues and the availability of individual and family mental health consultations. a multi-systemic lens and drawing on the family systems illness model can provide a psychosocial map to guide individuals, couples, and families meet the myriad challenges of covid- . as a worldwide crisis, the covid- pandemic gives us a sense of belonging that can promote solidarity and increase global empathy and caring for each other. the coronavirus disease (covid- ) outbreak and mental health: current risks and recommended actions for older people, despair, as well as covid- , is costing lives. the new york times racial and ethnic disparities in access to and use of paid family and medical leave: evidence from four nationally representative datasets accepted article this article is protected by copyright. all rights reserved race, class, ethnicity, and disaster vulnerability handbook of disaster research the pandemic paradox: the consequences of covid- on domestic violence covid- in racial and ethnic minority groups vital signs: racial disparities in age-specific mortality among blacks or african americans-united states protecting the psychological health of children through effective communication about covid- coronavirus disease in geriatrics and long-term care: the abcds of covid- u.s. house of representatives energy and commerce committee hearing on oversight of the trump administration's response to the covid- pandemic risk perceptions and health behavior moral injury: an integrative review when couples fight about virus risks medical bankruptcy in the united states accepted article this article is protected by copyright. all rights reserved rituals in contemporary couple and family therapy loneliness: a signature mental health concern in the era of covid- changing gender norms in families and society cardiovascular complications in covid- the covid- pandemic: a family affair hospitalization and mortality among black patients and white patients with covid- convergent antibody responses to sars-cov- in convalescent individuals anticipatory loss: a family systems developmental framework the expanded family life cycle: family and social perspectives helping couples and families navigate illness and disability: an integrated practice approach the family, chronic illness, and disability: an integrated practice model accepted article this article is protected by copyright. all rights reserved applying a family systems lens to proxy decision making in clinical practice and research the untold toll -the pandemic's effects on patients without covid- voices from the pandemic. the washington post psychological distress, coping behaviors, and preferences for support among new york healthcare workers during covid- pandemic neurological and neuropsychiatric complications of covid- in patients: a uk-wide surveillance study. the lancet psychiatry strengthening family resilience a longitudinal study on the mental health of general population during the covid- epidemic in china healing the healer: emergency health care workers' mental health during covid- key: cord- - b hijhv authors: moriarty, andrew k.; friedberg, eric; pyatt, robert s.; everett, catherine; mcadams, christopher title: what might your practice look like post-peak covid- ? date: - - journal: j am coll radiol doi: . /j.jacr. . . sha: doc_id: cord_uid: b hijhv nan the acr commission on general, small, emergency and/or rural practice (gser) organized a panel to discuss the response of several different types of radiology practices to the coronavirus disease (covid- ) pandemic and planning for the resumption of services across multiple practice settings [ ]. the practice leaders represented the perspective of general, small and rural practices, practices serving in critical access hospitals in addition to a community division of a large academic institution, a national radiology practice, and a teleradiology practice. the presenters share their unique practice responses and future outlooks based on the most currently available knowledge at the time while planning initial stages of recovery during the rapidly evolving covid- pandemic. the practice leaders anthony gabriel, md, mba, co-founder of radiology partners, presented the perspective of a national radiology physician practice management company including , radiologists in states. benjamin w. strong, md, chief medical officer of vrad, discussed the teleradiology company perspective and their response to a greater than percent reduction of imaging volume early in the pandemic. the practice includes over radiologists serving over , sites across all states. cathrine e. keller, md, managing physician of lake medical imaging reported on the perspective of a member out-patient only radiology practice primarily servicing elderly patients in a highly competitive local market. daniel a. rodgers, md, president of kanawha valley radiologists, a six-person radiology practice in rural west virginia, assessed the benefits and challenges the pandemic presents for small rural practices and critical access hospital practices. howard b. fleishon, md, mmm, facr, vice chair of the acr board of chancellors, presented the perspective of the community division of emory university as chief of radiology services. the division provides comprehensive coverage for hospitals, outpatient imaging centers, and other ventures outside of the main downtown emory campuses in the greater atlanta area. lyndon k. jordan iii, md, facr, president and managing partner of wake radiology, described the challenges facing his -physician radiology group in raleigh, nc and the innovative solutions in partnering with local businesses. initial response, recruitment, and future imaging volumes multiple panelists commented that current recruitment efforts and service expansion plans would be paused or significantly reconsidered as practices tried to model future volumes and different scenarios for staged recovery. however all indicated that currently signed contracts would be honored and most indicated that new hires would start on-time. the smaller and outpatient-based practices both indicated that groups were short staffed at the initial pandemic and that these groups dealt with the initial imaging reduction by having partners voluntarily take additional time off the schedule or distributing extra vacation days equitably across all individuals. during the session, the national teleradiology organization highlighted infrastructure that allowed workload balancing by assigning case volumes to radiologists to balance the available cases with the desire of radiologists available to read while the national radiology practice indicated that based on existing practice structure most units formulated local solutions that varied by the individual practice size and preferences. a common theme was that the significant volume losses across the country were due to voluntary deferral and widespread (but heterogenously implemented) stay-at-home orders. at the time of presentation there was significant uncertainty as to the timing, rate, and overall resumption of outpatient and elective imaging as well as on the impact on patient preferences toward outpatient or hospital-based imaging options. leaders are closely monitoring trends, exploring ways to increase efficiencies, adjust compensation models and considering options to mitigate the uncertainties laying ahead. a specific note was made that the increased use of initial employment video interviews will likely persist after the pandemic ends to screen potential candidates safely and efficiently. some predict an opportunity to provide urgent imaging services at outpatient facilities for patients who have been appropriately triaged from urgent care centers and telemedicine visits rather than emergency departments or hospital-based facilities, especially during surge or peak covid volumes. outpatient centers may leverage this opportunity to create new strategic solutions for imaging coverage through and potentially beyond the covid- pandemic. this might include expanded hours of access that would allow for greater temporal and physical appointment spacing for more optimal patient safety in addition to the ability to increase same day add-on case scheduling. opinions were mixed on the overall impact from the pandemic on recent trends in radiology consolidation and corporatization. some felt that highly-leveraged entities may take time to re-organize or face increased risk of failure in current lending environments. others noted that some practices, especially smaller or resource limited groups, may be reconsidering a "go it alone" approach, especially if the pandemic is prolonged or there is a significant economic downturn. it is possible that the severe stress placed on many practices and health systems could lead to greater marketplace consolidation or bankruptcies [ ] . all practices have been impacted by reduced volumes, with some reporting greater than percent losses [ ] . leaders are modeling various scenarios for both recovery and potential subsequent waves of infections or stay-at-home orders for the coming years. most agreed that it is too early to tell what effect these changes may have on practice stability, and all leaders are examining how to remain viable under multiple different scenarios for short term solvency. panelists noted that local infection rates, system capacity, and other regional factors will have the biggest impact on imaging recovery. in this regard, single site or closely organized regional practices will likely have more uniform recovery conditions facilitating a cohesive plan and implementation compared to geographically dispersed practices. all panelists agreed that remote reading and tele-health services will see a significant increase following the pandemic, even though teleradiology has been a well-established and available service for many years. this corresponds to several anecdotal reports and surveys of practices performed early in the pandemic [ ] . those practices that had existing remote solutions in place were able to react quickly with off-site reading in the early days of the pandemic while expanded deployment was significantly accelerated for those practices which had not fully embraced teleradiology previously. several panelists noted that they were already seeing an increase in the number of current radiologists as well as job applicants requesting to work from home for personal and family safety concerns. they noted that practices may have to adjust current job offerings to attract the best candidates if volumes return quickly and the job-market tightens. during the recovery phase, hospitals may be more willing to negotiate the total number of on-site providers needed to facilitate an increase in teleradiology services. panelists highlighted the need to resume imaging operations safely and efficiently in the recovery and post-pandemic imaging phases. several noted that improved cleaning protocols and use of personal protective equipment are likely to persist long after the pandemic subsides while other measures such as eliminating waiting rooms may be relaxed gradually based on local infection statistics and patient acceptance. these plans will continue to evolve with experience and knowledge as different parts of the country and world move through the pandemic at different paces ]. panelists noted that it was particularly challenging to understand and apply for the various types of federal aid available during the pandemic, especially with the rapidly evolving relevant legislation and regulations. success required close coordination with accountants and attorneys, and the ability to utilize pre-existing relationships was highly beneficial. the acr created a comprehensive online portal early in the pandemic to provide practices with regularly updated resources and education material as it became available and evolved, including both public facing and member-only content [ ] . acr leaders who participated in the panel noted that the college is uniquely positioned to convene radiologists from multiple varied practice settings and help them learn from each other. the pandemic may accelerate investment in programs to develop radiologist leaders and their ability to participate in strategic decision making for their organization(s). all radiology practice types have been significantly impacted by the covid- pandemic. leaders representing a diverse group of practices in the general, small and rural community, critical access hospitals, a community division of a large academic institution, a national radiology practice, and a teleradiology practice provide different perspectives on the immediate post-recovery phase for radiology. these individuals highlight the need to safely and effectively resume imaging services based on local conditions, while simultaneously developing contingency plans for potential future forced imaging reductions or service disruptions. -issue/your-practice-post-peak-covid- -webinar-available-on-demand private equity-backed hospital investments and the impact of the coronavirus disease (covid- ) epidemic impact of the covid- pandemic on imaging case volumes off-site radiology workflow changes due to the covid pandemic acr statement on safe resumption of routine radiology care during the covid- pandemic the american college of radiology. acr coronavirus (covid- ) resources key: cord- -m rne l authors: cheema, s.; ameduri, m.; abraham, a.; doraiswamy, s.; mamtani, r. title: the covid- pandemic: the public health reality date: - - journal: epidemiol infect doi: . /s sha: doc_id: cord_uid: m rne l the coronavirus disease (covid- ), while mild in most cases, has nevertheless caused significant mortality. the measures adopted in most countries to contain it have led to colossal social and economic disruptions, which will impact the medium- and long-term health outcomes for many communities. in this paper, we deliberate on the reality and facts surrounding the disease. for comparison, we present data from past pandemics, some of which claimed more lives than covid- . mortality data on road traffic crashes and other non-communicable diseases, which cause more deaths each year than covid- has so far, is also provided. the indirect, serious health and social effects are briefly discussed. we also deliberate on how misinformation, confusion stemming from contrasting expert statements, and lack of international coordination may have influenced the public perception of the illness and increased fear and uncertainty. with pandemics and similar problems likely to re-occur, we call for evidence-based decisions, the restoration of responsible journalism and communication built on a solid scientific foundation. the number of confirmed infections with sars-cov- has reached million worldwide, and mortality from covid- is estimated to be above [ ] . all the evidence thus far available quite clearly shows that those at highest risk of a severe illness and death are the elderly, individuals with existing co-morbidities and the immunocompromised. undeniably, the covid- pandemic has resulted in loss of human life; it has wreaked havoc on healthcare systems worldwide, highlighting inequities in healthcare availability and access; it has resulted in drastic public health measures in most countries of the world. low-and middle-income nations with weak health systems, dwindling economies, high population density, a high reliance on informal employment, poor technological infrastructure and the double burden of non-communicable and communicable disease are, in particular, more vulnerable to the covid- challenge than high-income nations. as additional information about the infection and its effects becomes increasingly available, a number of questions which require an explanation arise. while these questions might have been premature a few months ago when very little was known about the epidemiology of the infection, in this commentary we argue that they are now very timely and that it is imperative these questions be addressed. the questions we specifically explore are: how serious is the covid- pandemic? how does it compare with the death burden from other causes? what have been the indirect health and social effects of the covid- pandemic? we also raise questions surrounding misinformation and its negative consequences on health. in exploring these questions and seeking possible answers, we first present data in two parts: (a) epidemiology of covid- and (b) comparison of covid- mortality with mortality from previous pandemics and other causes (for comparison, at the time of writing this paper, the total number of worldwide documented cases and deaths are and , respectively) [ ] . subsequently, we summarise the indirect repercussions of the covid- pandemic on non-communicable diseases, economy and lives of people. in the conclusion, we offer a few comments, share thoughts and raise some questions to help open a debate. based on a review of recent covid- literature, it is clear that the disease is minor in most cases [ , ] . the estimated infection fatality rate is in the range of . - . % [ , ] . the most recent systematic review and meta-analysis found a pooled infection fatality of covid- to be around % among studies with a low risk of bias (meyerowitz-katz and merone, , unpublished). the covid- case fatality rate, in principle an indicator of the virulence of the virus and severity of disease, has been a subject of debate. we now know that this rate may not accurately reflect the true infection fatality rate for a variety of reasons, examples of which include inadequate testing, the high number of mild/asymptomatic cases and failure to include those cases in computing the final rate and the country-specific methods of attributing deaths to covid- . a number of recent studies, primarily in the usa and in spain, which used antibody testing of population samples indicate that the number of undocumented infections is significantly high. these undocumented infections are often not included in computing the published case fatality rates. while the epidemiological implications of these results remain uncertain, they nevertheless strongly suggest that the infection fatality rate is much lower than the currently reported crude case fatality rate of . % [ ] . data are becoming available on the number of deaths per million population in the world health organization (who) weekly epidemiological reports. as of september , the who reported deaths per million in belgium, in the uk and deaths per million in the usa [ ] . this may be a truer reflection of the severity of covid- . we cannot and should not understate the severe disease paradigm in those at higher risk, which includes elderly individuals and those with underlying chronic conditions such as obesity, diabetes, heart disease, cancer, chronic lung conditions and an immunocompromised status. additionally, clinical presentation characterised by underlying pathological changes such as thromboembolism, cytokine release and inflammatory syndrome resulting in damage to the lungs, cardiovascular system, liver, kidneys, pancreas and nervous system, have been noted and described [ ] . here, we present data that pose questions on the magnitude of attention that the covid- pandemic has garnered compared to other public health issues that are in dire need of prevention and response. table compares the mortality of covid- with past pandemics of the th and st centuries. the mortality rate ratios (between past pandemics and covid- ) ranged from . times (for the lower estimate of the 'swine flu' pandemic) to over times (the upper estimate of the 'spanish' flu pandemic) that of covid- , after adjusting for population size. while coronavirus infection and death rates continue to escalate in some communities and decline in others, most experts agree that covid- continues to present a significant risk especially to the elderly and those with chronic conditions. it should be emphasised that the other causes of death during the covid- pandemic cannot be ignored. according to the institute for health metrics and evaluation (ihme), noncommunicable diseases account for over million deaths globally, while communicable and nutritional diseases claim over million lives [ ] . of the latter, . million deaths were from hiv/aids, tuberculosis, enteric infections, measles and other communicable diseases, most of which are preventable or effectively managed [ ] . in , there were million cases of malaria ( % confidence interval (ci): - million) worldwide, causing an estimated deaths [ ] . furthermore, we observe that deaths due to some acute and largely preventable causes far exceed covid- -related deaths. ihme data on mortality suggest that deaths due to injuries exceed those of covid- , as of september [ ] . road fatalities, including motor vehicles, cyclists and pedestrians, account for the largest proportion of these, at over . million. over % of injury-related fatalities and more than % of communicable and nutritional disease-related fatalities occur in low-income and low-middle-income countries. also, the who estimated that in , iatrogenic or medical errors caused . million deaths in the lower-and middle-income countries alone [ ] . these figures demonstrate that there are other concurrent problems causing distressingly high fatality rates that should not be overlooked as we continue to battle the covid- pandemic. while mortality is an important measure to ascertain the seriousness of covid- , its indirect serious health, social and financial consequences cannot be ignored. the presented data also suggest that the world today may be facing bigger public health challenges than covid- . is the world's reaction to the pandemic in terms of lockdown and travel restrictions disproportionate? we express our concern on the impact that these prevention measures have had, particularly on the mental health and livelihood of the poor and the most vulnerable populations. more importantly, the current scenario risks compromising the physical, mental and social health of individuals and communities [ ] . there are reports that persons with non-communicable diseases are failing to seek timely care due to fear of breaking lockdown rules, the threat of acquiring covid- during visits to healthcare facilities, and the choice made by hospitals to treat emergencies only [ ] . the risk of adverse health effects due to postponement of routine and elective care along with the severe mental stress and depression caused by this largely unprecedented situation is of grave concern. isolation, unemployment and loss of income may further compound the misery of already lonely individuals and families leading to a rise in self-harm and suicidal ideation, gender-based and domestic violence and the risk of substance use [ ] . the evidence of the dramatic economic impact of the measures undertaken in many countries to fight the spread of the disease is apparent. for example, in the usa, unemployment is at a record high and the economy is tumbling. nationwide, women, people of colour and the young are affected the most [ ] . the loss of income is likely to result in an increase of adverse health outcomes for many of the individuals affected, and the overall economic crisis will negatively impact the ability of entire countries to provide effective healthcare to their citizens. for individuals in low-and middle-income nations, loss of income, separation from loved ones and social isolation may be legitimately viewed as a bigger threat to long-term survival than the doom and gloom associated with the covid- pandemic. such a phenomenon has been observed during the economic crises faced by countries prior to the covid- pandemic. the financial crisis in greece, for instance, is estimated to have caused an additional deaths per month between september and december , due to cardiovascular disease, suicide and mental health illness disproportionately affecting women and people older than [ ] . job loss during a recession in the usa was associated with significant increases in mortality (hazard ratio: . ; % ci . - . ) [ ] . in brazil, a middle-income country, an analysis by hone et al. determined that a % rise in the unemployment rate was associated with . increase per each quarter in all-cause mortality and that unemployment resulted in additional deaths between and [ ] . hence, we believe that the mortality and disease burden during and after the covid- pandemic due to the social and economic consequences of the preventive measures and other factors can be substantially high. in addition to the direct effects on mortality, it is also feared that the economic disruptions could lead to the doubling of malnourished children in africa in the next - months [ ] . in a recent interview with the washington post, mark lowcock, united nations undersecretary general for humanitarian affairs, said, 'there's a huge covid- impact which is economic, and that is drowning out the disease itself' [ ] . it is hence critical to have an eye on the overall effects of the pandemic both on the short-and long-term. it is hard at this stage to reconstruct the sequence of events leading to the haphazard and incoherent response of most countries to the spread of the pandemic. however, we caution against fearmongering associated with sensational narratives and inappropriate media reporting, which can result in political pressures that global leaders, policymakers, employers and even some healthcare professionals may have been under, along with the initial uncertainties concerning the severity and nature of the disease. sensationalism, confusion stemming from contrasting statements from authority figures and the lack of international coordination have influenced the public perception of the illness, increasing fear and uncertainty. as an example, we cite the hydroxychloroquine saga. the sale of this medication in the usa jumped leaps and bounds with just a mention of its potential benefit from the us president [ ] . similarly, the differing recommendations on the use of masks from the who and the us centers for disease control have contributed to the public's confusion [ ] . in addition, the pervasive and increasing role that social media play in how people obtain and share information increases the risks of misinformation and confusion. misinformation can imperil the health of public in other ways. in a recent online us survey, it was observed that us adults are engaging in more frequent cleaning and disinfection of their home to prevent sars-cov- infection. the study points out that % use cleaning agents or disinfectants in an unsafe manner that presents health risks. for example, % reported using bleach on food (fruit or vegetables) and % reported using cleaning products on their skin [ ] . we should neither downplay nor overstate the pandemic risk. those at increased risk of severe disease should receive priority and be effectively managed. from a public health perspective, it is our opinion, that the lack of a timely internationally coordinated evidence-based approach, the inadequate preparedness of health systems and the absence of effective global leadership has driven us to the current health, economic and social disruptions. the lack of control and coordination over who is saying what, how, where and when, can propel misinformation, leading to fragmented decision-making and public confusion. should there not be an agreed upon deontological code to discourage sensational reporting? why are there not globally acceptable guidance statements on commonly used measures such as the use of face masks and chloroquine? the covid- pandemic continues to evolve. moving forward and with pandemics likely to re-occur, we call for health decisions to be made on the basis of science and public health evidence. restoration of responsible journalism and communication driven by scientific truth and valid data is of paramount importance. imparting public health education in school, college and community settings to inform learners about health, disease risks and general aspects of public health challenges such as infectious diseases is vital. worldometer database centers for disease control and prevention (cdc) database. available at imperial college london covid- response team estimates of the severity of coronavirus disease : a model-based analysis estimating the infection fatality rate among symptomatic covid- cases in the united states world health organization database world population history database reassessing the global mortality burden of the influenza pandemic the influenza pandemic: insights for the st century updating the accounts: global mortality of the - 'spanish' influenza pandemic world health organization (who) the h n influenza outbreak in its historical context novel swine-origin influenza a virus in humans: another pandemic knocking at the door world health organization (who) estimated global mortality associated with the first months of pandemic influenza a h n virus circulation: a modelling study institute for health metrics and evaluation (ihme) database world health organization (who) who-calls-for-urgent-action-to-reducepatient-harm-in-healthcare patients with chronic illness urgently need integrated physical and psychological care during the covid- outbreak covid- pandemic will have a longlasting impact on the quality of cirrhosis care the psychological impact of the covid- epidemic on college students in china unemployment soars to . %, job losses reach . million in april as coronavirus pandemic spreads total and causespecific mortality before and after the onset of the greek economic crisis: an interrupted time-series analysis recessions, job loss, and mortality among older us adults effect of economic recession and impact of health and social protection expenditures on adult mortality: a longitudinal analysis of brazilian municipalities world food program database the nutrition crisis of covid- will be even worse than the disease. the washington post association between us administration endorsement of hydroxychloroquine for covid- and outpatient prescribing covid- : what is the evidence for cloth masks? more than in us adults use disinfectants unsafely acknowledgements. we would like to thank ms. danielle jones (dj), lecturer, english as second language, pre-medical education weill cornell medicine-qatar for her english editing services. financial support. this research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. ethical standards. not applicable. data availability statement. the dataset(s) supporting the conclusions of this article is (are) included within the paper. key: cord- -kea a authors: sharpe, richard e; kuszyk, brian s; mossa-basha, mahmud title: special report of the rsna covid- task force: the short- and long-term financial impact of the covid- pandemic on private radiology practices date: - - journal: radiology doi: . /radiol. sha: doc_id: cord_uid: kea a the coronavirus disease (covid- ) pandemic resulted in widespread disruption to the global economy, including demand for imaging services. the resulting reduction in demand for imaging services had an abrupt and substantial impact on private radiology practices, which are heavily dependent on examination volumes for practice revenues. the goal of this article is to describe the specific experiences of radiologists working in various types of private radiology practices during the initial peak of the covid- pandemic. herein, the authors describe factors determining the impact of the pandemic on private practices, the challenges these practices have faced, the cost levers leaders adjusted, and the government subsidies sought. in addition, the authors describe adjustments practices are making to their mid- and long-term strategic plans to pivot for long-term success while managing the covid- pandemic. private practices have crafted tiered strategies to respond to the impact of the pandemic by pulling various cost levers to adjust service availability, staffing, compensation, benefits, time off, and expense reductions. in addition, they have sought additional revenues, within the boundaries of their practice, to mitigate ongoing financial losses. the longer-term impact of the pandemic will alter existing practices, making some of them more likely than others to succeed in the years ahead. this report synthesizes the collective experience of private practice radiologists shared with members of the radiological society of north america (rsna) covid- task force, including discussions with colleagues and leaders of private practice radiology groups from across the united states. the coronavirus disease (covid- ) global pandemic has resulted in . million confirmed infections and , deaths worldwide as of july , . ( ) businesses have paused operations or significantly adjusted their operations, and the u.s. economy has contracted at the fastest rate since the great depression. ( ) ( ) ( ) ( ) patients have shunned hospitals and medical services. ( ) examination volumes in radiology practices have decreased by - %, which some anticipate could persist for a few months to a few years. ( ) ( ) ( ) ( ) the initial surge of the pandemic is thought to be subsiding, the next phase is uncertain, and the full impact of the pandemic has yet to be determined. ( ) herein, we describe the impact of covid- on private radiology practices, which are particularly vulnerable to the pandemic. these radiologists who work outside of academic university settings accounted for approximately % of all practicing radiologists in . ( ) while we use the term "private radiology practices," that it is not the ideal term to describe these diverse practices. the goal of this article is to describe specific experiences of radiologists working in various types of private practices during the initial peak of the covid- pandemic. we present a detailed case study of a private radiology practice impacted by the pandemic. subsequently, we describe factors determining the impact of the pandemic on private practices, the challenges practices have faced, the cost levers leaders adjusted, government subsidies sought, and strategic adjustments that practices are making to their mid-and long-term plans to pivot for long-term success while managing the covid- pandemic. it is our hope that all types of radiology groups may benefit from early dissemination of the impact of the pandemic on private practices. the report synthesizes publicly available data with the collective experience of private practice radiologists informally shared with members of the radiological society of north america (rsna) covid- task force, including discussions with colleagues and leaders of private radiology practices from across the united states. fixed costs for practice a include building mortgages ($ . million), equipment loans ($ . million), full-time employee salaries, picture archiving and communications system fees ($ , per month), and service contracts. the practice has a $ million credit line. variable costs comprise a significant fraction of practice a's operating expenses as it has a large percentage of part-time technologists and work relative value unit (wrvu)-based payments for radiologists, who are assigned cases to interpret daily. a national billing vendor receives % of revenues. during the covid- pandemic, practice a adjusted its processes to safely image persons with mild symptoms suggesting, or a recent positive test for, covid- . the imaging centers implemented safety measures, including patient and employee screenings at the entrances, temperature checks, universal masking and mandatory self-isolation policy. two employees tested positive for covid- , bothwere exposed at other healthcare jobs they concurrently held. they self-isolated for more than days. how the pandemic impacted practice a the first covid- case in michigan was confirmed on march , . ( , ) . as of july , , , patients have tested positive for covid- within the state of michigan, accounting for . decreases in examination volumes occurred in each of the performed imaging modalities ( figure ) . mri was the most impacted, as the group performed and interpreted more than per week prior to covid- and interpreted a low of the week of march , . strategies to manage during the pandemic as examination volumes decreased, maintaining full operations would exhaust practice a's cash reserves within a few months and could place the practice into bankruptcy. the practice reflected on the family-like practice culture to balance protecting and supporting employees, caring for patients, and remaining financially solvent. the early response to the pandemic focused on reducing practice expenses. office hours and radiologist daily work hours were decreased. radiologists were paid per-wrvu, and thus costs were reduced due to reduced interpreted volume. part-time technologists are paid on an hourly basis, and the reduced days of operation and reduced volume lowered these payments. the practice received $ , from the center for medicare and medicaid services accelerated and advance payments program, which reimbursed providers for expected future services. mid-term strategies implemented march , further reduced future expenses and identified additional sources of revenue. part-time employees' hours were reduced, allowing the full-time staff to continue to receive their expected salaries. service contracts were reevaluated and renegotiated to account for pandemic-related periods of very low equipment utilization. the practice received $ , from the paycheck protection program. several factors contributed to practice a remaining financially solvent. the practice took early decisive actions to reduce part-time radiologist and technologist staffing, reduce expenses, and secure governmental financial support when possible. despite entering the pandemic from a position of relative financial strength, the impact of covid- on practice a has already been severe. radiologists estimate a decrease in compensation of % for calendar year . most part-time radiologists and staff members had few if any assigned shifts during april . a variety of factors resulted in office staff members and technologists leaving the practice. the previous close-knit family culture will need growth and nourishment to return to its pre-covid state. practice a is both guarded and optimistic that the pandemic will subside, that their practice will flourish beyond its pre-covid- state. factors determining the pandemic impact on private radiology practices for many practices, caring for patients with covid- increased the complexity of the financial impact. volumes of advanced imaging, a higher reimbursement service for many practices, were reduced while low reimbursement services, such as radiography, often increased. at the same time, performing these low reimbursement services in ways that minimized the risk of virus transmission to staff and other patients increased the time and resources required to perform these services. these challenges were often most pronounced in private practices that included a hospital-based component to their practice, and which cared for covid- patients with moderate and severe symptoms. radiology practices generally have different practice models: physician owned, corporate entity owned, and hospital or health system employed. for physician-owned private practices, revenue is earned from fees for imaging interpretation. radiologists are typically paid a base salary plus a bonus from revenues remaining after expenses are paid. these practices are not generally financially affiliated with larger entities. these practices could experience dramatically high or low profits depending on market factors. in the case of the covid- pandemic, may not have the same access to financial markets as do larger corporations. as a result, these practices experienced abrupt and substantial hardships. we anticipate that some physician-owned private radiology practices, such as small practices and those with large amounts of debt prior to the pandemic, may struggle to remain both independent and financially solvent. decreasing reimbursements, increasing technology costs, increasing regulations, and increasing market competition over the past two decades have led to some physician-owned private radiology practices selling their practices to corporate and private equity investors. ( ) ( ) ( ) ( ) these investors saw healthcare as being recession-resistant and aimed to consolidate fragmented networks of providers and extract resulting profits. prior to the pandemic, radiologists saw these entities as having access to capital markets, expertise in consolidation, and stability in a tumultuous radiology market. ( , ) investors in these private equity firms and/or publicly traded companies own a portion of the practice. these firms re-invest to develop business infrastructure and growth, and in turn receive a portion of profits generated by physician professional activity. however, the covid- pandemic exposed some of these firms as being more fragile than initially anticipated. like a slingshot already retracted to its breaking point, some of these firms were excessively leveraged at the outset of the pandemic. this was the result of a trend of leveraged buy-outs that depended on growth to succeed, and left little room for increased financial backing during the pandemic. some firms are now considering bankruptcy. ( , ) finally, hospital systems also employ radiologists. radiologists may have heterogeneous experiences in these practices. while some hospital systems operated on thin operating margins before the pandemic, others may be able to absorb some short-term financial losses by using financial reserves and securing government funds due to their essential role in providing care to local communities. ( , ) alignment with covid- best practices private radiology practices monitored evolving information from news sources, government officials, radiology specialty societies, and the rsna. at times, practices struggled to identify a single source of truth regarding the spread of the pandemic.. recommendations made by local, state and federal agencies were varied widely and were often vague. a lack of uniformity in messaging about the risks of covid, the projected length of the pandemic, and best practice strategies to address the clinical impact resulted in dramatically different interpretations among private radiology practices. tremendous variability in interpretations of state-level practice guidance existed, even in the early affected seattle area. for example, some practices in seattle maintained elective imaging appointments ( , ), while other groups only indicated plans to reschedule screening examinations, without mention of other elective imaging studies ( ) . still others have requested that patients postpone all elective imaging ( - ). one group directed patients to reschedule only if they were symptomatic ( ) . cost levers to mitigate the impact of the pandemic practice leaders carefully assess a group's culture, values, and expectations while pulling various cost levers in response to financial challenges. they thread a needle by pulling enough levers to capture cost reduction opportunities while minimizing the impact on group morale and practice effectiveness. table provides a sample multi-tiered strategic action plan similar to that used by several practices to respond to the pressures of the pandemic. table presents real world examples of the extent to which several practices pulled each of the common practice levers and details the impact of such adjustments. personnel costs often underwent dramatic adjustments. radiology executives in large private practice firms reduced their base salaries from - %. ( , ) radiologists anecdotally described similar substantial salary reductions. radiologist salaries were often reduced to maintain compensation for technologists, nurses, and other staff. some practices reduced fulltime radiologist work schedules to - days per week, required unpaid leave, and reduced or eliminated bonuses. these changes impacting radiologists were similar to media reports of other physicians experiencing work reductions and furloughs. ( ) ( ) ( ) ( ) several practices terminated or curtailed work for temporary and locum tenens contracted radiologists. some associate pre-partner radiologists were dismissed. administrative and educational time were often reduced. some practices removed stipends or extra compensation for after-hours, on-call, and contrast material injection coverage tasks, and incorporated them into regular work expectations. one practice absorbed after-hours contrast material coverage into the regular staff responsibilities for much of and plans to save $ , per practice site per year. some pension contributions were reduced by - %. several practices have suspended investment and system and infrastructure improvements. other practices have renegotiated facility or equipment leases and maintenance contracts and/or requested forbearance or interest rate reduction for outstanding debt expenses. ( ) practices carefully weighed the emerging financial picture of the covid- pandemic with commitments to those hired prior to the pandemic who were scheduled to begin work between march and july . some practices have rescinded offers for employment while others are honoring employment offers with modifications, such as salary decreases, work hour adjustments, unpaid leave, and delayed starting dates. the coronavirus aid, relief and economic security (cares) act, the paycheck protection program, and health care enhancement act provided $ billion in relief funds to hospitals and other healthcare providers that were supporting the coronavirus response, including radiology practices. individual publicly-traded hospital operators received up to $ million, and individual hospital systems received up to $ million. ( ) several radiology practices have applied for and received funding. los angeles, ca based radnet has publicly announced receiving almost $ million under the first cares act appropriation and almost $ million of accelerated medicare advance payments.( ) smaller allocations are not yet publicly available, and practices are understandably hesitant to share these financial details. details of these government programs are complex and beyond the scope of this manuscript. essentially, federal programs sought to provide cash infusions to practices experiencing financial distress as a result of the covid- pandemic. some of the funds are or may become grants, while others are loans. the precise criteria used to evaluate and award these distributions are not clear. various provisions of the cares act and related government assistance programs include payroll tax deferrals, income tax deferral, interest deductibility, temporary suspension of the medicare sequester, medicare advanced payment loans, and funding of a public health emergency fund. these programs can be critical for private practices attempting to support their teams while enduring volume losses. "pain now" versus "pain later" most of the private practices with which we have communicated aimed to closely pair expense reductions with revenue decreases. radiologists in these practices experienced a substantial income reduction, as their practice quickly adjusted to the new economic reality. this rapid "pain now" strategy aims to reduce cash expenses by modifying a previous operational model and aims to sustain the practice in the long term by more slowly utilizing financial reserves. larger and better capitalized practices may be able to amortize the impact of the pandemic over a longer time horizon. several radiologists whose practices are closely aligned with large hospital systems or corporations indicated they have not experienced changes from the pandemic, despite their practices experiencing substantial decreases in examination volumes. we believe these practices are pursuing a "pain later" strategy that is likely to have delayed or prolonged yet-to-be determined adjustments. long-term impact of the pandemic increased unemployment is likely to increase use of government healthcare insurance, effectively decreasing average revenue per examination across fee-for-service practice models. this could challenge future investment in technology and practice growth and may slow the rate of private equity and corporate investments in radiology practices. we anticipate practices will reduce costs and debt to preserve financial flexibility to protect against future unexpected decreases in imaging demand. some groups may prove unable to survive the covid- pandemic, potentially fueling trends either toward consolidation into larger radiology groups or toward increased employment by hospitals. we anticipate that small radiology practices may be at greatest risk for consolidation with larger radiology groups that have a more diversified practice model regarding inpatientoutpatient mix, subspecialty service lines, and geography. practices developed capabilities for radiologist remote reading during the pandemic that may persist offering more variable approach to work-life balance and to earning partnership while also controlling costs and managing potential future disruptions. we anticipate practices may adjust employed physician contracts to better mitigate practice risk from potential future volume disruptions. base salary may comprise a smaller portion of overall compensation, with the balance dependent on the overall financial performance of the organization and/or individual productivity. a,s organizations look to control costs and senior radiologists opt to delay retirement, the radiologist job market may change. there is precedent for this effect following the financial crisis of - . the popularity and subsequent availability of subspecialties hardest hit by volume decreases, such as breast imaging, may be impacted in the near-term. the covid- outbreak highlights the potential role of outpatient imaging centers in protecting patients from exposure while providing efficient urgent and emergent imaging. ( , ) some groups designated covid- imaging centers and facilitated efficient outpatient management of many suspected or confirmed cases. private practices appreciate the rapid dissemination of new data related to covid- by their academic radiology colleagues. variations in how academic and private practices, particularly those in more rural communities, have experienced the burden of disease has led to differing views on important issues, including the timing of starting and stopping routine screening mammography and non-urgent outpatient imaging. this phenomenon highlights the need for private practice community-based physicians to participate in the development of national trends and standards, and for those national trends and standards to incorporate appropriate flexibility for local healthcare environments. private practice radiology groups were especially vulnerable to abrupt financial losses as demand for imaging services greatly declined during the coronavirus disease (covid- ) pandemic. after reflecting on their values and priorities, private radiology practices crafted tiered strategies to respond to the impact of the pandemic by pulling various cost levers to adjust service availability, staffing, compensation, benefits, time off, and expense reductions. in addition, they have sought additional revenues, within the boundaries of their practice, to mitigate ongoing financial losses. the longer-term impact of the pandemic will alter existing practices, making some of them more likely than others to succeed in the years ahead. tables table . a sample tiered strategic action plan utilized by private practices to articulate their short-to mid-term pandemic response plan. (cme, continuing medical education; m, million) strategic action plan status private equity firm rapidly acquired several practices, is now highly leveraged and unable to access financial resources figure . graph of weekly examination volumes and work relative value units (rvus) generated in practice a. examination volume was steady in january and february , followed by an abrupt decrease in early march and subsequent increase thereafter, not returning to baseline by the end of may . the coronavirus crisis: u.s. economic slowdown in coming months expected to be worst on record economic research: unemployment rate covid- : briefing materials-global health and crisis response. mckinsey and company us economy shrinks at fastest rate since . british broadcasting corporation collateral damage of covid- pandemic: delayed medical care independent physicians push for expedited covid- aid the economic impact of the covid- pandemic on radiology practices planning framework for hospital leaders for the next phases of covid- envision healthcare to consider bankruptcy filing acr commission on human resources workforce survey executive order - -declaration of state of emergency mergers and acquisitions for the radiologist open-microphone session: navigating the landscape of changing practice models: private practice, corporate radiology, and enterprise systems white paper: corporatization in radiology survey of radiologists: practice characteristics, ownership, and affiliation with imaging centers hospital margins slump due to squeeze from volume, rates, investments patient info: visiting a radia imaging center coronavirus update - / / . skagit radiology incorporated professional services services update | covid- inslee to extend coronavirus stay-at-home order, outline how washington's economy will reopen. the seattle times published covid- ) update. inland imaging mednax top execs take % pay cut as radiology firm eyes covid- bounce back mayo clinic announces sweeping pay cuts, furloughs. mpr news a major medical staffing company just slashed benefits for doctors and nurses fighting coronavirus tenet health cuts employee benefits to meet covid- demand hospitals furloughing staff in response to covid- cutbacks for some doctors and nurses as they battle on the front line radnet reports first quarter financial results and announces strong liquidity position as a result of completing cost savings and cash conservation measures radiology department preparedness for covid- : radiology scientific expert panel policies and guidelines for covid- preparedness: experiences from the university of washington the members of the rsna covid- task force are as follows: eliminate locums radiologists key: cord- -ekajojon authors: kaukinen, catherine title: when stay-at-home orders leave victims unsafe at home: exploring the risk and consequences of intimate partner violence during the covid- pandemic date: - - journal: am j crim justice doi: . /s - - - sha: doc_id: cord_uid: ekajojon the novel coronavirus pandemic (hereafter covid- ) is likely to have unprecedented impacts on the incidence and impacts of crime and violence globally. this includes impacts to the risk, consequences, and decision-making of women experiencing violence by an intimate partner (hereafter ipv). most importantly, the covid- pandemic, and its impact on the risk of ipv is likely to differentially impact vulnerable populations, including minority women and those with long histories of victimization and mental health issues. this review paper explores the potential short- and long-term implications of covid- on the risk of ipv, highlighting some of the most recent preliminary data. the economic impact of the covid- pandemic, record levels of male unemployment, added stressors in the home, including the care and home schooling of children, and the social distancing measures required by the epidemiological response, may serve to undermine the decades of progress made in keeping women and children safe at home. victim police reporting, help-seeking decisions, and social service utilization during the pandemic are likely to be impacted by stay-at-home orders and social distancing requirements. the paper concludes with a discussion of the implications for providing safety planning and self-care for victims and their children. the novel coronavirus pandemic ) is likely to have unprecedented impacts on the incidence and impacts of crime and violence globally. this includes impacts to the risk, consequences, and decision-making of women experiencing violence by an intimate partner. there has been a dramatic decline in the risk of lethal and less-than-lethal intimate partner violence (hereafter ipv) since the early s (powers & kaukinen, ; xie, heimer, & lauritsen, ; lauritsen & heimer, ). catalano ( ) notes that between and there has been an overall decline of % in the rate of intimate partner violence in the united states. this decline can be found in both official data from law enforcement agencies, but also in survey-based victimization data. the decline in women's risk of lethal and less-than-lethal ipv is a function of women's declining risk exposure via changes in the economic status and well-being of women, declines in women's dependence on marriage (via increased employment of women, declining marriage rates, and increasing access to and rates of divorce), general awareness of the nature of intimate partner violence and decreasing stigma for victims to come forward and report that violence, and the expansion and availability of intimate partner violence services and interventions. the short-and longterm health consequences of covid- , stay-at-home orders and social distancing measures, family isolation, and the economic impacts of the pandemic are likely to impact both women's experience of ipv and their ability to navigate ending these violent relationships, and potentially reverse the declining trend in ipv. boserup, mckenney, & elkbul ( ) note that the social isolation associated with quarantining and mandatory stay-at-home orders may worsen the economic and health vulnerabilities of many ipv victims due to a lack of established social support systems. mazza, maranoa, laib, janiria, and sania ( ) have suggested that covid- stay-at-home orders and social distancing will likely lead to a woman's home becoming one of the most dangerous places for ipv victims due in large part to the requirement to quarantine day-after-day with their violent and abusive partner with limited access to those that might provide care and assistance. the economic impact of the covid- pandemic, record levels of male unemployment, added stressors in the home, including the care and home schooling of children, and the social distancing measures required by the epidemiological response, may serve to undermine the decades of progress made in keeping women and children safe at home. a recent article in the new york times by taub ( ) suggests that "movement restrictions aimed to stop the spread of the coronavirus may be making violence in homes more frequent, more severe, and more dangerous." the irony may be that in keeping many citizens safe from the health risks of covid- , we may be placing many women and children at greater risk for family violence. in looking at the way in which the covid- pandemic is likely to shape the incidence, prevalence, and impact of ipv it is important to note that scholars have explored how past natural disasters and epidemics have shaped trends in rates of violence, impacted the health and well-being of ipv victims, but also exacerbated the factors associated with violent behaviors and victimization. this includes work in the united states and abroad on the impact of hurricanes, earthquakes, and other natural and man-made disasters (parkinson, ; campbell & jones, ; chan & zhang, ; buttell & carne, ). there is strong evidence to suggest that women's physical and mental health and the risk of ipv is connected to the consequences of natural disasters and pandemics, including social isolation, economic instability, and increasing relationship and family conflict. given the likely impact of the covid- pandemic on the risk for a number of consequential health impacts, galea, merchant, & lurie ( ) point to the need for investments in efforts to ensure historically marginalized groups and those likely to be isolated during the pandemic receive outreach services. this includes older adults, women with historic victimization experiences, and those with mental illness and chronic health conditions. drawing on police calls for service and arrest data from the new orleans police department, both before and after hurricane katrina, buttell and carney ( ) found a significant increase in calls for service, along with increased rates of arrests for domestic violence related offenses. they also found an increase in the severity of ipv in the post-hurricane data. most importantly, buttell and carney ( ) note that the new orleans police department actively responded to ipv calls for service following hurricane katrina and that there was not an agenda to prioritize other demands on police time during and after the crisis. bell and folkerth ( ) have shown that survivors of natural disasters have significant health sequelae and that ptsd and depression are commonly seen in women who have lived through a natural disaster. their work also draws on data post-hurricane katrina and showed that rates of violence against women rose from . cases per , per day to well over cases per , per day among displaced populations following the hurricane. they found that one year after hurricane katrina those victims housed in fema trailer parks reported higher levels of negative mental health as compared to non-victims. in contrast, work by bell & folkerth ( ) note evidence suggesting that for some couples natural disasters may enhance intimate relationships, particularly among those individuals and couples with a strong sense of community and social cohesion, along with those with a strong integration into the workforce. these unprecedented events may provide increased time for couples to share coping mechanisms to manage the stress of these disasters, and may also provide motivation and incentives to draw on social support systems that enhance their intimate relationship and relationships with others. work by jenkins and phillips ( ) notes that while domestic-violence victims and survivors experienced heightened levels of violence during hurricane katrina and its aftermath, even in that difficult context, some women made the choice to call the police, report the violence, and leave their abusive situations. this suggests that the stress and impact of natural disasters and pandemics may impact the decision-making of ipv victims. they also noted that victim advocates responded in new ways to help these women meet their unique needs as both victims of ipv and post-katrina survivors. as with these natural disasters, and perhaps the covid- pandemic, there may be an impetus for some women with long histories of ipv to report to the police and seek assistance from diverse medical and social service entities. it may be that the pandemic will serve at the final crisis situation in their violent relationship. these natural disasters may therefore serve as a cathartic event for victims of ipv, leading to a turning point in attempts to bring an end to a violent relationship. for some victims, the pandemic may create the context in which they will proceed through what burke, gielen, mcdonnell, o'campo, & maman ( ) note as the key behavioral changes needed for ending and fleeing a violent relationship. this includes assessing the options for and preparing for leaving, selection of action(s), and the use of safety strategies to remain free from violence and abuse. what do we know so far? early data on the impact of covid- on ipv it will be challenging to fully document the early impact of the covid- pandemic on the incidence and impact of ipv due to the hidden nature of violence at the hands of an intimate partner. the low rates of police reporting and the challenges for scholars to quickly deploy a research plan that would be able to draw on diverse methodologies to measure victimization experiences among a representative sample of the population, will impact the ability to assess the connection between covid- and ipv. this is a consequence of the under-reporting of these crimes to law enforcement agencies, the under-utilization of victim and social service agencies by victims, and the challenge of collecting self-report victimization data during the pandemic. most importantly, researchers do not yet have access to the types of data that would most readily allow for an examination of the relationship between covid- and ipv. a recent article by the world health organization ( ) notes that many of the survey research methodologies drawn on traditionally in the violence against women literature, will not be practical during the pandemic and others research strategies may place women at risk of violence. yet, there is some early data from the united states and abroad that suggests there have been increased reports of ipv during the pandemic, particularly increases in officially reported ipv to police agencies, emergency rooms, domestic violence hotlines, and social service agencies. it is important to note that police reported crimes and victimization are not clearly correlated to actual levels of criminal and violent behavior. increased reporting to the police and victim service agencies may be (and is likely to be) a function of an increased number of victimization experiences of those victims who are most apt to call the police to report their experiences. these are more likely to be victims with the economic resources to be able to navigate ending a violent relationship and have the social support systems to assist. changes in official reporting rates may also be a function of a change in the experiences and decision-making of those who were victims of ipv prior to the pandemic. the pandemic may serve as the catalyst for victims to report their experiences. importantly, the early data on the relationship between covid- and ipv come from news agencies who report data from police agencies, domestic violence shelters, and/or emergency rooms from individual or small groups of cities. for example, taub's ( ) new york times article notes evidence for the relationship between covid- and increased rates of ipv citing significant increased calls to domestic violence emergency support lines in china, italy, and spain. yet the source, nature, and quality of the data for these reports is not clear. bradbury-jones and isham ( ) similarly note that the leading ipv organization in the united kingdom reported that calls to its domestic violence hotline increased by % within the first week of the tighter social distancing and stay-at-home measures. similarly, azpirir ( ) also notes that a vancouver-based domestic violence crisis line had experienced a % increase in calls amid the covid- pandemic. victims have also increased their utilization of internet based resources. this includes increased internet browsing traffic to a united kingdom-based website, which has seen a % surge in traffic after the government lockdowns (bradbury-jones & isham, ). campbell ( ) has suggested that "the growing global trend of increasing reports of domestic violence cases is likely to continue throughout the pandemic and may only represent a "tip of the iceberg" as many victims still find themselves trapped with the perpetrator and unable to report the abuse." the increasing sale of guns and ammunition during the pandemic also give rise to added concern for women's safety, given the link between firearm access and the risk of lethal ipv. an additional concern is the increased risk of children's exposure to ipv given stay-at-home orders and school cancellation. these are alarming increases in documented reporting via law enforcement agencies and victim service providers with consequential health and mental health impacts. importantly, they do not have the ability to tell us about the experiences of victims that do not seek assistance or are unable to make such calls due to shared quarantining with their abuser. what will be needed as we proceed through the pandemic is the triangulation of diverse data sources from both criminal justice and social service agencies and self-report victimization data to explore the relationship between covid- and ipv. to fully understand the extent of ipv as function of the stressors associated with covid- , stay-at-home orders, and social isolation researchers will need to identify the characteristics of the women and children that are/were most at risk during the pandemic. research by piquero, riddell, bishopp, narvey, reid, and piquero ( ) , published in this special issue, provides an initial exploration of the way in which the stayat-home measures associated with the covid- pandemic may be correlated with domestic violence calls for service. using domestic violence incident reports for dallas, texas and an intervention time-series methodology, they compared domestic violence crimes for an -day period before the mandated stay-at-home orders to a -day period thereafter. they conclude that there is some evidence pointing to a short-term increase in the two weeks immediately following the stay-at-home orders in dallas, but also note a decrease after the initial rise in officially reported ipv incidents. the authors are cautious to attribute the increase to covid- orders as the cause of this increase, as they note, appeared to have been part of an increasing trend in officially reported ipv prior to the stay-at-home orders. they also note that the short-term upward trend in domestic violence incidents may have been associated with citizens voluntarily following cdc recommendations to social distance and quarantine. piquero, et al. ( ) also note that work looking to examine the association between covid- lockdown orders and changes and trends in domestic violence need to recognize the importance of exploring the factors associated with the economic implications of the pandemic that are associated with the risk of ipv, including the social isolation associated with remote work and the financial stress of layoffs and furloughs. the longstanding body of research on the reporting (and under-reporting) of ipv to the police will be important in the context of the work that will be needed to explore the connection between covid- and ipv. the extensive scholarship on police reporting and ipv highlights the fact that the domestic violence crimes brought to the attention of the criminal justice system are not representative of all incidents of ipv (or ipv victims), and that the majority of these crimes remain unrecorded by official statistics. police calls for service are therefore not a good measure of true incidence of ipv, and this may be particularly true during covid- . there are a number of factors that are likely to shape increases, stability, or declines in ipv calls for service to the police, and the incidence of actual violent behavior and victimization is just one of those. these are discussed below. if we rely on data on social service utilization during covid- , we are also likely to see a decline in this type of help-seeking and reporting because of social distancing measures that will prevent victims from accessing services. we will therefore need to expand our data collection efforts beyond police reported incidents, emergency room admissions, shelter data, and data from diverse social service providers. in examining women's risk for intimate partner violence during covid- , self-report victimization surveys offer an advantage over official law enforcement estimates. the use of large-scale representative victimization data will help avoid some of the problems associated with law enforcement and clinical sample bias, providing researchers with a larger estimate of the extent and dynamic nature of ipv. yet a different form of selectivity will bias these estimates, particularly during covid- . self-report data typically underrepresent the most severe and violent forms of intimate partner violence and abuse, particularly among women with chronic health conditions and disabilities. the samples from self-report data may therefore not include all women who are the victims of the most severe types of ipv or those who are victims of covid- disease. this points to the need for careful joint analyses of self-report survey data, estimates from law enforcement agencies, and clinical data during and after covid- to tap diverse types of intimate partner abuse and also explore the way in which covid- disease progression may place women at further risk for physical violence, emotional and financial abuse, and coercive control. this may be particularly true for older victims of ipv, and would be exacerbated by covid- disease and symptoms. this points to the need for leadership at the state and national level to organize and coordinate data collection for research and policy decision-making. we likely will not have a good selfreport measure of ipv during the pandemic, perhaps some researchers will be able to measure in smaller regions with national science foundation rapid grants and other funding mechanisms, but a national level data collection seems unlikely. if this were to happen, the leadership for the national crime victimization survey would need to move very quickly to develop measures that could tap changes in ipv, both during and immediately after the pandemic, but also measure the factors that might correlate with both ipv and covid- , including the social isolation and stressors associated with social distancing and quarantine and the economic impacts of the pandemic on families. there are a number of predictions that could be made with regard to the impact of covid- and police reports of ipv. it is likely that we will see an increase in domestic violence calls for service to the police because of an actual increase and change in the level of violent behavior by some batterers and abusers. this is likely to be the case among the same set of women who were victims of ipv prior to covid- , and who might also during covid- experience a greater number of individual incidents of violence by their previously abusive partner and perhaps more severe types of abuse. this increase in the incidence and severity of violence by historic abusers may lead to new reporting behaviors by these victims, and/or someone else in their household or neighborhood might increase their reporting to the police. it is also likely that we will see a new set of victims experience violence due to the consequences of social distancing measures and stay-at-home orders. these measures have placed those most vulnerable to violence and abuse in close proximity to their potential abuser, and this may lead to an increase in the risk factors associated with ipv. the cause of this increase is likely to be shaped by a variety of factors that are associated with ipv more generally, but that will be more prevalent during the covid- pandemic. this includes social isolation and increased attempts by abusers to exert power and coercive control, unemployment, economic distress, marital conflict, and substance use and abuse. these are discussed further below. the covid- epidemic may also serve at a turning point for some victims of ipv, creating the crisis and catharsis that leads to attempts to flee and end the violent relationship. alternatively, the rates of police reporting (victim calls for service) during covid- could stay relatively flat. we might actually see those who have been victims of ipv prior to the pandemic to now be less apt to call the police during covid- . so, while actual behaviors by offenders may stay the same or incidents of violence may go up during the pandemic, some victims during covid- may be less likely to call the police or seek help. this could be for a number of reasons, including the lack of access to a secure place to call the police and reach out for help, and/or the inability to find a safe place to research options for leaving (including safety planning, organizing paperwork, and packing) due to quarantine and stay-at-home orders. the lack of economic resources to leave the abuser during the pandemic and fear of reprisal by the offender, leading to greater violence, will also impact victim decision-making. rates of police reporting may also decline. there may be some women who will be less likely to call the police during the pandemic because they want to reserve these essential services for those in immediate needspecifically covid- patients. it may be that during covid- , that in some jurisdictions, rates of police reporting could go down, and rates of police reporting among some types of ipv victims decline. actual violent behaviors may stay the same (or go up) or incidents of violence experienced by women who have been experiencing ipv prior to the pandemic may stay the same (or go up), but now women are even less likely during covid- to call the police to seek help for fear of reprisal and inability to find a safe place to call due to social distancing. illness associated with covid- disease may also impact a victim's ability to reach out for assistance with ipv. calls for service would therefore decline during this time. during covid- social distancing and stay-at-home orders may expand a current perpetrator's coercive control and power over their victim. with victims and perpetrators in close proximity, batterers will be able to increase their ability to be in control of decision-making, determine day-to-day outcomes, and monitor and socially isolate their victim from family and friends. bradbury-jones and isham ( ) note that the home is often a sphere where the dynamics of power are distorted and subverted by perpetrators. during covid- this is made worse due to the lack of outside scrutiny from family and friends. for many victims, this will lead to increased physical violence, emotional and financial abuse, and coercive control. alternatively, for those victims who have learned to adapt to their batterers control techniques and read the cues for their use of violence and abuse, the use of ipv by some batters may decline. given stay-at-home orders, the batterer will be better able to exert day-to-day control over household decision-making, and there may be less perceived "need" by the abuser to use physical violence since the batterer is able to exert control and manipulate their victim. during stay-at-home orders, abusers may be better able to know where their victims are and control their victim's access to their family and friendspreventing access via the phone, computer, and/or other technologies. for these batterers, their ability to gain control and manipulate their victim, may lead them to not "need" to use physical methods to gain coercive control. there are a number of elements of the covid- pandemic that may also serve as mechanisms of control by abusers. for example, batterers use a variety of methods to exert control over their victims and keep their victims in a constant state of fear. these may be expanded during the pandemic. covid- may be used by offenders (both those currently with their victim and those who are separated or divorced) as a way to control the victim via threats to expose them and their shared children to the novel coronavirus. victims may also fear their abuser taking their children outside of the home during the outbreak and not be able to control who their children are exposed to or whether proper hygiene and social distancing measures are practiced. other violent partners (and ex-partners) may use a victim's risk for covid- (sucha as those who are healthcare providers, grocery store workers, working in transportation, etc.) as a way to seek custody of their shared children during the pandemic and this custody may continue after the pandemic. healthcare providers may be particularly vulnerable to this type of abusive behavior since children may be social distancing with the abusive partner while the victim is forced to quarantine in another area of their home or outside of the home due to their ongoing risk for covid- . the risk factors for ipv victimization and the factors that limit women's ability to leave violent relationships include economic dependence on male partners (i.e., lack of education, income, and employment) and the responsibility for children both before and after divorce. a history of violent victimization also places women at risk. demographic factors also shape risk, including age (younger), race/ethnicity, and marital status (cohabitation and dating). finally, male partners with drug and alcohol problems, chronic unemployment, and prior intimate partner violence are at greater risk for perpetration, and these factors may be particularly prevalent during the covid- pandemic. it is difficult to know whether during the pandemic we might see violence by new offenders (men who were not previously violent to their partner) or an increase in violence by previously violent men due to increased proximity and exposure between victims and offenders, and the exacerbation of these risk factors for ipv. the question researchers will need to explore both during the early stages of the pandemic and long-term is whether there has been (or will be) an increase in ipv among men who were not previously violent due to factors that enhance the risk for ipv that also correlate with the covid- pandemic (see below). alternatively, will we may be most likely to see an increased incidence and severity of violence by perpetrators who were previously violent, but now covid- has exacerbated the role of those risk factors. stress frustration perspectives posit that any form of negative affect or distress is likely to increase the likelihood of violence and aggression. stressful life events produce aggression and violence because they create negative affect. stress-frustration theories (holtzworth-munroe, bates, smutzler, & sandin, ) suggest that diminished economic resources within the family lead to stress, frustration, and conflict in intimate relationships that heightens the risk of male-perpetrated violence against women. this suggests that during covid- women with unemployed partners would be at the greatest risk for ipv and abuse. the economic uncertainty during the pandemic and record levels of unemployment are likely to add to the stress experienced by both men and women, heightening the risk of marital conflict and violence. economic and marital dependency of female partners on their husbands will place many women at risk for new or continued ipv during covid- , and also create financial challenges to women navigating ending a violent relationship. women's lack of employment and financial resources during the pandemic, and their disproportionate responsibility for children will limit their ability to end violent relationships and/or identify mechanisms for leaving their abuser. some feminist research (kaukinen, ; anderson, ) also suggests that economic variables are often symbolic in nature and that men who do not have access to marital power via employment and economic resources will use violence in an attempt to re-establish their power at home, given their lack of access to economic resources to establish a traditional masculinity. the financial stress of the covid- pandemic will be unprecedented. we have already seen the highest rates of unemployment in the last years. for those couples in which the female partner may be able to continue working (remotely or otherwise), while the male partner is unemployed, will experience a shift in economic and symbolic power, particularly among couples in which the male partner previously held that "breadwinner" role. in exploring the role of covid- and the risk of ipv, social distancing and stay-athome orders will likely lead to increased conflict, disagreements, and arguments due to increased daily proximity of couples. this in turn could lead to an increased prevalence of common couple violence among both couples with and without previous ipv. johnson ( ) notes that this type of intimate partner violence does not include severe acts of violence, is likely to be mutual between partners (gender symmetric), and does not exhibit a general pattern of coercive control by the male partner. a recent new york times article by taub ( ) on china noted that some victims stated that "during the epidemic, we were unable to go outside, and our conflicts just grew bigger and bigger and more and more frequent," "everything was exposed." for some couples, particularly those experiencing financial and family stressors during the pandemic, they will likely have an increase in the number of arguments and conflicts during sustained social isolation and physical proximity. increases in common couple violence is a likely consequence of the pandemic, particularly among young and newly formed intimate relationships. the risk and impact of ipv during the covid- pandemic may also be shaped by rates of drug and alcohol use and abuse. there is research (brooks, webster, smith, woodland, wessely, greenberg, & rubin, ) to suggest that quarantine and other social isolating conditions are associated with alcohol abuse, depression, and posttraumatic stress symptoms. while researchers (fals-stewart, ; leonard & quigley, ) have pointed to a strong correlation between drinking, and in particular heavy alcohol consumption, and the risk of intimate partner violence, the exact mechanism is less clear. some scholars have suggested that problematic drinking and the risk of ipv perpetration may share a common etiology, a need to achieve personal power and control. my own research has shown that women with male partners who engage in heavy episodic drinking are also more likely to engage in both physical violence and coercive control. the exact relationship between alcohol (and drug) use and abuse and the risk of ipv is complicated. substance abuse, along with the economic stressors associated with covid- will provide perpetrators with an excuse (and justification) for their violent and abusive battering behaviors, and an explanation for victims to excuse their abuser. alcohol allows perpetrators to justify their violent behavior, and for victims to explain it and excuse it. it is therefore best to view substance use as a risk marker for ipv, while not a direct cause. at the same time, drinking may increase the frequency or severity of male perpetrated violence against women. clay and parker ( ) note the importance of public health approaches that explore the public health effects of long-term social isolation related to covid- on alcohol use and misuse noting the need to protect the most vulnerable individuals from excessive alcohol consumption during the pandemic. in addressing the connection between substance use and the stressors associated with covid- , da, im, & schiano ( ) note the need to put in place awareness and telehealth strategies to curb what is likely to become a serious consequence of the coronavirus pandemic. many ipv victims will be reluctant to seek help from healthcare providers or engage in social service utilization during the pandemic. for some victims, they may be reluctant to seek healthcare or other emergency care for their ipv-related injuries due to the fear of contracting covid- due to enhanced exposure in healthcare settings. other victims might believe they should reserve those healthcare services for the people most in need, those suffering from covid- disease. many ipv victims will have reduced access to victim services during the pandemic since many of these services are limited by social distancing and stay-at-home orders and are only operating remotely. remote type therapies and services are likely to place many victims at risk for further violence by their abuser or may lack access to phones and internet during covid- due to financial hardships or coercive control by their abuser. access to housing and other advocacy services will continue to be limited during the early days of stay-at-home orders due to social distancing and quarantine requirements, with many of these services temporarily shut down, including courthouses for example. a fall outbreak of the pandemic will make worse women's experiences with ipv and further limit their options for leaving a violent partner. there will be the need for strong federal and state leadership to expand victims' access to support services and economic resources during the pandemic. we will need to be creative in our thinking on how to outreach to victims and provide awareness messaging to bystanders. we will need to create ways in which ipv victims will be able to safely access both in-person and telehealth options in discrete ways without alerting their perpetrator. bradbury-jones and isham ( ) also point to the importance of protecting the advocates who work in a voluntary manner to support victims and the need for personal protective equipment to be provided. boserup, mckenney, & elkbul ( ) note the importance of making ipv screening tools and assessments more readily available in diverse clinical settings and among telehealth providers during the pandemic. social workers, advocates, and others who work with victims will need to identify ways to safely work with victims on safety planning and self-care, but also plans for victims to leave their violent partner. there will need to be collaboration and creative thinking on how to expand the availability of services and diversify the nature of transitional housing, particularly for victims who may have contracted or been exposed to covid- . for those victims who report to the police, there will be a need for more intensive police and social service follow-up both during and after the covid- pandemic. this will be particularly true for women who remain in their home with the abuser. finally, we will need to change the way in which awareness campaigns have provided information to ipv victims and bystanders. reliance on public spaces for this information is no longer the most effective way to outreach to victims. boserup, mckenney, & elkbul ( ) therefore suggest that diverse social media outlets should seek to identify ways to reach a wider audience during city lockdowns and stay-at-home orders. gender, status, and domestic violence: an integration of feminist and family violence approaches women's mental health and intimate partner violence following natural disaster: a scoping review alarming trends in us domestic violence during the covid- pandemic the pandemic paradox: the consequences of covid- on domestic violence the psychological impact of quarantine and how to reduce it: rapid review of the evidence examining the impact of hurricane katrina on police responses to domestic violence the process of ending abuse in intimate relationships: a qualitative exploration of the transtheoretical model an increasing risk of family violence during the covid- pandemic: strengthening community collaborations to save lives an innovative response to family violence after the canterbury earthquake events: canterbury family violence collaboration's achievements, successes, and challenges intimate partner violence female victimization and intimate partner violence after the may alcohol use and misuse during the covid- pandemic: a potential public health crisis? the lancet: public health covid- hangover: a rising tide of alcohol use disorder and alcohol-associated liver disease the occurrence of partner physical aggression on days of alcohol consumption: a longitudinal diary study the mental health consequences of covid- and physical distancing. in the mental health consequences of covid- and physical distancing: the need for prevention and early intervention a brief review of the. research on husband violence. part i: maritally violent versus non-violent men battered women, catastrophe, and the context of safety after hurricane katrina status compatibility, physical violence, and emotional abuse in intimate relationships gender and violent victimization drinking and marital aggression in newlyweds: an event-based analysis of drinking and the occurrence of husband marital aggression danger in danger: interpersonal violence during covid- quarantine investigating the increase in domestic violence post-disaster: an australian case study staying home, staying safe? a short-term analysis of covid on dallas domestic violence trends in intimate partner violence a new covid- crisis: domestic abuse rises worldwide violence against women and girls data collection during covid- violence against women in us metropolitan areas: changes in women's status and risk key: cord- -lkfhtb w authors: davahli, mohammad reza; karwowski, waldemar; sonmez, sevil; apostolopoulos, yorghos title: the hospitality industry in the face of the covid- pandemic: current topics and research methods date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: lkfhtb w this study reports on a systematic review of the published literature used to reveal the current research investigating the hospitality industry in the face of the covid- pandemic. the presented review identified relevant papers using google scholar, web of science, and science direct databases. of the articles found, papers met the predefined inclusion criteria. the included papers were classified concerning the following dimensions: the source of publication, hospitality industry domain, and methodology. the reviewed articles focused on different aspects of the hospitality industry, including hospitality workers’ issues, loss of jobs, revenue impact, the covid- spreading patterns in the industry, market demand, prospects for recovery of the hospitality industry, safety and health, travel behavior, and preference of customers. the results revealed a variety of research approaches that have been used to investigate the hospitality industry at the time of the pandemic. the reported approaches include simulation and scenario modeling for discovering the covid- spreading patterns, field surveys, secondary data analysis, discussing the resumption of activities during and after the pandemic, comparing the covid- pandemic with previous public health crises, and measuring the impact of the pandemic in terms of economics. on december , , the government of wuhan, china, announced that health authorities were treating dozens of new virus cases, identified as coronavirus disease (covid- ) [ ] . since then, covid- , a new strain of sars (sars-cov- ), has grown into a global pandemic and spreading across many countries. a highly transmissible respiratory disease, covid- spreads through contact with other infected individuals, with symptoms such as fever, cough, and breathing problems [ ] . transmission can also occur from asymptomatic individuals, with up to % of infected persons remaining asymptomatic [ ] . other factors that facilitate infection include ( ) speed and efficiency of covid- transmission; ( ) airborne transmission [ ] ; ( ) close contact between infected and non-infected individuals; ( ) vulnerability of immunocompromised individuals with specific underlying health conditions (e.g., hypertension, diabetes, cardiovascular disease, respiratory problems); ( ) susceptibility of persons over ; and ( ) contact with persons who have traveled to locations with a high number of cases [ ] . rq . what aspects of the hospitality industry at the time of the covid- pandemic have been studied? rq . what research methodologies have been used to investigate the impact of covid- on the hospitality industry? in order to address the above questions, a search strategy was developed to list and review all relevant scientific papers by (a) defining keywords and identifying all relevant materials, (b) filtering the identified records, and (c) addressing the risk of any bias [ ] . one of the main steps in a systematic review is developing specific keywords. herein, our objective was to target all critical segments of the hospitality industry (e.g., hotels, restaurants) and the broadly defined tourism industry. the defined keywords are shown in table . web of science, science direct, and google scholar were used as database search tools. keywords were used to discover relevant articles and identify articles with relevant content. because this topic is rapidly evolving, it is important to mention that article discovery was finished at the end of august . after developing the main database and identifying all relevant papers, a formal screening process based on specific exclusion and inclusion criteria was followed. because of the very timely issue of the covid- pandemic, we included documents in the forms of peer-reviewed academic publications, grey literature, and pre-print articles. however, we excluded secondary sources that were not free or open access, letters, newspaper articles, viewpoints, presentations, anecdotes, and posters. the screening of the titles, abstracts, conclusions, and keywords in the identified records after removing duplication (n = ) resulted in excluding articles (n = ) because of not enough relating to the topic. the remaining articles (n = ) were read in full against the eligibility principle, and three articles were excluded for not addressing the research questions. selection bias in a systematic review can occur by the erroneous application of inclusion/exclusion criteria and/or the specification of included papers' dimensions. to address the first type of bias, two researchers (md and wk) independently reviewed the title, abstract, and conclusions of the identified records to select articles for the full-text review. subsequently, the two researchers compared their selected articles to reach a consensus. after reading the full text of the selected papers, the authors decided whether to include the article-which was considered and included upon reaching an agreement. disagreements were resolved by the input of the other two authors (s.s. and y.a.). to address the second type of bias, two researchers (md and wk) independently specified the included papers' classifications and subsequently compared the results, resolving disagreements by consultation with the other authors (s.s. and y.a.). the selection strategy, as per prisma guidelines, is illustrated in figure all included articles were categorized and stored in the main database according to year, source of publication, the industry segment, geographic location, research approach, aspect of the hospitality industry, and methodology. the characteristics of the included papers are shown in table . table . characteristics of the included papers. title segment of industry geographic location approach [ ] pandemics, tourism and global change: a rapid assessment of covid- airlines, accommodation, sports events, restaurants, cruises comparing covid- with previous public health crises [ ] hedging feasibility perspectives against the covid- for the international tourism sector tourism expenditure, inbound and outbound tourism, conference tourism, pilgrimage tourism, virtual reality tourism comparing covid- with previous public health crises [ ] how all included articles were categorized and stored in the main database according to year, source of publication, the industry segment, geographic location, research approach, aspect of the hospitality industry, and methodology. the characteristics of the included papers are shown in table . table . characteristics of the included papers. title segment of industry geographic location approach [ ] pandemics, tourism and global change: a rapid assessment of covid- airlines, accommodation, sports events, restaurants, cruises global comparing covid- with previous public health crises [ ] hedging feasibility perspectives against the covid- for the international tourism sector the publication sources of the included papers are illustrated in figure . the most popular publication sources include tourism geographies, international journal of infection diseases, and journal of tourism and hospitality education. discussing resumption of activities during and after the pandemic [ ] navigating hotel operations in times of covid- discussing resumption of activities during and after the pandemic the publication sources of the included papers are illustrated in figure . the most popular publication sources include tourism geographies, international journal of infection diseases, and journal of tourism and hospitality education. to generate a better picture of the included papers, the map of the co-occurrence of terms in the title and abstract is shown in figure . the colorful nodes are associated with specific terms, and their to generate a better picture of the included papers, the map of the co-occurrence of terms in the title and abstract is shown in figure . the colorful nodes are associated with specific terms, and their sizes represent the frequency of term occurrence, and links between two nodes indicate the co-occurrence of the terms. in this figure, frequently co-occurring terms create clusters and appear closer with the same color. a first glance at figure sizes represent the frequency of term occurrence, and links between two nodes indicate the cooccurrence of the terms. in this figure, frequently co-occurring terms create clusters and appear closer with the same color. a first glance at figure reveals the central cluster (blue color) with terms including covid- , health, travel, effect, and global tourism. sizes represent the frequency of term occurrence, and links between two nodes indicate the cooccurrence of the terms. in this figure, frequently co-occurring terms create clusters and appear closer with the same color. a first glance at figure reveals the central cluster (blue color) with terms including covid- , health, travel, effect, and global tourism. the included papers used different research approaches to investigate the impact of covid- on the hospitality industry (see figure ). each approach is explained in the following section. the included papers used different research approaches to investigate the impact of covid- on the hospitality industry (see figure ). each approach is explained in the following section. the reviewed papers used different research approaches and focused on various subjects related to the hospitality industry during the covid- pandemic. however, all papers have been classified into six groups as follows: ( ) developing simulation and scenario modeling, ( ) reporting impacts of the covid- pandemic, ( ) comparing the covid- pandemic with previous public health crises, ( ) measuring impacts of the covid- pandemic in terms of economics, ( ) discussing the resumption of activities during and after the pandemic, and ( ) conducting surveys. since some of the reviewed papers belong to more than one group, these have been assigned to the dominant group. eight included papers in this review applied simulation & scenario modeling to estimate aspects of tourism demand and the covid- spreading pattern. the studies used different models and analyses, including a dynamic stochastic general equilibrium (dsge) model, supply and demand curve, agent-based model, epidemiological model, and susceptible exposed infected recovered (seir) model. yang et al. [ ] applied dsge, a macroeconomics technique that depicts economic phenomena based on the general equilibrium framework, to investigate the impacts of increasing health disaster risk (the pandemic) and its persistence on the model parameters such as tourism demand. he incorporated two indicators (health status, and health disaster) and three categories of decisionmakers (the government, households, and producers) into the dsge model concerning the tourism sector. the findings are not surprising and point out that the longer pandemic will have a more devastating effect on the hospitality industry. bakar and rosbi [ ] utilized a supply and demand curve to analyze the economic impact of covid- on the hospitality industry. in order to develop the supply and demand curve, the demand function was created by using factors of price setting of selected goods, tastes and preferences of customers, customers' expectations, the average income of certain countries, and the number of buyers. the reviewed papers used different research approaches and focused on various subjects related to the hospitality industry during the covid- pandemic. however, all papers have been classified into six groups as follows: ( ) developing simulation and scenario modeling, ( ) reporting impacts of the covid- pandemic, ( ) comparing the covid- pandemic with previous public health crises, ( ) measuring impacts of the covid- pandemic in terms of economics, ( ) discussing the resumption of activities during and after the pandemic, and ( ) conducting surveys. since some of the reviewed papers belong to more than one group, these have been assigned to the dominant group. eight included papers in this review applied simulation & scenario modeling to estimate aspects of tourism demand and the covid- spreading pattern. the studies used different models and analyses, including a dynamic stochastic general equilibrium (dsge) model, supply and demand curve, agent-based model, epidemiological model, and susceptible exposed infected recovered (seir) model. yang et al. [ ] applied dsge, a macroeconomics technique that depicts economic phenomena based on the general equilibrium framework, to investigate the impacts of increasing health disaster risk (the pandemic) and its persistence on the model parameters such as tourism demand. he incorporated two indicators (health status, and health disaster) and three categories of decision-makers (the government, households, and producers) into the dsge model concerning the tourism sector. the findings are not surprising and point out that the longer pandemic will have a more devastating effect on the hospitality industry. bakar and rosbi [ ] utilized a supply and demand curve to analyze the economic impact of covid- on the hospitality industry. in order to develop the supply and demand curve, the demand function was created by using factors of price setting of selected goods, tastes and preferences of customers, customers' expectations, the average income of certain countries, and the number of buyers. meantime, the supply function is developed by using elements of production techniques, resource price, price expectations, price of related goods, supply stocks, and numbers of sellers. the supply and demand curve was then developed in the market equilibrium condition where the demand in the market is equal to the supply in the market. finally, changes in market equilibrium as the result of the covid- outbreak were investigated. the results indicate that the pandemic created some "panic" level among people and consequently decreased overall demand in the tourism and hospitality industry [ ] . the study urged governments to discover a vaccine as quickly as possible and identify policies to prevent the further decrease in demand for tourism and hospitality services during the post-pandemic period [ ] . d'orazio et al. [ ] used an agent-based model to determine the virus spreading in tourist-oriented cities and, consequently, discover sustainable and resilient strategies [ ] . the model represented simulated individuals' movement and the contagion virus spreading approach (the epidemic rules based on previous studies) in a touristic urban area. the model calculated the probability that an infector: (i) could infect a susceptible individual j based on a linear combination of the current incubation time of (i), the exposure time, and the mask filter adopted by both i and j. the model evaluated the number of infectors within the touristic urban area over time and the number of visitors who return home being infected over time. after analyzing different scenarios, such as "social distancing-based measures" and "facial mask implementation", the results reveal that "social distancing-based measures" were related to significant economic losses [ ] . this phenomenon appears to be an effective policy in locations with the highest infection rates [ ] . however, "social distancing-based measures" lose their advantage in areas of low infection rates and a high degree of "facial mask implementation" [ ] . five studies investigated covid- cases and spreading patterns on the diamond princess cruise ship. on february , , a disembarked passenger from the ship tested positive for covid- [ ] , after which the passengers were quarantined [ ] . by the end of the quarantine, more than passengers were infected with covid- [ ] . fang et al. [ ] developed the flow of passengers (crowd flow simulation model) on the diamond princess cruise ship, and then created the virus transmission rule between individuals to simulate the spread of the covid- caused by the close contact during passengers' activities. mizumoto and chowell [ ] and mizumoto et al. [ ] developed an epidemiological model based on discrete-time integral equations and daily incidence series. rocklöv et al. [ ] collected data on confirmed cases on the diamond princess cruise ship. they used the seir model (compartmental technique estimating the number of susceptible (s), exposed (e), infected (i), and recovered (r) individuals) to calculate the primary reproduction number. the basic reproduction number is the expected number of cases directly generated by one case in a population where all individuals are susceptible to infection [ ] . zhang et al. [ ] collected data of daily incidence for covid- on the diamond princess cruise ship, data of a serial interval distribution (the time between successive cases in a chain of transmission [ ] ), and applied "projections" package in r to calculate the basic reproduction number. the studies concluded that the cruise company's immediate response in following recommended safety guidelines and early evacuation of all passengers could prevent mass transmission of covid- [ ] [ ] [ ] [ ] [ ] . seventeen papers applied secondary data analysis to report covid- pandemic's impacts on the hospitality industry. because of the ongoing pandemic and publication time of included papers, secondary data sources have been invaluable for most studies in this review. the studies reported impacts of the pandemic on different aspects of the hospitality industry, including job loss, revenue losses, access to loans, market demand, emerging new markets, hostile behaviors towards foreigners, and issues of hospitality workers and hotel cleaners. nicola et al. [ ] summarized the pandemic's impact on the global economy by reviewing news distributed by mass-media, government reports, and published papers. to better understand the impacts of the pandemic, the study divided the world economy into three sectors of primary (including agriculture, and petroleum & oil), secondary (including manufacturing industry), and tertiary (including education, finance industry, healthcare, hospitality tourism and aviation, real estate, sports industry, information technology, and food sector). they reported job loss, revenue losses, and decreasing market demand in the hospitality, tourism, and aviation sectors [ ] . ozili and arun [ ] provided a list of covid- statistics, including confirmed cases, confirmed deaths, recovered cases in several countries and continents, and discussed the global impact of covid- on the travel and restaurant industries. the study reviewed different policy measures implemented by different countries around the world to deal with covid- . ozili and arun [ ] categorized these into four groups of ( ) human control measures; ( ) public health measures; ( ) fiscal measures; and ( ) monetary measures. in the human control policies measures, different actions including foreign travel restrictions, internal travel restrictions, state of emergency declarations, limiting mass gathering, closing down of schools, and restricting shops and restaurants, have also been identified [ ] . several studies reported the effect of covid- on specific critical domains of the hospitality industry, such as undocumented workers and hotel cleaners. williams and kayaoglu argued that the most vulnerable workers in the industry need governmental financial support but cannot receive assistance, most likely because they are undocumented immigrants [ ] . furthermore, rosemberg [ ] highlighted the issues of job insecurity, risk of exposure to covid- , lack of health insurance, added pressure due to increased workload, and extra time required for ensuring complete disinfection during the pandemic [ ] . other studies focused on the pandemic's impacts on specific countries, including china, malaysia, nepal, and india. wen et al. [ ] reviewed literature and news on chinese tourist behavior, tourism marketing, and tourism management; they concluded the growing popularity of luxury trips, free and independent travel, and medical and wellness tourism post-covid- period [ ] . they indicated that new forms of tourism would be more prevalent in post-covid- , including ( ) slow tourism, which emphasizes local destinations and longer lengths of stay, and ( ) smart tourism, which uses data analytics to improve tourists' experiences [ ] . another study used automated content analysis to investigate newspaper articles and identified nine key themes among newspaper articles, including, "covid- 's impact on tourism, public sentiment, the role of the hospitality industry, control of tourism activities and cultural venues, tourism disputes and solutions, national command and local response, government assistance, corporate self-improvement strategies, and post-crisis tourism product" [ ] . two papers compared the covid- pandemic with previous public health crises. in the first study, lessons learned from previous crises and pandemics are discussed, including malaria, yellow fever, ebola, zika virus, middle east respiratory syndrome (mers-cov), avian influenza (h n ), creutzfeldt-jakob disease (mad cow disease), swine flu (h n ), and severe acute respiratory syndrome (sars) [ ] . this paper concluded that the impacts of covid- on the global economy and china's tourism and hospitality industry, in particular, are likely to differ from previous pandemics, from which the tourism and hospitality industry recovered relatively quickly [ ] . gössling et al. [ ] reviewed the impact of previous crises on global tourism, including the middle east respiratory syndrome (mers) outbreak ( ), the global economic crisis ( - ), the sars outbreak ( ), and the september terrorist attacks ( ) [ ] . the authors indicated that previous crises did not have long-term impacts on global tourism. the authors also warned about increasing pandemic threats for several reasons, including the fast-growing world population, rapidly developing global public transportation systems, and increasing consumption of processed/low-nutrition foods [ ] . gössling et al. [ ] also discussed the impact of covid- on different hospitality industry sectors. the authors distinguished the impact of covid- in view of two different aspects of ( ) observed impacts (e.g., declines in hotel occupancy rates, liquidity problems in the restaurant industry); and ( ) projected impacts (e.g., revenue forecasts in the accommodations sector, estimation of revenues) [ ] . the still-evolving understanding of the coronavirus's behavior makes it difficult to predict the industry's recovery in the near future. however, suggestions have already been made for post-covid- management of the tourism and hospitality industry. these include: ( ) focusing primarily on domestic tourism; ( ) ending mass tourism and pilgrimage tourism; ( ) focusing more on conference tourism, virtual reality tourism, and medical tourism; and ( ) building a more sustainable tourism and hospitality industry rather than a return to "business as usual" [ , ] . five papers measured the impacts of the pandemic on the hospitality industry in terms of economics. these studies used different models and analyses, including seasonal autoregressive integrated moving average model, scenario analysis, and trend analysis. the economic impact of covid- on the tourism and hospitality industry has been examined in terms of lost earnings or jobs. centeno and marquez [ ] developed seasonal autoregressive integrated moving average models for the philippines' tourism and hospitality industry, forecasting the total earnings loss of around . billion php (philippine peso)-equivalent to $ . billion-from covid- just until the end of july . to ease the pandemic's effects on the hospitality industry, the authors propose dividing the country into two regions according to the level of infection risk (high-risk and low-risk of to allow domestic travel into low-risk regions or areas [ ] . günay et al. [ ] applied a scenario analysis technique to calculate the impact of covid- on turkey's tourism and hospitality industry. their model predicts the total loss of revenues in the best and the worst scenarios as $ . billion and $ . billion, respectively, for [ ] . the worst-case scenario involves the closing of borders for four months without any economic recovery [ ] . the authors indicated that this would be one of turkey's worst tourism crises under the worst-case scenario, exceeding the losses from public health crises due to swine flu, avian flu, and sars [ ] . mehta [ ] estimated the effect of covid- on india's economy at an earnings loss of about $ billion in , along with % job losses for tourism and hospitality workers, and mass bankruptcies [ ] . trend analysis was also used to examine the impact of covid- on the global tourism and hospitality industry and global gdp [ ] . according to priyadarshini [ ] , the real global gdp growth will drop from . % in to . % by the end of , while global revenues for the tourism and hospitality industry will drop by % compared to . the study also predicts that north america, europe, and asia will experience the most massive losses in global revenues. the tourism and hospitality revenues will fall in the u.s., germany, italy, and china by %, %, %, and %, respectively [ ] . cajner et al. [ ] analyzed the covid- pandemic impact on the u.s. labor market. the study calculated that about million paid jobs were lost between march to , . to better understand this number's significance, the authors pointed out that only nine million private payroll employment jobs were lost during the great recession of the s (less than % of the pandemic job loss) [ ] . the study also highlighted that the leisure and hospitality industry was the hardest hit and most affected industrial sector [ ] . thirteen papers recommended various remedial and management actions for the resumption of activities during and after the pandemic. the consequences of covid- on the hospitality industry, such as empty hotels and loss of jobs, are discussed in one paper that offers a positive outlook that the industry will receive a significant flow of guests upon the easing of travel bans and restrictions [ ] . the author stressed the importance of support for the hospitality industry during the pandemic and the need for proper guidance to ensure successful reopening during the post-pandemic period. taking a different perspective, another study suggests that the hospitality industry may not do well after the lifting of travel bans and mobility restrictions [ ] . the study refers to a survey that found more than half of the participants would not order food even after the pandemic ends. the author also recommends a series of actions for restaurants to attract customers in the post-covid- period, such as including island-sitting arrangements to assure maximum physical distances between people, live cooking counters to allow customers to watch their food being prepared to instill confidence in its safety, and having appropriate hygiene and cleaning procedures throughout [ ] . bagnera et al [ ] investigated the impact of covid- on hotel operations and recommended a series of actions for hotel owners and managers, including using fewer rooms (reducing hotel capacity); emphasizing take-out or delivery options to reduce public dining, implementing intensified cleaning/sanitizing protocols; committing to the use of personal protective equipment (ppe) for workers and increasing attention to personal hygiene; communicating new covid- policies to guests and employees; implementing physical distancing practices in public areas, and implementing protocols for guests exposed to or infected by covid- [ ] . it should be noted that the world health organization (who) produced a guide titled "operational considerations for covid- management in the accommodations sector" to provide practical assistance to the hospitality sector in particular [ ] . the report is divided into sections for the management team, reception and concierge, technical and maintenance services, restaurants and dining rooms and bars, recreational areas for children, and cleaning and housekeeping with a list of responsibilities to help manage the threat of covid- [ ] . furthermore, jain discussed different hotel industry strategies to bring back customers, including disposable utensils in rooms, emphasizing staff health and hygiene, and using uv light to disinfect [ ] . specific steps for an exit strategy and the reopening of activities in different business sectors are presented by peterson et al. [ ] . primary steps include implementing widespread covid- testing, having enough ppe supply, lifting social distancing and mobility restrictions, using electronic surveillance, and implementing strategies to decrease workplace transmission [ ] . emphasis was placed on the daily screening of hospitality sector staff for covid- by using real-time reverse transcription-polymerase chain reaction or serology tests [ ] . in this aspect, another study used primary and secondary data and applied the descriptive analysis method to explore revitalization strategies for small and medium-sized businesses, especially in the tourism industry, after covid- in yogyakarta [ ] . the study recommended several policies, such as implementing banks' credit policies with simpler processes and lower interest [ ] . several papers discussed redesigning and transforming the tourism and hospitality industry after covid_ pandemic. the proposed ideas include increasing resilience and security of the tourism and hospitality workforce in post-covid- by cross-training and teaching different skills to workers [ ] ; exploiting the unique opportunity presented by covid- to transform and refocus the tourism and hospitality industry towards local attractions rather than global destinations, and redesigning spaces to assure a -foot distance between tourists [ , , ] . hao et al. [ ] developed a covid- management framework as a result of reviewing the overall impacts of the covid- pandemic on china's hotel industry. the framework contains three main elements of an anti-pandemic process, principles, and anti-pandemic strategies. the anti-pandemic process adopted the six phases of disaster management, including the pre-event phase (taking prerequisite actions), the prodromal phase (observing the warning signs), the emergency phase (taking urgent actions), the intermediate phase (bringing back essential community services), the recovery phase (taking self-healing measures), the resolution phase (restoring the routine). hao et al. [ ] recommended four principles for the different phases of disaster management, including disaster assessment, ensuring employees' safety, customer & property, self-saving, and activating & revitalizing business. finally, the study discussed the main anti-pandemic strategies in the categories of leadership & communication, human resource, service provision, corporate social responsibility, finance, and standard operating procedure. recently, sönmez et al [ ] reviewed the impacts of the covid- pandemic on immigrant hospitality workers' health and safety. the study indicated that while a significant rise in occupational stress has been observed in immigrant hospitality workers over the past - years, the covid- pandemic can add more pressure on workers and potentially deteriorate their mental and physical health condition. the authors recommended different actions in aspects of public and corporate policy, workplace policy, and future research areas. five papers conducted survey studies to investigate different hospitality industry aspects, including social costs, customer preference, expected chance of survival, and travel behavior. qiu et al. [ ] developed the contingent valuation method to estimate costs borne by residents of tourist destinations (social costs) due to the covid- pandemic. contingent valuation is a survey-based economic technique for the valuation of non-market resources [ ] . the survey asks questions about how much money residents would be willing to pay to keep a specific resource. the study attempted to investigate how residents perceive the risk of tourism during the covid- pandemic. by considering three chinese urban destinations, qiu et al. [ ] quantified tourism's social costs during the pandemic. the results indicate that most residents were willing to pay for risk reduction, but this payment differs based on respondents' age and income. alonso et al. [ ] focused on the theory of resilience and conducted a survey from a sample of small hospitality businesses to answer questions about participants' main concerns regarding the covid- pandemic. how small hospitality businesses are handling this disruption. furthermore, what are the impacts of the pandemic on day-to-day activities. alonso et al. [ ] analyzed the qualitative responses through content analysis. the study highlighted nine theoretical dimensions about owners-managers' actions and alternatives when confronted with the covid- pandemic. kim and lee [ ] studied the impacts of the perceived threat of the covid- pandemic on customers' preference for private dining facilities. the study conducted a survey and concluded that the salience of the covid- increases customers' preference for private dining facilities. bartik et al. [ ] discussed the impact of covid- on the u.s. small businesses, especially restaurants and tourism attractions, and highlighted their fragile nature in the face of a prolonged crisis. such companies typically have low cash flow, and in the face of this pandemic, they will either have to declare bankruptcy, take out loans, or significantly cut expenses [ ] . their restaurant owners' survey found that the expected chance of survival during a crisis lasting one month is %, for a crisis that lasts four months is %, and for a crisis that lasts six months is %. the result also indicated that more than % of u.s. small businesses want to take up the cares act paycheck protection program (ppp) loans, even though most of them believe it would be challenging to establish eligibility for receiving such loans [ ] . finally, a survey study by nazneen et al. [ ] investigated the pandemic's impact on travel behavior and reported that it had significant impacts on tourists' decisions to travel for the next months. the authors also concluded that respondents are concerned about hotels' safety and hygiene, recreational sites, and public transports [ ] . it has also been postulated that hygiene and safety perception will play a significant role in travel decisions in post-covid- times [ ] . even though included papers studied different aspects of the hospitality industry during the covid- pandemic (see figure ), the main topics relate to recovery of the industry ( % of papers), market demand ( % of papers), revenue losses ( % of papers), the covid- spreading patterns in the industry ( % of papers), job losses ( % of papers), safety and health aspects ( % of papers), issues related to the employment of hospitality workforce ( % of papers), travel behaviors ( % of papers), preferences of customers ( % of papers), and social costs of pandemic ( % of papers). actions for the resumption of activities during and after the pandemic. travel behaviors, preferences of customers, and social costs were mainly analyzed in the "conducting surveys" approach. the reviewed papers used a variety of research models and analyses to study the hospitality industry in the face of covid- (see figure ) . secondary data analysis was utilized to study almost all aspects of the hospitality industry. covid- spreading patterns were investigated by using several quantitative models, including the seir models, epidemiological models, agent-based models, and crowd flow simulation models. the seasonal autoregressive integrated moving average model was used to calculate job loss and revenue losses. the contingent valuation method, content analysis, and analyzing questionnaire data were parts of the "conducting surveys" approach and were used to analyze social and behavioral aspects of the hospitality industry response to the covid- epidemic. the employment issues of hospitality workers have been mentioned by % of papers in the categories of "reporting the impacts of the covid- pandemic" and "discussing the resumption of activities". these papers discussed job insecurity, financial, and health issues among documented and undocumented workers. ten percent of included papers reported or measured job losses in the hospitality industry as the result of the covid- pandemic. revenue losses, market demand, and recovery of the industry were the most popular aspects of the hospitality industry, and %, %, and % of the included papers, respectively, discussed these topics. it should be noted that these aspects were mainly discussed in the framework of "reporting the impacts of the covid- ". the aspect of covid- spreading patterns was the most popular topic in the approach of "developing simulation & scenario modeling." eight percent of included papers recommended different safety actions for the resumption of activities during and after the pandemic. travel behaviors, preferences of customers, and social costs were mainly analyzed in the "conducting surveys" approach. the reviewed papers used a variety of research models and analyses to study the hospitality industry in the face of covid- (see figure ). secondary data analysis was utilized to study almost all aspects of the hospitality industry. covid- spreading patterns were investigated by using several quantitative models, including the seir models, epidemiological models, agent-based models, and crowd flow simulation models. the seasonal autoregressive integrated moving average model was used to calculate job loss and revenue losses. the contingent valuation method, content analysis, and analyzing questionnaire data were parts of the "conducting surveys" approach and were used to analyze social and behavioral aspects of the hospitality industry response to the covid- epidemic. all aspects of the hospitality industry. covid- spreading patterns were investigated by using several quantitative models, including the seir models, epidemiological models, agent-based models, and crowd flow simulation models. the seasonal autoregressive integrated moving average model was used to calculate job loss and revenue losses. the contingent valuation method, content analysis, and analyzing questionnaire data were parts of the "conducting surveys" approach and were used to analyze social and behavioral aspects of the hospitality industry response to the covid- epidemic. this paper provides a systematic review of the published research topics relevant to the understanding of the hospitality industry in the time of covid- pandemic. by selecting keywords and following prisma guidelines, we explored two main research questions related to the objective. a total of papers that met the predefined inclusion criteria were included in the review. the following two research questions have been explored: rq . what aspects of the hospitality industry at the time of the covid- pandemic have been studied? rq . what research methodologies have been used to investigate the impact of covid- on the hospitality industry? the included papers were classified into six thematic groups, including: ( ) developing simulation and scenario modeling, ( ) conducting surveys, ( ) reporting impacts of the covid- pandemic, ( ) comparing the covid- pandemic with the previous public health crises, ( ) measuring impacts of the covid- pandemic, and ( ) proposing different remedial and management actions (discussing resumption of activities). these papers focused on different aspects of the hospitality industry, including the recovery of the industry after the pandemic, market demands, revenue losses, the covid- spreading patterns in the industry, job losses, safety and health, employment issues of hospitality workers, travel behavior, preference of customers and social costs. the reviewed papers used a variety of research methodologies, such as the seir model, epidemiological model, agent-based model, supply and demand curve, dsge model, crowd flow simulation model, secondary data analysis, seasonal autoregressive integrated moving average model, scenario analysis, trend analysis, descriptive analysis, contingent valuation model, content analysis, and analyzing questionnaire data. in general, conducting a systematic literature review has several limitations. the first limitation is identifying and analyzing papers published in a specific time frame. the second limitation is the inability to discover individual relevant papers arising from a limited number of keywords. the third limitation is using a limited number of search databases for article discovery. although we defined several search keywords and followed prisma guidelines, it is possible that some papers that met the inclusion criteria were not considered in our review. we did not include the papers published after august as several papers on the topic have just started to emerge. second, we selected papers only from web of science, science direct, and google scholar databases. third, we could not include articles where authors investigated the hospitality industry at the time of the covid- pandemic without mentioning the hospitality industry, tourism industry, event industry, hotel industry, and restaurant industry. fourth, one of the main challenges of this review was defining inclusion criteria. because of the very timely issue of the covid- pandemic, we defined broad inclusion criteria. therefore, we could not include several studies that met inclusion criteria but generated by institutions outside of the traditional academic publishing and distribution channels. despite the above limitations, we identified the hospitality industry's main aspects in the face of the covid- pandemic. these include the recovery of the hospitality industry (discussed by % of included papers), market demand ( % of papers), revenue losses ( % of papers), the covid- spreading patterns in the industry ( % of papers), job losses ( % of included papers), safety and health aspects ( % of papers), issues related to the employment of hospitality workforce ( % of papers), travel behaviors ( % of papers), preferences of customers ( % of papers), and social costs of pandemic discussed by % of included papers. it should be noted that there are numerous other fertile research areas and methodologies that can be applied by multidisciplinary research teams to study the effects of the covid- pandemic on the hospitality industry. such approaches and methods include ( ) using complex system science frameworks such as syndemics, ( ) developing simulation modeling in different types of system dynamics, discrete event simulation, agent-based modeling, and monte carlo/risk analysis simulation, ( ) investigating the application of new technologies such as educational technology, information technology, and robotics in response to the pandemic, ( ) using artificial intelligence in different types of machine learning, deep learning and neural networks, and ( ) developing the best practices concerning the pandemic (see figure ). these research approaches can be used to analyze the main aspects of the hospitality industry at the time of the covid- pandemic, such as developing sustainable industry, recovery and resilience of the hospitality industry, the safety of customers, issues of undocumented workers, market demand, and emerging the new market, hostile behavior toward customers, and the risks of resumption of activities during the pandemic. information technology, and robotics in response to the pandemic, ( ) using artificial intelligence in different types of machine learning, deep learning and neural networks, and ( ) developing the best practices concerning the pandemic (see figure ). these research approaches can be used to analyze the main aspects of the hospitality industry at the time of the covid- pandemic, such as developing sustainable industry, recovery and resilience of the hospitality industry, the safety of customers, issues of undocumented workers, market demand, and emerging the new market, hostile behavior toward customers, and the risks of resumption of activities during the pandemic. for example, due to the complex and dynamic nature of the current pandemic, the use of a wide array of complex systems science frameworks and simulation modeling can make an important contribution by examining how the synergistic effects of work and living conditions, as well as covid- government and corporate responses, can influence the long-term health and safety of tourism and hospitality workers. along these lines, the development and application of new technologies and equipment in the hospitality industry should protect guests and workers alike. finally, other potential areas of research include the use of machine learning and artificial intelligence in building a more sustainable tourism and hospitality industry and developing the best practices in improving the industry's resilience in the future. for example, due to the complex and dynamic nature of the current pandemic, the use of a wide array of complex systems science frameworks and simulation modeling can make an important contribution by examining how the synergistic effects of work and living conditions, as well as covid- government and corporate responses, can influence the long-term health and safety of tourism and hospitality workers. along these lines, the development and application of new technologies and equipment in the hospitality industry should protect guests and workers alike. finally, other potential areas of research include the use of machine learning and artificial intelligence in building a more sustainable tourism and hospitality industry and developing the best practices in improving the industry's resilience in the future. author contributions: methodology and writing-original draft and revisions, m.r.d.; conceptualization, writing-review and revisions, editing, and supervision, w.k.; review and revisions, and editing, and methodology, s.s.; review and revisions, editing, and methodology, y.a. all authors have read and agreed to the published version of the manuscript. effect of coronavirus disease (covid- ) to tourism industry coronavirus pandemic and tourism: dynamic stochastic general equilibrium modeling of infectious disease outbreak airborne transmission of sars-cov- : the world should face the reality covid- ) epidemics, the newest and biggest global health threats: what lessons have we learned? million americans have filed for unemployment benefits in the last four weeks key milestones in the spread of the coronavirus pandemic-a timeline economic impact of the hotel industry showcases potential negative impact of coronavirus pandemic, american hotel and lodging association american hotel & lodging association (ahla). state of the hotel industry analysis: covid- six months later. . ahla. available online nearly % of hotel rooms in the us are empty, according to new data counting the cost of covid- on tourism the prisma statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration a systematic review of research on abusive supervision in hospitality and tourism hotel brand loyalty-a systematic literature review eco-innovation in hospitality research ( - ): a systematic review artificially intelligent device use in service delivery: a systematic review, synthesis, and research agenda impact of coronavirus syndromes on physical and mental health of health care workers: systematic review and meta-analysis the psychological and mental impact of coronavirus disease (covid- ) on medical staff and general public -a systematic review and meta-analysis a system dynamics simulation applied to healthcare: a systematic review pandemics, tourism and global change: a rapid assessment of covid- hedging feasibility perspectives against the covid- for the international tourism sector. . preprints . .v . preprints how are small businesses adjusting to covid- ? early evidence from a survey ud din, n. covid- crises and tourist travel risk perceptions. . ssrn. . ssrn social costs of tourism during the covid- pandemic effect of covid- on preference for private dining facilities in restaurants covid- , aftermath, impacts, and hospitality firms: an international perspective tracking labor market developments during the covid- pandemic: a preliminary assessment. ; federal reserve board how much did the tourism industry lost? estimating earning loss of tourism in the philippines assessing the short-term impacts of covid- pandemic on foreign visitor's demand for turkey: a scenario analysis covid- : a nightmare for the indian economy a survey on some of the global effects of the covid- pandemic. . rs. .rs- /v . research square how many infections of covid- there will be in the "diamond princess"-predicted by a virus transmission model based on the simulation of crowd flow transmission potential of the novel coronavirus (covid- ) onboard the diamond princess cruises ship estimating the asymptomatic proportion of coronavirus disease (covid- ) cases on board the diamond princess cruise ship covid- outbreak on the diamond princess cruise ship: estimating the epidemic potential and effectiveness of public health countermeasures estimation of the reproductive number of novel coronavirus (covid- ) and the probable outbreak size on the diamond princess cruise ship: a data-driven analysis sustainable and resilient strategies for touristic cities against covid- : an agent-based approach a pandemic in times of global tourism: superspreading and exportation of covid- cases from a ski area in austria covid- outbreak associated with air conditioning in restaurant expected tourist attractions after pandemic covid- a content analysis of chinese news coverage on covid- and tourism the effect of coronavirus (covid- ) in the tourism industry in china covid- risk and lockdowns: global evidence. . ssrn. . ssrn impact of covid- pandemic on the tourism sector the movement control order (mco) for covid- crisis and its impact on tourism and hospitality sector in malaysia effects of coronavirus disease (covid- ) on tourism industry of india. stud. indian place names indian tourism industry and covid- : present scenario the socio-economic implications of the coronavirus and covid- pandemic: a review health and safety considerations for hotel cleaners during covid- spillover of covid- : impact on the global economy. . ssrn. . ssrn. available online an initial assessment of economic impacts and operational challenges for the tourism & hospitality industry due to covid- a preliminary study of novel coronavirus disease (covid- ) outbreak: a pandemic leading crisis in tourism industry of nepal covid- : potential effects on chinese citizens' lifestyle and travel covid- and undeclared work: impacts and policy responses in revitalization strategy for small and medium enterprises after corona virus disease pandemic (covid- ) in yogyakarta socialising tourism for social and ecological justice after covid- . tour effect of covid- on restaurant industry-how to cope with changing demand. . ssrn. . ssrn would hotel industry have to redo the rooms/housekeeping standards post covid? instilling greater confidence to bring back the customers. . ssrn. . ssrn. available online: https: //papers.ssrn.com/sol /papers.cfm?abstract_id= (accessed on reconnecting tourism after covid- : the paradox of alterity in tourism areas. tour a post-covid- model of tourism and hospitality workforce resilience. socarxiv. . socarxiv/ quga covid- -we urgently need to start developing an exit strategy coronavirus and tourism operational considerations for covid- management in the accommodation sector interim guidance; world health organization covid- and china's hotel industry: impacts, a disaster management framework, and post-pandemic agenda understanding the effects of covid- on the health and safety of immigrant hospitality workers in the united states possible evolutionary pathways towards the transformation of tourism in a covid- world. tour what the cruise-ship outbreaks reveal about covid- basic reproduction number a dictionary of epidemiology contingent valuation funding: this research received no external funding. the authors declare no conflict of interest. key: cord- -s pnm wv authors: ashikalli, louicia; carroll, will; johnson, christine title: the indirect impact of covid- on child health date: - - journal: paediatr child health (oxford) doi: . /j.paed. . . sha: doc_id: cord_uid: s pnm wv since the detection of covid- in december , the rapid spread of the disease worldwide has led to a new pandemic, with the number of infected individuals and deaths rising daily. early experience shows that it predominantly affects older age groups with children and young adults being generally more resilient to more severe disease ( – ). from a health standpoint, children and young people are less directly affected than adults and presentation of the disease has shown different characteristics. nonetheless, covid- has had severe repercussions on children and young people. these indirect, downstream implications should not be ignored. an understanding of the issues is essential for those who hope to advocate effectively for children to prevent irreversible damage to the adults of the future. this article reviews some of the evidence of harm to children that may accrue indirectly as a result of pandemics. it explores the physical and psychological effects, discusses the role of parenting and education, offering practical advice about how best to provide support as a health care professional. one of the 'positives' to emerge from the covid- pandemic in the uk has been a dramatic increase in the availability and use of remote consultations ( ) . driven initially by a need to protect and safeguard patients and healthcare professionals, the early experiences have shown that many routine reviews and some acute consultations can be successfully managed remotely. telemedicine or telehealth is becoming the new norm and can be used as an alternative to face-toface consultations, eliminating the risk of infection ( figure ) ( ) . any technology available such as phone and texting, email, and video, has now been employed to be able to provide therapy. by being able to employ many different means of communication, it makes telemedicine available to a greater number of patients. even so, there can still be inequalities in accessing healthcare as within different communities there is a difference in availability of communications means. it has been clear from early experience in the uk that there is a great difference in the availability of high quality internet connectivity between families which has limited the use of some approved, data-secure platforms such as attend anywhere. the issue of health disparities, the gap in access and quality of care are still present. solutions for the nhs have not been cheap. however, in the longer term these may be cost effective and eliminate some expenses e.g. travel, parking for families. some aspects of routine care for children have been hampered. the significant reduction in availability of lung function testing for children with chronic respiratory diseases is a concern. in some instances, these have been partially overcome with provision of home testing with either peak flow meters or portable spirometers which allow more nuanced care and advice to be given ( ) . engaging the public in planning and decision making, together with educating parents and children efficiently, has proven useful when implementing public health strategies ( ). some strategies appear to have an evidence base. for instance it is suggested that social distancing might be more adhered to if public health officials portray it as an act of altruism, giving a sense of duty to protect the child's loves ones ( ) . the direct approach may also be helpful and has certainly been tried. for example, the canadian prime minister specifically thanked children for their efforts which could only be accounted as an act to increase the feeling of social duty to the youth ( ). the universal use of face masks and the inclusion of younger children within any guidance is still being debated. when it comes to children there are more issues to consider including the availability of masks of different sizes to fit well on the face as well as the risk of suffocation in children younger than two years ( ) . additionally, when it comes to younger children, it is more challenging to persuade them not to take the mask off. innovative ideas have started to emerge, with disney designing fabric face masks with the children's favourite characters to help children in accepting to use them ( ) . whilst initial data does not suggest that children with comorbidities are at particularly increased risk of severe covid- disease ( ) ( ) ( ) , the challenge of maintaining a good continuity of care for existing patients and adequate diagnostic care for children presenting for the first time remains. children with chronic diseases and their carers have been particularly anxious about the impact that covid- could have on them. this can be partially resolved for many by maintaining communication with these families, providing reassurance, advising on hygiene measures, and educating on covid- . where children fall outside clear guidelines, tailored and individualised plans offer reassurance for all of those involved with the provision of care. at the start of this pandemic in the uk the advice given to the families with children with many chronic diseases was to shield the whole household to prevent the risk of severe illness. in hindsight, some of the advice was unduly cautious but faced with uncertainty public health authorities, paediatricians and primary care physicians erred on the side of caution. for some families, the increased anxiety may have longer term consequences. the act of shielding can have severe impacts on a child's physical and mental health. for example, going back to school could be beneficial for children with cerebral palsy or musculoskeletal problems as school provides developmental support and gives access to therapies. as ongoing research suggests a low disease severity amongst the young and the negative effects of shielding, experts questioned whether shielding children with many comorbidities was ever justified. this led to the reformation of the strict guidelines. with social distancing rules being slowly lifted and school re-opening, the rcpch has provided new guidelines for shielding ( ) . one of the medical sectors highly affected by the pandemic is the emergency department (ed) ( ) . normally, in the uk the emergency services are unnecessarily overused, leading to overcrowding and stretching of resources particularly during weekends and evenings. however, regional data suggests that there was a decrease of more than % in the cases of children presenting to the paediatric ed by march and this decline in activity has been maintained into the summer. this has certainly helped to prevent services from being deluged and allowed time for new processes and health protection procedures to be put in place. whilst this change in behaviour could discourage unnecessary attendance to ed, it could also put at greater risk children with serious pathologies that require treatment. in the uk, safeguarding has always been an important concern ( ). during a time of a global pandemic, where focus is on the direct results of the disease, vulnerable children experiencing maltreatment and neglect at home are put on the side-line. long home confinement, together with frustration, agitation, and aggression, creates opportunities to harm children. moreover, the loss of the safety net provided by schools, social care and health professionals decreases the number of abuse cases reported. without spotting narratives or signs of abuse, home becomes a very dangerous place for the vulnerable children. unfortunately, there is a trend of increasing incidences of domestic violence and calls to child support lines reported ( ) . children and teenagers exposed to violence, either as witnesses or victims could experience detrimental effects on their physical and mental health. incomplete immunisation has always been a worrying issue and unfortunately, during a pandemic, this issue can be easily neglected. this could expose communities at risk of an outbreak of a vaccinepreventable disease. for this reason, the who have declared immunisation as a core health service that should be safeguarded and conducted under safe conditions. consequently, they have prepared documents that explain the reasoning behind this and respond to any questions the public or health authorities might have. ( , ) . in recent years, weight gain during periods of school closure, especially during summer vacations, has been a worrying issue amongst the paediatric community ( ) . when comparing behaviours during summer and school season, accelerated weight gain is observed during the summer holidays ( ) . a school closure during a pandemic is not equivalent to summer vacations. nonetheless, there are distinct similarities such as the lack of structure during the day, the increase in screen time and a change in sleeping routines ( figure ). in fact, a small longitudinal observational study conducted in verona italy during this pandemic, has shown that the unfavourable trends in lifestyle discussed above, were observed amongst obese children and adolescents ( ) . the covid- pandemic has further risk factors that might exacerbate the epidemic of childhood obesity ( ) . firstly, as out-of-school time has increased more than a regular summertime, it has increased the period that children are exposed to obesogenic behaviours. secondly, parents are stocking up shelves with highly processed and calorie dense food. this action is justified by the need to maintain food availability and minimise the number of trips outside. this, however, exposes children to higher calorie diets. thirdly, social distancing and stay-at-home policies introduce the risk of decreasing opportunities for physical activity. school physical activities were removed, playgrounds could not be kept clean, parks closed their gates, community centres offering afterschool programs shut their doors. children living in urban areas, confined within small apartments are at a greater risk of adopting a sedentary lifestyle. lastly, there has been an increasing trend on the use of video games which counts as a sedentary activity and leads to excessive screen use ( ). this obesogenic behaviour needs to be taken seriously and tackled as it could have profound consequences which are not easily reversible. moreover, we should have in mind that adult obesity and its comorbidities are associated with covid- mortality ( ) , which raises the question whether overweight or obese children will have more severe repercussions upon contracting covid- . therefore, there is a need to maintain a structured day routine for the children which includes playtime and exercise time, a restriction on calories, a regular sleep pattern and supervision of screen time ( figure ). although emphasis is given to the obesogenic effects of the pandemic, there is also the issue of malnourishment as many students rely on school meals. in fact, school meals and snacks could represent up to two thirds of the nutritional needs in children in the usa ( ) . in addition to not receiving the appropriate nutrition through school, children could be exposed to cheaper, unhealthy food choices. in the uk a partial safety-net has been established and maintained over the summer period following a successful campaign by the english footballer, marcus rashford ( ) . this will offer some support to children who already received free school meals. however, not all children in the uk and many others worldwide will be protected. insecurity over food availability causes longterm psychological and emotional harm to the children and parents. a collaboration amongst who, unicef and ifrc has provided comprehensive guidance to help protect schools and children, with advice in the event of school closure and for schools that remained open ( ) . important points in this guidance document are the emphasis given to a holistic approach towards children by tackling the negative impacts on both learning and wellbeing and to educate towards covid- and its prevention. even so, these guidelines can only be considered as checklists and tips for each government to use accordingly. china provided a successful example of an emergency home schooling plan ( ) , where a virtual semester was delivered in a well organised manner through the internet and tv broadcasts, yielding satisfactory results. however, digital learning is an imperfect system that brings to the surface the inequalities caused by poverty and deprivation. many children have had either limited, shared or no online access either as a result of a lack of equipment (laptops or tablets) or internet access. some parents struggled with the provision of adequate supervision. this issue was significantly more challenging for parents with additional educational needs e.g. adhd or learning difficulties, for those with many children of different ages and for those children who might have additional carer responsibilities. it was also much more difficult for parents who were being expected to work from home at the same time. the full effects of a temporary 'pause' in many children's education in the uk remain to be seen but the effects are likely to widen the gap between children from more deprived backgrounds. since the beginning of the st century, there have been several major disease outbreaks including the severe acute respiratory syndrome (sars) in , the h n influenza pandemic in and the ebola in . however, mental health research was largely overlooked. the absence of mental health services during previous pandemics increased the risk of psychological distress to those affected ( ) . there are variable psychological manifestations as a result of a pandemic. early childhood trauma can affect a child in many ways ( ) . it can increase the risk of developing a mental illness and it can also delay developmental progress. moreover, early childhood trauma in the form of adverse childhood experiences (aces) can have profound effects that manifest in later life such as an increase in substance abuse and problems with relationships or education as well as increase the risk of chronic diseases such as asthma, obesity and attention deficit hyperactivity disorder ( ) . about % of isolated or quarantined children during the h n pandemic in the united states of america met the criteria for post-traumatic stress disorder (ptsd) ( ) . this study noted the lack of professional psychological support to these children during or after the pandemic. out of the much smaller percentage of children that did receive input from mental health services, the most common diagnoses were anxiety disorder and adjustment disorder. moreover, the same study also showed that one quarter of parents would also fulfil the criteria for ptsd which shows that parental anxiety and mental health can be reflected upon other members of the family including the children. events and conditions can have effects on our physical and mental health. these act as stressors or triggers and can predispose anyone, including children to adverse responses; either physical or psychological. the stressors that could impact a child during a pandemic are shown in figure . the duration of the lockdown appears to be particularly important. researchers have shown that the longer the quarantine, the higher the chances of mental health issues emerging in adults. it is unknown whether the same applies to children ( ) . some children and young people (cyp) will be more vulnerable to the adverse consequence of any stressors and these pre-pandemic predictors should also be considered. in a child, such predictors could include the age of the child and a history of mental illness. there is a complex link between mental health and social background. families with lower incomes face tough choices about how to cope with the day-to-day challenge of providing basic necessities (e.g. food, clothing and heating) and may be less able to give priority to the mental health of their children (or themselves). when considering what can influence mental health, the link between physical and mental health should also be considered. the physical health of a child can be affected either directly or indirectly by covid- . this raises the question of how this could affect the psychological wellbeing too and if it would lead to a vicious cycle. the sudden advance in telemedicine in the uk has been one of the unexpected changes brought about by covid- . it has been helpful in maintaining some health care for physical ailments ranging from acute illness to review of children with chronic conditions like asthma, diabetes and cystic fibrosis. it can also be used for psychological counselling for parents or children. this can help children learn how to cope with mental health problems via professional help within the security of their own house ( ) . telemedicine for mental health is already established in some countries. the psychological crisis intervention, is a multidisciplinary team program developed as a collaboration amongst a few chinese hospitals that uses the internet to provide support ( ) . telemedicine is most probably not sufficient in managing and providing for the mental health needs of the high numbers affected. when the already limited access to trained professionals is struck by a global pandemic, the shortage of professionals and paraprofessionals becomes noticeable and therefore the needs of the high number of patients are not met ( ) . when dealing with mental health a hierarchal and stepwise approach that starts in the community is helpful ( figure ). integration of behavioural health disorder screening tools within the response of public health to a pandemic is crucial to cope with demand. these should recognise the importance of identifying the specific stressors and build on the epidemiological picture of each individual to identifying those cyp at greatest risk of suffering from psychological distress ( ) . following the correct identification of patients in the community, the next step involves an appropriate referral. interventions can vary according to the individual's presentation and can include psychoeducation or prevention education. any behavioural and psychological intervention should be based on the comprehensive assessment of that patient's risk factors ( ) . for instance, researchers have shown that specific patient populations such as the elderly and immigrant workers may require a tailored intervention ( , ) . this hypothesis could therefore be stretched to children and teenagers as their needs are different to adults. the rapid changes that both parents and children are forced to face and the uncertainty of an unpredictable future have been compared to the loss of normalcy and security that palliative care patients are faced with and paediatric palliative care teams may be well-placed to provide psychological support to families ( ) . community organisations have a significant role to play in addressing mental health problems. they empower communities and provide tailored support. when this support comes from organisations which understand the community, the community's beliefs are embodied within the programs offered. it is therefore becoming obvious that best results will only be yielded if different bodies work together. this stresses how crucial it is to maintain good communication between community health services, primary and secondary care institutions. this is to ensure patients receive a timely diagnosis and better follow-up ( ) . conversely, poor communication could delay meeting the needs of the patients. the internet is a potentially useful tool for the provision of mental health support. there are a lot of reliable resources online that anyone could use effectively without being in direct contact with professionals. large organisations such as unicef have provided online documents to help teenagers protect their mental health during the pandemic. many books about the current pandemic and its psychological impact are being released electronically for free for the public ( ) . likewise, online self-help interventions such as cbt for depression can be used by anyone experiencing such symptoms. this type of intervention and signposting of lower risk cyp and families to safe, well-constructed resources is highly efficient, allowing mental health professionals to focus more intensive interventions on higher risk individuals. the online world is more easily accessible and much more appealing to older children and teenagers. as young people are becoming the experts of this virtual world, it is only logical to use social media for our benefit. successful mental health campaigns in the past used hashtags on social media like instagram and twitter to increase awareness of mental health problems ( ) . with more bloggers and social media influencers talking about mental health, together with the use of hashtags, the societal benefits become apparent. a strong feeling of empowerment is built that helps combat the stigma of mental health. moreover, there is a therapeutic benefit through the provision of information on how to find professional support or self-management strategies. even though online gaming can have negative impacts on young people's physical health, during a period of home confinement, it provides a mean for friends to stay in contact. both online gaming and the yet extensive use of social media have the potential of bringing people closer together and gives a feeling of solidarity. regarding young children, using online resources on their own might not be an easy task, although they are surprisingly becoming experts of the web too. nonetheless, there are many resources designed with the purpose to explain the pandemic to children and alleviate their anxiety as well as promoting good hygiene. a good example is the collaboration of sesame street with headspace, a mindfulness and meditation company, to create youtube videos that help young children tackle stress and anxiety. parents, carers, or older siblings could all help the young ones to access these resources. the power of technology and the artificial world is becoming a turning point for societies today. interestingly, an artificial intelligence program has been created with the purpose of identifying people with suicidal ideations via scanning their posts on specific social media platforms. once identified, volunteers take appropriate steps to help these individuals. during a time of extensive home confinement, where the use of the web becomes even more prominent, such programs might again provide a service to society by identifying teenagers struggling with mental health ( ) . healing through creative expression is a popular tool amongst child therapists and is has proven useful in previous pandemics too ( ) . during the ebola break, a dynamic art program was established for liberian children. it focused on how therapeutic expressive arts could teach coping skills and build healthy relationships in a safe and supportive space for children to express themselves and experience healing; interventions that showed positive results early on. the advantage of art programs like this is that once they are built by mental health professionals and child health specialists, they can be delivered in the communities using paraprofessionals who receive appropriate training. this allows the projects to be implemented at a wider area while more children benefit from. parents should provide a core pillar of support for children, with school and teachers, the rest of the family and friends providing robust supporting pillars. with home confinement, these supporting pillars break down and the parent becomes the only resource for a child to seek help from. when the wellbeing of the child is at risk, it is important for parents to monitor the children's behaviours and performance. open communication is necessary to identify any issues; physical or psychological. having direct conversations about the pandemic can prove useful in mitigating their anxiety. a common notion is for parents to shield their children from bad news to protect them. it is true that most of the information about the pandemic that children are exposed to is not directed to them and it hence becomes overwhelming. however, children will still ask important questions and ask for satisfactory answers. shielding the world from them is not the right answer. parents should practice active listening and responding appropriately to any questions the child might have as well as adapting their responses to the child's reactions. narrating a story or encouraging the child to draw what is on their mind might enable the start of a discussion. attention also needs to be given to any difficulties sleeping and the presence of nightmares as it could be a sign that the child is not coping well. although strict monitoring of behaviours is required, it is a very delicate issue and it should not put the child into an uncomfortable position. with daily home confinement, it is important to respect the children's privacy and identity. whilst it may seem overwhelming to families to provide all the information required to children there are already many reliable resources available online about how best to maintain the health and wellbeing of their children through this pandemic. unicef has provided online resources for parents to use with emphasis given on how to talk to a child about the pandemic and provide comfort. similarly, the who have also provided a series of posters on parenting during the pandemic again with the purpose of promoting the wellbeing of children. parents and carers are often portrayed as superheroes. however, even these superheroes may experience anxiety and fear during a pandemic. the psychological health of parents and their children seem to be inextricably linked and ptsd is commoner in children whose parents are experiencing it too ( ) . as parents with poorer mental health might not be able to respond to the needs of their children effectively, then addressing this is important. alleviating their stressors will help improve mental health. priority should be given in ensuring that the basic needs of these families are met, including food provisions, financial support, and healthcare access. once these are provided, there are higher chances that any psychological support can have a positive effect on parents. such support can have multiple different dimensions and various tools can be utilised. such tools should be easily accessible, put to practice quickly and aim to strengthen mental resiliency. for instance, behavioural practitioners are suggesting the use of acceptance and commitment therapy ( ). anecdotally the consequence of a prolonged period of lockdown for some families in the uk has been a positive one. home confinement can benefit interactions and help children to engage in family activities. this may help strengthen family bonds and meet the psychological needs of a developing mind. collaborative games fight loneliness and strengthen family relations. other activities that families could do together include learning new skills like cooking or taking up new hobbies like building puzzles. researchers have also shown that during the brief school closure due to the a/h n influenza pandemic in , as time went by, parents became more prepared and started planning more activities. this gave more reasons to young people to stay at home and helped in encouraging social distancing; which proved harder at the start of the influenza pandemic ( ). the impact of the covid- pandemic goes beyond the risk of a severe acute respiratory response. it has posed severe social and economic consequences worldwide. children and young people have been exposed to very severe repercussions which if not addressed, could have even worse outcomes in the future. therefore, governments, communities, non-governmental organisations and healthcare professionals need to work in collaboration to prevent causing irreversible damage to a generation. systematic review of covid- in children shows milder cases and a better prognosis than adults covid- epidemic: disease characteristics in children covid- in children: initial characterization of the pediatric disease european and united kingdom covid- pandemic experience: the same but different promoting and supporting children ' s health and healthcare during covid- -international paediatric association position statement managing asthma during covid- : an example for other chronic conditions in children and adolescents including the public in pandemic planning: a deliberative approach the psychological impact of quarantine and how to reduce it: rapid review of the evidence prime minister appeals to canadian children to follow social distancing rules | cbc news to mask or not to mask children to overcome covid- disney creates fabric face masks for children | daily mail online challenges in chronic paediatric disease during the covid- pandemic: diagnosis and management of inflammatory bowel disease in children new clinical needs and strategies for care in children with neurodisability during covid- covid- is no worse in immunocompromised children, says nice covid- -'shielding' guidance for children and young people where have all the children gone ? decreases in paediatric emergency department attendances at the start of the covid- pandemic of child health in in england : comparisons with other wealthy countries. r coll paediatr child heal isolated at home with their tormentor": childline experiences increase in calls since closure of schools guiding principles for immunization activities during the covid- pandemic frequently asked questions ( faq ) immunization in the context of covid- pandemic understanding differences between summer vs. school obesogenic behaviors of children: the structured days hypothesis lockdown on lifestyle behaviors in children with obesity living in covid- -related school closings and risk of weight gain among children telehealth solution for vulnerable children with obesity during covid- feeding low-income children during the covid- pandemic covid- : ifrc, unicef and who issue guidance to protect children and support safe school operations mitigate the effects of home confinement on children during the covid- outbreak recommended psychological crisis intervention response to the novel coronavirus pneumonia outbreak in china: a model of west china hospital playing to live: outcome evaluation of a community-based psychosocial expressive arts program for children during the liberian ebola epidemic adverse childhood experiences: assessing the impact on physical and psychosocial health in adulthood and the mitigating role of resilience posttraumatic stress disorder in parents and youth after health-related disasters online mental health services in china during the covid- outbreak. the lancet psychiatry psychological interventions for people affected by the covid- epidemic. the lancet psychiatry a nationwide survey of psychological distress among italian people during the covid- pandemic: immediate psychological responses and associated factors mental health services for older adults in china during the covid- outbreak the neglected health of international migrant workers in the covid- epidemic applying palliative care principles to communicate with children about covid- understanding why people use twitter to discuss mental health problems behavioral and emotional disorders in children during the covid- epidemic •% of total enrolled learners: . % • country-wide closures •affected learners: , •% of total enrolled learners: % • country-wide closures •affected learners: , key: cord- -tvy uo u authors: brock, rebecca l.; laifer, lauren m. title: family science in the context of the covid‐ pandemic: solutions and new directions date: - - journal: fam process doi: . /famp. sha: doc_id: cord_uid: tvy uo u the coronavirus disease (covid‐ ) pandemic has precipitated substantial global disruption and will continue to pose major challenges. in recognition of the challenges currently faced by family scientists, we share our perspectives about conducting family research in the context of the covid‐ pandemic. there are two primary issues we address in this article. first, we present a range of potential solutions to challenges in research, resulting from the pandemic, and discuss strategies for preserving ongoing research efforts. we discuss approaches to scaling back existing protocols, share ideas for adapting lab‐based measures for online administration (e.g., using video chat platforms), and suggest strategies for addressing missing data and reduced sample size due to lower participation rates and funding restrictions. we also discuss the importance of measuring covid‐ relevant factors to use as controls or explore as moderators of primary hypotheses. second, we discuss how the covid‐ pandemic represents a scientifically important context for understanding how families adjust and adapt to change and adversity. increased stress precipitated by the pandemic, varying from acute stress associated with job loss to more chronic and enduring stress, will undoubtedly take a toll. we discuss ways that family scientists can contribute to pandemic‐related research to promote optimal family functioning and protect the health of family members. the novel coronavirus disease has profoundly impacted society at large. in addition to economic disruptions and significant burden placed on healthcare systems, the covid- pandemic has undermined -and will continue to undermine -the physical and mental health of individuals across the globe. as family scientists, we must navigate unforeseen challenges as we abruptly pivot to salvage ongoing research and make plans for the future of our research programs. moreover, we are uniquely positioned to investigate how to best build resiliency in families amidst large-scale systemic changes that can undermine family functioning. the primary aims of this article were to (a) present a range of potential solutions to problems threatening the rigor of ongoing research and (b) propose new directions in family science aimed at understanding how families adapt to change and adversity arising from the pandemic. one of the most pressing questions facing many family scientists is how to preserve the rigor of ongoing research that has been derailed by the pandemic (e.g., longitudinal studies put on hold, resulting in missed assessments during critical periods of development). there are numerous challenges to address that could require sweeping changes to research designs. in-person data collection might not be advisable when considering participant safety-or could be expressly prohibited at times-which limits the feasibility of certain methods commonly employed in family research (e.g., behavioral observations in controlled laboratory settings, neuropsychological testing, biological measures, in-person interventions or experimental manipulations). additionally, both researchers and participants might be coping with elevated stress and adversity while adapting to altered roles and routines. consequently, research participants might be less engaged in research or unwilling to participate altogether, thereby threatening the reliability and validity of scores and contributing to elevated rates of missing data. researchers may not have as much time or energy to devote to data collection efforts as in the past and may feel overburdened in anticipation of potential budget cuts or limits on extensions to grant funding in the upcoming months and years. another challenge faced by investigators is restricted access to offices, laboratory spaces, and on-site resources. as such, difficult decisions must be made about which aspects of carefully constructed research designs, if any, can be changed to accommodate new constraints and loss of resources. we this article is protected by copyright. all rights reserved now turn to a discussion of possible adaptations to consider for ongoing research, drawing largely from existing tools and approaches that are established in the literature. online data collection has become relatively mainstream, particularly for administering questionnaires. as such, a relatively straightforward adaptation to lab-based research involves asking participants to complete surveys from home rather than in the laboratory. of course, even this is not a simple transition, as it requires institutional review board approval, an appropriate device (e.g., smartphone) and reliable access to internet connection in participants' homes, and clear instructions to minimize confounds (e.g., asking participants to complete the survey in a private location with minimal distractions). however, research has demonstrated psychometric equivalence of paper-and-pencil and internet formats of questionnaires often used in family research (brock et al., (brock et al., , . as such, validity and reliability concerns associated with this shift in approach are minimal. for investigators who routinely use lab-based methods such as behavioral observation paradigms in carefully controlled environments, experimental manipulation, in-person interventions, or methods that require equipment that is not easily transported, new ways of measuring constructs of interest should be considered. of course, these changes will not be feasible in all circumstances. for example, neuroimaging in the home is not an option. but, by stepping back and thinking creatively, there is the potential for considerable innovation in family science. fortunately, many lab-based measures and protocols can be adapted for online administration. telehealth and video conferencing are increasingly used for clinical interventions and are viable options for investigators conducting treatment outcome research (e.g., arnberg et al., ; perle & nierenberg, ) . further, prior to the pandemic, researchers were already effectively transitioning to video chat platforms for administering assessment tools that require interactions with investigators (e.g., bridgers et al., ; sheskin & keil, ) . there are numerous benefits inherent to home-based assessments, including increased ecological validity, more diversity in samples, reduced barriers such as travel and parking costs, and enhanced participation rates. further, in the context of safety concerns related to covid- , participants might experience elevated stress and anxiety when attending in-person appointments, which could introduce significant confounds. further, it is unlikely that participants who are at greater risk of complications from contracting covid- (e.g., those who are immunocompromised or this article is protected by copyright. all rights reserved pregnant) will be receptive to attending lab appointments which could decrease generalizability of findings. as such, the benefits of remote assessments that allow for research participation from the comfort and safety of one's home are not trivial. of course, there are also drawbacks to consider when collecting data remotely and adapting lab-based protocols for use on video platforms. most notably, participants must have reliable internet access and a device that can be used with the required software. there are also extra steps that need to be taken in service of standardization and preserving the internal validity of scores derived from these approaches. for example, observational paradigms of family interactions can be implemented by stipulating where and for how long the interaction will take place, asking if the parent and child can be alone in a room together so that other family members do not interrupt or influence relationship dynamics, and standardizing the props used during interactions as much as possible (e.g., perhaps you mail or deliver a toy in advance of the interaction that the child can then keep as a gift). as is customary with lab-based paradigms, we carefully track and record any potential confounds (e.g., the presence of significant distractors, technology failures, etc.) that emerge and account for these in the data analysis stage; however, this becomes absolutely essential when altering study protocols midstudy. when analyzing data, it will also be important to control for where and when participants complete the study procedures (e.g., in the home post-covid versus in the lab pre-covid) if these changes are made in the context of an ongoing project. plan for higher rates of missing data and smaller sample sizes. careful planning goes into research to ensure (a) adequate power to test hypotheses and (b) maximum retention and participation rates. these considerations are particularly important to family scientists who often employ advanced quantitative techniques that require larger sample sizes. yet, in the context of the covid- pandemic, the reality is that we might not reach our original goals for recruitment and participation. fortunately, numerous scholars have laid valuable groundwork for navigating these challenges. planned missing data designs can help to guide this process (little & rhemtulla, ). an example with particular relevance to family science is the two-method missing design, an approach used when there is a gold standard measure of a construct (e.g., behavioral observations of family interactions) that cannot be administered to all participants due to time, money, resources, or, in the case of covid- , social distancing guidelines. consider whether there is a more feasible or this article is protected by copyright. all rights reserved inexpensive measure to administer (e.g., an online questionnaire) that is intended to assess the same construct. if so, a random subgroup of the sample will complete the more intensive, gold standard measure whereas the entire sample will complete the "inexpensive" measure. the gold standard measure completed by the subset of the sample enhances the validity of scores, and the inclusion of the inexpensive measure allows for a larger sample size and the corresponding benefits (e.g., power, generalizability). this design could be particularly useful if in-person data has already been collected from a subsample of a cohort using an intensive protocol (e.g., behavioral observations of parental responsiveness). if there is an inexpensive measure that was used with that subsample (e.g., a parenting questionnaire), and it is correlated with scores from the more intensive measure, the inexpensive measure can be administered remotely (e.g., online survey) with subsequent participants. in the context of longitudinal research, a wave missing design (little & rhemtulla, ) could help reduce participant burden and provide a solution for salvaging ongoing data collection that has been put on hold or now has insufficient funding. in these designs, some participants are intentionally omitted from certain waves; as such, not all participants are required to complete every time point of data collection. finally, a multiform design (little & rhemtulla, ) involves randomly assigning participants to complete different versions of a survey that contain different combinations of items rather than administering a full battery of questionnaires to everyone. this approach can minimize participant burden while still providing rigorous assessments of your study constructs by using otherwise lengthy questionnaires with strong psychometric properties. finally, in anticipation of reduced sample sizes, we must carefully consider which of our hypotheses will still be sufficiently powered (for a brief guide to power and a list of resources, see murray et al., ) . are there empirical questions we can adequately address with a smaller n? if not, are there analytic approaches that well-suited for smaller samples to which we can turn? for example, although bayesian methods are not currently mainstream in family science, they are effective in addressing small sample problems. specifically, bayesian methods may be better suited to producing accurate parameter estimates in smaller samples relative to more traditional frequentist methods. for a detailed discussion of considerations when implementing a bayesian analytic framework with small samples, please refer to mcneish ( ). this article is protected by copyright. all rights reserved recommendation for ongoing research is to routinely assess the numerous ways that families are impacted by the pandemic. these measures will provide important contextual information for including as controls in hypothesis testing and for determining whether study effects are altered (i.e., moderated) by features of the pandemic. for example, our lab has been conducting a large-scale longitudinal study of families who completed numerous waves of data collection prior to a national emergency being declared in the united states (where the research is being conducted) as a result of covid- . one of the primary goals of the study is to examine trajectories of change in family processes and the mental health of family members over several years, and identify factors predicting adaptive versus maladaptive trajectories. yet, the global nature of the pandemic-and corresponding stress and expected changes to family functioning-could greatly alter the nature of those trajectories if we include new data collected in the context of covid- . as such, we are asking parents to complete home surveys to assess the various ways they have been impacted as a family to measure potential confounds. we acknowledge that, in some ways, this recommendation contradicts our earlier suggestion to scale back protocols; however, accounting for potential confounds that could alter your results is so essential that making concessions in other elements of your study to accommodate these measures might be advisable. further, these covid- specific assessments do not necessarily need to be time-consuming or expensive. for example, the epidemic-pandemic impacts inventory (epii; grasso et al., ) is a relatively comprehensive measure of pandemic impacts that only takes - minutes to complete and assesses multiple domains of functioning (e.g., work and employment, education and training, home life, social activities, economic, emotional health and well-being, physical health problems, physical distancing and quarantine, infection history, positive change). if administering a questionnaire is not feasible, even a brief phone conversation with research participants about how they have been impacted by the pandemic could subsequently be used for a thematic analysis (braun & clarke, ) , and quantitative codes could be assigned to reflect degree of impact and adversity. we have presented several potential solutions for adapting to the current circumstances to preserve the quality of ongoing research. however, there might ultimately be certain research questions that are not well-suited to the current circumstances and, as such, it might be better this article is protected by copyright. all rights reserved to postpone data collection until life returns to a state of relative normalcy (e.g., routine access to facilities and resources is restored; social distancing guidelines are relaxed and research personnel and participants feel safe attending in-person appointments). if it is not feasible to collect data remotely, and you are navigating pauses in ongoing data collection, consider staying in touch with participants while things are on hold to keep them invested. something we have implemented in our research is maintaining a study website to keep participants in our longitudinal projects engaged, which has helped to minimize attrition. we share results as they are published, provide resources, and post answers to common questions. in the wake of the covid- pandemic, we adapted our website to include status updates on the study and a list of resources for helping families talk to their children about covid- and manage stress. finally, there might be ways to adapt and evolve a research program in new directions, pursuing empirical questions that had not been previously considered. indeed, we now turn to a discussion of how the covid- pandemic represents a scientifically meaningful context for studying families. covid- represents not only a global public health emergency, but also the beginning of a major mental health crisis (united nations, ). exposure to adversity and stress is a robust predictor of mental health difficulties across the lifespan (e.g., benjet et al., ; juster et al., ; mclaughlin, ) , and research examining causal pathways of risk and modifiable factors that interrupt those pathways (e.g., high quality support, access to resources) is vital to inform prevention and early intervention efforts. experimental manipulation is touted as the gold standard approach for examining causality; however, as family scientists, we abide by ethical standards that prohibit us from subjecting individuals to extreme levels of stress and adversity. in the absence of experimental manipulation, disaster-based research offers an alternate approach for understanding the impact of stress on the family system. because they emerge suddenly and are outside of human control, natural disasters approximate the randomization of a true experiment, with stress quasi-randomly "assigned" to individuals (king et al., ) . further, norris ( ) states that "disasters generate an array of individually and collectively experienced stressors of varying degrees of intensity that interact with accepted article multiple characteristics of the person and environment to produce diverse outcomes that evolve over time" (p. ). thus, the covid- pandemic represents a scientifically important context for elucidating temporal relations between stress and family functioning. before we explore potential avenues for research, it is important to acknowledge the factors that make the pandemic a unique context for studying the effects of stress and adversity. what is unique and significant about the covid- pandemic? relative to more isolated natural disasters (e.g., floods, tornadoes), the covid- pandemic will affect individuals across the world. as of july , , covid- had impacted nearly every country or region ( of ), with over million confirmed cases and half a million deaths worldwide (johns hopkins university, ; united nations, ). further, the pandemic has triggered a collective experience of acute stress and psychological distress. social distancing measures, albeit varied in scope, have been implemented in countries and territories to help prevent the spread of covid- (international energy agency, ). though certainly effective in minimizing the spread of the virus, these measures have also resulted in significant occupational, educational, and personal disruptions that warrant further attention. in particular, the covid- pandemic has prompted acute, unprecedented job loss and disruption. as of april , the international labour organization, a specialized agency of the united nations, reported that full or partial lockdown measures impacted % of the global workforce (international labour organization, ) . unemployment rates in the united states rose sharply to nearly % in april, reflecting the economic impact of the pandemic and efforts to contain it (u.s. bureau of labor statistics, ). lower socioeconomic status (ses) is associated with an increased risk for mental health problems across the lifespan (reiss, ; santiago et al., ) . in particular, childhood ses predicts long-term physical and mental health outcomes (cohen et al., ; conroy et al., ) . ses is also a robust predictor of relationship quality and stability, parenting, and child development (see conger et al., for a review). thus, as more and more individuals worldwide experience job disruption and financial instability, we should expect the economic challenges spurred by the covid- pandemic to exert a toll on both individual and family functioning (e.g., gilman et al., ; kingston, ) . further, certain populations might be at particular risk for adversity stemming from covid- . for example, black americans not only suffer from higher rates of this article is protected by copyright. all rights reserved unemployment, but they are also more likely to work in front-line jobs deemed essential (gould & wilson, ) . covid- has also disproportionately impacted black americans, and race is associated with mortality rates (ferdinand & nasser, ) . as such, underrepresented and marginalized populations warrant particular attention amidst the pandemic. beyond the acute stress and uncertainty associated with job disruption, the covid- pandemic has the potential to contribute to chronic stress burden (e.g., baum et al., ; lantz et al., ) . there are enduring sources of stress related to covid- that will vary across individuals and families, including fear of becoming infected or infecting others; inadequate supplies to meet basic needs; insufficient information from health and government officials; and the potential for stigma (brooks et al., ) . a robust body of literature demonstrates that stress and adversity impact family functioning (e.g., masarik & conger, ; randall & bodenmann, ; story & bradbury, ) . indeed, stress resulting from external (e.g., occupational) demands can spill over into the family system and undermine individual mental health, relationship satisfaction, and parenting behaviors (e.g., bakker & demerouti, ; bass et al., ; bolger et al., ; brock & lawrence, ) . for couples, stress experienced by one person may cross over to impact their partner. increased stress might also result in one person demonstrating increased family involvement to compensate for their partner's decreased involvement (nelson et al., ) . amidst the covid- pandemic, parents may be at increased risk for role strain as they adapt to changing -and potentially conflictingoccupational and family demands. for instance, some families may be navigating job loss and economic adversity, while others might have job security but are adjusting to new roles and expectations, such as working from home while providing childcare or homeschooling. for some families in dual parenting households, one parent may be leaving the home to work, potentially in a high-risk environment (e.g., hospitals, pharmacies), while the other parent navigates responsibilities at home. thus, the pandemic will generate high levels of between-subject variability in objective and subjective stress, as all families will experience adversity but to different degrees and in diverse ways. further, social distancing measures enacted to minimize the spread of the virus may interfere with important social connections that help us to regulate and cope with our emotions (van bavel et al., ; williams et al., ) . social distancing can also contribute to feelings of isolation and frustration (brooks et al., ) . in addition to the stress associated with major transitions and role this article is protected by copyright. all rights reserved changes, many families have been forced into proximity with one another for an extended period of time (van bavel et al., ) . in combination with elevated levels of stress, forced proximity may be detrimental to family functioning. indeed, research demonstrates that stress experienced by one partner often places a heavy burden on caregiving partners, who report poor marital adjustment and increased subjective distress (dekel et al., ) . the covid- pandemic may prevent family members from accessing external sources of social support that help mitigate distress (e.g., ergh et al., ; rodakowski et al., ) . in addition, partner support, which buffers the association between stress and mental health trajectories (brock et al., ) , may be compromised if both partners are experiencing high levels of subjective stress. conversely, research demonstrates that partners who boast strong support skills may experience greater relationship satisfaction, particularly during times of increased stress (brock & lawrence, ) . further, forced proximity may be beneficial for some families by increasing time spent together to establish family rituals that were not previously feasible due to competing demands. as such, it is important to identify the factors that contribute to adaptive versus maladaptive outcomes in the context of pandemic stress (e.g., communication, support processes, intrapersonal coping resources, division of labor, conflict management skills). further, the consequences of forced proximity of family members -and reduced connection with important social contacts outside of the household (e.g., grandparents, extended family members, friends, coworkers)represents a novel area of research worth closer attention. this might be of particular relevance among families with adolescent children given that adolescence is characterized by an increased need for autonomy and independence and, in turn, the potential for increased parent-child conflict (mcelhaney et al., ; steinberg, ) . finally, with no clear end in sight, the chronic nature of the covid- pandemic is particularly notable. indeed, longer durations of confinement are associated with poorer mental health, particularly trauma-related symptoms (brooks et al., ) . currently, there is a tremendous amount of ambiguity about the future, including which businesses will survive, future job prospects (e.g., for recent graduates), and how much the way we work and live will be altered for the long-term. this chronic uncertainty poses a significant risk to mental health and the family system more broadly (afifi et al., ) . finally, it has become apparent that there are diverse perspectives about the pandemic, the threat associated with the covid- disease, and what constitutes appropriate and this article is protected by copyright. all rights reserved reasonable safety measures. disagreements about the best way to proceed as a family could increase conflict, put strain on collective decision-making efforts, and undermine vital coping resources originating within the family (e.g., high quality support, a sense of belonging and shared values). though covid- is a biological disease by nature, mental health research has emerged as an immediate priority (holmes et al., ) , as evidenced by numerous calls for research by various funding agencies. in fact, the national institutes of health has devoted existing resources and emergency funding to support administrative supplements and competitive revisions that would allow active grants to investigate urgent research questions related to covid- , such as how remotely delivered stress management strategies impact mental and physical health outcomes, resilience to covid- infection, or symptom severity (not-at- - ). as family scientists, we are uniquely poised to contribute to pandemic-related research. drawing on past research and theory, we can investigate the specific impact of the stress and adversity arising from covid- on individual mental health and family functioning and identify modifiable risk and resiliency factors to target in interventions. leveraging ongoing longitudinal data collection will be vital to determine causal mechanisms associated with poor mental health outcomes (e.g., depression, anxiety) and family dysfunction (e.g., couple conflict, child neglect, decreased responsiveness during parenting). indeed, research utilizing existing cohorts, among whom mental health and family functioning have been previously assessed, offers a unique opportunity to examine the longitudinal impact of covid- and to identify a range of risk and protective factors that can be harnessed to promote family functioning. further, integrating quantitative and qualitative data, often staples in family science, allows researchers to explore the specific family processes and relationships that contribute to adaptive and maladaptive outcomes amidst the pandemic. in the absence of ongoing longitudinal studies, the covid- pandemic presents another avenue for family scientists to pursue new research on the impact of stress and adversity on family functioning. for example, prospective studies can be designed to study the immediate and long-term effects of exposure to varying levels of stress from the pandemic on family functioning, especially for high-risk populations. in sum, we have identified several key themes at the intersection of family science and the covid- pandemic. building off of these themes, there are a range of unique questions to consider this article is protected by copyright. all rights reserved in pursuit of a more nuanced understanding of family processes. some of these questions include, but are not limited to: how do stress and adversity impact couples in different relationship stages? are dating couples impacted in unique ways relative to more established, long-term couples? how has forced proximity and lack of access to social contacts outside of the family impacted sibling relationships? how are divorced and remarried family systems navigating custody agreements and shared responsibilities in the context of social distancing and travel restrictions? how are families impacted when a family member tests positive for covid- ? what if certain family members are at higher risk for complications resulting from covid- ? how are individuals working in essential jobs maintaining family relationships? what impact has this had on parenting? how has covid- uniquely affected pregnant women and their partners? how might this contribute to the intergenerational transmission of stress and psychopathology? in this article, we have presented (a) a series of potential solutions to problems arising when conducting ongoing research during the covid- pandemic and (b) ideas for new directions in research that explicitly address issues related to the experience of the pandemic for families. it is important to recognize that the time, energy, and resources available to devote to research will vary across investigators, and perhaps by region, as some areas of the world have been impacted by the pandemic more than others. thus, our intention was to present a series of potential solutions and ideas ranging from more intensive, time-consuming efforts to relatively small, but meaningful, steps that can be taken in family science in response to the pandemic. we also acknowledge that this is by no accepted article means an exhaustive list of strategies or approaches. we have shared some of the key considerations made in our own research, along with ideas shared by colleagues who are navigating similar challenges. we look forward to learning more about the new and innovative ways that family scientists respond to this crisis and move the field forward. the impact of uncertainty and communal coping on mental health following natural disasters internet-delivered psychological treatments for mood and anxiety disorders: a systematic review of their efficacy, safety, and cost-effectiveness the spillover-crossover model new frontiers in work and family research do job demands undermine parenting? a daily analysis of spillover and crossover effects socioeconomic status and chronic stress: does stress account for ses effects on health? chronic childhood adversity and onset of psychopathology during three life stages: childhood, adolescence and adulthood the contagion of stress across multiple roles using thematic analysis in psychology whom will granny thank? thinking about what could have been informs children's inferences about relative helpfulness annual conference of the cognitive science society internet administration of paper-and-pencil questionnaires used in couple research accepted article this article is protected by copyright. all rights reserved online administration of questionnaires assessing psychological, physical, and sexual aggression: establishing psychometric equivalence a longitudinal investigation of stress spillover in marriage: does spousal support adequacy buffer the effects partner support and maternal depression in the context of the iowa floods the psychological impact of quarantine and how to reduce it: rapid review of the evidence. the lancet childhood socioeconomic status and adult health socioeconomic status, family processes,and individual development poverty grown up: how childhood socioeconomic status impacts adult health emotional distress and marital adjustment of caregivers: contribution of level of impairment and appraised burden predictors of caregiver and family functioning following traumatic brain injury african-american covid- mortality socio-economic status, family disruption and residential stability in childhood: relation to onset, recurrence and remission of major depression black workers face two of the most lethal preexisting conditions for coronavirus-racism and economic inequality the epidemic -pandemic impacts inventory (epii) multidisciplinary research priorities for the covid- pandemic: a call for action for mental health science oil market report ilo monitor: covid- and the world of work coronavirus resource center a transdisciplinary perspective of chronic stress in relation to psychopathology throughout life span development using natural disasters to study the effects of prenatal maternal stress on child health and development economic adversity and depressive symptoms in mothers: do marital status and accepted article this article is protected by copyright. all rights reserved perceived social support matter? stress, life events, and socioeconomic disparities in health: results from the americans' changing lives study planned missing data designs for developmental researchers stress and child development: a review of the family stress model. current opinion in psychology handbook of adolescent psychology: individual bases of adolescent development future directions in childhood adversity and youth psychopathology on using bayesian methods to address small sample problems caring about power analyses family stress and parental responses to children's negative emotions: tests of the spillover, crossover, and compensatory hypotheses disaster research methods: past progress and future directions how psychological telehealth can alleviate society's mental health burden: a literature review accepted article this article is protected by copyright the role of stress on close relationships and marital satisfaction socioeconomic inequalities and mental health problems in children and adolescents: a systematic review role of social support in predicting caregiver burden socioeconomic status, neighborhood disadvantage, and poverty-related stress: prospective effects on psychological syndromes among diverse low-income families thechildlab.com a video chat platform for developmental research autonomy, conflict, and harmony in the family relationship understanding marriage and stress: essential questions and challenges frequently asked questions: the impact of the coronavirus (covid- ) pandemic on the employment situation for policy brief: covid- and the need for action on mental health using social and behavioural science to support covid- pandemic response key: cord- -d pb kik authors: cheval, sorin; mihai adamescu, cristian; georgiadis, teodoro; herrnegger, mathew; piticar, adrian; legates, david r. title: observed and potential impacts of the covid- pandemic on the environment date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: d pb kik various environmental factors influence the outbreak and spread of epidemic or even pandemic events which, in turn, may cause feedbacks on the environment. the novel coronavirus disease (covid- ) was declared a pandemic on march and its rapid onset, spatial extent and complex consequences make it a once-in-a-century global disaster. most countries responded by social distancing measures and severely diminished economic and other activities. consequently, by the end of april , the covid- pandemic has led to numerous environmental impacts, both positive such as enhanced air and water quality in urban areas, and negative, such as shoreline pollution due to the disposal of sanitary consumables. this study presents an early overview of the observed and potential impacts of the covid- on the environment. we argue that the effects of covid- are determined mainly by anthropogenic factors which are becoming obvious as human activity diminishes across the planet, and the impacts on cities and public health will be continued in the coming years. the earth is a dynamically changing planet, permanently shaped by socio-ecological interactions. variations and changes are common in a nonlinear and dynamic system such as our planet but passing certain thresholds may push the stability of the systems into a new regime which can have significant consequences at different spatial and temporal scales. understanding and early prediction of the impacts of such dramatic changes is a challenge for all sciences (including economics, social or medical sciences) but also for our society as a whole [ , ] . extreme variations in natural processes and phenomena, in many cases enhanced or even caused by human actions, generate hazards that lead to risks for both communities and the environment, and as a result, sometimes disasters occur. the concept of disaster has evolved over time, and here we use an adapted intergovernmental panel on climate change (ipcc) definition: a disaster is an event, which severely alters the functioning of a community due to hazardous physical, biological or human related impacts leading to widespread adverse effects on multiple scales and systems (environment, economic, social). immediate emergency the main cause of pandemic events and epidemic diseases is the close interaction between human populations with both domesticated and wildlife pathogens [ ] . most pathogens pass from wildlife reservoirs and enter into human populations through hunting and consumption of wild species, wild animal trade and other contact with wildlife. urban areas are especially vulnerable through the high population density and mobility. the covid- dwarfs the six previous large scale epidemics of the st century in terms of spatial extent and societal consequences [ ] , and it is the only pandemic with widespread and complex environmental impacts. we briefly present a few characteristics of the other large-scale epidemic events of the st century. a. the severe acute respiratory syndrome (sars) occurred in , leading to more than infections with a mortality rate of approximately % and an impact limited only to local and regional economies [ ] . the epidemic ended abruptly in july and no human cases of the sars coronavirus have been detected since. b. the h n influenza virus (swine flu) was a pandemic which first appeared in mexico and the united states in march and april of . it became a global pandemic as a result of global mobility and airline travel and led to an estimated . % case fatality [ ] . c. middle east respiratory syndrome (mers) was first identified in humans in saudi arabia and jordan in [ ] . mers is considered a zoonotic pathogen, with infected dromedary camels being the animal source of infection to humans [ , ] . by contrast to sars, which was contained within a year of emerging, mers continues to have a limited circulation and causes human disease with intermittent sporadic cases, community clusters and nosocomial outbreaks in the middle east region with a high risk of spreading globally [ ] . d. the ebola virus was first detected in in zaire (presently the democratic republic of congo). since the virus was first detected, over known outbreaks of ebola have been identified in sub-saharan africa, mostly in sudan, uganda, democratic republic of congo and gabon [ ] . at present, no vaccine or efficient antiviral management strategy exists for ebola [ ] . although the ebola virus has substantial epidemic and pandemic potential (due to the ease of international travel), as shown by the - west-african ebola virus epidemic with approximately , confirmed cases and , deaths [ , ] , ebola outbreaks have been geographically limited [ ] . e. the zika fever ( - ) was first isolated in from a febrile rhesus macaque monkey in the zika forest of uganda. since , when the first cases in humans were reported, the zika virus had only limited sporadic infections in africa and asia. however, a large outbreak with approximately , to , , cases spread from brazil to countries in the americas in [ ] . in november , who announced the end of the zika outbreak. f. avian flu (bird flu) was first reported in in hong kong with only infections and human deaths. more than cases of the avian flu have been reported from over countries [ ] of the reported outbreaks occurred in in china [ ] . in the absence of any effective treatments, sars-cov, mers-cov and sars coronaviruses are of very high societal concern since they could unexpectedly become a global pandemic at any time [ ] . as a result, coronaviruses in general have been studied to anticipate their societal and environmental impact. this has immediate application to the covid- virus. furthermore, [ ] summarizes relevant knowledge on the causative agent, pathogenesis and immune responses, epidemiology, diagnosis, treatment and management of the disease, control and prevention strategies of the covid- . a calendar of the covid- events potentially related to the environmental impacts is presented as list s . the development and spread of covid- under the control of environmental factors justify the scientific interest for the combined studies of coronaviruses on one side and socio-ecological systems (including the interplay between climate, water, soil) on the other side. the number of scientific publications examining such topics has constantly increased in recent decades, and the covid- pandemic strongly motivates the record ( figure ). saharan africa, mostly in sudan, uganda, democratic republic of congo and gabon [ ] . at present, no vaccine or efficient antiviral management strategy exists for ebola [ ] . although the ebola virus has substantial epidemic and pandemic potential (due to the ease of international travel), as shown by the - west-african ebola virus epidemic with approximately , confirmed cases and , deaths [ , ] , ebola outbreaks have been geographically limited [ ] . e. the zika fever ( - ) was first isolated in from a febrile rhesus macaque monkey in the zika forest of uganda. since , when the first cases in humans were reported, the zika virus had only limited sporadic infections in africa and asia. however, a large outbreak with approximately , to , , cases spread from brazil to countries in the americas in [ ] . in november , who announced the end of the zika outbreak. f. avian flu (bird flu) was first reported in in hong kong with only infections and human deaths. more than cases of the avian flu have been reported from over countries [ ] of the reported outbreaks occurred in in china [ ] . in the absence of any effective treatments, sars-cov, mers-cov and sars coronaviruses are of very high societal concern since they could unexpectedly become a global pandemic at any time [ ] . as a result, coronaviruses in general have been studied to anticipate their societal and environmental impact. this has immediate application to the covid- virus. furthermore, [ ] summarizes relevant knowledge on the causative agent, pathogenesis and immune responses, epidemiology, diagnosis, treatment and management of the disease, control and prevention strategies of the covid- . a calendar of the covid- events potentially related to the environmental impacts is presented as list s . the development and spread of covid- under the control of environmental factors justify the scientific interest for the combined studies of coronaviruses on one side and socio-ecological systems (including the interplay between climate, water, soil) on the other side. the number of scientific publications examining such topics has constantly increased in recent decades, and the covid- pandemic strongly motivates the record ( figure ). in general, temperature, humidity, wind and precipitation may favour either the spread or the inhibition of epidemic episodes. however, while some research found that local weather conditions of lowered temperature, mild diurnal temperature range and low humidity may favour the transmission [ ] , other studies claim there is no evidence that warmer weather can determine the decline of the case counts of covid- [ ] . increased ultraviolet light, as occurs particularly during the summer months, leads to inactivation of the coronaviruses and [ , ] analyse the subject comprehensively and find that warming weather is unlikely to stop the spread of the pandemic. to understand the relative importance between physical and social parameters that favour the spread of the virus, an area in which different health and social policies have been equally in general, temperature, humidity, wind and precipitation may favour either the spread or the inhibition of epidemic episodes. however, while some research found that local weather conditions of lowered temperature, mild diurnal temperature range and low humidity may favour the transmission [ ] , other studies claim there is no evidence that warmer weather can determine the decline of the case counts of covid- [ ] . increased ultraviolet light, as occurs particularly during the summer months, leads to inactivation of the coronaviruses and [ , ] analyse the subject comprehensively and find that warming weather is unlikely to stop the spread of the pandemic. to understand the relative importance between physical and social parameters that favour the spread of the virus, an area in which different health and social policies have been equally implemented on a variety of environmental and climatic conditions must be examined. italy is a viable experimental model to examine the impact of different health policies, as stated by the government authorities themselves [ , ] . in italy, the regionalization of public health has addressed the pandemic following completely different schemes from one region to another and represents an important test to verify the scientific hypotheses on the behaviour of sars-cov- . given that coronaviruses tend to spread in lowered temperatures and drier conditions during the winter months (i.e., during a period of reduced solar radiation), it is surprising that italy was the first european country severely affected by the pandemic and its hospitals were suddenly overrun. northern italy experienced a very dry and mild winter caused by the presence of a strong polar vortex. the winter of - was one of the driest winters in years (https://www.arpae.it/dettaglio_n otizia.asp?idlivello= &id= ). the impact on the social and economic structure of the country immediately gave rise to concerns about the potential transmission pathways of the virus and the spread at european scale. the impact of the covid- pandemic on the environment raised attention from the very beginning of the crisis, consisting of (a) observations and analysis of the immediate effects and (b) estimations related to long-term changes. qualitative assumptions prevail, while consistent quantitative research must wait for relevant data sets and additional knowledge. most facets of the environmental impact of the covid- pandemic have not directly resulted from the virus itself. the consequence of abruptly limiting or closing economic sectors, such as heavy industry, transport, or hospitality businesses, has affected the environment directly. moreover, the impact of the covid- pandemic on socio-ecological systems may be highly variable, from radical changes in individual lifestyle, society and international affairs [ ] , to simply facilitating a faster change than would normally have emerged [ ] . from an anthropocentric perspective, the pandemic may lead to a more sustainable future, including increased resilience of the socio-ecological systems or shorter supply chains, which is a positive development. however, it is still possible that some nations will opt for less sustainability by pursuing rapid economic growth and focusing less concern on the environment. while negative impacts on the economy and society in general are probably huge, it is very likely that the global-scale reduction of economic activities due to the covid- crisis triggers a lot of sensible improvements in environmental quality and climatic systems. however, not all the environmental consequences of the crisis have been or will be positive. this includes an increased volume of nonrecyclable waste, the generation of large quantities of organic waste due to diminish agricultural and fishery export levels and difficulties in maintenance and monitoring of natural ecosystems [ ] . the temporal resolution of the coronavirus impact ranges from immediate (days to weeks), short-term (months) and long-term (years), and different examples are provided in a matrix ( figure ). while the first impacts are divided between rapid environmental improvements, such as urban air and water quality, and pollution episodes, such as the ones caused by the sanitary disposals, the estimated short-and long-term impacts are mainly positive. impacts are rarely limited to a single physical system. however, for the sake of better inventory and understanding, the impact of the covid- on the physical systems focuses on the air, water and soil individually, with an emphasis on urban areas. large cities or megacities are often very centralized structures providing a certain degree of comfort and protection for the citizen, but they increase the exposure to specific threats. for example, the higher population densities favour higher exposure to hazards. in contrast to rural areas, where the population tends to have gardens, the effects of the lockdown conditions in cities showed more severe effects on the mental health of individuals living in close quarters. the covid- crisis is driving towards a new paradigm that brings urban policies closer to present and strengthens the future needs of urban population and public health. one of the key characteristics of the pandemic event in focus in this study is the spatial extent but also versatility of the scale of the impact. no other disaster has covered the whole planet with comparable intensities over so many urban areas with multifaceted threats that are challenging our cities during the crisis. air quality is highly sensitive to anthropogenic emissions. in the european economic area countries (eu, norway, liechtenstein and iceland), the energy used by industrial processes and the road transportation sector is responsible for about % of the nonmethane volatile organic compounds (nmvoc), % of the nox, % of pm . and % of sox emissions [ ] . the covid- crisis has caused severe impacts to the energy and resources, high-tech and communications, retail, manufacturing and transportation sectors, in terms of personnel, operations, supply chain and revenue [ ] . by mid-april, a % to % decline in economic activity was estimated as a result of the draconian disease-suppression policies, and severe multiquarter economic impacts in multiple markets became imminent [ ] . consequently, the impact on air quality was rapidly visible at various spatial scales. even as early as the end of march , reductions in air pollution were reported in china, italy and new york city, and sharp declines in global greenhouse-gas emissions have been predicted for the rest of the year [ ] . moreover, an overview focused on several european countries impacts are rarely limited to a single physical system. however, for the sake of better inventory and understanding, the impact of the covid- on the physical systems focuses on the air, water and soil individually, with an emphasis on urban areas. large cities or megacities are often very centralized structures providing a certain degree of comfort and protection for the citizen, but they increase the exposure to specific threats. for example, the higher population densities favour higher exposure to hazards. in contrast to rural areas, where the population tends to have gardens, the effects of the lockdown conditions in cities showed more severe effects on the mental health of individuals living in close quarters. the covid- crisis is driving towards a new paradigm that brings urban policies closer to present and strengthens the future needs of urban population and public health. one of the key characteristics of the pandemic event in focus in this study is the spatial extent but also versatility of the scale of the impact. no other disaster has covered the whole planet with comparable intensities over so many urban areas with multifaceted threats that are challenging our cities during the crisis. air quality is highly sensitive to anthropogenic emissions. in the european economic area countries (eu, norway, liechtenstein and iceland), the energy used by industrial processes and the road transportation sector is responsible for about % of the nonmethane volatile organic compounds (nmvoc), % of the no x , % of pm . and % of so x emissions [ ] . the covid- crisis has caused severe impacts to the energy and resources, high-tech and communications, retail, manufacturing and transportation sectors, in terms of personnel, operations, supply chain and revenue [ ] . by mid-april, a % to % decline in economic activity was estimated as a result of the draconian disease-suppression policies, and severe multiquarter economic impacts in multiple markets became imminent [ ] . consequently, the impact on air quality was rapidly visible at various spatial scales. even as early as the end of march , reductions in air pollution were reported in china, italy and new york city, and sharp declines in global greenhouse-gas emissions have been predicted for the rest of the year [ ] . moreover, an overview focused on several european countries reveals that the reduction of the weekly no , pm and pm . concentrations during march and april is quasigeneral ( figure s ). one possible cause of the impact of the pandemic in northern italy is that a high concentration of particulate matter (pm, including pm and pm . ) makes the respiratory system more susceptible to infection and complications of the coronavirus disease. higher and consistent exposure to pm (particularly for the elderly) leads to a higher probability that the respiratory system is compromised before the onset of the virus. this was a serious concern right after the publication of a position paper by sima (italian environmental medical society), where correlations were found between pollution levels and the spread of the virus [ ] . strong evidence exists on the greater predisposition of the respiratory system to serious diseases [ ] , but the hypothesis that pollutants can be a carrier for the virus in the free atmosphere seems very unlikely. the spread of droplets produced by sneezing or coughing is necessary so that high viral concentration and a lack of air circulation and exchange can be potentially very dangerous [ ] [ ] [ ] [ ] . the analysis of the demographic and economic characteristics of the two italian regions most affected by the pandemic help to understand that the spread of the virus is dependent on parameters other than simply air transport [ ] . the most affected regions are quite similar demographically; lombardy has a population density of per km while veneto has a density of per km and the average age of the populations is practically identical. economic indicators also reveal a gross domestic product of lombardy of , €/capita and veneto of , €/capita. the number of beds in the healthcare facilities for intensive care are nearly identical in the two regions, while there is a public health laboratory for every , , inhabitants in lombardy and for every , people in veneto. the healthcare structure is a very important aspect that explains the notable difference between the two regions, as the home care service for the elderly and disabled is more than double in veneto than in lombardy [ ] . for neighbouring regions with similar pollution levels, the infection rate is extremely uneven. thus, it appears unlikely that pm is a viable vector for the virus, but it does illustrate the concern over disparate regional healthcare systems. this also has an important impact on future exit strategies from the pandemic and on the use of personal protective equipment (ppe) as the virus may vector using healthcare workers [ ] . it is very likely that the italian case provides lessons for other european countries and validates the measures taken to limit the effects of the pandemic. as for the environmental impacts, physical and ecological systems have been affected in many places, as addressed and detailed in the next sections. the massive lockdowns of entire cities, economies, schools and social life for weeks led to unknown large-scale and extensive restrictions in mobility as a response to social distancing guidance related to covid- ( figure ). globally, largest reductions in mobility are visible for western and southern europe (e.g., spain- %, italy- %, france- %) and south america (e.g., bolivia- % or columbia- %). in south america, mobility in the period april to april showed a mean decrease of % compared to the -week period january- february . other continents showed a mean decrease of around %. south korea was the only country that showed a slight positive trend of + . % for the analysed period. the reason here is that the mobility trends for places like national parks, public beaches, marinas, dog parks, plazas, and public gardens increased significantly, although other mobility categories (e.g., workplaces, transit stations) showed a decrease. even if general mobility characteristics may vary by country and the period of strongest reductions in mobility may not be evident in april, figure shows the global picture of the effects of the covid- pandemic. in particular, one of the most hit sectors was the aviation that contributes about - % of global greenhouse gas emissions [ ] and about - % of global co emissions [ ] . between january and april , travel restrictions caused air traffic to decline by around % in the total number of flights and about % in the number of commercial flights ( figure ). the latest scenario of the international air transport association (iata) suggests that air traffic will fall by % for [ ] . even if the aviation sector returns to its pre-pandemic levels, % of the passengers indicate they will wait at least six months before returning to air travel. specifically, % indicate they will wait for their financial situation to stabilize [ ] . the strong decrease in both short-term and mid-term aviation travel will lead to a reduction in greenhouse gas emissions, particularly co . additionally, the reduction in contrails may increase the daily temperature range [ ] . the reduction of contrails will probably lead to a decrease in air temperature due to the decreasing greenhouse effect [ ] . in particular, one of the most hit sectors was the aviation that contributes about - % of global greenhouse gas emissions [ ] and about - % of global co emissions [ ] . between january and april , travel restrictions caused air traffic to decline by around % in the total number of flights and about % in the number of commercial flights ( figure ). the latest scenario of the international air transport association (iata) suggests that air traffic will fall by % for [ ] . even if the aviation sector returns to its pre-pandemic levels, % of the passengers indicate they will wait at least six months before returning to air travel. specifically, % indicate they will wait for their financial situation to stabilize [ ] . the strong decrease in both short-term and mid-term aviation travel will lead to a reduction in greenhouse gas emissions, particularly co . additionally, the reduction in contrails may increase the daily temperature range [ ] . the reduction of contrails will probably lead to a decrease in air temperature due to the decreasing greenhouse effect [ ] . in particular, one of the most hit sectors was the aviation that contributes about - % of global greenhouse gas emissions [ ] and about - % of global co emissions [ ] . between january and april , travel restrictions caused air traffic to decline by around % in the total number of flights and about % in the number of commercial flights ( figure ). the latest scenario of the international air transport association (iata) suggests that air traffic will fall by % for [ ] . even if the aviation sector returns to its pre-pandemic levels, % of the passengers indicate they will wait at least six months before returning to air travel. specifically, % indicate they will wait for their financial situation to stabilize [ ] . the strong decrease in both short-term and mid-term aviation travel will lead to a reduction in greenhouse gas emissions, particularly co . additionally, the reduction in contrails may increase the daily temperature range [ ] . the reduction of contrails will probably lead to a decrease in air temperature due to the decreasing greenhouse effect [ ] . regarding the transport sector, motor vehicles were responsible for % of the greenhouse gases emissions in austria, for example. this was the second largest source of greenhouse gas emissions in austria, behind the energy and industry sectors, which together contributed % [ ] . regarding the transport sector, motor vehicles were responsible for % of the greenhouse gases emissions in austria, for example. this was the second largest source of greenhouse gas emissions in austria, behind the energy and industry sectors, which together contributed % [ ] . regarding the transport sector, motor vehicles were responsible for % of the greenhouse gases emissions in austria, for example. this was the second largest source of greenhouse gas emissions in austria, behind the energy and industry sectors, which together contributed % [ ] . the covid- crisis has led to a substantial reduction in motor vehicle traffic with not only a reduction in greenhouse gas emissions and particulate pollution but also a major reduction in traffic noise and tire wear on road surfaces. in vienna, with a population of . million, car and truck traffic were reduced by % and %, respectively, between march and the first week of april [ ] . these reductions, extrapolated to similar urban areas in europe, have led to significantly improved air quality. in milan, average concentrations of no for the - march period was % lower than for the same week in . in bergamo, average concentrations of no in were % lower than in for the same week, and similar reduction of average no concentrations have been observed in other major cities (e.g., barcelona, %; madrid, %; lisbon, %) [ ] . data also show a reduction in the urban pm concentration. reduced concentrations of pm . in seoul (south korea) were % lower from february to march when compared to the same period in . los angeles (united states) observed its longest continuous period of clean air on record, lasting over days from march to . pm . concentration levels were lower by % from the same time last year and down % from the average of the previous four years (https://www.iqair. com/blog/air-quality/report-impact-of-covid- -on-global-air-quality-earth-day). for barcelona, [ ] reported approximately % reduction of no and black carbon, % decrease of pm and - % increase of o concentrations, very likely due to the lockdown of the city. however, the favourable role of meteorological conditions was also granted. well-known for its high level of pollution, milan is considering a shift from car traffic to pedestrian and bicycle over km of streets, as a result of the coronavirus crisis (https://www.theguardian.com/ world/ /apr/ /milan-seeks-to-prevent-post-crisis-return-of-traffic-pollution). milan launched on april a new strategy for adaptation asking for an open contribution from the population [ ] where it is clearly stated that the mission is to elaborate a new strategy to exit from pandemic, called phase . the objectives are to remake the city by accounting for problems faced during the pandemic. public transportation is one of the main foci along with the protections of elderly people. the immediate impact of the covid- pandemic on aquatic systems and water resources is very limited, but water quality and resources may be affected on monthly and annual perspectives. due to less boat traffic and tourist activities, venice waters cleared during the coronavirus lockdown of the city in march and april (figure ) . reference [ ] first detected the presence of the sars-cov- in sewage and indicated it as a sensitive tool to monitor the circulation of the virus. although the viral rna has been detected in wastewater, this does not necessarily imply a risk [ ], either to the public or to the environment. reference [ ] showed that coronaviruses die off rapidly in wastewater and are inactivated faster in warmer water (i.e., days in water at • c and > days in water at • c). disposal of sanitary consumables, such as ppe, is already creating concern about the impact of the pandemic event on water bodies. by may , many reports have claimed significant harm on the aquatic environment especially along the shorelines (e.g., in hong kong and canada) due to sanitary disposal resulting from medical activities or personal protection. the covid- crisis has and probably will exhibit longer-term impacts on water resources usage and management. the economic effects of the covid- pandemic, changes in national budgets and changes in funding priorities may lead to lack of funding for water related infrastructure and water utilities. the impacts of underfunding (e.g., increased forthcoming losses or lack of investments to improve efficiency) may only manifest after a few years. reference [ ] first detected the presence of the sars-cov- in sewage and indicated it as a sensitive tool to monitor the circulation of the virus. although the viral rna has been detected in wastewater, this does not necessarily imply a risk [ ], either to the public or to the environment. reference [ ] showed that coronaviruses die off rapidly in wastewater and are inactivated faster in warmer water (i.e., days in water at °c and > days in water at °c). disposal of sanitary consumables, such as ppe, is already creating concern about the impact of the pandemic event on water bodies. by may , many reports have claimed significant harm on the aquatic environment especially along the shorelines (e.g., in hong kong and canada) due to sanitary disposal resulting from medical activities or personal protection. the covid- crisis has and probably will exhibit longer-term impacts on water resources usage and management. the economic effects of the covid- pandemic, changes in national budgets and changes in funding priorities may lead to lack of funding for water related infrastructure and water utilities. the impacts of underfunding (e.g., increased forthcoming losses or lack of investments to improve efficiency) may only manifest after a few years. during lockdown conditions, water utilities from germany and austria report that the daily peak in water consumption in the morning is shifted by around . to h. generally, a dampening effect and a more even distribution in water consumption during the day is observed. regarding the amount of water consumed, increases as well as decreases of around % are reported. increases are explained by higher demands due to watering of gardens-surprisingly, not due to increased hand washing-and decreases by fewer commuters, students and pupils in supply areas [ ] [ ] [ ] [ ] [ ] . by contrast, municipalities with high touristic activity-a leading cause of water demand [ , ]-will exhibit important reduction in water consumption. reports from the strong tourism heritage of tirol, austria, suggest reductions in water consumption of up to % in municipalities where tourism plays an important role [ ] . depending on the return of tourism following the end of the pandemic, a noteworthy reduction of water demand and pressures on water resources can be expected. during lockdown conditions, water utilities from germany and austria report that the daily peak in water consumption in the morning is shifted by around . to h. generally, a dampening effect and a more even distribution in water consumption during the day is observed. regarding the amount of water consumed, increases as well as decreases of around % are reported. increases are explained by higher demands due to watering of gardens-surprisingly, not due to increased hand washing-and decreases by fewer commuters, students and pupils in supply areas [ ] [ ] [ ] [ ] [ ] . by contrast, municipalities with high touristic activity-a leading cause of water demand [ , ] -will exhibit important reduction in water consumption. reports from the strong tourism heritage of tirol, austria, suggest reductions in water consumption of up to % in municipalities where tourism plays an important role [ ] . depending on the return of tourism following the end of the pandemic, a noteworthy reduction of water demand and pressures on water resources can be expected. industrial water consumption, a generally poorly measured quantity, has certainly decreased. the longer-term impacts on water resources will depend on economic developments following the crisis. in comparison to domestic and industrial water demand, the highest pressures on water resources come from the agricultural sector. here, long-term forecasts will depend on the return of agriculture following the crisis, although short-term effects are probably visible in reduced irrigation demand. soil provides essential ecosystem services for human society, ranging from agricultural production to carbon sequestration, which are fundamental for several sustainable development goals (sdgs), such as "zero hunger" or "life on land" [ ] . the immediate impact of the pandemic or other similar disasters on the soil environment is linked with the increasing risks of food insecurity and disruption of the food supply chain. the persistence of sars-cov- on different surfaces is a key issue for successfully controlling its spread. reference [ ] found the viruses can remain viable on surfaces for several days. other studies investigated the survival of different viruses in soils and sediments [ ] . at present, there is no clear evidence about the role of the soil environment in hosting and transmission of the sars-cov- nor about the impact of this coronavirus on the soil surface, and calls for collecting eventual results have been issued [ ] . from an ecological perspective, the covid- crisis is fundamentally related to the relationships between society and ecosphere. while the origin in a wuhan wet market or industrial livestock or other source is not yet fully clarified [ ] , it is well known that mers-cov, sars-cov and sars-cov- are all animal coronaviruses which infected people and then succeeded to spread in different communities at large scale. around the globe more than . million people are dying from zoonosis in a year [ ] , but the impact is even greater as the zoonosis are also affecting human health, livestock sector and agriculture and usually the poorer human populations are more affected. the coronavirus crisis is most probably one of the many challenges our society will have to face in the forthcoming decades as an indirect consequence of the impact of climate change on the ecosphere through many mechanisms, including diminishing species habitats [ ] , changing species distributions [ ] and an increasing influx of alien invasive species [ ] . currently, economic development focuses on continuous growth without considering the conservation of natural systems. in a letter sent to the who (world health organisation) in april , more than animal welfare and conservation organisations stressed the need to recognise the link between wildlife markets and pandemics (https://lioncoalition.org/ / / /open-letter-to-world-health-organisation/). however, this is related with the need to act on existing international conventions, such as cites (the convention on international trade in endangered species of wild fauna and flora, also known as the washington convention) to protect endangered plants and animals from trafficking. as this is not the first time such outbreaks have occurred (see the sars event between and ), conventions like cites should be reinforced. forest landscape fragmentation also may facilitate more often human contact with wild animals, increasing the likelihood of transmission risk of animal-to-human viruses [ , ] . the pandemic has also had an impact on ecological research, field work and experiments. in many cases, this research activity has been diminished or halted, with important consequences on conservation of species and habitats. there is also a possible economic impact on conservation programs around the globe as a result of pandemic and different programs are assessing their long-term viability (such as the global environmental fund) [ ] . even after the pandemic ends, a danger exists that both research and conservation programs will be diminished mainly due to miscommunication between decision makers and scientists. however, perhaps the most important impact of the pandemic on the ecological transition focuses on sustainability and the still possible choices that the society could make to ensure its long-term survivability. as explained in figure , the coupled natural-human system is on a path of transitioning from an unsustainable development towards sustainability being under pressure from different drivers. the instability caused by the pandemic is characterized by variables that have sudden and multiple impacts on both the natural environment and on society and could push the system into three different potential states. the fast variables are characterizing the instability phase and the slow variables act as controlling variables [ ] [ ] [ ] . only one of these potential states is the desirable one, moving away from unwanted events and ensuring that the pandemic was a painful but still a "learning event" that drove towards a "better future". the main characteristic of the pandemic is that it is acting like a shock that pushes the system towards a regime shift with difficult to predict consequences. system into three different potential states. the fast variables are characterizing the instability phase and the slow variables act as controlling variables [ ] [ ] [ ] . only one of these potential states is the desirable one, moving away from unwanted events and ensuring that the pandemic was a painful but still a "learning event" that drove towards a "better future". the main characteristic of the pandemic is that it is acting like a shock that pushes the system towards a regime shift with difficult to predict consequences. reference [ ] advocates that nature is part of the solution for recovery and sustainable reconstruction. nevertheless, the effect of the covid- pandemic on ecological systems has not yet been fully realized, and further monitoring will bring new findings and perspectives. it is very likely that the covid- pandemic will reshape the economic and environmental policies at an international scale. the strength of some bilateral agreements and international partnerships has been tested by this pandemic. whereas china persistently invested in africa's natural resources and infrastructure projects, the treatment of african citizens living in china and the frustration at beijing's opposition on granting debt relief could deteriorate the chinese economic and political supremacy in africa [ ] . reference [ ] also discusses the impact of the crisis on african economies with unpredictable environmental consequences. the roles that china and the usa currently play for mitigating risk include an ecological emphasis to the pandemic strategy preparedness in order to better protect the global community from zoonotic disease [ ] . the coronavirus epidemic could significantly impact the italians' relationship with the eu, as indicated by the widely spread perception that the eu was not efficient in supporting the fight against coronavirus [ ] , at least in february-march (i.e., % of italians believed so in march ). such changes are expected to generate indirect long-term environmental impacts. climate changes are often perceived as a risk driver at the global scale and covid- has offered an excellent example of how a single underestimated threat can challenge the foundations of global security, economic stability and democratic governance [ ] . according to analyses before the reference [ ] advocates that nature is part of the solution for recovery and sustainable reconstruction. nevertheless, the effect of the covid- pandemic on ecological systems has not yet been fully realized, and further monitoring will bring new findings and perspectives. it is very likely that the covid- pandemic will reshape the economic and environmental policies at an international scale. the strength of some bilateral agreements and international partnerships has been tested by this pandemic. whereas china persistently invested in africa's natural resources and infrastructure projects, the treatment of african citizens living in china and the frustration at beijing's opposition on granting debt relief could deteriorate the chinese economic and political supremacy in africa [ ] . reference [ ] also discusses the impact of the crisis on african economies with unpredictable environmental consequences. the roles that china and the usa currently play for mitigating risk include an ecological emphasis to the pandemic strategy preparedness in order to better protect the global community from zoonotic disease [ ] . the coronavirus epidemic could significantly impact the italians' relationship with the eu, as indicated by the widely spread perception that the eu was not efficient in supporting the fight against coronavirus [ ] , at least in february-march (i.e., % of italians believed so in march ). such changes are expected to generate indirect long-term environmental impacts. climate changes are often perceived as a risk driver at the global scale and covid- has offered an excellent example of how a single underestimated threat can challenge the foundations of global security, economic stability and democratic governance [ ] . according to analyses before the covid- pandemic, if countries are unable to implement the nationally determined contributions as ratified through the paris agreement, the emissions reduction efforts would cost the whole world about . - . trillion dollars until [ ] . plans prepared for reinforcing the emission reduction goals established under the paris agreement are not only postponed until , but they will probably suffer consistent adjustments in the new economic circumstances. in the short term, it is hard to assume that climate change and environmental sustainability will be priorities for the world governments or local authorities, while the long-term cost for emission reduction could be raised. the coronavirus crisis also threatens local commitments to implement climate change adaptation and mitigation measures that have been initiated in the recent period [ ] . both national and international governance will be affected. the impact of coronavirus on the eu climate plan was already the subject of discussions in several meetings in brussels and there are concerns that the targets set for now will be difficult to reach especially due to the necessity for a rapid economic recovery. poland, in particular, expressed doubts on reaching the targets set for (http://www.caneurope.org/publications/press-releases/ -eu-aims-f or-net-zero-emissions-by- -now-it-needs-to-work-on-raising-the- -target). big industries such as car manufacturers also have expressed concerns of not being able to meet the targets set (https://ww w.carbonbrief.org/daily-brief/eu-leaders-agree-to-consider-climate-in-coronavirus-recovery-plan). during the s, environmental efforts have intensively addressed the generous framework of the "transforming our world: the agenda for sustainable development" [ ] . this agenda includes sustainable development goals (sdgs) designed to eradicate poverty and achieve sustainable development by . we argue that most of these goals were immediately impacted by the covid- pandemic, while longer-term effects are also expected ( table ) , most of them directly connected to urban areas and population health. it is very likely that the concept and implementation of the agenda must be reconsidered according to the new findings related to our exposure, vulnerabilities and resilience to global disaster risks. the discovery of the permanence of the virus on surfaces and in aquifers requires a revision of the purification and sanitation systems. days to years [ ] : affordable and clean energy alternative energy sources and backup storage and transport systems should be developed to secure societal needs during crises. years to decades [ ] : decent work and economic growth the pandemic has shown that there are groups of workers most exposed to risk to health and life by requiring a revision of the working methods in industry, commerce and health. months to decades [ , ] : industry, innovation and infrastructure technological innovation and a close link with the research invention, also to the advantage of a change in production methods, has proved to be an unavoidable condition for the solution of global problems months to decades [ , ] : reduced inequality improvements in access to information technologies to reduce inequalities in poor and large families who have to use remote school systems and access to other resources. days to months [ , ] : sustainable cities and communities revisions of adaptation plans are foreseen for major cities to increase health resilience in citizens and to better protect elderly population. months to decades [ , , ] revision of production systems from the global to the local scale to ensure access and distribution of strategic resources with consequent enhancement of territorial activities. months to decades [ ] months to decades [ , ] : peace and justice strong institutions the importance of strong coordination between institutions has been markedly indicated for national ones but, above all, for international ones where the exchange of exact and punctual information can indicate safe ways for solving problems on a global level. months to decades [ , ] : partnerships to achieve the goal the efficiency of international agreements have been dramatically challenged, and the need for rethinking regional and global partnerships emerged. days to decades [ ] the covid- crisis has challenged environmental monitoring and climate services, creating both adversities in observations as well as challenges to create better preparedness. lack of reliable data on the spread of covid- could lead to not only a once-in-a-century pandemic but also a once-in-a-century decision fiasco [ ] . the crisis has revealed the crucial need to access long-term, real-time data for supporting policy makers and reaction at different scales, and it has motivated environmental scientists to reinforce our monitoring capacity to address sustainability issues the pandemic has raised [ ] . challenges like the dearth of airborne meteorological measurements or the maintenance of environmental monitoring in protected areas will gradually be resolved once previous levels of social and economic activity resume [ ] . however, actions are needed now to build reliable responses to future threats. the covid- crisis has strongly biased the production and delivery of both weather forecasting (https://news.un.org/en/story/ / / ) and climate services (i.e., climate-based information and products tailored for various end-users related to the present climate and adaptation to different scenarios) as well as the observation of oceans and remote locations (https://www.theguardian.com/sc ience/ /apr/ /climate-monitoring-research-coronavirus-scientists#maincontent). the pandemic has dramatically lowered the quantity and quality of aircraft weather observations, thereby adversely impacting weather forecasts and modelling efforts. the european centre for medium-range weather forecasts (ecmwf) has noted a reduction of % in aircraft reports received between march and march (figure ). on april, the world meteorological organization (wmo) issued its concern about the impact of the crisis on the global observing system [ ] . however, the exceptional slowdown of societal activities that began in march of has generated opportunities to capture environmental information of a novel event. for example, the "noise" associated with human activities that adversely affect seismographic records dropped sharply around the world, improving the ability to detect seismic waves and the locations of number of daily aircraft reports over europe received and used at ecmwf. source: https://www.ecmwf.int/en/about/media-centre/news/ /drop-aircraft-observations-could-h ave-impact-weather-forecasts. however, the exceptional slowdown of societal activities that began in march of has generated opportunities to capture environmental information of a novel event. for example, the "noise" associated with human activities that adversely affect seismographic records dropped sharply around the world, improving the ability to detect seismic waves and the locations of earthquake aftershocks [ ] . transmission of diseases by population mobility within the context of climate change received scientists' attention before the current pandemic [ , ] . the examination of the relationship between climate and coronavirus focuses on two queries: (a) how the climate can modulate the spread and persistence of the virus, and (b) the extent of the impact of the virus on economic policies taken to offset climate impacts. the first aspect is inherently scientific and mainly involves the atmospheric and epidemiological disciplines. the second is much more complex as the economic, political and social dynamics will affect processes that will alter our worldview. climatic effects on the coronavirus are currently difficult to estimate given that this pandemic is still under development. these effects, therefore, can only be speculated by comparing them to the characteristics of other coronaviruses. reference [ ] investigated the observed growth rate of coronavirus worldwide and related it to the climate, making a prediction for forthcoming seasons. they argue a specific climate exists in which the coronavirus spreads optimally. outbreak dynamics also were investigated in terms of climate and environmental conditions [ ] to link directly daily growth rates to the local climate. the correlation found was significant leading them to conclude that such a link was valid, but their study also highlighted the fact that population density could be a confounding variable. these results, although very speculative, have led to initial hypotheses on the transmission conditions of sars-cov- under different combinations of atmospheric parameters [ ] and to forecast conditions for the summer of [ , ] . an analogy with the other coronaviruses becomes fundamental to validate such hypotheses but it is not currently possible to establish whether the virologic characteristics of the new pathogen can be assumed to be like other coronaviruses. analysing the direct and indirect effects of the pandemic on the climate is more complicated as forecasts must resolve not just the contagion dynamics but also incorporate economic, social, and political aspects of the virus propagation. direct effects on climate change could result mainly from the global slowdown of production activities and transportation. at this stage, the overall effects are not easily determined but, for example, emissions in china-the country with the longest period of closure-have decreased by % [ ] , corresponding to a decrease of about million tons of co in february alone [ ] . nevertheless, the possible decrease in global co emissions is likely to be around % worldwide [ ] (reuters, ). for the representative concentration pathway (rcp) climate change scenario, scripps research institute [ ] suggests a possible trend in emissions ( figure ) which shows an immediate drop followed by a recovery when activities resume. this projection leads to fundamental speculations as to what indirect effects coronavirus will have on the earth's climate. we note that following the - economic crisis, co emissions exhibited rapid growth [ ] and we suggest that a similar response will follow this pandemic. experts suggest one of two sharply divergent paths will arise from the demise of the pandemic [ ] . on the one hand, a feeling exists that the coronavirus will support the government, science, and business infrastructure in addressing environmental issues, including climate change [ ] . although the coronavirus and climate change operate on different time scales, they represent similar phenomena in terms of the evolution and impacts of the problem. thus, lessons from the pandemic provide lessons to be learned in environmental protection. recovery from the pandemic, therefore, may lead the focus away from environmental concerns [ ] . surely something has already changed. covid- has undermined the basic tenets of global manufacturing. companies must now reconsider the multistep, multi-country supply chains that dominated production and derivative production [ ] . individuals too must reconsider life choices as profound changes also await us [ , ] . scripps research institute [ ] suggests a possible trend in emissions ( figure ) which shows an immediate drop followed by a recovery when activities resume. this projection leads to fundamental speculations as to what indirect effects coronavirus will have on the earth's climate. we note that following the - economic crisis, co emissions exhibited rapid growth [ ] and we suggest that a similar response will follow this pandemic. experts suggest one of two sharply divergent paths will arise from the demise of the pandemic [ ] . on the one hand, a feeling exists that the coronavirus will support the government, science, and business infrastructure in addressing environmental issues, including climate change [ ] . although the coronavirus and climate change operate on different time scales, they represent similar phenomena in terms of the evolution and impacts of the problem. thus, lessons from the pandemic provide lessons to be learned in environmental protection. recovery from the pandemic, therefore, may lead the focus away from environmental concerns [ ] . surely something has already changed. covid- has undermined the basic tenets of global manufacturing. companies must now reconsider the multistep, multi-country supply chains that dominated production and derivative production [ ] . individuals too must reconsider life choices as profound changes also await us [ , ] . the covid- pandemic has triggered unprecedented environmental impacts in terms of spatial extent, complexity and even uniqueness. it is the first time in history that the metabolism of all the urban agglomerations with more than million inhabitants from europe was virtually stopped regarding movement, traffic and economic exchanges. the societal and economic measures adopted to contain the pandemic led to local, regional and global impacts, both negative and positive, spanning from immediate to long-term consequences. the full evaluation of the impacts is far from being possible with an ongoing disaster of epic proportion and tremendous complexity, and this paper pledges for several directions to be pursued by further research. the covid- pandemic provides a clear demonstration that human and planetary health are intimately interconnected [ ] , and the role of interdisciplinary approaches in finding solutions has been clearly highlighted [ ] . the disaster reached the planetary scale within only two months (i.e., february through march ). despite six other pandemic outbreaks having occurred during the st century, humankind was still not prepared to deal with a global event. most countries adopted a strict lockdown of economies and societal activities, triggering immediate impacts on many physical and ecological systems. longer-term consequences are also assumed, and a systemic approach is required to support the prevention, early warning, and similar impacts of environmental degradation. the covid- pandemic has triggered unprecedented environmental impacts in terms of spatial extent, complexity and even uniqueness. it is the first time in history that the metabolism of all the urban agglomerations with more than million inhabitants from europe was virtually stopped regarding movement, traffic and economic exchanges. the societal and economic measures adopted to contain the pandemic led to local, regional and global impacts, both negative and positive, spanning from immediate to long-term consequences. the full evaluation of the impacts is far from being possible with an ongoing disaster of epic proportion and tremendous complexity, and this paper pledges for several directions to be pursued by further research. the covid- pandemic provides a clear demonstration that human and planetary health are intimately interconnected [ ] , and the role of interdisciplinary approaches in finding solutions has been clearly highlighted [ ] . the disaster reached the planetary scale within only two months (i.e., february through march ). despite six other pandemic outbreaks having occurred during the st century, humankind was still not prepared to deal with a global event. most countries adopted a strict lockdown of economies and societal activities, triggering immediate impacts on many physical and ecological systems. longer-term consequences are also assumed, and a systemic approach is required to support the prevention, early warning, and similar impacts of environmental degradation. the coronavirus pandemic has generated an active involvement of the research community and has garnered an early response from international, national, and local authorities. since the events are ongoing and the end is still difficult to predict, we shall refer only to preliminary results and possible lessons to be learned. the reaction of the scientific community to the crisis was prompt and led to rapid accumulation of knowledge and operational decisions. faced with an unprecedented interruption of data from aeronautical meteorological service providers (amsps) and other observational platforms, the wmo has enumerated preliminary guidelines to assist the amsps [ ] at the beginning of april . eventually, problems associated with environmental monitoring have reinforced the need to secure backup systems to collect information, as such data are crucial for operational forecasting of ecological, weather and hydrological conditions. of note, relationships between weather conditions and the spread of the virus are still unclear and more research is needed to derive relevant conclusions. the advancements of new specific techniques would be of great interest for controlling the environmental dissemination of coronaviruses [ ] , and more precise and extended monitoring would favour the collection of more relevant information. early developments with this crisis have revealed that monitoring of socio-ecological conditions is crucial for an early intervention to limit the scale of the epidemic and the pandemic hazard. reference [ ] argues that better monitoring of immigrant tracks and travel volumes could have helped countries be better prepared to contain the spread of the novel coronavirus. data, tools and lessons learned may provide significant improvements in preparation to fight potential pandemics in the future [ ] . this global crisis has convincingly demonstrated that the disaster research, climate change diplomacy and ecosystem services must reconsider their strategic and integrated development considering even the most unlikely events. eventually, the covid- pandemic will determine profound changes of the social and economic behaviour at the planetary scale, and this study highlights the environmental dimension of the consequent impacts resulting from the emerging pandemic. supplementary materials: the following are available online at http://www.mdpi.com/ - / / / /s , list s : calendar of events relevant for covid- impact on environment ( december - april ), figure s : average weekly no concentration between january and april in urban areas from spain, france, united kingdom, italy, austria and poland. source: https://www.eea.europa.eu/themes/air/air-quality-a nd-covid /monitoring-covid- -impacts-on. predicting population responses to environmental change from individual-level mechanisms: towards a standardized mechanistic approach ten principles to integrate the water-energy-land nexus with climate services for co-producing local and regional integrated assessments managing the risks of extreme events and disasters to advance climate change adaptation: special report of the intergovernmental panel on climate change defining disaster: the emergency department perspective defining disaster: an evolving concept medium-and long-term health effects of earthquakes in high-income countries: a systematic review and meta-analysis pandemics: risks, impacts, and mitigation who declares covid- a pandemic who director-general's opening remarks at the media briefing on covid- - quantifying sars-cov- transmission suggests epidemic control with digital contact tracing united nations development programme can you put a price on covid- options? experts weigh lives versus economics transition from democracy-loss of quality, hybridisation and breakdown of democracy long-term memory for the terrorist attack of september : flashbulb memories, event memories, and the factors that influence their retention the / attacks-a study of al qaeda's use of intelligence and counterintelligence the deterioration of democratic political culture: consequences of the perception of inequality polarization and the global crisis of democracy: common patterns, dynamics, and pernicious consequences for democratic polities the socio-economic implications of the coronavirus and covid- pandemic: a review nuclear war as a global catastrophic risk the academic analysis of the financial crisis: round rapidly expanding nuclear arsenals in pakistan and india portend regional and global catastrophe stability of democracies: a complex systems perspective covid- : disease, management, treatment, and social impact coronavirus disease (covid- ): a literature review detection and attribution of observed impacts host range and emerging and reemerging pathogens the first pandemic of the st century the first influenza pandemic of the st century middle east respiratory syndrome enzootic patterns of middle east respiratory syndrome coronavirus in imported african and local arabian dromedary camels: a prospective genomic study a case-crossover analysis of the impact of weather on primary cases of middle east respiratory syndrome middle east respiratory syndrome ebola virus: a global public health menace: a narrative review heterogeneities in the case fatality ratio in the west african ebola outbreak - anatomy of an epidemic a literature review of zika virus history of highly pathogenic avian influenza global avian influenza outbreaks - : a systematic review of their distribution, avian species and virus subtype impact of meteorological factors on the covid- transmission: a multi-city study in china association between ambient temperature and covid- infection in cities from china inactivation of influenza virus by solar radiation the relationship between coronavirus (covid- ) spread and the weather pandemic's new epicenter the recovery from the covid- crisis must lead to a different economy the pandemic will accelerate history rather than reshape it ratios, benchmarks, and research advisories for it management tracking the global impact of the coronavirus outbreak climate vs coronavirus: why massive stimulus plans could represent missed opportunities position paper relazione circa l'effetto dell'inquinamento da particolato atmosferico e la diffusione di virus nella popolazione home | state of global air does air pollution influence covid- outbreaks? atmosphere is the coronavirus airborne? experts can't agree droplets and aerosols in the transmission of sars-cov- lack of covid- transmission on an international flight inquinamento atmosferico e covid- mascherine per tutti? available online civil aviation, air pollution and human health a post-carbon aviation future: airports and the transition to a cleaner aviation sector remarks of alexandre de juniac at the iata media briefing on covid- contrails reduce daily temperature range contrail cirrus radiative forcing for future air traffic verkehr in wien halbiert air pollution goes down as europe takes hard measures to combat coronavirus changes in air quality during the lockdown in barcelona (spain) one month into the sars-cov- epidemic presence of sars-coronavirus- in sewage survival of coronaviruses in water and wastewater how covid- impacts water consumption | aquatech wie sich unser wasserverbrauch in corona-zeiten verändert - - _artikel_orf_-_cov_fuenf_prozent_mehr_wasserverbrauch.pdf mitigating vulnerability of water resources under climate change. wp -vulnerability of water resources in see.-report version vulnerability of water resources to climate change in south-east europe united nations official document aerosol and surface stability of sars-cov- as compared with sars-cov- ranking hazards pertaining to human health concerns from land application of anaerobic digestate what do we know about the sars-cov- coronavirus in the environment? the proximal origin of sars-cov- mapping of poverty and likely zoonoses hotspots impacts of the coronavirus pandemic on biodiversity conservation using species distribution model to predict the impact of climate change on the potential distribution of japanese whiting sillago japonica does global change increase the success of biological invaders? habitat fragmentation, livelihood behaviors, and contact between people and nonhuman primates in covid- and nature are linked. so should be the recovery special feature: interactions of fast and slow variables in ecosystems using fast and slow processes to manage resources with thresholds resilience of ecosystems: local surprise and global change coronavirus ends china's honeymoon in africa covid- pandemic, a war to be won: understanding its economic implications for africa. appl health econ synergistic china-us ecological research is essential for global emerging infectious disease preparedness coronavirus shows we are not at all prepared for the security threat of climate change self-preservation strategy for approaching global warming targets in the post-paris agreement era floor | new; t . . . , n. - u.| how covid- could impact the climate crisis united nations | peace, dignity and equality <br> on a healthy planet available online the impact of covid- on gender equality united nations. policy brief: the impact of covid- on women water sector preparation, vigilance crucial impact of covid on customers and society recommendations from the european power sector. union of the electricity industry-eurelectric aisbl boulevard de l'impératrice, -bte - brussels covid- ) outbreak: rights, roles and responsibilities of health workers, including key considerations for occupational safety and health the innovation ecosystem, united against coronavirus how novel coronavirus could change the map on global manufacturing covid- , school closures, and child poverty: a social crisis in the making covid- could affect cities for years. here are ways they're coping now planners and pandemics: identifying problems and providing solutions covid- may be delivering a local manufacturing renaissance spread of sars-cov- coronavirus likely to be constrained by climate covid- at sea: impacts on the blue economy, ocean health, and ocean security could coronavirus lead to a "positive peace the role of environmental ris in the context of the current covid- crisis: a position by elter-lter in europe impacts on the global observing system coronavirus lockdowns have changed the way earth moves the impact of climate change and population mobility on neglected tropical disease elimination climate change and infectious disease: is the future here? environ. health perspect climate affects global patterns of covid- early outbreak dynamics high temperature and high humidity reduce the transmission of covid- will coronavirus pandemic diminish by summer? causal empirical estimates suggest covid- transmission rates are highly seasonal economic slowdown as a result of covid is no substitute for climate action analysis: coronavirus temporarily reduced china's co emissions by a quarter coronavirus could trigger biggest fall in carbon emissions since world war two correspondence: rapid growth in co emissions after the - global financial crisis. nat after the coronavirus, two sharply divergent paths on climate how the world will look after the coronavirus pandemic. foreign policy the real impact on the climate-geographical magazine covid- and air pollution: a deadly connection. available online covid- : epidemiology, evolution, and cross-disciplinary perspectives coronavirus and migration: analysis of human mobility and the spread of covid- a data ecosystem to defeat covid- this article is an open access article distributed under the terms and conditions of the creative commons attribution (cc by) license we thank very much the four reviewers for their valuable comments and suggestions. the authors declare no conflict of interest. key: cord- - bhiattk authors: farmaki, anna; miguel, cristina; drotarova, maria hadjielia; aleksić, ana; Časni, anita Čeh; efthymiadou, fani title: impacts of covid- on peer-to-peer accommodation platforms: host perceptions and responses date: - - journal: int j hosp manag doi: . /j.ijhm. . sha: doc_id: cord_uid: bhiattk the covid- pandemic has brought international tourism at a standstill. peer-to-peer (p p) accommodation, in particular, has been greatly affected with platforms being heavily criticised for lacking a strategic response to users’ needs. drawing from semi-structured interviews with p p accommodation hosts, this study aims to explore: a) their perceptions of the short-term impacts of the pandemic on their hosting practice, b) their responses to the pandemic and c) their perceptions of the long-term impacts of the pandemic on the p p accommodation sector. the study offers a continuum of host pandemic responses which illustrates different types of hosts in relation to their market perspective and intention to continue hosting on p p platforms. the continuum carries theoretical implications as it offers insights to academics exploring crisis impacts on p p accommodation. it is also of practical value to platforms and practitioners as it may lead to improved crisis management strategies. Τhe tourism and hospitality industry is no stranger to pandemics, having been impacted by sars in the early s and mers more recently (jamal and budke, ) . nonetheless, the emergence and rapid spread of a new coronavirus has had unprecedented effects on the global tourism and hospitality market. initially detected in the chinese city of wuhan in early december (yang et al., ) , covid- spread rapidly and by may there were over . million reported cases of infected people and reported deaths worldwide (who, ) . as a result, governments around the world imposed strict restrictions prohibiting travel while closing their borders, bringing international travel at a standstill. specifically, airlines have grounded their fleet and suspended operations (sahin, ) . likewise, the international hospitality and leisure industry has been experiencing tremendous economic problems as hotels in most countries were forced to shut down due to governments' lock-down response to the pandemic. for example, % of hotel employees have been laid off or furloughed, leading to a $ . billion loss in weekly wages and . million hospitalitysupported jobs being lost (ahla, ) . unsurprisingly, with a % reduction in revenues (oxford economics, ) , was named the worst year for hospitality in terms of occupancy rates since the great depression (cbre, ) . although crises in general have long-lasting adverse effects on travel patterns, tourist demand and destination image (chew and jahari, ; chien and law, ; corbet et al., ) , the tourism and hospitality industry has proven to be resilient in the past. indeed, in most cases destinations recover (seabra et al., ) particularly when crisis management strategies are in place (alonso-almeida and bremser, ) . for instance, after sars in china, travel bounced back relatively quickly to normal levels (dombey, ) . nonetheless, the unparalleled situation brought about by covid- has led to concerns over the future of global tourism and hospitality industry, which is one of the worst-affect industries by the pandemic (tidey, ) . specifically, scholars estimate that the effects of covid- on tourist risk perceptions and destination marketing will be long-lasting even after the pandemic is controlled (e.g. ying et al., ) , especially on the operational aspects of the industry. for instance, hospitality companies have issued announcements that their cleaning protocols will be revised. in this context, a range of practices such as the use of germ-zapping robots, the removal of breakfast buffets, a -hour gap between check-out and check-in time and even the issuance of a 'clean and safe' certificate has been suggested by hospitality associations and international hotel chains (bagnera and steward, ) . the peer-to-peer (p p) accommodation sector has attempted to follow suit, with platforms such as airbnb and booking.com responding to the effects of covid- in numerous ways. for example, the platforms have sought to establish a new, optional cleaning protocol for properties which requires a -hour waiting time between bookings as well as the use of specific cleaning products to eliminate possible coronavirus transmissions (wood, ) . in addition, the platforms have issued a refund policy which, nonetheless, angered a large majority of guests as they discovered that refunds are partial, dependent on the host and/or given in the form of travel credit (schuk, ; webster, ) . concerns from p p accommodation hosts have also been voiced as many struggled financially during the pandemic due to the loss of reservations (johnson and davis, ) . in relation to this point, hosts on p p accommodation platforms expressed that they felt largely unsupported as many local governments deemed p p accommodation as non-essential business (evans, ) , granting them no financial support and leaving the companies to foot the bill. airbnb, for instance, announced its intentions to provide more than $ million to support its host community. likewise, booking.com has asked financial aid from the dutch government to pay the salaries of its netherlands based staff (sharma, ) . even so, the platforms have been criticised heavily for demonstrating a lack of strategic thinking in response to covid- (carpenter, ) . with airbnb being forced to lay off % of its staff while observing its value depreciate from $ billion in march to $ billion in may (evans, ) and booking.com informing employees that lay-offs are probable (stevens, ) , it is not surprising that some media reports are suggesting that the pandemic might signal the end of p p accommodation. drawing from the perspectives of p p accommodation hosts, this study aims to explore indepth the perceived impacts of the covid- pandemic on host practice specifically and p p accommodation in general. more precisely, we examine p p accommodation hosts' perceptions of the short-term and long-term impacts of the pandemic as well as their associated responses. overall, the study offers several contributions. first, it advances existing knowledge on the pandemic-tourism nexus which has mostly concentrated on destination-level and sectoral-based analyses . while there are past studies examining the impacts of and responses to pandemics in hospitality (e.g. alan et al., ; henderson and ng, ) , these tend to overlook the perspectives of micro-level stakeholders. by drawing from accommodation service providers, this study thus responds to this gap in the literature. second, to the best of our knowledge, this study is the first to examine the associated impacts of the covid- pandemic on the increasingly popular p p accommodation sector (farmaki and kladou, ) . given that health, safety and cleanliness are considered key elements in hospitality decision-making (zemke et al., ) , findings from this study will therefore shed light on the ongoing discourse on p p hosts' practices which have been argued to shift to more institutionalised hospitality services (farmaki and kaniadakis, ) . third, the increase in infectious diseases across the world (jamal and budke, ) will likely preoccupy hospitality practitioners in the foreseeable future. to this end, this study contributes insights that may lead to improved health crisis management strategies in hospitality. the rest of the paper is organised as follows. first, the literature on the effects of pandemics on hospitality is reviewed before considering the impacts of the covid- pandemic on the p p accommodation sector. then, the methodology guiding this study is explained and justified before the findings are presented and discussed. last, the theoretical and practical implications emerging from this study are drawn as conclusions. the threat of pandemic emergence has increased in the st century as a result of various reasons including: the growing mobility of the population, urbanisation, the industrialisation of food production processes and the expansion of global transport networks which contributes to the transmission of pathogens (connolly et al., ; hall, ) . the outbreak of diseases like sars, mers, the ebola and zika viruses and more recently covid- stands as evidence of the growing pandemic threat. in this context, the global tourism industry has been identified as a contributor to the spread of diseases (nicolaides et al., ) as the more people travel, the more likely it is for a disease to spread internationally. on the other hand, the industry was also recognised as being highly susceptible to pandemics, incurring significant economic costs (kuo et al., ) as pandemics negatively influence j o u r n a l p r e -p r o o f tourist demand and destination perceptions (novelli et al., ) . one sector of the tourism industry that is regarded as highly impacted by pandemics is hospitality, given its vulnerability to health-related crises (mckinsey and company, c) . numerous studies examining the effects of pandemics on hospitality may be found in the literature (e.g. alan et al. ; chen et al., ; chien and law, ; kim et al., ; wu et al., ) . this pool of work illustrates the adverse effect of a pandemic on hotel occupancy rates, revenues and stock performance, reminding us of the importance of sanitation and hygiene within the sector (naumov et al., ) . evidently, pertinent studies highlight the significance of response mechanisms of hospitality businesses to epidemics (henderson and ng, ; kim et al., ) whilst identifying customers' self-protective behaviours as equally important (chuo, ) . in this context, hospitality businesses' reactions to pandemics through risk assessment, formal planning and integrated, contingency plans have been noted as particularly critical for the recovery of the sector (jayawardena et al., ) . likewise, support from national governments through assistance programmes was identified as a key factor contributing to sector recovery (chien and law, ) . equally, human resource strategies were acknowledged as important in crisis management efforts during pandemics, with leung and lam ( ) suggesting unpaid leave and involuntary separation as common immediate solutions by hotels. in this context, pandemic-related studies indicate that travel behaviour tends to return to normal as soon as the situation is controlled by authorities. drawing from the sars experience, several studies point out to the risk-taking behaviours of travellers (e.g. lau et al., ) whilst reporting that travel resumes to normalcy as soon as the situation allows it (dombey, ; zeng et al., ) . while much of the previously noted pandemics were shortlived , the newly emergent covid- virus though is anticipated to have long-lasting effects on the tourism and hospitality industry (ying et al., ) . although there are instances of tourists demonstrating irresponsible behaviours during the covid- pandemic (e.g. guy, ) , in most cases travel behaviour has been greatly affected as many individuals will opt for domestic holidays in (euronews, ) . as a result of increasing fears among the general public, industry stakeholders have expressed plans to improve hygiene standards. for instance, hotel companies have announced revisions in their cleaning protocols and food and beverage offerings (bagnera and steward, ) with robotics adoption emerging as a preferred option to minimise human contact (zeng et al., ) . whilst the traditional hospitality industry seems willing and capable of adjusting its operations, concerns have been raised over the future of the p p accommodation sector and, specifically, the ability of hosts to follow suit. p p accommodation has emerged as a disruptor on the traditional hospitality sector due to their growing popularity (sigala, ) . referring to online networking platforms through which individuals can rent out for a short period of time their under-utilised property space (belk, ) , p p accommodation has grown immensely as a result of the numerous benefits it may offers to travellers and property owners. for travellers (guests), it offers a convenient, valuefor-money accommodation option (stors and kagermaier, ; tussyadiah, ) that is generally regarded as more authentic and localised than hotel stays paulauskaite et al., ) offering a 'home away from home' feeling (liang et al., ) . for property owners (hosts), p p accommodation offers opportunities for entrepreneurship (zhang et al., ) and additional income (farmaki and kaniadakis, ; guttentag, ) that improves individuals' standard of living (lutz and newlands, ) . similarly, through hosting individuals have the opportunity to engage in social interaction (moon et al., ) and share experiences, particularly when hosts rent rooms in their homes . in addition, it has been argued that through p p exchanges hosts receive gratification for providing a good hospitality service (lampinen and cheshire, ) . these economic and social benefits drive p p accommodation users to engage with platforms either as hosts or guests. in recent years changes have been observed in the p p accommodation sector as the growth of certain platforms (i.e. airbnb) and the competition among hosts has led to the adoption of professional hospitality standards (farmaki and kaniadakis, ; . the professionalisation turn in p p accommodation was also encouraged by the decision of platforms like airbnb to open up their space to professional accommodation providers such as boutique hotels and attract people who would never thought of staying in a p p accommodation before like business travellers (guttentag and smith, ) . for example, airbnb introduced new search tools for business travellers allowing more customised search results. likewise, the platform launched a 'superhost' and 'superguest' badge that resemble hotel loyalty schemes and award benefits (i.e. discounts) to dedicated users (liang et al, ) . another recent addition of the platform was 'airbnb plus' which refers to an elite selection of properties that have "exceptional hosts" and 'airbnb luxe' that includes luxury properties that come with the services of a dedicated concierge (farmaki and kaniadakis, ) . in this context, p p accommodation hosts started to offer services such as airport pick-ups, meals and concierge service that resemble those of hotels (farmaki and kaniadakis, ) in a bid to reach superhost status and improve their search results and profitability. evidently, while the provision of a clean, functionable property and quality tangibles moon et al., ) continues to be a key prerequisite for guest satisfaction (priporas et al., ) , the recent changes in the p p accommodation sector point towards increasing guest expectations (farmaki and kaniadakis, ) . several studies identify cleanliness and tidiness as key factors for p p accommodation guest satisfaction (lyu et al., ; tussyadiah and zach, ) alongside other elements such as location, amenities and facilities (cheng and jin, ) . nonetheless, there is a growing number of studies that highlight the increasing demand for host friendliness, responsiveness and hospitableness (chen and jin, ; gunter, ; xie and mao, ) in addition to hotel-like products and services. hence, what influences the guest experience and drives demand for p p accommodation is a combination of tangible elements as well as intangible practices, reflecting host attitudes and personality (sthapit and jimenez-barreto, ; zhu et al., ) that denote the quality of the overall service offered (ju et al., ) . as such, it is not surprising that a hybrid form of service is emerging in the hospitality industry combining home feeling with professional hospitality service provisions the outbreak of the covid- pandemic, nonetheless, has challenged p p accommodation host practices, revealing the sector's vulnerability to pandemics. according to industry analysts, hotels will have an advantage over p p accommodation rentals in the post-covid era primarily due to the lack of standardisation in p p accommodation host practices which, in turn, may make the public wary regarding the hygiene of their properties and the fairness of their terms (glusac, ) . although the morality of hosts in maintaining responsible behaviours and hosting practices was previously noted , it was especially highlighted during the covid- pandemic and in relation to practices such as cancellation of bookings. also, while many hosts offered their properties for free to covid- responders and health workers (gtp, ), others driven by economic motives defied lockdown laws and advertised their properties as 'covid- retreats' (criddle, ) . another hosting aspect that is impacted by the pandemic is the interaction with the guest which represents an essential element of the experience ), yet is compromised by the social distancing guidelines imposed by national governments as a measure to combat the spread of j o u r n a l p r e -p r o o f the covid- virus. indeed, the pandemic led individuals and accommodation providers to engage in protective behaviours. although hosts were urged to follow prevention measures (jamal and budke, ) , cost-benefit evaluations tamper hosts' decision to engage in protective behaviour (cahyanto et al., ) . in this context, the perceptions of hosts and their responses to the covid- pandemic emerge as significant in determining the future of the sector. given the purpose of the research, a qualitative approach to research was regarded as more appropriate. qualitative research may provide thick descriptions of people's perceptions and, hence, reveal new understandings of a phenomenon (ezzy, ) . in particular, from may to june semi-structured interviews were performed with p p accommodation hosts from the following countries: croatia, cyprus, greece and spain. located in the mediterranean basin that has been greatly affected by the covid- pandemic, these countries represent suitable contexts for examining hospitality issues as they are popular tourist destinations with an abundance of p p accommodation properties. nonetheless, each country has witnessed different experiences during the covid- pandemic and showed varying responses. for example, greece has been commended for its timely measures against the pandemic which led to a relatively low number of infected cases and deaths whereas spain witnessed a national tragedy, with covid- related deaths exceeding cases (pappas, ) . such differences in experience are likely to shape host perceptions of and reactions to the impacts of the pandemic. purposive sampling was used to select participants. purposive sampling is a sampling technique where participants are selected based on specific pre-selected criteria (etikan et al., ) . therefore, at the first instance, we selected p p accommodation hosts purposively according to the following criteria: a) participants had to be active hosts on p p accommodation platforms and b) participants had to be available and willing to participate in the study as well as be able to describe their perceptions (bernard, ) . the rationale of purposive sampling rests on the fact that the researchers, based on their a-priori theoretical understanding of the topic, assume that certain individuals may have important perspectives on the phenomenon in question (robinson, ) . in so doing, the researcher(s) from each country posted an open call on various social media platforms and p p accommodation forums inviting members to participate in the research whilst ensuring their anonymity and data confidentiality. in order to minimise self-selection bias (bethlehem, ) , the researchers tried to ensure that the sample from each country was diverse enough (ritchie et al., ) in terms of gender, age and host type. data collection came to an end when no new information was observed in the data (fusch and ness, ) and the researchers were confident that data saturation was reached (glaser and strauss, ) in accordance to the leading questions and, thus, ensuring that adequate evidence for each theme was obtained to reach conclusions (saunders et al., ) . overall, interviews were conducted with p p accommodation hosts. the profile of the participants may be seen in table . the type of property of each participant was categorised according to the p p accommodation host typology of farmaki and kaniadakis ( ) which includes: hosts sharing a room in their house, hosts with or listings renting the entire property and hosts renting an entire property that manage multiple listings (their own and of others). due to the lockdown measures imposed across europe at the time of the data collection, the interviews were conducted over skype or zoom, in accordance to the participants' date and time preference. before each interview, the researcher(s) explained to the participants the purpose of the study and the ethical implications involved and obtained their signed consent to being recorded. the interviews lasted approximately to minutes each and were conducted in the local language of the researcher(s) before being translated into english. each interview proceeded from a number of 'grand tour' questions (mccracken, ) seeking to establish the hosting profile of the participants before moving into the topic of: a) hosting motives in order to understand the drivers for engaging in p p accommodation, b) impacts of the pandemic on host practices and their related responses and c) host perceptions of the longterm impacts of the pandemic on their hosting and p p accommodation in general. table illustrates the questions asked. what are the short-term economic impacts of the pandemic on your hosting activity? how has your hosting practice and operational activity changed as a result of the pandemic? have you received petitions of cancellations of bookings asking for % refund pushed by the platforms? have you received phone calls from 'customers service' to encourage you to cancel bookings? which measures are you planning to take to ensure a good level of hygiene is provided in your property(ies)? have you received any requests or enquiries from guests asking about hygiene? have the platforms (e.g. airbnb) been supportive in terms of the impacts hosts have incurred as a result of the pandemic? did you receive any support from the government as a result of the pandemic? what do you think the long-term economic impacts of covid- will be? how do you foresee your hosting practice evolving in the near future as a result of the pandemic? do you plan to move to a long-term rental mode? in your opinion, how has the pandemic changed the p p accommodation sector? any long-term threats or even opportunities emerging from this situation? the translated transcripts were checked by each researcher for accuracy and then imported to the nvivo software to be analysed using thematic analysis (braun and clarke, ) . data analysis was conducted by two researchers who employed the three coding rounds prescribed by gioia et al. ( ) . in more detail, during the first coding round the researchers 'adhered faithfully to informant terms' (gioia et al., : ) by reading the transcripts line by line without imposing restrictions on the text to be analyzed (strauss and corbin, ) . then, the transcripts were analysed more closely with the researchers identifying key topics in a "theorydriven" manner (braun and clarke, : ) . to maximise analytical integrity and ensure the robustness of findings, each researcher undertook an initial round of open coding separately before converging the first set of findings in a process called triangulation. flick ( ) posited that investigator triangulation is an effective method to balance subjective research interpretations due to the collective comparison of coding schemes. hence, in this study researcher triangulation ensured that interviewees' perceptions of the pandemic as pertaining to their hosting practice were objectively interpreted. subsequently, a second round of coding was undertaken whereby emerging topics were grouped into interrelated themes by copying, re-organising and comparing thematic categories whilst refining the data under each theme to identify sub-categories (goulding, ) . in this way, thematic categories were expanded and clarified. last, a third round of coding was used to combine sub-categories with the themes initially identified. in this way, relationships were validated and thematic categories were refined and further developed (strauss and corbin, ) to enhance elaboration on key issues (hennink et al., ) . the following steps were undertaken to ensure reliability in data analysis. first, we ensured interpretative and evaluative rigor (kitto et al., ) was maintained. for instance, in addition to participant validation of the data collected, the transcripts were read and compared by both researchers involved in the analytical process through investigator triangulation (golafshani, ) ; thus, minimising researcher bias. second, in completing the abstraction process, we grouped concepts and/or overlapping categories according to similarities and differences between categories which were discussed between the key researchers following the separate round of coding as proposed by bryman and burgess ( ) . taking thomas and harden's approach ( ) , as part of thematic synthesis the independent researcher identification of themes was followed by discussion among the researchers of overlaps and divergencies until agreement was reached. in so doing, the researchers followed a thorough process of recordkeeping to maximise the consistency of the data interpretation and to clearly demonstrate the decision trail of grouped concepts (noble and smith, ) ; thus maximising transparency. also, we ensured the coding process reflected the richness of the data collected (moretti et al., ) ; as such, we included thick verbatim descriptions of the interviewees' accounts to support key findings. at the first instance, we asked participants to describe the reasons that led them to host on p p accommodation platforms. understanding host motives was important not only to set the background and identify differences between hosts but also to gain a better insight of their perceptions of the pandemic impacts and associated responses. indeed, posited that p p accommodation host behaviours are likely to be influenced by hosting motives. some participants argued that they host for the social benefits (farmaki and stergiou, ) emerging from the interaction with the guest and the enjoyment of hosting people in their house. for these hosts, continuous bookings are not necessarily a concern as they view hosting more as a hobby or a temporary arrangement as a result of personal life changes (i.e. children moving away from home) from which they get personal gratification. generally, though, financial gains emerged as the primary motive for hosting in line with extant literature (e.g. guttentag, ) . around a third of the participants claimed that p p accommodation was their first source of income. as the discussion progressed, it became obvious that many of those hosts emerged as 'professionals' in the p p accommodation domain (farmaki and kaniadakis, ) , often managing multiple listings that are not just their own but also the properties of others. for these hosts, p p accommodation has proven to be a lucrative employment option (zhang et al., ) that is simultaneously flexible. for example, a participant argued that managing p p accommodation properties offers her a good work-life balance, stating that "this job does not distract me from my baby" [p , cyprus] . in their majority, 'professional' hosts seem to have started hosting using a or personal properties and then used their profits to acquire additional ones to expand their business. within this type of hosts, we also identified participants that were previously involved in long-term renting; yet, they decided to switch to short-term rentals via p p accommodation platforms as their popularity grew, allowing them to earn more money. a few participants, though, stated that they continue to manage long-term rentals alongside p p accommodation properties "depending on the type and location of the property and demand" [p , greece]. in addition, for some 'professional' hosts, the transition to p p accommodation came about as a result of negative experiences with tenants. in the words of a participant: "[(the tenant) left without telling me anything…left the apartment in very bad conditions…the deposit didn't cover all the damage. so, i thought i had to control the apartment closer" [p , spain]. further on, we asked the participants to state which platforms they use to advertise their properties, explaining which is their favourite. although several participants, especially professional hosts, seem to use various platforms (e.g. expedia, lastminute, splendia, homeaway, mrbnb, wimdu and other local ones) for greater exposure, airbnb and booking.com emerge as the most popular. some participants seemed to prefer booking.com as they claim it offers more reservations or a higher quality clientele; nonetheless, the majority identified airbnb as their favourite, citing numerous reasons for their choice. for instance, participants stated that airbnb is more user friendly, popular and flexible to use whilst commands lower commission fees than booking.com. participants also added that airbnb is more "pro-people" [p , spain] and "host-oriented" [p , croatia] as it allows hosts to review guests as well while laying down their own house rules. regardless, hosts on both airbnb and booking.com commented on the ease of using the features of platforms to synchronise calendars across platforms, which also explains why most hosts do not use a channel management app. following, we asked participants to elaborate on the impacts of the covid- pandemic on their hosting practice. unsurprisingly, all the participants stated that they have been directly and negatively affected by the measures undertaken by governments to control the spread of the pandemic. indeed, many participants are based in tourist destinations, with a large proportion of their bookings coming from foreigners who at the time of the pandemic were unable to fly (sahin, ) . specifically, hosts argued that they not only saw their bookings cancelled but also requests to book their properties ceased, illustrating similar pandemic effects as in mainstream hospitality (e.g. chien and law, ; kim et al., ; wu et al., ) . with the exception of a few participants who said that they had booking requests from locals who wished to stay in their properties (i.e. healthcare workers distancing from their families, people stranded in the country), hosting for most was basically put on hold. in fact, some participants claimed to have closed their property on the platforms to ensure it is not available for bookings during the pandemic, fearing contagion or platform collapse. the following extracts reflect such sentiments: "if i host someone in my apartment who is not very careful, i can get the virus from this person. the host is always risking to get the virus by hosting" [p , spain] . "my parents live downstairs, they are old and vulnerable. also, i see there are problems with airbnb as it has fired employees…so i changed the limit of the money that airbnb can transfer as i was afraid the platform would collapse" [p , greece]. even so, 'professional' hosts seemed to have experienced the greatest impact as hosting represents their main source of income. while hosts in general expressed difficulty in paying their mortgages/rents and covering maintenance costs as a result of the loss of bookings, 'professional' hosts in particular found themselves in a dire economic situation. for example, participants expressed difficulty in "paying rent to property owners" [p , cyprus] or even covering the salaries of employees such as cleaners, indicating that the pandemic has had an effect on other actors as well. as a participant put it: "i have no job and i cannot pay the lady who is cleaning our properties. i feel very sad about this situation…the unemployment office pays only about % of your original salary…if my husband doesn't work, we are near to bankruptcy…" [p , cyprus] . in order to try to adapt their hosting activity to the pandemic, participants reported different strategies. for example, to boost demand they claimed that they will "lower prices...to attract new guests this year" [p , croatia] although a few participants said they might "raise prices…to recover the lost profit" [p , spain] . other practices participants are contemplating on adopting include: targeting domestic tourists, introducing self-check in to minimise human context, offering antiseptic gels to guests, disinfect the apartments, invest in buying ozone machines for better cleaning and allow hours between bookings. these practices seem to be in line with those suggested within the mainstream hospitality industry (bagnera and steward, ) . in this context, some participants commented on how they previously maintained "high levels of hygiene" [p , croatia] with some, though, acknowledging that such practices may not have been adopted by everyone and even suggesting "some kind of certification of cleaning so that it is not done by individuals or the hosts themselves" [p , greece]. when asked if they thought the platforms were supportive of hosts during the pandemic, the majority of participants answered negatively. as a participant put it, "airbnb returned the full amount to all users of its services without asking the host" [p , croatia] . other participants agreed, commenting how platforms "reacted spontaneously" [p , croatia] as the situation was new to them, leading to host resentment (johnson and davis, ) . more critical participants argued that "the platforms are always pro-guests" [p , spain], with some participants highlighting that airbnb especially was never supportive to hosts as their main strategy is "to grow its clientele" [p , greece] . this argument is in line with past studies claiming that the airbnb is becoming guest-oriented (farmaki and kaniadakis, ) . the major controversy was related to the fact that hosts, who had a strict cancellation policy on airbnb or non-refundable in other platforms like booking and usually receive % of the amount of the booking in case of cancellation, were forced to provide a % refund. as some hosts explained, this was perceived as a betrayal of the platform since they had compromised with less bookings due to that policy to secure some funds. for example: "airbnb cancelled the bookings on my behalf. airbnb didn't respect the hosts cancellation policies. there was a kind of contract between the platforms and the hosts where each host could choose the type of cancellation policy: strict, moderated or flexible. obviously each cancellation policy has pros and cons. for instance, if you choose a strict cancellation policy, you may not have so much demand, compared to a more open cancellation policy, but you secure part of the payment in case of cancellation" [p , spain]. nonetheless, some participants felt that the platforms were communicative and did their best given the unprecedented situation. demonstrating a more empathetic stance, a participant stated that the platforms "informed us in a timely manner of the situation affecting us, but neither could perform miracles" [p , croatia] . others claimed they cancelled the bookings because they put themselves in guests' shoes. "i would do the same [as a guest]. i'd ask for a refund, it is a superior force [pandemic] i did not expect what airbnb would say, it is an issue of being humane" said a participant [p , greece]. another host explained how he appreciates that airbnb launched a $ million fund aimed to help hosts who had strict cancellation policies while pointing that booking did not offer any help: "airbnb has prepared $ million in support for paying all people % of what they should have received as the cancellation fee. to put it simply, if you had a strict policy that pays you % of the total price in case of cancellation, you get % of that %, which is ultimately . % of the total price. although it is only a tenth of the total price, airbnb's consideration for the hosts was appreciated. i point out that airbnb takes only % commission from the hosts and booking.com that did not help the hosts in any way takes %" [p , croatia] . in relation to this point, participants highlighted the positive outcome of receiving at least part of the booking with some going further and suggesting amendments in platform policies such as the issuance of "a travel insurance in case of cancelling bookings" [p , cyprus]. one j o u r n a l p r e -p r o o f host explained how he reacted very quickly and cancelled all his bookings, which then prevented him for getting the support: "i did a small mistake because i cancelled my bookings and return all money back to my guests at the very beginning. so, i am not allowed to get any refund out of these. because, if my guests would cancel their stay and not me, then i would get some money back, but i did not know about this" [p , cyprus]. the way airbnb announced the 'help scheme for hosts' was deemed misleading by some hosts. the information was not very clear and many hosts believed the help was for all hosts and not only for the hosts with strict cancellation policies. also, hosts complained about the lack of information about the 'superhost help scheme' aimed at superhosts who only have one property and depend % on the earnings from that property. some superhosts who fit the requirements called airbnb to request information and they were told they would be contacted by airbnb but never received any communication. as a host put it, "airbnb lied to us, they told us they were going to help us but they didn't" [p , spain]. in addition, some participants pointed to platforms' indirect 'manipulation' of the situation commenting that they "contacted the guest to suggest to cancel the booking under the covid- protocol where the set cancellation policy is not applicable and the guest could receive % refund" [p , spain] whilst "keeping their fee" [p , spain] . such arguments confirm p p accommodation platforms' pro-guest mentality, as previously highlighted by farmaki and kaniadakis ( ) . unsurprisingly, many hosts expressed feeling marginalised from the platforms, suggesting that the platforms "don't treat hosts as partners" [p , cyprus]. as such, hosts commented on how there was poor communication with the platforms as in some cases hosts had made their own arrangements with guests; thus, confirming reports of p p accommodation platforms' lack of strategic thinking in the pandemic (carpenter, ) and support past studies that emphasise contingency plans of hospitality companies as key for their recovery (jayawardena et al., ) . in addition to refunds, participants stated that platforms promised to offer guests a change of dates in bookings or travel vouchers, which came after hosts expressed dissatisfaction with the refund policy (schuk, ; webster, ): "booking.com is starting to offer a change of dates or a voucher to travel in the future. but at the beginning they were just refunding everyone % because of force majeure" [p , spain]. nonetheless, as participants explained, in many cases these alternatives were not preferred by guests, who usually preferred the % refund. participants were also equally critical of governments, citing lack of support to hosts despite their important role in assisting the hospitality sector to recover (chien and law, ) . although 'professional' hosts claim to have received some money from government as part of their subsidy to companies, many participants highlighted the unregulated context in which p p accommodation operates as limiting the potentiality of compensation from governments. in the words of a participant, "i do not think that the government would like to give to hosts any help, since some policy makers believe that they are cheating and not paying their taxes to the government" [p , cyprus] . in fact, several participants said that they don't expect monetary assistance from the government. consequently, we diverted our attention to hosts' long-term perspectives and intentions following the pandemic. in relation to this point, participants expressed varying views leading j o u r n a l p r e -p r o o f us to categorise them accordingly. specifically, as analysis progressed, we identified two main types of hosts in terms of their perspectives: the 'optimistic hosts' and 'pessimistic hosts' which we were able to further categorise according to their decision to exit the platforms or not. overall, five types of hosts were identified and categorised on a continuum (figure ) according to their long-term perspective (i.e. decision to continue hosting on p p accommodation platforms) and level of practice adjustment. <insert figure about here> . . pessimistic hosts on the right-hand side of the continuum, 'pessimistic hosts' stated that they intent to either "sell the property given the situation" [p , spain], "give up renting altogether" [p , croatia] or "switch to long-term renting" [p , cyprus] . for these hosts, the pandemic has exposed the vulnerable aspects of the p p accommodation sector, threatening its existence as "the system has become weak" [p , greece] . such arguments support previous research findings which postulate that the power dynamics in p p accommodation, fostered by platforms' favouring approach to guests, is driving hosts out of the platforms (farmaki and kaniadakis, ; . pessimistic hosts also claimed that tourists would choose hotels over p p accommodation in the current situation, for example: "tourists will probably choose hotels rather than private accommodation because hotels have some standards and for private accommodation there is always a surprise factor" [p , cyprus]. we also identified 'cautious hosts' who appear to contemplate on shifting or returning to longterm rental, albeit temporarily as a reaction to the current situation and until things improve. "(will move to long-term rental) at least for or years. we need to make some money, so the best solution is long-term accommodation" said a participant [p , cyprus] . likewise, some 'cautious hosts' argued that to maximise their feeling of security, they'll opt to rent both shortterm and long-term type of properties. in the words of a participant, "we have created a website where we are going to mix long-term and short-term rental" [p , spain]. in the middle of the continuum, we placed hosts who claimed that it is not possible to foresee the future of the sector due to the unknown outcome of the pandemic. as such, these hosts which we labelled 'ambivalent hosts' stated that they will wait to see "how the situation unfolds" [p , cyprus] before making any decisions to continue hosting on p p accommodation platforms or exit. as a participant explained, "i am waiting for the airports to open first and see what type of people will come…" [p , greece]. moving towards the left-hand side of the continuum, there were 'indolent' hosts who stated that they will continue renting through p p accommodation platforms due to a number of reasons. for example, several participants argued that they cannot switch to long-term renting as their properties are in touristic locations and thus "not suitable for long-term renting" [p , croatia] . other participants explained that renting through p p accommodation platforms is preferable as they can achieve higher profits than long-term renting or, in many cases, longterm renting is not possible as the rented property is attached or within the ground of the host's house. another key factor that seems to deter hosts from renting long-term is that "long-term renting has many problems" [p , greece] including damages to the property that the owner is not being compensated for, unpaid rents and in some legal contexts inability to evict unruly tenants. even so, these hosts seemed unwilling to change their hosting practices as a result of increased hygiene and safety risks. in the words of a participant, "i don't intent to change anything. i prefer to have it closed than go into the mentality of being a labourer of the property" [p , greece]. on the other end of the continuum, there were participants who emerged as 'optimistic hosts' as they believed that the pandemic has brought opportunities that will positively transform the p p accommodation sector. specifically, participants claimed that the pandemic will reinforce demand for p p accommodation as hotels run greater risk of infection and, thus, people will prefer to stay in more isolating types of accommodation with less personal contact. such statements counteract initial estimations by media reports that the p p accommodation sector will be negatively affected by the pandemic due to the lack of standardisation in host practices that reinforces concerns over health and safety criteria (e.g. glusac, ) . in the words of a participant, "there is going to be a complete shift in the way we travel. massive tourist trip, trips for just a weekend, low cost travel, all of that is going to change" [p , spain] . within this context, participants argued that "there will be a cleaning up" [p , spain] in the sector as the pandemic is removing the opportunists. as a participant summed it up "the image that 'anyone rents a property in airbnb' will change" [p , greece] . in relation to this point, some participants commented on how the transition of some hosts to long-term renting will be good for the society as long-term rent will decrease. generally, 'optimistic hosts' seem to plan their future hosting practices accordingly and expressed their intentions of making adjustments. for example: "i have always left one day in between bookings. now i may even leave days" [p , spain]. overall, three conclusions are derived from this study. first, the pandemic's effects have been equally great on p p accommodation as on mainstream hospitality providers (e.g. wu et al., ) , with hosts experiencing both losses of revenue and future booking requests. in the case of professional hosts, the effects of the pandemic extended into inability to pay for salaried staff (i.e. cleaners) and other company-related expenses. second, with economic benefits driving individuals to host on p p accommodation platforms (guttentag, ) , it is not surprising that hosts are contemplating to continue hosting on the platforms in hope that the situation will improve and they will resume making profits. nonetheless, our study identified hosts that have decided to exit the platforms and recover by turning to long-term renting. the decision to exit the platforms seems to have been encouraged by hosts' disappointment over the minimal support received from platforms which, according to our findings, are exhibiting a "pro-guest" mentality that victimises hosts. for instance, hosts expressed frustration over the way the platforms handled the pandemic by encouraging guests to ask for full refunds. this leads to the third finding of our study which reveals a variety in host responses with regard to the pandemic's impacts. specifically, we depict the different types of hosts on a continuum (figure ) in accordance to their long-term market perspective and hosting practice adjustment depending on their decision to stay or exit p p accommodation platforms. in light of these conclusions, this study carries both theoretical and practical implications. although the relationship between pandemics and hospitality has been previously investigated (e.g. chen et al., ; henderson and ng, ) , this study represents the first attempt to examine the impacts and associated responses of pandemics in a p p accommodation context. as such, the study sheds light on p p host practices during a pandemic by exposing the factors driving host decision-making, which does not revolve around economic benefit solely but encompasses personal aspects including ability to respond to health and safety expectations. specifically, the study advances theoretical understanding of the pandemic-hospitality nexus which has insofar focused on destination-level and sectoral-based analyses by investigating micro-level stakeholders' perspectives. in so doing, the study reveals a variance in perceptions and responses of hosts to pandemics which led us to categorise them along a continuum in terms of their market perspective and intention to continue hosting on p p platforms. on the one end of the continuum, there are 'optimistic hosts' that will continue hosting on platforms whilst altering their practices to comply to the emerging need for better health and safety standards. these hosts seem to understand that health and safety are regarded as key in hospitality provision (zemke et al., ) and are willing to adapt their strategies, contrary to 'indolent hosts' who plan to continue their hosting activities without adaptation of their practices. the sentiments of 'indolent hosts' seem to emanate from their belief that their practices are adequately responsive to health standards or their decision to withstand the additional pressures of the platforms and guests on their practice (buhalis et al., ; . on the other end of the continuum, there are 'pessimistic hosts' who intend to cease p p hosting altogether and turn to long-term renting as well as 'cautious hosts' who prefer to maintain both short-term and long-term rentals for greater safety. additionally, we identified hosts that were ambivalent towards their future responses to the pandemic, preferring to see how the situation will unfold before making a decision. the figure can serve as the basis for further investigation into the effects of pandemics on p p accommodation users, primarily by illustrating the need to acknowledge existing variance in service providers' perceptions and responses to crises. correspondingly, the figure may enable researchers to identify specific behaviours and, thus, understand influencing factors and relationships between actors in p p accommodation in order to articulate more targeted questions and designs within their research. the study also offers practical implications. for instance, our typology of host pandemic responses (figure ) can be useful to p p accommodation platforms as it may offer some indications related to the improvement of their governance. as the figure illustrates, there are several types of hosts that depict varying responses in the midst of pandemics. as such, platforms need to adopt a more targeted approach in the development of their crisis management policies and strategies as well as their overall support measures to hosts. otherwise platforms run the risk of losing members, especially individual hosts who tend to share their space and are often unable to meet the increasing needs of guests and/or even platform themselves (farmaki and kaniadakis, ) . considering that many users of p p platforms seek a sharing type of property for social reasons , such a risk might prove to be unprofitable for platforms. in this context, platforms may consider establishing travel insurance features on bookings that will safeguard hosts and/or providing a range of support measures depending on varying types of hosts. given the unregulated environment of p p accommodation which fosters the lack of governmental support towards hosts during the pandemic, it is important that platforms step up to ensure responsibility towards all of their members. in this sense, this study could also inform policymakers in order to help them design appropriate policies to regulate the p p accommodation market sector. although questions have been raised over the future of the p p accommodation sector as a result of the pandemic, the unprecedented situation revealed underlying opportunities which platforms may exploit (glusac, ) . for example, our study found that 'optimistic hosts' anticipate demand for p p accommodation to grow as they are more isolated than hotels. thus, platforms need to promote the related benefits of staying in p p accommodation opposed to traditional accommodation whilst, simultaneously, ensuring that hosts adhere to the required health and safety standards. as such, platforms need to promote a proactive evaluation process before booking in addition to post-stay reviews by, perhaps, offering specific health certifications to hosts who fulfil a set of required criteria. even though health and safety are core to the hospitality product (naumov et al., ) , cleanliness and tidiness are key factors for guest satisfaction in p p accommodation (lyu et al., ; tussyadiah and zach, ) . the covid- pandemic has highlighted the importance of such factors further, heightening them into a prerequisite determining the future of the sector. the supportive stance of platforms is of particular importance for 'ambivalent hosts' who are still indecisive of their future responses. in this context, out typology may be of use to practitioners of p p accommodation allowing them to self-identify with a specific category of host pandemic response and adopt the tactics that are most suited to their needs, preferences and capabilities. this study drew from a european context only; hence, it is advisable that future research examines hosts' perceptions and responses to pandemics within other cultural contexts. similarly, as this study focused on host perspectives it may be worth if future research considers guest views in order to identify potential gaps between guest health and safety expectations and host practices. likewise, researchers may also examine the social impacts of the pandemic on hosts sharing a room in their house as these are more likely to engage in hosting due to social motivations. researchers may also embark on a comparative investigation in terms of the crisis management strategies adopted in p p accommodation and mainstream hospitality to observe areas of convergence and divergence as well as best practices. furthermore, the views of policymakers on the impacts of the pandemic, especially in terms of long-term renting, and their related responses is another area of investigation worth considering. generally speaking, the outbreak of the covid- pandemic has had a profound effect on the global tourism and hospitality market ; nonetheless, the pandemic has opened pandora's box for p p accommodation platforms exposing the vulnerable aspects of the sector. as such, the future of the sector remains to be seen. crisis management and recovery: how restaurants in hong kong responded to sars strategic responses of the spanish hospitality sector to the financial crisis covid- 's impact on the hotel industry navigating hotel operations in times of covid- you are what you can access: sharing and collaborative consumption online qualitative data analysis i: text analysis selection bias in web surveys using thematic analysis in psychology analyzing qualitative data predicting information seeking regarding hurricane evacuation in the destination airbnb demonstrates lack of strategic thinking in response to covid- insights and implications of covid- pandemic the impact of the sars outbreak on taiwanese hotel stock performance: an event-study approach what do airbnb users care about? an analysis of online review comments destination image as a mediator between perceived risks and revisit intention: a case of post-disaster japan the impact of the severe acute respiratory syndrome on hotels: a case study of hong kong restaurant diners' self-protective behavior in response to an epidemic crisis extended urbanisation and the spatialities of infectious disease: demographic change, infrastructure and governance the impact of terrorism on european tourism airbnb hosts defy lockdown laws with 'covid- retreats'. bbc news [access online th the effects of sars on the chinese tourism industry comparison of convenience sampling and purposive sampling airbnb's future is uncertain as it continues to struggle through its covid- response. cnbc [accessed online taiwan kickstarts domestic tourism after containing coronavirus spread. euronews [accessed online th qualitative analysis: practice and innovation a lefebvrian analysis of airbnb space power dynamics in peer-to-peer accommodation: insights from airbnb hosts why do airbnb hosts discriminate? examining the sources and manifestations of discrimination in host practice escaping loneliness through airbnb host-guest interactions self-perceptions of airbnb hosts' responsibility: a moral identity perspective an introduction to qualitative research are we there yet? data saturation in qualitative research discovery of grounded theory: strategies for qualitative research hotels vs airbnb: has covid- disrupted the disrupter? new york times seeking qualitative rigor in inductive research: notes on the gioia methodology understanding reliability and validity in qualitative research pandemics, tourism and global change: a rapid assessment of covid- grounded theory: some reflections on paradigm, procedures and misconceptions. working paper series airbnb hosts provide housing to covid- responders. greek travel pages [accessed th what makes an airbnb host a superhost? empirical evidence from san francisco and the bay area airbnb: disruptive innovation and the rise of an informal tourism accommodation sector assessing airbnb as a disruptive innovation relative to hotels: substitution and comparative performance expectations spanish island closes party strip after rowdy tourists flout coronavirus laws. cnn travel [accessed online th biological invasion, biosecurity, tourism, and globalisation pandemics, transformations and tourism: be careful what you wish for. tourism geographies responding to crisis: severe acute respiratory syndrome (sars) and hotels in singapore qualitative research methods tourism in a world with pandemics: local-global responsibility and action sars: lessons in strategic planning for hoteliers and destination marketers airbnb hosts struggle with loss of reservations, income due to pandemic. nbc los angeles exploring airbnb service quality attributes and their asymmetric effects on customer satisfaction the effects of sars on the korean hotel industry and measures to overcome the crisis: a case study of six korean five-star hotels quality in qualitative research assessing impacts of sars and avian flu on international tourism demand to asia hosting via airbnb: motivations and financial assurances in monetized network hospitality sars preventive and risk behaviours of hong kong air travellers crisis management during the sars threat: a case study of the metropole hotel in hong kong exploring the relationship between satisfaction, trust and switching intention, repurchase intention in the context of airbnb be a "superhost": the importance of badge systems for peer-to-peer rental accommodations consumer segmentation within the sharing economy: the case of airbnb experiencing p p accommodations: anecdotes from chinese customers the long interview parallel pathways to brand loyalty: mapping the consequences of authentic consumption experiences for hotels and airbnb going back to its roots: can hospitableness provide hotels competitive advantage over the sharing economy? peer-to-peer interactions: perspectives of airbnb guests and hosts a standardized approach to qualitative content analysis of focus group discussions from different countries sanitation and hygiene as factors for choosing a place to stay: perceptions of the bulgarian tourists public-private collaboration for disaster risk management: a case study of hotels in matsushima hand-hygiene mitigation strategies against global disease spreading through the air transportation network issues of validity and reliability in qualitative research no ebola… still doomed'-the ebola-induced tourism crisis latest global outlook why greece succeeded as italy, spain failed to tackle coronavirus. greek reporter [accessed online th living like a local: authentic tourism experiences and the sharing economy service quality, satisfaction, and customer loyalty in airbnb accommodation in thailand qualitative research practice sampling in interview-based qualitative research: a theoretical and practical guide saturation in qualitative research: exploring its conceptualization and operationalization the influence of terrorism in tourism arrivals: a longitudinal approach in a mediterranean country lufthansa applies for short-time work assistance, anadolu agency book.com seeks dutch government's aid to stay hopeful during pandemic. silicon canals airbnb customers fuming over covid- refund policy. the silicon valley voice collaborative commerce in tourism: implications for research and industry booking.com plans for lay-offs after landing $ billion loan. short-term rentalz exploring tourists' memorable hospitality experiences: an airbnb perspective motives for using airbnb in metropolitan tourism-why do people sleep in the bed of a stranger basics of qualitative research: grounded theory procedures and techniques methods for the thematic synthesis of qualitative research in systematic reviews coronavirus in europe: tourism sector 'hardest hit' by covid- . euronews factors of satisfaction and intention to use peer-to-peer accommodation booking.com suspends uk bookings after pressure from mps. the national airbnb is establishing a new cleaning protocol for hosts to limit spread of covid- coronavirus disease (covid- ) situation report the impact of infectious diseases on hotel occupancy rate based on independent component analysis the impacts of quality and quantity attributes of airbnb hosts on listing performance coronavirus pandemic and tourism: dynamic stochastic general equilibrium modeling of infectious disease outbreak rethinking game consumption in tourism: a case of the novel coronavirus pneumonia outbreak in china hotel cleanliness: will guests pay for enhanced disinfection? short-term perturbations and tourism effects: the case of sars in china from high-touch to high-tech: covid- drives robotics adoption a qualitative investigation of microentrepreneurship in the sharing economy sentiment and guest satisfaction with peer-to-peer accommodation: when are online ratings more trustworthy? the study was funded by the erasmus+ programme -key action strategic partnerships for higher education. negative market perspective figure : continuum of host pandemic responses hosts intend to exit p p accommodation platforms by stop renting altogether or switching to long-term renting hosts will continue on platforms and adapt hosting practices and adopt marketing strategies hosts intend to continue hosting due to no best alternative but are unwilling to adjust hosting practices intention to exit platforms hosts intend to temporarily exit the platforms or maintain both short-term and long-term renting hosts not certain what to do and wait for situation to unfold to make decision key: cord- - vp fwv authors: simonsen, lone; higgs, elizabeth; taylor, robert j; wentworth, deborah; cozzi-lepri, al; pett, sarah; dwyer, dominic e; davey, richard; lynfield, ruth; losso, marcelo; morales, kathleen; glesby, marshall j; weckx, jozef; carey, dianne; lane, cliff; lundgren, jens title: using clinical research networks to assess severity of an emerging influenza pandemic date: - - journal: clinical infectious diseases doi: . /cid/ciy sha: doc_id: cord_uid: vp fwv background: early clinical severity assessments during the influenza a h n pandemic (ph n ) overestimated clinical severity due to selection bias and other factors. we retrospectively investigated how to use data from the international network for strategic initiatives in global hiv trials, a global clinical influenza research network, to make more accurate case fatality ratio (cfr) estimates early in a future pandemic, an essential part of pandemic response. methods: we estimated the cfr of medically attended influenza (cfr(ma)) as the product of probability of hospitalization given confirmed outpatient influenza and the probability of death given hospitalization with confirmed influenza for the pandemic ( – ) and post-pandemic ( – ) periods. we used literature survey results on health-seeking behavior to convert that estimate to cfr among all infected persons (cfr(ar)). results: during the pandemic period, . % ( . %– . %) of ph n -positive outpatients were hospitalized. of ph n -positive inpatients, . % ( . %– . %) died. cfr(ma) for ph n was . % ( . %– . %) in the pandemic period – but declined -fold in young adults during the post-pandemic period compared to the level of seasonal influenza in the post-pandemic period – . cfr for influenza-negative patients did not change over time. we estimated the pandemic cfr(ar) to be . %, -fold lower than cfr(ma). conclusions: data from a clinical research network yielded accurate pandemic severity estimates, including increased severity among younger people. going forward, clinical research networks with a global presence and standardized protocols would substantially aid rapid assessment of clinical severity. clinical trials registration: nct and nct . in , uncertainty about the emerging ph n virus' clinical severity hindered the early global response. although the rapid spread of the virus around the world fulfilled the traditional pandemic definition, its global mortality impact in the end proved to be smaller than any th century pandemic [ , ] . however, its relative mildness was not known in the early months of the outbreak. the earliest estimate of the case fatality ratio (cfr) was on par with the rating for the catastrophic pandemic, and a june assessment put it in the pandemic range (table ) [ ] . an evaluation of the pandemic response ordered by the world health organization's (who) director general [ ] found that a systematic way to assess both transmissibility and clinical severity-also known as its "seriousness" [ ] -is needed in the early phase of a future pandemic to assess the level of threat accurately and to mobilize resources appropriately. cfr is one important measure of clinical severity; others include the risk of admission to the intensive care unit (icu) and the need for mechanical respiratory support. a who task force is currently developing the data inputs and study designs needed to generate timely estimates of clinical severity [ ] . the centers for disease control and prevention has proposed a scheme for comparing pandemic and seasonal influenza graphically, plotting attack rates against clinical severity [ ] . in , uk public health england spearheaded what has become a standard first-line approach to assessing the clinical severity of a pandemic, known as the "first few hundred" (ff ) [ ] . these and similar studies gather data on the earliest cases that come to medical attention through outpatient facilities and hospitals and provide important descriptive data about symptoms, risk factors, and risk of progression to severe illness or death [ ] [ ] [ ] [ ] [ ] [ ] [ ] . these data can in turn be combined with other data on population attack rates to forecast national and global hospitalization and mortality estimates using a pyramid modeling strategy [ , ] . standard ff studies, however, lack historic controls in the form of a baseline from recent seasonal influenza seasons. they are also subject to selection bias, as the first cases that come to attention are likely to be more severe [ ] . unless an ff study is set in an existing surveillance system or ongoing clinical research data collection scheme, there is no obvious seasonal influenza baseline against which to compare the clinical severity of the pandemic virus. moreover, unless the pandemic is severe, an ff study in the outpatient setting alone will not have the statistical power to accurately estimate the cfr unless many thousands of patients are enrolled. global clinical research networks that study mild and severely ill influenza patients could be used to overcome many of these problems. two ongoing clinical cohort studies of influenza are conducted under the international network for strategic initiatives in global hiv trials (insight) umbrella, sponsored by the national institutes of health. since , insight has undertaken cohort studies- outpatient (flu ) and inpatient (flu )-specifically to address gaps in clinical research on the emerging influenza pandemic, including factors linked to disease progression and severe outcomes [ ] . insight annually enrolls hundreds of patients with suspected or confirmed influenza, with intake sites in countries. at these sites, experienced teams use a standardized protocol to collect extensive clinical data, perform long-term follow-up (at and days for inpatients, days for outpatients), and bank patient samples for further study. several articles on influenza have been published using insight data, including protocol descriptions and preliminary data [ ] , an exploration of biomarkers of influenza case severity [ ] , patient outcomes after ph n infection [ ] , and phylogeography of the ph n virus [ ] . we used insight data collected in the pandemic period ( - ) to retrospectively demonstrate how clinical research networks can provide essential early insights into pandemic clinical severity and other epidemiological parameters. to "leverage" the cfr computation, we multiplied the conditional probability of progression from outpatient to hospitalization by that of progression from hospitalization to death. to underscore the importance of having baseline data, we compared the estimated ph n clinical severity to that of seasonal influenza types and subtypes and noninfluenza respiratory patients in the post-pandemic period ( ) ( ) ( ) ( ) . our cfr estimates were in reasonable agreement with final global cfr estimates based on excess mortality estimates from time series of nationwide vital statistics data and seroepidemiology data-final estimates of a type that would only be available several years after the next pandemic emerges [ , , ] . here, we discuss what it would take to move a clinical research network like insight from routine research operation into emergency mode to generate timely and robust clinical severity assessments. the national institute of allergy and infectious diseases (niaid)-funded insight network initially focused solely on hiv but expanded first to include ph n and then all influenza types and subtypes and emerging respiratory pathogens such as middle east respiratory syndrome and severe acute respiratory syndrome. sites, located in of world regions (figure ), consecutively enroll adult patients aged ≥ years with suspected influenza. flu recruits patients who present at a physician's office or clinic with influenza-like illness (ili), defined as fever with either cough or sore throat. flu recruits patients with known or suspected influenza who require hospitalization. at enrollment, patient medical history and demographic information are recorded, and blood and oropharyngeal swabs are analyzed and stored. testing for influenza is done both locally and at an insight central laboratory. all patients are followed up, regardless of influenza test result, at days after enrollment in flu and at and days in flu . we extracted insight data on demographics, illness onset, medical history, and vital status at follow-up visit from the protocol databases. we defined the pandemic period as the to follow-up were treated as missing and removed from the analysis. we identified relevant case series in the literature reporting data on patients aged > years. after excluding studies with fewer than patients or with a specialty population (such as high-risk patients), we chose outpatient studies, set in the united states [ ] and in the united kingdom [ ] , and inpatient studies [ , ] , both set in the united states, for comparison with flu and flu ph n laboratory-confirmed patients during the pandemic period (table ) . we calculated the medically attended cfr (cfr ma ) from the probability that a medically attended ili (flu ) patient would progress to hospitalization by day and the probability that a hospitalized (flu ) patient would die by day : where h = hospitalization and d = death to estimate cfr among all infected persons (cfr ar ), we used findings from a uk health behavior survey that found that % of patients aged ≥ years with ili sought care for their illness [ ] and a uk serology study that found that % of influenza-infected adults aged - years were symptomatic [ ] . assuming that the nonmedically attended and asymptomatic influenza cases would not progress to severe illness, we have: , where "infection" is defined as a person who responded immunologically. the % confidence intervals (cis) on the cfr estimate were generated from the variance of the product of the proportions, p(h/ili) × p(d/h), using the delta method or a first-order taylor series expansion. we assumed the proportions were independent. in small samples with large variability, this may not be a good approximation. in some cases, negative values for the cis may be obtained. data analysis was done using sas, version . , and excel. the flu and flu protocols were approved by the institutional review boards or institutional ethics committees at the university of minnesota and at each of the participating clinical sites. all patients (or their proxies) gave signed informed consent prior to enrollment. during the pandemic period (october through september ), ili and hospitalized patients tested influenza ph n positive. of these, . % of ph n -infected flu outpatients were aged - years compared to only % of the flu inpatients. during the post-pandemic period (october through september ), ili and hospitalized patients were ph n positive; of these, % of ili outpatients and % of hospitalized patients were aged - years. in the pandemic period about / of outpatients and / of inpatients were from european sites, while during the post-pandemic period, after the network expanded to sites in world regions, these figures were / of outpatients and / of inpatients. we found that demographic and clinical characteristics of insight pandemic period ph n patients were similar to those described in published ff -like studies of adult ph n patients [ ] with respect to mean age, prevalence of symptoms and underlying diseases, mortality rates, and other characteristics ( table ) . five percent of ph n -confirmed ili patients were hospitalized, and . % of ph n -positive inpatients died (table , figure ). this yielded a ph n cfr ma of . % ( . %- . %) both for all adults and for adults aged - years. the cfr ma for patients aged ≥ years could not be established with confidence due to the small number of older outpatients in the study. as a nonhistoric control, the all-ages cfr ma of influenza testnegative patients was . % during the pandemic period, albeit with wide cis. it was not possible to establish a seasonal influenza comparison for the pandemic period because non-ph n influenza cases (h n , b) in the pandemic period were rare. the cfr ma for ph n cases in the post-pandemic period was . % for patients aged - years, -fold lower than the value for the pandemic period and comparable to the influenza-negative patients of the same age. we could not reliably assess ph n cfr ma for the ≥ years age group due to small numbers in the post-pandemic period; however, cfr ma was . % for seniors aged ≥ years positive for any influenza virus in the post-pandemic period vs . % for younger adults positive for any influenza virus. for the post-pandemic period (any subtype), we also estimated the conditional probabilities and the cfr ma by region (table ) . because the final who cfr estimate from the pandemic was based on attack rates as revealed by serology data, we sought to convert our medically attended cfr to one based on the attack rate. to do so, we used data from a study that indicated that approximately % of all cases are asymptomatic [ ] and from survey data that indicate that approximately % of adult ili cases sought medical attention [ ] . we found the cfr ar to be . % ( . %- . %; table ), or -fold lower than the cfr ma . who has recently expanded its pandemic definition to include clinical severity. this means that rapid and accurate estimates of pandemic clinical severity are needed to characterize the threat level and guide the global response. our analysis combining data from inpatient and outpatient insight cohorts demonstrates how preestablished global research networks could immediately begin rigorous studies to estimate the cfr, a key parameter of clinical severity of an emerging pandemic. assessments of the clinical severity in the pandemic became less dire as time passed [ ] . the earliest estimate of cfr, an ff -like case series of hospitalized patients in mexico, was a disturbing % of influenza-positive patients. however, as studies of the first (summer) wave in the united states, the complete southern hemisphere season in new zealand, and further studies from mexico were completed, it became clear that the pandemic would be relatively mild (table ) . several factors contributed to the early confusion in . the most important was probably selection bias toward sicker patients in the earliest ff -type case series studies [ ] . another factor was simply that studies reported on different types of cfr-either as a proportion of medically attended cases (cfr ma ) or as a proportion of all infected individuals (cfr ar ). most early assessments were of the cfr ma type, but these were not directly comparable. our method, retroactively applied to insight databases, yielded a cfr ma estimate of . %. using literature values that indicated that the probability of symptomatic people seeking medical treatment was % [ ] and that the probability of infected individuals being asymptomatic was also % [ ] , our cfr ma value would be equivalent to a cfr ar of . %, which data are for the pandemic and post-pandemic periods, computed as the product of the risk of flu influenza-like illness outpatients getting hospitalized and the flu hospitalized patients having died at day . abbreviations: p (d|h), probability of death given hospitalization; p (h|ili) , probability of hospitalization given influenza-like illness. *case fatality rate not calculated when fewer than outpatients or inpatients contained in any stratum. is in reasonable agreement with the final global who cfr ar estimate of . % [ , , ] . in addition to an absolute measurement of cfr, data from previous seasons can provide a relative comparison of pandemic to seasonal influenza severity; even if the absolute estimate of cfr is uncertain, it would be useful to know if an emerging pandemic has a cfr far higher than previous seasonal influenza experiences. thus, we also estimated cfrs for influenza patients from seasonal influenza epidemics - , as a surrogate for pre-pandemic baseline seasons. age greatly influences both seasonal and pandemic clinical severity estimates. in all influenza pandemics since , mortality was higher than normal in younger people and lower than normal in seniors, sometimes dramatically so [ ] . in the post-pandemic period ( - ) we found that the cfr ma of ph n for patients aged - years had fallen -fold from the pandemic period value, becoming similar to that of a/h n and b. this suggests that the emerging virus had settled into a seasonal epidemic pattern due to accumulated population immunity. moreover, in the post-pandemic period patients aged ≥ years with any influenza virus had a cfr ma approximately -fold higher than patients aged < years. these results corroborate a previous metaanalysis of ff studies that concluded that age is an important confounder of cfr estimates for ph n pandemic influenza [ ] . they also show how important it is to take into account both the age group and the type of cfr being calculated when comparing across regions and time. it is also possible that discrepancies in early assessments of cfr may in fact have reflected true geographical differences. for example, a comprehensive study of pandemic mortality that applied a uniform methodology to different regions found the mortality impact in central and south american countries table was approximately -fold higher than in europe [ ] . this indicates that early reports of higher severity in mexico than in new zealand may not solely have been the result of ascertainment bias. clinical severity can even increase substantially over time, as was seen in the influenza pandemic when a milder summer wave preceded the severe autumn waves [ ] . the best way around the measurement problems that occur early in a pandemic would be to compute the same type of cfr with the same protocol in multiple geographical settings. if possible, estimates should be stratified by risk factors, such as pregnancy and chronic illness, and baseline data should be collected during seasonal epidemics. while some countries have created ff protocols since the pandemic, a global standard along the lines we have outlined here would be helpful. we recognize limitations to our approach to computing cfr by multiplying conditional probabilities of disease progression. first, we used distinct groups of outpatients and inpatients who were recruited under different circumstances at different sites, often in different countries. it is therefore possible the cohorts differed in age composition, health status, or other important respects that could bias the result. however, we argue that the approach, while not ideal, would nonetheless supply timely and useful data, especially if it could be compared to baseline seasons. we also note that the characteristics of the insight ph n outpatients and inpatients in the pandemic period - are reassuringly similar in terms of age, symptoms, comorbidities, and outcomes to published uk and us ff studies of adult ph n influenza outpatients and inpatients ( table ) . a second possible caveat-that insight inclusion criteria might have varied over time and explained the drop in cfr ma over time-could be dismissed on the grounds that the influenza-negative patients did not have a significant drop in cfr ma between the pandemic and post-pandemic period. this means that the measured decrease in ph n clinical severity was real and not due to ascertainment or other bias. our retrospective analysis of pandemic clinical severity indicates that it is possible to use research networks to assess both the absolute magnitude of the clinical severity of a future pandemic and the relative increase compared to a seasonal influenza baseline. even if the seroepidemiology and health-seeking behavior surveys needed to convert cfr ma to cfr ar could not be done rapidly, comparison of cfr ma to previous seasons would reveal much about the relative magnitude of the emerging threat. to be useful in a prospective scenario, however, it would be necessary to ramp up the network's pace of operations from routine to emergency mode. for insight, that would mean, at a minimum, enhancing enrollment in sites located in areas initially affected by the emerging pandemic and increasing the tempo of laboratory processing of specimens and data analysis. in addition to assessing clinical severity, global research networks could play other key roles in pandemic response including studies of comorbidity patterns, risk factors, hospital and icu utilization, and mortality risk of hospitalized patients. moreover, protocols that enroll children could be used to understand the pathogen in this key age group. once a future pandemic outbreak begins, studies set in these networks could both characterize pathophysiology to optimize clinical management and provide a platform for rigorous clinical trials of new therapeutics. we suggest, therefore, that a specific role for clinical research networks carrying out ongoing rigorous research compliant with international standards be added to the international health regulations that govern international and national responsibilities for public health emergencies of international concern. notes acknowledgments. we thank and acknowledge all the patients who participated in this study. disclaimer. the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. potential conflicts of interest. l. s. and r. j. t. report earning consulting fees from sage analytica, llc, during the conduct of the study. r. l. reports serving as co-editor on a book on infectious disease surveillance published by wiley blackwell, with royalties donated to the minnesota department of health. all remaining authors: no reported conflicts of interest. all authors have submitted the icmje form for disclosure of potential conflicts of interest. conflicts that the editors consider relevant to the content of the manuscript have been disclosed. global mortality estimates for the influenza pandemic from the glamor project: a modeling study estimated global mortality associated with the first months of pandemic influenza a h n virus circulation: a modelling study case fatality risk of influenza a (h n pdm ): a systematic review report of the review committee on the functioning of the international health regulations ( ) in relation to pandemic (h n ) infection fatality risk of the pandemic a(h n ) virus in hong kong novel framework for assessing epidemiologic effects of influenza epidemics and pandemics pandemic (h n ) influenza in the uk: clinical and epidemiological findings from the first few hundred (ff ) cases human infection with new influenza a (h n ) virus: clinical observations from mexico and other affected countries pandemic potential of a strain of influenza a (h n ): early findings epidemiologic analysis of the laboratory-confirmed cases of influenza a(h n )v in colombia pandemic influenza a(h n )v in new zealand: the experience from the severity of pandemic h n influenza in the united states estimating age-specific cumulative incidence for the influenza pandemic: a meta-analysis of a(h n ) pdm serological studies from countries. influenza other respir viruses pandemic influenza a (h n ) in saudi arabia: description of the first one hundred cases critically ill patients with influenza a(h n ) in mexico insight flu : an anti-influenza virus hyperimmune intravenous immunoglobulin pilot study hospitalized patients with h n influenza in the united states systematic review of clinical and epidemiological features of the pandemic influenza a (h n ) factors associated with death or hospitalization due to pandemic influenza a (h n ) infection in california utility of the first few approach during the influenza a(h n ) pandemic in the netherlands optimizing the precision of case fatality ratio estimates under the surveillance pyramid approach potential biases in estimating absolute and relative case-fatality risks during outbreaks surveillance of illness associated with pandemic (h n ) virus infection among adults using a global clinical site network approach: the insight flu and flu studies the association between serum biomarkers and disease outcome in influenza a(h n )pdm virus infection: results of two international observational cohort studies outcomes of influenza a(h n )pdm virus infection: results from two international cohort studies extensive geographical mixing of human h n influenza a virus in a single university community emergence of a novel swine-origin influenza a (h n ) virus in humans using an online survey of healthcare-seeking behaviour to estimate the magnitude and severity of the h n v influenza epidemic in england comparative community burden and severity of seasonal and pandemic influenza: results of the flu watch cohort study preliminary estimates of mortality and years of life lost associated with the a/h n pandemic in the us and comparison with past influenza seasons epidemiologic characterization of the influenza pandemic summer wave in copenhagen: implications for pandemic control strategies flu clinical site investigators: argentina: laura barcan key: cord- -l zwvt authors: lumpkin, murray m; lim, john cw title: pandemic best regulatory practices: an urgent need in the covid‐ pandemic date: - - journal: clin pharmacol ther doi: . /cpt. sha: doc_id: cord_uid: l zwvt as large numbers of candidate drugs and vaccines for potential use in the covid‐ pandemic are investigated, medicines regulators globally must now make urgent, informed, contextually risk‐based decisions regarding clinical trials and marketing authorizations. they must do this with the flexibility demanded by the pandemic while maintaining their core risk assessment and public safety functions. we lay out the critical role of regulators in the current crisis and offer eight “pandemic best regulatory practices.” as large numbers of candidate drugs and vaccines for potential use in the covid- pandemic are investigated, medicines regulators globally must now make urgent, informed, contextually riskbased decisions regarding clinical trials and marketing authorizations. they must do this with the flexibility demanded by the pandemic while maintaining their core risk assessment and public safety functions. we lay out the critical role of regulators in the current crisis and offer eight "pandemic best regulatory practices." these should support both the regulatory public heath imperative and assure timely patient access to effective, safe, quality products worldwide during this emergencythus contributing to ending this pandemic as quickly, effectively, and safely as possible. the covid- pandemic is different in many ways from other recent public health emergencies, especially in its massive global impact on human life and economic activities. researchers globally are working tirelessly to develop therapeutics, vaccines, diagnostics, protective equipment, and other items needed to control the pandemic. there is pressure on the world's leading national regulatory authorities (nras) for medicines and medical devices to take urgent, informed, contextually risk-based decisions regarding clinical trials authorizations, emergency use authorizations, site inspections, and post-authorization commitments. this, in turn, creates pressure for similar actions in many other countries, especially those whose nras are significantly underresourced. while developing effective therapeutics and vaccines is the immediate challenge, once they are available, an equally complex and formidable challenge will be responding to immediate global demand for equitable access to these products in terms of cost and time. assuring almost this article is protected by copyright. all rights reserved simultaneous global access to quality versions of these products will require new approaches in many aspects of the chain of events (viz. regulatory, utilization policy, procurement, delivery) that leads ultimately to patient access. new product roll-out only to a few countries or gradual roll-out across the globe will not be acceptable. the regulatory component is a vital link in the event chain ensuring patient access to quality therapies in an emergency. the work of nras is often over-looked, under-appreciated, and even maligned. we have, however, learned in other public health emergencies that without interpretable data to guide their actions, the heroic efforts of first responders and medical personnel are severely hampered. this has already been experienced to varying degrees in the initial stages of the current pandemic. eichler et al described recently the current clinical and ethical challenges of large numbers of uncoordinated covid- clinical trials, which, by design and conduct, are destined to be non-informative . the only thing worse than no diagnostic or no treatment is an unreliable diagnostic or an uninformed treatment. millions of people are placing their hopes on new medical interventions, and they deserve better than non-scientific hunches. it is an inconvenient truth: we cannot simply "wish" these products to work. the role of regulators -particularly critical in emergencies -is to assure that data about needed products are transparent, interpretable, and reliable. this enables practitioners, patients, families, and government to make truly informed decisions. for regulators to perform this vital role in a pandemic effectively requires flexibility. this is not flexibility in applying fundamental scientific principles, but rather in how regulators work together to minimize redundancy and time loss, thus maximizing the available human, scientific, and financial regulatory resources, which are vastly constrained internationally. while effective medical interventions are currently being developed, nras must now simultaneously work to prepare for rapid global regulatory actions once interpretable data are developed in order to help expedite patient access to safe, good quality, and reliable diagnostics and effective therapies. this article is protected by copyright. all rights reserved due to the work of many regulators and organizations over the past few decades , , , , there are already established pathways through which regulators work collaboratively and have aligned on many basic approaches to the performance of their responsibilities. these regulatory harmonization, convergence, alignment, and reliance initiatives have been a prescient preparation for this moment in history. if not now, when? many countries and the who have established regulatory pathways for handling emergencies , , . we do not need to reinvent the regulatory wheel in the middle of this worldwide crisis.. we need to use these established emergency pathways transparently, confidently, and globally. to ensure that the regulatory steps in the patient access chain are implemented efficiently and effectively in the current situation, a "pandemic best regulatory practices" approach should be used. these must be immediately actionable practices that have the support of industry, regulators, and governments. as our knowledge of this pandemic evolves, we will continually learn what should be added to these pandemic best regulatory practices. some of these may not be feasible under routine agency practices, but a pandemic is not routine. most governments have provisions to allow special procedures during emergencies to meet extraordinary needs without compromising fundamental aspects of science or product quality. the practices described below will help nras most efficiently and effectively reference and utilize the actions and work products of other regulatory authorities they trust to help inform their own decisions. this will help them make timely, well-informed, efficient, appropriate, and scientifically robust public health decisions for their jurisdictions during this pandemic. this article is protected by copyright. all rights reserved regulatory agencies. given the gravity of the current situation and limitations on travel, the need for such "regulation through reliance" on the work products of trusted agencies to assure efficient, yet scientifically robust, assessments requires full reports be made available immediately either on demand or, better, on an agency website for ease of access by other regulators. the default position should be that companies concur with this process and will not raise "confidentiality" or "trade secret" arguments that result in time-consuming redactions and documents with inadequate information for the receiving agency. uninformative reports compel duplication of assessments already performed by other agencies, which in the context of a pandemic leads to an unconscionable waste of time and resources. as highlighted in one of the recommendations of a recent us national academies of sciences, engineering and medicine consensus study report, with access to such full reports, nras are better positioned to determine more efficiently and robustly if a product is appropriate for their health care systems and populations. this is especially true now in the context of the pandemic. amount. in addition, there should be a qr code that links directly to all authorized package labeling and summary of product characteristics/package inserts and patient leaflets for all countries where the product is either fully or emergency authorized. this should generally be hosted on the manufacturing company's website. one should be able to read the authorized labeling by scrolling to the labeling authorized in a specific country. if a hard copy is needed, printing would be easily done on site. in addition, there is assurance of immediate access to the most recent version of the authorized labeling, which may be changing rapidly with increasing knowledge of how the product should be used in the pandemic. this would also facilitate transfer of the product from country to country without having to relabel, thus saving valuable time, human and financial resources, and would allow a scarce product to be use where it is needed most rapidly. this would be especially helpful for frozen vaccines, as it would mean products would not have to be thawed for re-labeling if they were going to be used in a country different from where the original label was intended. electronic common technical dossier format , or hardcopy if necessary, and should be accepted in that format by all jurisdictions without any local or regional adaptations, other than language and local specifics (module ). nras. the discussion and reasons for the action taken by the initial authority will then be better understood and can be more quickly incorporated into the decision-making of these other agencies. companies should not assert confidentiality or trade secret reasons for limiting such access by global regulators and who prequalification assessors, given the pandemic situation. authorized by the trusted reference agency. any differences in the manufacturing process and/or site and other version differences should be highlighted and explained in the initial cover sheet of the documentation presented to the receiving nra. many versions of a new product will quickly appear, both legitimate and, sadly, some that are substandard or falsified. nras must assure that a product in its jurisdiction is what it is labeled to be and that it will perform as expected. this means assurance of compliance with international standards of quality manufacturing and evidence of reliable performance in patients if it is a different version from that assessed by the initial reference nra. this article is protected by copyright. all rights reserved [ ] local clinical efficacy and safety trials should not routinely be required for authorization during a pandemic, unless there is a strong scientific argument that the data in the dossier are not extrapolatable to the local population or health care system. if local trials are necessary to assure local population specific questions are addressed, these should be designed and powered to adequately address the questions raised. systems for maximum visibility and quick information dissemination to regulators globally. we have defined this initial list of pandemic best regulatory practices to prompt nras globally to review their readiness and processes to expedite sound and scientifically robust regulatory reviews of therapeutic products emerging during the current pandemic. we recommend that who should maintain such an evolving list of on its website and advocate strongly for their implementation. using these and other additional pandemic best regulatory practices will facilitate global regulatory excellence in helping assure timely patient access to effective, safe, quality products worldwide, and thus contribute to ending this pandemic as quickly, effectively, and safely as possible clinical trials for covid- : can we better use the short window of opportunity? international coalition of medicines regulatory authorities website international conference of drug regulatory authorities website food and drug administration -emergency use authorization website emergency use listing procedures website regulating medicines in a globalized world key: cord- - ju fcf authors: arthi, vellore; parman, john title: disease, downturns, and wellbeing: economic history and the long-run impacts of covid- date: - - journal: explor econ hist doi: . /j.eeh. . sha: doc_id: cord_uid: ju fcf how might covid- affect human capital and wellbeing in the long run? the covid- pandemic has already imposed a heavy human cost—taken together, this public health crisis and its attendant economic downturn appear poised to dwarf the scope, scale, and disruptiveness of most modern pandemics. what evidence we do have about other modern pandemics is largely limited to short-run impacts. consequently, recent experience can do little to help us anticipate and respond to covid- ’s potential long-run impact on individuals over decades and even generations. history, however, offers a solution. historical crises offer closer analogues to covid- in each of its key dimensions—as a global pandemic, as a global recession—and offer the runway necessary to study the life-course and intergenerational outcomes. in this paper, we review the evidence on the long-run effects on health, labor, and human capital of both historical pandemics (with a focus on the influenza pandemic) and historical recessions (with a focus on the great depression). we conclude by discussing how past crises can inform our approach to covid- —helping tell us what to look for, what to prepare for, and what data we ought to collect now. the health and economic toll of the covid- pandemic continues to expand throughout the globe, impacting countries both rich and poor. as it does so, the virus exposes the strengths and weaknesses of our healthcare systems, political institutions, media, and our economies themselves. much of the discussion to date has understandably focused on stemming the immediate costs of the covid- crisis: among them, mortality, business failures, job losses, and foreclosures. this pain is salient, and as such, very obviously demands an urgent response. however, there are potential outcomes of the current pandemic which, while perhaps less salient, also merit urgent attention: namely, long-run damage to human capital and wellbeing. it is to these particular long-run effects that we turn our attention in this paper. the potential for long-run harm to human capital arises from two main facts about the current pandemic. first, key features of covid- -among them its geographic reach, its relatively high ease of transmission, its comparatively low lethality, and its many emerging sequelae-have given rise to widespread and potentially lasting morbidity among its many survivors. second, the pandemic has sparked an unprecedentedly large downturn, which in its own right has the capacity to permanently scar trajectories of health and income, even for those who do not fall ill themselves. while the costs of these long-run effects may seem far away, they are latent today and could become massive down the line: burdening healthcare systems and government assistance programs, suppressing work capacity and human capital investment, and reducing economic prosperity more generally. luckily, the returns to avoiding these harms, or to acting swiftly to compensate for them before they have a chance to compound, tend to be much higher the sooner interventions can be made (see, e.g., heckman, ; almond & currie, ) . together, the potential for diffuse and latent adverse effects, and the cost-effectiveness of early remediation, suggest that in addition to any efforts to address the immediate pain of the pandemic, our eyes should also be on the future-and on actions we can take now to mitigate the long-run pain for affected cohorts, and therefore, the wider economy. but what, exactly, is the long-run human fallout of covid- likely to be-and who will bear the brunt of this crisis? to answer these questions, we need the sort of long-run view that only history can provide. an obvious starting point is to look to evidence from historical pandemics. despite potential differences in empirical settings and epidemiological characteristics, the sheer number and diversity of past pandemics means that covid- has many close historical analogues as a health crisis. for instance, while the current pandemic is frequently described as unprecedented, in many ways, its immediate effects on health are not altogether anomalous. with cases first appearing in december , sars-cov- , the pathogen behind covid- , spread throughout the world in a matter of weeks, with deadly consequences. by the end of april , worldwide cases had topped million, and fatalities exceeded , . as of this writing in late october , and with the pandemic still spreading, cases exceed . million, and fatalities have surpassed . million. for context, deaths from h n (swine flu) in - were smaller in magnitude, with estimates of over , deaths attributable to the virus (dawood et al., ) . while at million deaths, the hong kong flu of is comparable to covid- in its death toll to date, the asian flu of was substantially deadlier, killing million people. likewise, cholera, typhus, smallpox, measles, and tuberculosis all have had high death tolls, including during the th century. reaching even further back, the black death left a devasting imprint on the world, killing a third of europe's population. clearly, historical pandemics offer a rich evidence base that can help shed light on the range of possible long-run effects of covid- through morbidity and mortality. however, there is one crucial aspect of the current pandemic that sets it apart from all but the most catastrophic historical disease outbreaks : the presence of an acute public health crisis alongside massive and widespread economic disruptions. not just that-it is the fact that this health crisis has precipitated an economic one. to wit, efforts to stop the spread of the virus, alongside failures to contain it, have contributed to a dramatic slowdown of the global economy. consider, for instance, the economic dislocation experienced in the u.s., a country which quickly came to lead the world in both confirmed covid- cases and deaths. in march and april of , roughly percent of the united states' labor force filed unemployment claims. double-digit unemployment would continue through the summer. the dow jones fell by over percent. for contrast, during influenza pandemic, responsible for roughly , deaths in the u.s. (glezen, ; simonsen et al., ) , unemployment peaked at . percent, and the dow fell percent-certainly a recession, but nothing on the order of what we have already experienced during the covid- outbreak, just a few months in. the unprecedented scale of the covid- economic downturn relative to past pandemics is apparent in figure , which shows the evolution of u.s. gdp over time, with major epidemics highlighted. notes: annual gdp per capita data for through are taken from https://www.measuringworth.com. quarterly real gdp per capita data for and are taken from https://fred.stlouisfed.org/series/a rx q sbea and deflated to plague would continue to impact economies into the th century, with an outbreak in san francisco infecting individuals and killing (echenberg, ) . the san francisco outbreak presents interesting parallels to . despite health officials identifying the plague and urging action, california's governor, henry gage, denied there was an outbreak, partly out of a desire to prevent business losses from a quarantine. it took the intervention of federal authorities and a new governor to implement proper measures to stop the spread of the plague. california officials reacted quite differently to covid- , at least initially, swiftly imposing stay-at-home orders. a century later, the calculus of weighing an economic slowdown against the spread of disease has changed. despite a much larger population, and a much more widespread pandemic, covid- had claimed under lives in san francisco county as of late october , thanks in part to these relatively early and stringent interventions. for instance, the aids crisis and the black death may be some of the only other major pandemics where mass morbidity and mortality were accompanied by dramatic and widespread economic dislocation. dollars to match the historical data. code to generate the figure and the underlying data for it can be found at open-icpsr (https://doi.org/ . /e v ). clearly, this feature of the current pandemic calls for complementary evidence if we are to understand its potential for long-run harm: there is no suitable all-in-one historical analogue for covid- , and evidence from past pandemics alone is likely to understate the potential for damage to (or intervention in) health and welfare through income and labor-market channels. indeed, to continue with our u.s. example, the two-trillion-dollar coronavirus aid, recovery, and economic security act's closest comparison, is not to be found in past responses to health crises, but rather in the response to past macroeconomic crises-e.g., the american recovery and reinvestment act in the case of the great recession, and the new deal in the case of the great depression. federal outlays as a percentage of gdp rose from . percent at the start of the great depression to . percent by . the cares act alone is equal to roughly percent of gdp, and this does not account for additional relief that may be approved in the coming months. asset purchases in response to the great recession increased the federal reserve's balance sheet from $ . billion in to $ . trillion in . that balance sheet has gone from $ . trillion in february of to $ . trillion just four months later. by nearly any metric, covid- has generated both an economic crisis and a government response of historic scale. studying how individuals emerged from these primarily economic disasters, and what role government fiscal interventions played in their recovery, may therefore help us flesh out the incomplete perspective we would gain from studying past health shocks alone. turning to a combination of historical crises, then-past pandemics and recessions, both-allows us to consider events that in many ways more closely mirror current circumstances, and whose contextual differences can themselves be informative of our current situation first, and most crucially, these events have had time to fully unfold: the short-, medium-, and long-run consequences of these events can be directly observed. second, the diverse array of historical events, settings, and mechanisms provides a set of reasonable analogues for covid- , even as our understanding of covid- evolves. third, the economic history literature shows how much can be learned with clever analysis of even incomplete or imperfect data. missing and inaccurate health data is unfortunately directly relevant to assessing the spread of covid- , given, for instance, current issues with testing and coordination. thus, a historical perspective allows us to use rich data to look at not only the short-term effects of crises like covid- on health, labor, and human capital, but also the long-term and intergenerational impacts along these dimensions for both individuals and the wider economy. in so doing, it can offer us insight on the current crisis-telling us what to look for, what to prepare for, and what data we ought to collect now. put another way, understanding the lingering health and economic impacts of these past crises offers valuable insight for anticipating and responding to the potential long-term impacts of covid- . to examine how history can inform our view of the coronavirus pandemic and associated policy responses as they relate to long-run wellbeing, we begin in section ii by reviewing the features of covid- that will determine its potential health and economic impacts, and placing these features in historical context. then, in sections iii and iv, respectively, we narrow our focus to two of the closest analogues to the current pandemic-one, the influenza pandemic, which speaks to -direct‖ health-channel effects; and another, the great depression, which speaks to -indirect‖ effects through the labor market and wider economy. there, we review the economic literature on the short-and long-term effects on cohorts exposed to these massive shocks, and discuss how these short-run experiences can give rise to lasting, and sometimes hidden, damage. we conclude by discussing what economic historians and researchers of covid- can offer each other. before we can look to historical evidence on how covid- 's effects may unfold in the long run, it is useful to fix ideas about key features of the current crisis-its epidemiology, its demographics, and the policy responses to date. comparing these features to those seen in past pandemics offers a sense of which historical pandemics might serve as the most useful points of reference going forward. we draw here on the principles outlined by morens et al. ( ) to categorize pandemics. they point to eight characteristics common to most accepted definitions of a pandemic: ) wide geographic extension and ) disease movement, which speak to the disease's spatial reach; ) high attack rates and explosiveness, ) infectiousness, and ) contagiousness, which speak to how it spreads; ) severity, which speaks to its potential for population scarring and culling; and ) minimal population immunity and ) novelty, which speak to the scope for harm and the speed with which preventive and therapeutic responses can be marshalled. by all measures, covid- presents these hallmark features of a pandemic. understanding exactly how covid- reflects each dimension is essential for understanding the likely short-and long-run consequences of the pandemic. the widespread nature of pandemics makes their health and economic impacts particularly devastating: with effects felt everywhere, it becomes increasingly difficult to shift economic activity to, or medical resources from, unaffected areas. while the true extent and timing of covid- cases is yet to be determined, the evidence to date indicates that the global spread of the virus has been incredibly rapid. the earliest reported cases appeared in december in wuhan, china. that same month, the virus made it to france. by january , there were confirmed cases throughout asia, europe, north america, and africa, and by the end of the month, the number of cases worldwide reached , . in the months that followed, that number rose sharply-first to , in february, , in march, and over , , by the end of april. by may , only sovereign states had no confirmed cases, of which are island nations in oceania. covid- had become a truly global pandemic by the end of spring , and both cases and fatalities have continued to rise across the globe in the months that followed. this feature of covid- surely has much to do with the highly globalized nature of our modern economy. indeed, we see similar patterns in historical pandemics, reaching as far back as we have had extensive trade routes. nearly every country with reliable mortality statistics displayed excess deaths from the influenza pandemic . similarly, the plague pandemic originating in canton and hong kong in spread to ports across five continents (who, ) , and even the justinian plague of reached asia, africa, and europe. even in a historical era where countries were less tightly integrated than they are today, as of late october , there have been nearly million cases of covid- worldwide, and over million deaths-and, as winter dawns on the northern hemisphere, and as we enter a new and possibly more lethal wave of the pandemic in many parts of the world, these numbers seem poised to rise further. even though world economies are substantially more tightly integrated than in the past, even in the preindustrial era, alfani & murphy ( ) document that it was common for disease to be transmitted along trade routes or through inter-regional commercial contact. big trading centers in particular, such as amsterdam, london, and venice, frequently faced outbreaks of plague (see alfani ( ) , biraben ( ) , and curtis ( ) for the underlying studies). the only thing that truly spared an area from pandemics was isolation. with the increase over the last few centuries in both global connectedness and population density, the implications for our current crisis are clear. the speed with which a disease spreads directly impacts the difficulty of containing it. indeed, it is these transmissibility-related features that account for many of the public health measures seen in response to the current crisis-some, such as early international travel restrictions, which tried to contain a disease that in many countries was already being spread locally via community transmission; and some, such as stay-athome orders and mask-wearing, which have been more effective in slowing transmission once it was too late for a containment strategy to be tenable. high attack rates and explosiveness (multiple cases appearing in a short time span) make it hard to stay ahead of a disease. these characteristics are functions of a disease's infectiousness and contagiousness: its ability to spread from person to person. covid- is transmitted by respiratory droplets and aerosols produced when an infected person coughs or sneezes. this has led to covid- having a daunting rate of transmission, with early estimates of a basic reproductive rate of between and (sanche et al., ) . as a point of reference, these transmission numbers are akin to those seen for past sars, polio, mumps, yellow fever, and influenza outbreaks (see figure ). the economic history of these pandemics thus provides a guide for what we might expect from the covid health crisis. for contrast, the economic history of measles-which presents far higher transmission rates, with estimates of basic reproductive rates greater than (guerra et al., )-offers a sense of how much worse things could be. notes: case mortality rates are for untreated patients. for covid- , basic reproduction rates are taken from https://wwwnc.cdc.gov/eid/article/ / / - _article. all other reproduction and fatality rates are taken from https://docs.google.com/spreadsheets/d/ khcewy-d hxlwrft jjrq xf whqlmwyrxel wjxkw /edit#gid= (the data the opening up of regions to trade, or conquest, has generated a large literature on the role of disease in shaping economies. see in particular the literature on the columbian exchange (nunn & qian, ) . the basic reproductive rate is the number of expected cases directly generated by one case when all individuals in the population are susceptible to infection. like the disease's ease of transmission, the severity with which it manifests symptoms will also be a crucial determinant of both its consequences for individuals and the wider economy, and the nature and magnitude of the government response. for instance, a highly lethal pandemic may generate extensive and indiscriminate mortality; a less lethal pandemic may generate culling (selective mortality related to a specific health threshold); and an even less lethal pandemic may generate very little mortality, but substantial health scarring among survivors. if a disease is so mild that many of those who are infected remain asymptomatic, this can, in the absence of widespread testing, undermine efforts to slow transmission. likewise, rates of infection, in combination with severity considerations, will help determine whether governments intervene, or merely wait for the disease to -take its course‖ on the way to achieving herd immunity. in its april , covid- strategy update, the world health organization note that percent of those infected experience moderate disease, including pneumonia, and percent experience severe disease. they cite a crude clinical case fatality rate of over three percent that rises to percent or higher in individuals over the age of . as shown in figure , the crude mortality rate for covid- in its first months is similar to that of the influenza pandemic and of measles, but far lower than the deadlier recent outbreaks of mers, ebola, sars, and lower still than the truly devastating historical toll of smallpox, which had an average case fatality rate of percent (ellner, ) . this rich historical spectrum of pandemic severity, in turn, demonstrates that both mild and severe diseases impact the economy, albeit in very different ways. for instance, the eradication of hookworm in the u.s. south-a disease which is not fatal, but which primarily causes lethargy and anemia-improved returns to schooling, educational attainment, and incomes in areas with high prior infection rates, but did little to change to overall demographic, economic, or institutional structure (bleakley, ) . for contrast, the black death and other pre-modern outbreaks of plague, which had extraordinarily high death tolls, fundamentally reshaped the global economy through their effects on population size and demographic structure. in this context, covid- 's wide scale and relatively low lethality will surely have a bearing on the scope, magnitude, and timescale of damages. as we will see in later sections, it suggests that we might ultimately expect to see the greatest harm only in the long run, with widespread generational scarring arising from short-run morbidity and economic disruptions. the novelty of a pandemic virus contributes to its potential for destruction: it takes time to identify a new disease, understand key features of its epidemiology, develop treatments and vaccines, and achieve a degree of population immunity. in the meantime, everyone represents a potential victim. as a novel coronavirus, it is worth emphasizing that even if a patient survives covid- , they may still face substantial harm. for instance, emerging research suggests that some covid patients may experience persistent symptoms well beyond the normal recovery period, and that others-even some with relatively mild cases-may nevertheless suffer permanent respiratory, cardiovascular, and neurological damage. voigtländer & voth ( a , b argue that the increased wages due to labor shortages from plague mortality increased demand for urban products, driving a cycle of urbanization and additional disease that moved europe out of a malthusian trap into a modern world of permanently higher per capita incomes. dittmar & meisenzahl ( ) demonstrate that outbreaks of plague aided the spread of reformation laws and the expansion of public goods. for more on the economic history of plagues, see alfani & murphy ( ) . covid- struck a population with neither natural nor acquired immunity: wherever the virus spread, it had the potential to be devastating. with little immediate means of preventing, testing for, or treating it, some of the only short-run mitigation strategies available have been relatively brute-force ones such as lockdowns and border closures. consequently, economic shutdowns-resulting both from official government actions and from individuals taking actions to avoid exposure-have been widespread, leaving no major economies or populations spared. interestingly, because medical technology was limited for much of the past, and societies could only count on some degree of population immunity, even endemic (i.e., non-novel) diseases could have the sort of destructive potential we only typically see today in new disease variants such as the novel coronavirus. for instance, in a variety of past pandemics studied by economic historians, cases of an endemic disease would sporadically rise sharply, with substantial consequences for living standards and economic organization. indeed, a large literature considers the impact of such diseases on the growth trajectories of countries over the long run, often focusing on tropical diseases like malaria, yellow fever, dengue, and others. one strand of studies considers the direct impact of disease on human capital formation (see, for example, bleakley ( bleakley ( , on malaria). another strand focuses on the impact of these endemic diseases on institutional development, finding that disease environments inhospitable to colonial settlers drove them to rely on extractive institutions that were ultimately harmful to economic growth (acemoglu et al., ) . finally, scholars have considered the way that one society's acquired immunity to an endemic disease can devastate the economy of another society lacking that immunity (diamond, ; mcguire & coelho, ; tang, ) . together, this historical evidence gives us a picture of what our circumstances might look like today if we are unable to adequately ramp up our capacity for disease prevention and treatment, and are instead forced to rely on acquired immunity, the nature of which for covid- is still poorly understood. age has been at the forefront of discussions about the disparate impact of the current crisis, and shutdown efforts have been framed in part around protecting older individuals and other vulnerable populations, such as the immunocompromised, while societies work to expand medical capacity and develop a vaccine. in this respect, covid- is much like many infectious disease outbreaks in the past-though young people can both transmit the disease and become ill, it is the elderly and those with poor baseline health are at greatest risk. cdc estimates put the risk of hospitalization five times higher, and the risk of death from covid- times higher, for to year-olds compared to individuals in their twenties. likewise, despite claims in some quarters that covid- is -the great equalizer,‖ it is already becoming clear that socioeconomic status will be central to understanding the demographics of this crisis. one of the ways low-income populations will be affected is through differential exposure to pandemic risks. individuals who continue to do their jobs in person during the pandemic-including service-industry workers with extensive contact with customers, healthcare professionals, and other frontline workers-will that is, it is improved medical knowledge that has allowed us to escape from the sort of flare-ups of endemic disease so frequently observed in the past, and it is relative our lack of knowledge about covid- , as a new virus, that makes our current situation in some ways comparable to even past endemic disease outbreaks. economic historian joel mokyr expands on this idea regarding the evolution of knowledge regarding infectious disease outbreaks in a recent op-ed: https://www.cnn.com/ / / /opinions/struggle-between-people-and-microscopic-pathogens-mokyr/index.html. retrieved from https://www.cdc.gov/coronavirus/ -ncov/covid-data/investigations-discovery/hospitalizationdeath-by-age.html, august , . the mirror image of differential exposure is differential transmission risk. this is one reason why some have called for prioritizing the strategic testing of workers at highest risk of spreading the novel coronavirus to others, particularly asymptomatic ones. bear a disproportionate burden of the pandemic's health impacts. these workers are more likely to be in low-paying jobs, and are more likely to be women and minorities, than their counterparts with jobs allowing them to work from home. consider, for instance, meat and poultry workers in the u.s. the mean annual wage in the industry is only $ , (bls, ) . among laborers in the food manufacturing industry, percent are black and percent are hispanic (eeoc, ). three-quarters of full-time, year-round healthcare workers are female, with that share even higher among the lower paid nursing and health aide occupations, critical occupations with severe risk of exposure to this disproportionate exposure to virus for lower income groups, women, and minorities is exacerbated by differences in these groups' access to healthcare and the quality of that health care-factors that affect both vulnerability and resilience to pandemic disease. membership in more than one of these groups will tend to compound disadvantage even further. preliminary research suggests that black patients exhibiting covid- symptoms were six times less likely to get treatment or testing than white patients. this is not unique to covid- : similar patterns have been observed for other modern pandemics including the h n influenza outbreaks (quinn et al., ) . the outsized impact of pandemics on minority populations and people of lower socioeconomic status has historical precedent. the influenza pandemic hit the poor first and hardest (sydenstricker, ; mamelund, ) , a point we will return to in section iii. explanations for this relationship mirror modern ones: poorer populations lived in denser housing units under worse conditions, and had occupations that increased exposure to the virus. moreover, low incomes constrained their ability to avoid exposure and seek treatment. historical evidence shows that to escape a th century outbreak of yellow fever, wealthier residents often left the city-an option unavailable to low-income workers with tenuous job security. this is a pattern that we see as well during outbreaks of plague in earlier centuries, and is part of dittmar & meisenzahl's ( ) explanation for why the black death paved the way for institutional reform: the old elites simply left town (dinges, ; isenmann, ) . this sort of regional flight is unlikely to be a central dimension along which covid- has differential impacts across income levels-but it does raise important issues that set the current crisis somewhat apart https://www.bls.gov/oes/ /may/oes .htm https://www.eeoc.gov/statistics/employment/jobpatterns/eeo / /national-naics /table?naics= &state=&cbsa= figures are based on the u.s. census bureau's calculations using american community survey data (https://www.census.gov/library/stories/ / /your-health-care-in-womens-hands.html). https://www.nytimes.com/ / / /us/coronavirus-african-americans-bias.html the relationship between pandemic exposure and socioeconomic status has not always been constant. as alfani & murphy ( ) note, studies of the plague in europe find the black death to have been universally deadly. however, plagues of the fifteenth and sixteenth centuries exhibited the negative relationship between socioeconomic status and mortality found in more recent pandemics (see, for example, slack ( ) , alfani ( ) , and carmichael ( )). however, the final major plagues of the seventeenth century once again tended to have severe consequences across all classes. mamelund ( ) note that in norway, the impacts of the pandemic were most severe for transport, hotel and industry workers, paralleling the observations above about covid- . these factors also translated into worse outcomes for minorities. as the exception that proves the rule, black americans fared better than white americans during the pandemic (crosby, ; Økland & mamelund, ) . crosby ( ) argues that the black population had disproportionately high exposure to the early, less virulent summer wave of the pandemic due to their worse occupations and living conditions, conferring some degree of immunity to the more deadly later wave. a similar mechanism operated during historical yellow fever outbreaks, albeit resulting in advantages for native-born individuals over immigrants. individuals born in an area with endemic yellow fever and exposed at a young age often contracted a mild form of the disease, and then developed immunity. as a consequence, adult immigrants were far more likely to die in yellow fever outbreaks in the united states than either native-born whites or blacks (patterson, ) . saavedra ( ) exploits this pattern to demonstrate that earlylife yellow fever exposure negatively impacted adult occupational outcomes, with white males born to immigrant mothers during yellow fever pandemics less likely to become professionals than the sons of native-born mothers. from other historical pandemics: the spatial distribution of population within and across cities, the degree of interconnection between rural and urban areas, and the extent of urban health penalties. while cities are much healthier today than in the past, societies today are also much denser, more urbanized, and better connected-all factors that would tend to make modern pandemics both faster to spread and harder to control than in centuries prior. and indeed, while covid- has hit dense metropolitan areas particularly hard, as in the past, under the current crisis, rural communities have not been spared. this is in part because of the relative ease with which people circulate between communities with our modern transportation networks, but also because of the way that the nature of modern work tends to place individuals in close contact with each other, even in less densely populated areas. to wit, major rural clusters of covid- in the united states have been tied to large meat and poultry processing facilities, with workers at these facilities experiencing case rates an order of magnitude higher than the general u.s. population (dyal et al., ) . moreover, rural areas' demographic composition (often older and less affluent) and healthcare infrastructure (often sparser) can also contribute to their difficulties with pandemic disease. to respond effectively to pandemics in the moment, and to deal with their long-run fallout, will require an understanding of its distributional effects over time and space. we explore these central consideration in depth in section iii. evaluating the policy response to covid- and how it compares to historical pandemics requires recognizing that information on the disease and how to stop its spread has been limited to date, and is still evolving. this issue stems in part from covid- being a novel disease-developing treatments and vaccines takes time, and public health recommendations can change as knowledge advances. it also stems from incomplete and inaccurate data: limitations on covid- testing has often meant relying on mortality rates rather than case rates. incidentally, this is the same approach economic historians are often required to take. morbidity data are rare historically and, when available, may be unrepresentative and inaccurate. mortality data are both far more prevalent and reliable, even if it is morbidity that is typically more relevant to the economic impacts of a pandemic, particularly less lethal ones. for health officials today, the need to assess the spread of covid- through mortality data leads to the frustration of identifying the arrival of cases with a substantial lag. for the economic historian, this lag is irrelevant, but the issue remains that only those places experiencing excess mortality can be identified; diseases leading to widespread morbidity but little mortality may be equally important for the evolution of economies, but far more difficult to identify prior to modern medical records. again, this suggests that evidence from crises that have run their course can be informative of what to expect going forward. while some of the challenges in developing effective covid-control responses have stemmed from incomplete and rapidly evolving knowledge of the disease, they have also stemmed from issues of state capacity, political will, and ideology. for instance, policymakers, firms, and individuals have been hamstrung by not only limited testing and contact tracing capacity, but also by a failure at times to deploy these tools efficiently. constraints such as these are a product of both the limitations of medical technology, and broader issues of political leadership and coordination. the inability to identify and isolate individuals at risk of spreading the disease, in turn, has necessitated rather blunt policy tools, such as business closures and stay-at-home orders. in the u.s. in particular, these covid-control efforts have been aggressively decentralized, and have tended to prioritize both commerce and individual liberty-even where these might be at odds with each other, or lead to ineffective disease control. to wit, business owners and public officials have struggled to gain widespread compliance with (and have often declined to enforce) precisely the sorts of behaviors-e.g., mask-wearing, social distancing-that would allow for the safe reopening of businesses. indeed, it appears that the fear and uncertainty created by the failure to control the spread of disease, in turn, has contributed to prolonging economic pain (goolsbee & syverson, ) . challenges such as these, related to culture and institutions, are nothing new-in fact, they characterize the u.s.'s historical experience of managing epidemic disease. in his excellent the pox of liberty, troesken ( ) lays out how the very institutional features-among them a decentralized federal system, a focus on property rights and commerce, and protection of individual liberties-that led to the u.s.'s rapid economic development also often undermined its attempts to control past outbreaks of smallpox, typhoid, and yellow fever. the examples he provides have uncanny parallels to the u.s.'s approach so far to managing covid- . strategies to manage the spread of covid- have been varied, with many jurisdictions pursuing multiple complementary approaches, often including coordinated sourcing and distribution of protective equipment, reallocation of medical capacity, virus and antibody testing, contact tracing, frequent sanitizing of public facilities, social distancing, mask-wearing, managing congestion in public places by staggering timings and moving activities outdoors, limiting large gatherings, quarantining infected individuals, and minimizing the risk of disease exposure via closures of businesses and schools and broader stay-at-home orders. of these strategies, shutdowns and quarantines have been some of the most accessible, widely used, and hotly debated under covid- . a shutdown-centered approach such as this also has strong historical precedent. in fact, closures and quarantines were some of the only tools available to societies prior to the virology advances of the th and th centuries. though the shutdown of firms has been more comprehensive under covid- than in many past pandemics, the primary measures being taken now, such as quarantining sick individuals, restricting public gatherings, and closing schools, were all implemented during the pandemic (markel et al., ; hatchett et al., ) , albeit with a smaller scope and shorter duration. likewise, when england was combatting the other countries offer a contrast on one or more of these dimensions. for example, though some of these early gains have since dissipated, taking a more authoritarian and centralized approach, china and india had some initial success in containing the virus following swift and complete lockdowns, underscoring the potential importance of state capacity and centralization in pandemic control. likewise, south korea's response demonstrated the importance of relative novelty: due in part to experience with past respiratory pandemics, pre-existing public health infrastructure and greater public buy-in with mask-wearing allowed them to respond more quickly and effectively to the greater use of firm closures as a disease-control strategy today could be due, for instance, to improvements over time both in the safety net and in remote-work capabilities. this more widespread pause on non-essential activities may in turn lead to fairly different effects of covid- relative to past pandemics, e.g., in terms of patterns of disease transmission or total economic impact. while cities employed a diverse set of non-pharmaceutical interventions (npis) during the pandemic, only a small fraction of these interventions (namely, closures of public facilities, isolation policies, bans on public gatherings, and making influenza a notifiable disease) were widely practiced across localities (hatchett et al., ) . moreover, markel et al. ( ) document that npis were in place for only months or less in out of the cities in their sample; even the maximum duration in their sample ( days, in kansas city, missouri) still falls far short of the u.s.'s experience of covid- npis to date. indeed, barro ( ) suggests that the short average duration of npis during the pandemic led them to be relatively ineffective in curtailing mortality. the efficacy of npis depends on factors including the type of intervention, when it is first implemented, how long it is in place, and the strictness with which it is implemented. because of this, and although npis under covid- have been in place longer than during the pandemic, it is difficult to say at this stage whether this necessarily means that they will have been more effective in reducing morbidity and mortality-particularly because covid- npis in the u.s. have tended to be implemented somewhat late in the pandemic's course, have tended to be intermittent and noncomprehensive, and have tended to be leniently enforced, all factors which undermine efficacy and which may themselves be contributing to the need for longer npi duration. plague in the s, they quarantined ships from other countries, closed ale houses, and limited the number of lodgers allowed in a house, actions that would sound familiar to cruise ship passengers and restaurant owners during the covid- pandemic (bell, ) . indeed, it is striking-maybe even alarming-how little has changed about our best options for fighting pandemics, despite centuries of advances in medicine, public health, and living standards. this policy response, necessitated by factors including inadequate testing and broader uncertainty about key epidemiological parameters-even those as basic as precisely how and through whom the disease can be transmitted, and whether it is possible to become re-infected-makes the economic history of policy responses to pandemics particularly relevant for studying the current crisis. even when we contemplate a world where successful covid- vaccines are available, history sounds a note of caution: the same underlying issues that have made mask-wearing both incomplete and fraught in settings, like the u.s., with a strong institutional commitment to liberty and rugged individualism, could also be expected in the context of covid- vaccination. as troesken ( ) notes, anti-vaccinationism has a long history in the u.s., bolstered by the common failure to appreciate the extent of infectiousdisease externalities (the choice not to vaccinate can be individually rational, even if people understood externalities, which they largely do not), as well as by a belief in both minority rights (individuals cannot be forced to vaccinate) and federalism (individuals preferring not to vaccinate can sort into amenable jurisdictions). while troesken documents that mandatory vaccination was frequently enforced in the past via fines, or by denying access to schools or other public services, it is difficult based on the nature of the u.s. covid- response to date to imagine such enforcement mechanisms being implemented. instead, in heterogeneous, strongly pro-individual, pro-freedom societies, we may need to rely on a stylized fact that troesken demonstrates using data from th century smallpox epidemics in germany: vaccinations rates rise in pandemic years, because during pandemics, the risk of infection rises sharply, and the private costs of non-vaccination are clearly outweighed by the private benefits. for thinking about the direct effects of pandemics on the health and wellbeing of individuals in the shortand long-run, the influenza pandemic, or the -spanish flu,‖ provides a useful point of reference. covid- to date parallels the pandemic in several key ways, including its rate of transmission, global spread, and crude mortality rates. the spanish flu was one of the most acute and widespread natural disasters in modern history. taubenberger & morens ( ) estimate that during the pandemic, roughly million individuals, equivalent to roughly a third of the world's population at the time, were infected and symptomatic. case fatality rates, at over . percent, were at least times as high as in other influenza pandemics, making the virus especially lethal. all told, somewhere between and million individuals perished globally. the death toll in the u.s. alone exceeded that from all american combat deaths over the twentieth century (almond, ) . see for example markel et al. ( ) on the effectiveness of school closures in combatting the spread of the influenza pandemic, meyers and thomasson ( ) on the effects of polio-related school closures on educational attainment, and alfani & murphy ( ) on city-level quarantines during pre-modern plagues. cultural features like distrust of scientific expertise, and of institutions more generally, may also undermine vaccine compliance. troesken ( ) notes that the underlying legal theory behind vaccination non-compliance fines gained further credence after the supreme court upheld the affordable care act's insurance mandate in national federation of independent business v. sebelius, u.s. ( ). there are challenges to drawing lessons from the pandemic. much remains unknown about the origins and epidemiology of the virus and its economic impacts are confounded by the effect of world war i. the pandemic itself was sharp, sudden, and concentrated over the span of little more than a -month period. the virus, an h n strain similar to that which caused the swine flu outbreak, spread roughly simultaneously across europe, asia, and north america, in three distinct waves over the year beginning in spring . the first of these waves, appearing in march , was relatively mild. it was followed by a substantially more catastrophic one from september to november , and another in the early months of (taubenberger & morens, ) . in some parts of the world, particularly in east asia, a further major wave of pandemic influenza hit as late as (lin & liu, ; ogasawara, ) . this sort of timing and spacing was unprecedented among influenza pandemics, as was its distinctive mortality profile. where influenza death rates by age typically follow a u-shape, with high mortality rates among the very young and the very old (as is also the case with the sars-cov- , the virus behind covid- ), the strain followed a w-shape, with a sharp peak in mortality risk among young adults as well. indeed, almost half of all influenza-related deaths during the pandemic period accrued to those aged - (taubenberger & morens, ) . the age pattern associated with this strain of influenza was in fact so unusual that it has been exploited as a diagnostic tool in recent studies. for instance, while the influenza pandemic is typically thought to have emerged in full force in europe around the summer of , and in a milder form somewhere in the central u.s. in spring , detailed age-by-month mortality statistics allow olson et al. ( ) to uncover evidence that an early -herald‖ wave of pandemic influenza was actually present in new york city well beforehand, from february to april of . during this period, the age profile of excess influenza mortality had started to shift from the older ages typical of interpandemic seasons to the younger ages that characterize pandemic seasons. this underscores the value of accurate and disaggregated data in tracing the origins and spatiotemporal spread of pandemics, and the need to strengthen not only rapid-response public health infrastructure, but also that to support ongoing disease surveillance. turning to morbidity, those under the age of , and particularly, those aged - , had disproportionately high incidence of influenza-however, the latter group had a much lower death rate from influenza and pneumonia than other ages, further sharpening the middle peak in the morbidity-adjusted pandemic mortality curve (taubenberger & morens, ) . age, however, was not the only major factor that contributed to pandemic mortality risk, and a range of recent studies have emerged cataloging the often interrelated features of countries, cities, and individuals that led to disparities in the immediate mortality burden of the flu. on these mechanisms, the evidence is mixed-surely in part because of diverse empirical settings and disciplinary approaches-but certain patterns do emerge. first, baseline health status mattered: both pre-pandemic pneumonia, a bacterial condition with a strong biological interaction with the influenza virus, and infant mortality rates, a proxy for population health, contributed to higher pandemic flu mortality (acuna-soto et al., ; clay et al., ) . likewise, high levels of air pollution, an environmental factor that aggravates respiratory conditions and depresses baseline health, also raised pandemic mortality. for instance, clay et al. ( ) examine evidence from a panel of u.s. cities, and find that the air pollution generated by coal-fired electricity plants was a significant contributor to pandemic mortality, with effect sizes roughly half those associated with measures of population health and poverty. together, they estimate that these factors accounted for approximately half of all cross-city variation in pandemic mortality. in another study, they find that both infant and all-age mortality were impacted adversely by the presence of coal-burning plants, with poor air quality responsible for - percent of total pandemic mortality in high-and medium-pollution cities, a figure equivalent to some , - , excess deaths beyond those attributable to the pandemic alone (clay et al., ) . , second, population density and related concerns, such as housing quality and the number and composition of social interactions, were also important factors in pandemic mortality. in europe as in the u.s., the pandemic came to cities earlier, and was more devastating there, a phenomenon linked to urbanization and residential crowding (chowell et al., ; mamelund, ; murray et al., ) . transmission was localized, and influenza and pneumonia mortality exhibited significant and rather tight (e.g., - , m) spatiotemporal clustering (grantz et al., a,b; tuckel et al. ) , though proximity to high-risk population centers like wwi military bases appears to have had little effect (clay et al., ) . although urban centers were associated with higher pandemic mortality, the opposite population gradient prevailed when comparing among cities, or among rural areas: in both cases, smaller, less dense localities fared worse (acuna-soto et al., ; chowell et al., ) , suggestive perhaps of capacity constraints in the healthcare workforce and medical infrastructure. third, factors-such as illiteracy and foreign-born status-that might have prevented individuals from adopting public health recommendations were strong predictors of elevated mortality, often above and beyond their association with poverty. higher rates of illiteracy were linked to higher rates of influenza mortality during the pandemic, across both cities and neighborhoods (clay et al., ; grantz et al., a, b) . likewise, foreign-born status not only predicted higher pandemic mortality in hartford, connecticut, but the relationship between nativity and mortality persisted even after controlling for socioeconomic status, population density, and neighborhood ethnic composition, indicating perhaps a role for social factors, or language or cultural barriers to the adoption of relevant public health measures (tuckel et al., ) . crucially, the consequences of these barriers were not limited to the foreign-born: holding all else equal, native-born individuals living in areas with a higher share of foreign-born had higher mortality rates than their counterparts living alongside a lower share of foreign-born neighbors. this emphasizes the importance of neighborhood spillovers in infectious disease transmission-and, of course, demonstrates the interrelated nature of individual-and neighborhood-level mechanisms. it is possible that indoor pollution and seasonality also played a role in air quality-influenza interactions, both during and outside pandemic times. for instance, influenza is generally prevalent in the winter, a time when coal smoke from home heating also tended to peak in this era (barreca et al., ) . clay et al.'s ( ) observation that modern levels of pollution in parts of the developing world, including india and china, are on par with those in the early th century u.s., sounds an ominous note in light of the current crisis-though the circumstances today (e.g., improved medical technology, the higher baseline share of trafficrelated emissions, a fall in pollution due to widespread economic shutdowns) may be just different enough to ameliorate concerns over the lethal interaction between pollution and pandemic influenza. while pollution can lower baseline health by undermining the respiratory system, it is worth noting that pollution may also be associated with higher baseline health, insofar as it proxies economic activity. for instance, clay et al. ( ) find evidence of crucial tradeoffs between the income generated through industrial activity on the one hand, and the pollution generated on the other in the u.s. from the s to the s. in less developed localities, infant mortality followed a u-shaped pattern with respect to the expansion of coal capacity: first falling as rising incomes and cleaner residential energy sources buoyed infant health, and then rising as subsistence health needs were met and the concentration of pollution grew. the net health effects of a pandemic that dampens economic activity (and so reduces pollution), then, is therefore likely to be context-specific, depending on factors such as the level of baseline health and income, the extent of medical infrastructure, and the strength of social safety nets. troesken ( ) also points to individualism and liberty as cultural/institutional values that tend to lower individual-level compliance with public health recommendations. when considering these biological, demographic, and socioeconomic factors in quick succession, it is difficult not to see the overarching hand of income in all of these mechanisms-though, to be clear, several of these studies are careful to disentangle these factors from their association with income. in theory, income gradients in pandemic mortality could arise through a number of channels, including many of those hinted at above: e.g., the tendency of those with higher incomes to have better baseline health status, rendering them biologically less vulnerable and more resilient to infection; higher-quality and lower-density housing, reducing the chances of viral transmission; better public health knowledge, the human capital necessary for individuals to effectively assimilate this knowledge and to adopt life-saving recommendations, and timelier and more robust public health interventions, all slowing the spread of illness; better access to healthcare and medical infrastructure, improving the probability of survival conditional on infection; and a greater capacity for individuals to undertake avoidant, adaptive, and compensatory behaviors, both throughout and following the pandemic. crucially, these channels can operate at both individual and institutional (e.g., city or country) levels, with both richer people and localities-and certainly, the interaction of these-theoretically better equipped to weather the crisis. the fact that some of these channels are highly correlated, of course, can make it difficult to pinpoint the underlying mechanisms: higher-socioeconomic status (ses) individuals are likelier to be both healthier, protecting them from infection, and more educated, rendering them better able to adopt public health measures; cities tend to be richer in both income and infrastructure, but they are also more heterogeneous and densely populated than rural areas. nevertheless, the literature can still shed light on the role of income on net. while some studies explicitly looking at its role in pandemic severity have shown little relationship between pre- economic development and pandemic mortality (brainerd & siegler, ) , a great many indicate that poverty exacerbated mortality risk. for instance, murray et al. ( ) document tremendous (i.e., over thirty-fold) within-and cross-country variation in excess mortality due to the pandemic, with nearly half of this variation explained by baseline per capita income. taking a finer-grained look at these issues, grantz et al. ( a,b) explore the socioeconomic determinants of pandemic mortality and transmissibility using detailed data from chicago. among the associations they find between health and various poverty proxies are large, statistically significant, and negative associations between census tract-level homeownership rates and mortality. these findings are consistent with the lower baseline health of lower-ses neighborhoods, their poorer access to medical care, and their lower awareness and adoption of public health recommendations. shanks & brundage ( ) add that these factors may be proxying other features of low-ses populations, such as a higher risk of sequential infections (e.g., pandemic influenza followed by a secondary bacterial infection such as pneumonia), or the larger number and lower-ses composition of their social interactions. all of these could have contributed to higher cumulative pandemic mortality through faster and more widespread disease transmission, higher incidence of infection, or higher case fatality rates. these results suggest that rather than acting as a democratizing force, the pandemic further entrenched preexisting socioeconomic disparities. the clear implication of studies documenting the immediate health effects of the outbreak is that the damage from pandemics has, and remains likely to, fall disproportionately on disadvantaged communities. apart from its effects on health, however, the pandemic also had important consequences for population dynamics. one such effect pertains to temporal and cross-disease mortality spillovers resulting from pandemic-era mortality patterns. noymer ( ) shows that the influenza pandemic hastened the decline of tuberculosis in the u.s. through a harvesting mechanism. specifically, he suggests that independent competing risks may be responsible for this phenomenon, driven by substantial age overlap in the profile of prospective tuberculosis and (pandemic-type) influenza victims. this -passive selection‖ contrasts with -active selection‖ based on biological interactions between influenza and tuberculosis. this harvesting, in turn, had long-lived implications for sex differences in post-pandemic mortality rates: because tuberculosis morbidity disproportionately affects men, and because the influenza pandemic reduced the pool of those who might die of tuberculosis in the years following, the pandemic had the effect of eroding women's longevity advantage over men. we might expect similar outcomes in the context of covid- given that a large share of those dying have one or more co-morbidities, though the distinct age profile of pandemic deaths versus covid- deaths may complicate these dynamics. studying brazil, guimbeau et al. ( ) likewise find rather larger reductions in sex ratios at birth following the influenza pandemic, consistent with the greater vulnerability of male fetuses to adverse in utero shocks-a phenomenon often seen in the literature on famines and environmental disasters. such changes in the sex ratio, or in sex-specific survival, may well have had long-run implications for marriage and labor markets. another major area in which the pandemic affected demographic behavior relates to marriage and fertility. in some cases, this was largely a function of pandemic psychology. mamelund ( ) shows that a climate of fear and uncertainty in norway, alongside social distancing efforts and peculiarities of norwegian marriage laws (which imposed a one-year waiting period before widows could remarry), led to a drop in births in , as families deferred childbearing. higher rates of maternal mortality and miscarriage during the pandemic likely also contributed to a drop in birth rates. this pent-up demand for children (alongside -replacement‖ demand for children lost to the pandemic) was released after the crisis passed, resulting in a baby boom in . elsewhere, as was the case in nearby sweden, changes in fertility arose from the way that pandemic mortality affected markets for marriage and labor: boberg-fazlić et al. ( ) find evidence of a drop in fertility during the pandemic, followed by a short-lived rebound in post-pandemic fertility. the net effect in the long term, however, was to reduce fertility-due in part to persistent disruptions to marriage markets (particularly in rural areas and poorer cities); the adverse effects on income; as well as to behavioral changes induced by the pandemic, including a rise in female labor supply (and so, an increase in the opportunity cost of childrearing) in regions with high male pandemic mortality rates. perhaps most noteworthy, the short-run post-pandemic fertility increase was selective in nature: a child born during this boom was more likely born to mothers who were married or who were high-ses city-dwellers. this was largely driven by postponement fertility, and particularly, selective postponement. finally, pandemic-related mortality affected childbearing through its effect on survivors' incomes. donaldson and keniston ( ) show that the high pandemic death toll in some regions of india implied a substantial increase in per capita incomes, as survivors assumed the agricultural land of pandemic victims. in light of this rise in incomes, they find an increase in both the quantity and quality (given by literacy and height) of children born following the pandemic in india. phenomena such as these, which change the sex-and age-composition of the population-not to mention the average health status of successive cohorts-are likely to have long-lived effects on economic development, population health, and individual wellbeing. the lethality and peculiar age profile of the pandemic also give rise to long-run considerations. these may be especially relevant in light of covid- , where the vast majority of people who become sick ultimately survive. during the pandemic, young adults-including prime childbearing-age womenwere some of the likeliest to fall ill: in some parts of the u.s., roughly a third of all mothers (relative the about percent of the general population) became infected during the crisis (almond, ) . moreover, across settings, evidence of replacement fertility is rather more limited. note however that covid- appears to be less prevalent, and possibly less severe, among prime-aged people. consequently, it is possible that scarring through the health channel under covid- may end up being less severe, and/or less widespread, than that following the influenza pandemic. scarring through the income/labor-market channel, however (explored in more detail in section iv), could well be substantially worse following covid- than the pandemic, given the latter's relatively mild and short-lived effects on the economy. despite the very high mortality rates from this pandemic, most of those infected ultimately survived. this left considerable scope for maternal morbidity-and, through the impact of maternal stress and illness on intrauterine hormones, nutritional resources, and other factors-for insults to fetal health. in what is perhaps the seminal study in economics of the influenza pandemic's long-run effects on wellbeing, almond ( ) finds wide-ranging adverse effects on later-life human capital and labor market outcomes among u.s. cohorts exposed to the pandemic in utero. these include substantial reductions in high school completion rates, wages, and socioeconomic status, alongside large increases in the probability of living in poverty, the receipt of welfare payments, the likelihood of incarceration, andparticularly among men-the probability of physical disability. that these adverse outcomes exist in spite of a pandemic-induced increase in miscarriages, stillbirths, and infant mortality rates (see, e.g., guimbeau et al., ; mamelund, )-all culling forces which likely resulted in a pool of survivors if anything positively selected on health-is a testament to the catastrophic extent of post- scarring. almond's initial study has also since spawned a large and varied literature interrogating the long-run effects of the pandemic across a range of global settings. a first set of studies dig deeper into the u.s. case. one such study shows that birth cohorts (and in particular, those born in quarter of , who were in utero at the height of the pandemic), are percentage points (or percent) more likely to report fair or poor health than their counterparts born in surrounding years; see a statistically significant - percent increase in a range of functional limitations, including trouble hearing, speaking, lifting, and walking; and are also likelier to experience diabetes and stroke (almond & mazumdar; . others debate the possibility of pandemic-induced selection into fertility, which could confound estimates of the long-run health effects of early-life pandemic exposure. these studies ultimately conclude that the positive selection of wwi recruits, and the corresponding negative selection of pandemic-era fathers, does not substantially alter the conclusion that fetal exposure to the pandemic was a major and direct cause of these cohorts' later-life disadvantage (brown & thomas, ; beach et al., ) . a newer set of papers, focusing on non-western, and particularly, lower-income, settings, shows that the evidence on the pandemic's long-run penalties is robust across a range of empirical contexts, each with different levels of baseline income and health status, different institutional responses to the pandemic, and different degrees of involvement in wwi. for instance, as in the west, in taiwan there is evidence of permanent scarring: cohorts exposed to the pandemic in utero faced penalties with respect to educational attainment, heights, kidney disease, circulatory and respiratory issues, and diabetes (lin & liu, ) . in low-income settings with minimal public health intervention, even higher incomes only did so much to buffer these shocks: in a sample of high-ses children in japan, ogasawara ( ) finds that in utero exposure to the influenza pandemic reduced boys' and girls' heights by . cm and . cm, respectively-magnitudes which in other studies have been associated with substantial increases in the probability of type ii diabetes, osteoarthritis, and heart disease. the long-run results seen in japan, as in guimbeau et al. ( ) in brazil, are consistent with sex differences in resilience to adverse health shocks. now quite common and influential in economic research, the conceptual framework linking early-life conditions to later-life health and wellbeing is termed the -barker‖ or -fetal origins‖ hypothesis. this hypothesis holds that certain chronic conditions stem from deficits in the fetal environment (barker, ) . based on this initial literature in epidemiology and medicine, which focused on evidence from historical famines, a growing literature in economics has used these ideas to model the technology of human capital formation, and to identify sensitive and critical periods for the development of a range of outcomes contributing to labor market success and general wellbeing, including cognitive and non-cognitive skills, metabolism, and longevity (heckman, ; almond & currie, ) . meanwhile, swedish pandemic survivors saw reductions in life expectancy (helgertz & bengtsson, ) . the reduction in the health, human capital, and labor market prospects of cohorts exposed in utero also appears to have dampened their marriage market prospects in ways that continue to carry intergenerational consequences. while both men's and women's own educational attainment was lower among exposed cohorts, only exposed women appear to suffer a marriage market penalty: they marry earlier, to spouses with lower levels of education (fletcher, ) . these are factors generally understood to reduce household incomes, female control of household resources, and the budget share allocated to child-centric expenditure. as such, these effects could represent a mechanism-alongside, e.g., epigenetics, or the more direct role of parental education in facilitating children's access to quality healthcare and schooling-by which we see intergenerational persistence in the consequences of early-life exposure to the influenza pandemic of . indeed, moderate adverse effects on educational attainment, occupational prestige, and family socioeconomic status have been documented up to the third generation, i.e., the grandchildren of those exposed in utero (cook et al. ) . what action, if any, did households take to shield their children from these effects, or to help them recover? while surprisingly little has been written in the context of the pandemic on questions of individual-and household-level avoidance, adaptation, and remediation, parman ( ) is a noteworthy exception. drawing on linked microdata from the u.s., he finds evidence of reinforcing investments in response to the influenza pandemic: that is, families with a child in utero during the crisis shifted resources to the child's older siblings, leading the latter children to higher educational attainment. parman explicitly rules out changes in family size, birth spacing, or selectivity in any such changes, underscoring that the effects observed here are directly a function of parents reallocating limited resources away from affected children, and toward the child with a higher human capital endowment at birth. thus, household responses may have if anything compounded any early-life disadvantage associated with the shock. historical pandemics can help us think about potential long-run effects on wellbeing arising directly through the current pandemic's patterns of morbidity and mortality. but what about the impacts resulting from its disruption of daily economic life? one of the central features of the current coronavirus pandemic is the sudden, extreme, and widespread economic disruption it has caused. on this count, it has perhaps less in common with other recent pandemics. indeed, the immediate economic disruption caused by the pandemic pales in comparison to that caused by so, while this historical pandemic can some work has, however, addressed the broader policy responses (and lack thereof) to the pandemic in the u.s. for instance, hatchett et al. ( ) find that cities that simultaneously implemented multiple non-pharmaceutical interventions (consisting of, e.g., isolation of sick individuals, bans on public gatherings, mandatory notification of disease, and closure of public gathering places, staggered business hours, and no-crowding rules) early in the pandemic had peak mortality rates roughly half that of cities that did not implement such interventions, and substantially lesssteep epidemic curves. no single intervention was responsible for these gains; rather, it was the combination of multiple mutually reinforcing interventions that were effective. these findings are in line with markel et al. ( ) , who emphasize the importance of early and sustained non-pharmaceutical interventions during the pandemic. while many cities were successful in taking such a multi-pronged approach to pandemic management, on the whole the u.s. policy response to the pandemic was rather weak, undermined by a preoccupation with world war i-related efforts. until the covid- crisis, there had been relatively little work on the effects of the pandemic on economic activity, largely for lack of high-frequency, spatially disaggregated data on local economic conditions (see beach et al. (forthcoming) for an excellent overview of both the state of this literature and related empirical challenges). indeed, the precise magnitude and temporal reach of these economic effects are still being debated (see, e.g., basco et al. ( ) , barro et al. ( ) , correia et al. ( ) , lilley et al. ( ) , and velde ( )), and a challenge for many of these studies in identifying pandemic effects on the economy remains the confounding effect of world war give us insight into long-run effects on wellbeing through the health channel (-direct‖ effects), we must look elsewhere to think about the long-run consequences of pandemics through corresponding economic downturns (-indirect‖ effects). but where to look for a suitable comparison? in some ways, episodes such as the black death or the aids crisis in sub-saharan africa would seem to present closer analogues than the influenza pandemic, as health events with massive and lasting economic ramifications. the catastrophic loss of life under these pandemics fundamentally reshaped entire societies and economies, with, for instance, the resulting labor scarcity driving up the real wages of survivors, and, in some cases, precipitating other major demographic, economic, social, cultural, and institutional changes (young, ; alfani & murphy, ) . indeed, some point to the former plague as a major contributor to sustained rises in western european living standards even under a malthusian regime (voigtländer & voth, , a , and to the region's rapid economic development and eventual divergence from the rest of the world over the early modern period (clark, ) . notes: the insured unemployment rate is based on employees covered under unemployment insurance as reported to states by employers. covid- cases are relative to the entire state population. unemployment data were retrieved from https://oui.doleta.gov/unemploy/claims.asp. covid- data were retrieved from https://github.com/nytimes/covid- -data. the code and data needed to generate the figure are available at open-icpsr (https://doi.org/ . /e v ). in each of these pandemics, mass mortality led to rapid and dramatic changes in population density and age i. moreover, it is worth noting that the -focused studies that have emerged in the wake of covid- tend to conflate the economic effects of the pandemic that arise from within and outside the -direct health-shock‖ channel. to disentangle these channels and use a shock of comparable magnitude, we focus primarily on the great depression when examining the long-run human effects of economic dislocation. see alfani & murphy ( ) for an excellent and in-depth review of the literature on pre-industrial plagues, their long-run socioeconomic consequences, and parallels to modern pandemic control efforts. structure, which in turn affected factor prices and labor markets. thankfully, mortality rates under covid- are not on such a scale as to produce the sort of fallout seen with these events. instead, it appears it may be a combination of factors other than the virus's actual toll on morbidity and mortality that is the source of economic dislocation in this instance. indeed, as figure shows, the severity of the immediate health effects has not been a clear predictor of a locality's economic downturn. likewise, emerging evidence complicates the popular conception that pandemic-control measures themselves, such as stay-at-home orders, are primarily responsible for the downturn associated with covid- . for instance, while gupta et al. ( ) suggest that % of the decline in employment in the early months of the pandemic was driven by state and local social distancing policies, kahn et al. ( ) show that the labor market effects of covid- to date have been broader-based than is typically thought. all u.s. states exhibited a collapse in job vacancies in march , and a corresponding rise in unemployment insurance (ui) claims, irrespective of either the intensity of the virus's initial spread or the timing of stay-at-home orders. these phenomena were seen for the most part across both essential and non-essential sectors, directly-and indirectly-affected sectors, and across occupations with and without work-from-home capabilities. they conclude that -the current damage done to the economy is not solely caused by the stay-at-home orders; it is too large and pervasive.‖ exploring the drivers of the collapse in economic activity, goolsbee & syverson ( ) suggest that -individual choices were far more important [than government restrictions,] and seem tied to fears of infection.‖ these voluntary disease-avoidance strategies by individuals are likely connected to the lack of decisive and coordinated policy responses, and to broader uncertainty about this novel disease. it remains to be seen whether other plausible mechanisms may also have a role-e.g., global supply chains that allow covid-related firm slowdowns in one country or sector to propagate to others, or changes in firm production decisions under covid uncertainty. clearly, both the current crisis and our understanding of it are still rapidly evolving. what we do know, however, is that the downturn this pandemic has precipitated is substantially larger than in other modern pandemics, and unlike in some pre-modern plagues, is likely unrelated to either mortality-related changes in demography or to immediate reductions in labor supply or work capacity due to contemporaneous morbidity. as such, crises of primarily economic origin, such as historical recessions-and in particular, the great depression-may make the best analogues: while the coronavirus pandemic is a public health crisis, to be sure, it has manifested above all as a massive economic disruption, both in terms of magnitude and reach. accordingly, we might want to think about its health and human capital consequences through this -livelihoods‖ channel as well. indeed, it is these effects that are likely to be most relevant to our current situation. beginning with short-term effects, we can look to a large literature on business cycles and health. these studies indicate that the net effects of downturns on morbidity and mortality will likely be highly contextdependent. this is because health is multidimensional, there are many countervailing channels through which local economic conditions can affect wellbeing, and because the particulars of the empirical even while modern globalization has made disease transmission faster and harder to control, and even while increased efficiency in healthcare systems and global supply chains have complicated efforts to quickly ramp up treatment and control responses, other modern factors have made the current pandemic less dangerous to health than those that came before it-among them, improved medical technology, which has made it easier to manage secondary infections, and higher incomes, which have made human populations both less vulnerable and more resilient to infectious disease. this is certainly true at least in a distributional sense. while adverse effects will certainly be severe through direct morbidity/mortality channels, these will nevertheless be relatively concentrated. for contrast, adverse spillovers from these direct health effects, and from broader disease-control efforts, will be much more diffuse, even if less acute. consider, for instance, that unlike the health-channel scarring effects of pandemics discussed in section iii, the economy-channel shocks apply to everyone to one extent or another, not just those who survive infection. setting-e.g., the size, nature, and origin of the shock; the baseline level of population health; and the strength of social safety nets-will ultimately govern which of these effects dominate (arthi et al., ; cutler et al., ) . recessions have been shown to improve health, for instance, by freeing up time for health-promoting activities such as exercise, childcare, and breastfeeding (dehejia & lleras-muney, ; miller & urdinola, ; ruhm, ) ; by reducing the income available to sustain unhealthy behaviors such as alcohol, tobacco, and drug abuse (ruhm & black, ; ruhm, ) ; by reallocating high-skilled but displaced healthcare workers toward higher-risk populations (stevens et al., ) ; and by limiting individuals' exposure to environmental and work-related hazards, including traffic accidents, on-the-job injuries, and pollution (muller, ; chay & greenstone, ; miller et al., ). meanwhile, adverse income shocks can compromise access to basic needs such as nutrition, medical care, and housing (griffith et al., ; painter, ) ; and can cause psychological stress that in turn raises rates of self-harm and risky behaviors (eliason & storrie, ; sullivan & von wachter, ) . while in theory, the net effect of local economic shocks on health is ambiguous, in practice, the bulk of the evidence drawn from modern and rich-country settings suggests that on net, total mortality rates fall during recessions (arthi et al., ) . in addition to setting-specific features like higher baseline health and stronger safety nets, the fact that beneficial channels tend to dominate in these settings may be in part because this evidence comes principally from small fluctuations in local economic conditions: using cross-country evidence over two centuries, cutler et al. ( ) show that mild downturns lower mortality, while large ones raise it. the downturn caused by covid- would surely qualify as the latter. the evidence is much more mixed in developing-country and historical settings, where levels of baseline income and health are low, where safety nets are weak, and where cutting-edge medical technology is less accessible (see, e.g., baird et al. ( ) and ferreira & schady ( ) ). in such settings, even small losses in income can be devastating to health (costa, ; heckman, ) , and there is less scope for the sort of offsetting positive spillovers and behavioral changes seen in more modern and affluent settings. consequently, this evidence seems to more often indicate countercyclical mortality. for instance, arthi et al. ( a) show that even in the presence of adaptive migratory responses, the cotton famine, a major s downturn in britain's cotton textile-producing regions, substantially raised mortality in cotton regions, particularly amongst the elderly (who were more sensitive to income shocks), amongst cotton households (who faced unemployment and reduced hours), and amongst those working in non-tradeables the case of pollution in particular underscores how complex the interactions between health and the economy can be-all the more so during a respiratory pandemic that has precipitated an economic crisis. tied as pollution is to economic activity, a downturn that reduces pollution (and so reduces direct health hazards) also reduces income (and so raises indirect health hazards). moreover, it does so unevenly across space and demographic groups. add to this long-standing (i.e., baseline) distributional considerations around who is most exposed to environmental and pandemic hazards (see, e.g., chay & greenstone, ; currie et al., ) ; and who, conditional on exposure, is most sensitive to income shocks, environmental shocks, infectious disease shocks, or even all three simultaneously (see, e.g., hsiang et al. ; almond & currie, ) ; and a key question for assessing covid- 's effects through economy-environment interactions then becomes, from both an aggregate and distributional standpoint, whether and for whom the losses in health and human capital through the income channel are offset by the gains in health through actions taken to reduce the spread of influenza, the reduction of pollution, and the interaction of these factors. see arthi et al. ( ) for a much more detailed review. note as well that under covid- stay-at-home orders and supply-chain disruptions, the effects through many of these mechanisms are likely to be much more extreme, since the reduction in economic activity has been much more acute (in some cases, nearly absolute). this is the case even in rich countries, but especially in poor ones. in the latter, as discussed above, even smaller economic fluctuations can raise net mortality. consequently, we might expect developing countries to face the greatest tension between the desire to limit the direct health costs of covid- on the one hand, and the desire to limit those health costs arising from the corresponding economic contraction on the other. this is especially the case if pandemic-control measures are seen as helping the former objective while harming the latter, though it is worth noting that it is still unclear the extent to which pandemic-control measures are responsible for the contraction caused by (whose livelihoods depended on the success of the local cotton industry). diverse historical evidence such as this can help us think about how the effects of the covid- crisis might out play out differently in other economies, particularly in the long run-something we cannot get from modern data, and especially, from modern u.s. data, alone. likewise, turning to the great depression, a more recent and thus perhaps more comparable setting to today's, stuckler et al. ( ) find at best mixed evidence of a beneficial health effect of the downturn: while there was a small reduction in all-cause mortality during this crisis, only those reductions in heart disease (small) and traffic fatalities (rather larger) could plausibly be linked to contemporaneous local economic shocks; other recession-related causes of death identified in the literature, such as suicide, rose substantially. fishback et al. ( ) similarly find that had new deal relief spending not intervened, the great depression would have created a -demographic disaster,‖ depressing birth rates and elevating death rates relative to prior trends (particularly among infants, those perhaps most vulnerable to short-run income fluctuations). their results emphasize the importance of government responses to economic crises that in turn become health crises (and vice-versa): for instance, they note that while all-cause non-infant mortality rates were largely unaffected by relief spending, such income support nevertheless did help reduce rates of certain salient causes of death such as suicide, one of the few causes of adult mortality identified in stuckler et al. ( ) as seeing a marked increase during the great depression. while current debates around covid- are understandably focused on the immediate impact of pandemic-induced recession conditions, the economic history literature teaches us that we should be equally-perhaps even more-concerned about the long-run scarring effects arising from this economic dislocation. indeed, this channel may be especially relevant in more modern, high-income, and robustsafety net settings where most people survive an adverse shock, only to contend with the long-term and sometimes latent fallout. some of these scarring effects stem from the immediate impact on household incomes. depression-era resource deficits have been shown to affect cohorts that were in utero at the time well into adulthood, lowering their college completion rates and later-life incomes, and raising their rates of later-life poverty and disability-adverse effects that were only more pronounced in poorer areas, and areas that received less relief spending (arthi, ; fishback & thomasson, ) . meanwhile, other long-run penalties arise from disruptions to labor markets and human capital acquisition. a large contemporary literature studies the phenomenon of labor market scarring, or the idea that economic conditions at the time of labor market entry may have lasting effects on training decisions, occupational choice, career trajectories, and lifetime income. this evidence, much of it taken from college graduates around the recession, is mixed: some studies suggest that the impact of initial labor market conditions diminishes over the course of an individual's career-often within the first decade-while others find that some penalties associated with early-career shocks can be cumulative and permanent (see rothstein ( ) for an in-depth review; see also, kahn ( ) ). these effects are often heterogeneous by skill level, and may be driven by mismatch in initial job placement (faberman & mazumder , liu et al. , oyer , Şahin et al. , van den berge ), lower initial wages (which may be partially related to job mismatch; the stress of adverse shocks may also be transmitted intergenerationally through epigenetic channels. see, e.g., costa et al. ( ) . likewise, there is evidence that both pandemics and recessions-as traumatic and stressful events-can shape the attitudes and preferences of those exposed during formative years in ways that can have lasting political and economic consequences (see, e.g., campante et al. ( ) ; giuliano & spilimbergo ( ) ; malmendier & nagel ( ); and schoar & zuo ( ) ). while this literature focuses on adverse shocks at the time of labor market entry, note that compared to other recessions, long-run labor market scarring could even extend to a different and younger range of cohorts in the covid- case, because of widespread school closures. other covid- -related mechanisms, such as the loss of parental income, would tend to compound these effects further. oreopoulos et al. ( ) ), reduced working time (cockx & ghirelli ) , and delays in finding employment (genda et al. ) , among other factors. moreover, strategic responses to these shocks, such as migration (feigenbaum ) , temporary exit from the labor force (hershbein ) , and human capital acquisition (charles et al. , barr & turner , may themselves have implications for short-and long-run labor market prospects, as separate from those arising directly from the initial shock. these studies thus strongly suggest that downturns may have important -overhang‖ that may potentially -reduce prosperity for decades to come,‖ both for directly-affected cohorts and the wider economy (rothstein , p. ) . accordingly-and bearing in mind that under covid- , peak unemployment rates for younger workers have been nearly three times the national average -very-long-run and even intergenerational evidence on these issues can be especially valuable. recent work in economic history has looked to the great depression in order to offer precisely this sort of perspective. these studies show substantial and persistent penalties for all workers in severely-hit areas, but especially for new labor market entrants, who faced very different constraints and scope for adaptation than did incumbent workers. moulton ( ) , for instance, finds a substantial earnings penalty amongst less-educated american men just entering the labor market in . while there are large adverse effects for those born in severely-affected states, this age-at-downturn penalty disappears in lessaffected states. likewise, examining evidence on labor force transitions using large-scale linked microdata from the u.s., arthi et al. ( b) show that many younger workers during the depression accepted work that they otherwise might not have considered in better economic times-whether because of their now-dire need, the additional competition from older workers, or some combination of these factors. moreover, many young people seeking work were locked out of the labor market completely by their older counterparts, who now remained in the labor force (or even re-entered it) at higher rates. evidence on occupational transitions and socioeconomic mobility also suggest important career-stage gradients in scarring: younger workers were crowded out of the best local job opportunities by their older counterparts, with young workers in more rural areas pushed out of farming by older workers who retained these jobs at higher rates, and into general laborer and non-occupational positions; and those in more industrial areas being pushed into farming, the less desirable class of occupations in these areas. importantly, while both of these outcomes represent a short-run penalty for newer labor market entrants, the long-run implications for wellbeing may be very different, given the rapid urbanization and the incipient decline of the agricultural sector that was to come. indeed, by providing the impetus to leave agriculture (or by prompting higher rates of out-migration-younger labor market cohorts irrespective of sector were also likelier to have moved across state lines or into urban areas during the depression, perhaps in response to the dearth of local opportunities for inexperienced workers), the great depression may have had a small silver lining for young rural workers. however, at least in the short run, it served to hamper upward mobility-or even, to induce downward mobility. for instance, liu & fishback ( ) show that though concerns over skill depreciation and mismatch during spells of un-or underemployment animated depression-era policymakers, new deal programs largely failed to match workers to jobs that used their skills, often resulting in lower incomes and transitions into lower-skilled employment or unemployment-though at least some general human capital was maintained. meanwhile, feigenbaum ( ) finds that by , intergenerational mobility had fallen for men growing up in cities severely hit by the depression. migration-in particular, the superior destination choices of the sons of richer fathers-was an important mechanism behind these results, again emphasizing the capacity of large adverse shocks to exacerbate rather than level preexisting inequalities. the history of past pandemics and economic downturns provides sobering guidance for what we might expect from the current covid- crisis. there is a complicated relationship between health and economic productivity that will shape the immediate and latent effects of covid- in both obvious and subtle ways. given that these latent effects unfold over decades and even generations, economic history is uniquely capable of providing evidence on the potential long-term costs of the pandemic. experience from both historical pandemics and historical recessions can inform our view of the possible long-run effects of covid- , and how we might mitigate these costs. the experience of the influenza pandemic suggests that disease exposure can impact individuals throughout their lifetimes, both directly through poorer ongoing health, and indirectly through reduced investment in human capital. the costs were not limited to those individuals directly exposed; instead, they spilled over within households and across space, sectors and generations. moreover, while mortality is salient, and the saving of lives remains perhaps the primary objective during a pandemic, avoiding and compensating for morbidity is arguably as important a matter of policy concern, especially in the context of possible long-run effects. particularly in a pandemic where large shares of prime-aged people fall ill (as in the pandemic), or in pandemics where many are infected but ultimately survive (as in both the pandemic and covid- ), experiences of pandemic illness may have lasting effects over the life-course, either through the initial illness (which may, for instance, compromise fetal nutrition, reduce work capacity, or permanently damage health), or through its sequelae later in life. the great depression points to other long-term effects that are likely to emerge from the pandemic-related slowdown in economic activity: both being born or entering the labor market during the great depression led to economic penalties well into adulthood, and constraints on migration had adverse effects on individuals and firms. importantly, history shows us that these two types of harms are mutually reinforcing: damage to health tends to undermine labor market prospects in the long run, while damage to labor market prospects tends to undermine health in the long run. researchers and policymakers should therefore consider the potential for these long-run costs when weighing the short-term costs and benefits of pandemic control and fiscal intervention. history suggests potentially massive future costs for both the economy and the safety net arising from the dampened economic fortunes, chronic health issues, and foregone fertility of cohorts impacted by covid- . given that human capital investments are generally more productive the earlier they are implemented, this suggests that policy interventions undertaken now, such as cash relief, could be especially cost-effective, and their net long-run benefits tremendous. economic history also reveals that we cannot think of the health and economic impacts of covid- independently of one another. past pandemics indicate that regardless of the pathology of a disease, its impacts are often a function of economic conditions. while some pandemics spared no class, many disproportionately impacted individuals of lower socioeconomic status due to a variety of factors including their occupations, living conditions, and access to healthcare. these individuals are at greater risk of exposure, face greater harms conditional on exposure, and are less able to remediate these harms. we have already seen this taking place with covid- , and need to remain aware that the spread of the disease and the severity of its effects will be in part a function of the spatial distribution of residence, economic activity, and environmental harms. these disparate impacts of the virus itself will be compounded by the associated economic downturn. to the extent that the covid- economic downturn limits exposure to environmental and work-related hazards, or reduces spending on unhealthy behaviors, non-coronavirus related dimensions of health may actually improve. however, both the modern literature on developing countries and the u.s.'s experience during the great depression suggest that the severe economic downturn may compound health problems in areas with lower baseline incomes and weaker safety nets. identifying the channels through which income loss and general recession conditions impact health is necessary for properly interpreting any observed changes in population health levels during covid- , and for designing effective policies to safeguard health. successful implementation of these policies also requires a firm understanding of history-roadblocks to public health initiatives during past pandemics associated with institutional structures and individual attitudes offer cautionary tales for our current crisis. while economic history provides useful insights for the current pandemic, the way in which the pandemic is unfolding also provides a fresh perspective with which to revisit the past. we are witnessing the actions that individuals and families, workers and firms, citizens and public officials alike, take to guard against the pandemic, and the damage it has done to the economy. we are witnessing how these responses change as new information on covid- emerges. the current pandemic affords us unprecedently rich and disaggregated data that, even while still evolving, can give new insights into which groups might warrant additional study in past pandemics. all of these dimensions of covid- can help us reshape the roadmap for studying the economic history of pandemics. one of the most important ways the covid- experience can shape the direction of economic history may not be in seeking out the similarities but rather focusing on differences. while the rate of transmission and severity of the effects of covid- have historical analogues, many relevant features of the world are meaningfully different-among them, the global nature of production; flows of people, goods, and information; urbanization; baseline living standards; medical technology; public health infrastructure; and the role of government. these differences can help us understand both past and present pandemics better; moreover, they help us understand how and why things have changed. for example, the covid- shutdowns have been more far-reaching, and the corresponding economic downturn more damaging, than we might have predicted from previous pandemics. can these differences explain the far greater economic costs of covid- relative to similarly lethal pandemics of the th century? this suggests an important direction for future economic history work: identifying why the nature of the response to public health crises differed, and why the resulting economic consequences were often smaller historically. engaging in this work also allows us to grapple with challenging questions about tradeoffs between population health and economic activity. these tradeoffs are incredibly difficult to tackle head on in the face of an unfolding crisis; they force unfathomable but unavoidable choices on policymakers often working with limited information. by offering insight into not just the actions but also the short-and long-run outcomes of governments, firms, and individuals, economic history can guide us to better decisions in this and future crises. the colonial origins of comparative development: an empirical investigation infuenza and pneumonia mortality in large cities in the united states in years surrounding the pandemic plague in seventeenth-century europe and the decline of italy: an epidemiological hypothesis is the influenza pandemic over? long-term effects of in utero influenza exposure in the post- u human capital development before age five.‖ pages the influenza pandemic and subsequent health outcomes: an analysis of sipp data the dust was long in settling': human capital and the lasting impact of the american dust bowl . -recessions, mortality, and migration bias: evidence from the lancashire cotton famine estimating the recession-mortality relationship when migration matters.‖ nber working paper # labor market scarring in the very long run: evidence from large-scale longitudinal microdata -disease, downturns, and wellbeing: economic history and the long-run impacts of covid- aggregate income shocks and infant mortality in the developing world fetal and infant origins of adult disease: papers out of work and into school: labor market policies and college enrollment during the great recession smoke, and death‖ bituminous coal and american home heating.‖ nber working paper # non-pharmaceutical interventions and mortality in u.s. cities during the great influenza pandemic, - .‖ nber working paper # the coronavirus and the great influenza pandemic: lessons from the "spanish flu" for the coronavirus's potential effects on mortality and economic activity (no. w ) the redistributive effects of pandemics: evidence on the spanish flu.‖ universidad carlos iii de madrid working papers in economic history # - forthcoming. -the influenza pandemic and its lessons for covid- fetal shock or selection? the influenza pandemic and human capital development.‖ nber working paper # the great plague in london in . the great plague in london in les hommes et la peste en france et dans le pays européens et méditerranées disease and development: evidence from the american south disease and development: evidence from hookworm eradication in the american south malaria eradication in the americas: a retrospective analysis of childhood exposure disease and fertility: evidence from the influenza pandemic in sweden.‖ iza discussion paper # the economic effects of the influenza epidemic on the long term effects of the u.s. influenza pandemic the virus of fear: the political plague and the poor in renaissance florence housing booms and busts, labor market opportunities, and college attendance does air quality matter? evidence from the housing market the impact of air pollution on infant mortality: evidence from geographic variation in pollution shocks induced by a recession pandemic influenza and socioeconomic disparities: lessons from chicago.‖ proceedings of the national academy of sciences the - influenza pandemic in england and wales: spatial patterns in transmissibility and mortality impact.‖ proceedings. biological sciences a farewell to the alms: a brief economic history of the world what explains cross-city variation in mortality during the influenza pandemic? evidence from u pollution, infectious disease, and mortality: evidence from the spanish influenza pandemic canary in a coal mine: infant mortality, property values, and tradeoffs associated with mid- th century air pollution.‖ nber working paper # scars of recessions in a rigid labor market.‖ labour economics multigenerational effects of early-life health shocks.‖ demography pandemics depress the economy, public health interventions do not: evidence from the flu health and the economy in the united states from to the present intergenerational transmission of paternal trauma among us civil war ex-pows america's forgotten pandemic: the influenza of environmental health risks and housing values: evidence from , toxic plant openings and closings was plague an exclusively urban phenomenon? plague mortality in the seventeenth-century low countries economic conditions and mortality: evidence from years of data estimated global mortality associated with the first months of pandemic influenza a h n virus circulation: a modelling study guns, germs, and steel: the fates of human societies pest und staat: von der institutionengeschichte zur sozialen konstruktion. neue wege in der seuchengeschichte state capacity and public goods: institutional change, human capital, and growth in historic germany how positive was the positive check? investment and fertility in the aftermath of the influenza in india.‖ mimeo covid- among workers in meat and poultry processing facilities - states plague ports: the global urban impact of bubonic plague does job loss shorten life smallpox: gone but not forgotten is there a skills mismatch in the labor market?‖ chicago fed letter intergenerational mobility during the great depression aggregate economic shocks births, deaths, and new deal relief during the great depression hard times in the land of plenty: the effect on income and disability later in life for people born during the great depression the effects of in utero exposure to the influenza pandemic on family formation long-term effects of a recession at labor market entry in japan and the united states growing up in a recession emerging infections: pandemic influenza fear, lockdown, and diversion: comparing divers of pandemic economic decline .‖ nber working paper # disparities in influenza mortality and transmission related to sociodemographic factors within chicago in the pandemic of reply to shanks and brundage: many plausible mechanisms of pandemic mortality disparities.‖ proceedings of the national academy of sciences food expenditure and nutritional quality over the great recession the basic reproduction number (r ) of measles: a systematic review the brazilian bombshell? the long-term impact of the influenza pandemic the south american way.‖ nber working paper # effects of social distancing policy on labor market outcomes.‖ nber working paper # public health interventions and epidemic intensity during the influenza pandemic the economics, technology, and neuroscience of human capability formation.‖ proceedings of the national academy of sciences the long-lasting influenza: the impact of fetal stress during the influenza pandemic on socioeconomic attainment and health in sweden graduating high school in a recession: work, education, and home production the distribution of environmental damages die deutsche stadt im mittelalter - : stadtgestalt, recht, verfassung, stadtregiment the long-term labor market consequences of graduating from college in a bad economy labor demand in the time of covid- : evidence from vacancy postings and ui claims.‖ nber working paper # public health interventions and economic growth: revisiting the spanish flu evidence.‖ mimeo does in utero exposure to illness matter? the influenza epidemic in taiwan as a natural experiment good skills in bad times: cyclical skill mismatch and the long-term effects of graduating in a recession effects of new deal spending and the downturns of the s on private labor markets in / .‖ explorations in economic history depression babies: do macroeconomic experiences affect risk taking? can the spanish influenza pandemic of explain the baby boom of in neutral norway?‖ population pandemic morbidity: the first wave hits the poor, the second wave hits the rich a socially neutral disease? individual social class, household wealth and mortality from spanish influenza in two socially contrasting parishes in kristiania - nonpharmaceutical interventions implemented by u.s. cities during the - influenza pandemic parasites, pathogens, and progress: diseases and economic development can pandemics affect educational attainment? evidence from the polio epidemic of why are recessions good for your health? -cyclicality, mortality, and the value of time: the case of coffee price fluctuations and child survival in colombia what is a pandemic the great depression of income: historical estimates of the longer-run impact of entering the labor market during a recession business recession, alcohol consumption, drinking and driving laws: impact on oklahoma motor vehicle fatalities and fatal crashes estimation of potential global pandemic influenza mortality on the basis of vital registry data from the - pandemic: a quantitative analysis the influenza pandemic hastened the decline of tuberculosis in the united states: an age, period the columbian exchange: a history of disease, food, and ideas the long-run effects of pandemic influenza on the development of children from elite backgrounds: evidence from industrializing japan race and influenza pandemic in the united states: a review of the literature epidemiological evidence of an early wave of the influenza pandemic in new york city.‖ proceedings of the national academy of sciences the short-and long-term career effects of graduating in a recession the making of an investment banker: macroeconomic shocks, career choice, and lifetime income what happens to household formation in a recession?‖ th annual areuea conference paper childhood health and sibling outcomes: nurture forcing nature during the influenza pandemic.‖ explorations in economic history yellow fever epidemics and mortality in the united states racial disparities in exposure, susceptibility, and access to health care in the u.s. h n influenza pandemic the lost generation? scarring after the great recession are recessions good for your health? healthy living in hard times does drinking really decrease in bad times? early-life disease exposure and occupational status: the impact of yellow fever during the th century high contagiousness and rapid spread of severe acute respiratory syndrome coronavirus . emerging infectious diseases shaped by booms and busts: how the economy impacts ceo careers and management styles,‖ the review of financial studies variable mortality during the influenza pandemic in chicago the impact of influenza epidemics on mortality: introducing a severity index the best of times, the worst of times: understanding pro-cyclical mortality banking crises and mortality during the great depression: evidence from u.s. urban populations, - job displacement and mortality: an analysis using administrative data the incidence of influenza among persons of different economic status during the epidemic of the engine and the reaper: industrialization and mortality in late nineteenth century japan influenza: the mother of all pandemics the pox of liberty: how the constitution left americans rich, free, and prone to infection the diffusion of the influenza pandemic of in hartford bad start, bad match? the early career effects of graduating in a recession for vocational and academic graduates what happened to the us economy during the influenza pandemic? a view through high-frequency data.‖ federal reserve bank of chicago working paper how the west ‗invented' fertility restriction malthusian dynamism and the rise of europe: make war, not love the three horsemen of riches: plague, war, and urbanization in early modern europe who report on global surveillance of epidemic-prone infectious diseases. world health organization. . covid- strategy update the gift of the dying: the tragedy of aids and the welfare of future african generations key: cord- -dc tyu authors: zahid, marij; ali, arif; baloch, naveed jumman; noordin, shahryar title: effects of coronavirus (covid- ) pandemic on orthopedic residency program in the seventh largest city of the world: recommendations from a resource-constrained setting date: - - journal: ann med surg (lond) doi: . /j.amsu. . . sha: doc_id: cord_uid: dc tyu the coronavirus (covid- ) pandemic has hit the entire world hard. since its inception from wuhan china the whole world is affected now. health care facilities and workers are overwhelmed and the situation is changing on daily basis. with the changes in the dynamics of the hospitals, residency and fellowships training programs have also suffered undoubtedly. due to decreased elective cases and outpatient clinics surgical training gets compromised, however on the other side this physical distancing and isolation have proven to be effective measures in controlling the disease. in this article we share our experience of effect of covid- pandemic on our orthopedic residency program and how we coped along with it. we also discussed some way forwards in the article. seventh largest city of the world: recommendations from a resource-constrained setting. abstract: the coronavirus (covid- ) pandemic has hit the entire world hard. since its inception from wuhan china the whole world is affected now. health care facilities and workers are overwhelmed and the situation is changing on daily basis. with the changes in the dynamics of the hospitals, residency and fellowships training programs have also suffered undoubtedly. due to decreased elective cases and outpatient clinics surgical training gets compromised, however on the other side this physical distancing and isolation have proven to be effective measures in controlling the disease. in this article we share our experience of effect of covid- pandemic on our orthopedic residency program and how we coped along with it. we also discussed some way forwards in the article keywords: coronavirus; quarantine; orthopedic surgeons; pandemics; medical education introduction: since the inception of novel coronavirus in wuhan, china, the global situation has changed dramatically in every sector of life. the changes are dynamic and constantly evolving, even more so as our country has not yet reached the peak, as we were quick to learn and implement social distancing from the world. furthermore, our government has been following the process of screen, test and quarantine for confirmed cases which has resulted in containing the disease. in the beginning of march , pakistan sealed its borders with china, iran and afghanistan and international arrivals through flights were also curtailed as our airports were closed. our hospital diagnosed the first covid- pcr positive case in the country on february who was a student returned from iran [ ] . our section of orthopedic surgery was the first in our tertiary care hospital to cut down outpatient clinic numbers by restricting practice to only "must be seen" follow-up patients especially who have underwent surgery in prior weeks and so on, even before our university hospital published their guidelines. as of morning of may , total corona virus cases in pakistan are , with mortalities [ ] . the city of karachi, where our tertiary care hospital is located is in lock down since march , which as per the last government announcement was switched to a smart lockdown (re-opening of some semi-essential sectors) on may . the two vital practices of "social distancing" and "quarantine" have been key to control the situation both in our community and hospital setup [ ] . health care workers being at the front line are more likely to contract the virus due to the current pandemic; yet it is also important to maintain a healthy resident workforce to sustain the ongoing patient care. as orthopedic surgeons are not the usual front line health care providers, adapting to these protective practices in our day to day inpatient and outpatient clinical work faced us with several challenges. various practices have been adopted by the hospitals worldwide to fight this issue which patient assessment and surgical hands on skills [ ] . in the few past months, the surgical residency program has suffered a lot worldwide in terms of suspension of elective cases as a sequelae of succumbing to a lower patient load [ ] . despite the lower patient surgical hands on for residents however, this pandemic has a brighter side in that it has opened multiple positive avenues and learning opportunities for residents that were never explored before. it is still unpredictable when this pandemic will be under control and the situation slowly normalizes. will there be a second peak and how badly would it hurt? everyone is currently living in such ambiguity. we in this article share our experience of orthopedic residency program in an urban tertiary care center and delineate our division of work force during this pandemic and propose few recommendations. education. currently we are in the upsurge phase of the pandemic and different mathematical models have projected that we may see the peak in the next two months, depending upon which model is considered. if this pandemic turns into an endemic in our part of the world in the near future, then we should be able to accommodate for the time lost, otherwise strategies such as increasing the duration of the residency program may have to be considered. this approach would seems to be essential to make up for loss of resident hands on and clinical experience before they step into their surgical career, in order to ensure we graduate safe and appropriately trained surgeons from the program. despite of decreased clinical work, our hospital has not resorted to layoffs and furloughs. % bedside care staff will not take any pay cuts. senior level faculty and staff including management will have pay cuts that have been announced for three months with review thereafter. this has allowed us to manage our workforce and set policies in place to ensure we hit the road running quarantine role in the control of corona virus in the world and its impact on the world economy residency and fellowship program accreditation: effects of the novel covid- ) pandemic strategic planning and recommendations for healthcare workers during the covid- pandemic key: cord- -muybvyqa authors: fan, victoria y; jamison, dean t; summers, lawrence h title: pandemic risk: how large are the expected losses? date: - - journal: bull world health organ doi: . /blt. . sha: doc_id: cord_uid: muybvyqa there is an unmet need for greater investment in preparedness against major epidemics and pandemics. the arguments in favour of such investment have been largely based on estimates of the losses in national incomes that might occur as the result of a major epidemic or pandemic. recently, we extended the estimate to include the valuation of the lives lost as a result of pandemic-related increases in mortality. this produced markedly higher estimates of the full value of loss that might occur as the result of a future pandemic. we parametrized an exceedance probability function for a global influenza pandemic and estimated that the expected number of influenza-pandemic-related deaths is about per year. we calculated that the expected annual losses from pandemic risk to be about billion united states dollars – or . % of global income – per year. this estimate falls within – but towards the lower end of – the intergovernmental panel on climate change’s estimates of the value of the losses from global warming, which range from . % to % of global income. the estimated percentage of annual national income represented by the expected value of losses varied by country income grouping: from a little over . % in high-income countries to . % in lower-middle-income countries. most of the losses from influenza pandemics come from rare, severe events. few doubt that major epidemics and pandemics will strike again and few would argue that the world is adequately prepared. since the - ebola virus disease outbreak in western africa, the united states national academy of medicine and several other groups [ ] [ ] [ ] have pointed to gaps, and the need for greater investment, in preparation against epidemics and pandemics, of ebola virus disease and other infectious diseases. attempts to justify greater investment have mostly been based on estimates of the industrial and macroeconomic losses attributable to influenza pandemics. [ ] [ ] [ ] [ ] [ ] [ ] [ ] we have recently extended the loss assessment to include a valuation of the lives lost as a result of the increases in mortality resulting from influenza-pandemic risk. the inclusion of such a valuation increased the estimated loss attributable to modelled pandemic risk several fold. below, we discuss our method and summarize our findings. box presents the definition of several of the terms we are using in this paper. most previous economic studies on global influenza pandemics have focused on income losses, through reductions in the size of the labour force and productivity, increases in absenteeism and, importantly, as the result of individual and social measures that interrupt transmission, but disrupt economic activity. while measures such as the per-capita gross national income include the effect of pandemics on income, they also exclude the value of changes in mortality risk to individuals. if, in assessments of investments in pandemic preparedness and mitigation, we neglect this dimension of loss, we will underestimate the value of such investments, relative to alternative uses of public finances. the broader approach that we recently applied, to the assessment of economic losses attributable to pandemic influenza, factors in the intrinsic loss associated with increases in mortality. in effect, this approach assigns a dollar value to small changes in mortality probabilities, using values derived from empirical studies of how individuals and societies actually value changes in mortality risk. [ ] [ ] [ ] [ ] this approach has already been employed extensively in environmental economics , and has also been used in global health, by the lancet commission on investing in health. , past literature we searched google scholar and pubmed® for studies on the economic losses from influenza. almost all of the previous studies examined economic losses in terms of income and ignored the value of, and the loss associated with, mortality risk. the world bank, for example, generated estimates of global income losses under different influenza pandemic scenarios. , it found that a pandemic of the same severity as the influenza pandemic might reduce global gross domestic product by about % and that the disruptive effects of avoiding infection would account for about % of that reduction. another study of the consequences of a range of pandemic severities included an extremely severe scenario that would lead to income losses of over % of gross national income worldwide, including losses of over % of the gross national incomes of lower-income countries. we found other integrative estimates of the magnitude of pandemic risk in two partially proprietary sources. , several studies have examined specific dimensions of the economic impacts of annual influenza, such as direct costs, e.g. medical and hospitalizations costs, and indirect costs, e.g. lost earnings due to illness and productivity costs. there are examples of such studies based in the americas, , , [ ] [ ] [ ] [ ] asia , and europe. , other models have added an estimated value of the intrinsic undesirability of nonfatal illness or of pandemic fear, as seen in the population response to severe acute respiratory syndrome in asia. media coverage may also lead populations to overreact to mild pandemics. abstract there is an unmet need for greater investment in preparedness against major epidemics and pandemics. the arguments in favour of such investment have been largely based on estimates of the losses in national incomes that might occur as the result of a major epidemic or pandemic. recently, we extended the estimate to include the valuation of the lives lost as a result of pandemic-related increases in mortality. this produced markedly higher estimates of the full value of loss that might occur as the result of a future pandemic. we parametrized an exceedance probability function for a global influenza pandemic and estimated that the expected number of influenza-pandemic-related deaths is about per year. we calculated that the expected annual losses from pandemic risk to be about billion united states dollars -or . % of global income -per year. this estimate falls within -but towards the lower end of -the intergovernmental panel on climate change's estimates of the value of the losses from global warming, which range from . % to % of global income. the estimated percentage of annual national income represented by the expected value of losses varied by country income grouping: from a little over . % in high-income countries to . % in lower-middle-income countries. most of the losses from influenza pandemics come from rare, severe events. economic losses of pandemic risk victoria y fan et al. we found only two articles that included estimates of the loss from the elevated mortality associated with influenza pandemics. , of the studies included in a recent systematic literature review on the costs of influenza, only one took account of the value of mortality risks. one strand of economic research has examined the intrinsic value of mortality risks, which is commonly expressed as the so-called value of a statistical life. this value is derived either from questionnaires that canvass how much compensation an individual would demand, to accept a small increase in the probability of their death, or from quantitative studies of the labour market that investigate the trade-offs between small fatality risks and income. , beyond influenza, the value of mortality risks has been included in estimating the costs of vaccine-preventable diseases and in evaluating the economic burdens posed by rheumatic heart disease. far more studies have assessed the burden of specific environmental risk factors. , the value of a statistical life, which is sometimes expressed as the value of a standardized mortality unit (smu), i.e. an increase in the annual risk of death of in , varies by both the age and income of the individual involved. , , in general, the value of mortality is elastic to age and to income, i.e. younger individuals place a higher value on mortality than older individuals, and higher-income individuals generally value mortality more than lower-income individuals. the main findings of our recent study appeared consistent when, in robustness and sensitivity checks, we used estimates that were unconditional on age and estimates with varying income elasticity with respect to the value of mortality. given the uncertain nature of an influenza pandemic, in terms of both when it may occur and how large the mortality risks will be, we applied an expected-loss framework that accounts for the uncertainty over a long period of time. an expected-loss framework incorporates information on the risk of an uncertain event, e.g. a pandemic, with information on the severity or value of that event, e.g. the increase in mortality. although it has been estimated that the - ebola virus disease outbreak led to about deaths, the death toll from a severe influenza pandemic might be times higher than this. in any given year, however, the risk of a severe influenza pandemic is much smaller than that of an ebola epidemic. the use of an expected-loss framework allows policy-makers to compare the expected losses associated with events with relatively high annual probability, but low mortality, e.g. an ebola outbreak, with those of events with relatively low probability but high mortality, e.g. the influenza pandemic. expected-loss frameworks are commonly used, by actuaries in the insurance industry, to calculate the size of premiums, e.g. for flood or health insurance. to value the consequences of uncertain events appropriately, the insurance industry estimates so-called exceedance probability functions. these functions generate estimates of the probability that, over a specified time frame, losses from an uncertain event, e.g. an influenza pandemic, would exceed any specified level. for our analysis, we developed an exceedance probability function for a global influenza pandemic. to parameterize the function, we turned to historical data on global influenza pandemics since the s. [ ] [ ] [ ] [ ] six pandemics in this period led to excess mortality rates ranging between . % and . % of world population. in , this range would be the equivalent of between million and million excess deaths globally. a modelling exercise for the insurance industry concluded that the annual risk of an influenza outbreak on the scale of the pandemic lies between . % and . %. for more severe pandemics, we fitted a parametrized exceedance probability function to modelled data that had been previously reported. , following common practice in the insurance industry, we defined risk, r(s), in terms of the annual probability of a pandemic having a severity exceeding s smus and the return time for s as the expected number of years before a pandemic of at least severity s will occur. if t(s) is the return time, then t(s) = r(s) − . for example, if the annual probability of a pandemic of severity at least s is %, then its return time will be years. if we had access to a function r(s) showing exceedance probability as a function of severity, our analysis could proceed using the expected value of severity of all pandemics. because r(s) is the complementary cumulative of the density for s, we would have expected value of: we calibrated this model using historical estimates of the frequency and severity of influenza pandemics, which we obtained from our literature search on pubmed® and google scholar. for mortality data relating to the influenza pandemic, we also searched the libraries at harvard university and the university of hawai'i for historical documents and life tables. studies were restricted to those with abstracts in english. the consequences of a pandemic, in terms of lost income or lost lives. the expenditures made to prepare for -or recover from -a pandemic. excess death attributable to a given influenza pandemic (expressed in this paper in standardized mortality units or smus -a unit of per per year). the estimated probabilities that, in any given year, pandemics of varying degrees of severity will occur. defined in the probabilistic sense as the sum, across severities, of the losses associated with a pandemic of any given severity multiplied by the probability that a pandemic of that severity will occur in the coming year. note: much of this nomenclature accords with that of the insurance industry. policy & practice economic losses of pandemic risk victoria y fan et al. like other economic studies of pandemic influenza, we identified two main influenza pandemic scenarios in terms of aggregate mortality: moderate and severe. our review classified the pandemic as severe. as the world population in was about million and historical data indicate that there were at least million pandemicrelated deaths in that year, the excess death rate associated with the pandemic was at least . %. a closer examination of the data from india indicate that the true global rate was probably far higher than . %, the pandemic led to million deaths in india [ ] [ ] [ ] and it seems implausible that india accounted for % of all of the pandemic-related deaths at a time when it had % of the world population. however, to be conservative, we estimated an expected annual excess mortality rate of . smus. in the corresponding model for moderate pandemics, we used a global expected excess mortality rate of . smus, as seen in historical moderate pandemics. our calibration pointed to a very fat-tailed distribution. thus, compared with an exponential function, the hyperbolic family of complementary cumulative distributions provided more natural candidates for r(s). we parameterized the hyperbolic function in terms of its expectation and the fatness of its tail. thus: the estimated proportion of annual national income represented by the losses varied according to country income grouping, from a little over . % in high-income countries to . % in lower-middle-income countries ( table ) . the expected-loss framework distinguishes between the loss associated with a certain event that occurred, e.g. the mortality that occurred as a result of the influenza pandemic, and the expected loss associated with an uncertain event over a period of risk exposure. the expected loss combines both the risk of a moderate or severe pandemic and the losses from that event should the event occur. the expectedloss framework thus produces estimates of expected losses of an uncertain event, rather than actual losses of a certainly occurring event. we estimated the expected number of pandemic-related deaths to be about per year. this level of mortality is on a similar scale to that attributable to other, more certain, causes of death, including other major infectious causes of death. importantly, we concluded that most of the expected loss from influenza pandemics results from extreme events. another effort to estimate exceedance probability functions indicated that, among all pathogens that can cause a pandemic, influenza virus was likely to be the predominant cause of pandemic-related mortality. the implication is clear: any efforts at pandemic preparedness need to be most strongly focused on influenza and on preparation for a severe scenario. our results present losses much higher than those found in studies limited to income losses. income losses have been estimated to represent around % and % of the total economic losses associated with a severe pandemic and a mild pandemic, respectively. , in previous studies, across modelled pandemics of all severities, mean income losses were estimated to be us$ billion per year , , i.e. about % of our estimate of total pandemicrelated costs. in terms of the percentage of global income, our estimate of total pandemicrelated losses ( . %) falls within the corresponding intergovernmental panel on climate change's estimates of the costs of global warming ( . - . %). however, the magnitude of future global warming and the associated economic losses are still uncertain. , the same is true for future pandemics. many of the hundreds of studies on the potential costs of climate change have been hampered by the wide variation in estimates of the so-called social cost of carbon. if this cost is set at about us$ per tonne, the cost of the carbon dioxide emissions in would have been about % of global income. , as in many previous attempts to estimate the economic losses associated with a pandemic, many previous attempts to estimate the social costs of carbon have focused on national income accounts, without any explicit valuation of the increases in mortality resulting from climate change. the mortality-associated costs of climate change may be relatively small, however, since the slowness of climate change should allow for compensatory human adaptation. our study had several limitations. first, we ignored the intrinsic undesirability of nonfatal illness and/ or pandemic fear. intense media coverage may lead populations to overreact to mild pandemics. second, our estimates of future pandemic risk and severity, and the economic estimates based on these epidemiological estimates, are relatively crude partly because pandemics remain rare and uncertain events. future modelling should lead to improved estimates over time. third, the assignment of monetary value to small changes in mortality risk and, particularly the relationship between valuation of such risk and both individual income and age at death, remains controversial. however, the results of sensitivity analyses, in which we applied a range of assumptions on these parameters, indicated that our main findings were reasonably robust. in addition to pathogens of pandemic potential, an expected-loss framework may also be applied usefully to malaria and other diseases that have fluctuating incidence. as cases of the disease become rarer as the result of effective interventions, malaria becomes less visible politically and financially, and policy-makers in some countries may have responded by reducing control efforts prematurely. policy-makers, and the societies they serve, could benefit by using an expected-loss framework to estimate the losses associated with uncertain and rare events across the full range of potential outcome severities. this could lead to appropriate and beneficial adjustments to each policy-maker's sense of risk and sense of value and to improved national policies on epidemic and pandemic preparedness. a recent united states national academy of medicine report argued that, given the risks we estimated, policy attention has fallen short. il est nécessaire d'investir davantage dans la préparation contre les grandes épidémies et les pandémies. les arguments en faveur de cet investissement s'appuient en grande partie sur les estimations des pertes au niveau du revenu national que pourrait entraîner une grande épidémie ou une pandémie. récemment, nous avons élargi ces estimations pour y inclure la valeur des pertes faisant suite à des hausses de mortalité dues à des pandémies. cela a donné des estimations nettement plus élevées de la valeur totale de la perte que pourrait occasionner une future pandémie. nous avons paramétré une fonction de probabilité de dépassement pour une pandémie mondiale de grippe et avons estimé que le nombre escompté de décès dus à cette pandémie de grippe était d' environ par an. nous avons calculé que les pertes annuelles découlant du risque de pandémie représentaient environ milliards de dollars des États-unis, soit , % du revenu mondial par an. cette estimation rejoint (dans la fourchette inférieure) celles du groupe d' experts intergouvernemental sur l' évolution du climat quant à la valeur des pertes dues au réchauffement de la planète, qui vont de , % à % du revenu mondial. le pourcentage estimé du revenu national annuel représenté par la valeur escomptée des pertes variait selon la catégorie de revenu des pays: d'un peu plus de , % dans les pays à revenu élevé à , % dans les pays à revenu intermédiaire-tranche inférieure. la plupart des pertes découlant de pandémies de grippe sont dues à des événements rares et graves. Требуется увеличение инвестиций в подготовку к борьбе с крупными эпидемиями и пандемиями. Аргументы в пользу таких инвестиций в значительной степени основаны на оценках потерь в национальном доходе, которые могут возникнуть в результате крупной эпидемии или пандемии. Недавно авторы расширили эту оценку, включив в нее количество людей, погибших в результате увеличения смертности, связанной с пандемией. Это привело к более высоким оценкам полного ущерба, который может возникнуть в результате будущей пандемии. Авторы параметризовали функцию вероятности превышения смертности для глобальной пандемии гриппа и подсчитали, что прогнозируемое число смертей от гриппа и пандемии составляет около в год. Мы подсчитали, что ожидаемые ежегодные потери из-за риска пандемии составляют около млрд долларов США (или , % мирового дохода) в год. Эта цифра находится в пределах оценки (ближе к нижней границе), полученной Межправительственной группой экспертов по изменению климата для оценки риска глобального изменения климата, которая составляет от , до % от глобального дохода. Предполагаемый процент годового национального дохода, представленный ожидаемой величиной потерь, варьировался по группам стран в зависимости от уровня дохода: от немногим более , % в странах с высоким уровнем доходов до , % в странах с низкими и средним доходом. Большинство потерь от пандемии гриппа происходят по причине редких тяжелых явлений. hay una necesidad no satisfecha de invertir más en la preparación para grandes epidemias y pandemias. los argumentos a favor de dicha inversión se basan, en gran parte, en las estimaciones de las pérdidas en los ingresos nacionales que podrían darse como resultado de una gran epidemia o pandemia. recientemente, ampliamos el cálculo para incluir la valoración de las vidas perdidas como resultado del aumento de la mortalidad relacionado con la pandemia. esto dio como resultado unas estimaciones notablemente más altas del valor de la pérdida que podría resultar de una futura pandemia. hemos parametrizado una función de probabilidad de excedencia para una pandemia de gripe mundial y estimado que el número esperado de muertes causadas por una pandemia de gripe es de aproximadamente por año. calculamos que las pérdidas anuales esperadas del riesgo de pandemia son de unos millones de dólares estadounidenses, o el , % de los ingresos mundiales, por año. esta estimación se encuentra dentro, pero cerca del mínimo, de las estimaciones del panel intergubernamental del cambio climático sobre el valor de las pérdidas por el calentamiento global, que oscilan entre el , % y el % de los ingresos globales. el porcentaje estimado de los ingresos nacionales anuales representado por el valor esperado de las pérdidas varió según la agrupación de ingresos del país: de poco más del , % en los países con ingresos altos al , % en los países con ingresos medios o bajos. la mayoría de las pérdidas por pandemias de gripe provienen de casos raros y severos. assessment of economic vulnerability to infectious disease crises from panic and neglect to investing in health security: financing pandemic preparedness at a national level financing of international collective action for epidemic and pandemic preparedness in search of global governance for research in epidemics global macroeconomic consequences of pandemic influenza. sydney: lowy institute for international policy the economic impact of pandemic influenza in the united states: priorities for intervention. emerg infect dis economic losses of pandemic risk victoria y fan et al total economic consequences of an influenza outbreak in the united states. risk anal valuation of the risk of sars in taiwan. health econ on sars type economic effects during infectious disease outbreaks. washington: world bank world bank evaluating the economic consequences of avian influenza. washington: world bank the loss from pandemic influenza risk the cost of air pollution. health impacts of road transport valuing mortality risk reductions from environmental, transport, and health policies: a global metaanalysis of stated preference studies global health : a world converging within a generation the income elasticity of the value per statistical life: transferring estimates between high and low income populations boston: air worldwide pandemics: risks, impacts, and mitigation the annual impact of seasonal influenza in the us: measuring disease burden and costs. vaccine direct medical cost of influenza-related hospitalizations in children economic impact of influenza. the individual's perspective economic costs of influenza-related work absenteeism. value health the cost of influenza in thailand the macroeconomic impact of pandemic influenza: estimates from models of the united kingdom, france, belgium and the netherlands the possible macroeconomic impact on the uk of an influenza pandemic influenza cost and cost-effectiveness studies globally-a review the value of individual and societal risks to life and health during the ' decade of vaccines, ' the lives of . million children valued at $ billion could be saved. health aff (millwood) the economic impact of rheumatic heart disease in developing countries geneva: world health organization the next influenza pandemic: can it be predicted? jama a history of influenza the chronicle of influenza epidemics introduction to pandemic influenza through history modelling a modern-day spanish flu pandemic the population of india and pakistan influenza in india : excess mortality reassessed estimation of potential global pandemic influenza mortality on the basis of vital registry data from the - pandemic: a quantitative analysis observations on mortality during the influenza pandemic characterizing the amount and speed of discounting procedures expert judgments of pandemic influenza risks preparing for the next pandemic climate change temperature impacts on economic growth warrant stringent mitigation policy. nat clim chang updating estimation of the social cost of carbon dioxide global problems, smart solutions: costs and benefits using and improving the social cost of carbon economic aspects of global warming in a post-copenhagen environment the neglected dimension of global security: a framework to counter infectious disease crises the neglected dimension of global security -a framework for countering infectious-disease crises we thank peter sands and bradley chen. vyf has a secondary appointment with harvard t h chan school of public health, boston, united states of america. key: cord- -q pxpw f authors: bradshaw, ralph a.; stahl, philip d. title: on pandemics, pandemonium, and possibilities… date: - - journal: faseb bioadv doi: . /fba. - sha: doc_id: cord_uid: q pxpw f nan we are now over months into a viral pandemic (covid ) that has already left a trail of death and destruction, wreaking social and economic havoc, and disrupting, in most parts of the world, just about every aspect of life-and it is far from over. it is therefore a source of some pride that the scientific and medical professions have responded in exemplary fashion and continue to do so. despite the interruptions to their research programs and careers, scientists have pooled resources and expertise, and health care providers have manned the trenches. the levels of cooperation and sharing throughout the global community are unprecedented as medicine and science have collectively taken on a common foe, often accompanied by the refocusing of individual work at the expense of established activities. there are multiple efforts afoot to develop a vaccine; a number of antivirals are being tested, as are pharmacopoeias of approved drugs that might be repurposed for treating covid ; and new drug development using the powerful tools of modern cell and molecular biology have been launched. indeed, medicine and the biomedical research community has much to show for itself already, and these efforts have certainly justified the generous public support of medical research over the years. this is an important message that needs to be heard on capitol hill, and it is a great time, particularly with work and travel restrictions still largely in place, to contact representatives and senators and remind them that there is no better dollar spent by the government than that which supports biomedical research. the possibilities that could emerge after the pandemic has wound down are truly unique-a potential watershed moment for science, sparked by a new focus on science teaching and training, and by investments in basic and applied research (including science policy), that could better prepare governments and the citizenry for existential threats in the future: pandemics, climate change, food production, etc. continued investments in biomedical research will also continue to yield exciting advances in the treatment of other killers such as cancer, heart disease, and neurodegeneration that, unlike the pandemic, will not have faded away. indeed, there are likely to be many permanent changes in how we live and work that will emerge from the pandemonium (the chaos all around us may not be pandemonium in the usual sense-although merriam-webster does define pandemonium as "a chaotic situation"-but when one considers the economic/social disruptions that have already occurred, it does not seem like such a bad description). for example, there have been significant (positive) effects on air quality resulting from the dramatic reductions in local, domestic, and international travel, and it is likely that telecommuting will become a much more attractive proposition for companies and businesses that are able to incorporate such programs into their operations. similarly, web-based teaching will almost certainly become more prevalent, and there are apt to be substantial changes in how higher education is managed by colleges and universities. although only a couple of months ago most people did not even know the word, pandemics are not new. in fact, we are only just past the th anniversary ( - ) of the worst (modern) pandemic, commonly known as the spanish flu, caused by the influenza a (h n ) virus. since there remains essentially no living memory, the populace today are not really aware of the extent and consequences of this scourge: estimated number of people infected: ~ million (or about one-third of the world's population at that time) and estimated number of deaths: million worldwide (~ occurring in the united states, or about . % of the us population of about million at that time). if one-third of today's world population eventually contracted covid , it would affect ~ . billion people and, at the presently calculated level of lethality, cause over million deaths. there have also been three other influenza pandemics that occurred in - , , and , each triggered by a new influenza virus variant. none of these were as deadly as the agent, but in the first two instances, there were still over million deaths. of course, the influenza a (h n ) and sars-cov- viruses and the diseases they cause are not directly comparable nor are the circumstances in which the pandemics occurred. while the management of the - flu was hampered by a complete lack of knowledge of the causative agent or how to test for it, the identification and a complete structural analyses of the sars-cov- coronavirus occurred very rapidly after the onset of the pandemic in december , and assays of different types for it were developed in just weeks, albeit making these tests widely available has been a major challenge (but this is a political not a medical problem). this is a very significant difference since they do share two key aspects: the causative viruses are unique, that is, no one was exposed to either before, and there was and is (presently) no effective treatment for either affliction. both then and now, prophylaxis that limits or prevents person-to-person transmission was and still is the only effective means for stemming the spread of the pandemic with all the limits and impact on society that that approach must confront. therefore, being able, at least in theory, to identify (and potentially track) individuals who test positive is an enormous advantage that health care providers in did not have; we have the great strides of bioscience to thank for this. the h n flu occurred in three waves in the united states over a period of a little greater than a year, first appearing in april and ending in the summer of . whether covid will follow a similar course is not at the moment predictable. while there is clear evidence that "social distancing" combined with "shelter at home" and the elimination of all social events characterized by any-sized groups of unrelated people has helped to flatten the curve of new infections, it has also come with severe consequences. unhappily, it is not hard to conclude that at least a part of the problems introduced may have arisen from the unintended consequences that often accompany precipitous, hasty, and not well thought through decisions. indeed, worldwide leadership from national to local levels has not been uniformly inspiring, being often slow to act and then overreaching. postulations about possible treatments/approaches based on wishful thinking are not a substitute for scientific facts. it is particularly disturbing to realize that scientists, health care providers, and related experts had anticipated the eventuality of another pandemic. they issued warnings and prepared detailed management plans for just such an event that were to a large degree unheeded. it may have not been possible with the tools and knowledge available a hundred years ago to have significantly curtailed the spanish flu, but the lessons learned from that experience provided excellent guidance of how to react in the future, and that was sadly largely ignored till the magnitude of the covid outbreak became unavoidably clear. like earthquakes, one does not know when the next pandemic will occur, only that it will, and that when it does, science and medicine will be called upon to address it. we need to be better prepared. call your congressional representatives and remind them of that. pandemic (h n virus); rev term=sever e+acute +respi rator y+syndr ome+coron aviru s+ % borg anism % d . accessed centers for disease control and prevention. severe acute respiratory syndrome (sars); rev key: cord- -nma w of authors: de oliveira collet, giulia; campagnaro, ricardo; podadeiro de andrade, mariana; pedro da silva lopes salles, joão; de lourdes calvo fracasso, marina; lopes salles scheffel, debora; maria salvatore freitas, karina; cristina santin, gabriela title: covid- pandemic and pediatric dentistry: fear, eating habits and parent’s oral health perceptions date: - - journal: child youth serv rev doi: . /j.childyouth. . sha: doc_id: cord_uid: nma w of background: severe measures have been implemented around the world to reduce covid- spread with a significant impact on family dynamics. aim: to assess the impact of the pandemic on fear, dietary choices and oral health perceptions of parents. design: questionnaire containing questions was remotely applied to , parents of children aged - years. the questions addressed topics regarding changes in daily routine, dietary habits, fear level, oral health, and variation of income during the pandemic. data analysis included the description of the relative and absolute frequencies of the variables. association tests were performed using fisher's exact and kruskal-wallis tests. results: % of respondents reported income loss. five hundred sixty-eight people denied seeking medical or dental care. . % of respondents revealed changes in the dietary pattern; most of them mentioned an increase in food intake. most parents ( . %) would only seek urgent dental care. there was an association between parents’ willingness to take their children to dental appointments with the fear level (p< . ). conclusions: most families have experienced changes in daily routine and eating habits during the pandemic. parents fear covid- and it impacts their behavior regarding seeking dental care for their children. on march th , the world health organization (who) characterized the coronavirus disease as a pandemic. the disease was first reported in december to who china office as pneumonia of unknown cause. in january , a novel coronavirus (sars-cov- ) was identified, and its genome sequencing was released (world health organization, c) . by september th , the world had registered , , covid- cases and , deaths (european centre for disease prevention and control, ), numbers widely higher than those reported during the two outbreaks with coronaviruses in the recent past. during during - , cases of the severe acute respiratory syndrome (sars) and deaths were registered (world health organization, ) , while , laboratory-confirmed cases of the middle east respiratory syndrome (mers) were reported between - with deaths (world health organization, a). covid- has high contagiousness and rapid spread (sanche et al., ) , mainly through small droplets from the nose and mouth expelled when an infected person speaks, coughs or sneezes (world health organization, b) . even patients with no symptoms seem to be able to transmit the virus (world health organization, b) . the majority of the infections are mild or asymptomatic ( %), while about % are critical infections (world health organization, b) . governments have established policy responses to combat the coronavirus pandemic, including measures to restrict people's transit, business operations, social distancing, cancellation of services, reservations and events (coulthard, ; ministry of economics; peloso, ferruzzi, et al., ) . those measures have led to stay-at-home orders, social distancing, lockdowns, job losses, insecurity, concerns, fears, and a decrease in the quality of life of families worldwide (ornell et al., ) . the suspension of school programs and sports activities during the pandemic has led children and adolescents to spend longer periods at home. the new routine may result in an increase in food intake, including ultra-processed and calorie-dense foods (creswell et al., ; di renzo et al., ) . pietrobelli et al. ( ) suggested that potato chips, red meat, and sugary drink intakes significantly increased in italy during the lockdown. high-carbohydrates diets may lead to several health issues, such as obesity, diabetes, as well as poor oral health. frequent sugar intake favors dental biofilm accumulation and contributes to the development of caries lesions and periodontal disease (colombo & tanner, ) . meanwhile, the pandemic has challenged health professions such as dentistry. concerns regarding dentist's and patient's safety pushed to the reduction of routine dental care (cotrin et al., a; coulthard, ; faccini et al., ; pereira et al., ) , compromising preventive appointments. brazil is the second country in the number of confirmed cases of covid- , with one of the fastest growing coronavirus epidemics in the world (candido et al., ) . the increasing number of cases has divided opinions regarding the economy reopening and resumption of once-routine daily life. it has directly affected habits, bringing concerns toward the future in general. the changes in diet, economic issues, general concerns, fear, added to the lack of preventive dental care, could impact the oral health of children during the enforced stay-at-home orders. thus, this study aimed to assess the fear level, dietary choices and parent's oral health perceptions during the stay-at-home orders period in brazil. a cross-sectional study was carried out using non-probabilistic sampling, with parents of children aged to years, from all geographic regions of brazil (north, northeast, southeast, south, and center-west) . this study was conducted after approval by the research ethics committee of _______________ (protocol # __________). the representative sample size was estimated using a % confidence level and margin of error of %. the sample calculation considered . million children aged - years in brazil in (ibge, ) . the sample size was estimated at a minimum of respondents. a structured questionnaire was developed according to the cherries recommendations (eysenbach, ) . a pilot study was performed to verify the functionality of the questionnaire. for the pilot study, parents ( % of the sample size calculation) were randomly selected from the files of the patients of a single private dental office and they were not included in the final sample. the questionnaire contained mandatory questions about socioeconomic and demographic dates, fear income variability, eating habits and parent's oral health perceptions. the original questionnaire was an open survey, written in brazilian portuguese using the google forms platform and forwarded to parents and caregivers of children aged - years through social media and message apps from may th to june th , . it was available for days. all parents who fit the criteria of having children under years of age could answer the questionnaire. the translated questionnaire is shown in table . all the respondents had access to the consent statement and requested to agree with it before being included in the present study. the informed consent included the object of the study, the responsible researchers and their contact information. the approximate time for the answer to the questionnaire was informed, being about five minutes. the answers and data obtained were stored by the researchers and used only for this study. to ensure the anonymity of each respondent, no identifying information was collected. before sending the questionnaire, participants could change their answers many times as they wish. no duplicate response control tool was used, but if identical responses in sequence were observed, one was excluded. the answers obtained were tabulated in excel (microsoft corp., redmond, usa), and the statistical analysis was performed using the ibm-spss . software. for statistical analysis, some variables were categorized. the 'state' variables were scored according to the number of cases per , inhabitants, according to national data at the time of the study, being 'up to , cases', ' , to , cases', ' , to , cases' and 'over , cases'. the fear level was categorized into ' to ', ' to ', ' to ' and ' to '. fear levels - and - were considered moderate and high fear, respectively. data analysis included the description of the relative and absolute frequencies of the variables. association tests were performed using fisher's exact and kruskal-wallis tests for ordinal variables. a total of , questionnaires were filled in by people from states and the federal district. no response was obtained from the state of acre (north). the great majority of respondents ( . %) were parents (mother/father), with an average age of . years (s.d.= ± . ). most families ( %) disclosed a reduction in income, with . % reporting a slight reduction and . % drastic reduction or total loss of income. regarding the number of people living in each house, . % of the households had three to four people, and . % of respondents had or children aged to years. no association was found between these variables and the reported presence of caries lesions, dental pain or dental trauma (p> . ). only . % of respondents had confirmed covid- , and . % had symptoms but were not tested. five hundred sixty-eight people declared not leaving their houses for medical or dental appointments, and were not doing leisure activities. forty-three percent said they were leaving their houses only when necessary, and . % stated leaving their houses to work. . % of respondents reported changes in eating habits during the pandemic; most of them revealed an increase in food intake ( figure ). of those who claimed changes in eating habits, only . % said they were choosing healthier foods, while the others increased the consumption of processed foods, pasta and snacks ( figure ). families with drastic or total loss of income are eating less than before or opting for cheaper food (p< . ) ( table ) . no association was found between the caries perception of parents and changes in food consumption (p= . ). regarding their children's oral hygiene, . % of parents reported brushing their children's teeth during the pandemic, . % brushed sometimes and only . % did not brush. there was no significant association between brushing the teeth and the variables tooth pain, presence of dental caries and change in dietary pattern. regarding oral health, . % of parents/caregivers reported their children were undergoing dental treatment before the pandemic. however, only . % of total respondents are willing to take their children to dental care regardless of the procedure; . % would only seek urgent care, and . % would not seek dental care at all. the frequency of distribution of dental pain reports, the presence of caries lesions and dental trauma are shown in table . fifty-one people declared their children experienced dental trauma during the pandemic. however, % of them did not seek dental care. association was found among parents/caregivers' willingness to take their children to dental appointments, fear level (p< . ), and the local number of covid- cases (p< . ) ( table ) . when the fear level was assessed, . % of respondents reported a level of fear between and , while . % said their fear level is between and . for billions of people across the world, daily life has changed dramatically in the past months. the coronavirus pandemic has required adaptations from adults, youth and children in the way they study, work and interact with others. the new routine may impact family wellbeing by reducing its income, raising fears, increasing anxiety, stress, and instability (cotrin et al., b; ornell et al., ; parsons, ; peloso, pini, et al., ) . in the course of the present work, brazil recorded an increasing number of daily cases of covid- , reaching its highest number of new confirmed cases ( , ) on june th . this compelled the extension of stay-at-home orders, social distancing and restrictions, exacerbating the risk of an economic recession. this study found that % of the participants from states and the federal district of brazil lost income during the pandemic, . % of them reported drastic reductions in family income. in a single-hit scenario, brazil's gdp is expected to fall by . %, while a decrease by . % may be experienced if a second wave of the pandemic imposes further lockdowns. financial instability, unemployment, economic crises, social distancing, self-isolation, and potentially life-threatening diseases are impacting people's concerns and mental health around the world (knipe et al., ) . in the present study, over % of respondents reported fear levels equal to or higher than when the likert scale was applied, while . % declared fear levels or . fear is present since the early stages of human development (papalia & feldman, ) . it is a non-pathological emotion, consequence of real or imagined threat (burnham & gullone, ) and results from risk assessments (papalia & feldman, ) . however, high levels of fear may produce negative health outcomes and ultimately may cause emotional and physical damage, as it impedes people from naturally performing daily activities (balan et al., ) . a significant association was found between the level of fear, the local number of contaminated and seeking dental care. families living in areas with higher numbers of covid- cases fear more for safety than those living in less affected areas. it results in greater precaution regarding the seek for dental treatments since parents with higher levels of fear are also those who would either take their children to the dentist only in dental urgencies ( . %) or would not take them at all ( . %) . the concerns of parents/caregivers regarding covid- may be especially high when it comes to children since its sign and symptoms are not well established at young ages (mallineni et al., ) . adverse manifestations of covid- have been reported in children, such as the kawasaki disease-like illness related to the infection by sars-cov- observed in europe and the united states (choi, ) . however, ludvigsson ( ) found, in a systematic review, that infected children presented milder symptoms of covid- and also a better prognosis than adults. studies have shown that people have postponed medical treatments due to the fear of contracting covid- , which may increase the risk of serious health issues in the near future (karacin et al., ; omarini et al., ; teoh et al., ) . a similar trend was observed in the present study regarding oral health. about % of respondents said they are not leaving their houses to attend to medical or dental appointments, and % of those who reported that their children were victims of dental trauma during the pandemic did not seek dental care. besides that, . % of the children had their dental treatment temporarily suspended. the lack of preventive and curative care may negatively impact the oral health of children all over the country and trigger the need for future public actions to address those impacts. the new routine, work-at-home for parents, remote classes for children and economic instability have contributed to changes in dietary habits (di renzo et al., ) . about % of respondents said they increased the intake of high-carb foods. pietrobelli et al. ( ) correlated the social distancing period to the summer vacation, when children's carbohydrate intake considerably increases, with a direct impact on childhood obesity. families with drastic or total income loss reported eating less or choosing cheaper foods during the pandemic. more affordable foods may include pasta, sandwiches, snacks, and other foods with low nutritional value and high sugar content. those diet changes not only affect general health but also increases the risk of caries development. in addition to the damage caused by the change in dietary pattern to oral health, this change can cause an increase in obesity, nutritional deficiencies, among others. at the same time, there are the psychological effects of the pandemic on children (spinelli et al., ) , which are somehow linked to the changes in food intake patterns and oral hygiene routine. although this study found no association between parents' perception of caries lesions, food intake and oral hygiene, one has to consider that the questionnaire was filled in a relatively early stage of the pandemic in brazil. the effects of dietary habits and decreased care with oral hygiene may become more evident in the next months. the present study concluded that the covid- pandemic has negatively impacted the eating habits and dental care of children in brazil. furthermore, it has trigged moderate and high levels of fear among parents/caregivers. as an alternative to offer dental assistance during these unusual times, future studies should evaluate the effectiveness of 'teledentistry'. it has been approved in brazil by the federal council of dentistry ( ) and allows parents and children to have video or phone appointments, with dentists providing a safe triage, sharing information on oral hygiene and health (aziz & ziccardi, ) . there are no fundings to declare. no potential conflict of interest was reported by the author(s). the data are available from the authors upon request. . on a scale of to , where is no fear and is terror, indicate the option that best describes your fear of the pandemic. ; ; ; ; ; ; ; ; ; ; . which alternative best describes the impact of the pandemic on your family income. family income not impacted; slightly reduced; drastically reduced; total loss of income; increased during the pandemic. . there has been any change in food consumption in your home during the pandemic? yes, we are eating cheaper foods; eating less than before; eating more than before; there was no change in food intake; other (the volunteer could write the answer). . there has been any change in eating habits at your home during the pandemic? (volunteer could select one or more options). we are consuming more processed food with sugar such as soft drinks, sweets and cookies; consuming more pasta and carbohydrates; consuming more healthy food such as fruits and vegetables; consuming more snacks and/or frozen food; nothing has changed. . how is your family's daily routine during the pandemic? we are not leaving the house for anything; leaving the minimum necessary (pharmacy, supermarket, etc.); leaving just to work; leaving the house as usual. . do you or anyone in your household have had symptoms of covid- ? yes, but the person was not tested; yes, the test was negative for covid- ; yes, the test was positive for covid- ; no one has had kruskal-wallis test telemedicine using smartphones for oral and maxillofacial surgery consultation, communication, and treatment planning fear level classification based on emotional dimensions and machine learning techniques the fear survey schedule for children--ii: a psychometric investigation with american data evolution and epidemic spread of sars-cov- in brazil. science, eabd can we get a clue for the etiology of kawasaki disease in the covid- pandemic? the role of bacterial biofilms in dental caries and periodontal and peri-implant diseases: a historical perspective urgencies and emergencies in orthodontics during the coronavirus disease pandemic: brazilian orthodontists' experience impact of coronavirus pandemic in appointments and anxiety/concerns of patients regarding orthodontic treatment dentistry and coronavirus (covid- ) -moral decision-making research review: recommendations for reporting on treatment trials for child and adolescent anxiety disorders -an international consensus statement eating habits and lifestyle changes during covid- lockdown: an italian survey covid- situation update worldwide improving the quality of web surveys: the checklist for reporting results of internet e-surveys (cherries) dental care during covid- outbreak: a web-based survey resolution cfo continuous national household sample survey (pnad how does covid- fear and anxiety affect chemotherapy adherence in patients with cancer mapping population mental health concerns related to covid- and the consequences of physical distancing: a google trends analysis systematic review of covid- in children shows milder cases and a better prognosis than adults coronavirus disease (covid- ): characteristics in children and considerations for dentists providing their care brazil's policy responses to covid- cancer treatment during the coronavirus disease pandemic: do not postpone, do it! pandemic fear" and covid- : mental health burden and strategies psychosocial development in second childhood in human development covid- , children and anxiety in notes from the field: concerns of health-related higher education students in brazil pertaining to distance learning during the coronavirus pandemic. evaluation and the health professions how does the quarantine resulting from covid- impact dental appointments and patient anxiety levels? biological and social aspects of coronavirus disease (covid- ) related to oral health lockdown on lifestyle behaviors in children with obesity living in high contagiousness and rapid spread of severe acute respiratory syndrome coronavirus parents' stress and children's psychological problems in families facing the covid- outbreak in italy a global survey on the impact of covid- on urological services summary of probable sars cases with onset of illness from mers situation update q&a on coronaviruses (covid- ) were any of your children ( - years old) undergoing dental treatment before the pandemic? (volunteer could select one or more options). no; yes, orthodontic treatment; yes, caries treatment; yes, because of toothache; yes the pandemic? yes, for any procedure; yes, but only for urgent treatments if not, for what reason? risk of contracting covid- ; the dental treatment is not urgent; my child/i has/have symptoms of covid- have you been able to brush your children's teeth during the pandemic? yes; no; sometimes has any of your children experienced dental trauma during the pandemic? no; yes, i sought care right after the trauma and my child was assisted; yes, but i did not seek care; yes, i sought care other (the volunteer could write the answer) have you noticed any cavities/caries in your children's teeth during the pandemic? no; yes, i sought care and my child was assisted yes, but i did not seek care; yes, i sought care has any of your children experienced toothache during the pandemic? no; yes, i sought, and my child was assisted yes, but i did not seek care; yes, i sought care key: cord- - qqyixun authors: preti, emanuele; di pierro, rossella; fanti, erika; madeddu, fabio; calati, raffaella title: personality disorders in time of pandemic date: - - journal: curr psychiatry rep doi: . /s - - -w sha: doc_id: cord_uid: qqyixun purpose of review: we report evidence on the negative psychological effects of pandemics in people with personality disorders (pds) and on the role of personality pathology in compliance with mitigation-related behaviors. considering the paucity of studies, after a description of the main features of pds, on the basis of the current literature on pandemic and quarantine mental health impact, we trace some clinical hypotheses. recent findings: paranoid traits and detachment (cluster a) might lead to worse psychological outcomes. cluster b patients may show more intense stress-related reactions and react strongly to social distancing, especially considering borderline personality disorder. cluster c patients might be particularly prone to anxiety and stress due to fear of contagion and may be less flexible in adaptation to new routines. evidence on compliance with mitigation measures is mixed, with lower compliance in cluster b patients and higher in cluster c ones. summary: we suggest that pd patients might be particularly affected by pandemics. furthermore, they might react differently, according to their main diagnosis. similarly, compliance with mitigation measures may differ according to specific pds. our results should be considered as a starting point to reflect on therapeutic strategies to be adopted in the post-covid- situation. coronavirus disease (covid- ) represents a major threat to public health. after the first outbreak in wuhan (hubei, china) in december and the declaration of a global pandemic by the world health organization (who) on march , , the virus is still consistently spreading in countries, with more than million patients infected and more than , deaths by the time we are writing. in light of these events, psychological responses to pandemic situations have become a major topic of interest, both from a research and clinical point of view. empirical studies and scientific reviews about the consequences of pandemics and quarantine measures in terms of mental health are concordant in concluding that both short-and long-term negative psychological effects can be observed in community people [ , ] and healthcare workers [ ] . moreover, a recent review suggests relevant negative psychological effects of pandemics also in people with pre-existing mental health disorders [ ••] . however, little is known on the specific effects of pandemics on patients with personality disorders (pds). empirical literature on the effect of pandemic on patients with personality pathology, however, lacks. pds are severe mental disorders that manifest with moderate to severe impairment in both self and interpersonal functioning [ ] [ ] [ ] . that is, such patients show serious difficulties in emotion regulation and interpersonal relationships. since pandemic showed to be a stressful event with consequences on emotions [ ] and social life [ ] , we can expect that it might represent a relevant risk factor for the exacerbation of negative psychological consequences specifically connected to personality pathology. furthermore, the pathological personality traits showed by individuals with pds might pose difficulties in compliance with mitigation measures needed during pandemic outbreaks. for these reasons, we performed a narrative review of studies investigating pandemic-related mental health issues and in particular including only issues related to pds and personality traits. considering the paucity of studies on this topic, after a description of the main features of pds, on the basis of the current literature on pandemic and quarantine mental health impact, we aim at tracing some clinical hypotheses on the negative psychological effects of pandemic situations in people with pds. furthermore, we aim at investigating the role of personality pathology in compliance with mitigation-related behaviors. we searched for original studies published in pubmed until july using the medical subject headings (mesh) "pandemic," "oubreak," "covid*," "lockdown," "quarantine," "sars," "influenza," "flu," "mers," "ebola" combined with "mitigation measures," "compliance," and "adherence" and with "personality," "trait," "temperament," and "personality disorder." we considered only studies published in the english language. we also reviewed the list of references to identify other studies of interest. considering the paucity of studies on this topic, we adopted the following steps in the description of results: ( ) we provided a description of the main features of pds for each cluster; ( ) we mentioned the main literature investigating the association between pds of each cluster and other psychiatric disorders; ( ) on the basis of the literature on pandemic (e.g., [ ••] ) and quarantine (e.g., [ ••] ) mental health impact, we hypothesized a plausible relation between pds of each cluster and specific psychological/psychiatric outcomes, as well as problems in compliance with mitigation measures. we present a synthesis of our results in table . the table reports a brief description of pds, the traits and symptoms that are likely to play a role in response to pandemics, and the negative psychological outcomes due to pandemics and quarantine that we hypothesize might be bolstered by personality pathology. negative psychological impact patients with cluster a pds are usually highly introverted, emotionally detached, and hypersensitive to interpersonal threats due to paranoid tendencies (e.g., [ , ] ). as a consequence, patients with paranoid, schizoid, or schizotypal pds may be at higher risk for serious psychological issues during pandemic emergencies. in pandemic situations, other people represent potential threats to one's own survival, and intense fear for contagion is a natural psychological reaction to these events [ ] . in cluster a pds, patients', however, fear of contagion may intensify pre-existing paranoid tendencies and exacerbate suspect toward others, by supporting pre-existing persecutory representations of others. in fact, within kernberg's object relation theory framework, personality pathology is sustained by massive use of splitting defense mechanism which lead patients to divide the world in all-good and all-bad objects, producing unstable, polarized, dissociated, fragmented, and distorted views of both self and significant others [ , ] . according to this view, projection into others of one's own negative parts contributes to a persecutory view of others, typical of patients with paranoid tendencies [ ] . moreover, it is reasonable to expect that intensifications of paranoid tendencies may lead cluster a pds patients to experience high levels of psychological distress, depressive feelings, and anxiety symptoms. there is now evidence that the covid- pandemic caused a sharp increase in the prevalence of anxiety and depressive problems in both the general population [ ] and clinical samples [ ] . furthermore, . % of outpatients with pre-existing psychiatric disorders reported a deterioration in their condition during the covid- pandemic [ ] . as for cluster a pds, high levels of depressive feelings in patients may be linked to presumed perception of untrustworthy others [ ] , and their constant need of keeping a watchful eye on others may be responsible for high psychological distress and anxiety (e.g., [ ] ). furthermore, claims that the coronavirus pandemic would have originated in laboratory have emerged during the covid- outspread [ ] [ ] [ ] . since paranoid pd patients show a pervasive and long-standing suspiciousness and mistrust of others, they may be particularly suitable for believing and spreading conspiracy theories about pandemics. this hypothesis is in line with recent findings [ ] showing a positive association between paranoid traits and conspiracist ideation. moreover, the wide use of "war metaphors" by healthcare workers and journalists during the covid- pandemic may have a detrimental effect in these patients, by fostering splitting defense mechanisms and by strengthening interpretation of external reality in terms of winners and losers [ ] . finally, social distancing measures may also have peculiar psychological impacts on cluster a pds patients. in a sense, these recommendations may bolster their proneness to introversion, social withdrawal, and isolation (e.g., [ , ] ). for instance, it is plausible to expect that patients with paranoid, schizoid, or schizotypal pds would significantly reduce their social contacts during pandemic emergencies, with great difficulties in restoring them when lockdown measures end. as a consequence of their prevailing traits of detachment [ ] , cluster a pds patients are likely to show reduced emotional wellbeing [ ••] and higher levels of depression, anxiety, and *impact reported for both pandemics (e.g., [ ] ) and quarantine (e.g., [ ] ); p, pandemic impact; q, quarantine impact stress [ ••] during pandemics. furthermore, social isolation, and limitations in contacts with mental health professionals, may lead patients to experience feelings of depression and loneliness, especially in the case of schizotypal pd. albeit socially isolated, indeed, schizotypal patients usually desire to have social contacts [ , ] . we may expect that some dispositional tendencies, such as paranoid thoughts and social withdrawal, make cluster a pds patients-paranoid pd patients particularly-prone to high compliance with mitigation measures. in line with this hypothesis, some studies [ , ] have recently shown that people high in extroversion have difficulties in keeping social distancing and in adhering to other mitigation measures. as a result, we may expect that the higher the detachment (which is opposed to extroversion), the higher is the tendency to be compliant with social distancing and mitigation measures during the outbreak. however, these results were not replicated by another study describing a positive correlation between extroversion and preparatory behaviors (i.e., face mask, hand sanitizer, toilet paper, food, travel cancelation) [ ] . on the other hand, schizoid individuals suffer from communication and cognition impairments and have an unconventional life-style [ , ] , which often leads them to live as marginalized subjects. similarly, schizotypal individuals have an impaired cognition, being deficient in attention, executive function, abstraction and memory, suffering from deficits in verbal learning, and lacking cognitive flexibility [ , ] . moreover, they have an impaired self-monitoring function, leading them to struggle to differentiate inner thoughts and reactions compared to those generated by the external [ ] , and often suffer from auditory hallucinations, delusions, and magical thinking [ , ] . these lack of functioning in several areas, paired with the high prevalence of cluster a pds disorders in homeless people [ ] [ ] [ ] [ ] , might prevent them to be compliant to mitigation measures and especially to hygiene norms. negative psychological impact cluster b pds have unstable interpersonal relationships, and show behaviors that are overly emotional, impulsive, dramatic, and erratic. since their vulnerabilities might be attributable to underlying hyper-responsiveness to stress and hypersensitivity to threat (e.g., [ , ] ), we expect that pandemic emergencies would seriously impact mental health in these patients. in line with our expectation, negative affectivity was found to be a risk factor for reduced emotional well-being during the covid- pandemic [ ••] . moreover, negative affectivity was associated with high levels of depression, anxiety, and stress [ ••] . coherently, neuroticism, which is the adaptive corresponding trait of negative affectivity, was linked to reduced psychological well-being [ ] , more concerns, and longer pandemic duration estimates [ ] . pandemic emergencies force people to drastically reduce contacts with significant others for a quite long time, with relevant consequences in terms of disruption of daily life routines and conditions of social isolation. being forced to keep distance from significant others (e.g., parents, partners, friends) may be particularly critical for both borderline and histrionic patients. in fact, borderline and histrionic pds share a strong need for emotional and physical proximity with others [ , ] . moreover, borderline patients suffer from abandonment fears, rejection sensitivity, and paranoid preoccupations under conditions of stress [ , ] . in this sense, the experience of lockdown may be particularly exhausting for these patients. it is reasonable to expect that such isolation may trigger negative feelings about oneself and the others, with an intensification of interpersonal conflicts, due to misinterpretation of others' distance in terms of abandonment or disinterest. as a consequence, borderline patients perceiving distance of others in terms of abandonment might be more likely to engage in substance misuse as a form of selfmedication [ ] [ ] [ ] and in both suicidal behaviors and nonsuicidal self-injury to cope with loneliness [ ] . in addition, emotion dysregulation and difficulties in reading others' emotional expressions (e.g., [ ] ) might lead borderline patients to read in advance subtle emotional expressions of fear or anxiety in their significant others and this, in turn, might trigger intense reactions such as anger outbursts, high irritability, and impulsive behaviors (e.g., maladaptive eating behaviors). this expectation is in line with a recent study [ ] showing that cyclothymic temperament, which is best expressed by cluster b patients [ ] , was related to greater psychological distress during the coronavirus outbreak. researchers have found evidence that conscientiousness was related to higher psychological well-being [ ] , less pandemic duration estimates, less concerns in general, and more concerns about community [ ] . since conscientiousness is opposed to traits of disinhibition which, according to the alternative model of personality disorders (ampd; [ ] ), are distinctive of borderline patients, we may hypothesize that such patients may experience less psychological well-being during the outbreak, estimate longer pandemic duration, and do not care about community. as for histrionic pd patients, they usually show attention-seeking behaviors and an excessive need for attention [ ] . again, the mass indoor quarantine may lead histrionic patients to feel deeply alone, with consequent high levels of anxiety and depressive feelings [ ] . narcissistic features, on the contrary, may prevent patients from experiencing maladaptive psychological outcomes during pandemic outspreads. in particular, grandiose narcissistic individuals are self-absorbed (e.g., [ , ] ), socially cold and dominant (e.g., [ ] ), and base their self-view on agentic traits rather than on communal ones (e.g., [ ] ). in a sense, such attributes might protect narcissists from experiencing psychological distress during pandemics. gupta and parimal [ ] , however, have recently found that traits of agreeableness relate to greater psychological well-being during pandemics. since both narcissistic and antisocial patients, according to the ampd [ ] , share high traits of antagonism (which is opposed to agreeableness), they might show poor psychological well-being during pandemics. furthermore, recent studies show that pathological narcissism include both grandiose and vulnerable manifestations [ ] , and that psychological distress usually relates to vulnerable traits [ ] . therefore, we might expect that forced social isolation limits narcissists' occasions to search for admiration from others, with consequent feelings of hopelessness which are typical of vulnerable manifestations of narcissism. finally, social isolation might lead antisocial patients to experience psychological distress by limiting their chance to express their hostility toward others, as they usually do. overall, we may expect poor compliance with social distancing and mitigation measures in cluster b pds patients. for instance, impulsiveness may affect seriously the ability of borderline patients to keep social distancing. indeed, conscientiousness, as opposed to disinhibition, was positively linked to social distancing, hand washing, and hygiene [ , ] . in line with these findings, brouard and colleagues [ ] noted a positive link between conscientiousness and adherence to mitigation measures, while aschwanden et al. [ ] reported the trait to be associated with more precautions. so, people with higher disinhibition may be prone to act less social distancing, hygiene, and to be less adherent to mitigation measures. we might expect that both narcissistic and antisocial patients are poorly motivated to follow mitigation measures. in fact, narcissistic patients have a grandiose self-view [ ] and this, in turn, may lead them to think they are exempt from mitigation norms. moreover, antisocial pd comprises failure to conform to social norms [ ] and disregard for others [ ] . these expectations are also supported by aschwanden et al. [ ] showing that agreeableness (which is opposed to antagonism) is positively related to social distancing during the outbreak. negative psychological impact patients with cluster c pds display anxious and fearful thinking and behaviors. these features may make patients with avoidant, dependent, or obsessive-compulsive pds at high risk to develop serious psychological outcomes during pandemic outspreads. in particular, these patients may be particularly sensitive to anxious feelings originating from fear of contagion during pandemics. in fact, during the covid- pandemic, anxiety and depression were found to be positively associated with fear of infection about oneself and loved ones [ ] . since traits of anxiety are central in avoidant pd according to the ampd [ ] , and patients with avoidant pd "feel fearful, apprehensive, or threatened by uncertainty" ( [ ] ; p. ), these patients may suffer from serious anxiety symptoms during pandemics. in fact, pandemic emergencies force us to live in a constant state of uncertainty (e.g., job uncertainty). avoidant pd, along with the other cluster c pds, is characterized also by traits of detachment, and recent findings suggest that such traits relate to reduced emotional wellbeing [ ••] , depression, anxiety, and stress [ ••] during pandemic outbreaks. moreover, bacon and corr [ ] found that behavioral inhibition was related to higher depression and anxiety in response to the covid- pandemic. some studies on the effect of adaptive personality traits on psychological reactions to pandemics, however, do not confirm such associations. in fact, extroversion (which is opposed to detachment) was found to be linked to less psychological well-being [ ] and greater concerns [ ] during pandemics. as well known, dependent pd patients are unable to be alone and they rely on others for reassurance and support [ ] . therefore, they may experience high levels of anxiety, psychological distress, and sleep disturbances in response to intense worries about others' survival: the idea that the people they depend on can get sick and no longer be available would be intolerable for them. in this sense, dependent patients may be at high risk to develop depressive symptoms and posttraumatic conditions if their significant others are affected by the disease, as well as to show post-traumatic conditions in case of serious medical conditions (e.g., conditions requesting hospitalization) or death of significant others. as discussed above, studies have demonstrated that negative affectivity is a risk factor for reduced emotional well-being [ ••] , depression, anxiety, and stress [ ••] , and neuroticism was related to less psychological well-being [ ] , more concerns, and longer duration estimates related to covid- [ ] . besides anxiety and depression, evidence of post-traumatic stress disorder in the post-illness stage of previous coronavirus epidemics was reported [ ] . patients with obsessive-compulsive pd may be also particularly sensitive to anxiety and depressive symptoms during the coronavirus emergency, since they are inflexible and show excessive need for control, extreme perfectionism, and excessive devotion to work. such dispositions may lead these patients to experience high levels of both anxiety and depressive symptoms in response to the need of facing disruptions of daily life routines (e.g., [ ] ). in fact, the lockdown period forced individuals to adopt highly flexible working models, and to full-time cohabitation for weeks. moreover, obsessivecompulsive pd individuals show difficulties in coping with uncertainty [ ] , and are intolerant to changes and deviations in their routine (e.g., [ ] ). in line with our assumptions, anxious and depressive temperament, which are best expressed by cluster c patients [ ] , are related to greater psychological distress during coronavirus outbreak [ ] . our expectations regarding compliance with mitigation measures in cluster c pds patients are somewhat mixed. on the one hand, we may expect high compliance with mitigation measures, since dispositions toward high anxiety and fearful thinking and behaviors of these patients well fit in with the governments' guidelines for pandemic mitigation strategies. on the other hand, however, these patients may show difficulties in following some mitigation measures due to their rigidity and inflexibility, as in the case of obsessive-compulsive pd patients [ , ] . our hypotheses are not univocal also when considering the role of pathological personality traits describing cluster c pds, according to the ampd [ ] . for instance, studies on the association between detachment and adherence to mitigation measures are not available, and empirical findings on the role of extroversion (which is opposed to detachment) are mixed. extroversion has been found to be negatively associated with social distancing [ ] and adherence to other mitigation measures [ ] . on the contrary, aschwanden et al. [ ] found a positive association between extroversion and preparatory behaviors. the same is for negative affectivity. in fact, abdelrahman [ ] found that neuroticism is related to greater social distancing, whereas brouard et al. [ ] showed that it was negatively correlated to covid- mitigation behaviors. consistent with brouard et al. [ ] , however, aschwanden et al. [ ] found that emotional instability related to fewer precautions. after all, previous studies showed that people who are emotionally unstable appraise their coping ability not enough to face acute stress, and this may lead them to freeze/not act [ ] . with this review, we aimed at investigating the negative psychological impact of pandemic situations in patients with personality pathology. since impairments and manifestations of personality pathology differ according to the specific type of disorder, we hypothesized that pandemics might affect differently patients, according to their main pd diagnosis (table ) . we based our hypotheses on clinical understanding of pds, and we supported our statements by mentioning some recent empirical findings. in fact, at the moment, empirical studies on the effects of pandemics on patients with pd diagnosis are lacking. there are, however, some available studies inspecting the effect of pathological personality traits [ , ] , adaptive personality traits (e.g., [ ] ), and temperamental dimensions (e.g., [ ] ) on dysfunctional reactions to pandemics. our review suggests that pd patients might be particularly affected by pandemic situations. furthermore, they might react differently to pandemics, according to their main diagnosis and related manifestations. considering cluster a pds, we hypothesize that paranoid traits may foster conspiracy theories and negative views of the other and that detachment might interact with quarantine measures in worsening social isolation. cluster b patients may show stress-related reactions, including impulsive and risky behaviors. this is particularly true for borderline patients: difficulties in emotion regulation and fear of abandonment and rejection might render social distancing particularly painful for these patients. on the other hand, we might expect that narcissistic patients, due to their self-absorption, might be relatively protected from the negative effects of isolation, although difficulties in nourishing their grandiose view of self. finally, cluster c patients might be particularly prone to anxiety and stress reactions in response to fear of contagion and may show serious disturbances in response to intense worries about others' survival. furthermore, rigidity and intolerance to change might interfere with the need of flexible adaptation to new routines. similarly, we showed that compliance with mitigation measures and social distances may differ significantly according to specific pds. detachment might be a factor that makes cluster a patients more prone to following mitigation measures. however, severe cognitive and functional impairments in these patients pose a threat to following organized behaviors. impulsiveness and disinhibition of cluster b patients might render them less compliant with mitigation measures, and this might be particularly true for patients with narcissistic and antisocial personality disorder, due to their grandiose selfview and disregard of others. finally, cluster c patients might present mixed levels of compliance. on the one hand, due to anxiety and fear of contagion, they might be more probe to follow prescribed measures; however, rigidity (especially in obsessive-compulsive pd) might pose difficulties in changing behavioral routines and adapting to the mitigation behaviors. as a final note, limitations in the provision and accessibility of mental health services can have a particular impact on patients with pds. mitigation measures and the global emergency led to partial or total disruptions of some forms of treatment [ ••] . some of these treatment options have a particular relevance for complex mental health conditions such as pds. reduced inpatient treatment capacities and early discharges [ ] [ ] [ ] [ ] might have detrimental effects on patients with pds. also, group interventions (e.g., skills training groups or peer support meetings) are a treatment component in many therapies for patients with pds, and their reduction or cancelation [ , ] can affect the course of treatment for these patients. to the best of our knowledge, this is the first review attempting to trace some hypotheses on pd patients' reactions during epidemics. the paucity of related studies represents a limitation of this review. in particular, not only negative impact but also symptomatologic amelioration may have been registered, especially during the initial phase of the lockdown, revealing adaptive coping strategies in these patients [ ] . the present results should thus be considered as a starting point to reflect on therapeutic strategies to be adopted in the post-covid- telepsychology and telepsychiatry revolution [ , ] . funding open access funding provided by università degli studi di milano -bicocca within the crui-care agreement. conflict of interest the authors declare that they have no competing interests. human and animal rights and informed consent this article does not contain any studies with human or animal subjects performed by any of the authors. open access this article is licensed under a creative commons attribution . international license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons licence, and indicate if changes were made. the images or other third party material in this article are included in the article's creative commons licence, unless indicated otherwise in a credit line to the material. if material is not included in the article's creative commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. to view a copy of this licence, visit http://creativecommons.org/licenses/by/ . /. particular interest, published recently, have been highlighted as: •• of major importance the psychological impact of quarantine and how to reduce it: rapid review of the evidence psychological interventions for people affected by the covid- epidemic the psychological impact of epidemic and pandemic outbreaks on healthcare workers: rapid review of the evidence how mental health care should change as a consequence of the covid- pandemic american psychiatric association. diagnostic and statistical manual of mental disorders disturbed relationships as a phenotype for borderline personality disorder interpersonal dynamics in personality and personality disorders unprecedented disruption of lives and work: health, distress and life satisfaction of working adults in china one month into the covid- outbreak how the covid- pandemic is focusing attention on loneliness and social isolation assessing interpersonal aspects of schizoid personality disorder: preliminary validation studies bifactor structure of the schizotypal personality questionnaire (spq) covid- as a psychological contagion: a new pandora's box to close? the inseparable nature of love and aggression: clinical and theoretical perspectives a psychoanalytic theory of personality disorders severe personality disorders anxiety and depression among general population in china at the peak of the covid- epidemic mental health response to the covid- outbreak in china association between interpersonal trust, reciprocity, and depression in south korea: a prospective analysis are you looking at me? understanding and managing paranoid personality disorder lópez seguí f. covid- and the g conspiracy theory: social network analysis of twitter data statement in support of the scientists, public health professionals, and medical professionals of china combatting covid- coronavirus conspiracy beliefs, mistrust, and compliance with government guidelines in england covid- pandemia and public and global mental health from the perspective of global health security waging war on war metaphors in cancer and covid- [published online ahead of print levels of social sharing and clinical implications for severe social withdrawal in patients with personality disorders impaired social functioning and symptoms of personality disorders assessed by peer and self-report in a nonclinical population dysfunctional personality features, non-scientifically supported causal beliefs, and emotional problems during the first month of the covid- pandemic in italy a nationwide survey of psychological distress among italian people during the covid- pandemic: immediate psychological responses and associated factors this is one of the few studies investigating the associations between maladaptive personality traits and psychological outcomes related to the covid- outbreak the expression of positive and negative schizotypy in daily life: an experience sampling study the neglected link between adult attachment and schizotypal personality traits sociodemographic and psychological correlates of compliance with the covid- public health measures in france personality differences and covid- : are extroversion and conscientiousness personality traits associated with engagement with containment measures? trends psychiatry psychother psychological and behavioural responses to coronavirus disease : the role of personality cognitive therapy of personality disorders specific types of personality disorders cognitive and brain function in schizotypal personality disorder schizotypal personality disorder: a current review neurophysiological evidence of impaired self-monitoring in schizotypal personality disorder and its reversal by dopaminergic antagonism the oxford-liverpool inventory of feelings and experiences (o-life): further description and extended norms dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring personality disorders in homeless drop-in center clients study of the influence of mental disorders on the problems of social rehabilitation schizoid personality traits among the homeless mentally iii: a quantitative and qualitative report personality disorders and treatment drop out in the homeless borderline personality disorder: hypothalamus pituitary adrenal axis and findings from neuroimaging studies neural correlates of emotional action control in anger-prone women with borderline personality disorder relationship between personality dimensions and psychological well-being among university students during pandemic lockdown comparison of attachment styles in borderline personality disorder and obsessive-compulsive personality disorder cluster b personality traits and attachment reviewing the clinical significance of 'fear of abandonment' in borderline personality disorder trust and rejection sensitivity in personality disorders postdisaster course of alcohol use disorders in systematically studied survivors of disasters tobacco use after experiencing a major natural disaster: analysis of a longitudinal study of young adults consumption of cigarettes, alcohol, and marijuana among new york city residents six months after the september terrorist attacks suicidal thoughts and behaviors and social isolation: a narrative review of the literature heightened sensitivity to facial expressions of emotion in borderline personality disorder affective temperament, attachment style, and the psychological impact of the covid- outbreak: an early report on the italian general population temperament traits and personality disorders. predictors for personality disorders depression in histrionic personality disorder exploring the structure of narcissism: toward an integrated solution the narcissism spectrum model: a synthetic view of narcissistic personality initial construction and validation of the pathological narcissism inventory narcissistic subtypes and contingent self-esteem: do all narcissists base their self-esteem on the same domains? grandiose and entitled, but still fragile: a network analysis of pathological narcissistic traits abdelrahman m personality traits, risk perception, and protective behaviors of arab residents of qatar during the covid- pandemic pathological narcissism and narcissistic personality disorder factorial structure of traits delineating personality disorders in clinical and general population samples coronavirus (covid- ) in the united kingdom: a personality-based perspective on concerns and intention to self-isolate psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and metaanalysis with comparison to the covid- pandemic obsessive-compulsive personality disorder and component personality traits intolerance of uncertainty and obsessivecompulsive personality disorder relationship between hypochondriasis and obsessivecompulsive personality disorder: close relatives separated by nosological schemes? factor analysis of symptom subtypes of obsessive compulsive disorder and their relation to personality and tic disorders capacity to delay reward differentiates obsessive-compulsive disorder and obsessive-compulsive personality disorder the association of coping to physical and psychological health outcomes: a meta-analytic review ensuring mental health care during the sars-cov- epidemic in france: a narrative review mental health policy in the era of covid- the behavioral health system and its response to covid- : a snapshot perspective mental health services in lombardy during covid- outbreak challenges and priorities in responding to covid- in inpatient psychiatry covid- disease emergency operational instructions for mental health departments issued by the italian society of epidemiological psychiatry adaptations of an outpatient dialectical behavioral therapy during the covid- pandemic and consequences of the confinement on patients with borderline personality disorder path analytic modeling of psychologists' openness to performing clinical work with telepsychology: a national study telehealth for global emergencies: implications for coronavirus disease (covid- ) publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -jzke fop authors: hollingsworth, t. déirdre; klinkenberg, don; heesterbeek, hans; anderson, roy m. title: mitigation strategies for pandemic influenza a: balancing conflicting policy objectives date: - - journal: plos comput biol doi: . /journal.pcbi. sha: doc_id: cord_uid: jzke fop mitigation of a severe influenza pandemic can be achieved using a range of interventions to reduce transmission. interventions can reduce the impact of an outbreak and buy time until vaccines are developed, but they may have high social and economic costs. the non-linear effect on the epidemic dynamics means that suitable strategies crucially depend on the precise aim of the intervention. national pandemic influenza plans rarely contain clear statements of policy objectives or prioritization of potentially conflicting aims, such as minimizing mortality (depending on the severity of a pandemic) or peak prevalence or limiting the socio-economic burden of contact-reducing interventions. we use epidemiological models of influenza a to investigate how contact-reducing interventions and availability of antiviral drugs or pre-pandemic vaccines contribute to achieving particular policy objectives. our analyses show that the ideal strategy depends on the aim of an intervention and that the achievement of one policy objective may preclude success with others, e.g., constraining peak demand for public health resources may lengthen the duration of the epidemic and hence its economic and social impact. constraining total case numbers can be achieved by a range of strategies, whereas strategies which additionally constrain peak demand for services require a more sophisticated intervention. if, for example, there are multiple objectives which must be achieved prior to the availability of a pandemic vaccine (i.e., a time-limited intervention), our analysis shows that interventions should be implemented several weeks into the epidemic, not at the very start. this observation is shown to be robust across a range of constraints and for uncertainty in estimates of both r( ) and the timing of vaccine availability. these analyses highlight the need for more precise statements of policy objectives and their assumed consequences when planning and implementing strategies to mitigate the impact of an influenza pandemic. in the event of the emergence of a new human influenza a strain with a high case fatality rate indicating the possibility of a global pandemic with severe impact, control strategies primarily aim at limiting morbidity and mortality rather than halting transmission completely. this is because transmission of influenza a is difficult to block due to its short generation time and efficient transmission characteristics [ ] . in the early days of the h n influenza pandemic in mexico in [ ] , social distancing measures were implemented with the aim of slowing the epidemic during its early stages. for any future pandemic of a directlytransmitted infectious agent, it is expected that similar strategies will be used in high resource settings while the pathogen is being identified, epidemiological studies to both characterize transmission [ , , , , ] and determine pathogenicity are completed [ , ] and strain-specific control options, such as vaccines, are being developed [ , ] . for influenza, policy options are clearly outlined in national pandemic plans, but there is rarely any clear statement of policy objectives [ ] . the problem is that these different objectives are potentially conflicting in their effects, and clear prioritisation is therefore necessary. is the aim to minimize mortality and morbidity, is it to limit the peak prevalence of serious disease so that public health resources are not overwhelmed or is it to minimise the impact of the intervention on society and economy? in this paper we form a framework for policy makers to consider these potentially conflicting objectives. a number of studies have investigated the role of targeted interventions at different phases of the epidemic based on mathematical models which include various levels of population structure and spatial complexity [ , , , , , , , ] . however, none of these studies have addressed how multiple policy objectives are met by the common interventions, or how a clear statement of the key policy aims guides which set of interventions work best. it is typically assumed by policy makers that the more intervention measures implemented as early as possible in the course of the epidemic the better the outcome in terms of mitigation. reservations about this strategic approach rest on the costs, and societal impact plus economic implications of sustaining control measures over a long period of time. in recognition of this the usa pandemic plan, for instance, mentions a maximum duration of weeks for many transmission-reducing interventions [ ] . however, there has been no quantitative analysis of when such an intervention should be initiated. should it be as soon as the first cases are discovered, or later in the outbreak when more cases have arisen? neither has it been acknowledged that planned levels of coverage with antiviral treatment or pre-pandemic vaccines may implicitly determine the magnitude of social distancing interventions required. studies have shown that during the - influenza pandemic public health control strategies and changes in population contact rates lowered transmission rates and reduced mortality and case numbers [ , ] . similar measures were arguably effective for h n in mexico in [ ] . strategies used then, and to be considered in future, include social distancing measures, such as school closures [ , ] , restaurant and cinema closures [ ] , and transport restrictions [ , , ] . there are a number of other measures, such as hand washing and the use of face masks [ ] , which may reduce contact rates [ , ] . transmission will also be affected by changes in human behaviour in response to a pandemic, as was observed in travel and mixing patterns during the severe acute respiratory syndrome (sars) outbreak in [ ] . within the last years, there have been two international outbreaks of a directly transmitted pathogen with high case fatality rates in which social distancing measures were implemented. the first was the influenza pandemic of , where non-pharmaceutical public health strategies were effective at reducing morbidity and mortality in a number of settings [ ] . however, the impact of these interventions on transmission was highly variable. an analysis of cities in the usa showed reductions in transmission ranged from approximately - % ( figure ). these interventions were held in place from week to months. one might expect that interventions with higher impact were held in place for shorter time, but there was no systematic relationship between the duration and the impact of interventions (figure , black circles) . during the sars outbreak of , the aim of intervention strategies was to eliminate transmission, not only to mitigate the effects of the epidemic. elimination was possible due to the characteristics of the virus -post-symptomatic transmission and a long generation time [ ] . large scale reductions in the transmission rate of sars (. %, figure , [ ] ) were brought about by a number of public health interventions. these interventions were held in place for several weeks. the small amount of data available perhaps suggest a trend towards lower impact interventions being held in place for longer to achieve elimination ( figure , open triangles), but an important driver of the duration of these interventions was the number of cases that were present when the interventions started. these empirical data from two severe outbreaks suggest that moderate reductions in influenza transmission can be achieved and maintained at a population level for a number of weeks. the impact of any particular intervention is difficult to estimate from past epidemics due to variation in the viral strain and its transmission properties, and due to the concurrent effects of many different behavioural responses and government led initiatives. planning therefore depends increasingly on the predictions of mathematical models of viral spread that permit analyses of the potential impact of various interventions, alone or in combination [ , , , , , , ] . in this paper we consider the effectiveness of contact-reducing interventions during the first six months after the initial cases, before a pandemic vaccine is available, and evaluate optimum interventions for a range of policy objectives or constraints, such as a limited stockpile of treatments or non-specific vaccine. analyses are based on a mathematical model of virus transmission and the impact of control measures. we focus on the identification of policies that minimise peak demand for public health services and those which minimise the potential costs or socio-economic impact as evaluated by a simple cost function. this paper is not designed [ ] (open triangles) and during the influenza pandemic in cities in the usa [ ] (closed circles). a transmission reduction of % reflects an intervention which was estimated to have no effect on transmission. doi: . /journal.pcbi. .g in the event of an influenza pandemic which has high mortality and the potential to spread rapidly, such as the - pandemic, there are a number of non-pharmaceutical public health control options available to reduce transmission in the community and mitigate the effects of the pandemic. these include reducing social contacts by closing schools or postponing public events, and encouraging hand washing and the use of masks. these interventions will not only have a non-intuitive impact on the epidemic dynamics, but they will also have direct and indirect social and economic costs, which mean that governments will only want to use them for a limited amount of time. we use simulations to show that limitedtime interventions that achieve one aim, e.g., contain the total number of cases below some maximum number of treatments available, are not the same as those that achieve another, e.g., minimize peak demand for health care services. if multiple aims are defined simultaneously, we often see that the optimal intervention need not commence immediately but can begin a few weeks into the epidemic. our research demonstrates the importance of tailoring pandemic plans to defined policy targets with some flexibility to allow for uncertainty in the characteristics of the pandemic. to give specific policy guidance. box outlines a number of factors which should be considered in designing policy which are not covered here. our aim is to develop an understanding of how different policy objectives determine the optimal mix, timing of introduction and duration of implementation of the available mitigation strategies. all results have been obtained with a model based on the wellknown deterministic sir-model, that has proven its value in many studies of infectious diseases [ , ] . we parameterized the model with a mean infectious period of . days (recovery rate c = / . ), and a basic reproduction number r = . (see ferguson et al [ ] ) with a population of size n = . million. the population was subdivided into proportions of the population in the classes of x susceptibles, y infectives, and z immunes, with dynamics given by the parameter b t ð Þ is the transmission rate, i.e. the number of contacts an infective has per day in which the infection is passed on, and has the baseline value b ~r c~ : = : . simulations were started with infective, n susceptibles, and no immunes. we investigated the impact of a social distancing intervention on transmission through a constant reduction in transmission, w, resulting from an unspecified combination of public health measures, maintained over a time period, d. in model terms, the transmission rate b t ð Þ was assumed to change during intervention from the baseline rate b to a reduced rate {w ð Þb . this happened from t~t , the start of the intervention, until t ~t zd, the end of the intervention of duration d. for the duration we considered three options, first an intervention that is kept in place indefinitely, second an intervention with a fixed duration of twelve weeks, which is the maximum duration mentioned in the usa national pandemic plan [ ] , and third an intervention until the a pandemic specific vaccine is available, after six months. in the 'indefinite' scenario, the duration of the epidemic was formally defined as the time until ynv . transmission-reducing public health interventions for influenza are unlikely to completely halt transmission [ , , , ] . it is most likely that mitigation strategies will be 'sub-critical' interventions which reduce the effective reproduction ratio (the mean number of new infections per infected individual) towards, but not below, . thus, we assumed that wv { =r ~ : . numerical simulations of the model were used to evaluate the impact of the interventions twelve months after the first case. impact is primarily measured by (the reduction in) the total number of cases. we also evaluated two other measures of effectiveness: firstly, the (reduction in) peak prevalence, since high prevalence may overwhelm public health facilities and as such increase both morbidity and mortality; and secondly, the socioeconomic costs of the interventions, determined both by the level of intervention and the duration they are in place, calculated as the simple cost function w|d. many countries have stockpiled antiviral drugs in preparation for an influenza pandemic [ ] . whilst these may be used prophylactically to reduce transmission [ , , ] , most pandemic strategies advocate the use of antivirals to treat cases of infection or to treat those cases where other risk factors suggest that disease severity may be high [ ] . the treatment of cases will reduce morbidity and mortality and has been shown to be cost-effective for high risk patients [ ] . we focus on the treatment of cases in combination with transmission-reducing intervention as above. we make the assumption that treatment of cases does not affect transmission. the assumption is made firstly because drugs are given upon case notification, which is when much infectiousness may have passed [ ] , and secondly because symptomatic patients will be advised to remain at home reducing their contacts. the additional transmission reduction in transmission due to antivirals will thus be minor. the use of antivirals for severely ill patients could have implications for occupancy and therefore availability of isolation units and high dependency beds. whilst this might change the infectious profile of the few severely ill patients who would have access to these facilities, it does not affect the majority of cases and detailed consideration of these logistics is outside the scope of this study. in addition, we do not include the possible effect of mass treatment on resistance [ ] and therefore on the efficacy of the drugs. consideration of these effects may lead to a range of different policy objectives, taking into account combination therapy or sequential deployment of different lines of therapy [ ] . as well as stockpiling antivirals, it may be possible to reduce transmission and severity of disease by stockpiling a partially-box . epidemic-specific characteristics affecting suitability of interventions. n epidemiological characteristics of a future pandemic are not yet known and will be uncertain early in the epidemic. however, transmission estimates used for influenza pandemic planning proved to be close to those observed during the h n pandemic [ ] . key parameters include r , epidemic growth rate, generation time distribution, age-specific attack rate, asymptomatic case ratio, case fatality ratio, hospitalisation rates, treatment requirements, cross-immunity, drug resistance. n setting specific parameters will affect the growth rate and peak prevalence of an outbreak. these include age structure of the population, contact rates within and between age-groups, household structure, school attendance patterns, pre-existing immunity. n spatial structure may be important in certain settings, particularly population density, transport links and accessibility of health care services. therefore interventions may be applied differently in different areas, depending on the spatial scale. influenza growth rates are very rapid, so spread between areas could be rapid. n the early course of an outbreak. when there are small numbers of cases and variable importation rates, there will be stochastic effects which will facilitate or slow the transition from localised outbreaks to exponential growth of the epidemic. this will affect the optimal timing of interventions. protective pre-pandemic vaccine in advance of the pandemic [ ] . even partially effective vaccines can have large beneficial effects because the unvaccinated are indirectly protected from infection by those portions of the vaccinated population who are not infected or are less severely affected and possibly have reduced infectiousness ('herd' immunity -see [ ] ). use of an imperfect vaccine can, however, also lead to increased incidence if reductions in infectiousness are associated with corresponding increases in the infectious period [ , ] . effectiveness estimates for a prepandemic vaccine are not available, but evidence from crossprotection studies led to the assumption that both susceptibility to infection and infectiousness may be reduced by % [ , ] . the duration of infectiousness is assumed to be unchanged, precluding any increased incidence in the presence of the vaccine. we evaluate a partial vaccination strategy, in combination with a transmission reducing intervention, aiming to keep the number of unvaccinated cases (epidemic size) less than % of the population. to consider vaccination with a pre-pandemic vaccine, the transmission model was adjusted to include infection of vaccinated individuals: in this adjusted model, x v , y v , and z v are the proportion of vaccinated individuals, and e i ( = . ) and e s ( = . ) are the relative infectiousness and susceptibility of vaccinated versus unvaccinated individuals. it is assumed that vaccinated cases would not require treatment, and therefore were not included in the epidemic size or peak prevalence. simulations were carried out with a vaccine coverage of %, starting with one unvaccinated infective. to place our results in a more realistic context whilst not giving precise policy guidance, we consider two scenarios for pandemic planning in high resource settings. they are scenarios which are covered in a number of pandemic plans. we will outline the range of interventions which can achieve these aims. scenario : a strain-specific vaccine is expected to be available within months of the start of a pandemic. in order to minimize morbidity and mortality, social-distancing interventions will be used to 'buy time' until the vaccine is available. antiviral drugs are available to treat symptomatic cases with a stockpile for up to % of the population. social-distancing interventions will be used to ensure that symptomatic cases are kept below this level and to minimize socio-economic impact and peak demand for hospital and other public health services by minimizing prevalence in the population. scenario : this scenario is very similar to scenario , except that in addition a pre-pandemic vaccine is available which can be rapidly rolled out to % of the population. the question of interest will be the extent to which the pre-pandemic vaccine will reduce the level of intervention required. since we are considering interventions implemented early in the epidemic, key epidemiological parameters may still be in the process of being estimated. therefore, we investigated which strategies are least sensitive to incorrect estimation of r , i.e. r = . or . . in addition, availability of a pandemic vaccine may be delayed, or the pre-pandemic vaccine may be less effective than anticipated, so we ran our simulations out to an eight-month period and with a vaccine efficacy of e s~ei~ : ( % less reduction in transmission). we first investigate the impact of social distancing interventions alone. the received wisdom of outbreak control strategies is that the maximum level of control measures should be put in place as rapidly as possible. however, there may be delays before control strategies are implemented due to difficulties in identifying the early stages of a novel outbreak, as well as other logistical, political and economic constraints. because the interventions considered here are sub-optimal, cases will continue to occur whilst the intervention is in place, but at a slower rate than in the unconstrained epidemic. this means controls may need to be held in place for a long time, which may be costly. detailed derivations of the analytical results are given in a text s . one possible policy choice is to maintain an intervention irrespective of cost until the last case has recovered from the disease. this will always reduce the total number of cases and peak prevalence. these quantities can be expressed or approximated by analytical expressions, which we derive in text s and illustrate using numerical simulations. the final proportion of the population affected by an unconstrained epidemic, a ni , is given by solving [ , ] the final size increases monotonically with increasing r and does not depend on the generation time of the infection [ ] . for a long term intervention, implemented at t and held in place until there are no cases (figure ), the final epidemic size, a li (proportion of the population who have been infected) is given by where i t ð Þ is cumulative incidence up to time t . in the exponential growth phase, the cumulative incidence can be approximated by where r is the epidemic growth rate, given by r~r { ð Þc. for our parameter values, this approximation works well until about t = days ( weeks), when equation ( ) overestimates i t ð Þ by %. the final epidemic size decreases monotonically as the timing of the intervention, t , becomes earlier, and as the size of the intervention, w, becomes larger ( figure ). however, before week i t ð Þ is very small, so interventions starting earlier do not have much effect (figure ). in the absence of an intervention the maximum prevalence occurs when dy=dt~ , or when x~ =r , and the maximum prevalence is (using the equations above and x ð Þ& approximations to the initial conditions) is [ ] which increases with increasing r , and, as with the unconstrained epidemic size, does not depend on the generation time. in the presence of the intervention, maximum prevalence is dependent on the proportion of the population who are still susceptible at the time of the intervention. if the intervention is initiated before the peak in the unconstrained epidemic, and if cumulative incidence is sufficiently high and the proportion of the population still susceptible at the start of the intervention is less than = r {w ð Þ ð Þ , then peak prevalence will be at the start of the intervention, y t ð Þ. on the other hand, if the cumulative incidence is less than { = r {w ð Þ ð Þthere will be a peak during the intervention (figure ), which is given by if the intervention is initiated after the peak of the unconstrained epidemic, then there will not be another peak in prevalence during the intervention, since there will be too few susceptible individuals. these analytical results can be used to understand the effect of an intervention on the final size and peak prevalence, but we do not have neat expressions for the resulting duration of the whole epidemic (time until final case recovers) when an intervention is in place, and therefore we turn to simulation (figure ). the higher the transmission rate, the shorter the epidemic, which may be a desirable policy outcome. for influenza-like parameters, a few weeks delay may have only moderate deleterious consequences for peak prevalence, peak incidence or epidemic size (figure ) . this delay will result in higher peak prevalence, but it will also result in a considerably shorter epidemic than an early intervention (figure a circular inset and b) . this may be a desirable outcome in economic terms. the level of reduction in transmission has similar effects, where a more effective intervention put in place early in the epidemic will lead to the smallest epidemic size and peak prevalence, but the longest epidemic duration ( figure c and d) . in brief, the earlier a long term intervention is put in place and the more effective it is at reducing transmission, the greater the beneficial effect in terms of total epidemic size and peak prevalence. interventions of this kind are likely to be the most costly, and, counter-intuitively, may have to be held in place the longest. a strong argument to start an intervention early, however, is that the epidemic peak occurs later for early interventions (figure a) , allowing time to prepare public health facilities, to manufacture a strain specific vaccine and because there is great uncertainty about severity in the early stages of an outbreak [ ] . the drawbacks of a long intervention period are recognised in the usa national pandemic plan, where a maximum duration of weeks intervention is anticipated -another policy choice we considered. as above, we first consider some analytical expressions, and illustrate them using numerical simulation. for a single short term intervention from t to t ~t zd, the final epidemic size, a si , is given by note that, although i t ð Þ can still be approximated during the exponential phase of the epidemic (equation ( )), we cannot approximate i t zd ð Þ . in this case, the relationship between the final epidemic size and intervention parameters is more complex because cumulative incidence at the time the intervention is lifted depends both on cumulative incidence at the time the intervention is initiated and the size of the intervention, w. for example, if the duration of the intervention and its starting time are fixed, the epidemic size is optimized for intermediate values of the size of the intervention, w ( figure b, d) . with a short-term intervention, there are three possible maximum prevalence points. firstly, prior to the intervention (equation ( )), during the intervention (equation ( )), or after the intervention (note that i t ð Þvi t zd ð Þ ). the peak value could also occur at the point at which the intervention starts, i.e. when y~y t ð Þ. the conditions for each peak being the maximum are given in table . a large magnitude intervention (large w) may actually be deleterious, leading to a larger resurgence in prevalence after the intervention than an intervention with a smaller reduction in transmission. with a short-term intervention, there is no longer a monotonic relationship between the policy outcomes and the magnitude and length of the intervention. therefore strategies which contain the epidemic size below certain levels are unlikely to be the same interventions which contain peak prevalence below particular targets. for influenza-like parameters a -week intervention will almost certainly lead to a resurgence of the epidemic once the controls are lifted ( figure a, c) . if peak prevalence is very much lower during the intervention than it would be with no intervention, the implemented policy may even result in almost no change in the total epidemic size (figure ). for late, or less effective, interventions, prevalence during the intervention is higher than for early, or more effective, interventions,, resulting in fewer susceptible individuals remaining when the intervention is lifted. in this case the second peak is smaller, and reductions in total epidemic size are larger (figure ). for short term interventions, in contrast to long-term strategies, peak prevalence, peak incidence, and epidemic size cannot all be minimized by the same strategy. for instance, a % reduction in transmission timed to minimise total epidemic size ( figure a , b, initiated week ) may not be the intervention which minimises peak prevalence ( figure a , b, initiated week ). both these strategies have small and late resurgent epidemics ( figure a , circular inset), with cases beyond the end of the year. similarly, an intervention initiated at week may minimise peak prevalence for a % reduction in transmission ( figure c, d) , or minimize epidemic size with a % reduction in transmission ( figure c , d), but neither of these strategies are optimal if the aim is to have the epidemic exhaust itself most rapidly, with the quickest epidemic being the one without any intervention. the intervention always reduces peak prevalence from what it would have been in the absence of an intervention. however, which particular value is the peak value is determined by the timing of the intervention and the magnitude of the intervention ( table ) . each of these vary according to the characteristics of the intervention, and the underlying epidemic. for a fixed starting time and duration, there is a non-linear relationship between peak prevalence and the reduction in transmission, w (figure ). the value of w for which peak prevalence is minimized is almost certainly not that at which the total epidemic size is minimized (figure ). it is not possible to achieve a symptomatic epidemic size of % of the population with a week intervention for these parameter values. we therefore consider a scenario in which an intervention is initiated in the first weeks or months of the outbreak and held in place until months after the start of the outbreak. many different interventions can be used to constrain the epidemic size to % of the population. they range from an early intervention with a mild reduction in transmission, to a late, more impactful intervention ( figure a ). to achieve this aim whilst minimising peak prevalence it is not necessary to initiate the intervention early, in fact a delay may even be beneficial ( figure b ). but, the intervention must start before weeks (for these parameter values), when the number of cases prior to the intervention becomes large. if we evaluate the socio-economic 'cost' of these interventions as a simple product of the duration of the intervention and the reduction in transmission achieved, a delay also reduces the costs of the intervention, and the ideal intervention is more clearly defined ( figure b ). delay is valuable because transmission is being reduced, not eliminated, and therefore some of the effort in constraining the epidemic at the early stages is redundant. choices about intervention policy will be made early in the epidemic when parameters are uncertain. for example, r and the date of availability of the vaccine could be over or under estimated. of course, designing this intervention based on an overestimate of r means that the epidemic is smaller than expected, and so the intervention is too large and there are fewer cases overall ( figure c ). an underestimate in r means that the epidemic is larger than expected and so the intervention is not large enough to contain the epidemic and there are more cases than expected ( figure c ). in either of these cases, the intervention would have to be adjusted during the outbreak. if the 'optimum' intervention, which minimised peak prevalence, is chosen, it is more robust to changes in r than the other options ( figure c ). the interventions range from late interventions at the top of the a delay in the availability of vaccine increases the number of cases, but picking a late intervention minimises this effect. use of an imperfect vaccine for only % of the population results in a slower epidemic with fewer cases ( figure ) . the use of a pre-pandemic vaccine means that interventions which contain the total number of cases and peak prevalence can be rolled out later ( figure a ), compared to the non-vaccination scenario. also, as can be seen from the simple cost function (figure b ), the level of intervention can be reduced if pre-pandemic vaccines are used. the true economic value of this reduction in costs depends on the relative costs of vaccination, cases and interventions. the general picture remains the same as without vaccination. to minimize peak prevalence, the intervention should be initiated earlier than to minimize costs, but both objectives require interventions that commence several weeks into the epidemic growth phase ( figure b ). sensitivity to the value of r or the effectiveness of the pre-pandemic vaccine highlights that once again the most robust strategies are those that are minimize peak prevalence ( figure c ). in the absence of detailed analyses, it is often argued that epidemic outbreak control is best achieved by putting all mitigation options into play as early as is feasible. there may be delays before control strategies are implemented due to difficulties in identifying the early stages of a novel outbreak [ ] , as well as other logistical, political and economic constraints. of course, if interventions are held in place until a pandemic vaccine is available a greater level of reduction and earlier start of intervention will result in fewer cases, and a lower peak prevalence and incidence if intervention starts before the peak. however, not only are the costs of an intervention held for a long time likely to be high, but high demand for health services will be extended over a longer time period. our results indicate that an intervention starting at a few weeks into the epidemic is almost as effective at reducing epidemic size and peak prevalence as one starting at week . as such, given that the social and economic burden will be greater when starting earlier, starting a little bit later may be a better policy option. however, this will crucially depend on the socio-economic costs of both cases and interventions and on the estimated severity of the epidemic, which may be uncertain in the early stages of the epidemic [ ] . as noted in the introduction, the drawbacks of a long intervention period are recognised in the usa national pandemic plan, where a maximum intervention duration of twelve weeks is anticipated [ ] . using a twelve-week intervention, we have illustrated how the introduction of a short term intervention complicates the dynamics and increases the potential for conflict between policy aims. interventions of limited duration are very likely to result in a resurgence of the epidemic once they are lifted, unless it is imposed late in the epidemic or with low effectiveness. however, the height of this resurgence can be managed. a twelveweek interventions minimizing peak logistical pressure (peak prevalence and incidence) need not be very strong but require a timely start. on the other hand, an intervention that minimizes total epidemic size needs to be stronger and can start later, preventing a second peak. a number of american cities experience a second peak in mortality following the lifting of interventions during the pandemic [ , ] . re-analyses of a number of cities showed that multiple interventions were more effective at controlling transmis- figure . comparison of intervention strategies which 'buy time' until a strain-specific vaccine is available months into the epidemic and contain symptomatic cases to utilize a stockpile of treatments for % of the population. a uncontrolled epidemic (black dotted curve) and epidemic curves for five different strategies, starting at different times: t = , , , , or weeks into the epidemic. the required reductions in transmission are w = %, %, %, % and %. b peak prevalence (solid curve) and costs of interventions calculated as wt (dashed curve), in relation to the time of commencement of intervention. c excess number of cases for the five strategies if the parameters of the epidemic are different to those for which these interventions were designed: the availability of a strain specific vaccine is delayed until months (black), transmission has been overestimated and r = . (dark grey), or transmission has been underestimated and r = (light grey). doi: . /journal.pcbi. .g sion than single interventions [ ] . in addition, it was found that the later multiple interventions were implemented, the less effective they were in reducing mortality [ , ] . this was most notable when controls were implemented when excess mortality was higher than , per , [ ] . this conclusion cannot be so easily drawn in epidemics for which interventions were initiated prior to this threshold [ ] . here, we have shown that for short term interventions implemented during this early part of the epidemic earlier commencement is not always better, and that the outcome is highly sensitive to the timing and effectiveness of interventions. our two scenarios for policy design illustrate that applying one objective and then another sequentially (e.g. limiting total cases and then minimising peak prevalence for that epidemic size) can be used to resolve potentially conflicting aims. our results also show that the most extreme and earliest mitigation interventions are not always the best, and not always the least costly. it has not previously been highlighted that the level of stockpiles will quantitatively affect the required magnitude of social-distancing interventions so that all those who require treatment will receive it. any level of stockpiled antiviral drugs will reduce morbidity and mortality and therefore reduces the need for transmission-reducing interventions, as not all cases need to be prevented, but the availability of drugs means that demand for these drugs should not exceed supply. in addition, our results illustrate that even low coverage with imperfect vaccines can lead to reductions in the required interventions level to meet a defined objective for control. there are many complexities involved in quantifying the effect of interventions which are not included here, the complexities of transmission by age and spatial heterogeneities, the likely behavioral changes during an epidemic that affect transmission, seasonal variation in transmission, the logistics of delivery of prepandemic vaccines and drugs, the economic costs of an outbreak and potential development of resistance to antiviral drugs. detailed investigations are required to tailor general policies to particular settings, and therefore we are not attempting to make quantitative policy recommendations (see box ). however, uncertainties with regard to characteristics of the next pandemic strain will make it difficult in general to do very detailed optimization analyses. decisions on stockpiling must be based on knowledge from previous pandemics and seasonal influenza, but when a pandemic is at hand one has to work with the stockpiles available. intervention measures can be additionally imposed if a shortage of drugs is expected, or lifted to reduce the impact of intervention on society and economy, if drug supplies permit. our analyses show that there is indeed some time to choose the appropriate level of control, as very early commencement of intervention is hardly ever optimal for these time-limited interventions. our analyses also illustrates that even a simple inclusion of 'costs' changes what is optimal by comparison with analyses that are just based on impact on epidemiological measures. economic costs typically enter the equations in a non-linear term as indicated in our model formulation. however, including empirically derived cost functions will probably lead to the inclusion of more highly non-linear functions. this highlights the need to include more robust economic constraints into future epidemiological model analyses for public health policy support. in our view, this is a more urgent need than that of increasing the complexity of epidemiological description within models of infectious disease control. concomitantly, there is the associated need for measurement of the appropriate cost functions. data is available for both drug and vaccine purchase but this is regarded as confidential at present as neither the pharmaceutical industry nor government figure . addition of a pre-pandemic vaccine for % of the population. comparison of intervention strategies which 'buy time' until a strain-specific vaccine is available months into the epidemic and contain symptomatic cases to utilize a stockpile of treatments for % of the population when % of the population are vaccinated with a vaccine which reduces susceptibility and infectiousness by %. a uncontrolled epidemic (black dotted curve) and epidemic curves for five different strategies, starting at different times: t = , , , , or weeks into the epidemic. the required reductions in transmission are w = %, %, %, % and %. b peak prevalence (solid curve) and costs of interventions calculated as wt (dashed curve), in relation to the time of commencement of intervention. c excess number of cases for the five strategies if the parameters of the epidemic are different to those for which these interventions were designed: the pre-pandemic vaccine is less effective (black), transmission has been overestimated and r = . (dark grey), or transmission has been underestimated and r = (light grey). doi: . /journal.pcbi. .g health departments are keen to say how much was paid per dose as a function of total volume purchased. future research must address the detail of cost and benefit, both in terms of measurement of direct and indirect socio-economic costs, the costs of stockpiling and the benefits of reducing the impact of the epidemic and in terms of using a template for analysis that reflects the dynamics of virus transmission and the impact of control measures. in our model we have considered contact-reducing interventions, the use of antiviral medication, and vaccination with a prepandemic vaccine. for insight into the effect of other control options, it is useful to understand what characterizes these three particular control measures. antivirals work on the individual level, contact reduction on the population level, and vaccination on both. contact reduction and vaccination are preventive measures, whereas treatment is reactive. treatment and vaccines require stockpiling, and both are flexible with respect to possible timings of introduction during the epidemic. contact reduction is flexible in both planning and timing, but has major implications for the normal functioning of society. this flexibility implies that a broad range of more complex strategies could be envisaged, for example implementing and lifting a hierarchy of controls in response to the dynamics of the epidemic and importation of cases. however, the simple scenarios illustrated here highlight the complexities in selecting the best intervention policy, in terms of magnitude, timing and duration of interventions. the optimum intervention in terms of minimising peak logistical pressures (peak prevalence or incidence), may not be the same as one which minimises total epidemic size, and will almost certainly not be the one minimising direct social or economic impact from the intervention itself. the aims of a public health intervention policy must therefore be clearly defined, so that in the early phase of a pandemic sufficient resources can be put into characterizing the virus strain and measuring key epidemiological parameters as an essential template for decisions on what is the optimal mitigation strategy. text s detailed derivations of the mathematical expressions for epidemic size and peak prevalence. found at: doi: . /journal.pcbi. .s ( . mb pdf) factors that make an infectious disease outbreak controllable pandemic (h n ) pandemic potential of a strain of influenza a (h n ): early findings estimation of the reproductive number and the serial interval in early phase of the influenza a/h n pandemic in the usa pros and cons of estimating the reproduction number from early epidemic growth rate of influenza a (h n ) the early transmission dynamics of h n pdm influenza in the united kingdom use of cumulative incidence of novel influenza a/h n in foreign travelers to estimate lower bounds on cumulative incidence in mexico assessing the severity of the novel influenza a/h n pandemic early epidemiological assessment of the virulence of emerging infectious diseases: a case study of an influenza pandemic consultation on priority public health interventions before and during an influenza pandemic how prepared is europe for pandemic influenza? analysis of national plans progress and shortcomings in european national strategic plans for pandemic influenza strategies for mitigating an influenza pandemic targeted social distancing design for pandemic influenza mitigation strategies for pandemic influenza in the united states age-prioritized use of antivirals during an influenza pandemic analysis of the effectiveness of interventions used during the a/h n influenza pandemic optimizing infectious disease interventions during an emerging epidemic distribution of vaccine/antivirals and the 'least spread line' in a stratified population vaccination against pandemic influenza a/h n v in england: a real-time economic evaluation interim pre-pandemic planning guidance:community strategy for pandemic influenza mitigation in the united states-early, targeted, layered use of nonpharmaceutical interventions the effect of public health measures on the influenza pandemic in u.s. cities quantifying social distancing arising from pandemic influenza estimating the impact of school closure on influenza transmission from sentinel data closure of schools during an influenza pandemic sars in hong kong: from experience to action: severe acute respiratory syndrome (sars) expert committee of hong kong delaying the international spread of pandemic influenza modeling the worldwide spread of pandemic influenza: baseline case and containment interventions will travel restrictions control the international spread of pandemic influenza physical interventions to interrupt or reduce the spread of respiratory viruses: systematic review non-pharmaceutical interventions for pandemic influenza, national and community measures the effectiveness of contact tracing in emerging epidemics different epidemic curves for severe acute respiratory syndrome reveal similar impacts of control measures large-scale spatial-transmission models of infectious disease containing pandemic influenza with antiviral agents optimizing influenza vaccine distribution mitigation of pandemic influenza: review of costeffectiveness studies investment decisions in influenza pandemic contingency planning: cost-effectiveness of stockpiling antiviral drugs antiviral treatment for the control of pandemic influenza: some logistical constraints infectious diseases of humans: dynamics and control mathematical epidemiology of infectious diseases: model building, analysis and interpretation simulating the effect of quarantine on the spread of the - flu in central canada public health interventions and epidemic intensity during the influenza pandemic reducing the impact of the next influenza pandemic using household-based public health interventions strategies for containing an emerging influenza pandemic in southeast asia pandemic influenza: are europe's institutions prepared? cost-benefit of stockpiling drugs for influenza pandemic antiviral resistance and the control of pandemic influenza hedging against antiviral resistance during the next influenza pandemic using small stockpiles of an alternative chemotherapy potential public health impact of imperfect hiv- vaccines imperfect vaccines and herd-immunity to hiv strategy for distribution of influenza vaccine to high-risk groups and children epidemiology, transmission dynamics and control of sars: the - epidemic the authors thank maria van kerkhove for assistance with reviewing the literature and christophe fraser for helpful discussions. we also thank anonymous reviewers for helpful comments. key: cord- -zm ih y authors: gani, raymond; hughes, helen; fleming, douglas; griffin, thomas; medlock, jolyon; leach, steve title: potential impact of antiviral drug use during influenza pandemic date: - - journal: emerg infect dis doi: . /eid . sha: doc_id: cord_uid: zm ih y the recent spread of highly pathogenic strains of avian influenza has highlighted the threat posed by pandemic influenza. in the early phases of a pandemic, the only treatment available would be neuraminidase inhibitors, which many countries are considering stockpiling for pandemic use. we estimate the effect on hospitalization rates of using different antiviral stockpile sizes to treat infection. we estimate that stockpiles that cover %– % of the population would be sufficient to treat most of the clinical cases and could lead to % to % reductions in hospitalizations. substantial reductions in hospitalization could be achieved with smaller antiviral stockpiles if drugs are reserved for persons at high risk. r ecent outbreaks of highly pathogenic avian influenza in poultry in east asia (h n ), canada (h n ), and the netherlands (h n ), and their subsequent transmission to humans, have intensified concern over the emergence of a novel strain of influenza with pandemic potential. three influenza pandemics occurred during the th century, with varying degrees of severity; outcomes ranged from the high levels of illness and death observed during the spanish flu pandemic (estimates of deaths range from to million [ ] ) to the much lower levels observed during the pandemics of and (≈ million deaths each [ ] ). while recognizing that the characteristics of future influenza pandemics are difficult to predict, the world health organization (who) has recommended that nations prepare pandemic contingency plans ( ) . several have been drafted, and some have been published ( ) ( ) ( ) ( ) , although all are subject to continuous refinement. surveillance, on both a local and global scale, will enable policy makers and practitioners to act during the early phases of a pandemic. however, the likely rapid global spread of a pandemic strain will limit the time available to implement appropriate mitigating strategies, and preemptive contingency planning is needed. a number of intervention strategies can reduce the impact of influenza pandemics. during interpandemic years, influenza vaccination is used to reduce deaths and disease. however, vaccine is unlikely to be available in time or in sufficient quantities for use during a pandemic ( , ) . other, nontherapeutic, disease control options may be used, such as those used during the outbreak of severe acute respiratory syndrome ( ) . however, groups of antiviral drugs are available for the treatment and prophylaxis of influenza. these are the adamantanes (amantadine and rimantadine) and the neuraminidase inhibitors (oseltamivir and zanamivir). the adamantanes may be effective against pandemic strains, but concern exists about adverse reactions and the development of antiviral resistance. resistance to amantadine has been demonstrated in a number of avian h strains ( ) and its use for treatment of influenza is not recommended ( ) . the neuraminidase inhibitors (nis) reduce the period of symptomatic illness from both influenza a and b viruses ( ) and both are recommended for use in the united kingdom for treatment of at-risk adults who are able to begin treatment within hours of onset of symptoms. oseltamivir is also recommended for the treatment of atrisk children > months of age ( ) . the development of antiviral resistance has been reported for nis, particularly related to oseltamivir use in children ( ) , although current evidence suggests that resistant strains are pathogenically weakened ( ) . the use of nis for treatment of pandemic influenza remains an option since they may improve individual disease outcomes and the effect of the disease in the population. an influenza pandemic is likely to increase demands on healthcare providers, especially in hospitals. except in japan, current levels of ni use are low. any strategy involving ni use would require stockpiles of these drugs. the potential use of antiviral agents for prophylaxis has been investigated elsewhere and may be of greatest use in the earliest phases of a pandemic to retard the spread of the virus ( , ) . earlier pandemic influenza modeling studies have also focused on the economic effect of vaccination ( ) and the use of ni prophylaxis for disease control ( ) . we assessed the potential effect of using nis for treatment on the estimated number of influenza-related hospitalizations likely to occur during a pandemic. unlike in previous studies ( ) , we have also taken into account the reduction in infectivity that antiviral treatment may have on community transmission. our models focused on using nis to treat different age and risk groups and the potential effects treatment might have on influenza hospitalizations. these effects have been quantified by using the mathematical model described in the online appendix (available from http://www.cdc.gov/ ncdod/eid/vol no / - _app.htm). the length of the latent, noninfectious period was assumed to be days ( ) , and the infectious period was assumed to be days ( , ) . hospitalization rates for the baseline scenario were calculated by using data from interpandemic influenza and are given for different and age risk groups (table ) . to be effective, ni treatment must be administered within hours of symptom onset. the efficacy of ni treatment appears to prevent % of hospitalizations, mirroring efficacy rates against developing complications; this efficacy rate is approximately the same for oseltamivir and zanamivir ( ) . symptoms were also reduced by ≈ . days; treatment was assumed to produce the same decrease in the infectious period. the population was stratified as for seasonal influenza; persons were considered to be either at high risk for severe outcome or at low risk ( ) . the at-risk group included those with chronic respiratory disease, chronic heart disease, chronic renal failure, diabetes mellitus, and immunosuppression; this group also included all persons living in long-term care facilities, such as nursing homes ( ) , and all those > years of age ( ) . demographic data used in the model were based on age-specific distribution of the uk population (office for national statistics, http://www.statistics.gov.uk). the model was used to simulate a number of scenarios, on the basis of contingency plans and previous pandemics, to investigate the effect of targeting nis to different age and risk groups on the expected number of hospitalizations during a pandemic. the baseline scenario for this study was that advocated by who ( ) and was also used previously by meltzer et al. ( ) . this scenario assumes a clinical attack rate, in the absence of interventions, of % of the population, which occurs during a single wave. assuming that half of infections are nonclinical or asymptomatic (i.e., a serologic attack rate across the population of %) ( ), a value for the basic reproduction number, r , of . can be calculated. when these parameters are used in the model in the online appendix, the effect of different-sized antiviral stockpiles on the overall clinical attack rate can be estimated. the outputs from the first set of simulations are shown in figure . the baseline scenario is shown alongside a range of other clinical attack rates ( %- %) (i.e., varying r from . to . ) in the absence of interventions. for these scenarios, antiviral treatment is assumed to be possible within hours of onset for all symptomatic patients until the stockpile is exhausted, with the exception of those < year of age, who are not treated at any stage (treatment for this age group is contraindicated [ ] ). the points on the curves in figure , where the gradients change from vertical to horizontal, indicate the points at which the stockpile is sufficient to treat all patients; increasing the stockpile size would produce no additional depicted are clinical attack rates before interventions of %, %, %, %, and %, with corresponding values for the basic reproduction number (r ) of . , . , . , . , and . respectively. the precipitous decreases observed with the % and % attack rates result at the points at which the stockpile becomes large enough to last long enough to prevent a recrudescence of the epidemic by suppressing the effective reproduction number. benefit and would therefore result in a surplus of antiviral treatments. for the baseline scenario, a stockpile large enough to treat % of the population (i.e., a % stockpile) would be sufficient to treat all patients, even if the clinical attack rate in the absence of treatment is %. this difference is due to a reduction in the effective reproduction number of the disease, r ε , caused by shortening the infectious period of those treated by . days. across the different attack rates, stockpiles sufficient to treat < % of the population are unlikely to result in major changes to disease dynamics. outputs are most sensitive to the clinical attack rate when the reduction in the infection period caused by treatment is sufficient to bring r ε < . when r ε is < , the number of secondary cases produced by each person is < , and incidence, therefore, decreases. the value of r ε can be calculated as where s is the proportion of the population susceptible. with treatment, this equation can be rewritten as where i t is the decrease in the infectious period due to treatment, i p the infectious period, and c i the proportion of infections in each of the different population subgroups, i, that are treated. for the scenarios in figure , i t = . days, i p = . days and c i = . for all groups except those < year of age, who only constitute . % of the population. therefore, the term within the brackets for this scenario can be calculated as . . at the start of the pandemic, s is assumed to be ; therefore, if r is < . , the outbreak can be controlled by treating all patients. for pandemics in which r is > . , depletion of susceptible persons through infection is also required before r ε decreases to < , which is equivalent to s = ( . r ) - . the effect of different treatment strategies on hospitalization rates was generated from the baseline scenario: treating all patients, only at-risk groups, only children and the elderly ( - and > years of age), and only the working population ( - years of age). these scenarios were of potential interest to public health planners; outputs are shown in figure . given a large enough stockpile, the best option to minimize hospitalizations would be to treat all patients; for this scenario, a % antiviral coverage would reduce hospitalizations by up to %. an alternative strategy of treating the whole working population reduces the hospitalization rate by up to % but requires a similar antiviral stockpile size, and treating the working population consistently fails to reduce the number of hospitalizations below the number that would be expected if everyone were treated, regardless of stockpile size. this increase is because the hospitalization rate for the working population is less than the average in the population and also because treating a smaller proportion of the population has less effect on the overall transmission rate. for stockpile sizes only large enough to treat < % of the population, the best strategy would be to treat at-risk groups; this strategy is also best for stockpile sizes up to %, with hospitalizations at this level reduced by up to %. for stockpile sizes from % to %, the best strategy is to treat children and the elderly (reducing hospitalizations by up to %) and for stockpile sizes > %, to treat everyone. the optimum treatment strategy is therefore dependent on treating those at highest risk for hospitalization. the simulations for the baseline scenario were based on a uniform age-specific attack rate and on age-and risk-specific hospitalization rates from interpandemic years because of the uncertainty over the precise characteristics of a future pandemic. since the age-specific clinical attack rate has varied between pandemics, we repeated the analysis above, as far as possible, using the age-specific attack rates from previous pandemics ( - ) ( table ) for comparison with the baseline scenario. the uk pandemic began with imported cases in july ; deaths peaked in november , with a reported overall clinical attack rate of % ( ) . the proportion of infections resulting in clinical illness was calculated from a small serologic survey of general practitioners; only % of the general practitioners surveyed with a positive antibody titer actually had symptoms ( ) . the serologic attack rate was calculated as %, which would require r = . . the epidemic curve that this figure would generate is shown in figure a , with the curve scaled to fit the epidemic curve for deaths ( ) . the only additional change from the baseline scenario is the hospitalization rate, which was reported to be / , population ( ) . using the age-specific attack rates for (table ) in the model, we scaled hospitalization rates to achieve an overall hospitalization rate of / , ( table ) . the results ( figure b) show that a %- % antiviral stockpile would be sufficient to treat all patients during the first wave, a figure that is larger than that seen for the baseline scenario, as both the clinical and serologic clinical attack rates were higher. however, qualitatively, the results are similar in spite of the differences in attack rates between different age groups. with a stockpile as large as %- %, an estimated reduction in hospitalizations of ≈ % could be expected. as in the baseline scenario, effective targeting of smaller stockpiles to at-risk groups can also be used to produce large reductions in hospitalization rates. for stockpiles < %, the best strategy is to treat those at risk, which results in a reduction of %. for stockpiles sizes from % to %, the best strategy is to treat the young and elderly, which results in a % reduction. the highest reduction from treating the working population is % and remains a suboptimal strategy for any stockpile size. the implications of different treatment strategies on the hospitalization rates with a % stockpile are shown in figure c . strategies with larger proportions of the % stockpile had the greatest effect on the epidemic, steadily delaying, but not diminishing, the peak of hospitalizations. treating only the working population results in a % decrease in hospitalizations, treating all patients results in a % decrease, and treating children and the elderly a % reduction. with each of these strategies, the antiviral stockpile is exhausted before the end of the pandemic, whereas the fourth strategy of treating at-risk groups reduces hospitalizations by % and only requires a % stockpile. therefore, treating those at risk is the most efficient strategy, but further targeting may be considered to avoid surplus treatments. the pandemic was characterized by waves, the first relatively small, occurring from february to april ; the larger wave occurred from november to january ( ) . we predominately considered the second wave. a confounding factor is that a proportion of the population would have been immune because of the first wave. weighting age-specific clinical attack rates ( ( ) . b), estimated hospitalization rates from a simulated pandemic with available parameters from the pandemic, as influenced by stockpile size and treatment strategy. c), impact of treatment strategy on the time course of hospitalizations when the stockpile size is fixed at % of the population, the stockpile is fixed at % of the population and all clinical cases are treated, and when no treatment is administered. overall clinical attack rates for the first and second waves to be % and %, respectively ( ; office for national statistics [http://www.statistics.gov.uk]). the serologic attack rate was derived by fitting the model to the data for the second wave from the royal college of general practitioners (provided by douglas fleming; http://www. rcgp.org.uk); we assumed a similar proportion of asymptomatic cases in both waves. the fit of the model to the data is shown in figure a , from which is derived a % residual immunity from the first wave and a % serologic attack rate for the second wave, which produces an effective reproduction number of . for the second wave. the overall hospitalization rate for the second wave was reported as per , ( ) , and using the age-specific attack rates for in table , we adjusted the values in table to fit this value. the size of the stockpile required to treat all patients is ≈ % (which is relatively small compared to the pandemic because of the lower clinical attack rate), which leads to fewer patients being treated and less reduction in overall transmission. if all persons whose infections resulted in clinical illness (i.e., patients) were treated, the hospitalization rate would drop by ≈ % ( figure b ). for the pandemic, the effects of the different antiviral targeting strategies were different than in the previous scenarios as a result of the different age-specific attack rates, which are shifted more towards the working population (table ) . thus, relatively small stockpiles are required to treat either the at-risk group or the young and elderly group (≈ % for each group), since most patients are in the working population and neither of these groups. for stockpiles of up to %, treating the at-risk group is marginally better than treating the young and the elderly ( % reduction in hospitalization as opposed to %), and for stockpiles > %, treating all clinical patients would be the best strategy. the effects of the different treatment strategies with a % stockpile are shown in figure c . hospitalizations would drop by ≈ % if all patients were treated and by % if the working population were treated; both treatment strategies would lead to the stockpiles' being exhausted. as above, treating those at risk would reduce hospitalizations by %, whereas treating only children and the elderly would reduce hospitalizations by % and only require a % stockpile per group. of these strategies, treating the at-risk groups is the most efficient, but given surplus stockpile, further extension of the groups to be targeted may be considered. the characteristics for the pandemic differ substantially from the other in that distinct waves occurred; the age-specific attack rates were highest for those in their teens, s, and s; and the mortality rates were higher ( ). in addition, age-specific attack rates and mortality rates differed for each of the waves ( ) . modeling based on the pandemic was therefore considerably less straightforward than for the previous pandemics, and an approach was taken to fit the transmission model to each of the waves, separately. no cross-immunity was assumed between different waves since studies suggested only weak effects; indeed, some studies suggested greater susceptibility in the third wave if a person had had influenza in the first pandemic wave ( ) . clinical attack rates were calculated from reported weekly mortality data and clinical case-fatality rates ( ) . serologic attack rates were then fitted separately to each of the curves ( figure ), from which values of r = . , . , and . were derived from each of the respective waves. the estimate for the second wave is lower than other estimates of ≈ ( ) derived from us cities and is probably because our estimates were derived from data from throughout england and wales, thereby incorporating spatial heterogeneity. since hospitalization rates were not available for any of the waves, we considered the effect of antiviral treatment on death. the potential efficacy of antiviral treatments in preventing death between waves may have differed, but it was assumed to provide % protection against death. this estimate was based on the assumption that % protection from the more serious outcomes of influenza can be translated to equivalent protection from death ( ) . a pandemic with the characteristics of that in would, without antiviral treatment, produce an estimated number of deaths equivalent to ≈ . % of the population across all waves. however, a % stockpile sufficient to treat all patients across the waves would result in ≈ % reduction in deaths. with a smaller stockpile of %, the reduction in deaths was only % because the stockpile becomes exhausted during the second wave, before most of the deaths occur ( figure ). the baseline scenario with an overall clinical attack rate of %, as currently advised by who ( ), is roughly in accordance with data from previous pandemics. the general conclusion from our study is that antiviral treatments for % to % of the population are likely to be sufficient to treat all patients for pandemics with characteristics that have been observed to date. the size of the stockpile required will depend on the clinical attack rate of the pandemic and the r value. however, with smaller stockpile sizes, substantial reductions in hospitalizations can be achieved through targeting. for the smallest stockpiles, the best strategy was to treat conventional influenza at-risk groups. treating the young and elderly is only slightly less effective. treating the working population may have benefits beyond reducing hospitalizations, such as reducing illness-related absenteeism, but it consistently fails to be the best strategy for reducing hospitalizations. for large stockpiles, treating all patients is consistently the best strategy in reducing hospitalization and transmission. when all patients are treated, the marginal effect of treatment on reduced transmission increases with the number of patients treated, until all patients have been treated. further studies regarding the effects of antiviral treatments would improve the robustness of the parameter estimates. in particular, better estimates on the efficacy of ni treatment against hospitalization and death rates for different age and risk groups and estimates on the reduction in the infectious period are required. also, the issue of antiviral resistance needs to be resolved since it could compromise ni effectiveness. the scenarios above assume that clinical patients were treated within hours of onset of symptoms; however, in reality, some cases will be diagnosed or reported too late, and other patients will be administered drugs mistakenly. to maximize the benefits of antiviral treatment, patients should be strongly encouraged to seek treatment and treatment should be supported by sound clinical judgment and ( ) . b), estimated hospitalization rates from a simulated pandemic with available parameters from the pandemic as influenced by stockpile size and treatment strategy. c), impact of treatment strategy on the time course of hospitalizations when the stockpile size is fixed at % of the population, the stockpile is fixed at % of the population and all clinical cases are treated, and when no treatment is administered. diagnostic capability. if high levels of treatment are not achievable, disproportionately higher hospitalization rates than those calculated here would ensue. in addition, identifying groups with higher transmission rates for targeting treatment would result in greater reductions in transmission than reported here. assessments will need to be recalculated in the earliest phases of a pandemic with real-time data to confirm or update the assumptions used and ensure that the model parameters are appropriate. therefore, were a pandemic to occur, intensive analysis of its dynamics would be required at its start. updating the accounts: global mortality of the - "spanish" influenza pandemic the epidemiology and clinical impact of pandemic influenza world health organization. influenza pandemic plan. the role of who and guidelines for national and regional planning. geneva: the organization influenza pandemic preparedness plan for the united states uk pandemic influenza contingency plan influenza pandemic: preparedness planning in germany canadian pandemic influenza plan, health canada are we ready for pandemic influenza? pandemic influenza and the global vaccine supply evaluation of control measures implemented in the severe acute respiratory syndrome outbreak in beijing amantadine resistance among hemagglutinin subtype strains of avian influenza virus full guidance on the use of zanamivir, national institute for clinical excellence. full guidance on the use of zanamivir, oseltamivir and amantadine for the treatment of influenza the treatment of influenza with antiviral drugs resistant influenza a viruses in children treated with oseltamivir: descriptive study neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir tackling the next influenza pandemic tackling the next influenza pandemic: ring prophylaxis may prove useful early on, but is unlikely to be effective or practical to implement once the pandemic is established the economic impact of pandemic influenza in the united states: priorities for intervention containing pandemic influenza with antiviral agents pandemic influenza and healthcare demand in the netherlands: scenario analysis a bayesian mcmc approach to study transmission of influenza: application to household longitudinal data the population at risk in relation to influenza immunisation policy in england and wales. health trends department of health. influenza immunisation. cmo's update influenza: quantifying morbidity and mortality joint public health laboratory service/royal college of general practitioners working group london: her majesty's stationary office influenza - incidence in general practice based on a population survey report on the pandemic of influenza - . london: her majesty's stationary office impact of epidemic type a influenza in a defined adult population transmissibility of pandemic influenza we thank members of the uk department of health steering group for their comments and help with setting model parameters.financial support for this work was provided by the uk health protection agency. the views expressed in this publication are those of the authors and not necessarily those of the health protection agency.dr gani is a mathematical modeler. his research interests are the impact of pandemic influenza and other emerging and reemerging infectious diseases on human populations and assessments of policy options available to mitigate these impacts. key: cord- -qeuvymu authors: banai, reza title: pandemic and the planning of resilient cities and regions date: - - journal: cities doi: . /j.cities. . sha: doc_id: cord_uid: qeuvymu the emergence of the coronavirus pandemic motivated this paper, which revisits the nexus of public health and the city, itself a main source of a pandemic which similarly threatens the lives and properties of the world population gradually one glacier at a time: climate change. we argue that pandemics expose both the vulnerability and resilience of the urban system expansively, from rooftop to the region, but also serve as change agents for the planning of resilient cities and regions globally. the discussion of the urban system and the pandemic is comparative, with the recent coronavirus and climate change, a persistent, long-lasting pandemic. the historical and critical review and synthesis of the durable concepts of the urban system at the kernel of the theories and practices of urbanism is highlighted by place matters, cyberspace, density, access, and the city-region. we note the implications for reconfiguring the resilient urban system of the future effectively with pandemic as change agent and the comprehensive plan and its regulatory zoning ordinance as implementation tool. public health and city planning have common disciplinary purposes. city planning's professional identity is defined as a guardian of "public interest." standard city planning enabling act (scpea, u.s. department of commerce ) is even more specific, defining municipal planning's promotion of "health, safety, and general welfare" of the population. public health is about identification, control, and prevention of disease. the common references to parks and open spaces with a physiological metaphor-the "lungs" of the city-connotes the nexus of public health and the city explicitly. city planning's focus is the physical layout of the city in a manner that promotes health and prevents the occurrence of diseases in the first place. concomitantly, city and regional planning and design theories, concepts, regulations, and practices emerge historically in response to public health crises, including pandemics, pollution with rapid industrialization, congestion with urbanization, and loss of green space in cities. the origin of modern city planning is aligned with sanitary, housing, and social reforms since the mid-nineteenth century and around the turn of the twentieth century-movements dealing with inadequate sanitation-itself a pandemic response-and limited access to air and sunlight in crowded tenement housing and dilapidated slums. the coronavirus pandemic has at least temporarily significantly reconfigured city life-the relation of work and residence, and leisure, use of public space, safety and security of transportation, both public and private-and posed fundamental equity of access to resources. a smart planning scenario could not have anticipated and illustrated the wide-ranging, impactful socio-spatial dimensions of the coronavirus pandemic in entirety this vividly, let alone applied standard urban planning tools-the comprehensive plan and zoning regulations-proactively (banai, a; kelly, ) . it turns out, planning's tool set are disproportionately limited piecemeal or disjointed compared to the magnitude and wide-ranging scope of the better known, durable pandemic of climate change. however, the global experience of the coronavirus pandemic also informs and suggests what kind of planning is commensurate with the dimensions of the challenges posed by climate change. it turns out, pandemics expose the vulnerability and resilience of the urban system, ironically with durable concepts of urbanism, highlighted from the rooftop to the region. the paper is organized by a discussion of durable concepts of urbanism, with implications for reconfiguring the urban system, aided by invoking urban planning's standard tool-the comprehensive plan. the paper concludes with a discussion of planning resilient urban form of the future in the era of climate change. oxford dictionary defines pandemic with its greek origin in midseventeenth century, pandēmos, all (pan) people (demos) "prevalent over a whole country or the world." arguably, climate change, which is prevalent globally, fits that definition, just as coronavirus does. a question is immediately raised: which pandemic is more costly-coronavirus or climate change? hint: one pandemic is a one-hundred-year event, compared to the other, with an incubation period that started with the industrial revolution in s. however, the two pandemics have a similar pattern of spread: exponential. measured by loss of human life, unemployment, underemployment, social isolation, public expenditures, reduction in gross domestic product, and supply-chain interruption, the costs of coronavirus are immense. however, compare the cost of climate change. green house gas (ghg) traps pollutants in cities. combine tailpipe and smokestack pollution from vehicles, buildings, factories, and heat islands in cities, and there is recipe for respiratory illness, including asthma and cardiovascular disease, consequential for the children, the elderly, and populations predisposed with genetic chronic health conditions. parenthetically, people with respiratory and cardiovascular illness and diabetics, which are also linked to urban form-induced obesity as well as poor diet, have a lower chance of surviving the other pandemic: coronavirus. furthermore, consider the costs of entire islands inundated due to sea-level rise, or so-called king (or high) tides that infiltrate coastal cities' groundwater table with sea salt, threatening drinking water or causing frequent surficial flooding depositing sewage into rivers and lakes (chicago), and disrupting traffic in city streets (miami). add the mitigation costs of levee, dike, and sea-wall construction in coastal cities globally, like new york city, new orleans, amsterdam, venice, and london. include droughts that threaten agriculture, causing food insecurity that subsequently threatens employment and national security (even a source of failing states), and induces population migration in search of survival. this is not an exhaustive itemized costs brought about by the silent pandemic of climate change gradually taking its toll on the built and natural environments. the evidence of climate change pandemic and its consequences for cities and regions is compelling. the itemized list in the comparison of pandemics of climate change vs. coronavirus is tentative with respect to consequences of coronavirus. the juxtaposition of the two pandemics, however, is instructive. ironically, one pandemic has a positive impact on the other (see fig. ). images in the media show clearer skylines and iconic, ground-level landmarks, such as the eiffel tower, to be more visible than usual due to quarantines in otherwise congested, polluted, populated, heated-up cities. there are even the images of venice's canals and waterways looking clearer than ever, as the coronavirus quarantine leaves them undisturbed. u.s. environmental legislation has ensured public health of the city with clean air and clean water for the past half-century, abating ghgs-carbon dioxide, sulfur dioxide, nitrate dioxide. similarly, clean water legislation regulated the disposal of cities' waste into rivers, the sources of drinking water and aquatic life. ohio's cuyahoga river was once so polluted that it caught fire, but owing to the clean water act, it's now home to marine life. however, the images of clean waterways and clear skylines during the coronavirus epidemic suggests next steps toward further management of waterways and air pollution in cities. we hope for a vaccine that will cure the coronavirus, but no such thing can solve the pandemic of climate change. it takes more than a shot in the arm. surreal images of cities known for their population density, air pollution, and traffic during the pandemic appeared in the media-skyline visibility but with empty streets, deserted downtowns, blighted parking lots surrounding commercial retail stores, empty office buildings, locked college and university gates, and desolate public parks. in the pre-coronavirus era, empty stores and parking lots and desolate public spaces were regarded as indicators of intolerable blight, justification for urban revitalization. ironically, among the vestiges of blight and sprawl is the drive-in movie theatre, revived because of the pandemic as a safer alternative than the big-box movie theatre. and the impact of social isolation on mental health is also recognized. how could cities and regions sustain the public health benefits of cleaner air and water with a resilient urban form and a smaller ecological footprint post-coronavirus? the coronavirus pandemic, despite its devastatingly inimical tolls on humans, sheds light on the architecture of urbanism, revealing strengths and vulnerabilities of the urban system. the pandemic has in effect enabled a social experiment with controls that are usually possible only in the closed system of a laboratory, not in the open system of a society; however, this experiment calls for a rethinking the urban system with expansive concepts of resilience in planning cities and regions. we note the implications for the comprehensive plan in the face of climate change. the literature on the importance of place, and the related discussion of place-making in urban studies abound. much of the discourse of the new urbanism which emerged in the s is about civic places, which disappeared in the private, subdivided spaces of suburbia (katz, ) . the american dream of a house, a yard, and car excluded community, as hayden ( ) argued (see also calthorpe, ; mcharg, mcharg, / . the mainly residential suburbs bereft of civic spaces could not accommodate a social place for the teenage population without the car, with the exception of vacant lots and buildings under construction. suburbia segregated commercial-residential-public land use, in contradistinction to the historic american main street with fine-grained, mixed land use, and an accessible park. the comprehensive (master) design plans of new urbanism aimed to remedy this shortcoming with integrated land use and pedestrian-friendly access, with enhanced public realm elements, which occupy prominent landmark locations with water feature and articulated surficial materials of the sidewalks anchored by gazebos and pocket parks, heeding the pedestrian as well as vehicular circulation. when the pandemic limited or prohibited access to the public realm, its significance became even more apparent, albeit with an eerie sense of a public realm that is no longer a public domain. the longing for the city's public realm, temporarily off-limits during the pandemic, was expressed through the building balcony, which architecturally transitions between public and private space. the balcony substituted for an inaccessible public realm-from the street, the town square, the park, the waterfront, the cemetery, to places for religious gatherings, church, synagogue, mosque-places that functioned, albeit with some adaptation, aided in cyberspace, and occasionally in defiance of any imposition of control (see also oldenburg's ( oldenburg's ( / ) notion of the necessity of "the third place" where essential human interaction occurs beyond work and home; see also calthorpe & fulton's, , page elaboration). the limit of the experience of physical place via cyberspace is readily revealed if reminded by lynch's ( ) cognitive mapping of the five elements that makes the city legible or imageable, and the sense of place attributes including ambience, sound, smell, topography (steepness of roads) and the like. if eclipsed in dense theoretical academic writing, commercial and social media alike exemplified the significance, actual experience of and the longing for the city's public realm, particularly during a pandemic. the vitality of the city is determined by place. where else? vitality is among the five "performance dimensions" of good city form, defined by lynch ( , page ) as "… the degree to which the form of the settlement supports the vital functions, the biological requirements and capabilities of human beings-above all, how it protects the survival of the species." (see also banai & rapino, .) where better to observe the function (or dysfunction) of the settlement form but in the city's public realm, particularly in a pandemic. it is not just the pandemic of an infectious disease that is consequential for the vitality of the city's public realm. climate change's extreme weather pattern with heavy rain events threatens city's vital public realm element with street flooding. the point-and non-pointsource pollution during intense rain events threatens city's water bodies. the comprehensive plan can increase cities' resilience by rezoning blighted, abandoned industrial and commercial properties as green open space buffers that absorb or slow surficial runoff that creates hot spots of pollutants in cities' rivers, creeks, and streams. a dominant element of the public realm is the suburban arterial street. the wide arterial street is enhanced if "shared" equitably accommodating movement of pedestrians and vehicles. the long-term comprehensive plan is a tool to accomplish this aim, by physical design alterations that "calm" traffic and thereby increase public safety. integration of green space in the arterial street in the form of medians or embankments enhances pedestrian safety while abating runoff during the intense rain events that characterize climate change. telecommunications technology and cyberspace substitutes for risky in-person communication in physical space during an easily transmittable pandemic. communication theorists widely touted the benefits of interaction at a distance even pre-coronavirus. among others, webber ( ) argued the case for "community without propinquity." the coronavirus effectively revived and reminded us of the merits of the arguments for and against more widespread online communication. arguments in favor of communities of place rather than communities of interest in cyberspace (calthorpe & fulton, ) , however, suggest plausibility with the experience of communication during pandemic and the longing for interaction in physical space of place and neighborhood, and the (physical) public realm, even in defiance of state control. economic and urban theorists up the ante by privileging the benefits of interaction with economies of agglomeration in physical space necessary for efficient business transaction (see also lynch ) . notwithstanding the facility of communication in cyberspace, still an urban form of the future-the aerotropolis-is defined by a physical space that accommodates agglomeration of firms and business transactions in a central location akin to the city's central business district (cbd) (kasarda, , kasarda, , kasarda and lindsay . the pandemic showed us the inequity of access due to lack of broadband technology-the digital divide-so the comprehensive plan is an ideal tool for enhancing city's resilience by a planning infrastructure that not only includes water, sewer, and roads, but also broadband service (see also kelly, ) . we learned from the pandemic how vital functions are interrupted-education, from pre-school to college; health care; and access to jobs and services. broadband access is not a luxury but a necessity when in-person access is interrupted or not an option. parenthetically, a similar logic holds in planning transit-supportive or transit-oriented developments. the urban form, with its land-use mix and proximity to the centrally located retail and office services are desirable features because of walkability, regardless of the availability of transit (calthorpe, ; calthorpe & fulton, ). the environment-behavior nexus was investigated more than half a century ago by the then-burgeoning subfield of environmental psychology. these well-known laboratory experiments revealed how rats develop abnormal behavior when subjected to crowding. concomitantly, the classic environmental-behavior studies informed how urban form likely impacts the physical and mental health of the urbanists. even obesity (body-mass index) is linked to urban form (walkability), elucidated in the contrast of compact vs. urban sprawl (e.g., frumkin et al., ; ewing et al., ) . commentators, backed by empirical evidence, touted the public health benefits of cities that promoted walkability with multi-modal regional mobility, thereby abating obesity, and which contained places of work as well as residence and leisure, thereby minimizing stressful commuting to work. (ewing et al., ; frumkin et al., ) . the urban-studies literature has given considerable attention to density. density figures prominently in urban studies since the feasibility of a vital element of urban form-public transit-is contingent on population density's minimum threshold. however, even predating the laboratory experiments of the environmental psychologists, an english thinker (howard, (howard, / around the turn of the century proposed and later constructed a garden city that meant to address the health, safety, and general welfare of industrial city residents exposed to all the negative consequences of industrialization, crowding, congestion, pollution, sprawl, and lack of parks and open green space. arguably, the small, low-density garden city land use in balance with the natural environment is a more resilient model of urbanism than the compact, high-density new york city in the face of epidemic guidelines that call for social distancing and low population density of the public realm. durable concepts of urbanism originate prominently in the contrast of two prominent thinkers, one english and the other french. the french modernist architect-urbanist le corbusier ( corbusier ( / ) touted his tower-in-the-park skyscraper concept of contemporary city as a better solution to the rapid urbanization of population and congestion spurred by industrialization. the contemporary city accommodated times the population of the garden city with only , that his english predecessor, howard ( howard ( / had proposed in skyscrapers (legates & stout, ) . the "popular response" to plan voisin, a later version of the contemporary city proposed for central paris in , was "outrage" (legates & stout, ; see also birch, ). however, corbusier's concept of a dense, modern urbanism with the iconic skyscraper endures globally in cities, famously in the iconic new york city (see lang, ) . the pandemic cast a negative image of urban density, and its corollary, public transportation, as hotspots of the coronavirus (new yok city, los angeles, and compact spanish, italian, and english cities). density figures prominently in contemporary accounts of new urbanism since density correlates with walkablity in the "transit metropolis" (cervero, ) . even before the coronavirus pandemic, the dense high-rise buildings-particularly for public housing in neighborhoods disconnected from the rest of the city-connoted the image of the vulnerability of their impoverished, isolated, low-income residents. the destruction of st louis's pruitt igoe-designed by a renown modernist architect-demonstrated the unsustainability of the high-rise public housing project. in contrast, modern high-rise buildings could densely accommodate residents in resort towns with a premium view and rent. their residents could weather the lock-down, shelter in place guidelines during the pandemic. however, public housing, following federal guidelines like hope vi and choice neighborhood, is now lowrise with a front porch that resembles houses in older american city neighborhoods before the suburbanization of businesses and population spurred by post-war national interstate highway system. however, density is still a hard sell in popular discussions of realestate markets. low-density single family rather than multi-family housing is politically palatable to politicians who count votes with rooftops, even though compact land development is arguably environmentally more sustainable particularly in the face of climate change and demographic shift (immigration) that increase demand for housing and ancillary urban services-water, sewer, and road. in urban-studies literature, discussions of density and how higher thresholds are tolerated, particularly by urbanites accustomed to low-density suburban sprawl, extend to the justification of trade-offs, i.e. how density is plausibly compensated with other factors, (urban) design features that enhance aesthetics of place, and (land-use) diversity that improve proximity of housing to jobs, services, and amenities like parks and open space-so-called ds (for impact on travel, see cervero & kockelman, ) . density correlates with demography. in the context of the pandemic, still other factors must be added to the ds in deference to public health: demography, disaggregated by racial composition, ethnicity, age, and income. the correlations among the factors are instructive. at risk are residents characterized by compact living and commuting, transit-dependent population, or workplace-residence separation exacerbated by the digital divide. for the purposes of public health during the epidemic, the aforementioned factors require optimization simultaneously. the comprehensive city plan is a logical tool for that optimization. let us posit the concept of access inclusively with lynch ( ) as a dimension of the performance of urban form, not merely by modes of travel to work or services, but also availability of resources. perlman and o'meara ( ) remind us that the urban poor are likely located in "ecologically fragile areas of cities," without adequate water and sewers. coronavirus-prevention guidelines include frequent handwashing. how could these hygiene standards be met when there is no access to running water in poor settlements of the global north and south? the navajo settlement is but one example in the u.s. (see also www.digdeep.org). war-stricken regions of the world whose populations are victimized by global power play, such as libya, yemen, syria, turkey, and afghanistan, and refugees in greek islands, are among other examples. once again, pandemics-be they climate change or the coronavirus-reveal the vulnerability of the population in urban, periurban, and rural areas with global inequity of access to the resources fundamental to human survival. the coronavirus pandemic had a positive effect too, with the u.n. directorate's declaration to halt ongoing wars globally, particularly in the middle eastern countries most heavily impacted. the impact of military conflicts on the global population and environment is rarely discussed in the literature of climate change. the advocacy planning argument of the s and s that posed the limit of comprehensive master plans and stressed the necessity of the "plural plan" responsive to the underrepresented, marginalized, disenfranchised, colonized population revives the discussions of the equity of access to resources with environmental justice in the twenty-first century, particularly in the face of pandemics (see davidoff, ) . the wealth of nations is created in cities, jacobs ( ) reminds us. global environmental sustainability starts with urban environmental sustainability (perlman & sheehan, ) . cities provide economies of agglomeration, and of scale with efficiencies of resource utilization. however, the idea of abating pressure on resources concentrated in urban centers, like london and new york, and striking a balance of nature and development by spreading population to the larger region did not stop in england with howard's concept of the garden city, noted above. the garden city idea influenced a group of regionalists, or de-centralists with english connections in new york. a multidisciplinary team, journalist (howard) , socio-cultural critic (mumford), social reformer (bauer), economist (chase), biologist (geddes), sociologist (perry), forester-naturalist (mackaye), a developer (bing), and several architects (ackerman, whitaker, wright and stein) formed the regional plan association of america (rpaa, s; see also banai, banai, , b ). an exemplary feature of this regional planning is its multi-scale scope: from neighborhood to the region. it turns out, the "neighborhood unit" (perry, ) is an enduring concept manifested in new urbanism that emerged in s. cities ( ) the economist member of the regional plan association of america (rpaa s), stuart chase, considered the bigger picture of the efficiency of the urban and regional economy as a problem, stated thus: "the regional planning of communities would wipe out uneconomical national marketing, wipe out city congestion and terminal wastes, balance the power load, take the bulk of coal off the railroads, eliminate the duplication of milk and other deliveries, short circuit such uneconomic practices as hauling pacific apples to new york customers by encouraging local orchards, develop local forest areas and check the haulage of western timber to eastern mills, locate mills near cotton fields, shoe factories near hide producing areas, steel mills within striking distance of ore beds, food manufacturing plants in small giant power units, near farming belts." (quoted in hall, , pp. - ) for further discussions of local vs. global, economic vs. ecologic tensions in urban development, see korten's ( ) political-economic critique of capital markets, deemed as exacerbating ecological systems, shuman's ( ) "replacing imports" in self-reliant local communities in a global age, and roseland and soots' ( ) "strengthening local economies." the break in the global supply chain during the coronavirus pandemic made the dire consequences abundantly clear, particularly for the health-care sector with loss of life. how "uneconomical," chase might ask, is the practice of offshoring industrial and manufacturing production and sending the finished products, in whole or part, back to the country of origin by air, sea, river, rail, and road? parenthetically, airline tickets now relay magnitude of carbon footprint in trans-atlantic passenger flights. for a sustainability assessment of a futuristic concept of urban form anchored by a "globally networked economy's airport"-the aerotropolis-see banai ( ) . air transportation's contribution to global climate change remains awaiting the development of technologies that economically sequester atmospheric carbon. the idea of the city and the region as a unit is at the kernel of how the u.s. census defines the metropolitan region, metropolitan statistical area (msa) determined by commuting (see banai & wakolbinger, ) . parenthetically, this very commuting among inner city and suburban municipalities aids in the transmission of coronavirus, from high-density urban to low-density rural counties. young ( ) quotes the governor of new york, "many people in the new york city metro area live and work across three states' borders, so just as they coordinated shutting down various businesses [during coronavirus], it makes sense to eventually together bring people back." the holistic concept of the metropolitan region that highlights the functional links among urban and regional economies also reveals the strengths and limits of the urban system, and thereby informs the comprehensive city plan's objectives of enhancing sustainability and resilience of the built and natural environments of climate change. human activity's gradual degradation of the natural environment has a long history that has only intensified since the onset of the industrial revolution, with exponential growth in carbon emission due to burning of fossil fuel-coal, oil and natural gas-sources of ghs. a poplar idiom is aptly invoked. the planet earth's holding capacity, like the proverbial camel, is finite, continually burdened with harmful human activity, diminishing gradually by each melting glacier, like straw on a camel's back. (formally, economists use the term "margin," or "last unit" to explain concepts, as in the cost of producing one more unit of a product, the marginal cost of production.) the precise tipping point, or better stated, breaking point for the planet earth beyond any recovery, is in debate. the signs are visible in the built and natural environments, with droughts, fires, floods threatening food security, national security, employment security, rising poverty, inequality, and global diaspora (brown, (brown, , . wackernagel and rees ( ) measure ecological footprint by amount of land needed to sustain human needs for production of food and disposal of waste. land is a finite resource. by that definition, wackernagel and rees ( ) illustrate that if everyone lived like people in the netherlands, then two additional planet earths would be needed. parenthetically, the netherlands example is ironic, given the compact dutch urban form integrated with nature and exemplary sustainability practices (see beatley ) . furthermore, amsterdam's schiphol airport is regarded as a model for the "aerotropolis," a futuristic concept of urban form (kasarda and lindsay ) . there is no literature on the public heath aspects of the aerotropolis; however, comparing it to the exemplary amsterdam metropolitan region that contains the airport (schiphol) offers some clues. the region is characterized by the historic structures, integrated urban development and nature, compact, mixed-land use with multi-modal regional mobility architype of european cities (see beatley, ). european countries with net zero are the ideal of how we should live next. however, pacala and socolow ( ) offer a variety of existing technological solutions that limit carbon emission over the next fifty years(see also calthorpe, ) . the limit is achieved by a combination of alternative sources, from renewable energy (solar, wind, hydro) to conservation to nuclear power. interestingly, in spain, a country hit hard by one pandemic (coronavirus), the road to recovery is through solutions to the other pandemic-climate change-such as pledging to outlaw fossil fuel-coal, oil, natural gas-toward % renewable sources of energy. the pandemic has a global reach, by definition. the method of the approach and presentation of this paper is comparative by juxtaposing the pandemics of climate change and coronavirus, and through a historical and critical review and synthesis of the durable concepts of the urban system at the kernel of the theories and practices of urbanism expansively, from rooftop to the region, highlighted by place matters, cyberspace, density, access, and the city-region. the urban system connotes a holistic approach, with a synthesis of concepts of the urban system elements that are heretofore regarded individually particularly in dealing with resilience. the holistic notion of the urban system thus sheds new light on the resilience of system parts when regarded as a whole. we have juxtaposed the recent coronavirus pandemic with climate change, a persistent, long-lasting pandemic which threatens civilization, not merely urbanization (brown, (brown, , . pandemics expose the vulnerability and resilience of the urban system ironically with durable concepts of urbanism, from rooftop to the region. the recent pandemic has posed the dilemma of physical vs. virtual space. the accounts of this distinction appear with durable concepts of place and space in urban studies, which shed light on recent pandemic-related discussion. cyberspace and physical space are related concepts. the distinction made between "community of place" vs. "community of interest" is revisited in urban studies, particularly with the concepts of placemaking. there are limits and possibilities in both cyberspace and physical spaces. the critical role of access is also posed in both spaces, with respect to efficiency and justice. one space asserts the dilemma of a "digital divide," whereas the other asserts the dilemma of public vs. private transportation with equity and efficiency. place density is also a durable, controversially held concept of urbanism. we have highlighted discussion of density dating from first decades of the twentieth century, relating to the challenges of public health. the recent pandemic posed anew the challenge of public health with urban density. pandemics, while exposing the vulnerabilities of the urban system, are also a driver of positive change in planning resilient urban form of the future. reconfiguring the urban system in the era of climate change is compelling with the majority of world population living in cities and regions. at the outset of the paper (pages - ), we pose the kind of planning that is commensurate with the dimensions of the challenges posed by the pandemic needed for resilient cities. we argue the case for comprehensive planning, and provide specific interventions toward resilience, with place matters, cyberspace, density, access, and the cityregion. the logic of the long-term comprehensive plan is compelling given the interrelated elements of the urban system. the argument is that resilience of the whole is dependent upon the resilience of the individual parts. the paper thus provides specific areas of how the parts are addressed with elements of the urban general or comprehensive plan. for brevity , the discussion of the application of comprehensive planning as a mode to enhance resilient cities is limited. the comprehensive plan with a legal backing is long-term oriented, with parts that account for key physical elements that prepare the urban and regional system to confront the challenges of climate change. the comprehensive plans rarely include physical elements that enhance the urban and regional resilience proactively in the face of climate change. we have identified how the urban system is reconfigured, from the infrastructure of the public realm (the street, town square, park, and open space) to place density with a human-scale, telecommunication, regarded at par with essential infrastructure of water, sewer, and road, to integrated urban and regional economies that enhance efficient, sustainable local production and distribution of resources. further studies fruitfully build on our comparative, evaluative framework of pandemics as drivers of change toward resilient cities of the future. social theory and the region: from the regional planning association of america to the restructuring of socio-spatial theory, with policy implications plan vs project dilemma in urban and regional studies revisited: a progress review of urban and regional studies the metropolitan region: from concepts to indicators of urban sustainability the aerotropolis: urban sustainability perspectives from the regional city urban theory since a theory of good city form ( ): a progress review a measure of regional influence with the analytic network process planning for sustainability in european cities: a review of practices in leading cities planning for sustainability in european cities: a review of practices in leading cities the urban and regional planning reader plan b . : mobilizing to save civilization plan b . : mobilizing to save civilization journey to planet earth the next american metropolis-ecology, community, and the american dream urbanism in the age of climate change the regional city: planning for the end of sprawl transit metropolis: a global inquiry travel demand and the ds: density, diversity, design advocacy and pluralism in planning companion to urban design urban sprawl and public health cities of tomorrow building suburbia, green fields and urban growth to-morrow: a peaceful path to real reform/garden cities of tomorrow cities and the wealth of nations asia's emerging airport cities aerotropolis: the way we'll live next? the new urbanism: toward an architecture of community community planning-an introduction to the comprehensive plan civic engagement in creating future cities urban design: the american experience la ville radieuse (the radiant city) early urban planning - / ). design with nature the great good place: cafes, coffee shops, bookstores, bars, hair salons, and other hangouts at the heart of a community stabilization wedges: solving the climate problem for the next years with current technologies fighting poverty and environmental injustice in cities state of the world the neighborhood unit: a scheme of arrangement for the family-life community. regional study of new york and its environs, vii, neighborhood and community planning, monograph one - strengthening local economies. state of the world : our urban future going local: creating self-reliant communities in a global age our ecological footprint gabriola island the urban place and the non-place urban realm. explorations into urban structure new york will work with new jersey, connecticut to restart economy, cuomo says the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. key: cord- -xes g x authors: brindle, mary e.; doherty, gerard; lillemoe, keith; gawande, atul title: approaching surgical triage during the covid- pandemic date: - - journal: ann surg doi: . /sla. sha: doc_id: cord_uid: xes g x nan t he covid- pandemic has drastically changed surgical priorities in the united states and worldwide. patients with timesensitive surgical conditions or tumors have been prioritised, whereas patients with surgical conditions that require less urgent management such as asymptomatic hernias or obesity have been postponed indefinitely. as the spread of covid- places greater demands on health systems, further triage will be required. the american college of surgeons has provided guidance to aid in prioritizing cases, but challenges will remain both in this current time of crisis and over the several months after the peak of the pandemic. getting this right will be a challenge, and there are several considerations that will need to be taken into account as systems develop long-term strategies for surgical prioritization. surgical systems that have not deferred nonurgent operations may be too late to mount the necessary response to covid- . even those that have postponed these cases should be prepared for the impact of the pandemic to escalate sharply with little time to adapt. with the initial spread of covid- into north america, the american college of surgeons (acs) was quick to recommend the suspension of all elective surgery before the need hit. the adoption of these recommendations was not immediate nor was it complete. the harm caused by failure to modify the surgery schedule has been clearly demonstrated in countries like china where ongoing elective operations and nonessential clinic visits contributed to early rates of in-hospital covid- transmission ; and from italy where resources consumed through elective surgery including personal protective equipment left health care workers vulnerable when the pandemic crested. empty operating rooms and inpatient beds before the peak of the pandemic are necessary preparation to ensure that hospitals are not crippled by a large volume of critically ill patients presenting within a short timeframe. lifesaving operations should be prioritized with a clear plan to move to triage based on quality of life years attainable if resources become scarce. prioritizing cases that are immediately or urgently lifesaving offers the greatest benefit for lives saved during crisis and is the current form of triage undertaken across most of the united states and canada. under extreme circumstances, triage shifts to consider prioritizing patients for whom the greatest number of quality life years can be salvaged. this form of triage has been enacted in italian critical care units, where patients most likely to recover have been prioritized over the sickest. other hospitals in the unites states and canada have developed similar frameworks to consider adopting ''crisis standards of care'' if resources become scarce. alternatives to surgery may also allow for operative room resource conservation but may consume other resources and contribute to patient morbidity. in making recommendations around case urgency and alternatives, the acs has aimed to balance these risks. for example, treating appendicitis with antibiotics was suggested as an alternative to surgery. however, there was immediate backlash to this suggestion from surgeons who were concerned with the failure rate and the potential need for prolonged admissions. , the concerns about these failures may be overestimated; and surgical biases can be difficult to separate from best evidence dictating best management. antibiotics for appendicitis is first line therapy in a number of hospitals across the globe. although nonoperative care of appendicitis may have a failure rate between and %, the majority of patients will get out of hospital without surgery and will not consume the human and material resources that are most needed in covid- management. , decision-making must balance the concerns of surgeons advocating for what they consider best management with what is most acceptable in the face of a rapidly evolving public health emergency. when feasible, nonoperative solutions that may require future operation but spare current resources should be considered. different specialties, such as oncology, require different approaches to triage. for example, diagnostic procedures such as biopsies that offer the potential for early potentially curative intervention should be prioritized as lifesaving. when considering the management of patients with operable cancers, the meaningful survival benefits achievable with optimal and timely surgery need to be weighed against the potential survival achieved with less optimal approaches including delayed surgery, radiation, and chemotherapy. large and complex oncologic resections and transplants can consume large amounts of resources including blood and intensive care support. in situations of extreme scarcity, it is possible that centers may not be able to offer these procedures. when lifesaving operations cannot be offered because of resource scarcity, every attempt should be made to transfer patients to centers that have sufficient resources to provide necessary surgical care. the perspectives of clinical experts as well as administrative leaders are essential in balancing clinical need and operational capacity. recommendations for systems to consider before the peak of the pandemic: . stop all nonurgent operations as soon as possible (if not already stopped) in all ambulatory and nonambulatory centers. . define time-sensitive cases within each specialty following standard criteria such as those provided by the acs. these should be centrally reviewed, aligned between specialties, and strictly enforced. . define life-or-limb cases before triage based on these criteria is required. . high resource but lifesaving operations such as transplant will need to be constantly reviewed and may necessarily become a second priority if resources become scarce. . develop a framework with the aid of ethicists to consider triage to maximize the quality of life years saved to be used when demand for health system resources exceeds supply. . develop protocols for the nonoperative management of common and uncommon emergent, urgent, and elective conditions. this should include strategies to palliate and otherwise care for patients not able to receive urgent intervention due to triage criteria. . develop pathways to transfer surgical patients to centers with greater capacity if resources become scarce. . communicate clearly with patients who are delayed or postponed including the rationale, recommended treatment until surgical intervention, and indications for them to recontact the surgeon. . establish a clear process for surgeons to present special cases for consideration that do not fit strict triage criteria. . prepare for moral distress and frustration within surgical systems and provide ample support for providers. when human and resources become more available, the volume of cases will pose significant challenges for recovering systems. delays will persist, many patients will have more complicated and further advanced disease and triage will be essential. during the early stages of the pandemic, operative cases that need to be done urgently and those that can wait several months with no morbidity are usually easily differentiated. however, there remains a third group; where delays add significantly to the burden of disease experienced by the patient. as time passes, knowing how to manage these patients will become more challenging. this large and diverse population have conditions that not are not immediately life threatening but for whom surgery should not be postponed (eg, biopsies for presumed malignancy), and patients who may run the risk of acute exacerbation of their disease (eg, biliary colic), chronic deterioration (eg, bariatric surgery), or persistent disability and pain (eg, severe osteoarthritis requiring joint replacement). it is inevitable that many patients from this group will require emergency surgery that could have been avoided, whereas others may suffer unnecessary pain, disability, or death if the period of triage is prolonged. the importance of planning for resumption of expanded medical and surgical services post-covid is crucial but difficult to contemplate in the current environment. the world health organization has recommended that health systems develop an organized approach to recovery after a pandemic, but there is no good blueprint for exactly how this should be done. the experience of hong kong post-sars provides a good illustration of the issues encountered when dealing with a backlog of , cases after suspension of % of medical services when operating capacity returned to normal. the recovery process for hospitals took years. the scope of hong kong's problem will likely pale in comparison to what the united states will experience. there will be a tremendous burden of surgical care acquired over many months of delay and, no doubt, some of this burden will be made more challenging due to progression of disease and neglect. in addition, the workforce prepared to take on this burden will be diminished, under strain from the stresses of personal and financial losses as well as physical exhaustion from the care delivered during the pandemic. as in toronto after sars, significant financial resources will likely be consumed by hospitals and health systems to deal with this backlog of cases. developing an approach to prioritization of nonurgent cases that have waited variable amounts of time will require thoughtful sequencing. triage is as crucial during this phase as it is at the early stages of the pandemic and should include reevaluation of patients who have suffered from significant delays. patients suffering from acquired and persistent morbidity should still be prioritized over those with less severe conditions. lucrative but nonurgent cases should be delayed. a staggered recovery across and within hospitals, states and territories may allow for sharing of resources and distribution of cases, allowing patients to access systems earlier and unburdening those centers that have seen the greatest impact to care delivery. recommendations for systems to consider after the peak of the pandemic: . once the peak of the pandemic has passed, regularly and realistically assess the hospital systems capacity to expand surgical services. . expand surgical services slowly but early. . maximize capacity by transferring patients to ambulatory centers or other nearby systems that have capacity for surgery. . rapidly reassess and retriage patients who have been delayed beyond the recommended timeframe. . cancer cases and oncology diagnostic tests that have been delayed beyond optimal windows for treatment or have undergone less optimal alternative therapies should be prioritized. . second level reprioritization should consider sustained but reversible morbidities incurred during waiting, prolonged pain, and increasing projected complexity. . for patients who are likely to be asymptomatic with a risk of acute deterioration (eg, infant hernias) operations can continue to be delayed with good counselling. . patients that are waiting to undergo surgery without direct benefit to health (eg, minor cosmetic surgeries) should be delayed. ambulatory centers should help to address the burden of delayed before addressing less urgent operations. . covid- surgical care pathways and a covid- operating room will need to be maintained after the peak of the pandemic has passed as patients with covid- will continue to present with conditions requiring surgery. approaches developed during the pandemic should be integrated into hospital practices for use in future cases with high infectious transmission risks. . ongoing provider support during the time of increased demand is crucial. during the next several months, deliberate decision-making around surgical priorities will save lives. these decisions will not be made easily and will become even more challenging over time. the course of the pandemic and its impact on surgical systems will be variable between and within countries. the acs has provided the groundwork for developing a surgical triage strategy for the initial stages of the covid- pandemic. the tremendous burden of surgical disease that will accumulate due to delayed and cancelled operations will demand new, system-wide strategies. as with the planning for the early stages of the pandemic, preparation for this phase of the pandemic is necessary. the relief that will be eagerly anticipated by surgical systems at the end of covid will not occur until some time after the peak of the pandemic has passed. covid- : elective case triage guidelines for surgical care characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of , cases from the chinese center for disease control and prevention facing covid- in italy-ethics, logistics, and therapeutics on the epidemic's front line members of harvard medical school center for bioethics' a message to the public from mass. doctors, nurses, and ethicists about the coronavirus' the high failure rate of nonoperative management of acute appendicitis with an appendicolith in children outpatient laparoscopic appendectomy should be the standard of care for uncomplicated appendicitis nonoperative management of appendicitis in adults: a systematic review and meta-analysis of randomized controlled trials world health organization. pandemic influenza preparedness and response: a who guidance document. geneva: world health organization spread of sars slows disaster preparedness lessons learned and future directions for education: results from focus groups conducted at the apic conference learning from sars in hong kong and toronto key: cord- - elnvjk authors: abdelnasser, mohammad kamal; morsy, mohamed; osman, ahmed e.; abdelkawi, ayman f.; ibrahim, mahmoud fouad; eisa, amr; fadle, amr a.; hatem, amr; anter abdelhameed, mohammed; hassan, ahmed abdelazim a.; shawky abdelgawaad, ahmed title: covid- . an update for orthopedic surgeons date: - - journal: sicot-j doi: . /sicotj/ sha: doc_id: cord_uid: elnvjk the covid- pandemic has affected our world in a short period of time, and the orthopedic surgery practice was not an exclusion. elective care was deferred in most health care facilities and emergency care was continued with strict precautions. with rapid progression of the pandemic, the response of the medical community is also rapidly changing in all aspects of delivering care. this led to a large number of publications with reports, guidelines, measures, ways to react to the crisis, and post-pandemic predictions and speculations. in this review we aimed at summarizing all the relevant information to the orthopedic surgery community. to do this, a comprehensive search was performed with all related terms on two scientific search engines, pubmed and scopus, and the results were filtered by the preferred reporting items for systematic reviews and meta-analyses (prisma) method. the result was articles that were further reduced to articles after full text reading. the resultant information was organized under main headings; the impact of pandemic on the orthopedic practice, covid- and the trauma patient, elective and emergency surgeries during the pandemic, peri-operative management of the patient with covid- , miscellaneous effects of the pandemic such as those on training programs and the evolution of telemedicine. this review represents the most up to date information published in the literature that is a must-know to every orthopedic surgeon. covid- or sars-cov- was first identified as a potential infectious threat in china in december , [ ] [ ] [ ] and declared as a pandemic by the world health organization on march , [ ] . with the massive burden on health systems around the world, covid- has heavily impacted all aspects of the medical practice including specialities that are not directly related to its clinical effects such as orthopedic surgery. elective surgical procedures have been postponed in order to reduce the burden on health systems and allow for more availability of hospital beds for the more needy. management of emergent and urgent surgical cases has also been affected [ ] . a continuous need is present to address the daily new information and to employ them in our orthopedic practices. moreover, with more countries reaching their peak and plateau phase, healthcare facilities are getting ready to reopen and resume medical care. this will require a solid understanding of the precautions required for this resumption during such a critical phase, which may extend for a few months ahead, not to mention some speculations of a second wave of covid- infection in the near future. we aimed at delivering a comprehensive review summarizing the most recent information and guidelines relevant to the orthopedic community available in the literature to help us plan for the current phase and those yet to come. to provide the most relevant and up to date information for the orthopedic community, a systematic approach was used to gather information. a literature search was conducted on may nd on medline and scopus with the terms "covid- ", "covid ", "covid", "corona virus" or "corona", together with "orthopedic", "orthopaedic", "orthopedics", "orthopaedics", "surgery", and "surgical" including all possible combinations. the preferred reporting items for systematic reviews and meta-analyses (prisma) method and flowchart were used to filter the results of the search (figure ) [ ] . the search retrieved a total of articles, which were reduced to after omitting duplicates. screening by title and abstract further reduced the number to after exclusion of non-english language articles and those addressing details not relevant to the orthopedic specialty. the full texts of these articles were read, and articles were further excluded that lacked relevant information. relevant information was digested and organized under main headings; the impact of covid- pandemic on the orthopedic practice, covid- and the trauma patient, elective and emergency surgeries during the pandemic, perioperative management of the patient with covid- , miscellaneous effects of the pandemic such as those on training programs and the evolution of telemedicine. lack of sufficient evidence and the highly contagious nature of covid- led to drastic measures implemented by many countries varying from social distancing to total lockdown, which had tremendous global economic and social effects [ , ] . the covid- pandemic represents an unprecedented challenge to healthcare systems mainly due to the exponential expansion of the patient population in need of hospitalization surpassing available resources [ ] [ ] [ ] [ ] [ ] [ ] . with the risks posed by shortage of personal protective equipment (ppe) [ ] [ ] [ ] non-traditional solutions were developed such as d printed face shields, reusable gowns, and protocols for the re-use of ppe [ ] . moreover, the sudden overload of healthcare systems mandated institution of new hospitals as well as changing the bed capacity to increase respiratory care beds; this was coupled with initial reduction and later cancelation of all elective procedures in order to save the available resources and limit spread of the virus [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . in the midst of this crisis, the orthopedic surgeon was surely affected: from de-specialization and serving on the frontline, to upgrades from fellow to faculty and reassignment of residents to clinical care rotations [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . managing covid- patients with surgical emergencies and trauma with the risk of self-infection have led to a higher degree of anxiety and depression [ ] . with the mandatory decrease in face-toface encounters, online communication systems have flourished to provide meetings for faculty, quick and wide spread of knowledge, and outreach to patients through telehealth systems [ ] [ ] [ ] [ ] . so far, very few studies reported the association between covid- and trauma patients [ ] [ ] [ ] . given the fact that patients with fractures especially of the lower extremity and those with limited ambulatory capacity are more susceptible to respiratory infection [ ] , the association between covid- and trauma patients is not unlikely. mi et al. reported on trauma patients with covid- , seven of them ( %) had a nosocomial infection after admission to the hospital because of their fracture [ ] . although sars-cov- was positive in only patients, the characteristic ct ground-glass opacities were evident in all patients. clinical symptoms were not different from those present in patients without factures. lymphopenia was more common in patients with fractures. moreover, d-dimer and the median neutrophilic count were higher than the upper normal limits of the corresponding indicators. these might be special laboratory indicators of fractures in patients with covid- . four patients ( %) died and three others ( %) developed severe pneumonia. the authors concluded that the association between covid- pneumonia and fractures can lead to severe adverse outcomes and increased mortality [ ] . catellani et al. reported on patients of proximal femoral fractures positive for covid- [ ] . all patients presented with fever and oxygen desaturation on ambient air; of them required respiratory support. improved respiratory parameters were evident in out of patients who underwent early fracture stabilization. the authors concluded that early fixation may contribute to the overall patient stability, improvement in physiological ventilation, seated mobilization, and general patient comfort in bed [ ] . nevertheless, the association between covid- characteristic ct picture and trauma patients has also been reported in absence of symptoms related to covid- pneumonia [ ] . the necessity to choose which operations to proceed with and which can wait is a challenging and sometimes difficult decision during the pandemic crisis. in the light of the available literature, this review will try to address the most relevant questions to our practice. a. what is the definition of an elective procedure? in the time of the pandemic, it is important to identify elective procedures or in other terms, the ones that could be delayed. although this may sound simple, the pandemic itself has made such a sharp distinction impossible, creating a large gray zone. this question is particularly relevant to the orthopedic practice as % of the expenditure is from elective surgeries [ ] . with no consensus reached in the orthopedic community, some authors recommended that this should be individualized to each facility according to its resources and to each patient according to the condition [ ] [ ] [ ] . the ohio hospital association (oha) defined elective surgeries as those not meeting the following criteria "threat to the patient's life if surgery or procedure is not performed, threat of permanent dysfunction of an extremity or an organ system, risk of metastasis or progression of staging, or risk of rapidly worsening to severe symptoms" [ , ] . patients with stable diseases (low or moderate risk of clinical deterioration) can be postponed, while patients with unstable disease (risk of short-term clinical deterioration) should be considered for surgery with precautions [ ] . the covid- status of the patient whether positive, negative, or not tested is another important factor that affects the time of surgical intervention [ ] . reducing surgeries saves resources including hospital beds, ppes, as well as protecting the surgical staff [ ] . this can also diminish the risk of perioperative complications and mortality, [ , ] reduce unnecessary patient traffic and decrease the introduction and spread of disease among patients and health care providers [ ] . c. what should be offered to patients as an alternative to surgical intervention? delays of operative intervention in elective cases although temporary, might extend for months as a best estimate. patients should be offered sound alternatives to assist them bear the anticipated waiting times, this could be in the form of optimized medical treatment, individualized non-surgical options through multidisciplinary approaches, supportive online counseling, psychological support, and in pediatric patients engaging families and stressing on safety measures [ ] [ ] [ ] . many articles have tried to categorize various conditions according to urgency, [ , ] as well as guidelines put forth by international societies [ ] [ ] [ ] . awad et al. stratified orthopedic conditions into five categories according to urgency, a through e, a being the most urgent [ ] . open fractures, acute neurovascular derangements as well as acute infections were rendered as emergent (a) to be operated within h. closed fractures were grouped under b or c. deformities, arthroplasty and trigger finger were grouped under e [ ] . table gives relevant examples to these recommended categories. farrell et al. suggested some management plans for the pediatric orthopedic patient [ ] . in the pediatric trauma patient, modifications to standard care were mostly to the follow-up instructions and methods. table demonstrates two examples. as for elective orthopedic patient, the authors advocated either postponing the surgery or doing a minimally invasive procedure if feasible. table gives examples to these situations. donnally et al. published on triaging patients with spine pathologies according to the rothman institute guidelines during the covid- era [ ] . patients were classified into three levels according to the urgency of surgical intervention and the facility in which the patient should be operated upon. awad et al. recommended regional organization by assigning designated hospitals with orthopedic staff to treat only suspected or confirmed covid- patients and other hospitals in the same regions to treat exclusively non-infected patients [ ] . this may not be feasible in some regions or districts and in such a case, the same hospital should be divided into areas or wards according to the risk of exposure to the virus, with a stratified increase in ppe according to the increase in the level of probable exposure (figure ) [ ] . on the personnel level, all should apply the general selfprotection rules like, safe distancing, face masks, goggles for eye protection, hand disinfection, regular decontamination of all patient/staff contact points, and avoidance of touching one's eyes, nose, and face [ , ] . another notable recommendation is to establish a three-team approach where one team is working in the hospital involved in direct patient care, while the other teams are away from the hospital through days as a "quarantine" between episodes of direct patient care [ ] . this requires adequate number of medical staff which has not always been the case in the covid- pandemic. on the patient level, in hospitals still running outpatient clinics, patients should be screened for symptoms like (fever, cough, sore throat), if the patient shows positive symptoms consider delaying the outpatient management till test results are available. if a patient's operation could not be delayed for testing, then the patient should be re-triaged into the emergency category and presumed covid positive. all of this should be done with proper precautions such as wearing face masks, distancing, and well-aerated waiting areas [ , ] . as for patients in the emergency department (ed) and crowded triage areas, same protective precautions apply, and if the patient is oriented, he/she is asked for the suspect criteria for covid- infection. suspected or confirmed covid- patients should be isolated in a separate room and should keep at least feet distance from other patients or non-treating staff. covid- polymerase chain reaction (pcr) testing should be done for all patients that will be admitted or will undergo surgery. surgeons should not approach the triage area without the minimum standard ppe recommended. ppe should be exchanged if they are damaged or soiled or before leaving the ed. only required equipment and assessment tools should be brought into the triage room to minimize the number of items that need to be disinfected after the exposure [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . this should be incorporated into hospital plans and rules to face the pandemic, [ ] and can be subdivided into measures involving the operating room, personnel, anesthesia, the procedure, and postoperative precautions. separate operating rooms (or) should be designated for covid- positive patients, isolated from other operating rooms . the operating room is preferred to have a separate ventilation system with negative pressure [ , [ ] [ ] [ ] , which if not available, it is recommended to add high-efficiency particulate air (hepa) filters to positive pressure rooms [ ] [ ] [ ] [ ] . moreover, air conditioning should be turned off [ ] [ ] [ ] [ ] . only the materials necessary for the case should be brought into the or [ ] . all equipment and screens should be covered with plastic sheets to facilitate decontamination [ ] . consider attenuation of residual environmental contamination through cleaning with surface disinfectants and ultraviolet light (uv-c) [ ] . all traffic in and out of the or should be minimized . all doors should be closed once the patient is transferred in and during the whole operation [ ] . the path of the patient to and from the or should be kept clear and better to be separate from other operating rooms [ ] . patients should cover their face with a surgical mask [ ] . the patient should recover in the operating room and transferred directly to the isolation ward . the number of personnel inside the or should be kept to the minimum. services personnel should not enter the room compression fracture (without neurologic deficits) defer surgery or reconsider risks versus benefits of continued conservative management. consider course of steroid therapy (injection or oral). odontoid fractures in elderly will be managed conservatively, with option of treating symptomatic nonunion surgically in future. until enough time has elapsed for air changers to reduce the risk of contamination [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . sales representatives, residents, and fellows should be discarded from or unless essential . the fewest number of personnel possible is the main goal, with the highest skilled surgeon performing the procedure to avoid prolongation of the surgery [ , , , ] . all personnel in the operating room should wear the ppe which include association of advancement of medical instrumentation (aami) level iii surgical gowns, surgical hood (for head and neck covering), double gloves, facemasks and either n , filtering face piece (ffp ) respirators with a face shield/googles or powered air-purifying respirator (parp), fluid-resistant shoes or booties [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . donning and doffing of ppe should be done in an anteroom if available, with hand hygiene prior and after donning/doffing ppe [ ] . avoid self-contamination during ppe doffing. disinfect the first pair of gloves with an alcohol solution, before removing the surgical mask with the shield and the hair cap . consider placing a simple surgical mask on top of the n- to prevent gross contamination. each time n respirator is taken off, it must be double-checked for not being soiled or damaged before reuse [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . full face shield is preferred to protective eye goggles [ , [ ] [ ] [ ] [ ] [ ] [ ] . dedicated anesthesia machines should be exclusively designated for covid- positive cases [ ] . the most experienced anesthesiologist should intubate the patient in the shortest possible time with minimal airway manipulation, avoiding face mask ventilation and open-air way suction as possible [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . keep the minimum number of personnel inside the anesthesia room which should be separate from the operating room, which should not be entered for - min after intubation [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] . use deep anesthesia and neuromuscular blockage. preoxygenation should be performed via well-fitting face mask to avoid hypoxia in critically ill covid- patients with respiratory failure [ ] [ ] [ ] [ ] [ ] [ ] . it is preferred to avoid general anesthesia and use of regional/spinal anesthesia is recommended whenever possible [ ] . consider the use of minimally invasive approaches to decrease operating staff exposure and shorten case duration [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . use disposable medical supplies/instruments whenever possible, and absorbable sutures for wound closure to avoid a postoperative unnecessary visit [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the use of electrocautery should be reduced to minimize the surgical smoke and should be used in conjunction with a smoke evacuator [ , , , ] . care should be taken when using sharp objects to avoid sharp injury or damage of ppe [ ] . the use of power tools like bone saws, reamers, and drills should be reduced to the minimum and the power settings should be as low as possible, as they release aerosols, increasing the risk of virus spread. suction devices to remove smoke and aerosols should be used during their use [ ] . all body fluids as blood, secretions, urine, or pathological specimens should be collected in double sealed bags for inspection or destruction [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . all contaminated instruments and devices should be disinfected separately followed by proper labeling [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the transfer to isolation wards should be through dedicated corridors and elevators which should be carefully sterilized after transport [ , - ] . during the transfer, transport personnel should wear ppe which should not be the same as worn during the procedure and patients should be wearing n- /ffp masks and covered with disposable operating sheets [ , [ ] [ ] [ ] [ ] [ ] . surgeons must be aware of common postoperative complications from covid- infections. in the presence of fever and one of the symptoms of a respiratory infection (dry cough, etc.), laboratory tests for covid- diagnosis must be ordered. suspected cases should be reported immediately together with transfer of the patient to an isolation ward [ ] . patients should receive adequate nutrition, fluid hydration, and electrolyte balance to promote immune recovery and rapid rehabilitation [ ] . frequent monitoring of temperature, laboratory complete blood count (cbc), c-reactive protein, and ferritin level should be done [ ] . severe covid- infection might cause a "cytokine storm syndrome", which is characterized by a fulminant and fatal hyper-cytokinemia with multiorgan failure. an increased level of ferritin occurs in approximately % of patients. all patients with severe covid- should be screened for hyper-inflammation markers [ ] . safe and effective patient care during the pandemic and telemedicine in order to resume safe patient care, telemedicine has been widely used during this pandemic [ ] [ ] [ ] [ ] . telemedicine allows health care providers to deliver clinical services to patients through the use of the widely available telecommunication technologies. it can be used for patient triage, postoperative follow-up and monitoring patients with chronic diseases. postoperative rehabilitation can be also resumed remotely via online educational programs or videoconferences. moreover, rehabilitation can be tele-monitored through special technologies such as wireless sensors for range of motion such as the knee following knee arthroplasty. nonetheless, telemedicine has its limitations. patients with sutures to remove, cast to change or need comprehensive clinical examination will still have to pay an in person visit to the health care facility. also, there are obstacles for wide implementation of such services such as infrastructure cost, provider and patient education, data protection, ethical consideration, legalization, and payment regulation [ ] . in order to facilitate the use of telemedicine, the office for civil rights at the u.s. department of health and human services on march , allowed physicians to utilize commercially available platforms, such as, skype, whatsapp, zoom, and facetime without imposing penalties for noncompliance. in all cases, documentation within the patient medical record is mandatory [ ] . the covid- crisis called for alternative methods to resume resident and fellow education [ ] [ ] [ ] , an example is the flipped virtual classroom method, in which the learners are asked to review the lecture online, with a subsequent virtual meeting focused on active learning and case-based discussions. other methods include online practice questions, academic webinars, and telehealth clinics with resident involvement. many applications such as webex, google classroom, microsoft teams, and zoom offer platforms for remote online conferences. the main drawback to this approach is that it cannot involve actual clinical or surgical skills teaching. others include difficulties some senior staff may have with utilizing modern technology, slow internet speed in some regions, and difficulties with viewing some pictures especially radiology [ ] . to overcome these obstacles high-definition d operative videos and surgical simulations are being employed. various simulation modalities are available including surgical skills laboratories, cadaveric dissections and procedural training, and computer-based virtual reality training [ ] [ ] [ ] [ ] . the annual meeting of american academy of orthopedic surgeons (aaos) is now being made available through the aaos website. this includes instructional course lectures, and ask expert sessions, in addition to the traditional research paper and poster presentations. the american association of hip and knee surgeons (aahks) has developed the focal initiative: fellows online covid- aahks learning, a series of online lectures by invited faculty to continue fellow education during this time [ ] . follow-up of the online training has to be followed up by the person responsible for resident and fellow training through recording attendance and completion of online sessions and modules, and completing online assessments and quizzes [ ] . making use of the crisis and planning for the post-pandemic era global cooperation and exchange of experiences are still to be improved. the pandemic is still in various stages in different countries. countries with increasing numbers of cases and mortalities are learning from those recovering from the crisis. the future requires better planning and re-allocation of resources to be prepared for such events. to make use of the available technologies in telemedicine is of utmost importance. remote triaging and examination techniques, feedback through mobile applications, and virtual interdisciplinary meetings should be encouraged. urgent legislative reforms to adapt to these changes are mandatory. e-learning, virtual conferences, webinars, and simulation training initiatives must be supported by the international scientific societies. curricula should be revised to adapt to these needs. non-technical skills should constitute integral part of learning programs. plans should be prepared to manage the accumulated long waiting lists of elective surgeries [ ] [ ] [ ] [ ] [ ] . prioritization should be rational without inferring excessive burden on the recovering health system after the crisis. all in all, the authors believe that the medical practice, including orthopedic surgery will differ after the pandemic is over. implementation of new technologies, restructuring our health systems with incorporation of telemedicine as well as reorganizing of our traditional training programs will be crucial for a more effective and optimal delivery of care. first case of novel coronavirus in the united states early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia understanding of covid- based on current evidence new options for vascularized bone reconstruction in the upper extremity managing covid- in surgical systems preferred reporting items for systematic reviews and meta-analyses: the prisma statement the surgeons and the covid- pandemic practice management during the covid- pandemic staiger do ( ) older clinicians and the surge in novel coronavirus disease (covid- ) a bioethical perspective for navigating moral dilemmas amidst the covid- pandemic ventilator stockpiling and availability in the us impact of the covid- pandemic on surgical services: early experiences at a nominated covid- centre critical supply shortagesthe need for ventilators and personal protective equipment during the covid- pandemic the toughest triageallocating ventilators in a pandemic prevention cfdca ( ) strategies for optimizing the supply of n respirators roles and responsibilities of the orthopaedic community and the society during covid- pandemic covid- pandemic and personal protective equipment shortage: protective efficacy comparing masks and scientific methods for respirator reuse rapid response of an academic surgical department to the covid- pandemic: implications for patients, surgeons, and the community crispr-mediated epigenome editing annotation: the covid- pandemic and clinical orthopaedic and trauma surgery covid- : initial experience of an international group of hand surgeons covid- and spinal surgery response of a european surgical department to the covid- crisis disruption of joint arthroplasty services in europe during the covid- pandemic: an online survey within the european hip society (ehs) and the european knee associates (eka) disruption of arthroplasty practice in an orthopedic center in northern italy during the coronavirus disease pandemic resource reallocation during the covid- pandemic in a suburban hospital system: implications for outpatient hip and knee arthroplasty surgical response to covid- pandemic: a singapore perspective effects of covid- pandemic in the field of orthopaedics maximizing the calm before the storm: tiered surgical response plan for novel coronavirus (covid- ) what's important: redeployment of the orthopaedic surgeon during the covid- pandemic: perspectives from the trenches psychological status of surgical staff during the covid- outbreak incidentally diagnosed covid- infection in trauma patients; a clinical experience characteristics and early prognosis of covid- infection in fracture patients treatment of proximal femoral fragility fractures in patients with covid- during the sars-cov- outbreak in northern italy risk of long-term infection-related death in clinical osteoporotic vertebral fractures: a hospitalbased analysis how to risk-stratify elective surgery during the covid- pandemic? a review of state guidelines for elective orthopaedic procedures during the covid- outbreak elective surgeries during the covid- outbreak we asked the experts: covid- outbreak: is there still a place for scheduled surgery? "reflection from pathophysiological data clinical characteristics and outcomes of patients undergoing surgeries during the incubation period of covid- infection recommendations for the care of pediatric orthopedic patients during the covid pandemic guidelines for ambulatory surgery centers for the care of surgically necessary/time-sensitive orthopaedic cases during the covid- pandemic orthopaedic surgical selection and inpatient paradigms during the coronavirus covid- pandemic perioperative considerations in urgent surgical care of suspected and confirmed covid- orthopedic patients: operating rooms protocols and recommendations in the current covid- pandemic surgical management of patients with covid- infection. recommendations of the spanish association of surgeons covid- contagion and contamination through hands of trauma patients: what risks and what precautions? triaging spine surgery in the covid- era working through the covid- outbreak: rapid review and recommendations for msk and allied heath personnel covid- & the general surgical department -measures to reduce spread of sars-cov- among surgeons the orthopaedic trauma service and covid- -practice considerations to optimize outcomes and limit exposure precautions for operating room team members during the covid- pandemic rules on isolation rooms for suspected covid- cases in gp surgeries to be relaxed novel coronavirus covid- : current evidence and evolving strategies covid- outbreak and surgical practice: unexpected fatality in perioperative period preparing to perform trauma and orthopaedic surgery on patients with covid- systematic review of recommended operating room practice during the covid- pandemic ventilation performance in operating theatres against airborne infection: review of research activities and practical guidance what we do when a covid- patient needs an operation: operating room preparation and guidance practical recommendations for critical care and anesthesiology teams caring for novel coronavirus ( -ncov) patients interventional radiology and covid- : evidence-based measures to limit transmission perioperative management of patients infected with the novel coronavirus: recommendation from the joint task force of the chinese society of anesthesiology and the chinese association of anesthesiologists perioperative covid- defense: an evidence-based approach for optimization of infection control and operating room management novel coronavirus and orthopaedic surgery: early experiences from singapore infection control measures for operative procedures in severe acute respiratory syndrome-related patients current evidence for minimally invasive surgery during the covid- pandemic and risk mitigation strategies: a narrative review minimally invasive surgery and the novel coronavirus outbreak: lessons learned in china and italy characterization of aerosols produced during surgical procedures in hospitals global guidance for surgical care during the covid- pandemic pulmonary involvement in patients with hemophagocytic lymphohistiocytosis covid- : consider cytokine storm syndromes and immunosuppression telehealth utilization in response to the novel coronavirus (covid- ) pandemic in orthopaedic surgery telemedicine in the era of covid- : the virtual orthopaedic examination internet of medical things (iomt) for orthopaedic in covid- pandemic: roles, challenges, and applications digital orthopaedics: a glimpse into the future in the midst of a pandemic what's important: weathering the covid- crisis: time for leadership, vigilance, and unity spine fellowship training reorganizing during a pandemic: perspectives from a tertiary orthopedic specialty center in the epicenter of outbreak covid and training in the uk -correspondence orthopedic surgery training during the covid- pandemic: dusting off my stethoscope using technology to maintain the education of residents during the covid- pandemic orthopaedic education during the covid- pandemic virtual surgical training during covid- : operating room simulation platforms accessible from home virtual interviews for surgical training program applicants during covid- : lessons learned and recommendations we asked the experts: virtual learning in surgical education during the covid- pandemic-shaping the future of surgical education and training reinstating elective orthopaedic surgery in the age of covid- resuming elective orthopaedic surgery during the covid- pandemic: guidelines developed by the international consensus group (icm) economic recovery after the covid- pandemic: resuming elective orthopedic surgery and total joint arthroplasty covid- -esska guidelines and recommendations for resuming elective surgery returning to orthopaedic business as usual after covid- : strategies and options abdelgawaad as ( ) covid- . an update for orthopedic surgeons the authors declare that they have no conflict of interest related to the submitted article.there is no funding source. this article does not contain any studies with human participants or animals performed by any of the authors. key: cord- -xt tl td authors: severo, eliana andrea; de guimarães, julio cesar ferro; dellarmelin, mateus luan title: impact of the covid- pandemic on environmental awareness, sustainable consumption and social responsibility: evidence from generations in brazil and portugal date: - - journal: j clean prod doi: . /j.jclepro. . sha: doc_id: cord_uid: xt tl td the covid- pandemic has become a major public health concern worldwide, which can impact environmental sustainability and social responsibility, as well as people's quality of life. in this context, environmental awareness, sustainable consumption and social actions of people have been effectively changed, as a period of quarantine, social isolation and health crisis caused by pandemic has been experienced. this study aims to analyze the impact of the covid- pandemic on environmental awareness, sustainable consumption and social responsibility, in the perception of baby boomers, x and y generations, residents in brazil and portugal. the method used was quantitative research, of a descriptive character, through a survey applied to people, which was analyzed with the use of structural equation modeling. the results indicate that covid- pandemic is an important vector in people's behavioral change, which reflects on environmental sustainability and social responsibility. it it is noteworthy that the impact of the covid- pandemic had a greater influence on sustainable consumption, followed by environmental awareness, and to a lesser extent, on social responsibility. there was also greater relevance in portugal, as well as the perception of the baby boomers generation. this study also provides a framework such as metrics to measure a transformational event, which is the covid- pandemic in socio-environmental aspects and conscious consumption. since the new coronavirus disease outbreak (covid- ) originated in wuhan, hubei province, china, in december , it has become a threat to the health and life of the world population, as a global pandemic has unleashed, and it is a severe acute respiratory syndrome . although this covid- pandemic reached south america a little later than other regions, such as europe and the united states of america (usa), all countries on the continent recorded cases of covid- jamaati et al., ; kirby, ; mansoor et al., ; sun et al., ) . the outbreak of a new coronavirus, covid- , is challenging international public health and medical care efforts (popescu, ) . the global expansion of covid- has put increasing pressure on the world health organization (who). in this context, several strategies have been taken to tackle the pandemic, including increased funding for who. however, according to jeyabaladevan ( ) , the increase in funding in itself does not facilitate the workload of health professionals, because, in addition to the high number of patients, there is a large number of contaminated employees, which causes problems for the meeting the demand of infected patients. these are unprecedented times and are affecting many health services. among people infected with covid- , the intensive care of critically ill patients in the intensive care unit (icu) needs substantial medical resources . in this scenario, the resources of the health systems have been shown to be fragile, insufficient, with several bottlenecks and inadequate, especially in the case of underdeveloped countries (chattu and yaya, ) , as in the case of brazil, and unlike portugal, which also has a smaller territorial scope. pandemic has been present in brazil on a large scale, due also to its territorial size, which has caused different preventive measures in the states, due to a large number of infected people, such as: personal protection measures (hand washing, cough etiquette, and facial coverage), closing trade and non-essential services, online education, conference calls, case detection, isolation, contact tracking, quarantine, social detachment, and the lockdown. according to chen et al. ( ) and khanna et al. ( ) , a single policy of social distance can reduce the spread of epidemics. still, generally several policiesincluding more restrictive measures, such as social isolation and quarantine -are implemented in combination to increase effectiveness. in brazil, pandemic data is alarming, the country confirmed the first case of contamination on / / . as a result of covid- , / / there were people infected, deaths (coronavírus brasil, ) , and with a lethality rate of . %, however, there is a great underreporting of infected cases, as well as deaths, as many patients do not they are subjected to the covid- detection tests, and others die in their own homes. in addition to this chaos, hospitals in brazil are overcrowded in most states, as well as a shortage of icu beds, mechanical ventilators, and respirators. it is up to the federal, state and municipal governments, managers, universities and researchers to integrate more, aiming at the development of actions, public policies and research to address the deficiency of the health systems, the adequate treatment for the infected, the maintenance of the quality of life of conservation of jobs and income, as well as the development of medicines and vaccines for covid- . in portugal, the first case registered by the general directorate of health (dgs), of covid- infection, was on / / . as of this date, the government started discussions to outline strategies to combat pandemic in the parents. the main measure implemented on march was the state of emergency decree -a/ , which establishes the terms of the exceptional measures to be implemented during the term of this decree, which was renewed until may (dpr, ) . given this pandemic context in portugal, and until / / , the number of deaths is , with a lethality rate of . %. also, in this period, confirmed cases were registered by the general health directorate (dgs) (dgs, ) . table shows the evolution and comparison of the epidemic and cases of covid- in brazil and portugal, in the period in which the research was carried out ( / / ). in this problematic scenario of pandemic, people can develop or worsen mental illnesses (zhai and du, ) , such as anxiety and panic attacks (blake et al., ) , insomnia, increase the consumption of psychotropics and alcoholic beverages, because besides to be socially isolated, there is a concern with the contamination and loss of family members who are at risk groups. the implications of the covid- pandemic on sustainability have not yet been seen, but profound and pervasive social changes are likely to occur in the coming months and years (sarkis et al., ) . it is noteworthy that the production of household and hospital waste increased at significant levels. according to zambrano-monserrate et al. ( ) , wuhan hospitals produced an average of tons of medical waste per day during the outbreak, compared to the previous average of less than tons. according to wuang an su ( ), pandemic also significantly reduced the concentration of nitrogen dioxide (no ) in the j o u r n a l p r e -p r o o f atmosphere, the decline initially occurred near wuhan and eventually spread across the country as the decline in economic activities and restrictions traffic leads directly to changes in china's energy consumption and further avoids polluting the environment, so quarantine measures can not only protect the public of covid- , but also have a positive impact on the environment. according to , energy efficiency has been neglected in economic recovery plans to respond to covid- in several countries, and trade protectionism is on the rise, especially in developed countries, so it is of great importance avoiding a retaliatory recovery in post-covid- carbon emissions, therefore improving energy intensity can also help to reduce carbon emissions after the covid- pandemic. the importance of environmental awareness and sustainable consumption by generations is highlighted, as these generations are responsible for current and future actions in organizations and society , which impacts on the regional economy (de guimarães et al., ; severo et al., ) , the preservation of the environment (dorion et al., ) and in people's quality of life. for jribi et al. ( ) , there was a positive impact on the social block of covid- on the awareness, attitudes, and behaviors of tunisian consumers related to food waste. for cohen ( ) , the covid- pandemic marks the beginning of a sustainable consumption transition. although sustainable production has been absorbed in the past three decades by the prevailing social commitments, governance structures, and business models, the associated notion of sustainable consumption has been striving to obtain equal attention (cohen, the theoretical framework will be based on the hypotheses that support the theoretical research model (fig. ). hallema et al. ( ) , emphasize that the environmental responses to the economic slowdown, triggered by the pandemic, resulted in a negative effect of human beings and organizations on the environment. in this scenario, the analysis of environmental awareness about water consumption represents an essential tool for water efficiency and decisionmaking procedures, aligned with the challenges that have arisen due to the scarcity of water resources (gómez-llanos et al., ) . another important element is air pollution, according to zambrano-monserrate et al. ( ), there is a significant association between covid- pandemic contingency measures and the improvement of air quality, clean beaches and reduction of environmental noise. according to tahir and batool, ( ) , the covid- pandemic decreased . % in global carbon dioxide emission, after the collapse of , due to the confinement of the local transport and aviation sector, which brings improving air quality for the next generation (rugani and cari, ) . however, according to zambrano-monserrate et al. ( ) , there are also negative secondary aspects, such as the reduction of recycling and the increase of waste, compromising the contamination of physical spaces, where the greatest waste and reduction of recycling are negative side effects of covid- . according to fattorini and regoli ( ) , long-term air quality data correlated significantly with cases of covid- in italian provinces (updated on april , ), providing further evidence that chronic exposure to contamination atmospheric exposure may represent a favorable context for the spread of the virus. coherently, pirouz et al. ( a) report that population density and climate conditions can affect covid- cases. however, sarkis et al. ( ) highlight that the coronavirus outbreak also has positive environmental consequences, that is, significant reductions in air pollution, due to the large-scale slowdown in economic activity. for sofo and sofo ( ) the research by jribi et al. ( ) , demonstrated that the social block for covid- improved the performance of food purchases and led to a positive behavioral change about food waste, where an economy, storage, and leftover consumption strategy occurred. however, according to the authors, the changes of consumers in the prevention of food waste may be more motivated by the socioeconomic context of the blockade of covid- (that is, availability of food, restricted movements, loss of income), than by a pro-environmental concern. according to muhammad et al. ( ) , the blockade due to covid- has drastic effects on social and economic fronts, however, this blockade also has some positive effect on the natural environment. still, according to the authors, data released by nasa (national aeronautics and space administration) and esa (european space agency) indicate that pollution in some of the epicenters of covid- , such as wuhan, italy, spain and the usa, has been reduced by up to %. the study by wuang and su ( ) highlights that the covid- pandemic reduced the concentration of nitrogen dioxide (no ) in the atmosphere, as well as the research by shehzad et al. ( ) , where there was also a significant decline in no in renowned states of india, namely delhi and mumbai. however, the research by collivignarelli et al. ( ) points out that in the metropolitan area of milan, where there was a severe limitation in the movement of people, after the partial and total blocking measures, it determined a significant reduction in the concentration of pollutants, mainly due to vehicle traffic, about sulfur dioxide (so ). the j o u r n a l p r e -p r o o f research by lal et al. ( ) , there was a substantial reduction in the level of no , a low reduction in carbon monoxide (co) and a low to moderate reduction in the optical depth of the aerosol, in the main hot spots of the covid- outbreak during february-march , which can also be attributed to mass blocks. in this scenario, the study by bashir et al. ( ) indicates that environmental pollutants such as pm , pm . , so , no and co have a significant correlation with the covid- epidemic in california, just as it becomes relevant to encourage regulators to promote changes in environmental policies, because controlling the source of pollution can reduce the harmful effects of environmental pollutants. according to hsu et al. ( ) , many lessons learned will serve as a model for dealing with future pandemics, but a new sustainable model is needed for the immediate future. quarantine policies have led consumers to increase their demand for online shopping for home delivery. consequently, the organic waste generated by households has increased; also, food purchased online is shipped packaged so that inorganic waste also increased (zambrano- monserrate et al., ) . in this context, sustainable consumption has been the subject of several scientific studies. for baier et al. ( ) , the constant increase in sustainable consumer behavior leads companies to strengthen their efforts to become socially and ecologically more sustainable, as sustainability offers are developed, for example, through recycled materials, circular business models, as well as adapted product, ranges with fewer fashion cycles. according to lo and liu ( ) , for efficient, sustainable consumption, the disposal, and separation of domestic solid waste, as well as recycling is essential for the local community. about inputs and natural resources, rauf et al. ( ) point out that energy consumption in the high-tech industry and economic growth deteriorates environmental quality. still, financial development and consumption of renewable energy have a favorable effect on the environment. the research by liu and song ( ) highlights that producing more food with limited water resources, as well as improving the efficiency of water use, is an urgent task, especially in arid and semi-arid areas with fragile ecosystems and severe water shortages. o´brien and bringezu ( ), on the other hand, report that the levels of wood consumption have increased considerably in recent years, being considered sustainable forest management practices, aiming at changes in the terrestrial system and the global distribution of common good resources, so that consumption levels are linked to sustainable supply capacities. in this context of the global covid- pandemic, sustainable development is considered a key concept and solution in the creation of a promising and prosperous future for human societies (pirouz et al., b) , where sustainable consumption must be global policies (cohen, ) , since the maintenance of natural resources must be sustainable so that the next generations have their needs met . therefore, h is listed. h : covid- pandemic (cov) positively influences sustainable consumption (sc). according to sarkis et al. ( ) , the covid- pandemic is a time when people are oriented to unite and support each other in society, and they must be learned to do it from a distance. however, according to the authors, behavior and changes are necessary, and some of them can provide useful insight into how it is possible to facilitate transformations towards more sustainable projects and supply and production. another aspect is the need for eminent new forms of learning (signori et al., ) in schools, favoring distance learning to guarantee physical distance. various measures, such as mobility restrictions, physical distance, hygienic measures, socioeconomic restrictions, communication mechanisms and international support have been used in several countries to minimize the impact of covid- (de bruin et al., ). according to bengtsson et al. ( ) , consumption and production volumes are closely associated with environmental impacts, indicating the need to reduce these volumes in order to safeguard social responsibility, which is unlikely to be possible without a restructuring of the existing socio-economic arrangements. however, low-and middle-income countries remain vulnerable to pandemics, as well as experiencing dramatic social and economic consequences (chattu and yaya, ) . in this scenario, for the effectiveness of social responsibility actions, it will be necessary to work to ensure the emergence and success of the adoption of new types of economic development and governance models, and these social changes will require reflection, new behaviors, and thoughtful action (sarkis et al., ) . tisdell ( ) francis and pegg, ; khan et al., ; tekleab et al., ) . what can be evidenced in the campaigns of institutions that help countries and people who are socially vulnerable, focused on homeless people, migrants, and refugees, drug users, the elderly, children, and people deprived of their freedom (unhcr/acnur ; médicos sem fronteiras, ; cruz vermelha brasileira, , actionaid, ). h : covid- pandemic (cov) positively influences a social responsibility (sr). as a moderating effect, it is admitted that intervening variables may occur in the dependency relations between the constructs. in this study, the possibility of the generations and the country in which the respondents reside was evaluated, as they may interfere in the intensity of the relationships, which alters the influence of covid- on environmental awareness, sustainable consumption and social responsibility. the generations were classified according to personal, behavioral characteristics and year of birth, as according to studies severo et al. ( ) , there is a difference in the perception of the baby boomers, x and y generations, on behavioral aspects related to socioenvironmental dimensions and conscious consumption. the criterion used to classify the generations was the period of year of birth: before (baby boomers); from to (generation x); and, after (generation y). based on this premise, the hypotheses of the moderating effect of generations (h a, h b, h c) were evaluated: h a: generations has a moderating effect on the relationships between cov and ea. h b: generations has a moderating effect on the relationships between cov and sc. h b: generations has a moderating effect on the relationships between cov and sr. in this sense, the research hypotheses (h a, h b, h c) that presupposes the existence of a moderating effect on the country in which the respondent resides emerges, which are described below: h a: the respondent's country of residence has a moderating effect on the relationships between cov and ea. h b: the respondent's country of residence has a moderating effect on the relationships between cov and sc. h b: the respondent's country of residence has a moderating effect on the relationships between cov and sr. the method used was a quantitative and descriptive research (hair jr. et al., ) , through a survey, with the perception of different generations, brazilians, and portuguese. the sample is non-probabilistic, for convenience (hair jr. et al., ) , which meets the sample size requirements (hair jr. et al., ) , in which respondents were obtained per observable variable, as well, the sample surpasses the premise of more than to valid cases (kline, ; hair jr. et al., ) , in which a total of responses were collected, cases were eliminated (univariate outliers) and cases by multivariate outliers (mahalanobis distance), resulting in valid cases. the questionnaire (table ) the the questionnaire statements and the preliminary results of the exploratory factor analysis (efa) are described in table . the total variance explained, which evaluates all variables together resulted in . %, as the variance explained for each construct (table ) obtained values above % based on the parameters described in fig. results), it is evident that the observable variables and constructs meet the requirements of normality, reliability and statistical validation, therefore the data indicate feasibility for the application of the sem methodology to evaluate the relationships between the constructs. based on the theoretical model ( fig. ) and the possible correlations between the observable variables of each construct, the integrated model (fig. ) from the parameters described in fig. , in item . evaluation of the quality of the measurement model and structural model, the adjustment indexes of the model were verified j o u r n a l p r e -p r o o f (table ). the nfi, ifi, tli and cfi indices were close to the parameters recommended by bentler and bonett ( ) , tanaka and huba ( ) , bollen ( ) , bentler ( ) , mcdonald and marsh ( ) and hair jr. et al. ( ) . the rmsea resulted in value within the established parameters. to assess the possibility of a moderating effect on generations, the se and chi-square difference values were calculated. table indicates that the se values present significant differences, which confirms the hypotheses h a, h b and h c. it is noteworthy that in cov ea relations generation y received less influence from covid- pandemic on ea (se = . ), however, this is a very high intensity of influence. however, in the cov sc relation, generation y has a higher intensity (se= . ), in comparison with the values of baby boomers and generation x, which are of high intensity. in the cov sr relation, the baby boomers generation (se= . ) presents a big difference in comparison with the other generations. the evaluation of the interference of the generations on the averages of the responses, measured by anova (table ) , identified that significant differences occurred (p< . ) in all constructs (cov, ea, sc, sr). in the cov construct, generations x and y had higher response averages than baby boomers, demonstrating that they are more affected by the situation of covid- pandemic. in the ea, sc and sr constructs, baby boomers have higher mean response values compared to generations x and y. they are demonstrating that the baby boomers generation has socio-environmental behaviors that are more adequate to the principles of sustainability. table shows the se values for brazil and portugal. the results confirm the h a and h c hypotheses, so the multigroup analysis reveals that there is a difference in chi-square and se values, showing that in portugal the cov ea and cov sr relations are higher compared to brazil, highlighting them it is noted that the influence of covid- pandemic on social responsibility is considered a high intensity among residents in portugal. the cov sc relationship does not present significant differences in the se and chi-square values. therefore, the h b hypothesis has not been confirmed. construct sc showed no differences between countries. anova identified that the constructs cov, ea and sr present higher average responses in brazil, which shows the concern with the situation of covid- pandemic, with the construction of a thought of greater socio-environmental responsibility. declared gender (male, female, another gender); ii) work position jobs (auxiliary, analyst/technical, manager, teacher, others, and work in the health field) iii) education (high school, undergraduate, post-graduate / specialization, master's degree, doctorate). the anova and mean values of the constructs of the declared gender, work position jobs, and education groups are expressed in table . regarding the impact of the covid- pandemic, a significant increase in the symptom of psychological disorder was identified: a high rate of . % of respondents who admit to feeling symptom of psychological disorder (insomnia, anxiety, panic, or depression) and . % of respondents say they are consuming more alcoholic beverage consumption. these indicators reinforce that the covid- pandemic, besides being a physical health problem, is a social phenomenon that promotes mobility restrictions, physical distance, hygienic measures and socioeconomic restrictions (de bruin et al., ) , which contributes to presenting symptoms mental illness and anxiety and panic attacks (blake et al., ; zhai and du, ) . another aggravating factor is that the activity in the home office modality, in which . % of the respondents who work, received incentives from companies to perform professional activities at home, which aggravates the situation, because in the family context, in many cases, there is the problem that the children are at home (schools are not working) and therefore add to this demand for care, in addition to professional activity in home office. the results of the hypothesis tests (table ) prove the influence of covid- pandemic (cov) on ea, sc and sr constructs, confirming hypotheses h , h and h . in this regard, the research findings indicate that people are being influenced by the context of the pandemic. therefore, there has been increased concern about socio-environmental issues and the consumption of environmentally sustainable products, which can be evidenced by the high intensity of relationships cov ea (se= . ) and cov sc (se= . ). the growing increase in environmental awareness and sustainable consumption can be partly explained by the pandemic situation and also by studies by cohen ( ) pandemic contingency measures improved air quality. another relevant factor in the research is the increase in respondents' environmental awareness, however, there is also an increase in the production of household waste, as well as infectious waste in health care units, as highlighted by zambrano-monserrate et al. ( ) , the production of medical waste in wuhan increased at significant levels. in the specific case of brazil, this fact is worrying, since the treatment and final disposal of domestic and hospital waste are often not adequate since some states do not yet have a selective collection system and landfill, which is already recommended by the brazilian legislation (brasil-pnrs, ; brasil-anvisa, ) . the results of cov sc (se= . ) show the influence of pandemic on social responsibility, however this relationship is the one that resulted in a less intense value, showing that respondents are less sensitive to social problems caused by covid- pandemic. these findings highlight that the respondents are not engaged or concerned with social issues, with people in social vulnerability, as well as with the least disadvantaged, diverging from the study by orcutt et al. ( ) , which shows that pandemic is changing people's behavior and social awareness. other research also points to these social changes, through the promotion of social campaigns, distribution of food, clothing, personal protective equipment and medicines (al reyaysa et al., ; francis and pegg, ; khan et al., ; tekleab et al., ) . the measurement of the moderating effect of the generations on the relationships between the constructs (table ) identified that there are significant differences in the se values, which confirmed the hypotheses h a, h b and h c. the research results showed the difference between the behavior of different generations, which corroborates the studies by severo et al. ( ) , who claim that baby boomers' behaviors tend to be more conservative and concerned with the quality of life of the family circle, and generation x is focused on career and job maintenance, just as generation y is highly connected with new information technologies and are prone to taking risks. this view of the study by severo et al. ( ) helps explain the baby boomers' responses that resulted in the high cov ea ( . ) and (table ) . respondents from brazil stand out in the list due to the high intensity of cov ea (se= . ), however the h b hypothesis has not been confirmed, since the chisquare difference values are not significant when comparing the two countries. anova also showed significant differences between the groups of respondents (countries) in the constructs cov, ea and sr, but the construct sc did not show significant differences between the means of the responses of the groups. table presents the summary of the hypothesis results. generations has a moderating effect on the relationships between cov and ea confirmed h b generations has a moderating effect on the relationships between cov and sc confirmed h c generations has a moderating effect on the relationships between cov and sr confirmed the respondent's country of residence has a moderating effect on the relationships between cov and ea confirmed the respondent's country of residence has a moderating effect on the relationships between cov and sc not confirmed the respondent's country of residence has a moderating effect on the relationships between cov and sr confirmed in the data analysis process, it wares identified that there are intervening variables, which can influence the results of the framework (fig. ) . anova tests between the groups of respondents declared gender, work position jobs and education ( the main contribution of the research is the framework (fig. ) criticism with the press and media, which causes distrust in society. however, in portugal, this situation is better resolved, in the cov sr relationship, as expressed by the results (table ). in brazil, the phenomenon of covid- did not influence people's awareness of social responsibility, so it is the role of governments, educational institutions, and companies to foster this feeling of helping socially vulnerable people, as well as welcoming people in difficulties, and the achievement donation. the survey results indicate that there is a high consumption ( . %) alcoholic beverage consumption and . % admit to experiencing symptom of psychological disorder (insomnia, anxiety, panic, or depression) due to the situation caused by pandemic. therefore, this finding indicates the urgency government action, for the development of public health programs, in support of people who are living in social isolation. in particular, the survey results point out that the group of health professionals ( . %) are presenting symptom of psychological disorder; therefore, managers of the health network must urgently establish intensive psychological support programs for this group of professionals. another important finding of the research is in the identification that generation y perceives with greater intensity the influence of cov sc (table ) , which is an optimistic data about the concern that the new generations have a more conscious consumption posture. baby boomers, on the other hand, are more sensitive to socio-environmental situations in the context of pandemic, with greater intensity in cov ea and cov sr relations, highlighting that baby boomers are more sensitive to sr actions. on the other hand, generation x, who, in most cases, are responsible for the personal and professional training of the new generations, as they occupy management positions, presented a perception very close to generation y, but without important highlights. another aspect that must be considered is the social and economic impacts of covid- pandemic, which are influenced by public policies adopted by countries to face the situation. in portugal, the government has taken health precautions and contingency plans seriously, maintaining special care to maintain political unity in combating the pandemic. the research, using multivariate data analysis, composed of the tests of normality, variability, afe, and reliability, contributed to the validation of the measurement model (scale with observable variables grouped in constructs). these tests are essential to reduce the impact of the study limitation, which is associated with the risk of using the likert type, which is made up of levels and there is no other source for data triangulation (opinions of respondents only), which may cause the formation of response biases, with the occurrence of common method variance (cmv) and the halo effect (wrong generalization) (bagozzi and yi, ; podsakoff et al., ; de guimarães et al., ) . the statistical tests and the evaluation of multivariate outliers through the calculation of mahalanobis distance, contributed to minimize the effect of cvm. another limitation of the study is directly related to the data collection that occurred using the snowball technique, which can lead to similar characteristics among respondents, since the sample's origin is the researchers' contacts, however using social networks (internet), the necessary randomness occurred to diversify the respondents, which can be seen in section .results, in which the characteristics of the people surveyed are presented. pandemic is more than a public health problem, it is a factor of social, environmental and economic influence, which will change the way people relate to each other and in society, how we relate to natural resources, and how organizations and governments transformed economic logic for wealth generation after the advent of the pandemic. nesta crise, não podemos deixar ninguém para trás the management of corporate social responsibility through projects: a more economically developed country perspective multitrait-multimethod matrices in consumer research the drivers of sustainable apparel and sportswear consumption: a segmented kano perspective correlation between environmental pollution indicators and covid- pandemic: a brief study in californian context transforming systems of consumption and production for achieving the sustainable development goals: moving beyond efficiency comparative fit indexes in structural equations significance tests and goodness of fit in the analysis of covariance structures mitigating the psychological impact of covid- on healthcare workers: a digital learning package lei nº . , de de agosto de resolução da diretoria colegiada nº / . regulamento técnico para o gerenciamento de resíduos de serviços de saúde a new incremental fit index for general structural equation models structural equation modeling with amos: basic concepts, applications and programming determinants of intention and behavior of low carbon commuting through bicycle-sharing in china emerging infectious diseases and outbreaks: implications for women's reproductive health and rights in resource-poor settings covid- control in china during mass population movements at new year. the lancet does the covid- outbreak mark the onset of a sustainable consumption transition? sustainability: science, practice, and policy introduction to the special section: innovative perspectives on systems of sustainable consumption and production. sustainability: science, practice, and policy lockdown for covid- in milan: what are the effects on air quality mais de mil pessoas já foram beneficiadas pela cruz vermelha brasileira no combate ao coronavírus initial impacts of global risk mitigation measures taken during the combatting of the covid- pandemic the influence of entrepreneurial, market, knowledge management orientations on cleaner production and the sustainable competitive advantage cleaner production and environmental sustainability: multiple case from serra gaúcha-brazil the use of organizational resources for product innovation and organizational performance: a survey of the brazilian furniture industry governance and quality of life in smart cities: towards sustainable development goals direção-geral da saúde (dgs) -ministério da saúde de portugal. relatório de situação número decreto do presidente da república n.º -a/ . estado de emergência em portugal hospital environmental and residues management: brazilian experiences environmental impact of the covid- pandemic-a lesson for the future role of the chronic air pollution levels in the covid- outbreak risk in italy. environmental pollution. , structural equation models with unobservable variables and measurement error socially distanced school-based nutrition program feeding under covid in the rural niger delta. the extractive industries and society analysis of consumer awareness of sustainable water consumption by the water footprint concept. science of the total environment multivariate data analysis: pearson new international edition. ed. pearson education limited pandemic spotlight on urban water quality. ecological processes a midpoint perspective on the covid- pandemic a fourteen-day experience with coronavirus disease (covid- ) induced acute respiratory distress syndrome (ards): an iranian treatment protocol covid- : an fy on the frontline positive mechanism of foreign direct investment enterprises on china's environment: analysis of host country regulation and parent company management covid- virus outbreak lockdown: what impacts on household food wastage? environment, development and sustainability an appeal for practical social justice in the covid- global response in low-income and middle-income countries. the lancet global health a multi-level institutional perspective of corporate social responsibility reporting: a mixed-method study covid- pandemic: lessons learned and future directions south america prepares for the impact of covid- . the lancet respiratory medicine principles and practice of structural equation modeling the dark cloud with a silver lining: assessing the impact of the sars covid- pandemic on the global environment recruiting mothers of children with developmental disabilities: adaptations of the snowball sampling technique using social media therapeutic strategies for critically ill patients with covid- modelling crop yield, water consumption, and water use efficiency for sustainable agroecosystem management towards sustainable consumption: a socio-economic analysis of household waste recycling outcomes in hong kong the effect of environmental innovation behavior on economic and environmental performance of chinese firms covid- pandemic and the risk of infection in multiple sclerosis patients on disease modifying therapies: what the bleep do we know? the effect of nonnormality on some multivariate tests and robustness to nonnormality in the linear model análise de equações estruturais: fundamentos teóricos, softwares & aplicações choosing a multivariate model: noncentrality and goodness of fit médicos sem fronteiras começa ação contra covid- no covid- pandemic and environmental pollution: a blessing in disguise what is a sustainable level of timber consumption in the eu: toward global and eu benchmarks for sustainable forest use global call to action for inclusion of migrants and refugees in the covid- response. the lancet common method biases in behavioral research: a critical review of the literature and recommended remedies roadblocks to infection prevention efforts in health care covid- response development of an assessment method for investigating the impact of climate and urban parameters in confirmed cases of covid- : a new challenge in sustainable development investigating a serious challenge in the sustainable development process: analysis of confirmed cases of covid- (new type of coronavirus) through a binary classification using artificial intelligence and regression analysis does sustainable growth, energy consumption and environment challenges matter for belt and road initiative feat? a novel empirical investigation impact of covid- outbreak measures of lockdown on the italian carbon footprint the impact of covid- as a necessary evil on air pollution in india during the lockdown. environmental pollution, a brave new world: lessons from the covid- pandemic for transitioning to sustainable supply and production. resources, conservation, and recycling cleaner production, social responsibility and eco-innovation: generations' perception for a sustainable future innovation and environmental sustainability: analysis in brazilian metal-mechanic industry gamification as an innovative method in the processes of learning in higher education institutions converting home spaces into food gardens at the time of covid- quarantine: all the benefits of plants in this difficult and unprecedented period lower mortality of covid- by early recognition and intervention: experience from jiangsu province covid- : healthy environmental impact for public safety and menaces oil market a fit index for covariance structure models under arbitrary gls estimation translating corporate social responsibility into action: a social learning perspective economic, social and political issues raised by the covid- pandemic doe agora e proteja refugiados do covid- a preliminary assessment of the impact of covid- on environment -a case study of china preventing carbon emission retaliatory rebound post-covid- requires expanding free trade and improving energy efficiency. science of the total environment indirect effects of covid- on the environment. science of the total environment addressing collegiate mental health amid covid- pandemic key: cord- - bx kxxh authors: christensen, sarah r.; pilling, emily b.; eyring, j. b.; dickerson, grace; sloan, chantel d.; magnusson, brianna m. title: political and personal reactions to covid- during initial weeks of social distancing in the united states date: - - journal: plos one doi: . /journal.pone. sha: doc_id: cord_uid: bx kxxh objective: to examine perceptions, behaviors, and impacts surrounding covid- early in the pandemic response. materials and methods: a cross-sectional survey of , u.s. adults was administered on march st, . this survey examined attitudes toward media, government, and community responses to covid- by political ideology and sociodemographic factors. knowledge, anxieties, and impacts of covid- were also assessed. results: conservatives were more likely to report that covid- was receiving too much media coverage and people were generally overreacting; liberals were more likely to report the government had not done enough in response to the pandemic. females and those with lower income experienced more covid- related economic anxieties. those working and with children at home reported higher social, home, and work disruption. social distancing behaviors were more common among liberals and were associated with increases in depressive symptoms. general knowledge about covid- was widely exhibited across the sample, however, black and hispanic respondents were less likely to correctly answer questions about the availability of a vaccine and modes of transmission. conclusions: public health experts should consider the political climate in crafting messaging that appeals to the values of those across the political spectrum. research on the covid- pandemic should continue to monitor the effects of social distancing on mental health and among vulnerable populations. and adherence to preventative behaviors in the wake of this ongoing global pandemic. in light of differences in vulnerability to covid- , access to information, sources of information, and timing of national, state, and local responses to covid- , it is reasonable to assume that individual responses in the midst of the pandemic vary widely. this study examines individual attitudes, behaviors, anxieties, mental health impacts, and knowledge early in the pandemic response, as well as those outcomes by sociodemographic characteristics and political ideology. the purpose of this study was to determine how complex factors within society shaped early perceptions of and responses to covid- . an anonymous cross-sectional internet survey was administered to , adults residing in the u.s. on march st, . the sample was recruited by qualtrics (provo, ut, usa). quotas for sex, race, and income, derived from u.s. census data, [ ] were used to increase demographic representation. implied consent was provided prior to the survey. participants were presented with information about the survey as well as potential risks, benefits and compensation. following this information participants were presented with a statement which read, "the completion of this survey implies your consent to participate. if you choose to participate, please proceed with the questions." compensation was valued at <$ u.s. the study was approved by the brigham young university institutional review board. questions assessed political ideology, scientific trust, and media consumption, as well as attitudes, anxieties, impacts, and knowledge related to covid- . respondents also assessed mental health and demographic information. three author-constructed questions assessed attitudes toward the response to covid- . respondents were asked about pandemic media coverage (too much, right amount, or too little), government action (not enough, responding correctly, or too much), and public response (overreacting, responding correctly, or too much). respondents also answered two true/false questions: if they believed their state would experience a major outbreak of the virus and if they would isolate if they contracted the virus. we used the political polarization in the american public survey, [ ] which has been validated as a reliable measure of political partisanship, [ ] to examine personal political ideologies through a series of dichotomous statements on political issues. responses were scored (liberal = - vs. conservative = + ), summed, and categorized as leans liberal, moderate, and leans conservative. respondents also self-characterized their political views on a -point scale (extremely liberal to extremely conservative). two additional items asked about attitudes toward global warming (most scientists think global warming is happening vs. there is a lot of disagreement as to whether global warming is happening) [ ] and trust in government to make vaccination decisions (i trust that the government makes the best decisions when it comes to vaccination requirements vs. i do not trust the government to make decisions about what vaccinations are required). [ ] a subset of questions from the reuters institute digital news report [ ] was used to assess media consumption. respondents indicated their usual sources of media (abc, fox, npr etc.) which were each given a bias score based on ad fontes media's source evaluations. [ ] pandemic-related behavior change was assessed by eleven author-constructed items asking respondents to compare their behavior on march st with their behavior before the pandemic on a -point scale from "much less than usual" to "much more than usual". behaviors included virtual communication, face-to-face contact, visiting restaurants/bars, stores, work, and travel. four items asked respondents to indicate agreement on a -point scale that "events related to covid- had interrupted" their social life, home life, work or vocational life, and/or hurt their mental health. fourteen author constructed items assessed pandemic-related anxieties using a -point agreement scale. four statements related to fear if they, an older family member, a young family member, or a healthy adult family member became ill with covid- . two statements assessed anxieties related to healthcare equipment and personnel, three statements assessed economic concerns, and four items assessed concerns related to children at home (e.g. routines affected, children without care, etc.). questions regarding work-and child-related anxieties were only asked of those working for pay before the pandemic and those who had children under in the household respectively. the last question assessed concerns that mental health would suffer due to social distancing measures. respondents assessed change in their own mental health from before the covid- pandemic on a -point scale from much worse to much better. respondents completed the phq- (a valid measure of depressive severity) [ ] retrospectively for the two-week period preceding social distancing and for the current two-week period. higher phq- scores indicated more depressive symptoms. an increase in depressive symptoms is indicated by a positive change score. true/false and multiple-choice items developed by the authors were used to assess respondent knowledge regarding common symptoms of covid- , recommended preventative measures, viral spread, and comparisons of covid- and seasonal influenza. respondents reported age, biological sex, race, ethnicity, marital status, education level, whether they were currently in school, employment status prior to the pandemic, average hours worked currently and prior to the pandemic, household size, household income, whether they received government nutritional program assistance, children at home, state of residence, and flu vaccination history. frequencies, proportions, and means were calculated. chi-square, t, and f tests were used to examine the influence of demographic characteristics, political ideology, and mental health on attitudes, knowledge, anxieties, behavior change, and impact variables. logistic regression was used to assess the relationship between political ideology and attitudes towards media, government, and community responses to covid- while controlling for sociodemographic characteristics, political ideology, media bias, global warming agreement, and trust in government vaccination requirements. initial covariate selection included all variables that were significant (p < . ) in bivariate tests, including: political ideology, bias score for consumed news media, attitudes toward global warming and vaccination, sex, race, poverty level, and education. the final model was achieved by sequentially removing non-significant predictors and assessing the impact on model fit using the bayesian information criterion and akaike information criterion. non-significant predictors were retained if removing them worsened model fit. two attitude questions were dichotomized for logistic regression, due to small cell counts. those who responded there was "too little media coverage" (n = ) were merged with those who responded "the right amount" of media coverage. similarly, those who responded the government had "done too much" (n = ) were merged with those who responded the government had "done the right amount" in response to the pandemic. logistic regression models were tested with the grouped categories as outlined above, and with the small categories coded as missing; results were similar. logistic regression was also used to assess the relationship between knowledge about covid- while controlling for sociodemographic characteristics and media bias. initial covariate selection included all variables that were significant (p < . ) in bivariate tests, including: bias score for consumed news media, sex, race, poverty level, and education. the final model was achieved by sequentially removing non-significant predictors and assessing the impact on model fit using the bayesian information criterion and akaike information criterion. non-significant predictors were retained if removing them worsened model fit. all analyses were completed in sas . . the sample included , u.s. adults from u.s. states and d.c. no respondents resided in vermont or wyoming. the sample was . % male, . % white, . % black, . % hispanic and . % asian. about % of the sample had children under living at home, about % were living under the federal poverty line, and about % had received government benefits in the last six months. sample demographics overall and stratified by political ideology are presented in table . the majority ( . %) felt that covid- was receiving the right amount of media coverage, with . % responding that the pandemic was receiving too much media coverage. conservatives were most likely to feel the pandemic was receiving too much media coverage ( %) compared to moderates ( . %) and liberals ( . %; p-value < . ). table provides the adjusted logistic regression analysis for the attitude questions. compared to conservatives, liberals had three times the odds (aor . ; %ci: . - . ) and moderates had twice the odds (aor . ; %ci: . - . ) of reporting that the media coverage was the right amount/too much. the majority ( . %) responded that the u.s. government had not done enough in response to covid- , while % felt the government responded correctly. just % felt the government had done too much. liberals ( . %) were most likely to respond that the government had not done enough in response to covid- , compared to . % of conservatives. nearly % of conservatives reported that the government had done too much in response to the pandemic (p-value < . ). in the adjusted logistic regression model ( table ) liberals had . ( %ci: . - . ) and moderates had . ( %ci . - . ) times the odds of responding that the government had not done enough in response to covid- compared to conservatives. those who consumed liberal leaning news media and who indicated there was scientific agreement about global warming also had higher odds of feeling the government had not done enough. approximately % felt that people were generally overreacting to covid- and % felt that people were generally under-reacting. conservatives ( . %) were most likely to feel that people were overreacting while liberals ( . %) were most likely to feel that people were under-reacting (p-value < . ). in the multinomial logistic regression model (table ) , compared to conservatives, liberals had approximately three times the odds of reporting people were responding correctly (aor . ; %ci . - . ) or under-reacting (aor: . ; %ci: . - . ). females and those who consumed liberal news had significantly higher odds of feeling people were under-reacting to covid- . despite variation in opinions regarding the response to covid- , % felt that their state would experience a major outbreak of the disease. a similar percentage of liberals and moderates felt a major outbreak would occur ( . %, . %), while a smaller percentage of conservatives ( . %; p-value = < . ) agreed. regardless of political ideology nearly all respondents ( . %) reported they would self-isolate in the event that they became ill with covid- . respondents reported moderate agreement with all four statements evaluating fear related to becoming sick or having a family member become sick with covid- . respondents agreed most strongly that they would be scared if an elderly family member contracted covid- (mean: . ; sd: . ), followed by a young family member (mean: . ; sd: . ), regarding events surrounding covid- , a majority ( . %) agreed they were afraid they may not be able to purchase supplies, food, and/or medication they needed. similarly . % of those who were working before the pandemic agreed they were afraid they may not be able to financially provide for themselves or their families if asked not to work due to social distancing, and . % agreed that they were afraid they would not be able to provide for themselves or their families if they became sick with covid- . table shows the distribution of economic anxieties by sociodemographic factors. after adjusting for the other factors in the table, females and those with lower income had higher mean agreement with all three economic anxieties statements as compared to males and those with higher income. in general, respondents reported changing their behaviors consistent with public health guidelines for social distancing. table shows the distribution of changes in behavior. the degree to which people reported their behavior changed differed by political ideology. liberals were more likely to report a change in their behavior in the desired direction compared to conservatives. in answer to a direct question, . % reported that their perceived mental health was worse than before the pandemic, while . % reported their mental health was better. we examined the change in depressive symptoms using the change in phq- scores. for behavior changes related to in-person contact with family, close friends, and colleagues, as contact decreased, there was a slight, but statistically significant increase in depressive symptoms (table ) . a similar pattern was seen for frequenting your usual place of work, restaurants and bars, and stores. there was no statistically significant association between reduction in travel or contact with strangers and depressive symptoms. overall, respondents indicated highest mean agreement that covid- had interrupted their social life (mean: . ; sd: . ). table provides the mean agreement scores and t-test analyses for differences in social life, work life, home life, and mental health interruptions due to covid- overall and across child and work status. those with children at home indicated higher agreement that the pandemic had interrupted social, work, and home lives and hurt their mental health compared to those who did not have children at home. those who were working before the pandemic similarly reported higher levels of interruption for social, work, and home life and worse mental health as opposed to those who were not working. the sample was generally knowledgeable about covid- . the vast majority ( . %) correctly identified that the world health organization had declared covid- a global pandemic. nearly all correctly identified that covid- was spread by respiratory droplets from coughs and sneezes ( . %), and by touching infected surfaces followed by touching your face ( . %). a smaller, but still large percentage, ( . %) correctly identified that at the time the survey was distributed (march st, ) there was no vaccination for covid- . a bivariate analysis showed that general knowledge largely differed by media bias and sociodemographic characteristics (sex, race, poverty level, and education). however, after adjusting for all parameters using logistic regression, education was no longer significant, sex was only significant on two of the four questions, while race and income were significant on three of the four questions (table ). while media bias was not significant for most questions, removing it from the model worsened model fit. ) of correctly reporting that one can contract covid- by touching infected surfaces and then touching one's nose or mouth. compared to those whose news bias score leaned conservative, those whose news bias score was moderate or leaned liberal had . ( %ci: . - . ) and . ( %ci: . - . ) times the odds of correctly reporting that covid- is primarily transferred through respiratory droplets. greater than % of respondents correctly identified fever, cough, and shortness of breath as symptoms for covid- . however, a majority also said that nausea ( . %), aches ( . %), and nasal congestion ( . %) were common symptoms of covid- . likewise, more than % of respondents correctly identified hand washing ( . %), not touching your face ( . %), avoiding contact with sick persons ( . %), avoiding large groups ( . %) and sanitizing surfaces ( . %) as recommendations from the centers for disease control and prevention (cdc) to prevent covid- . a smaller, but still large percentage identified avoiding eating in restaurants and bars ( . %) as recommended. a little over half ( . %) correctly identified wearing a facemask in public as not being an official recommendation of the cdc. this recommendation was released on april rd, (four days after the survey was administered). in comparing covid- to seasonal influenza, the majority ( . %) correctly identified covid- as having a higher case-fatality rate. however, % felt that seasonal influenza and covid- had similar risk of death and % reported that seasonal influenza was more deadly than covid- . those who were politically conservative were more likely (p-value < . ) to say that the seasonal influenza was more deadly than covid- ( . %) compared to moderates ( . %) and liberals ( . %). political ideology was the strongest factor associated with attitudes toward the covid- response. this finding is consistent with research suggesting that as new politicized issues emerge, ideology is predictive of adopting beliefs which are suggested to be consistent with an ideology. [ ] suggestions of beliefs that correspond with ideology may be implied by the deliverer of information (e.g. a conservative or liberal lawmaker) or through language cues in information sources, such as media. political ideology was further associated with behavior change surrounding covid- . this finding is consistent with the theory of planned behavior [ ] . as political ideology was associated with attitudes toward the covid- response, it is reasonable to assume that those with attitudes suggesting government or community over-response to the pandemic would be associated with beliefs that recommended behavior changes were unnecessary. the u.s. political climate continues to affect individual, organizational, and governmental responses as the pandemic evolves. however, our results suggest that, even early in the pandemic, political ideology played a large role in the attitudes and behaviors adopted by u.s. adults. the ability of political ideology (and related measurements such as news source bias) to predict an individual's attitudes about and adherence to recommended behaviors in response to a public health crisis raises concerns about the efficacy of existing strategies to manage such crises in this era of extreme politicization. [ ] this suggests the necessity of developing politically neutral strategies that facilitate effective communication surrounding public health crises. sociodemographic characteristics were associated with pandemic-related economic anxieties (sex, income, and race), attitudes toward the community response (sex and race), and knowledge (race) about covid- . many of these discrepancies point to persistent gender, income, and racial inequality in the u.s. these phenomena are particularly well illustrated when analyzing the disproportionate burden of economic anxieties felt by minority races, lower income individuals, and females. higher economic anxiety would be expected among those in lower income brackets, as they have a reduced ability to weather income loss or unexpected expenses. it is also unsurprising that racial minorities in the u.s. are experiencing higher economic anxieties, given the conflation of poverty and race in the u.s. increased economic anxiety in females is consistent with other research. this may be at least partially explained by poorer perceived economic stability relative to males. [ ] disparities in care-giving responsibilities may also help explain sex differences in economic anxieties. females generally have more care-giving responsibilities for home, children, and family, as dictated by societal tradition. [ ] responsibility for maintaining family schedules and routines during this pandemic would likely add disproportionately to the physical and emotional strain on females in the u.s. while general knowledge about covid- was high, most respondents also identified symptoms including nausea, aches, and nasal congestion which were not part of the initial symptom list. this finding may reflect the emerging nature of information about covid- or inaccurate information spreading by word-of-mouth rather than official sources. while general knowledge about covid- was widely exhibited across most sociodemographic and political characteristics (a promising demonstration of the wide reception of public health messages and recommendations), black and hispanic respondents were generally less likely to respond correctly to knowledge questions, which may be a result of a larger proportion of black and hispanic respondents lacking access to adequate resources or receiving misinformation. this is particularly concerning given racial differences in the rate of severe complications and deaths from covid- . [ ] at the time of writing, % of deaths due to covid- in chicago had occurred in african americans, despite the fact that their percent of confirmed cases ( %) mirrored their proportion of the chicago population ( %). [ ] unfortunately, these racial and economic disparities mirror well-documented disparities for many other respiratory infectious diseases, including severe outcomes from influenza. these disparities, rooted in historic, racially-motivated policies, limit african americans' access to care and information and exacerbate factors that place them at higher risk for pre-existing conditions. after only two weeks of social distancing in most areas of the country, one-third of respondents reported worse mental health than before covid- . this finding is consistent with research which identifies social isolation as a significant factor in mental health. as social distancing fundamentally requires separation from most sources of community (i.e. work, religious communities, friends, family, etc.), increases in loneliness as the pandemic progresses may be expected. [ ] social isolation and loneliness are linked to significant increases in morbidity and mortality, which raises concerns about population well-being in the event of protracted social distancing and supports the need to find means of social connection that are consistent with social distancing recommendations. [ ] disruption to social, work, and home life and worsened mental health due to covid- were higher for those with children at home and for those who were working for pay before the pandemic. due to school closures, many with children at home are managing new roles as full-time caregivers and managing educational activities, often while maintaining their own employment responsibilities. higher levels of disruption and worsened mental health among the employed likely results from disruption of daily routines, job insecurity, or an absence of valued social interaction. we acknowledge that these results were based off a cross-sectional study regarding an emerging infection. at the time of data collection, information about covid- was nascent. knowledge, best practices, attitudes, and impacts have rapidly changed since the collection of these data. therefore, the generalizability of our results are limited to adult populations in the u.s. during the early weeks of the pandemic's influence in the u.s. nevertheless, early stage information regarding this pandemic, may prove useful for future outbreaks of emerging infections. this study was conducted approximately two weeks after implementation of initial social distancing guidelines. as such, it provides the opportunity to examine the early impacts of covid- and associated social distancing in the u.s. population. although this provides useful information, it is unlikely to represent the attitudes, anxieties, and behaviors of the population throughout the pandemic. quota sampling for sex, race, and income provided a sample that is statistically similar to the overall population of u.s. adults; however, samples derived from internet panels may differ in unmeasurable ways from the u.s. population. our sample under-represents households with children at home ( . % of sample vs. . % u.s. households). [ ] conclusion these findings underscore the need to develop public health messaging that considers the influence of the political climate. strict fact-based messaging may simply be insufficient to engage the community in desired public health actions, particularly for highly politicized events such as covid- . public health experts should consider differential messaging that appeals to the values of those across the political spectrum. covid- ): cases and deaths in the factors associated with mental health outcomes among health care workers exposed to coronavirus disease a nationwide survey of psychological distress among chinese people in the covid- epidemic: implications and policy recommendations mental health outcomes among frontline and second-line health care workers during the coronavirus disease (covid- ) pandemic in italy mental health outcomes of the covid- pandemic. rivista di psichiatria immediate psychological responses and associated factors during the initial stage of the coronavirus disease (covid- ) epidemic among the general population in china effective communication during an influenza pandemic: the value of using a crisis and emergency risk communication framework. health promotion practice crisis leadership and hurricane katrina: the portrayal of authority by the media in natural disasters the theory of planned behavior. organizational behavior and human decision processes families by presence of own children under political polarization in the american public: how increasing ideological uniformity and partisan antipathy affect politics, compromise and everyday life. pew research center political polarization in the american public global warming's six americas vaccine hesitancy survey questions related to sage vaccine hesitancy matrix: examples of survey questions designed to assess determinants of vaccine hesitancy. who the media bias chart version the phq- : validity of a brief depression severity measure more than ideology: conservative-liberal identity and receptivity to political cues women and economic anxiety. marketplace-edison research poll housework: who did, does or will do it, and how much does it matter? social forces chicago's coronavirus disparity: black chicagoans are dying at nearly six times the rate of white residents, data show an overview of systematic reviews on the public health consequences of social isolation and loneliness loneliness and social isolation as risk factors for mortality: a meta-analytic review we thank william f. christensen for his comments and feedback. key: cord- - m u oz authors: settersten, richard a.; bernardi, laura; härkönen, juho; antonucci, toni c.; dykstra, pearl a.; heckhausen, jutta; kuh, diana; mayer, karl ulrich; moen, phyllis; mortimer, jeylan t.; mulder, clara h.; smeeding, timothy m.; van der lippe, tanja; hagestad, gunhild o.; kohli, martin; levy, rené; schoon, ingrid; thomson, elizabeth title: understanding the effects of covid- through a life course lens date: - - journal: nan doi: . /j.alcr. . sha: doc_id: cord_uid: m u oz abstract the covid- pandemic is shaking fundamental assumptions about the human life course in societies around the world. in this essay, we draw on our collective expertise to illustrate how a life course perspective can make critical contributions to understanding the pandemic’s effects on individuals, families, and populations. we explore the pandemic’s implications for the organization and experience of life transitions and trajectories within and across central domains: health, personal control and planning, social relationships and family, education, work and careers, and migration and mobility. we consider both the life course implications of being infected by the covid- virus or attached to someone who has; and being affected by the pandemic’s social, economic, cultural, and psychological consequences. it is our goal to offer some programmatic observations on which life course research and policies can build as the pandemic’s short- and long-term consequences unfold. covid- pandemic on individuals, families, and populations. this is not just about predictability but about the pandemic's implications for the organization and experience of transitions and trajectories within and across life's central domains. because covid- is a viral pandemic, we begin with its implications for health and then turn to matters of personal control and planning, social relationships and family, education, work and careers, and migration and mobility. it is our goal to offer some programmatic observations on which life course research can build, raising questions, generating hypotheses, and steering data collection as the pandemic's shortand longterm consequences unfold. in viewing covid- through a life course lens, we are able to identify risks, vulnerabilities, and inequalities that may come to individuals and groups, and for this reason, we also address some emerging policy concerns and hope to inform interventions. to anchor the paper, we briefly highlight the most central aspects of a life course perspective; its concepts and principles can be found elsewhere (e.g., ben-shlomo, cooper, & kuh, ; bernardi, huinink, & settersten, ; dannefer, ; elder, shanahan, & jennings, ; mayer, ) . a life course perspective on covid- requires attention to time and time- these dynamics must also be understood from subjective standpoints: that is, how people anticipate or project their lives looking forward, and how they review, interpret, and evaluate their lives in the present and looking backward. life courses should be analyzed with a dual emphasis on social structure and human agency: on one hand, a variety of social contexts play powerful roles in shaping the life course and creating both inequalities and shared experiences; on the other hand, human beings can take j o u r n a l p r e -p r o o f actions and make decisions, individually and collectively, that affect their life pathways and outcomes. finally, it is important to emphasize interdependencies across multiple levels of analysis (from inner-individual to macro levels), multiple life domains (e.g., education, work, family), and multiple interrelated people (the "linked lives" of family, friends, and acquaintances). the future course of the pandemic is unclear. we are writing during what may be a movement toward the pandemic's culminationor during what may prove to still be its beginning. we can say with certainty, however, that covid- is already one of the deadliest infectious diseases of the last years, that it has ruptured much of social life, and that its threat and disruptions will continue for some time. there are two distinct aspects to parse: ( ) having covid- , or being attached to someone who does, and ( ) being affected by the social, economic, cultural, and psychological consequences of covid- . in other words, there is an important difference between being infected and being affected. both things matter, and the analysis of both is served well by a life course perspective. the pandemic is at heart a health challenge. as the world awaits a medical solutionparticularly a vaccinethe most effective remedy has been behavioral: physical distancing. it is this behavioral remedy that has immediately and significantly altered every domain of lifethrough restricted mobility and social interaction, voluntary or involuntary quarantines, lockdowns for whole populations, remote working and learning, or loss of work altogether. physical it is difficult to know the pandemic's ultimate course, as knowledge about the virus is still accumulating while we are writing and modeling its diffusion is extraordinarily complicated. projected scenarios for individual countriesand for the world at largediffer dramatically by a variety of factors, including future orders related to migration, mobility, physical distancing, mask use, school and work closings and resumption criteria, testing, tracing, hospital capacity and equipment, and when an effective vaccination will be developed and available. this distinction was originally made by parfait eloundou-enyegue as a panelist in the international union for the scientific study of population's (iussp) webinar series, positioning population studies to understand the short and long-term impacts of the covid- pandemic, may , . distancing measures arise from a widely recognized need and political will to manage the virus, as political decisions and specific policies are guided by varying interpretations of the causes of the virus's spread, what should be done, and who is responsible for controlling it. two caveats moving forward. first, we are an international group, but our view is inherently western. we hope that our observations will stimulate questions and hypotheses that can be asked and tested in countries other than our own, which are themselves remarkably different in the spread of and response to covid- and also in their cultural characteristics and institutional arrangements. second, we actively decided to keep the number of citations to a bare minimum. research into the pandemic is rapidly evolving. at this time, it is largely focused on the virus itself and matters of public and allied health, and its quality is variable and many results unstable. our goal is not to generate a set of guidelines for future research based on a review of science during this early stage. instead, we use a more essayistic form, drawing freely on our collective knowledge and experience, with the intention of fostering a program of life course research on important questions that need to be asked and answered. epidemiological estimates of the covid- virus vary widely due to differences in testing and tracing systems. a large percentage of the population may eventually be infected, but smaller subsets become ill, require hospitalization, need intensive treatment, and die. knowledge about the short-term course of individual infections and effective treatments is improving but there is still much to learn about long-term health consequences. the health risks of the virus increase strikingly by age and are greater for men and for ethnic and migrant groups, which are intertwined with social disadvantage. exposure, infection, and quality of health care are directly and indirectly related to occupations and living conditions, especially in societies without universal healthcare. j o u r n a l p r e -p r o o f for example, workers in some fields like health, food, or transport services are more directly exposed to the virus. so are people who live in favelas or high-poverty neighborhoods or in cramped living quarters, such as labor migrants and refugees in camps. those in high-stress jobs, such as "gig economy" workers, may similarly have greater risks that come about indirectly, through the weakening of the immune system. an obvious link between the life course and covid- is the strong association between old age and the risk of developing a severe form of the disease and dying from it. the greater vulnerability of older people distinguishes the current pandemic from the spanish flu, for instance, which killed younger individuals at a much higher rate. yet an epidemiological or public health perspective on the life course reminds us that it is problematic to have too singular a focus on mortality and older people. infection cases that do not result in death can nonetheless have longterm consequences for the health and wellbeing of individuals, families, and populations of all ages. in addition, infection and post-infection risks are not equally distributed across the population and are likely to exacerbate existing social inequalities in health. a life course perspective emphasizes that the health risks of covid- depend on prior biological, psychological, and social exposures, including accumulated socioeconomic drawbacks. many of the known prognostic health factors of severe responses to the virus, such as some forms of diabetes, cardiovascular disease, and cancer, take years to develop through exposure to pollutants and toxins, poor diet, and lack of exercise. life course research in epidemiology and other fields has shown that major health and disease conditions in adulthood and later life often have early developmental origins, stemming even from the prenatal period. the underlying risk of developing a severe response to covid- can vary greatly between individuals of the same age, j o u r n a l p r e -p r o o f and a life course approach urges analyses beyond chronological age as a proxy for risks and instead toward a focus on lifetime exposures to the specific risk factors in question. such evidence needs to be taken into account when identifying interventions to mitigate the impact of the virus. a crucial sensitizing question is how lifetime exposure to relevant pathogens, such as previous coronaviruses, or environmental pollution might affect individual and cohort susceptibility to covid- . for example, the timing of an infection intersects with the lifetime trajectory of immune function of individuals and birth cohorts, including the adaptive immunity acquired in early life and immunosenescence (the gradual deterioration of the immune system due to normal aging) in older adultswhich may increase susceptibility to newly-emerging pathogens. indeed, one's history of risk factors is associated with markers of "immune age," which in turn may alter vulnerability to covid- . the covid- pandemic is an example of a global "macro" environmental event that may challenge the health of birth cohorts, or subgroups of those cohorts, across their lives. health can be affected by exposure and susceptibility to the virus and any immediate or delayed responses to an infection; government responses to control the virus; local, regional, and national health systems, which become a kind of life course repair system; and political systems that to varying degrees prioritize economic growth or stability over public healthwhen public health is also good for the economy. individuals will resist, recover, and adapt to the virus in ways that may risk or protect their health in the long term. dynamics related to the growth, maintenance, and decline of physical and mental capacities should be tracked, as well as the onset and progression of chronic diseases and their preclinical intermediate phases. evidence is already emerging that some survivors of severe covid- infection are taking a long time to fully recover or may even endure permanent negative j o u r n a l p r e -p r o o f health effects. to inform health care and epidemiology, it will be important to monitor the longterm health outcomes of those with both severe and more moderate responses to the virus. it will be ideal to study cohorts whose pre-infection capacities and diseases are known, permitting an examination of whether the infection produces a dip and recovery in their functional trajectories, a permanent reduction in function, and/or an accelerated rate of functional decline. research also needs to account for the psychological consequences of the virus, such as the fear and anxiety triggered by it, as well as the uncertainty of living with it, for oneself or loved ones, now and in the future. in many countries, the pandemic has been accompanied by unprecedented lockdowns, the enforcement of physical distancing, and the prioritizing of health systems for the care of covid- patients. research is needed to investigate the effects of these responses and their timing on shortand long-term health outcomes. the disruption of regular health, social care, and emergency services, as well as of informal family care not necessarily related to covid- , have led to additional deaths. less preventive care, later diagnoses, and delayed treatments for other illnesses and diseases are affecting population health. there are reports that domestic and child abuse, and mental health crises, including suicide, have increased during the pandemicand yet, these are likely to be underestimates because clinicians, teachers, and other mandatory reporters were not as often interacting with or observing women and children, and because reaching out to authorities may have been more difficult or risky. lockdowns have heightened these problems, as well as negative health behaviors like physical inactivity, alcohol and drug use, and overeating. lockdowns and requirements for face coverings have in some countries incited much social unrest related to government control and individual behavior that endangers others. lockdowns may be triggering prior, new, or future mental health j o u r n a l p r e -p r o o f crises to which individuals may be more or less susceptible at different ages or life stages. examples include children developing anxiety in seeing their parents distressed or being confronted with rules about dangers they cannot see; parents worrying about their parents; and elders worrying about their high risk of infection and death as well as that of children or grandchildren in high risk occupations. while it is natural to focus on the pandemic's immediate effects on adults, it may be children who suffer the deepest and longest effects. for parents in vulnerable groups, there may be a large negative two-generation effect of the pandemic, and the trickle-down consequences for children may not be revealed for decades. pandemic conditions are likely to harm the health, social, and material wellbeing of children, with the poorest children, including homeless children and migrant children, hit hardest because both covid- infections and the disruptions caused by the pandemic disproportionately affect disadvantaged populations. as children grow older, the pandemic may bring lasting scars through factors such as poor nutrition, anxiety, family instability, exposure to domestic violence, reduced access to services, or lower educational attainment. taking inspiration from sociologist glen elder's ( ) children of the great depression, it will be particularly important to observe the pandemic experiences of children in different stages of development, and to compare them as they grow older in order to estimate the distinct effects of the pandemic on their physical and mental health. the shadow of the pandemic may be longer and darker for toddlers and preschoolers than for preadolescents and teens, and interventions may be needed years after the pandemic for the former group and during and during or soon after the pandemic for the latter group. health and wellbeing will be indirectly affected by the economic decline and high rates of unemployment that have resulted from lockdowns. loss of livelihood is already a reality for many j o u r n a l p r e -p r o o f individuals and families. from a life course perspective, the timing of economic downturns in a cohort's biography can be important in the long-term. for example, as we will discuss in a later section, the working careers of young adults entering the labor market at such a time may never catch up to those of earlier or later cohorts; their continuing disadvantage can lead to poorer health outcomes later in life and widening inequalities. similarly, the effects of poverty and instability on children are long-lasting and affect learning and other developmental progress, which are also tied to later health outcomes. the pandemic has brought a pervasive sense of being unsettled and losing control, making it difficult for individuals to plan, let alone optimize or coordinate their plans. extreme loss of control could lead to disengagement from important life goals. under a common external threat, however, individuals might abandon individual agency for collective agencythat is, they might join with others to make social change that reduces or removes external constraints to future life course opportunities of whole populations or communities. the global movement to protest systemic racism, which arose after the killing of george floyd at the hands of the police in the u.s., has done just that, creating collective agency and a future perspective for those who have been hit hardest by the pandemic due to their greater exposure in high-risk jobs, inferior access to health care, and other vulnerabilities. collective agency was broadened and strengthened by the recognition that some of the pandemic's social, economic, and health risks are shared by the majority. in many countries, there have been increases in volunteering or helping others, especially the greater uncertainty created by the pandemic over the short and long term is likely to have somewhat different effects by age, social class, gender, and race/ethnicity and be modified by a country's welfare system and the emergency interventions of its institutions. consider young adults on the brink of finishing school and entering the workforce. the precarious life conditions of the pandemic might lead young people to lower their goals or limit their risk-taking in ways that return to post-world war ii values of material security and stability that are not well-matched to the realities of the labor market in the globalized world today. any disadvantages that young adults suffer in the short term may grow over time. in being young, though, they have a longer time horizon to adjust or recover. moreover, they tend to have greater optimism than their parents and grandparents. many youths are exploring life goals and choices in connection with a range of "possible selves" and anticipated futures, and their lives are not yet as "canalized" by prior choices as older adults. these circumstances make it easier to deal with the threat to control and planning brought about by the pandemic. the disruption to young adults may feel especially heavy, however, because they do not yet have a long history of experience or accumulated resources to fall back on as they rework life goals or adapt to life's disappointments. a shrinking labor market takes away opportunities to acquire experience or resources which, in turn, can have lifelong scarring effects. modern cohorts of youth and young adults have been socialized in ways that emphasize their agency and aspirations. the pandemic has underscored the reality that life's possibilities are limited. young people and their parents will naturally blame the pandemic for some outcomes that might not have been appreciably different without it. differences by socioeconomic status are likely to be substantial in this regard because reduced control and choices already characterize the lives of those with few family resources. they may be in "survival mode" without long-term backup plans j o u r n a l p r e -p r o o f for education, careers, and families. those who are more favorably situated may have a more difficult time adjusting their aspirations, but they may also more successfully surmount pandemic challenges, feeling ready sooner to resume striving for ambitious goals and be more confident going forward. those well into adulthood are more firmly embedded in family and work responsibilities. the pandemic's toll may be particularly acute for them and others who rely on them. their family statuses leave them with fewer choices if they need to reorient themselves in work. they typically shoulder responsibilities for supporting young adult children and caring for older parents. by midlife, one's time horizons are growing shorter and efforts are focused on building security for the later years. there are fewer opportunities to recover from hard times and it is too early to retire. in many countries, the safety nets for working-aged adults are intentionally temporary and meant to replace only a limited portion of lost income. likewise, midlife adults might more often need to change plans to help others, such as extending working life to support younger family members who are without jobs. the greater personal, social, and economic capital of those in midlife, however, might expand their choices or foster a sense of control. but just as these individuals have more capital to leverage for coping, they also have more to potentially lose. any control they feel may be precarious, and lower ses individuals have fewer resources at their disposal to redirect their lives. older adults, in further contrast, can be expected to focus more on the present than the future: immediate joys, uplifting daily events, the relationships of close family members and friendsthereby optimizing positive and minimizing negative affective experiences. their shrinking time horizon leads them to place a greater premium on goals and experiences that bring meaning. they have the least time to recover economically from any market consequences of the j o u r n a l p r e -p r o o f pandemic. their economic wellbeing is dependent on public and private pension plans, assets, and often on family members. older people have better emotion regulation, more advanced coping strategies, and a broader range of experiences within which to place the pandemic experience and judge its relative significance. these judgments will not only be rooted in purely personal experiences, but also in their historical location. a centenarian today would have been preadolescent at the start of the great depression and a young adult at the start of world war ii; a septuagenarian would have been born in the decade following world war ii and a young adult during the politically and socially turbulent late s and early s. even in these two examples, both anchored in later life, the pandemic will be interpreted through different historical lenses. more generally, older generations might, by virtue of their experience, take the perspective that "this, too, will pass" or to recognize that there are many things in life people do not get to decide or cannot control. these different ways of understanding the world and seeing life will be meaningful intergenerationally, especially in families, which are natural meeting places for different historical generations. when three or more generations are assembled together, families contain a patchwork of historical experiences that can span even a century. given the age segregation of many social environments today, families are the key forum for making sense of history. in both families and societies, these generational differences in worldviews can be both sources of tension and bridges to solidarity. amid covid- , there have been reports that ageism has been on the rise, on the older end perhaps driven by blame for lockdown measures that have brought so much disruption or of health system overload, and on the younger end perhaps driven by resentment of teens and young adults who have disregarded protective measures based on their belief that they are not at risk of illness or death. for older adults we can again expect socioeconomic differences in the effects of the pandemic. in many countries, the wealth (versus income) of older people is much greater than those of younger adult ages, but so are differences among older people, reflecting advantages and disadvantages that have accumulated across the life course. poor and minority elders, at least in countries like the u.s., live in dense and underserved communities or in badly run and understaffed nursing homes, where they are significantly exposed to infection risks and die under dreadful circumstances. these older adults are likely to feel significant loss of control and despair. later life is a highly precarious period: control capacity and self-efficacy are more possible when health, wealth, and social relationships are intact, but weaken as these resources come undone. an individual's attempts to adapt to the crisis will be shaped by their personality characteristics and worldviews. caspi and moffitt ( ) argue that times of crisis accentuate the role of personality in shaping individual responses and thus the long-term sequelae for the life course. personality characteristics will therefore interact with the pandemic in ways that uniquely shape and increase individual differences in short-and long-term outcomes. for example, those who are highly confident and engaged in pursuing ambitious goals might approach a lockdown with resilience and inventiveness, finding new ways and means to make progress under the changed circumstances. those who are less confident or engaged with their own prospects may suffer declines in goal expectations and social or cognitive functioning. again, social inequality will be important in determining whether someone can afford to embrace ambitious and risky goal engagement during a societal crisis. with respect to planning and control, men may be more shaken than women by the lack of predictability created by the pandemic. men's lives have traditionally been more linear in orientation and clockwork, and women's lives have traditionally been more contingent, whether j o u r n a l p r e -p r o o f in being more at the will of the body in with respect to biological clocks and cycles related to reproduction or in having greater interdependencies stemming from family roles and relationships. the immediate shock of the pandemic has shaken the relations among people. mobility restrictions created by physical distancing measures have left people painfully aware of how much their wellbeing is linked to others and how much they take for granted the ability to be with others. social integration likely makes a difference in people's capacity to cope during the pandemic, but the distancing measures also reveal and alter the quality of relationships. this also poses an interesting dilemma: feelings of loneliness affect the immune system, but interacting in the population could result in an infectious disease. the pandemic has not only severely impaired the ability of people to be in close physical face-to-face interaction with other humans, this has in turn blocked the intense human need to touch and be touched, preventing hugging and constraining the transition to parenthood has been especially affected by pandemic measures. hospitals and clinics have not allowed others to accompany mothers during labor, delivery, and recovery. the postpartum period of assistance from family and friends has been limited by travel restrictions and the at-risk status of potential family assistants (e.g., older parents). this may create feelings of isolation and despair. some new parents, on the other hand, might appreciate the fact that the social world is kept at bay to foster their private time and bonding. parents of young children might similarly appreciate the extra family time. fathers may be more present and involved in family life, especially in contexts without paternal leave. we may begin to observe pandemic-era changes in the timing, or anticipated timing, of family transitions, such as the postponement of cohabitations, marriages, or fertility, or accelerated separations and divorcesdue to any number of factors related to resources, markets, and uncertainties. it will be important to examine whether such changes, should they emerge, are temporary disruptions to the schedule for family transitions or longer-term trends that alter it in a more permanent fashion. in aggregate, these changes will affect population structure and dynamics, and larger societal consequences might include the intensification of delays in the transition to adulthood and growing rates of singlehood, childlessness, and population aging. the pandemic and physical distancing have the potential for immediate and long-term effects on young children's attachment. infants, toddlers, and preschoolers are extremely sensitive to changes in their environments but do not fully understand them. when quarantines began, there was great anxiety about the virus entering and spreading through the household and families struggled with how to safely express physical affection. in a lockdown, families are less worried j o u r n a l p r e -p r o o f because they are limiting contact with the outside worldexcept, of course, for those working in essential services and those with household members with vulnerable health. with reopenings, parents again worry about the virus coming into the household. worries are likely greater for those with teenage children, who may feel immune to the virus; and those with young children, who are not as able to manage physical distancing. when schools are closed, children and teens are unable to interact in person with friends. for teens, especially, peer groups and friendships are central to exploring identities. they also desire to be in large groups, dense settings, and on the move. of course, digital media permitted continuity in friendships and a lifeline to others. but lockdowns and school closures generate further isolation among young people who are socially marginalized in any number of ways. for some teens and young adults, the expression of their identities is stifled or not permitted at home; for example, there are reports of increased homelessness among lgbtq youth. for teens and adults seeking intimate relationships, the pandemic has restricted in-person possibilities for dating and sex. there are alternative modes for these pursuits, such as online platforms, but also questions about the emotional quality, need fulfillment, and survival of these relationships. the pandemic removed many adults from their workplaces and primary daily networks, forcing them to collaborate and sustain connections remotely. increased work at home can colonize family life. this problem has several dimensions, including the fact that it is employers who benefit most when employees use their private time, space, and other personal and relational resources to accomplish their work. it also reinforces or increases inequality due to differences in employees' personal resources and home situations that make it more or less difficult to work remotely. remote work can also increase stress through instant availability, high demands, the press of care for children and infirm relatives, and the blurring of work and nonwork boundaries. older people are more vulnerable socially because they are not permitted to be or are fearful of being with others, given their greater health risks, and because the toll of the pandemic is greater in their networks, triggering dynamics of loss. those who live alone experience the greatest risk of isolation. widowers are especially vulnerable, as older men are not as embedded in family and social networks and longstanding relationships. older people who are forced to shelter in place may feel a deep loss of independence. those struggling with illnesses at home or in care environments may not get the support they needor, especially for older women, give others the support they would like to give, such as grandchildren or sick relatives. older people are dying alone or saying goodbyes through plastic partitions or glass windows, phones, and computers. enforced lockdowns have generated more intensive family interaction and increased the interdependence of family members. households were more crowded at all hours due to unemployment or work from home, the need for home meals, lack of childcare, and responsibility for children's education when schools are closed, or limited care or health services, placing greater strain on women and mothers in particular. job loss and economic hardship have led some households to "double up" in an effort to conserve resources or accommodate those who could not pay mortgages or rent or were evicted. these conditions have undermined relationships. families with children or other members with special needs have suffered from the withdrawal of support services. partnerships that were vulnerable before the pandemic seem more likely to dissolve thereafter. family structure also made a difference in the ability of families to cope with economic challenges. lone parents with young children, who are often economically and psychologically more vulnerable, struggled not only to make ends meet but also to manage the organizational challenges of the pandemic. because these parents are more likely to be mothers, the burden of the j o u r n a l p r e -p r o o f pandemic is again shouldered by women. and yet, some families seem to be closer and more connected, prioritizing their relationships and settling into slower rhythms of family life. amid the pandemic, the normal use of video-calling in multi-local families diffused to all kinds of families to bring together multiple generations and extended families in ways they did not before, as well as the greater incorporation of both very old and very young members. in families where someone has contracted the virus, members may be thrust into caregiving roles to meet immediate, recovery, or long-term needs. in later life, a particularly painful role is that of outliving a spouse or an older adult child who has died of covid- . a pandemic like covid- dramatically increases the mortality that would normally occur in a particular period. at present, mortality risks remain most concentrated among older people, but these losses nonetheless ripple through family networks as the virus hastens the deaths of parents and grandparents. a life course perspective on education and training emphasizes the importance of transitions across levels in the process of educational attainment as well as from school to training and from school to work. whether these are accomplished "on-time" or "off-time" often has major implications for the subsequent life course, inviting a focus on the long-term consequences of earlier transition experiences. the immediate disruption to students of all ages was swift and acute, with virtually no time for teachers or students to prepare. it is difficult to know how long these challenges will last and what toll they will take on students' learning or academic achievement. it is again foreseeable that effects are likely to vary by the ages and social positions of students, and by how educational systems are organized. for elementary and secondary school students, the content and quality of the learning experience shifted from school to home. in the new homeschooling environment, some children are well equipped with computers, fast internet access, j o u r n a l p r e -p r o o f and a quiet place to study, whereas others are in cramped quarters, without the resources or wherewithal to accomplish distance learning. parents who are able to work remotely are at least somewhat more available to monitor their children's distance learning, although parents' confidence and ability to help will vary by their resourcefulness and educational levels. remote learning (and working) has also exposed status differences across students (and employees), as video connections put people's home lives and living conditions on display. educational systems vary in the extent to which they select and track students and allow students to switch tracks. systems that offer more structured educational pathways and curricula may more easily allow students to follow and complete their education, but if these are accompanied by fewer opportunities to change course, they can lead to unsuccessful transitions. educational systems that sort pupils into different tracks at young ages (e.g., germany, switzerland) create more inequality in educational outcomes than more comprehensive systems. it is plausible that the pandemic will heighten these inequalities, both because parents with more resources are more able to support their children's learning and because increased uncertainty may decrease students' willingness to pursue higher education -and parents' willingness to pay for it, or as much for it, in countries where the private costs of college are high. some youth have had to scale back their educational aspirations, staying close to home or planning a "gap year" when faced with the likelihood of continued remote learning (preventing a "true" college experience) or possible infections in group living and large in-person classes. delayed educational transitions may have more indirect effects on the life course by increasing the size of later graduating cohorts, resembling something like a baby boom. the life chances of these students would be altered by their position in an unusually large cohort of j o u r n a l p r e -p r o o f graduates simultaneously navigating labor, housing, and relationship markets in early adulthoodand competing with those who were already in the labor market but are still trying to recover. the transition from school to work is becoming more precarious with the now-historic unemployment and underemployment rates, business closings, and organizational downsizing. those who are completing degrees amid these conditions seem most likely to be negatively affected; studies of long-term earnings for those entering the workforce in prior recessions demonstrated negative effects throughout their occupational careers. this juncture is strongly governed by the link between educational and labor market institutions as well as welfare states. generally, the transition to work has been smoothest in countries such as germany and switzerland, which have strong links between education and the labor market due to their extensive vocational training and apprenticeship programs. the covid- crisis can disrupt the transition to work if companies scale back apprenticeships, bringing potential long-term consequences for the cohort entering the labor market during the crisis. the mechanisms disrupting the transition can take different forms in countries like the u.s. and u.k., which offer little institutional support for this transition, and where students have always had to rely on networks of family and friends, prior employers, or college career centers to find jobs. finally, in southern european countries with already high youth unemployment, youth are likely to experience an amplification of existing delays in leaving home and entering first jobs as part of an ongoing delay in the transition to adulthood more generally. the pandemic will also affect transitions back to education or training in adulthood. millions of displaced workers will require re-training, skill upgrading, and new degrees, enabling movement into growth sectors (e.g., health care, digital technology). the pandemic has brought growing opportunities for the expansion of online learning, potentially from a greater range of j o u r n a l p r e -p r o o f providers, creating more flexibility to manage education alongside work and family commitments and the possibility of "lifelong learning"a principle that many educational systems have been very slow to integrate into their functioning up to now. even then, the chances of attending and completing further educationwhether degrees, certificates, or shorter trainingdepend on adults' work and family commitments. in the pandemic, disruption to one's own or a spouse's employment, or the onset of illness for a family member, may be just enough to block or require withdrawal from education or training. furthermore, it has been clear for some time that the rate of knowledge growth and the changing nature and even continued existence of many jobs requires greater educational attainment or ongoing training. there has been some resistance to acknowledging and adapting to this fact. the pandemic has brought a seismic shift in the use of electronics, the internet, and remote learning in ways that could create more openness and responsiveness to the need for ongoing education and training over the life course. the pandemic and the policies used to combat it have had immediate labor market consequences. unemployment has increased exponentially. apart from analyzing the distribution of unemployment risks across age groups and life stagesas well as for different subgroups defined by gender, race, and nativitylife course researchers will be particularly interested in tracing how the short-term consequences of the pandemic's economic crisis are translated into long-term effects. prior research on economic recessions and depressions repeatedly demonstrates that earlier unemployment begets later unemployment and leaves a lasting mark on income. for some, unemployment is a short-lived experience, while for others it becomes the starting point of a longer-term process of labor market exclusion. the effects of unemployment on various aspects of individual and family wellbeing are most severe when it is prolonged. one might expect to find the strongest long-term effects for the cohort of graduates whose immediate transition from school to work is hampered by the pandemic, particularly if it lasts a long time. this could result in a kind of "lost generation" with shrinking opportunities in employment and truncated career and family formation, which would in turn have lifelong consequences. note, however, that the current evolving economic crisis can add "insult to injury" for those cohorts now in their thirties who were already penalized a decade ago when they entered the job market during the financial crisis (or "great recession") that began in , most of whom now have the additional economic demands of parenthood. the effects of the pandemic on work and careers are sure to be moderated by existing national support systems, such as the unemployment and social benefit systems, labor market regulations, and family policies; by individual and community resources; and by existing gender, race and other inequities. work organizations also play a role: the characteristics of pension systems, and their interactions with labor market institutions, shape pathways to retirement and thus affect older and younger cohorts of workers alike. with respect to individual resources, one wonders about the influence of social networks and especially of "weak ties" and "bridging ties," which have been shown to be powerful in generating occupation and employment opportunities. for many people, it would seem that during the pandemic strong ties remain strong, as family members and friends stay in touch, if sometimes inconveniently (e.g., with video-call programs). however, it is important to ask whether the pandemic might threaten, or perhaps even strengthen, weak or bridging ties, and what effects this might have not only on work and careers but on access to and exchanges of support to meet other needs as well. furthermore, the economic crisis of the pandemic, at least its early phase, has affected economic sectors differently. given how strongly education and occupational sectors are j o u r n a l p r e -p r o o f intertwined with occupational segregation, the sector-specific consequences of the crisis will shape career inequalities. self-employed and temporary workers are likely to be more affected in their career options than those with permanent contracts. those in low-wage service sectors have been especially hard hit with the reduction of restaurant meals, catering, travel, or entertainment. those in office-based service jobs, such as custodians and cafeteria workers, are more likely to permanently lose employment as work at home continues and jobs are replaced by automated technologies and artificial intelligence. these types of workers, who were in low-pay jobs before the pandemic, now face a severe lack of employment, reduction of income, and reliance on sometimes inadequate income support systems. however, the pandemic has highlighted the role of "essential" workers, many of whom are employed in less prestigious and poorly paid jobs, such as caring, transport, cleaning, and check-out staff. lockdowns, school closures, and care responsibilities associated with the pandemic can be expected to significantly and negatively impact women's employment and careers. women are more often found in lower-paid, less secure, or part-time and nonstandard work, and in more vulnerable sectors of the labor market. women are more likely to be responsible for providing immediate and lingering care to family members with covid- , which will take a toll on their careers. this is unusual, given that in a recession unemployment generally hits men harder than women because more men work in industries that are closely tied to economic cycles, such as construction and manufacturing. women, conversely, are more dominant in industries not tied to such cycles, such as healthcare and education. however, this time other factors played major roles. pandemic-based needs may prompt couples to revert to a more gendered division of labor, eroding progress toward gender equality. at the same time, it is possible that the pandemic-based crises in schools, care settings, and at home will raise the visibility and value of women's work. there are possible interactions to examine between age-and domain-specific effects and work and health outcomes. young people are at lower risk of being infected than older adults, but they are at greater risk of becoming unemployed than already established workers. older workers, particularly those in the retirement bracket, are more prone to infection but might be better protected economically, especially in countries with strong labor unionsif their pension funds are not eroded by the evolving economic crisis. older workers' greater risk of contracting the virus, and its greater health impacts, might increase discrimination in the (re)hiring of older workers and push them into retirement prematurely. many of the immediate effects of the pandemic resulted from the need to control it by restricting mobility and migrationfrom movement across international borders down to movement within spaces of everyday life. such constraints interfere in many ways with life course opportunities and outcomes of individuals and families. early restrictions on day-to-day mobility and travel were severe, with millions of people confined to their homes, institutions, or destinations. the closing of borders or the selective regulation of international travel alters many kinds of migration, including labor migration, family-related migration, refugee migration, student migration, and amenity migration. not only has initial migration been severely restricted, but many of those who had migrated before the pandemic continue to be stranded and cannot get back to their origin points. this is particularly problematic for those who have been laid off, have limited social protections or are without income, and cannot afford travel. short-and long-term consequences related to restrictions to migration are also likely to fall on faraway family members of international migrants, including children and elderly "left behind" in the seasonal migration of women and men in care or agricultural sectors, and whose quality of life depends on that work. in addition, the highly feminized migrant care workforce across the globe may undermine gender equalities and the status of women when they cannot provide a major source of family income. although seemingly less extreme by comparison, internal migration and residential mobility over shorter distances nonetheless affects life course opportunities and outcomes. it can interfere with the ability to move in order to find better jobs or schools, begin university, more easily manage work and family life, or give or get formal or informal care. it has been difficult to get elders into nursing homes or other care institutions, which have been a hotbed of virus transmission. moving forward, people may be afraid to seek necessary care in these environments and try to "age in place" as long as possible. the need for internal migration will increasingly be prompted by economic hardship and an inability to afford rent or mortgage payments, forcing families or individuals to downsize and move into less desirable areas with reduced access to health, education, and transport services. primary assets stored in homeownership may plummet if housing markets cool down, especially in densely populated cities or tourist destinations that have traditionally had greatest demand and highly inflated real estate values. the rise in unemployment will undoubtedly lower demand for labor migrants and create a corresponding decline in both internal and international migration. easy and affordable access to travel may become even more selective in the wake of covid- , especially through the limited supply and regulation of public transport and reluctance to use it. this will affect the direct costs of moving as a strategy to improve life chances. more fundamentally, new surges in the pandemic will reduce the possibility of back-and-forth travel after a move. people may be especially hesitant to move internationally or over long distances, thus reducing the globalization of labor markets. worry about travel might inhibit even shorterdistance moves from family and create a tendency to live closer to work, or to work from home altogether. even after the virus is under control, these changes in perspectives, norms, and practices may remain for many years to come. long-term life course consequences are likely to be particularly strong for those who were at a critical turning point in their lives when the pandemic hit, and whose lives took a different turn than envisaged before the crisis. important examples are entry into post-secondary education and the labor market. these transitions mainly take place at young adult agesprime ages of migration and mobility. as a consequence of the crisis, options for long-distance career moves or education j o u r n a l p r e -p r o o f abroad may not only be postponed, but also foregone. this could create disadvantages that cannot be undone later in life, or that can be overcome only with difficulty. in the very worst case, lives could be lost owing to a lack of options to find refuge from oppression, climate change, or virus outbreaks following from anti-immigration policies. those in lower socio-economic strata already tend to be less mobile, but their mobility is likely to be even more constrained because of their economic standing and the costs associated with moving. it will take several decades to reveal the life course consequences of policies meant to control the pandemic through public health practices and interventions. such policies have modified people's attachment to and the boundaries between life domains, as well as the interdependencies between people. lockdown measures, in particular, reduced institutional and organizational boundaries and created significant spillovers as homes became the hub of education, work, and family life. the physical separation of people reduced the potential for typical patterns of social exchange and support. of special concern are those with few social connections or who live alone, especially older people whose health was already compromised or might be compromised amid covid- . for those in unhealthy relationships or resource-deprived networks, dependence rather than isolation is likely to be the major issue through which the pandemic carries some of its negative consequences, as the increase in domestic violence against women and children in some countries has shown. because care work is relatively inflexible, unlikely to follow predictable rhythms, and heavily gendered, it is women who are especially being struck by a series of undesirable outcomes of responses to control the pandemic. pandemic-related measures have not only modified the organization of life for the initial months of the emergency phase, but also the graduated phases of resumption. these modifications j o u r n a l p r e -p r o o f are likely to bring many longer-term consequences for the life course. the pandemic has unveiled socioeconomic, ethnic/racial, and gender inequalities that are magnified by existing income and health inequalities. distinct policy contexts related to the economy and work, education, and health will be particularly central in fostering or hindering recovery and the redistribution of resources toward the most vulnerable. public policy systems that emphasize individual responsibility and reliance on private (family) support over public support have deepened the effects of the crisis for the most vulnerable, whether through insecurities related to food, housing, employment insecurity, or health insurance. even in more progressive welfare states, students, the self-employed, and undocumented immigrants have often been excluded from government schemes to address resources lost during the covid- crisis. these groups have had few options for financial assistance, other than what family members might provide. it is unclear whether policies designed for the general public will be effective in reaching and protecting those who are not embedded in social relationships or networks that might help offset the serious consequences of the pandemic, whether loss of employment, income or hope. policies must be designed to protect children, including dependent young adults, from the risks of poverty and other family hardships. the pandemic has significant implications for educational policy and inequalities among children, youth, and young adults. the revenues for schools are falling as municipalities and regional governments cope with the immediate health and economic effects of the pandemic. increasing aid for public education is a tough sell when there are other competing critical needs (e.g., hospitals, homeless shelters). during the pandemic, schools are facing even greater costs related to supplies, equipment, space, and personnel. to reduce inequalities, schools have to provide computers or tablets and subsidies for internet access. if nothing is done to augment j o u r n a l p r e -p r o o f educational budgets, the digital divide among parents will have long-term implications for the life courses of children and adolescents. moreover, if governments pull back on funding higher education, institutions will be forced to raise tuition, which occurred during the great recession. programs are needed to enable youth with limited resources to attend college and to open up higher education for a possible wave of school-returners after an unhappy period of job search, unemployment, or underemployment. an alternative is to make online courses a more viable alternative to traditional forms of education provision. moreover, policies are needed to smooth the transition between school and work. when students can realistically foresee a future job, they will have greater motivation to complete their educational programs, persist when challenges threaten their progress, and attain sought-after educational credentials. there is also a need to reintegrate and support the economic production sector through active labor market policies promoting employment, such as those investing in retaining, and policies contrasting labor shortages due to restricted seasonal mobilities and longerterm migration flows. environmental, cultural, and behavioral changes triggered by the pandemic may also have positive outcomes for population health and wellbeing in the longer-termfor example by improving individual health behaviors; decreasing tolerance for rising social inequalities; heightening informal social support and collective solidarity; making clear how government and programs that work well are necessary for everyone's wellbeing; and increasing support for a "one health" approach that views the health of people, animals, and the environment as interconnected. thus, the pandemic might increase support for social protections throughout the life course. but the economic burden created by the policies to control the pandemic might also produce a backlash less supportive of social programs and major redistributive policies. in addition, concerns j o u r n a l p r e -p r o o f with people's mobility and the diffusion of the virus may nourish nationalism and xenophobic attitudes, an upsurge in anti-immigration policies, or resistance to reopening borders to certain populations. these early months of the pandemic have served as a reminder that wellbeing and quality of life are not only about economic resources, and that a purely medical or epidemiological perspective in policy development is insufficient. well being and quality of life are to a great degree dependent on the boundaries and balance between work and private life, caring social relationships, good health, comfortable living arrangements, trust in politics and one another, and well-functioning social institutions and governments. the pandemic has also served as a reminder that health and wellbeing are not only individual characteristics but public goods that matter for the welfare and functioning of whole communities and populations. because most welfare-state schemes are designed to repair or normalize disrupted life courses, the degree to which welfare states are strengthened or weakened in the wake of the pandemic and its economic consequences will be a major source of life course stability, change, and precariousness. the same applies to new forms of social investment in welfare programs, including health insurance. in countries with loose-knit welfare systems, the prospect of largescale social decline should favor the reinforcement of the social safety net, especially with a view to older unemployed or economically-dependent persons who are threatened by the loss of support. covid- has opened a window to rethink current institutions and policies with the life course in mind. many institutions have responded to the pandemic with greater flexibility in normal practices and policies, openness to innovation, and more permissiveness and compassion toward the people learning, working, and living in those institutions. the pandemic has brought lessons in how systems might be reworked holistically to foster continuity. for example, greater j o u r n a l p r e -p r o o f awareness of the interdependencies across life domains creates an opportunity to find alternative and possibly long-term solutions to curbing work-family conflicts; greater awareness of the interdependencies across individuals creates an opportunity to develop more flexible and sustainable forms of interaction and cooperation. the pandemic has also raised awareness that social institutions and policies reproduce and even deepen inequalities, bringing lessons in how systems can be redesigned to address persistent disadvantages associated with gender, race, age, social class, and other social categories. the research community was quick to react to the spread of covid- and the unprecedented measures used to curtail it by launching numerous data collection efforts, not only in the health sciences but also in the behavioral and social sciences. as we have emphasized, the life course approach can fertilize research on the health, psychological, and social risks of covid- and the broader crisis, as well as investigations of their long-term consequences. it is important that data collection efforts do not become compartmentalized by discipline but remain broad and recognize the multiple facets of the pandemic. data will need to be gathered years after the pandemic to examine its various long-term consequences. life course researchers should remain active in guaranteeing expansive long-term data collection efforts of a variety of issues beyond, but also including, health. due to the centrality of time and time-related phenomena, longitudinal data will naturally be the most important data resource for life course research on the covid- pandemic. several established longitudinal data projects, such as national panel and cohort data, are already collecting or planning to collect modules or items specific to and during the covid- pandemic. life course researchers emphasize how earlier life experiencessuch as prenatal and early childhood health, childhood conditions, unemployment experiences, cumulative exposure to adverse health or other conditions, as well as exposure to previous historical eventscreate risk and shape the effects of subsequent experiences on individuals and entire cohorts. therefore, the greatest data gains will be made by building on ongoing longitudinal projects that link information on life before covid- to experiences during and specific to the pandemic. these projects have the additional advantage of building upon existing sampling frames and research organizations, which can add to their flexibility in collecting new data during the pandemic. inserting a supplementary module or items on covid- experiences at regular intervals will help adapt existing longitudinal studies to this new topic. ad hoc point-in-time studies that generate data using any variety of methods might provide relevant data even more rapidly, but these will often lack longitudinal depth (except for information that can reliably be gathered retrospectively) and the means to follow their pandemic samples over time. next to time and time-related phenomena, we have emphasized the distinction between being infected and affected by the new coronavirus, as well as the importance of social structure and context, and agency and subjectivity. understanding how exposure to risk factors over the life course affect health during the pandemic requires reliable information on whether one has been infected as well as the severity of the disease that followed. such data also are needed to analyze the effects of having been ill from covid- . ideally, infections would be measured using reliable serological tests. similarly, longitudinal data projects would preferably collect other biological data relevant to understanding covid- infections and their consequences, including data on predisposing health conditions and genetic data. as we have emphasized, covid- infections affect not only those who are infected but also family members and others in close vicinity. likewise, because the coronavirus spreads j o u r n a l p r e -p r o o f through social networks, becoming infected depends on who one lives and interacts with. both call for data on the "linked lives" of covid- . these data, as well as data on other ways in which the covid- pandemic has affected family lives and social relationships, will enrich many existing projects which have already traditionally acknowledged the importance of households and family lives in their longitudinal data collection efforts. this clustering means that people are differently exposed and affected depending on where they live, work, and socialize. this variation gives rise to natural experiments that should be exploited to design studies for analyzing the effects of exposure to the virus on the one hand, and physical distancing, school and workplace closures, and other measures that emerged in response to covid- on the other. this will require geographically and contextually granular data. the granularity creates data size demands that may not always be met with surveys or other common types of data. administrative data and national registries will be valuable due to their sheer size for many research questions regarding family dynamics, work and careers, and health outcomes, covid- represents a massive global crisis that behavioral and social scientists must study from a life course perspective. the pandemic creates a pressing need and unique laboratory to analyze how institutional structures, sociodemographic composition, types of stratification, and other dimensions of societal differentiation and regulation generate different responses to a j o u r n a l p r e -p r o o f common threatening external shockand, in turn, how those responses alter the organization and experience of the life course in a given society. as the pandemic unfolds, we must continue to monitor which societal changes will be temporary and which will be longer-lasting and even lead to permanent systemic change. a life course perspective provides a powerful lens for understanding these complex interdependencies over time. the life course perspective's emphasis on time invites diachronic (time-based) rather than synchronic (point-in-time) comparisons. the effects of the pandemic will likely depend on timing that is, on ages or life stages that are more or less vulnerable or sensitive to certain types of effects. the most severe health risks of the pandemic are strongly related to old age, whereas the pandemic experience shows more as a disruption to daily activities and social roles and as heightened social and economic insecurity for the young. the life course perspective also invites us to look beyond chronological age and to account for biographical and historical time. looking backward, the pandemic brings to the fore how individuals have different susceptibility to the virus itself and to the social and economic consequences of the pandemic, depending on their previous experiencesexperiences that can also determine the short-term and long-term consequences of the pandemic. a life course perspective demands that we read the life course through personal history as well as through its intersection with social history. the ages of people today are a window into their historical location, which affects the response to and effects of the pandemicas in the example of people now navigating the pandemic in their thirties, were just a decade ago navigating the great recession during their transition to adulthood. looking forward, a life course perspective also asks us to identify which pandemic experiences will turn into permanent scars or reorientations for individuals and their families, and j o u r n a l p r e -p r o o f which will be open to resilience and be compensated for or even forgotten with time. even more, it encourages researchers to account for heterogeneity by specifying for whom there will be scarring or resilience, and to account for environment and policy considerations by specifying the conditions under which there will be scarring or resilience. whether we are looking backward or forward in understanding the pandemic's effects, it is important to not only probe these dynamics at an individual level of analyses, but also to examine them for groups, especially birth cohorts or social generations. in historical moments like this, people of different ages are branded differently, not just because they are in distinct developmental periods but because their lives carry the imprint of prior historical experiences. the pandemic is reshaping transitions and trajectories in every domain of life, and instigating turning points that redirect life. many of these can be negative, or at least challenging. the transition to adulthood, for example, has become longer, more variable, and risk-laden in many countries in recent decades. the pandemic is likely to heighten these trends through its effects on educational transitions, youth labor markets, chances for regional mobility, family formation, and general trust in the future. likewise, at the other end of working life, the transition to retirement may become more difficult due to insecure pensions or insufficient savings or assets, just as leisure and volunteering activities or the grandparent role may become more difficult due to limited mobility or concerns about exposure to covid- . indeed, throughout the life course, the age-based rhythm of many transitions may loosen in the face of uncertainty and de-standardize life trajectories. some changes associated with the pandemic are positive and have direct relevance for life course analysis, interventions, and policies. the pandemic is raising awareness that experiences across life domains such as health, family, work, and education are highly interrelated, and that j o u r n a l p r e -p r o o f these spheres are overlaid with institutions that have different time-based expectations and rhythms. it is bringing newfound recognition that people and places both near to and far from us are linked in fundamental ways that must be made more visible. ironically, just as the pandemic has isolated people from one another, it also seems to be fostering a sense of collective solidarity, community action and cooperation, and the inherent need for mutual support. it is exposing inequalities in life course processes and outcomes, differentially affecting groups based on age, gender, race and ethnicity, social class, and other social categories. it is increasing consciousness that stability in human life is fragile and dependent on social institutionsand on governments and policiesthat are nimble, work well together, and address vulnerabilities and systemic inequalities in the life course. in many societies, these conditions are not met. it is challenging assumptions about the organization of the life course and opening opportunities for innovation and flexibility. broadly, the pandemic is triggering deep tensions in human experience that frame how the life course is understood by the individual members of any societytensions related to individualism and collectivism, autonomy and interdependence, freedom and control, rights and responsibilities, among others. perhaps the most profound axiom of modernity that is being undermined by the pandemic is that of predictability. the uncertainty and disruption it has created mimics a much earlier age, when time and life itself could not be counted on and when aspirations were more limited and planning less possible. one thing is sure: there is a time before covid- and a time after it. this watershed moment is marking the psyches and lives of individuals, families, and cohorts in ways both known and unknown. a life course perspective is necessary to bring these effects, and the mechanisms that create them, into focus for investigation and intervention. j o u r n a l p r e -p r o o f - ), who incorporated contributions from a first ( - ) and second ( - ) group of authors and led iterative rounds of revision with the entire team. authors are listed alphabetically in each group. acknowledgments special thanks are extended to jane falkingham, johannes huinink, and michael shanahan for their thoughtful comments, and to kara mcelvaine for her help managing the project for ingrid schoon, funding from the uk economic and social research council (esrc) for the centre of learning and life-chances in the knowledge economies legacy grant (es/t / ). for tanja van der lippe the "life course cube": a tool for studying lives when do individual differences matter? a paradoxical theory of personality coherence systemic and reflexive: foundations of cumulative dis/advantage and life course processes children of the great depression: social change in life experience handbook of child psychology and developmental science: ecological settings and processes in developmental systems the world we forgot: a historical review of the life course whose lives? how history, societies and institutions define and shape life courses continuities and discontinuities of psychological issues into adult life key: cord- -z fwtwqb authors: ahmed, taha; lodhi, samra haroon; kapadia, samir; shah, gautam v title: community and healthcare system-related factors feeding the phenomenon of evading medical attention for time-dependent emergencies during covid- crisis date: - - journal: bmj case rep doi: . /bcr- - sha: doc_id: cord_uid: z fwtwqb the current covid- crisis has significantly impacted healthcare systems worldwide. there has been a palpable increase in public avoidance of hospitals, which has interfered in timely care of critical cardiovascular conditions. complications from late presentation of myocardial infarction, which had become a rarity, resurfaced during the pandemic. we present two such encounters that occurred due to delay in seeking medical care following myocardial infarction due to the fear of contracting covid- in the hospital. moreover, a comprehensive review of literature is performed to illustrate the potential factors delaying and decreasing timely presentations and interventions for time-dependent medical emergencies like st-segment elevation myocardial infarction (stemi). we emphasise that clinicians should remain vigilant of encountering rare and catastrophic complications of stemi during this current era of covid- pandemic. the current covid- crisis has significantly impacted healthcare systems worldwide. there has been a palpable increase in public avoidance of hospitals, which has interfered in timely care of critical cardiovascular conditions. complications from late presentation of myocardial infarction, which had become a rarity, resurfaced during the pandemic. we present two such encounters that occurred due to delay in seeking medical care following myocardial infarction due to the fear of contracting covid- in the hospital. moreover, a comprehensive review of literature is performed to illustrate the potential factors delaying and decreasing timely presentations and interventions for time-dependent medical emergencies like st-segment elevation myocardial infarction (stemi). we emphasise that clinicians should remain vigilant of encountering rare and catastrophic complications of stemi during this current era of covid- pandemic. a dramatic and perplexing drop in st-segment elevation myocardial infarction (stemi) admissions has been observed during the current covid- crisis. anecdotal evidence suggests that the principal reason behind this is patient's anxiety to avoid seeking medical care at hospitals and overwhelmed healthcare systems due to the pandemic. patients are less inclined to visit hospitals with fear of acquiring covid- . many patients with risk factors of stemi may dismiss their angina symptoms as benign relative to this fear. this attitude of medical care avoidance has led to delay in hospital presentations, with dire consequences. furthermore, the covid- pandemic has impacted the healthcare system's maintenance of operational integrity of high-acuity patients. herein, we chronicle two cases of delayed presentations of stemi with rare complications that we encountered at our centre in the month of april . both patients belonged to the cuyahoga county of the state of ohio, usa. they avoided medical care for a timedependent medical emergency, despite having good social and financial support and easy access to tertiary percutaneous coronary intervention (pci) capable healthcare facilities. their dramatic presentation of stemi with a complicated clinical course and outcomes could have been prevented by an early referral to emergency medical services. this was the time period when the cuyahoga county was one of the most severely affected regions of ohio with the most covid- fatalities reported across the state. patient is a -year-old caucasian woman who presented to the emergency department (ed) with shortness of breath and dizziness for day. she stated having nausea and diarrhoea for weeks, associated with intermittent chest pain. she was hesitant getting medical attention and her symptoms got complicated with shortness of breath and dizziness. her medical history is significant for lifelong cigarette smoking, obesity (bmi of kg/ m ) and untreated hyperlipidaemia. on presentation, she had a blood pressure of / mm hg, heart rate of beats per minute (bpm), temperature of . °f and respiratory rate of breaths/ minute. physical examination showed an anxious woman with cold extremities, tachycardia with no murmurs and increased effort of breathing with a benign abdominal examination. while in the emergency room, patient became haemodynamically unstable and her rhythm converted to ventricular tachycardia (vt) requiring successful cardioversion on three subsequent occasions following which she was transferred to the intensive care unit (icu) for vt storm. ecg revealed a wide complex tachycardia at a rate of bpm (figure a), high sensitivity troponin t (tnt) was mg/l (normal < mg/l) and probnp of pg/ml (normal < pg/ml). covid- testing with nasopharyngeal swab was negative and chest x-ray revealed bilateral opacities. complete blood count showed leucocytosis, serum lactate . mmol/l (normal . - . mmol/l), alanine aminotransferase u/l (normal - u/l) and aspartate aminotransferase u/l (normal - u/l). synchronised cardioversion with three successive shocks were performed for vt storm, with global health conversion to sinus rhythm with repolarisation changes in inferior leads (figure b). she was intubated and transferred to icu on infusion of amiodarone and lidocaine. over the next hour, she became progressively hypotensive with cold extremities requiring vasopressor support. a transthoracic echocardiogram (tte) revealed severely reduced biventricular function. patient was transferred to the cardiac catheterisation laboratory, left and right heart catheterisation (lhc/rhc) performed. rhc revealed the patient to be in cardiogenic shock (table ) . lhc revealed total occlusion of the mid-distal right coronary artery (rca) and % stenosis of the left anterior descending artery (lad) (figure a and b). during an attempt to cross the rca lesion with a guidewire, patient became asystolic. advanced cardiac life support was instituted with return of spontaneous circulation in min. a temporary pacemaker was implanted and three drug eluting stents were placed in the rca with timi flow post-revascularisation. due to small diameter iliac arteries, an intra-aortic balloon pump was favoured over an impella device for haemodynamic support for cardiogenic shock. patient was transferred to the icu with an augmented systolic blood pressure of mm hg. she became progressively acidotic despite haemodynamic support and her lactate climbed to . mmol/l, indicating worsening cardiogenic shock. haemodynamic support was escalated to venoarterial extracorporeal membrane oxygenation (va-ecmo). patient remained on va-ecmo for days and was successfully decannulated on day . repeat tte revealed mildly decreased systolic function with an left ventricular ejection fraction (lvef) of %. patient is currently recovering on the regular medical floor. patient is an -year-old caucasian woman who presented to the ed with worsening shortness of breath and leg swelling for days. her history included coronary artery disease (cad) with remote angioplasty in , peripheral vascular disease, hypertension, hyperlipidaemia, gastro-oesophageal reflux disease and chronic smoking. she reported waking up with chest pressure followed by vomiting days prior to presentation. she was reluctant to visit the ed in ongoing viral pandemic and instead visited her primary care physician's office. ecg during the office visit was unremarkable, her symptoms were considered atypical and she was sent home on pantoprazole. however, new onset worsening shortness of breath prompted her to report to the ed. on presentation, she had a blood pressure of / mm hg, heart rate of bpm, temperature of . °f and respiratory rate of breaths/minute. physical examination revealed a systolic murmur in the third intercostal space along the left sternal border and crackles in the lung bases. ecg revealed st-segment elevations in leads v -v with q waves in leads i, avl, v -v (figure ). tnt was elevated to . ng/ml (normal - . ng/ml) and probnp was pg/ml. patient was administered aspirin mg and clopidogrel mg and started on a heparin infusion. an emergent tte revealed severely decreased lv function with an ef of %, right ventricular systolic pressure of mm hg and a muscular ventricular septal rupture in the mid anteroseptal wall (figure ). patient underwent combined lhc/rhc with saturation study. rhc was significant for a pulmonary capillary wedge pressure of mm hg and lhc revealed acute total occlusion of the proximal lad, diffuse % stenosis in the lcx, % stenosis of ramus intermedius and % stenosis of mid-rca (figure a-c). a left ventriculogram confirmed a muscular ventricular septal rupture (vsr) ( figure d ). there was oxygen step up in the right ventricle and pulmonary artery and the qp/qs was . (table ) . conservative management of the cad was pursued of concerns for reperfusion injury of infarcted myocardium. patient was discharged home on dual antiplatelet therapy, high-intensity statin, beta-blocker and daily furosemide. on a follow-up visit, week after discharge, patient reported worsening shortness of breath at rest. the symptoms were deemed secondary to increased shunting across the vsr. her ecg showed q waves in the inferior leads with residual st-segment elevations. a cardiac mri showed a small defect in the mid-anteroseptum (figure ). patient underwent percutaneous closure of vsr and tolerated the procedure well. currently, the patient is recovering on the medical floor with no symptoms of angina or heart failure. there is a delay and decrease in presentations and timely interventions for medical emergencies like stemi during the current era of covid- crisis. there is a resultant increase in mechanical and arrhythmogenic complications of stemi as a presenting encounter, a rarity in the age of primary ppi (ppci). healthcare providers need to be vigilant in identification and management of late presentations of stemi and its complications. acute stemi is the major cause of mortality globally. it is well established that early diagnosis and immediate reperfusion with ppci are the most effective to improve outcomes by lowering risk of post-stemi complications. however, the covid- outbreak has threatened to overwhelm healthcare systems worldwide, potentially overshadowing other medical emergencies, including stemi. the data from various countries of europe show a %- % drop in stemi presentations and admissions as compared with during the peak of pandemic. [ ] [ ] [ ] in the usa, a comparable decrease in stemi presentations is reported in different states irrespective of the state's burden of covid- . findings from the cleveland clinic foundation, a tertiary care referral centre, also show a consistent reduction in emergency transfers for stemi and other time-dependent emergencies coinciding with the covid- pandemic. garcia et al analysed and quantified stemi activations for nine high volume cardiac catheterisation laboratories in the usa and found a % decrease in stemi activations of cardiac catheterisation laboratories across the us during the covid- period. a recent international survey was conducted by the european society of cardiology (esc) looking at the perception of cardiology care providers with regards to stemi admissions to their hospitals. the investigators found a significant reduction in number of stemi admissions (> %), an increase in presentations beyond the optimal window for ppci or thrombolysis (> %). the data from hong kong reported an increase in time taken for stemis to reach the hospital from . min to min during the pandemic. as a consequence of this latest trend of stemidelayed presentation, the number of mechanical and arrhythmogenic complications of stemi has seen a rise, which is a rare occurrence in the age of ppci. it corresponds with our clinical experience with the forementioned patients who were reluctant to visit ed as they would have in normal circumstances. both of our patients had good family and social support, healthcare insurance to cover for medical expenses, but still evaded medical care for a time-dependent medical emergency. they belong to the cuyahoga county, one of the three largest counties of ohio, which has about hospital beds at registered hospitals, physicians and pci-capable healthcare facilities serving a population of approximately million. the decreased rate of hospital presentations for stemi has paralleled an increased incidence of patients presenting late after stemi onset. physicians around the world are reporting severe complications of stemi from delayed presentations or lack of reperfusion - (table ) . based on our review we hypothesise: . patients are not presenting to the hospital for medical emergencies . patients with angina symptoms and with/suspected/without covid- are presenting late to the hospital. delays in patients seeking medical care, delay in medical testing for suspected patients and delay due to severe covid- related symptoms are observed during the period of crisis. physicians are observing worsening left ventricular functions, massive myocardial infarctions, life-threatening arrhythmias and cardiogenic shocks as complications of stemi, a rarity in the age of ppci. - it has translated into an increased mortality, prolonged admissions to the icu, a grave concern in these times of scarce resources. the observed phenomenon can be attributed to numerable patient and healthcare-related factors. the establishment of covid- hospitals is making many patients reluctant to come to the hospital. patient had concerns whether the cleveland clinic was transformed into a covid- hospital. such misconceptions and confusions along with alterations in patient behaviours of fear of contracting nosocomial covid- are a potential culprit. moreover, patient attempted to self-medicate herself with pantoprazole until her symptoms got severe. reduced family contact and supports during lockdown and the stress associated with stay-at-home orders are potential factors for delayed and decreased presentations for time-dependent medical emergencies. low levels of exertion at home might not trigger cardiac symptoms and impaired manifestations of stemi related to neurotropic and neuroinvasive symptoms of covid- can play a role in those affected with the disease. misinterpretation of stemi being relatively benign compared with covid- disease along with the fear of infection spread via hospitalised patients and healthcare workers is a common perception among community dwellers. the covid- pandemic has put tremendous stress on the healthcare system across the world, even affecting countries with established medical resources. it has disrupted the established care pathways and work flow due to overwhelmed eds. there is a higher threshold of ed referrals by outpatient care providers, as observed with patient . healthcare personnel safety concerns are undeniable, especially with limited staffing resources from high healthcare worker infection rates. the increasing trend of using fibrinolytic therapies to manage stemis in the ed, in an attempt to mitigate system-based delays, has also been described as a causative for re-emergence of rare complications. there has been press releases from esc, american college of cardiology/american heart association, and healthcare experts have voiced concern in major newspapers for public awareness. [ ] [ ] [ ] [ ] [ ] many patients, their families and their caregivers have come forward to share their experiences during this period of crisis. on the media page of the cleveland clinic, global health cardiovascular experts have explained in simple terms the telltale signs of a heart attack as well as how delaying heart care in this covid- surge can lead to devastating consequences. as the pandemic continues, it is imperative to commit stern steps of mass education and public awareness. identification and correction of internal process delays is vital. the utilisation of telemedicine strategies, according to recent reports, was associated with improvement of stemi time of diagnosis and outcomes during the period of crisis. further studies comparing telemedicine to the conventional way of managing patients with acs are need of the hour. altogether, these findings should be taken into serious consideration and effective plans drawn and implemented in case a second wave of the pandemic develops as lockdown restrictions are currently eased worldwide. twitter taha ahmed @tahaahmedmdccf acknowledgements we would like to acknowledge the significant contribution from dr emad dean nukta, who provided us with valuable inputs regarding the interventional management of the patients. we are grateful to both our patients for giving us permission to write up their cases. contributors ta: designed the study, performed the literature review, drafted the manuscript, formulated the tables and reviewed the manuscript. shl: performed the literature review, contributed to the discussion and suggested pertinent modifications. sk: contributed to the case presentation and discussion, revised the manuscript critically for important intellectual content and gave final approval for the version published. gvs: managed the cases, contributed to the case presentation and did a critical review and supervision. funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. competing interests none declared. provenance and peer review not commissioned; externally peer reviewed. this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid- pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. table continued ► several community and healthcare-system-related factors delay and decrease the presentation and intervention for time-dependent non-communicable diseases such as stsegment elevation myocardial infarction (stemi) in the era of covid- crisis. ► as a consequence of these delays, healthcare providers should be vigilant in encountering and managing devastating complications of non-revascularised stemi, rarely encountered in the age of primary percutaneous coronary intervention. ► we present two intriguing cases of delayed presentation of stemi in the era of covid- pandemic with arrhythmogenic and mechanical complications, with a prolonged and arduous clinical course. ► this review focuses on several important patient and healthcare-system-related factors playing a vital role in this perplexing observation. ► several vital steps are postulated to halt this dangerous trend and assure the safety and well-being of general population in case a second wave of the pandemic develops. admission of patients with stemi since the outbreak of the covid- pandemic: a survey by the european society of cardiology collateral damage: medical care avoidance behavior amomg patients with myocardial infarction during the covid- pandemic be prepared how many hospital beds are near you? details by ohio county cuyahoga county reports most coronavirus deaths in the state esc guidelines for the management of acute myocardial infarction in patients presenting with st-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with st-segment elevation of the european society of cardiology (esc) stemi care during covid- : losing sight of the forest for the trees where have the stemis gone during covid- lockdown? decline of acute coronary syndrome admissions in austria since the outbreak of covid- : the pandemic response causes cardiac collateral damage impact of the covid- pandemic on healthcare activity in interventional cardiology in spain decrease in acute coronary syndrome presentations during the covid- pandemic in upstate new york stemi during the covid- pandemic -an evaluation of incidence impact of covid- pandemic on critical care transfers for st-segment-elevation myocardial infarction, stroke, and aortic emergencies reduction in st-segment elevation cardiac catheterization laboratory activations in the united states during covid- pandemic impact of coronavirus disease (covid- ) outbreak on st-segment-elevation myocardial infarction care in hong kong late stemi and nstemi patients' emergency calling in covid- outbreak ohio county profiles the covid- pandemic and cardiovascular complications what have we learned so far? st-segment elevation myocardial infarction in times of covid- : back to the last century? a call for attention as the covid- pandemic drags on, where have all the stemis gone? late presentation of acute coronary syndrome during covid- delayed presentation of acute st segment elevation myocardial infarction complicated with heart failure in the period of covid- pandemic -case report delayed stemi presentation during the covid- pandemic post-mi ventricular septal defect during the covid- pandemic ventricular septal rupture complicating delayed acute myocardial infarction presentation during the covid- pandemic complication of late presenting stemi due to avoidance of medical care during the covid- pandemic eapci position statement on invasive management of acute coronary syndromes during the covid- pandemic acute coronary syndrome in the time of the covid- pandemic fear of covid- keeping more than half of heart attack patients away from hospitals coronavirus and your heart: don't ignore heart symptoms knocking down fears, myths and misinformation about calling in the pandemic unusual stemi complications blamed on covid- hospital avoidance after man, , dies of heart attack, wife shares urgent message: go to the er. today health & wellness seek care for heart emergencies during covid- the obstacle course of reperfusion for stsegment-elevation myocardial infarction in the covid- pandemic telehealth strategy improves stemi care in latin america key: cord- - qzpo l authors: adalja, amesh a.; watson, matthew; toner, eric s.; cicero, anita; inglesby, thomas v. title: characteristics of microbes most likely to cause pandemics and global catastrophes date: - - journal: global catastrophic biological risks doi: . / _ _ sha: doc_id: cord_uid: qzpo l predicting which pathogen will confer the highest global catastrophic biological risk (gcbr) of a pandemic is a difficult task. many approaches are retrospective and premised on prior pandemics; however, such an approach may fail to appreciate novel threats that do not have exact historical precedent. in this paper, based on a study and project we undertook, a new paradigm for pandemic preparedness is presented. this paradigm seeks to root pandemic risk in actual attributes possessed by specific classes of microbial organisms and leads to specific recommendations to augment preparedness activities. the recent global experience with severe infectious disease epidemics has triggered much interest in understanding the broader pandemic threat landscape. a substantial proportion of pandemic and biological threat preparedness activities have focused on list-based approaches that were in part based on pandemic influenzas of the past, historical biological weapon development programs, or recent outbreaks of emerging infectious diseases (e.g., sars, mers, ebola) (centers for disease control and prevention ; casadevall and relman ) . but such an approach inherently fails to account for agents not currently known or those without historical precedent. for that reason, preparedness activities that are limited to these approaches may hamper preparedness and lessen resilience. the purpose of this study was to analyze the characteristics of pathogens that could be capable of causing a global catastrophic biological risk (gcbr). these would be events in which biological agents-whether naturally emerging or reemerging, deliberately created and released, or laboratory engineered and escaped-could lead to sudden, extraordinary, widespread disaster beyond the collective capability of national and international governments and the private sector to control. if unchecked, gcbrs would lead to great suffering, loss of life, and sustained damage to national governments, international relationships, economies, societal stability, or global security (schoch-spana et al. ) . given the severe potential public health consequences of pandemic events, there needs to be a vital interest in developing and maintaining a flexible, rapid, and robust response capability. anticipating the forms of microbial threats that might cause future pandemics can help strengthen preparedness and response capacities. this paper proposes a framework for considering future pandemic threats and provides recommendations for how this framework should inform pandemic preparedness. review of the published literature and previous reports: the project team surveyed the current biomedical literature on the topic of emerging infectious disease characteristics, the pathogenic potential of microbes, and related topics. the literature review was microbe-and species-agnostic, encompassing all classes of microorganisms and host species. the literature review was accomplished with extensive pubmed searches on these subjects. relevant us government policy and strategy were reviewed. interviews: the project team interviewed more than technical experts who work in and are intimately knowledgeable about this field. interviewees were drawn from academia, industry, and government. our goal was to ascertain the experts' views about the essential traits needed for a pathogen to become a gcbr, to contextualize historical outbreaks in light of these traits, and to determine which currently known infectious disease agents possess such characteristics. pandemic pathogen meeting: the project team completed a preliminary analysis that synthesized the results of our literature review and expert interviews. those findings were used to design and facilitate a meeting held on november , , that included many of those who had been interviewed for this project. the meeting was held at the johns hopkins center for health security in baltimore, md. the purpose of the meeting was to gain additional insight and input into the project analysis, examine assumptions, and test possible recommendations. participants included representatives of us and foreign academic institutions, the federal government, and other independent subject matter experts. this paper is based on the findings of the project and is modification of the project report (johns hopkins center for health security ). when a pathogen has the capacity to cause a pandemic, it will possess several attributes that other microbes, capable of causing only sporadic or limited human infections, will lack. these traits can be divided into several categories: spread via respiratory transmission; capable of spread during incubation period prior to symptom onset; no preexisting host immunity; and other possible intrinsic microbial characteristics. many of these characteristics have been captured and are reflected, in equation form, by casadevall (casadevall ) . microbes have varied routes of transmission, ranging from blood and body fluids to vector-borne to fecal-oral to respiratory (airborne and respiratory droplet). while each mode of transmission is capable of causing large outbreaks if sustained human-to-human transmission is possible and left unchecked, certain modes of transmission are more amenable than others to intervention. for example, the transmission of an infectious disease caused by blood and body fluid transmission can be halted with infection control measures such as gloves or gowns. of the various modes of transmission, the respiratory route is the mechanism most likely to lead to pandemic spread. this is chiefly due to the fact that interventions to interrupt this method of spread are more difficult to implement when the simple and universal act of breathing can spread a pathogen. the prolific spread of influenza, pertussis, measles, and rhinoviruses is testament to this fact (herfst et al. ) . by contrast, although pathogens spread by the fecal-oral route, such as vibrio cholera and the hepatitis a virus, can generate explosive outbreaks, even a modicum of sanitary infrastructure can quench the outbreak. vector-borne outbreaks are a special case of a non-respiratory-spread agent. indeed, the only postulated extinction of a mammalian species by an infectious organism, the christmas island rat, was caused by a vector-borne trypanosome (wyatt et al. ) . for most of the agents that use this class of transmission, the spread is limited by a geographically and climatologically restricted vector habitat. humans can protect against vectors, and they can change where they live, but the christmas island rat could not. these factors have generally served to limit the pandemic potential of microbes that are spread by vectors. exceptions to this general limitation of vector-borne viruses include microbes spread by anopheles and aedes mosquitoes. pathogens spread by these mosquitoes have higher pandemic potential, given the geographic breadth of their spread. for example, most of sub-saharan africa is hospitable to the malaria-transmitting anopheles mosquitoes, while residents in % of us counties-as well as half the world's population-are regularly exposed to aedes mosquitoes that serve as vectors for high viremia flaviviruses and alphaviruses. such phenomena are borne out by the prolific spread of dengue, chikungunya, and zika (sinka et al. ; centers for disease control and prevention ). the onset and duration of the period when a person is contagious during an infection also play a major role in spread. diseases that are contagious during a late stage of infection, when infected people are very sick and therefore have more limited opportunities for spread, may be delimited in their spread. on the other hand, diseases that are contagious prior to symptom development, during the incubation period, or when only mild symptoms are present have greater opportunities for spread as infected individuals are able to conduct their activities of daily living with little or no interruption. modeling studies with simulated outbreaks have shown that the presence or absence of this timing of transmission factor can be decisive in whether an outbreak can or cannot be controlled. if a microbe is contagious before a person is seriously ill while the disease is still incubating, then there is higher potential for pandemic spread. historical examples reinforce this idea, as the only human infectious disease to be vanquished from the planet-smallpox-was one that was not contagious during the incubation period (fraser et al. ) . by contrast, a microbe such as the influenza virus, which is contagious prior to symptom development and has a wide range of clinical severity, is able to infect widely and is not amenable to control (brankston et al. ). microbial pathogenicity cannot, in reality, be separated from host characteristics. as elucidated by pirofsky and casadevall's host damage framework, disease is a complex interplay between a host immune system and a microbe (pirofski and casadevall ) . in congruity with this paradigm, host features and microbial pathogenicity are discussed together. for a microbe to cause a gcbr-level pandemic, it will be necessary for a significant proportion of the human population to be immunologically naïve to the agent so that the microbe would have a high number of susceptible humans to infect. additionally, large quantities of a sufficiently effective countermeasure (vaccine or antimicrobial agent) would not be available. immunologic naïveté would be expected with a zoonotic pathogen. the microbe, correspondingly, would have to possess the ability to evade the host immune response through virulence factors, immunological camouflage, or other features that allow a productive infection to ensue. additionally, human receptors that are utilized by a pandemic-causing microbe would likely be widespread in the population, facilitating permissive infection in the majority of humans. receptors may also provide target organ tropism for the agent, allowing severe disease to occur (e.g., lower respiratory tract and central nervous system). case fatality rates (cfrs) need not be inordinately high to cause a gcbr-level event, as evidenced by the . % cfr reported for the influenza pandemic-the event closest to an actual human gcbr in the modern era (taubenberger and morens ) . a low but significant cfr adheres to the host density threshold theorem. according to this commonly held theorem, a microbe that kills too many of its hosts will run out of susceptible hosts and be extinguished (cressler et al. ) . while this may be true of pathogens that are closely linked to one host species, it is not applicable to sapronotic diseases such as amebic encephalitis and cholera (in certain contexts), which can infect and kill without jeopardizing future transmission or survival. indeed, many extinction-level amphibian infectious diseases are sapronotic in nature, such as the chytrid disease of salamanders and frogs (fisher ) . additionally, a gcbr-level event may not confer direct mortality. reproductive effects (i.e., in the manner of rubella or zika) or carcinogenic effects (e.g., htlv- ) could, in many ways, be highly detrimental to the future of humanity, as they could lead to significant curtailment of lifespans and diminishing birth rates, which could ultimately result in significant population collapse (rasmussen et al. ; tagaya and gallo ) . given the right context, any microbial organism could evolve or be engineered to be a gcbr. however, the most likely cause of a gcbr presently is a virus, with rna viruses being the most probable (woolhouse et al. ). historically, bacterially caused infections such as plague have had incredible impacts on the human species (raoult et al. ). however, the development of antibacterial therapies, beginning with the sulfonamides in and then penicillin in , has severely limited the ability of this class of microbes to cause a gcbr-level pandemic. in addition, the relatively slower speed of replication and accumulation of mutations also disadvantages this class over viruses. for example, a human infected with the hepatitis c virus (an rna virus) produces trillions of virions per day, whereas the doubling time of yersinia pestis, the cause of plague, is . h (neumann et al. ; deng et al. ) . the public health crisis of multiple-drug-resistant bacteria, such as carbapenem-resistant enterobacteriaceae (cre) and others, is very alarming (logan and weinstein ) . the spread of these bacterial agents, for which few if any treatments exist, threatens the entire practice of modern medicine, from cancer chemotherapy to joint replacement therapy. however, these organisms, which have variable attributable mortality, tend to be unable to efficiently infect human hosts that are not compromised or hospitalized. as such, the risk to the general public is constrained. large outbreaks of cholera and plague have represented true public health emergencies in yemen and madagascar, but their spread reflects severe infrastructure deficiencies caused by war and supply constraints rather than true global pandemic risk (qadri et al. ; roberts ). fungi represent prolific pathogens outside of the mammalian species. outbreaks of chytrid fungal disease in frogs and salamanders as well as snake fungal disease represent true existential threats to affected species (fisher ) . however, fungi are largely thermally restricted, and only limited members of this class of microbes can infect warm-blooded organisms such as mammals (casadevall ) . indeed, a fungal filter is hypothesized to have existed and may be partly responsible for mammalian warm-bloodedness. the success of the mammalian-adapted fungus that causes white-nose syndrome in bats is facilitated by the lower body temperature that occurs during their hibernation (foley et al. ) . human infections with fungi tend to be severely damaging only in an immunocompromised host. the human innate immune system contends with countless fungal spores that are present in every breath of air. as such, many endemic fungal diseases, such as histoplasmosis or coccidioidomycosis, do not cause harm in the majority of immunocompetent humans infected. even newly emerging fungi such as candida auris and cryptococcus gattii are largely subjected to this limitation (chowdhary et al. ; centers for disease control and prevention ). one of the most widespread fungal outbreaks-the exserohilum fungal meningitis outbreak-was abetted by direct injection of a contaminated medical product into the spinal region of humans, which is not a usual mechanism of infection (casadevall and pirofski ) . without thermal adaptation (which might be feasible with deliberate manipulation), fungi, many of which are sapronotic and do not rely on or need mammalian hosts, will not constitute a pandemic threat to humans. prions-transmissible infective proteins-are one of the most fascinating and understudied of infectious agents. these agents, which are responsible for diseases such as kuru and new variant creutzfeldt-jakob disease (vcjd, the human form of "mad cow disease") in humans, cause scrapie, chronic wasting disease, and bovine spongiform encephalopathy in other mammalian species (chen and dong ) . though highly damaging to humans and other species they infect, prions require specific conditions for spread. new variant creutzfeldt-jakob disease was to date the most highly publicized outbreak of a human prion disease; it resulted in human cases tied to the consumption of beef products primarily in england in the s and the s (hilton ) . other modes of transmission of cjd tied to iatrogenic spread via contaminated surgical instruments or cadaveric hormone products ceased once protective measures were put in place (bonda et al. ). kuru, a geographically restricted prion disease, was spread via human cannibalism in papua new guinea, and the outbreak abated once that practice was ended in the s (liberski et al. ) . the transmission characteristics of prion diseases are such that very extraordinary circumstances, on a par with human cannibalism or massive food contamination, must be present for a gcbr-level risk to be present for humans. additionally, and almost by definition, such an event would be slow-moving (prions were once known as "slow viruses"). protozoal organisms have the distinction of being the only infectious disease to have caused the extinction of a mammalian species. the christmas island rat, unable to outrun its vector, was felled by a vector-borne trypanosome (t. lewisi) during the early twentieth century on the australian island (wyatt et al. ) . human forms of trypanosomiasis have not risen to such a level of concern. human protozoal infections have exerted tremendous pressure on the species, and it is hypothesized that half of all humans who have lived died of malaria, which still kills approximately half a million humans annually (world health organization ). however, the development of antimalarial compounds and vector avoidance strategies has proved successful when they are able to be employed appropriately, and they have relegated malaria to a pathogen whose impact is amenable to control. nonetheless, one aspect of malaria is of particular concern: the development and spread of artemisinin-resistant forms, which render treatment extremely challenging with little to no effective antimalarial agents left for use. largely confined to specific regions of asia, such as cambodia and myanmar, this organism poses severe treatment challenges and, if artemisinin-resistant forms were to spread to africa, could represent a continent-wide catastrophic biologic risk (haldar et al. ). ameba, ectoparasites, and helminths all have limited pandemic risk, as they are constrained by pathogenicity, transmissibility, or both. clonally transmissible tumors-such as the notable devil facial tumor disease in tasmanian devils-are rare occurrences in humans, with restricted modes of transmission (maternal-fetal and organ transplantation). space-adapted organisms (e.g., salmonella that originates on earth but spends time in the space station before coming back to earth) can exhibit enhanced virulence; however, they still are susceptible to antibiotic treatment and normal control measures: there is no evidence they pose greater epidemic risk than normal salmonella (wilson et al. ). an alien microbe species that is obtained on mars or meteorites and brought back to earth, one of the focuses of the planetary protection program at the national aeronautics and space administration (nasa), was not deemed by our interviewees and meeting participants to be likely to pose a threat. and if such a species were found, it would be unlikely to be adaptable to an earthlike planet environment, as adaptations to its home planet's markedly different environments would likely preclude adaptations to earth. even though the chances of serious biological risk posed by such a sample return are deemed to be low, there are many uncertainties, and the highest level biocontainment procedures are being considered for specimens that might harbor such non-earth-based organisms (national research council ). traditionally, viruses have been ranked at the highest level of pandemic risk, and dedicated preparedness efforts often focus solely on viruses. a disproportionate focus on viruses is justified, however, based on several aspects unique to the viral class of microbes. the high rate of replication of viruses-for instance, over trillion hepatitis c virions are produced per day in a human infection-coupled with the mutability inherent in such short generation times gives viruses an unrivaled plasticity. this plasticity allows for host adaptability, zoonotic spillover, and immune system evasion. the lack of a broad-spectrum antiviral agent-like ones available for bacterial and even fungal organisms-also confers a special status on viruses. with no off-the-shelf treatment available to contain a viral outbreak, and likely no vaccine, containment efforts, at least in the early stages, will likely need to be made in the absence of a medical countermeasure (zhu et al. ) . there is a strong consensus that rna viruses represent a higher pandemic threat than dna viruses (kreuder johnson et al. ) . this assessment is derived from the fact that the stability of rna as a genomic material is less than that of dna, giving more genomic pliability to the rna viruses. dna viruses such as smallpox do challenge this assumption, and concern exists surrounding the related risks of monkeypox viruses, which are increasingly spreading in the absence of a smallpox vaccine campaign (kantele et al. ) . as monkeypox outbreaks continue to occur with longer chains of transmission, employing smallpox vaccines in target populations might be considered. another aspect of viral characterization is the location of replication. viruses with greater capacity for widespread have been shown in studies to be more likely to replicate in the cytoplasm of a cell (pulliam and dushoff ; olival et al. ) . this is postulated to be due to the higher affinity a virus must have for a particular type of host in order to be permitted entry into its nucleus, and this greater affinity would limit its zoonotic potential because it would be likely to be strongly tied to its usual host. in general, it is dna viruses that tend to have a nuclear replication cycle, while rna viruses have a cytoplasmic cycle. strikingly, smallpox-a dna virus with proven ability to cause pandemics-is a cytoplasmic replicator, while influenza-an rna virus with proven ability to cause pandemics -has a nuclear replication cycle. the exceptions to these rules argue against any overly strict adherence to them. other factors that may increase a virus' potential to cause a global catastrophic risk include a segmented genome (as exemplified by influenza viruses), a comparatively smaller genome size, and high host viremia (e.g., vector-borne flaviviruses). for example, the flu virus' segmented genome makes novel genetic assortment an eventuality, while a large genome may prevent nimble mutations. however, with each characteristic it is impossible to find a general rule, as exceptions abound. among currently studied viruses, the influenza a viruses are widely judged to pose the greatest pandemic risk based on historical outbreaks and viral characteristics (silva et al. ; imai et al. ). analysis of influenza risks is made in the centers for disease control and prevention (cdc)'s influenza rapid assessment tool (irat) which ranks h n as the most concerning influenza virus strain (centers for disease control and prevention ). there are several viral groups other than the orthomyxoviruses (which include the h n strain of influenza a) that are spread by respiratory routes, possess rna genomes, and merit enhanced attention: paramyxoviruses (especially these three genera: respirovirus, henipavirus, and rubulavirus), pneumoviruses, coronaviruses, and picornaviruses (especially these two genera: enterovirus and rhinovirus). based on our analysis and their inherent characteristics, these viral groups are the most likely source of a gcbr-level threat. there are efforts under way to construct viral catalogs of as many viruses as possible. the explicit aim of these projects is to reduce the uncertainty of outbreaks by extensively cataloging as many viral species as possible, so that a virus that causes a disease is less likely to be truly unknown. at the meeting and interviews for this project, a number of experts expressed concern that, while efforts to catalog and broadly sequence viruses in the animal world would provide new scientific discovery, we should not expect that it will identify the source of the next pandemic or that it can change the work being done for pandemic preparedness. broad viral sequencing would uncover many novel viruses. however, the vast majority of discovered viruses will not have the ability to infect humans let alone the prospect of widespread in the population. only a few viruses possess this ability. this work should be pursued with the objective of fundamental viral scientific discovery, rather than the goal of near-term improvement in pandemic preparedness. in the clinical practice of medicine, syndromic diagnosis-that is, making a nonspecific diagnosis, such as "sepsis," "pneumonia," or "viral syndrome," with little to minimal laboratory testing-is the norm. specific diagnosis (i.e., sending patient samples for definitive laboratory diagnosis) is often eschewed if it does not affect clinical management, is costly, and is not revealed with routine tests, and/or if the patient recovers. this practice has become enshrined not only in resource-poor areas in which access to diagnostic testing may be limited, but also in resource-rich areas, like north america and western europe, where specific diagnoses are viewed as superfluous. however, the yield from pursuing an etiologic diagnosis in infectious syndromes such as atypical pneumonia, sepsis, encephalitis, meningitis, and clinically significant fevers of unknown origin may be considerable, as it will provide important insight into the ongoing torrent of threats posed by the microbial world. by causing an infection with enough severity to come to medical attention, the culpable microbes have already established that they are damage-causing pathogens to humans-a feat that only a sliver of the microbial world can accomplish (woolhouse et al. ). many of these microbial diagnoses cannot be made through the routinely ordered diagnostics. therefore, a special effort would need to be made to get to a microbial diagnosis. if that were to be done more frequently and at a more strategic level around the world, it would provide an opportunity to develop new situational awareness regarding which microbes are circulating and infecting humans-information that is clinically valuable in its own right and more attuned to uncovering gcbr-level pathogens than broad viral cataloging. such efforts should not be limited to exotic "hot spots" of disease emergence but should be practiced in localities that are broadly representative of where these conditions occur. particular hot spots of emergence due to the presence of unique risk factors may be higher yield overall, but they should not be the sole sites of investigation. infectious disease emergence can occur anywhere, as evidenced by the h n pandemic, which was first recognized as the etiology behind a mild pediatric upper respiratory infection in california and west nile fever emerging in cases of undifferentiated encephalitis in the new york city metropolitan area in the late s (centers for disease control and prevention ; nash et al. ) . such a program would have significant cost and infrastructure implications in resource-constrained regions, so it would be most logical to set up sentinel or strategic sites for pursuing this level of microbial diagnosis in ways that are broadly representative. in developed nations such as the usa, these programs are available but underutilized because of lack of awareness or perceived lack of value by clinicians, for whom it will often not likely change therapeutic decisions. many participants in the project voiced the view that any microbe's pandemic potential could be substantially enhanced by human factors and poor preparedness, which could exacerbate a pathogen's spread or damage-causing potential. specific issues identified included gaps in hospital preparedness, medical countermeasure manufacturing capacity, medical countermeasure manufacturing locations, impacts on critical workforce members, and cascading effects on vital programs such as food production. for example, concentration of intravenous fluid manufacturing plants in puerto rico created massive shortages after a hurricane took the plants offline in (wong ) . the inability of hospitals to surge to meet enhanced patient needs for ventilators or icu beds is another potential constraint. human factors could also take the form of mistaken actions that are based on political considerations but are not supported by an evidence-based medical rationale, or scientific mistakes based on human error, such as misidentifying a microbe or misinterpretation of scientific or epidemiologic data. for example, early in the sars outbreak, mistakes regarding the etiology of the viral agent occurred, and the west african ebola outbreaks were initially thought to be cholera, delaying response efforts for months (world health organization ). some participants in this study were of the view that such factors as these could outweigh any intrinsic property possessed by a microbe or any physiologic vulnerability possessed by a human. magnification by human error could cause delays in response or awareness, allowing a pathogen to spread wider and deeper into the population and rendering containment more difficult, sowing panic, and severely stressing the healthcare infrastructure of a region. the majority view, however, was that intrinsic microbial characteristics are the main driver of a microbe's ability to cause a pandemic. pandemic preparedness should place a high priority on preparing for rna viral threats, given their frequent spread by respiratory route, cytoplasmic replication, and high mutability. surveillance, science, and countermeasure development programs and efforts should logically allocate significant resources to this class of microbes. except for influenza and certain coronaviruses, there are not major preparedness efforts being made for other viruses in this class of microbes. while rna viruses were at the top of the list of concerns, other classes of microbes, such as bacteria, fungi, and protozoa, should not be completely dismissed given characteristic that pose special concerns. cultivating and maintaining expertise in the epidemiology, surveillance, and pathogenicity of all classes of microbes, with explicit incorporation of a one health approach-which incorporates and integrates information from infectious diseases of plants, amphibians, and reptiles-will help foster the broad capacities needed for emerging pandemic and global catastrophic biological risks. pathogen-based lists, both usa and global, based on influenza precedents, historical biological weapon programs, and emerging infectious diseases were responsible for galvanizing early activities in the field of pandemic preparedness and have helped drive many important contributions. but these lists could create a sense of confidence regarding the prediction of future pandemic threats. lists can become frozen in the minds of those in the field and may be viewed as exhaustive rather than as starting points. additionally, inclusion in lists could also be sought for political (and not epidemiologic) reasons if inclusion carries with it the prospect of enhanced funding for a long-neglected endemic problem. one of the chief rationales behind this project was to attempt to move away from a strict list-based approach when considering pandemic threats and to develop a framework grounded in the facts of a microbe's biology and epidemiology. we recommend that risk assessment be rooted in the actual traits that confer pandemic or global catastrophic biological risks as opposed to a pathogen's presence on some earlier developed list. as respiratory-borne rna viruses have been identified as possessing heightened pandemic potential, it is important to strengthen surveillance activities around these viruses where they currently exist and establish them where they are not yet in place. currently, of the respiratory-borne rna viruses, only influenza and certain coronaviruses receive high priority for surveillance. while some efforts to understand coronaviruses, in the wake of sars and mers, exist, there is no systematic laboratory surveillance of coronavirus infections in humans. similarly, no such program exists for rhinoviruses, parainfluenza viruses, rsv, metapneumoviruses, and similar viruses. since this class of viruses is most likely to hold the future pandemic pathogen, constructing an influenza-like surveillance approach that better characterizes the prevalence, patterns, and geographic distribution of these viruses should be a priority. such an approach would focus on human infections, characterizing the epidemiology, virologic features, antiviral susceptibility (if applicable), and clinical manifestations in a fashion that mimics the extensive influenza surveillance conducted by the cdc and other international entities. currently, outside of anti-influenza antivirals, there is only one fda-approved antiviral for the treatment of respiratory-spread rna viruses (ribavirin). of the six fda-approved influenza antivirals-amantadine, rimantadine, baloxavir, zanamivir, oseltamivir, and peramivir-all target influenza viruses specifically and have no activity outside influenza, with two influenza a-specific agents (amantadine and rimantadine) rendered virtually obsolete because of resistance. the other antiviral agent (inhaled ribavirin) is approved for the treatment of respiratory syncytial virus (rsv) but has very limited use due to poor efficacy and major toxicity concerns for both rsv and parainfluenza viruses. there are currently no approved antivirals for any other respiratory-spread rna viruses in the world. prioritization of antiviral compounds against this group of viruses may lead to acceleration of drug development and (government and nongovernment) incentivizing programs. such antiviral compounds would have an advantage over many other emerging infectious disease countermeasures: these viruses exact a considerable toll in the form of community infections each year, providing a basis for a traditional pharmaceutical market as well as one for emerging infectious disease. pursuing not only broad-spectrum rna antivirals, but also those specifically targeted to specific viruses such as rsv, would increase the likelihood of yield. nontraditional molecules, such as monoclonal antibodies and immunomodulators, should also be investigated for a role in the treatment and prevention of rna virus respiratory infections (walker and burton ) . such adjunctive treatments may lead to improved clinical outcomes. to date, only one virally targeted monoclonal antibody is fda-approved: pavalizumab for prevention in high-risk infants. as with the above discussion regarding antivirals, the need for vaccines against respiratory-borne rna viruses should also be prioritized. currently, aside from influenza, for which a moderately effective but technically limited vaccine exists, there are no other vaccines for respiratory-borne rna viruses. experimental vaccines targeting rsv have made it into late clinical development only to fail. several important initiatives in this realm do exist and could be augmented to move beyond specific targets that have already been recognized. for example, the coalition for epidemic preparedness innovations (cepi) has selected a coronavirus (mers-cov) and a paramyxovirus (nipah) for vaccine development incentivizing (røttingen et al. ) . such a program could, in potential future initiatives, select additional vaccine targets from this group of viruses and even encourage the development of broadly protective vaccines against groups of viruses-for example, a vaccine that protects against all four strains of human parainfluenza viruses, both mers and sars covs, and both hendra and nipah viruses. additionally, the heightened interest at the national institutes of health (nih) in a universal influenza vaccine in the wake of the moderately severe - influenza season should be channeled to provide significantly increased resources to this endeavor (paules et al. ) . as certain avian influenza viruses are of the highest threat tier, a universal influenza vaccine (even one that just protects against a strains) could substantially hedge against an influenza virus attaining gcbr status. as was evident during the influenza pandemic and subsequent influenza seasons, the treatment of influenza is suboptimal, despite evidence-based guidance. the status of the treatment for other respiratory viruses is even less defined. while there currently is not a robust antiviral armamentarium against these viruses, there are important clinical questions that occur with their treatment that merit further study. for example, what adjunctive therapies are useful? what coinfections may be present? at what stage of illness are rescue oxygenation devices warranted? as many of these viruses are highly prevalent in the community and are frequently encountered by clinicians in both outpatient and inpatient settings, finding answers to these questions would render clinicians more adept at dealing with pandemic versions of these viruses. with respect to influenza, there is a growing literature on the use of antiviral agents in combination with anti-inflammatory agents such as nonsteroidal anti-inflammatory agents (nsaids) and macrolide antibiotics (hung et al. ) . untangling the nuances of these treatment effects in order to develop robust guidance would have an impact on the ability to cope with an influenza-driven gcbr. because of the higher likelihood that a gcbr-level threat might emerge from the group of rna viruses with respiratory-spread, special attention to research on these agents is warranted if such research could increase pandemic risks. while much research on this class of viruses would be low risk and managed by appropriate approaches to biosafety, experimentally engineered antiviral resistance, vaccine resistance, or enhanced transmission, for example, would raise major biosafety and biosecurity concerns. the appearance of the h n influenza a strain was thought to have resulted from laboratory escape (zimmer and burke ) . it is important to understand the kinds of work being performed with these agents and, in particular, to know of experiments that are being done or are being proposed that would result in increased pandemic risks. those experiments should have their own special review and approval process that is consistent with the risks and assesses the risks and benefits of this work before approval or funding of this work. as unknown infectious syndromes abound in all locations, and any given infectious syndrome may have as its etiology a potentially unknown or unappreciated microbe, specific diagnosis should be a routine endeavor. atypical pneumonias, central nervous system infections, and even upper respiratory infections often are treated without any etiologic agent being identified. as diagnostic technologies and devices improve in breadth, speed, and ease of use, the increasing uptake of these devices will provide a new opportunity to enhance situational awareness of an infectious syndrome in any location where they are deployed. such devices are currently being used in research projects in the developing world. the more routine use of devices, such as multi-analyte molecular diagnostic devices, has the capacity to provide a fuller picture of the microbiological epidemiology of any given syndrome, illuminating what has heretofore been biological dark matter (doggett et al. ; kozel and burnham-marusich ) . coupled with heightened surveillance of respiratory-borne rna viruses, the ability to capture an early signal of a potential pandemic pathogen will be greatly enhanced. to date, certain considerations have limited the uptake and use of these devices: cost, perceived lack of clinical impact, and constraints on hospital resources such as isolation beds. impacts on hospitals might be noted in laboratory testing volume as well as costs. however, when these devices are viewed in the context of pandemic preparedness, the cost-effectiveness calculation should change. these considerations could be moderated if they are considered part of a hospital's emergency preparedness activities and not exclusively as clinical (they also have benefit for antibiotic stewardship activities in both inpatient and outpatient settings). in fact, the use of these devices should be considered on a par with mechanical ventilators, vaccines, antivirals, and antibiotics in the context of pandemic preparedness. pilot projects demonstrating the feasibility of procuring such devices for infectious disease emergency preparedness could be conducted. understanding the microbial characteristics most importantly regarding the risks of pandemic or global catastrophic biological threats can help strengthen pandemic preparedness activities. while rna viruses pose the greatest risks, there are characteristics of other microbial classes that cause special concerns and are important to consider in scientific research agendas and in public health preparedness efforts. this analysis leads to a series of recommendations related to disease surveillance, antiviral and vaccine development, clinical research, and research oversight. taken together, assessment of key microbial class characteristics plus the focused actions that follow this assessment can broadly help improve preparedness for pandemic and global catastrophic risks. human prion diseases: surgical lessons learned from iatrogenic prion transmission transmission of influenza a in human beings fungi and the rise of mammals the pathogenic potential of a microbe exserohilum rostratum fungal meningitis associated with methylprednisolone injections microbial threat lists: obstacles in the quest for biosecurity? swine influenza a (h n ) infection in two children-southern california emergence of cryptococcus gattii-pacific northwest zika virus-potential range in us influenza-summary of influenza risk assessment tool (irat) results epidemiological characteristics of human prion diseases candida auris: a rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally the adaptive evolution of virulence: a review of theoretical predictions and empirical tests genome sequence of yersinia pestis kim culture-independent diagnostics for health security ecology: in peril from a perfect pathogen investigating and managing the rapid emergence of white-nose syndrome, a novel, fatal, infectious disease of hibernating bats factors that make an infectious disease outbreak controllable drug resistance in plasmodium drivers of airborne human-to-human pathogen transmission pathogenesis and prevalence of variant creutzfeldt-jakob disease efficacy of clarithromycin-naproxen-oseltamivir combination in the treatment of patients hospitalized for influenza a(h n ) infection: an open-label randomized, controlled, phase iib/iii trial a highly pathogenic avian h n influenza virus isolated from a human is lethal in some ferrets infected via respiratory droplets the characteristics of pandemic pathogens emerging diseases-the monkeypox epidemic in the democratic republic of the congo point-of-care testing for infectious diseases: past, present, and future spillover and pandemic properties of zoonotic viruses with high host plasticity kuru: genes, cannibals and neuropathology the epidemiology of carbapenem-resistant enterobacteriaceae: the impact and evolution of a global menace the outbreak of west nile virus infection in the new york city area in assessment of planetary protection requirements for mars sample return missions hepatitis c viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy host and viral traits predict zoonotic spillover from mammals the pathway to a universal influenza vaccine the damage-response framework of microbial pathogenesis and infectious diseases ability to replicate in the cytoplasm predicts zoonotic transmission of livestock viruses cholera in yemen-an old foe rearing its ugly head plague: history and contemporary analysis studying the effects of emerging infections on the fetus: experience with west nile and zika viruses echoes of ebola as plague hits madagascar new vaccines against epidemic infectious diseases global catastrophic biological risks: toward a working definition estimating disease burden of a potential a(h n ) pandemic influenza outbreak in the united states a global map of dominant malaria vectors the exceptional oncogenicity of htlv- influenza: the mother of all pandemics passive immunotherapy of viral infections: 'super-antibodies' enter the fray space flight alters bacterial gene expression and virulence and reveals a role for global regulator hfq hospitals face critical shortage of iv bags due to puerto rico hurricane. the guardian rna viruses: a case study of the biology of emerging infectious diseases assessing the epidemic potential of rna and dna viruses ground zero in guinea: the ebola outbreak smouldersundetected-for more than months historical mammal extinction on christmas island (indian ocean) correlates with introduced infectious disease broad-spectrum antiviral agents historical perspective-emergence of influenza a (h n ) viruses key: cord- -e it nxl authors: alahmadi, adel salah; alhatlan, hatlan m; bin helayel, halah; khandekar, rajiv; al habash, ahmed; al-shahwan, sami title: residents' perceived impact of covid- on saudi ophthalmology training programs-a survey date: - - journal: clin ophthalmol doi: . /opth.s sha: doc_id: cord_uid: e it nxl purpose: to evaluate the impact of the current pandemic on ophthalmology residency training in saudi arabia, focusing on its effects on clinical education, training, and the mental well-being of the trainees. methods: an online self-administered questionnaire was distributed among residents in the saudi ophthalmology training programs between july and , . in this study, we explored residents’ opinions regarding training disruption and virtual education. the patient health questionnaire (phq- ) was used to assess the covid- pandemic’s impact on their mental health. we used descriptive statistics for data analysis. results: out of registered ophthalmology residents, participated in this study. ninety-six participants ( . %) were rotated at a specialized eye hospital during the covid- pandemic, while ( . %) had rotations in the ophthalmology department at general hospitals. those who rotated in both types of hospitals were ( . %). according to the participants, there was a significant decline in exposure to surgical and office-based procedures compared to emergency eye consultations (friedman p < . ). the covid- pandemic’s effect on mental health was reported by ( . %) participants. eighty-five ( . %) respondents were satisfied with the virtual method of education. conclusion: covid- pandemic has disrupted residents’ clinical and surgical training in the saudi ophthalmology training programs. additionally, we believe that covid- may have a negative impact on trainees’ mental health. fortunately, the current pandemic provided an innovative education method that will likely be used even after the pandemic. in december , an outbreak of pneumonia emerged from wuhan, a city in china, caused by a new coronavirus. a few months later, the world health organization (who) declared it a pandemic. this pandemic has affected many sectors, including world economics, lifestyle, and the healthcare system. on march nd, , the first confirmed coronavirus disease (covid- ) case in saudi arabia was reported in the eastern region. as recommended by national and international ophthalmic societies, routine ophthalmic services ceased to operate and, only urgent and emergency services kept running. , unfortunately, this negatively impacted residents' surgical and clinical training. in response to the letter sent by the american academy of ophthalmology to its members about reopening of routine services, some centers have opted to reopen clinics and perform surgeries while implementing precautionary measures to limit the risk of exposure and transmission of the disease. , in addition to disruption in clinical and surgical teaching, didactic teaching programs such as grand rounds and lectures were administered through virtual platforms such as zoom, microsoft teams, and cisco webex. we believed that ophthalmology residents had experienced remarkable limitations in their clinical training and surgical exposure due to these dramatic changes. given the uncertainty of this pandemic's duration and impact on the residents' mental health, assessing residents' perception and well-being is crucial. in saudi arabia, the impact of covid on ophthalmology training was not studied yet. this study aimed to assess the pandemic impact on ophthalmology residency training by obtaining the residents' perspective as we believe that their perception is crucial and valuable to adapt to changes while maintaining a successful residency training. , we believe that identifying the pandemic's true impact on training from the residents' point of view will provide beneficial insight for program directors and decision-makers to implement solutions for disrupted clinical training and insufficient surgical exposure. moreover, exploring the efficiency of virtual teaching is important because of its novelty and the probability of permanently replacing the conventional teaching way. finally, mental health well-being is an essential part of the residents' overall health, and assessing it at the time of crisis is crucial since mental illness can have long-lasting negative effects on them, and recognizing them earlier allows for rapid interventions, subsequently a better outcome. the institutional review board at king khaled eye specialist hospital (kkesh) approved the current study (number: -p). all study conducts adhere to the tenets of the declaration of helsinki. a questionnaire was sent to all residents (n- ) currently enrolled in scfhs accredited ophthalmology training programs, between and july . participation was voluntary and complete anonymity was ensured. all participants provided informed consent to take part in this study. the survey (appendix ) consisted of questions. the questions covered mainly demographics data such as program location, type of hospital general or specialized, level of training, gender, marital status, and whether he/she lives alone or with family or friends. we included questions about the pandemic's impact on the training changes in clinical working hours, surgical exposure, on-call, emergency room coverage, and overall training. regarding the hospital policies/general health guidelines changes, we asked the participants whether the hospital kept operated or services forced to shut down, whether the participant was exposed to covid- cases or deployed to cover other services, personal protective equipment (ppe) availability, and types. specific questions were directed to a subset of residents who were diagnosed with covid- . additionally, the questionnaire included questions related to theoretical teaching and the quality of the virtual teaching. the effect of the pandemic on studying, research, and elective rotations was also explored. finally, we used the patient health questionnaire (phq- ) to assess the impact of covid- on mental health. , in a study conducted by kroenke et al, phq- was found to have a sensitivity of % and a specificity of % for diagnosing major depression. thereby, they concluded that phq- is a valid and reliable tool to assess depressive symptoms. the data was transferred from the surveymonkey platform into a microsoft xl spreadsheet. the data analysis was carried out using the statistical package for social studies (spss ) (ibm, ny, usa). the qualitative variables like gender, training level were presented as numbers and percentages. the quantitative variables like impact on training scores were studied for distribution. if the variables were not normally distributed, the median and interquartile range were estimated. to compare the impact score in subgroups, we used a nonparametric method, and for two independent variables, the wilcoxon p-value was estimated. for more than two independent variables, friedman p-value was presented. a p-value of less than . was considered statistically significant. of the -total number of ophthalmology residents in saudi arabia, ( . %) answered the submitted questionnaire. the comparison between ophthalmic residents and surveyed participants is given in table . those who participated were not significantly different from those who did not. among surveyed residents, eighty-six ( . %) were males, ( %) were unmarried, ( . %) were living with their family. during the covid- pandemic, participants ( . %) were rotated at a specialized eye hospital, while ( . %) had rotations in the ophthalmology submit your manuscript | www.dovepress.com clinical ophthalmology : department at general hospitals. those who rotated in both types of hospitals were ( . %). changes in the participants' clinical and surgical activities during the covid- pandemic are shown in table . only participants responded to these questions. according to the participants, the overall score suggested a significant reduction of . % compared to the pre-pandemic. compared to emergency eye consultations, there was a significant reduction in numbers of surgeries performed, office-based procedures such as corneal cross-linking and intravitreal injections, as well as laser for proliferative retinal diseases and maculopathy (friedman p < . ). the resources to protect health staff against the risk of covid- transmission as perceived by ophthalmic residents are summarized in table . our data indicate that programs provided masks to . % of the respondents. around % received gowns, and . % also received gloves. besides that, built-in shields for slit lamps were provided, as stated by . % of the participants. however, other protective equipment types such as face shields and goggles were only provided for . % and . % of the participants, respectively. additionally, . % of participants stated that programs provided updated protocols and guidelines on limiting sars-cov- transmission; however, according to %, there was a delay in providing these guidelines and protocols. moreover, the majority of the participants reported that the recommended precautionary measures were implemented, such as providing ppe for patients and staff, screening and triaging at entry gates for both patients and staff, practicing social or physical distancing by limiting the number of people sitting in waiting areas or offices to individuals in each room, shifting to telemedicine or virtual consultations. one hundred eight participants replied to the questions regarding the effect of the covid- pandemic on mental health. eight ( . %) residents reported no effect. mild and moderate depressive symptoms were observed in ( . %) and ( . %) of the trainees. sixteen ( . %) ophthalmology residents scored high (severe depressive symptoms) in the phq- scale. as many as ( . %) participants did not respond to this part of the survey. (figure ) ophthalmology resident's feedback on web-based training during the covid- pandemic suggested that one ( . %) resident was highly dissatisfied, ( . %) were dissatisfied, ( . %) were satisfied, and ( . %) were highly satisfied with the web-based ophthalmic education. twenty-four residents did not respond, and three residents said they did not attend any web-based training. the majority of residents ( . %) used zoom, one resident ( . %) used the microsoft team, and three residents ( . %) used other tools. (table ) . regarding the questions related to the covid- duties and infection, ( . %) residents were deployed to covid- areas. the polymerase chain reaction (pcr) test was negative in ( . %) trainees. at the time of conducting the current survey, the test result of ( . %) residents was pending. six ( . %) of the residents were tested positive. regarding the source of infection, one resident got the infection from a family member while the rest did not know its source. one resident was hospitalized, two received supportive treatment. residents with covid- positive status were looked after through the local employee health clinic. also, their program directors frequently inquired about their health. the current cross-sectional study aimed to explore covid- related experiences and perceptions of ophthalmology residents in various saudi programs. additionally, we aimed to assess their mental wellness during the current pandemic. according to the center for disease control and prevention (cdc), and international ophthalmic societies, hospitals were asked to postpone routine services such as outpatient clinics and elective surgical procedures to reduce covid- transmission risk and conserve healthcare resources. our data clearly illustrates the significant impact of these measures on the ophthalmology residency training programs in saudi arabia. the participants in this study believed that their training was severely affected. they reported a significant reduction in routine outpatient care and a dramatic decline in exposure to surgical training and minor procedures such as injections and lasers. however, no changes were noted in residents' emergency care exposure as emergency departments continued to run normally during the lockdown. these findings are in line with the recently published data from various residency programs worldwide. , , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] in the united kingdom, % were concerned about the impact of covid- on their training, specifically their surgical exposure and postponement of the board certification examinations. globally, the supply of personal protective equipment (ppe) is limited. the who has released guidance on how to optimize the ppe supply in case of shortage. in this study, we investigated the availability of ppe for ophthalmology residents. our data indicated that most participants were provided with ppe, built-in shields for slit-lamps, and updated protocols and guidelines on how to limit sars-cov- transmission. these protocols included providing ppe for all patients and staff, screening and triaging at entry gates for both patients and staff, limiting the number of people sitting in waiting areas or offices to individuals in each room, shifting to telemedicine, or virtual consultations. despite implementing precautionary measures, several studies reported that trainees were afraid of contracting the disease or transmitting it to their families. such fears may negatively influence the physician's critical thinking and decision making. in our survey, we used patient health questionnaire- (phq- ) to measure the severity of depression among trainees. nearly half of the responded participants to this part of the questionnaire demonstrated mild to moderate depressive symptoms, while around % have severe symptoms. civantos et al reported a high prevalence of burnout ( . %), anxiety ( . %), and distress ( . %) among otolaryngology residents and attending physicians. moreover, . % of the participants in their study scored positive for depression symptoms using the -item patient health questionnaire. in another study by robbins et al, the current pandemic negatively impacted the morale of . % of the residents. also, khanna et al found that many ophthalmologists who participated in their study were psychologically affected. overall, the findings in our study are alarming. seeking services that support the mental well-being of the trainees should be facilitated and encouraged. mishra et al also reported that . % of their study participants were stressed. additionally, they also reported that . % of their study participants were "unhappy" during the lockdown. redeployment of trainees to other areas of need during the covid- pandemic was associated with increased anxiety levels, especially if not proceeded with special training. in our study, only % of participants were asked to provide care in areas designated for covid- patients' care. six residents in our sample contracted the disease, and all of them received support and inquiry about their health from their program directors. interestingly, in a study conducted by khusid et al, the residency program's support was associated with a lower level of anxiety and depression. this pandemic has provided a unique opportunity for innovative teaching methods. as part of maintaining physical distancing, grand rounds and lectures are now delivered using virtual platforms and software. moreover, this new teaching method allows recording the lectures to be stored later and accessed by those interested. under the umbrella of the saudi commission for health specialties (scfhs), ophthalmology residency programs have organized and overseen more than virtual teaching sessions in april alone. according to our data, nearly half of the participants were satisfied with the new method. in line with this finding, this distance method of teaching was welcomed by participants in several studies. , , , after the pandemic concludes, medical education will likely adopt this teaching method in addition to traditional face-to-face education. , this study, however, has several limitations that are important to be acknowledged. we did not inquire whether participants tried to contact the scfhs mental health support services "daem" or not. additionally, we did not investigate whether these depressive symptoms are new or due to preexisting mental health conditions. in this study, to mental health. therefore, we cannot exclude the possibility of a non-response bias. those who did not respond to this part of the questionnaire may not have experienced mental health issues. we did not inquire about the reasons for dissatisfaction reported by approximately % of the participants regarding virtual education, whether these reasons were related to technical difficulties or was the time to conduct these activities unsuitable. as these lectures were mostly broadcasted in the evening time, conflicting with family responsibilities. despite these limitations, our study has several strengths. compared to other studies, the response rate in our study is high ( . %). , , , additionally, we used a validated questionnaire, patient health questionnaire- (phq- ), to assess depressive symptoms. in summary, the covid- pandemic has significantly altered the face of medical education and training. during the current crisis, clinical and surgical training has been disrupted. therefore, the adoption of alternative teaching methods is critical. we believe that covid- had significantly impacted trainees' mental health currently enrolled in the saudi ophthalmology residency programs. access to psychological support programs should be facilitated and encouraged. fortunately, the current pandemic provided the ophthalmology community with a great unique opportunity to boost knowledge. in the future, besides traditional teaching, e-learning will continue to be used in medical education. flexibility, embracing changes, and frequent curriculum revisions and evaluation will enable training programs to ensure continuity of a high-quality education even at disastrous events. the authors report no conflicts of interest for this work. outbreak of pneumonia of unknown etiology in wuhan, china: the mystery and the miracle world health organization. who director-general/speeches web site differences in sars-cov- recommendations from major ophthalmology societies worldwide protecting yourself and your patients from covid- in eye care parkeii dw returning to ophthalmology practice. academy blog web site ophthalmic asc checklist for reopening. practice management advice web site academic ophthalmology during and after the covid- pandemic reshaping ophthalmology training after covid- pandemic burnout during residency training: a literature review the phq- : validity of a brief depression severity measure accuracy of patient health questionnaire- (phq- ) for screening to detect major depression: individual participant data meta-analysis letter to the editor impact of the covid- pandemic on neurosurgical residency training in new orleans the impact of covid- pandemic on surgical residency programmes in italy: a nationwide analysis on behalf of the italian polyspecialistic young surgeons society (spigc) impact of covid- on surgical residency programs in pakistan; a residents' perspective. do programs need formal restructuring to adjust with the "new normal"? a cross-sectional survey study impact of covid- on canadian radiology residency training programs well-being and education of urology residents during the covid- pandemic: results of an american national survey living with covid- : a perspective from new york area ophthalmology residency program directors at the epicenter of the pandemic transforming ophthalmic education into virtual learning during covid- pandemic: a global perspective. eye (lond) impact of covid- pandemic on general surgery training program: an italian experience impact of the covid- pandemic on ophthalmology residency training in portugal the impact of covid- related lockdown on ophthalmology training programs in india -outcomes of a survey impact of covid- on ophthalmic specialist training in the united kingdom-the trainees' perspective. eye (lond) rational use of personal protective equipment for coronavirus disease ( covid- ) and considerations during severe shortages: interim guidance mental health among otolaryngology resident and attending physicians during the covid- pandemic: national study covid- impact on well-being and education in radiology residencies: a survey of the association of program directors in radiology psychological impact of covid- on ophthalmologists-in-training and practising ophthalmologists in india redeployment of ophthalmologists in the united kingdom during the coronavirus disease pandemic saudi commission for health specialties, scientific committee of ophthalmology orthopedic surgery residents' perception of online education in their programs during the covid- pandemic: should it be maintained after the crisis? effective use of virtual gamification during covid- to deliver the ob-gyn core curriculum in an emergency medicine resident conference available from: https:// w w w . s c f h s otolaryngology resident practices and perceptions in the initial phase of the u.s. covid- pandemic key topics include: optometry; visual science; pharmacology and drug therapy in eye diseases; basic sciences; primary and secondary eye care; patient safety and quality of care improvements. this journal is indexed on pubmed central and cas, and is the official journal of the society of clinical ophthalmology (sco). the manuscript management system is completely online and includes a very quick and fair peer-review system key: cord- -ph vrba authors: de’, rahul; pandey, neena; pal, abhipsa title: impact of digital surge during covid- pandemic: a viewpoint on research and practice date: - - journal: int j inf manage doi: . /j.ijinfomgt. . sha: doc_id: cord_uid: ph vrba the covid- pandemic has led to an inevitable surge in the use of digital technologies due to the social distancing norms and nationwide lockdowns. people and organizations all over the world have had to adjust to new ways of work and life. we explore possible scenarios of the digital surge and the research issues that arise. an increase in digitalization is leading firms and educational institutions to shift to work-from-home (wfh). blockchain technology will become important and will entail research on design and regulations. gig workers and the gig economy is likely to increase in scale, raising questions of work allocation, collaboration, motivation, and aspects of work overload and presenteeism. workplace monitoring and technostress issues will become prominent with an increase in digital presence. online fraud is likely to grow, along with research on managing security. the regulation of the internet, a key resource, will be crucial post-pandemic. research may address the consequences and causes of the digital divide. further, the issues of net neutrality and zero-rating plans will merit scrutiny. a key research issue will also be the impact and consequences of internet shutdowns, frequently resorted to by countries. digital money, too, assumes importance in crisis situations and research will address their adoption, consequences, and mode. aspects of surveillance and privacy gain importance with increase digital usage. by late may , at the time of writing of this article, over countries and territories in the world were affected by the coronavirus pandemic. this included most urban clusters and even rural regions. with the spread of the pandemic, almost all regions have implemented lockdowns, shutting down activities that require human gathering and interactions -including colleges, schools, malls, temples, offices, airports, and railway stations. the lockdown has resulted in most people taking to the internet and internet-based services to communicate, interact, and continue with their job responsibilities from home. internet services have seen rises in usage from % to %, compared to pre-lockdown levels. video-conferencing services like zoom have seen a ten times increase in usage, and content delivery services like akamai have seen a % increase of content usage (branscombe, ) . cities like bangalore have seen a % increase in internet traffic. the lockdowns across countries have entailed a rise in the use of information systems and networks, with massive changes in usage patterns and usage behaviour. employees are adjusting to new "normals" -with meetings going completely online, office work shifting to the home, with new emerging patterns of work. these changes have come across all organizations, whether in business, society, or government. the changes have also come suddenly, with barely any time for organizations and people to plan for, prepare and implement new setups and arrangements; they have had to adjust, try, experiment, and find ways that did not exist before. though now, in late may , the pandemic is receding and stabilized in certain countries, it is still on the increase in many others, and with serious threats. experts in most countries are wary of the possibility of the disease spread re-emerging, and that lockdown norms may be relaxed carefully and slowly with social distancing at the core of the new normal. it is in this context that we see the use of information systems to continue in the same vein for some time in the foreseeable future as during the lockdown. we examine the possible scenarios in this surge in information technology usage during and post the pandemic. our estimation of these effects assumes that there was a digital transformation already underway, before the pandemic set in, and it will take certain forms owing to the impact of the lockdowns. in the next section, we examine the impact of the covid- pandemic on the use of digital technologies where we discuss some possible scenarios and research issues of the post-pandemic world. the next section summarizes the implications for research and practice, and in the last section, we present our conclusions. in this section, we discuss some of the most pressing issues regarding the post-pandemic digital surge. these themes reveal the multiple directions in which is research can focus in relation to impacts on technology. as the use of video-and audio-conferencing tools increases significantly, organizations will ramp up their technology infrastructure to account for the surge. this will lead to increased investment in bandwidth expansion, network equipment, and software that leverages cloud services. with employees becoming j o u r n a l p r e -p r o o f acclimatized with the idea of work-from-home (wfh), meeting and transacting online, firms will shift to wfh as a norm rather than as an exception. this is being adopted by many firms (akala, ; bbc news, ; khetarpal, ) , which have the digital infrastructure in place to handle the required load and bandwidth. education is another domain in which there a dramatic shift to the online mode of transacting. since the beginning of the lockdown, schools, colleges, and universities around the world have shifted their classes to video conferencing platforms like zoom and google meet. along with these synchronous modes of teaching, asynchronous platforms like edx and coursera have also seen an increase in enrolments (shah, ) . some institutions are now shifting entirely to the online mode for the forthcoming academic year, with the exception of sessions that require a physical presence, such as the university of cambridge in the uk and the california state system in the us (new york times, ). digital transformation technologies such as cloud, internet-of-things (iot), blockchain (bc), artificial intelligence (ai), and machine learning (ml), constitute a bulk of the of what is being adopted by organizations as part of their transformation effort. blockchain (bc) technology presents an opportunity to create secure and trusted information control mechanisms (upadhyay, ). as education and healthcare services witnesses a shift to the digital domain, bcs enable a way to secure and authenticate certificates, health records, medical records, and prescriptions. research on the design of such systems, along with maintaining their ease-of-use and usefulness will gain importance. another issue is that of designing systems that work with smart contractshow the contracts are authenticated, how these contracts will be designed in a complex chain of processes with many agents involved, and how arbitration related to contracts will be handled. further, is research may point to regulatory aspects of bcs with regard to what must be encrypted and shared (such as for authenticating news and information sources), and how security will be managed. for instance, governments demand access to private keys to view blocks for surveillance and monitoring, versus the requirements of privacy and protection from persecution. the gig economy is driven by online platforms that hire workers on an ad hoc, short-contract, and mostly informal basis. well-known examples of these include uber and airbnb globally and ola and swiggy in india. these platforms have grown immensely since the wide availability of smartphones from onwards. during the lockdown, workers employed by these platforms have suffered heavily, as the demand for their services, taxi rides, rentals, or skill work, has disappeared (bhattacharya, ) . further, since these workers had no guaranteed salaries, their incomes dropped dramatically. in the post-pandemic scenario, there is likely to be, in the short term, a slow return of gig economy workers, as manufacturing and service firms return to their old activities. however, we anticipate that in the longer term as the threat of infection and spread recedes, the gig economy will thrive. this will also be driven by the wfh culture. work-from-home and gig work has received attention in is research, through topics in telecommuting, digital nomads, and virtual teams. one key issue is that of work allocation and collaboration, across and inside teams, and across projects. this issue will face a rise in scale and importance in the post-pandemic world, as the numbers of wfh and gig workers increase. research may focus on aspects of the design of work norms, work contracts, trust-building, and team-building, amongst others. research on telecommuting and virtual teams (belanger, collins, & cheney, ; morrison-smith & ruiz, ) has a long history in is literature. issues include the nature of "distance" whether temporal, spatial, or cultural, and the psychological needs of workers, the technological support and design for this kind of work, and many others. this research is important for the post-pandemic period. we anticipate that the "dark side" of virtual teams and dispersed work also assumes importance in the postpandemic world. substantive issues related to technostress -particularly work overload and presenteeism arise in these situations. research will have to address issues of design of collaborative work, evaluation, team performance and motivation, stress, and the issue of continuous learning. another aspect of digital use by large sections of the working population is that of constant workplace monitoring and being on-the-job continuously. those working from home using video conferencing technology find themselves under intense scrutiny and all interactions are "hyper-focused" (kalia, ) . digital technology makes it easier for bosses and managers to call and locate subordinates at any time, knowing that they can be reached at all times. though there is anecdotal early evidence that this has led to an increase in productivity, it has also led to increased technostress (ayyagari, grover, & purvis, ; tarafdar, tu, ragu-nathan, & ragu-nathan, ) where employees must learn new technologies, be available for work at almost all times, stay with digital devices all the time, and cope with multi-tasking. post-pandemic, it is likely that workers' organizations will demand no-digital hours, where they will find refuge from the constant work pressure. research may address the concerns of work equity, balance, and managing stress. along with the surge in the use of digital technologies, we are now witnessing a rise in online fraud, scams, intrusions, and security breaches. the pandemic has created a scenario of insecurity that is inviting fraudsters to exploit the crisis situation by extracting money or information or by creating vulnerabilities (agarwal, sengupta, kulshrestha, anand, & guha, ) many users are beginning to rely on digital resources extensively, some for the first time, and are becoming targets for fraud and scams. organizations and governments are aware of this threat and are taking countermeasuresfor instance, some governments took a strong stand against zoom sessions for education, forcing the platform provider to upgrade security (yu, ) . it is likely that these scams and frauds will increase in intensity after the pandemic. organizations will implement massive security arrangements, along with extensive information campaigns by government departments. security innovations and firms that offer security services will rise. research will likely focus on managing security, assess the causes of breaches, and the economic and social loss from them. information technology, and particularly the internet, will remain central to the post-pandemic scenario, where innovations will drive the surge in use. a key aspect of this surge will be the management and regulation of the internet itself. though the internet is a global resource and no one country can control its protocols and features, its local access and availability remain an in-country issue. during the pandemic to some countries have restricted access to the internet (chhibber, ) , for certain reasons. the regulation of the internet will become crucial after the pandemic as it will remain a policy tool for governments. they can intercede on aspects of monitoring, bandwidth control, surveillance, intermediary liability, and e-commerce. the pandemic has brought the world to a situation where those not connected to the internet are facing total exclusion. with strict social and physical distancing measures in place, new routines require accessing the internet for most services. hence, those on the wrong side of the digital divide are completely left out. reasons for the divide are many: unaffordable device access, unaffordable internet access, content relevance, access skills or government ordered internet shutdowns (armbrecht, ; scheerder, van deursen, & van dijk, ) in developing countries, the condition is more serious. thus, it becomes extremely important to explore the possibilities of ensuring connectivity. although these issues have been researched and discussed earlier (warschauer, ) , covid- has brought about a situation where internet access seems to have become necessary for survival. as a few studies have suggested, access or no-access to icts may reinforce societal inequalities (ragnedda, ) , where the post-pandemic situation may enhance this further. with the substantial use of technology in accessing basic requirements like health and education, it is imperative to understand the impact of the digital divide on social equality. therefore, it calls for researchers to examine the impact of connectivity to draw policymakers' interest and, perhaps, offer ways to enhance it towards better inclusion. the heavy use of the internet during the pandemic, for various purposes, has raised people's data requirements. with a significant digital divide in societies, this surge in the internet data requirement has revived the discussion on zero-rating plans. zero-rating plans enable firms to let users access data from their sites and services, without having to bear data charges. usually, this is not strictly permitted as it violates the basic principles of net neutrality, where internet traffic has to have the same priority and cost. india, for instance, had an exemplary record of regulating zero-rating plans. although the government did not permit the implementation of such plans, in the aftermath of the pandemic, the telecom regulatory authority of india (trai) decided to allow waiving charges for data and voice for certain websites (coai, ) (coai, ). the list primarily consisted of the sites related to covid- -such as the world health organisation and india's ministry of health and family welfare. the list also included some private players. the principal aim was to allow people, across all socio-economic levels, access covid- related information. given that zero-rating plans can be useful in exceptional circumstances, as is evident from the example of india, research on the conditions on various parameters where allowing zr plans may increase social welfare has enormous practical implications, both for firms as well as regulators. the existing literature on net-neutrality regulations and zero-rating plans (belli, ; cho, qiu, & bandyopadhyay, ) forms the basis to enhance literature in this aspect. issues to be studied include: expanding telecom infrastructure, providing subsidized internet devices, free extra data, or waiving off users' subscription fees (shashidhar, ) in current times, when the productivity of people depends significantly on the internet, its shutdown can be extremely detrimental to societies(isoc, ) however, internet shutdowns are not uncommon even in times like these. the internet was shutdown in kashmir, a union territory in india, since august th, j o u r n a l p r e -p r o o f and continued till may , making it the longest ever imposed in a democracy (masih, irfan, & slater, ) basic internet services, such as filing for driving licenses, were accessed by locals using the internet express, which is a train that shuttles kashmiris to the nearest town where they can get online. the kashmir chamber of commerce estimates $ . billion in losses owing to the internet shutdown (masih et al., ) . similar events are regularly noted across various other countries, arab spring being the significant starting point. with the pandemic, when the internet has become the most important tool available to citizens the impact of internet shutdowns has become grimmer. shutdowns lead to severe implications for all aspects of life, and there are many issues that require research in this regard. the impacts resulting from a climate of uncertainty can potentially discourage foreign investors and spillover on a wide range of sectors, including education, healthcare, press & news media, and e-commerce (kathuria, kedia, verma, bagchi, & sekhani, ) . it is important to understand the far-reaching human rights impact of internet shutdowns, which are exacerbated in the current scenario. shutdowns have deep political reasons and in many cases the consequences are indeterminate. research can focus on aspects of domino-effect consequences leading to grave political crises. digital payments and digital currencies to have a key role in the post-pandemic situation. as digital payments are contact-less they will be encouraged by governments, will likely see a surge. this will also be boosted by the gig economy and wfh situations. there are two distinct phenomena related to digital money that has aided the fight during the pandemic. first, banknotes and coins were suspected to be carrying the virus and digital payment was preferred to the 'dirty money' (gardner, ; samantha, ) . online delivery services were encouraging customers to make payments through digital payment systems like a credit/debit card or mobile payments, with mandates by the government in several parts of india (bhandari, ) . this is likely to result in a surge in digital payment usage, which will lead to work on the diffusion of digital payment technology. second, during the lockdown, there was a loss of jobs, and governments provided aid through payment apps and digital payment modes. these are a convenient mode of fund transfer from donors to recipients, as seen in previous crisis relief cases as well (pollach, treiblmaier, & floh, ) . in various crisis and disaster events, where the mobility of civilians was restrained, many mobile payment service providers (e.g. vodafone in afghanistan, safaricom in kenya, and orange in africa) provided quick funds transfer of remittances from migrants to their homes, and relief aid from the government to victims (aker, boumnijel, mcclelland, & tierney, ; pega, liu, walter, & lhachimi, ; wachanga, ) . this is once again observed in the covid- crisis and needs further examination. issues of surveillance and privacy are gaining prominence with digital usage during lockdowns. commentators, such as yuval harari, have written about the potential for state surveillance "under the skin" (harari, ) as governments rely on digital means to monitor the spread of the pandemic. as many governments have started using apps on smartphones to monitor infected persons and trace their contacts, civil society organizations have raised privacy and state surveillance concerns (pant & lal, ) . postpandemic, these measures of monitoring populations for epidemiological reasons with digital means are likely to continue and become prevalent. though the concerns of privacy and surveillance are valid and have to be addressed, these digital platforms are the most reliable and efficient way of tracking disease spread. "surveillance is a distinctive product of the modern world" (misa, brey, & feenberg, , p. ) , and today we are living in a surveillance society where any internet-based activity using a mobile phone or other electronic gadgets can be monitored and accessed in unfathomable ways (gilliom & monahan, ; lyon, ) . this has resulted in a surge in is research on implications of such web or app-based surveillance in applications including mobile health apps (lupton, ) , environment monitoring and pollution control apps (castell et al., ) , self-tracking apps (barassi, ) , and parental surveillance (ghosh, badillo-urquiola, guha, laviola jr, & wisniewski, ) . covid- has introduced a new application of surveillance for tracking citizens with the symptoms of the virus. this includes the covid- tracker in china (davidson, ) , the aarogya setu app for tracking infectious citizens in india (shahane, ) , and contact tracking apps in the united states (guynn, ) . while these technologies are innovations for fighting the global pandemic today, the issue of government surveillance on citizens has evolved repeatedly. research can focus on the multiple benefits of these apps, but also should not ignore the potential social complications that are possible to arise, including the historic problem of bureaucratic control by the government, using it (gandy, ) . closely related to surveillance is the issue of privacy that mobile apps, including covid- trackers, often tend to threaten users' personal information (gu, xu, xu, zhang, & ling, ; joy, ) . for example, online classes during the pandemic lockdowns have suffered issues of 'intrusion of privacy' as students and teachers are on camera in the private spaces of their homes (garcia, ) . privacy in the digital age has remained a research topic of high priority for is researchers (belanger et al., ; smith, dinev, & xu, ) . privacy has also been considered by is adoption and usage researchers, with privacy risk as a dominantly recurring factor in studies on mobile payments (e.g., johnson, kiser, washington, & torres, ; luo, li, zhang, & shim, ) , location-based mobile services (zhou, ) , and social networking sites (aghasian, garg, gao, yu, & montgomery, ; youn & hall, ) . it would be interesting to examine the different privacy concerns of users while adapting both covid- tracking apps, and online classroom applications. the risks involved in the breach of privacy by these two technologies are unalike and must be investigated with adequate contextual references. in this section, we revisit some of the key issues that are important for research and practice. our discussion is based on the assumptions about the post-pandemic situation and the aspects of is research presented above. . while deploying security technologies like the blockchain, it will be important to understand the implications of smart contracts, their integration in workflows, and their effectiveness in complex resource-constrained settings, as in developing countries. further, understanding the implications of secure and non-erasable technologies like blockchains will become relevant for regulation. . many research issues arise with regard to work-from-home and gig work, which include aspects of trust, measurement of performance, communication effectiveness, and collaboration. j o u r n a l p r e -p r o o f . it can be expected that the dark side of virtual work and gig work, will raise questions of stress, presenteeism, work overload, surveillance, and monitoring. new and severe forms of digital surveillance will have to be understood and their implications gauged. . though much work has been done in understanding the parameters and impact of the digital divide, it will be important to understand how those without access suffer more from the consequences of the pandemic when the world survives on digital communications and operations. . management of the internet within countries is important, and aspects of enhancing networks include regulating zero-rating plans cautiously, seeing their implications for welfare, and how they can enhance access. . internet shutdowns during and after a pandemic lead to severe difficulties for citizens, who have come to depend on these services. research has to examine the direct, second-order, and thirdorder impacts of these shutdown measures. . research on digital payments and their impact in crisis situations, for providing aid and subsidies to affected populations, and for disaster management. . surveillance issues about the extent of data collection by contact tracing apps are important areas of research. issues of persistence and elimination of data, the expanse of data collection, sharing of data between apps, and the multiple trade-offs involved. . design of secure technologies, like blockchain-based applications, for the surge in online education and healthcare activities. . policy for regulating digital infrastructure needed for increased digital transformation. . design of technologies for managing secure online interactionsfor education, healthcare, payments. . design of apps for contract tracing and disease surveillance that balance privacy versus public health. . managers will have to understand resistance to technology and ways to manage change, both among employees as well as customers. . given the significant role which the internet is about to play in times to come, internet intermediaries will work with government and civil society to address privacy and surveillance issues for better adoption of technology. we understand that a pandemic can have severe consequences (keys, ) , including changing the political contour of the world, destroying empires, and creating nations. for the covid- pandemic, we envisage a dramatic shift in digital usage with impacts on all aspects of work and life. how this change plays out remains largely dependent on our responses to and shaping of the emerging trends. in this paper, we have outlined what we see as some key trends and research issues that need to be examined urgently. they will have substantial consequences in the future. internet users to touch million by scoring users' privacy disclosure across multiple online social networks more big employers are talking about permanent work-from-home positions payment mechanisms and antipoverty programs: evidence from a mobile money cash transfer experiment in niger. economic development and cultural change reasons billion people are still offline society for information management and the management information systems … babyveillance? expecting parents, online surveillance and the cultural specificity of pregnancy apps twitter allows staff to work from home "forever technology requirements and work group communication for telecommuters net neutrality, zero rating and the minitelisation of the internet ahmedabad says no to cash on delivery to stop spread of covid- coronavirus lockdown has exposed the serious flaws of india's gig economy the network impact of the global covid- pandemic. the new stack mobile technologies and services for environmental monitoring: the citi-sense-mob approach militancy in kashmir peaked without g, but modi govt keeps forgetting this in court. the print less than zero? the economic impact of zero rating on content competition. the economic impact of zero rating on content competition request-for-non-charging-of-data.pdf.pdf chinese city plans to turn coronavirus app into permanent health tracker. the guardian the surveillance society: information technology and bureaucratic social control it's a new territory": professors and students face struggle to adapt to online classes. the collegian dirty banknotes may be spreading the coronavirus, who suggests. the telegraph safety vs. surveillance: what children have to say about mobile apps for parental control supervision: an introduction to the surveillance society privacy concerns for mobile app download: an elaboration likelihood model perspective apple and google release coronavirus contact tracing technology for public health mobile apps yuval noah harari: the world after coronavirus | free to read limitations to the rapid adoption of m-payment services: understanding the impact of privacy risk on m-payment services coronavirus: centre tones down mandatory clause on the zoom boom: how video-calling became a blessing -and a curse. the guardian anatomy_of_an_internet_blackout.pdf. indian council for research on international economic relations post-covid, % of . lakh tcs employees to permanently work from home by ' ; from % examining multi-dimensional trust and multi-faceted risk in initial acceptance of emerging technologies: an empirical study of mobile banking services m-health and health promotion: the digital cyborg and surveillance society the electronic eye: the rise of surveillance society india's internet shutdown in kashmir is the longest ever in a democracy challenges and barriers in virtual teams: a literature review aarogya setu app: a tale of the complex challenges of a rights-based regime. the wire unconditional cash transfers for assistance in humanitarian disasters: effect on use of health services and health outcomes in low-and middle-income countries the third digital divide: a weberian approach to digital inequalities dirty money: the case against using cash during the coronavirus outbreak determinants of internet skills, uses and outcomes. a systematic review of the second-and third-level digital divide moocwatch : pandemic brings moocs back in the spotlight -class central opinion: does aarogya setu really work? livemint net neutrality in the time of covid- information privacy research: an interdisciplinary review the impact of technostress on role stress and productivity ethnic differences vs nationhood in times of national crises: the role of social media and communication strategies technology and social inclusion: rethinking the digital divide gender and online privacy among teens: risk perception, privacy concerns, and protection behaviors singapore allows schools to resume zoom use for home-based learning examining location-based services usage from the perspectives of unified theory of acceptance and use of technology and privacy risk key: cord- -hs zo authors: kar, sujita kumar; arafat, s.m. yasir; sharma, pawan; dixit, ayushi; marthoenis, marthoenis; kabir, russell title: covid- pandemic and addiction: current problems and future concerns date: - - journal: asian j psychiatr doi: . /j.ajp. . sha: doc_id: cord_uid: hs zo nan to the editor, covid- pandemic is a global public health emergency. it affected more than , people with , confirmed deaths in countries by th march (organization, ) . the disease spread rapidly across the globe due to the unique properties of the virus (extraordinary genetic diversity, highly contagious, easy mode of spread, relatively unaffected by climatic variations) (mackenzie and smith, ) . people around the globe, during this crisis period, are expected to encounter several mental health challenges ranging from panic, phobia, health anxiety, sleep disturbances to dissociative like symptoms (banerjee, ) . along with these, addictive behaviors could be potential reasons for nuisance during the locked-down period and subsequently, newer behavioral addictions could emerge especially for the teens. people are advised to stay at home, maintaining social distancing and avoiding travel. schools, restaurants, pubs, offices, shops have been closed resulting in inaccessibility to substances. staying at home setting and isolating from the society, also reduces the risk of substance consumption. social celebrations and partying are restricted. these situations are conducive to substance use. to reduce the spread of covid- , social distancing technique is often promoted; the morality behind it is not to limit socialization but to enhance physical distancing to prevent the spread of infection. an individual is free to socialize online, rather than offline; however, online socialization is unlikely to build peer pressure to that extent, which expected to happen in direct socialization. social distancing and limited socialization also reduce the possibility of peer pressure for substance use. hence, people who were addicted to any kind of substance use independence pattern are expected to experience withdrawal symptoms. the above factors convey that the social restriction and locked down states in most parts of the world can be a risky affair in the short-run, as many of the individuals can have severe withdrawal symptoms, which can be life-threatening at times (for example-alcohol withdrawal seizures and delirium tremens). on the other hand, as the sources of pleasure are limited to indoor activities, people spend a substantial period watching television and their electronic gadgets. as the impact of pandemic lasting for a long time, the binge-watching of television and electronic gadgets are also likely to persist; which may later result in behavioral addiction. there are higher chances for the young generation to develop behavioral addictions, especially in developing countries. another important area to look at would be the patients with opioid dependence and undergoing daily dispensing agonist treatment. missing a single dosage at the time of lockdown would lead to relapse. when the whole world is preparing to fight the pandemic they could be missed (russell, ) . also, it is an accepted truth that the patients with substance use problems are vulnerable populations during the time of pandemic both for being infected or regarding complications (o'sullivan and bourgoin, ) . furthermore, those who are addicted to specific drugs and could not obtain any supply due to the lockdown period, they might try to make home-made alcoholic spirits. the spirits might have a high risk of alcohol toxicity and can cause poisoning and fatality. there is an urgent need to address the mental health issues of people during this pandemic. most of the countries in the world are adapting lockdown measure to reduce the spread of the infection, the health services are struggling to deal with the daily rise of infected cases hence little attention is provided to the substance user during this pandemic so proper measures and support services should be established to help this vulnerable community. it is highly important to address mental health emergencies like severe and complicated withdrawal symptoms of substance use. milder symptoms can be addressed through online psychiatric consultation (yao et al., ) . there is a need to sensitize people about the addiction-related issues during this pandemic. a mental health helpline may be useful to address specific queries. a special focus for the young person to prevent them from developing the behavioral addictions could be thought as they are more prone to develop it. the covid- outbreak: crucial role the psychiatrists can play covid- : a novel zoonotic disease caused by a coronavirus from china: what we know and what we don't vulnerability in an influenza pandemic: looking beyond medical risk coronavirus disease (covid- ) outbreak situation. coronavirus dis. covid- pandemic influenza pandemic, mental illnesses, addictions rethinking online mental health services in china during the covid- epidemic yasir arafat b , pawan sharma c , ayushi dixit d , marthoenis marthoenis e none. key: cord- -gowtohr authors: cox, rebecca c.; jessup, sarah c.; luber, maxwell j.; olatunji, bunmi o. title: pre-pandemic disgust proneness predicts increased coronavirus anxiety and safety behaviors: evidence for a diathesis-stress model date: - - journal: j anxiety disord doi: . /j.janxdis. . sha: doc_id: cord_uid: gowtohr although health anxiety and corresponding safety behaviors can facilitate disease transmission avoidance, they can be maladaptive in excess, including during the coronavirus pandemic. disgust proneness (i.e., tendency to experience and be sensitive to disgust) is one factor that may predict elevated coronavirus anxiety and safety behaviors during the pandemic, given the role of disgust in avoiding disease transmission. the present study examined the relations between pre-pandemic disgust proneness and coronavirus anxiety and safety behaviors in community adults who completed a study and were re-contacted on / / (n = ). interactions between pre-pandemic disgust proneness and current perceived stress were tested to examine a diathesis-stress model of the role of disgust proneness in anxiety response to the pandemic. increased pre-pandemic disgust proneness predicted increased coronavirus anxiety and safety behaviors, controlling for number of covid- cases by state. consistent with a diathesis-stress model, current perceived stress moderated this effect, such that highest coronavirus anxiety and safety behaviors were reported by those with high disgust proneness and high stress. trait disgust proneness may be a vulnerability factor for anxiety responses to the coronavirus pandemic, particularly among individuals experiencing high stress. assessing disgust proneness and current stress may facilitate targeted anxiety intervention during the pandemic. the coronavirus pandemic and its resulting condition, covid- have devastated society in a multitude of ways, such as the loss of human life, negative economic consequences, enforced social distancing, and the unemployment of countless workers. among these outcomes, there is concern about the impact of the pandemic on mental health, and who may be most vulnerable to psychological distress. it may be the case that individuals with certain personality traits (e.g., a heightened propensity to experience disgust) are at a greater risk of experiencing heightened coronavirus anxiety, or what a recently proposed model of fear during the coronavirus pandemic describes as fear for the body (schimmenti, billieux, & starcevic, ) . disgust proneness, health anxiety, and contamination fears (blakey et al., ; brand et al., ; wheaton et al., ) . these studies indicate the existence of identifiable predictors of anxiety during viral outbreaks and suggest the need for similar research during the coronavirus pandemic. compared to previous viral outbreaks, covid- appears to have a higher rate of transmissibility and a longer incubation period, the latter of which is associated with higher risk of asymptomatic individuals unknowingly infecting others prior to symptom onset (xie and chen, ). high rates of asymptomatic transmission are thought to contribute to rapid spread of the coronavirus (li et al., ) and may result in increased coronavirus anxiety due to decreased certainty about the health status of others and decreased predictability of one's own health status and role as potential disease vector. coronavirus anxiety may be conceptualized as a specific form of health anxiety, or obsessive and irrational worry about contracting a serious medical condition. indeed, recent studies indicate coronavirus anxiety responses are largely characterized by fear of contracting the virus (e.g., ahorsu et al., ; lee, ). an appropriate level of health anxiety facilitates adaptive reactions to physical symptoms to prevent and alleviate illness. however, health anxiety that is chronic and/or greater than the severity of the health-related threat may become maladaptive (taylor, mckay, & abramowitz, ) . health anxiety may also be accompanied by excessive safety behaviors (e.g., salkovskis, ) . although safety behaviors are intended to minimize the risk of illness (e.g., avoidance of contaminants, excessive washing, or overuse of medical supplies), they can also exacerbate distress and functional impairment by preventing the correction of mistaken anxious beliefs (see helbig-lang & petermann, for a review). indeed, one recent study found that health anxiety and excessive internet research on the coronavirus is associated with increased coronavirus anxiety (jungmann and witthöft, ) . thus, identifying additional theoretically informed risk factors that predict coronavirus anxiety and safety behaviors may inform treatment and preventive strategies amidst the pandemic. it has been theorized that a complex "behavioral immune system" functions to help humans avoid the harmful effects of pathogens (curtis, de barra, & aunger, ; schaller & duncan, ) . this system includes facilitated detection of potential infectious pathogens in the environment and pathogens-avoidance behaviors. evolutionary approaches contend that disgust is mobilized by this system to protect humans from disease (tybur, lieberman, & griskevicius, ). there may be individual differences in the extent to which the experience of disgust is deployed as a psychological first line of defense against pathogen threats in the environment. this individual difference process has been operationalized as disgust proneness, a personality trait that consists of two core components, disgust propensity or an individual's tendency to experience disgust, and disgust sensitivity, an individual's negative appraisal of a disgust experience (van overveld, de jong, peters, cavanagh, & davey, ) . disgust proneness may serve an adaptive function by facilitating avoidance of stimuli that present risk for uncleanliness, contamination, and disease. however, this trait has also been implicated as a risk factor for anxiety-related disorders characterized by contamination symptoms (olatunji, williams, lohr, & sawchuk, ) and has been shown to predict excessive health anxiety symptoms (e.g., thorpe, patel, & simonds, ; davey & bond, ; fan & olatunji, ) , further supporting a functional link between disgust and disease avoidance. disgust proneness may also confer risk for excessive coronavirus anxiety. consistent with this view, disgust proneness was correlated with swine flu anxiety during the swine flu pandemic (wheaton et al., ) . although those high in disgust proneness may be more likely to experience elevated anxiety related to the coronavirus pandemic, it is unknown whether this effect may be impacted j o u r n a l p r e -p r o o f disgust, stress, and coronavirus by features of an individual's current context. one such contextual feature is perceived stress. data from china suggest that nearly % of the general population reported experiencing moderate to severe levels of distress in the early stages of the pandemic (qiu et al., ; wang et al., ) . the coronavirus pandemic has also been a significant source of stress for reasons extending beyond fears of infection. indeed, economic instability due to loss of work, difficulties balancing childcare and work responsibilities while working from home, and diminished social support due to social distancing may contribute to psychosocial stress. importantly, there may also be differences in the amount of stress experienced given variability in the extent to which the individual perceives the stress as uncontrollable, unpredictable, and severe, and deems coping resources as insufficient. consistent with a diathesis-stress model (monroe and simons, ) , perceived stress may amplify the effects of an underlying diathesis, such as disgust proneness. though research on predictors of mental health during the coronavirus is nascent, one study found that increased stress during the pandemic was associated with maladaptive coping strategies, including behavioral disengagement and substance use, among adults with disabilities and chronic conditions (umucu et al., ) , and another study found higher resilience, or the ability to effectively cope with stress, is associated with lower anxiety during the pandemic (liu et al., ) . together these findings suggest that perceived stress may be an important process that modulates the effect of disgust proneness on coronavirus anxiety and safety behaviors. the identification of predictors of coronavirus-related anxiety responses is crucial to effectively address mental health issues during the pandemic. disgust proneness may be conceptualized as a diathesis, or predisposition, that interacts with the individual's subsequent stress response to produce maladaptive responses during the pandemic. thus the diathesis-stress model can be a useful framework for exploring how pre-existing traits j o u r n a l p r e -p r o o f disgust, stress, and coronavirus (diatheses) interact with environmental influences (stressors) to produce excessive coronavirusrelated anxiety responses. accordingly, the present study examines the relations between disgust proneness, perceived stress, and coronavirus-related anxiety and safety behaviors in a sample of adults who were assessed in and were re-contacted in the early stages of the coronavirus pandemic in the united states. it was hypothesized that pre-pandemic disgust proneness would predict increases in coronavirus anxiety and safety behaviors during the pandemic, and those with high current perceived stress and high disgust proneness years prior to the pandemic would report the highest coronavirus anxiety and safety behaviors. the sample consisted of adults who completed a survey study on anxiety-related symptoms who were re-contacted to participate in the present study (n = ). the sample included adults aged - who were recruited for a survey study related to sleep and anxiety symptoms (n = ). of the sample, . % participated when re-contacted. the sample was . % female with a mean age of . (sd = . ) at follow-up, ranging from to . the ethnicity composition was as follows: white (n = ; . %), african american (n = ; . %), asian (n = ; . %), hispanic/latino (n = ; . %), other (n = ; . %). information on state of residence and corresponding number of covid- cases can be found in table . . the cai is a -item self-report measure of fear related to the coronavirus pandemic (items are listed in table ). the cai was adapted for this study from a similar measure of ebola-related fear, the ebola fear inventory (efi; blakey et al., ) . in previous research, the efi demonstrated small to medium, significant correlations j o u r n a l p r e -p r o o f disgust, stress, and coronavirus with measures of disgust and contamination concerns (blakey et al., ) . items on the cai are rated on a likert scale from (not at all) to (very much), and higher scores indicate higher coronavirus fear. the cai demonstrated adequate internal consistency (α = . ) at time . (csbc) . the csbc is a -item self-report measure of engagement in behaviors to prevent contracting coronavirus (items are listed in table ). the csbc was adapted for this study from a similar measure of ebola-related safety behaviors, the ebola safety behaviors checklist (blakey et al., ) . in previous research, the efi demonstrated small to medium, significant correlations with measures of disgust and contamination concerns (blakey et al., ) . items on the csbc are rated on a likert scale from (none) to (extreme amount), and higher scores indicate higher engagement in coronavirus-related safety behaviors. the csbc demonstrated adequate internal consistency (α = . ) at time . (dpss-r; van overveld, de jong, peters, cavanagh, & davey, ) . the dpss-r is a -item self-report measure of the tendency to experience disgust in various contexts (i.e., disgust proneness). items on the dpss-r are rated on a likert scale from (never) to (always), and higher scores indicate increased disgust propensity. the dpss-r demonstrated good internal consistency (α = . ) at time . cohen, sheldon, kamarck, tom, & memelstein, ). the pss is a -item self-report measure of the degree to which an individual perceives their life to be unpredictable, uncontrollable, and overburdened in the past month. items on the pss are rated on a likert scale from (never) to (very often), and higher scores indicate increased stress. the pss demonstrated adequate internal consistency (α = . ) at time . data analysis was conducted in spss . prior to data analysis, for scale totals with one item missing, mean imputation was used to replace the missing item. measures with more than one missing item were considered missing and not included in analysis. two hierarchical linear regression models were tested to examine the predictive effect of pre-pandemic disgust j o u r n a l p r e -p r o o f disgust, stress, and coronavirus proneness on coronavirus fear and safety behaviors, respectively. number of covid- cases by state (i.e., the number of covid- cases in a given participant's state on / / ) was included as a covariate to control for relative risk of exposure to coronavirus. two moderation models were tested using the process macro (hayes, ) to examine whether current stress level moderated the relation between pre-pandemic disgust proneness and coronavirus fear and safety behaviors, respectively, controlling for number of covid- cases by state. predictor variables were mean-centered prior to analysis. significant interactions were probed with both a simple slopes analysis (aiken & west, ) and regions of significance analysis using the johnson-neyman technique (johnson & neyman, ) . descriptive statistics and associations between study variables are shown in table . prepandemic disgust proneness demonstrated small, significant, and positive associations with current stress and coronavirus fear and safety behaviors. table for the results of the regression model. two exploratory follow-up models testing disgust propensity and sensitivity as predictors j o u r n a l p r e -p r o o f disgust, stress, and coronavirus revealed that pre-pandemic disgust propensity but not sensitivity individually predicted coronavirus anxiety (p < . ). significantly contribute to the model, f( , ) = . , p = . . introducing pre-pandemic disgust proneness to the model explained an additional . % of the variance in coronavirus safety behaviors, and the r change was significant (p < . ). when number of covid- cases by state and pre-pandemic disgust proneness were included in the model, pre-pandemic disgust proneness predicted a small increase in coronavirus safety behaviors, b = . ,  = . , p < . . see table for the results of the regression model. two exploratory follow-up models testing disgust propensity and sensitivity as predictors revealed that pre-pandemic disgust propensity and sensitivity predicted coronavirus safety behaviors (p's < . ). . . coronavirus anxiety. there was a trend-level interaction between pre-pandemic disgust proneness and current stress level to predict coronavirus anxiety, r = . , f = . , p = . (see table ). conditional effects analysis revealed that there was no significant relation between pre-pandemic disgust proneness and coronavirus fear at low and medium levels of current stress (p's > . ). however, at high levels of current stress, there was a significant, positive relation between pre-pandemic disgust proneness and coronavirus anxiety, b = . , t = . , p < . (see figure ) . a regions of significance analysis identified . as the score on the pss at which the relation between pre-pandemic disgust proneness and coronavirus anxiety becomes significant. that is, those with current pss scores below . exhibited no link between pre-pandemic disgust proneness and coronavirus anxiety; in contrast, for those with j o u r n a l p r e -p r o o f disgust, stress, and coronavirus current pss scores of . or higher, coronavirus anxiety increase with increasing prepandemic disgust proneness. there was a significant interaction between prepandemic disgust proneness and current stress level to predict coronavirus safety behaviors, r = . , f = . , p < . (see table ). conditional effects analysis revealed that there was no significant relation between pre-pandemic disgust proneness and coronavirus safety behaviors at low levels of current stress (p > . ). however, there were significant, positive relations between pre-pandemic disgust proneness and coronavirus safety behaviors at medium, b = . , t = . , p < . , and high levels of current stress b = . , t = . , p < . (see figure ) . a regions of significance analysis identified . as the score on the pss at which the relation between prepandemic disgust proneness and coronavirus safety behaviors becomes significant. that is, those with current pss scores below . exhibited no link between pre-pandemic disgust proneness and coronavirus safety behaviors; in contrast, for those with current pss scores of . or higher, coronavirus safety behaviors increase with increasing pre-pandemic disgust proneness. the present study examined the predictive effect of pre-pandemic disgust proneness on coronavirus anxiety and safety behaviors during the pandemic, as well as the moderating effect of current levels of perceived stress. results of the regression models found that pre-pandemic disgust proneness significantly predicted increases in both coronavirus anxiety and safety behaviors, controlling for number of covid- cases by state. these findings replicate previous studies implicating disgust proneness as one factor associated with responses to previous viral outbreaks, including the swine flu pandemic (wheaton et al., ) and the ebola (blakey et al., ) and zika outbreaks (blakey and abramowitz, ) . evidence for an effect of prior disgust responses to viral outbreaks were due to acutely elevated disgust in response to said outbreaks (i.e., state disgust). the present study suggests that disgust proneness in the absence of a disgustrelevant threat (i.e., pre-pandemic trait disgust) contributes to an elevated anxiety response during the coronavirus pandemic. in other words, disgust proneness may be one individual difference factor that confers vulnerability for experiencing increased anxiety and engaging in excessive safety behaviors during the coronavirus pandemic. the present findings show that heightened disgust proneness before the pandemic results in an increased use of protective behaviors in the midst of the pandemic. this likely reflects the adaptive functions of the complex "behavioral immune system" that functions to help humans avoid contacts with pathogens (curtis et al., ) . indeed, it has been posited that experiencing disgust is a primary mechanism that is employed by the "behavioral immune system" to facilitate disease avoidance (olatunji et al., ) . it is important to note that disgust levels will also increase, as part of the "behavioral immune system", during pandemics given the threat of infection. this heightened disgust may then facilitate adaptive avoidance of situations and stimuli where contamination is likely to occur. one mechanism may be that those high in preexisting disgust proneness (trait) may experience even higher levels of (state) disgust during the pandemic which then motivates the use of more safety behaviors. although this process is largely adaptive, disgust proneness has been found to contribute to excessive safety behavior j o u r n a l p r e -p r o o f disgust, stress, and coronavirus usage in conditions like contamination-based ocd (e.g., phillips, senior, fahy, & david, ; woody & teachman, ) , as well as illness anxiety disorder (davey & bond, ) . heightened pre-pandemic disgust proneness may contribute to a response to the pandemic that exceeds that which is evolutionarily adaptive. this may occur when those with elevated pre-pandemic disgust proneness negatively appraise disgust-relevant stimuli and/or situations (e.g., "i will get sick and die if a stranger sneezes in close proximity to me," "i would not be able to tolerate the disgust associated with touching something a stranger has touched") in a way that exacerbates a fear response to the coronavirus pandemic. indeed, research has previously shown that disgust is significantly associated with both danger and germ spread appraisals (dorfan & woody, ) . safety behaviors are actions performed to prevent, escape, or minimize feared catastrophes and/or associated distress. safety behaviors become maladaptive when individuals misattribute their safety to the behavior itself, rather than the low probability of the feared outcome (e.g., "i am only safe because i washed my hands," rather than "it is unlikely i will get sick;" salkovskis, ). heightened pre-pandemic disgust proneness may also contribute to usage of safety behaviors that exceeds that which is adaptive. of note, safety behaviors are functionally related to anxious beliefs and are logical, if unnecessary (blakey & abramowitz, ) . for those high in disgust proneness, there may be a tendency to engage in safety behaviors (e.g., excessive handwashing) when such protective acts are not required. this may subsequently facilitate safety misattributions that maintain anxiety during the pandemic. this view is consistent with previous research indicating disgust proneness significantly mediates the relationship between contamination-related obsessive-compulsive symptoms and beliefs (e.g., overestimations of threat) and swine flu behaviors and fear (brand et al., ) . in moderation analyses also revealed that current perceived stress significantly interacted with pre-pandemic disgust proneness to predict coronavirus safety behaviors, while the interactive effect for coronavirus anxiety was at trend level. specifically, increased pre-pandemic disgust proneness predicted increased coronavirus safety behaviors for those reporting high and medium current perceived stress. in contrast, those reporting low current perceived stress did not demonstrate a significant relation between pre-pandemic disgust proneness and coronavirus safety behaviors. similarly, though at trend level, increased pre-pandemic disgust proneness predicted increased coronavirus anxiety for those reporting high, but not medium or low, current perceived stress. these findings are consistent with a diathesis-stress framework, such that the vulnerability for an anxiety response to the coronavirus pandemic conferred by elevated prepandemic disgust proneness is "activated" by stress. likewise, when perceived stress is low, prepandemic disgust proneness has no impact on response to the pandemic. indeed, a recent study found heightened covid- distress is associated with difficulties coping during the pandemic (taylor, landry, paluszek, fergus, & mckay, a) . one of the unanswered questions in the literature is why people vary in the degree to which they experience disgust (tybur, cinar, karinen, & perone, ) . these findings suggest that perceived stress may contribute to variability in disgust proneness and this variability may effect subsequent coronavirus fear and safety behaviors. this diathesis-stress approach offers preliminary insight into who may be most vulnerable to a disproportionate response to the coronavirus pandemic. the present findings may also have implications for clinical intervention during the pandemic. clinicians may consider assessing for disgust proneness and stress to facilitate identifying those who may be experiencing particularly high distress. further, stress reduction interventions may be beneficial for off-setting the detrimental effects of pre-pandemic vulnerability factors, such as disgust proneness. however, the findings of the present study must be considered in light of the study limitations. first, the sample was largely white and female, which limits generalizability to various demographic groups. second, this study used self-report instruments that may be incomplete measures of disgust proneness, stress, and coronavirus fear and safety behaviors, such that these subjective responses may diverge from responses to clinical interviews or behavioral tasks. third, although the longitudinal design establishes the temporal precedence of disgust proneness, the lack of manipulation of disgust limits causal interpretations. finally, given the unprecedented nature of the pandemic, the level of coronavirus fear and safety behaviors that can be considered maladaptive or disproportionate is presently unknown. thus, future research is needed to identify thresholds at which the distress response to the coronavirus is clinically significant and whether disgust proneness contributes to exceeding such a threshold. compliance with ethical standards. all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/ or national research committee and with the helsinki declaration and its later amendments or j o u r n a l p r e -p r o o f comparable ethical standards. this article does not contain any studies with animals performed by any of the authors. this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. ms. cox collected the data, performed the statistical analysis, and contributed to drafts of the manuscript. ms. jessup contributed to drafts of the manuscript. mr. luber contributed to drafts of the manuscript and data entry. dr. olatunji contributed to study design, oversaw data collection, and assisted with statistical analysis and manuscript preparation. all authors contributed to and have approved of the final manuscript. behaviors at values of current stress, controlling for number of covid- cases by state. prepandemic disgust and current stress were mean-centered prior to analysis, such that low, medium, and high represent the sample mean +/-one standard deviation. importantly, this effect is at trend-level. j o u r n a l p r e -p r o o f step the fear of covid- scale: development and initial validation multiple regression: testing and interpreting interactions the effects of safety behaviors during exposure therapy for anxiety: critical analysis from an inhibitory learning perspective psychological predictors of health anxiety in response to the zika virus tracing "fearbola": psychological predictors of anxious responding to the threat of ebola the relationship between obsessive compulsive beliefs and symptoms, anxiety and disgust sensitivity, and swine flu fears a global measure of perceived stress research electronic data capture (redcap): a metadata-driven methodology and workflow process for providing translational research informatics support introduction to mediation, moderation, and conditional process analysis: a regression-based approach stress-induced cortisol level elevations are associated with reduced negative affect after stress: indications for a mood-buffering cortisol effect health anxiety, cyberchondria, and coping in the current covid- pandemic: which factors are related to coronavirus anxiety? acute hpa axis responses, heart rate, and mood changes to psychosocial stress (tsst) in humans at different times of day coronavirus anxiety scale: a brief mental health screener for covid- related anxiety substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (sars-cov- ) factors associated with depression, anxiety, and ptsd symptomatology during the covid- pandemic: clinical implications for u.s. young adult mental health anxiety regarding contracting covid- related to interoceptive anxiety sensations: the moderating role of disgust propensity and sensitivity diathesis-stress theories in the context of life stress research: implications for the depressive disorders risk factors for hypochondriacal concerns in a sample of military veterans key: cord- -mbe dt v authors: sharif, salman; amin, faridah; hafiz, mehak; benzel, edward; peev, nikolay angelov; dahlan, rully hanafi; enchev, yavor; pereira, paulo; vaishya, sandeep title: covid -depression and neurosurgeons date: - - journal: world neurosurg doi: . /j.wneu. . . sha: doc_id: cord_uid: mbe dt v nan the novel coronavirus initially originated in china and has rapidly spread globally. the growing pandemic of severe acute respiratory syndrome coronavirus diseases (covid- ) has become a significant public health liability worldwide. the covid- pandemic has grown into one of the central health crises of a generation. it has affected people irrespective of nation, race, caste, and socioeconomic groups. on th jan , the who (world health organization) announced the emergence of the novel coronavirus. it declared a pheic (public health emergency of international concern), which is the sixth pheic under the ihr (international health regulations). the rapid increase in cases and evolving guidelines regarding protection and prevention of the spread of pandemic, with no confirmed treatment or approved vaccine has caused apprehension and anxiety among health care workers. unpredictability in the biological behavior of the virus, erratic changing instructions from who, variable guidelines regarding quarantine and management of the pandemic have increased the uncertainty. as of the first week of may , , , covid positive cases with , confirmed deaths have been reported worldwide and countries are affected by the pandemic. so far, more than , health-care providers have been infected with covid- in china, and more than doctors have died in italy , . in the united states, approximately , nurses, doctors, and other frontline health care workers have been infected by the disease, and dozens have died. across western europe, nearly percent out of confirmed coronavirus cases are medical professionals which is the highest reported cases among doctors and nurses. moreover according to the report on rd april , at least doctors have died,and more than , health workers have self-isolated in countries across asia and pacific region, therefore concerns among healthcare professionals are well-founded. the pandemic is serious and disruptive , yet despite the widespread infectivity and higher mortality than the common influenza virus, not much is known regarding management of critical cases, prevention and optimal measures to reduce its spread. scarce resources and an often inadequate availability of personal protective equipment (ppe) and lack of knowledge about their optimal usage can further lead to apprehension, distress, panic and anxiety in health care workers. the covid associated health crisis has disrupted working of all medical communities around the world, including delivery of essential medical and neurosurgical services. the hasty outpouring numbers of covid positive cases, not only presents a public health challenge but also have significant medical and ethical implications for the care of neurosurgical patients. currently, there is a paucity of literature guiding neurosurgery practice. neurosurgical societies have developed and published guidelinesto promote best practices for their patients. however, implementation of these guidelines is a challenge in many parts of the world where health care systems are not well established, but adjustments during an event like the covid- pandemic have been made. it may provoke even more distress and depression within the neurosurgical fraternity. a survey was developed to assess to stressors affecting neurosurgeons as a result of the pandemic. the goal of this survey was to determine the prevalence and factors associated with anxiety and depression among neurosurgeons during the covid- pandemic. while the full impact of the pandemic remains to be seen, this survey aimed to determine the frequency of depression among neurosurgeons during the pandemic and explore any modifiable factors that could be addressed to reduce the incidence of distress and mental illness among neurosurgeons. this was a cross-sectional study design conducted through an anonymous online questionnaire with only information about the city and no contact information to address ethical implications of the survey. the study duration was weeks (until the requisite sample sizewas achieved). the questionnaire was modified based on suggestions fromworld spinal column society (wscs) executive board members. majority of the members of the world spinal column society are neurosurgeons, who also perform spinal surgery. the survey was designed on google form and sent to neurosurgeons who were members of scientific societies globally through wscs executive committee. the survey was circulated to members of wscs on their social media, whatsapp groups and emails, and through snowballing technique locally and internationally. the neurosurgeons identified through these media were asked to forward the survey to other neurosurgeons in their professional circle and so on. out of total neurosurgeons who were approached, responded. a recent chinese study showed a . % ( / ) prevalence of mild to moderate depression among physicians during the covid pandemic. depression was assessed through a world health organization validated questionnaire (selfreporting questionnaire, srq- ). a cut-off score of or more was considered as positive for depression. dependent variable: depression graded on who srq - with a cut-off score of or more for a positive case of anxiety/depression. univariate binary logistic regression was applied to determine association of each independent variable with the outcome (anxiety/depression). multivariate logistic regression was used to measure the association of multiple independent variables with the outcome (anxiety/depression) by computing adjusted odds ratios and their % confidence intervals. variables with p-value < . in univariate analysis were subsequently included in the multivariate logistic regression model. statistical significance was assumed for p-value< . in the multivariate model. consent was taken from all those who filled the online questionnaire. the participant's identity and name of the institution was not disclosed. all data were kept confidential in a password protected computer. there was no financial compensation for participation nor any penalty for not participating. a total of neurosurgery trainees and consultants from countries and continents participated in the survey (figure ). the majority of the respondents were from asia (n= , . %) (figure ). table shows the distribution of socio-demographic factors among participants. the majority of the participants were consultants ( %) from low to middle-income countries ( %). more than half were younger than . among all participants, % worked in departments with or more staff ( %), while more than half of the respondents reported having less than trainees in their departments ( . %). table shows the distribution of responses regarding the covid- pandemic. almost % reported basic to moderate knowledge about the pandemic. sources of information are depicted in figure . the most common source of information was scientific publications, while almost half of them also used social media as a source for information. the majority ( %) of the participants thought that it would take more than two months for the pandemic to end. (figure ) majority of the participants ( %) said that enough information had been provided by their institutions regarding the covid pandemic. % reported that they had not been provided ppe by their hospital, though more than half have attended training courses arranged by their institutions. among consultants and trainees, . % reported that they did not feel safe during the pandemic. the majority ( %) had severe concerns regarding the safety of their families back home. % reported that they had been exposed to a covid positive case among colleagues. of these, % had been quarantined or self-isolated themselves, . % got admitted for quarantine. surprisingly, % continued work, while . % took no action at all on being exposed. . % of the respondents reported that their primary concern during this pandemic was the inadequate provision of ppe. the majority (n= , . %) of the neurosurgeons said that as a routine, their weekly surgery volumes were more than cases. in comparison, during the pandemic, ( %) said they were doing fewer than surgeries /week (p< . ). similarly, the majority (n= , . %) reported performing more than % elective surgeries before the pandemic, while ( . %) said that the number of elective surgeries during covid- pandemic reduced to % or less (p< . ). families of % of neurosurgeons did not feel safe for them going to work. about / ( %) of the participants were redeployed to a covid affected area for work during the pandemic, and the majority ( %) thought that redeployment would not be useful considering their knowledge and expertise. a . % prevalence of anxiety/depression was found among neurosurgery trainees and consultants in this study. among all participants, % felt tensed, . % were unhappy, % experienced insomnia, almost % had headaches, were easily fatigued or tired and thought that they were unable to play a useful part in their life, % had difficulty in decision making, % cried more than usual, while, % had suicidal ideation during the pandemic (table ) . table shows the univariate and multivariate analysis for the association of different factors with anxiety and depression among neurosurgical trainees and consultants. the likelihood of depression was higher among those who didn't receive information or self-protection from their institutions to combat the situation than those who got it (or= . , % ci: . - . ). those who reported that they didn't feel safe with provided ppe were also at a higher risk of depression (or= . , % ci: . - . ). anxiety and depression were less likely among those who had minor (n= , %) and moderate concerns (n= , . %) for the health of their families as compared to participants who were more concerned for their families during the current pandemic situation (n= , . %). univariate odds ratios showed that the likelihood of depression was significantly lower in neurosurgeons who had minor concerns as compared to those with significant health concerns for their families (or = . , % ci . - . ). the prevalence of depression was also significantly higher in participants whose families considered their workplace unsafe (or= . , % ci: . - . ). in multivariate analysis (table ) , effects of the following variables were controlled; age, selfrating of covid- knowledge, information regarding protection provided by hospital, feeling safe with provided protective equipment, degree of concern for family health, presence of positive covid- colleagues and families considering the workplace safe. after controlling for the effects of other covariates, the odds of depression were significantly higher in individuals who did not feel safe with the ppes provided to them than those were satisfied with provided ppes (or= . , % ci: . - . ). participants who had moderate concerns for their families had lesser odds of anxiety and depression than those with significant concerns (or= . , % ci: . - . ). being exposed to a covid- positive colleague significantly increased the likelihood of anxiety/depression, even after adjusting for other covariates (or= . , % ci: . - . ). the covid- pandemic is spreading across the globe at an exponential rate, creating apprehension and distress among all healthcare professionals. neurosurgeons being an essential part of the healthcare community are also affected in a major way. belonging to a fundamental surgical specialty, tackling emergencies and performing complex operations requiring significant dexterity, hypothetically enable them to deal with stressful situations, making them less prone to develop anxiety and depression . this may only be an assumption as we did not find any study to determine the frequency of anxiety/depression among this specialty before the pandemic. it is for the first time that depression was found among % of neurosurgeons. it cannot be said with conviction if this frequency is higher than that before the pandemic but a study done in among surgeons, demonstrated a rise in prevalence of depression post sars outbreak with a % increase in suicide. poor mental health is a social stigma moreover, a fear of being judged may explain neurosurgeons having a lower depression score as was seen in another study assessing level of stress among surgeons. this may be one of the reasons that despite mental health problems and psychosocial issues among health-care workers, most of them do not often seek mental health care. majority of the participants were consultants ( %), and almost half of them were years of age and above. the senior neurosurgeons were less likely to be anxious and depressed, though the results were not statistically significant. in relation to this finding, a recent nhs survey also indicated that % of young physicians suffered from mental health issues, while retired physicians and surgeons were more enthusiastic to volunteer for covid duties. , there was no difference in the frequency of depression among neurosurgeons working in private or government/ university hospitals. though, a significant decrease in workload may be a potential risk factor leading to psychological distress, yet a non-differential change between workload of private and public sector explains our finding, as confirmed by a recent survey by walter jean. the covid- pandemic has a global impact, irrespective of race, caste, color or creed, with widespread xenophobia especially among the medical fraternity regarding their families' and their own health (unpublished data). despite trying times, this survey showed no difference in depression among the neurosurgeons, whether they belonged to high-income ( . %) or middle/lower-income countries ( . %), european ( . %) or non-european ( %) countries. although, a recent chinese study reported a much higher prevalence of depression ( . %), anxiety ( . %) and insomnia ( %) among frontline health care workers. this translates to the fact that more than the income, specialty or region, the area of practice influences mental health, predisposing to an increased sense of insecurity and hence psychological distress. the requirement for quarantine, social distancing, and shelter-in-place orders have lead to an abrupt change in life styles and may be leading to increased apprehension among families especially of healthcare workers. not only families of neurosurgeons felt unsafe for them to go to work but the surgeons themselves reported concerns for the safety of their families back home. therefore a feeling of self-protection with provided ppe had a significant negative association with anxiety/depression while a positive covid colleague increased the likelihood of depression among neurosurgeons. a recent survey in uk reported half of health workers suffering from stress due to inadequate availability of ppe. this pandemic has disturbed functioning of all medical and surgical specialties. selected emergency neurosurgery cases are being performed in special circumstances only such as trauma, severe acute functional impairment and tumors causing impending disability. neurosurgical approaches through the nose and sinuses are being postponed due to high risk of viral transmission and updated neurosurgical guidelines for the treatment of positive or suspected covid patients have been circulated. the covid crisis has hence led to a considerable decrease in elective cases (p< . ). walter jean also showed a drop of more than % operative volume during the present pandemic. though our study did not find a significant association between this drop in elective cases and anxiety/depression among neurosurgeons, yet if this status quo is further extended, it may lead to impending depression as one third of our participants were unhappy, felt tensed, experienced insomnia, headaches and felt fatigued and tired. moreover, one in respondents cried more than usual and had suicidal ideation. this hypothesis is confirmed by another study conducted at liaquat national hospital on frontline physicians (unpublished data) which found that there was more depression in physicians who were working < hours a week compared to those who are working > hours during the pandemic. although the potential shortage of ventilators and icu beds necessary to care for the surge of critically ill patients has been well described, additional supplies and beds will not be helpful unless there is an adequate workforce. according to our data, about % of the participants were redeployed to a covid affected area, during the pandemic. nevertheless, % of neurosurgeons believed that their knowledge and expertise in an unknown environment would not be useful, and their work will not be meaningful if redeployed out of their specialty. to our knowledge, this is the first study ever to determine the frequency and factors associated with anxiety and depression among neurosurgeons from countries. the prevalence of depression and anxiety among neurosurgeons was found to be lower than the frequency reported among other frontline workers during the covid pandemic. yet, it is difficult to conclude the magnitude of the problem attributable to the pandemic, as there is a paucity of data regarding mental illness among neurosurgeons before the catastrophe. in a recent survey among neurosurgery residents, the risk of burnout was found to be . % and higher working hours was one of the drivers for burnout ( ) while another survey found a . % burnout among neurosurgeons ( ) . as both these surveys did not explore depression or anxiety, results of our study are not comparable, yet, as the working hours during the pandemic have considerably reduced, it can be extrapolated that the frequency of burn out would be consequentially less. , mental illness is a social stigma around the globe and this may be more of an issue among fraternities who are considered as the "resilient lot" such as the neurosurgical specialty, hence leading to an underreporting of symptoms. only one scale (srq- ) was used to screen for anxiety /depression, as asking too many questions on an online survey was inconvenient and would have lead to missing data. moreover in online surveys, there is always a high probability of participation bias because the participants, based on their state of mind at the time of the study, may or may not choose to participate in the study. though, it may lead to non-differential participation bias. with the evolving pandemic, the situation is still dynamic in various countries around the globe. circumstances have varied from day to day, and hence the response of participants may be different according to their changing situation. therefore, the survey being filled readily by participants having more concerns regarding the ongoing pandemic may have introduced a bias. although we tried to control for confounders during recruitment as well as analysis stage through multivariate analysis, yet there is a possibility that we may have missed potential confounders which may have exaggerated or masked the associations. yet, the factors associated with anxiety/depression among neurosurgeons in the multivariate analysis are all biologically plausible. the world is going through an unprecedented crisis, which caused turmoil in all the countries in the world. the health system in decades has not dealt with such a disaster. neurosurgeons, like all other specialties, are affected and experiencing challenges in their work and daily living. colleagues getting infected, feeling of being unprotected and concerns for the health of their families were factors found to be associated with anxiety/depression. we therefore recommended that the safety of the health-care workers be ensured by providing standard ppe and having optimum safety measures for them to regain confidence and hence reduce the incidence of mental ailments. less than weeks to weeks to months more than months don't know never death from covid- of health care workers in china doctors and healthcare workers at frontline of covid epidemic: admiration, a pat on the back, and need for extreme caution factors associated with mental health outcomes among health care workers exposed to coronavirus disease validation of the who self-reporting questionnaire srq- ) item in primary health care settings in eritrea stress in surgeons. the british journal of surgery uk military doctors; stigma, mental health and help-seeking: a comparative cohort study mental health and a novel coronavirus ( -ncov) in china clinical depression: surgeons and mental illness the impact of covid- on neurosurgeons and the strategy for triaging non-emergent operations: a global neurosurgery study factors associated with career satisfaction and burnout among us neurosurgeons: results of a nationwide survey we thank ms. noureen durrani for statistical analysis of the data and mr. imad ullah for helping throughout the study. key: cord- -vi dms authors: hanvoravongchai, piya; adisasmito, wiku; chau, pham ngoc; conseil, alexandra; de sa, joia; krumkamp, ralf; mounier-jack, sandra; phommasack, bounlay; putthasri, weerasak; shih, chin-shui; touch, sok; coker, richard title: pandemic influenza preparedness and health systems challenges in asia: results from rapid analyses in asian countries date: - - journal: bmc public health doi: . / - - - sha: doc_id: cord_uid: vi dms background: since , asia-pacific, particularly southeast asia, has received substantial attention because of the anticipation that it could be the epicentre of the next pandemic. there has been active investment but earlier review of pandemic preparedness plans in the region reveals that the translation of these strategic plans into operational plans is still lacking in some countries particularly those with low resources. the objective of this study is to understand the pandemic preparedness programmes, the health systems context, and challenges and constraints specific to the six asian countries namely cambodia, indonesia, lao pdr, taiwan, thailand, and viet nam in the prepandemic phase before the start of h n / . methods: the study relied on the systemic rapid assessment (sysra) toolkit, which evaluates priority disease programmes by taking into account the programmes, the general health system, and the wider socio-cultural and political context. the components under review were: external context; stewardship and organisational arrangements; financing, resource generation and allocation; healthcare provision; and information systems. qualitative and quantitative data were collected in the second half of based on a review of published data and interviews with key informants, exploring past and current patterns of health programme and pandemic response. results: the study shows that health systems in the six countries varied in regard to the epidemiological context, health care financing, and health service provision patterns. for pandemic preparation, all six countries have developed national governance on pandemic preparedness as well as national pandemic influenza preparedness plans and avian and human influenza (ahi) response plans. however, the governance arrangements and the nature of the plans differed. in the five developing countries, the focus was on surveillance and rapid containment of poultry related transmission while preparation for later pandemic stages was limited. the interfaces and linkages between health system contexts and pandemic preparedness programmes in these countries were explored. conclusion: health system context influences how the six countries have been preparing themselves for a pandemic. at the same time, investment in pandemic preparation in the six asian countries has contributed to improvement in health system surveillance, laboratory capacity, monitoring and evaluation and public communications. a number of suggestions for improvement were presented to strengthen the pandemic preparation and mitigation as well as to overcome some of the underlying health system constraints. background "world 'well prepared' for virus" is the title of a news article from the bbc on april , a day the world health organization (who) raised the level of influenza pandemic alert from phase to phase [ ] . the article cited a high-level who officer who commented that "the international community is better prepared than ever" to handle the potential influenza pandemic, because several years of preparation for avian flu had helped countries build up stockpiles of antiviral drugs globally. on the same day, a spokesman for the who regional office for the western pacific declared that "asia is better prepared and in a better position than others" citing experience in management of and response to the severe acute respiratory syndrome (sars) outbreak which affected the region in [ ] . having established a large antiviral stockpile and/or having experience with sars does not necessarily mean that a country is well equipped to face an influenza pandemic. preparedness is a complex phenomenon which involves many aspects, including disease surveillance, case management, command and control, and community containment [ ] . earlier studies on the completeness of national pandemic influenza preparedness plans in several regions reveal that many challenges and important gaps in preparedness remain [ ] [ ] [ ] [ ] [ ] [ ] . besides, these studies show that the level of preparedness varies hugely across and within regions. the situation in developing countries is the most worrisome as their public health infrastructure is often weak with severe shortage in financial, human, and technical resources [ , [ ] [ ] [ ] . since , asia-pacific, particularly southeast asia, has received substantial attention because of the anticipation that it could be the epicentre of the next pandemic. there has been active investment in preparedness strategy and planning in many countries by both domestic and international players. despite such strong interest and investment, a review of strategic pandemic preparedness plans in asia in and a report on regional preparedness published by the united nations system influenza coordinator (unsic) in reveals that the translation of these strategic plans into operational plans is still lacking in many countries in the region [ , ] . this paper presents the results from a rapid situation analysis (rsa) of health system and pandemic preparedness in six countries of the asia-pacific region prior to the h n / epidemic. taiwan had extensive experience with the sars outbreak, with over confirmed cases. viet nam, thailand, and indonesia also had sars cases (albeit fewer than taiwan) and, together with lao pdr and cambodia, have had human avian influenza cases. besides, endemicity of the influenza subtype h n is found in poultry in these five countries. the objectives of this rapid situation analysis are to describe the pandemic preparedness programmes and the health systems context in which these programmes have been established, and to identify challenges and constraints specific to the six countries. it is a part of a bigger project, the asiaflucap project, which aims to evaluate health system capacity in these countries in response to different phases of influenza pandemic. the study was conducted in the second half of with funding support from the european union and the rockefeller foundation. this study relies on the systemic rapid assessment (sysra) toolkit which is a systematic approach for gathering information about structures and modes of operation from complex health systems [ ] . it builds on the sysra framework, a conceptual and analytical framework initially developed by atun et al. to evaluate health systems and communicable disease control programmes [ , ] . the sysra analytical framework provides a conceptual, analytical framework and tool to evaluate health interventions that takes into account disease programmes, the general health system, and the wider sociocultural and political context. for the purpose of this study, this framework was adapted to pandemic influenza. our sysra toolkit comprises of two core elements: (i) the 'health systems element' and (ii) the 'pandemic preparedness programme element' (figure ). the health systems element focuses on structures and functionality of an overall health system (horizontal level). the 'pandemic preparedness programme element' assesses the specific pandemic influenza programme components embedded within a health system (vertical level). for each element, the components under review are: external context; stewardship and organisational arrangements; financing, resource generation and allocation; healthcare provision; and information systems. the study was conducted in the second half of . for each of the rsa modules qualitative and quantitative data were collected based on a review of published data, documentation and interviews with key informants in each country. as a first step, secondary data and documentation was reviewed and summarised for each country in order to determine what information was available and what data was lacking. afterwards, an interview team consisting of members (public health specialists) familiar with the health system and pandemic management programme in the country conducted interviews with key informants using a predefined semi-structured questionnaire, focusing especially on gaps identified in the initial literature review. the questions explored past and current patterns of health programme response, changes in pandemic response and other historical information about outbreak management. while conducting the interviews, additional qualitative and quantitative information were collected through an iterative process of information gathering. key informants were selected on the basis of their expertise in a broad range of health system and pandemic programme components. they were chosen from all administrative levels and from different institutions to provide a triangulated view of the health system and of the pandemic management programme. field visits occurred between october to december with up to key informants being interviewed in each country. no remuneration was provided to the informants. the lists of field researchers and the affiliations and roles of the key informants from each country are provided in the country case study reports available publicly accessible on the website: http://www.cdprg.org/publications. ethi-cal approval for this project was obtained from all participating countries. the scope of this study is limited to health system and health service response and preparation for pandemic influenza. non-health sector preparation and mitigation efforts are beyond the scope of this analysis. the choice of the six countries is based on an historical assessment that they would likely be at the epicentre of an influenza pandemic, the incidence of h n in poultry, and their experience with sars. the country contexts in the six study countries vary considerably. the political systems include republic (taiwan and indonesia), constitutional monarchy (thailand and cambodia), and socialist republic (vietnam and lao pdr). the level of economic development based on world bank's classification ranges from low income with high agricultural share (lao pdr, cambodia, and viet nam), middle income (thailand and indonesia) to industrialized and high income (taiwan). there is, however, similarity in that all countries enjoyed relative political stability (except recently in thailand) and continuous economic growth over the past decade preceding the current global economic crisis. health systems in the six countries vary in regard to the current health status and epidemiological profile, the level of health care resource, health financing mechanisms and health service provision patterns (table ) . • current health status and epidemiological profile taiwan shows a pattern of industrialized economies post epidemiological transition with low mortality, high life expectancy, and high disease burden from chronic diseases. in contrast to taiwan, lao pdr and cambodia have lower life expectancy with high morbidity and mortality from communicable diseases. • level of healthcare resources the level of health system resources reflects the level of economic development. taiwan has a high level of health spending and high density of hospital beds and health workforce per capita. on the other end of the spectrum, cambodia and lao pdr have low health spending and very low health facility and health workforce density. external resources are a significant source of health financing in cambodia and lao pdr. • health financing mechanisms only taiwan and thailand have universal coverage of health insurance. indonesia and viet nam have a number of health insurance schemes such as social security scheme and government employee health insurance for different sectors of the population. lao pdr and cambodia relied mainly on out-of-pocket payments with recent development of community financing. lao pdr is developing social security insurance. • health service provision health service provision patterns in the six countries are mixed. the private sector plays a major role in tai- wan. in both thailand and viet nam, the public sector has an extensive network of public health facilities. however, a significant proportion of population is increasingly using private sector health care providers such as drug stores and private clinics as their first source of health care. in indonesia, lao pdr, and cambodia, the availability of health facilities is quite limited as seen in the density of hospital beds which is at per , or less. one indicator of health service access is the proportion of skilled birth attendance. the statistics in shows that the proportion was over % in thailand and viet nam, around two-third in indonesia, nearly % in cambodia and less than % in lao pdr in . all countries in this study have experienced an outbreak of sars or avian influenza in humans ( table ) . during the sars outbreak, taiwan was severely affected with casualties. there were , nine, and two confirmed cases in vietnam, thailand and indonesia respectively [ ] . for avian and human influenza (ahi), more than human cases have been reported each in viet nam and indonesia, in thailand, eight in cambodia, and two in lao pdr. there were no ahi cases in taiwan. all six countries have developed national governance on ahi and pandemic preparedness. they all have national pandemic preparedness plans and ahi response plans. however, the governance arrangements and the nature of the plans differ across the countries. moreover, the operational procedures as well as strategic directions vary. this section presents the preparedness arrangements in regard to governance and stewardship, financial resources, other resources, and health service provision in the study period. • in all countries, the pandemic preparedness committees were headed by the president or prime minister or his/her representative. in indonesia, lao pdr, and thailand the national pandemic preparedness plans and the ahi response plans were integrated together with ahi response plan as a part of pandemic preparedness plan. the other countries had separated plans for pandemic preparedness from the ahi response plans. at the central/national level, there were three main patterns of pandemic preparedness governance. first, as in lao pdr and indonesia, a special coordination unit (national ahi coordination office (nahico) which recently changed its name to national emerging infectious diseases coordination office (neidco) in lao pdr, and national committee for ai control and pandemic preparedness (komnas) for indonesia) was established specifically to coordinate ahi and pandemic related activities as a priority programme (vertical policy approach). second, in vietnam, the governance relies on existing governance structure e.g. responsible agencies only. third, in cambodia, taiwan and thailand, pandemic preparedness is situated as part of programmes on disaster preparedness and mitigation so the preparation for pandemic is framed within the national disaster response. there was also a difference in the governance in regard to the level of responsibility. this reflects the existing governance structure and the nature of devolution of governing power in the country. in cambodia, lao pdr, taiwan, thailand, where resource allocation decisions are centralized, the budget allocation towards ahi and pandemic preparedness programmes was also decided mostly at central level. in indonesia and viet nam, central authority was important but local authorities also played crucial roles in the decision and priority setting of the level of pandemic preparedness investment in their regions. nevertheless, in all countries the operational activities of pandemic preparation at the local level were allocated to/integrated within the network of existing government bodies. • financial resource data on government and external spending for ahi and preparedness are not readily available and our best estimate shows that most countries spent around usd per capita per year or less on these activities (table ) . whereas the level of to the disease was highest in and , it declined in . funding solely or mostly originated from central budget, except in indonesia and viet nam where the local source of funding was also important, and to a lesser extent in thailand. all countries but cambodia, had discretionary budget for local level administration to use on ahi and pandemic preparation. external resources have been substantial for low income countries, particularly lao pdr and cambodia. almost the entire budget for ahi and pandemic preparedness activities in lao pdr and cambodia was provided by external donors and international organizations. indonesia also drew in a significant amount of external funding for ahi and pandemic preparedness, accounting for almost one-fourth of total budget. there was no external financial support for taiwan and less than percent in thailand. no data was available for vietnam. • other resources: human resource, vaccine, drugs, technology in all six countries, pandemic preparedness activities at the operational level relied on existing healthcare workforce in the public sector. hence human resources available for ahi are reflective of the health workforce situation in public health system. shortage of highly skilled workers was a major problem in all developing countries, especially in relation to physicians and nurses. in regard to specific knowledge and skills for pandemic influenza, additional trainings were provided to specific sections of the workforce in all countries, particularly to those working in surveillance, case detection, and infection control. most, except taiwan and viet nam, did not have a plan for surge capacity of health care workers during pandemic time. moreover, there is a question over potential absenteeism among existing workforce at the time of pandemic. all countries have strengthened their laboratory investigation capacity to prepare for the potential pandemic. all, except lao pdr, had biosafety level (bsl ) laboratory capacity and can conduct virus sequencing. these five countries were also capable of immuno-fluorescence assay (ifa) and reverse transcription-polymerase chain reaction (rt-pcr). only taiwan had the capacity to produce pre-pandemic vaccine and has a plan to increase its capacity towards pandemic vaccine production by . indonesia, thailand, viet nam had plans, or were in the process of conducting research, towards developing their pandemic vaccine production capacity. taiwan, thailand, and indonesia had local capacity to produce antiviral drugs from chemical entities. all countries had stockpiles of antivirals and personal protective equipment (ppe) but the size of the stockpiles varied across countries. in taiwan, the national stockpile was enough to treat % of population and there is a plan to increase this stockpile if necessary. the national stockpiles of thailand and indonesia covered approximately % of their population while in cambodia the national stock in phnom penh was enough for . % of the population ( , doses). we were unable to estimate the size of the stockpiles in lao pdr and viet nam from key informants or reviewed documents. in most countries, the antiviral stockpiles were located at both central level and at hospital and local health authorities. in addition to national stockpiles, there was an asean regional stockpile in singapore. • health service health service preparedness for pandemic influenza highly concentrated on surveillance and rapid containment activities in all countries but taiwan. the surveillance systems were mainly facility and community based surveillance systems where suspected cases are reported to the central level authority for further investigation and note: * only budget for adb cdc regional project; # government budget only containment. several channels for case reporting have been set up including telephone hotline, sms, email and websites. all countries except lao pdr also conducted laboratory surveillance of samples from influenza-like-illness cases. the surveillance system for pandemic influenza in the five countries with history of ahi focused on poultry related cases. when there were animal cases of avian influenza in the neighbourhood, patients with influenzalike illness with history of poultry contacts would be specially monitored. in these countries active collaboration between human and animal health sectors to conduct joint surveillance was reported. also, surveillance rapid response teams (srrts) have been set up at both central level and local level based on existing capacity, to be readily available for field investigation when there is a suspected case. in countries with shortage of qualified human resources, the surveillance and response capacity at local level remains a major challenge. only taiwan and viet nam had explicit plans for surveillance and response in time of pandemic. all countries have assigned referral hospitals to take care of ahi cases in the pre-pandemic phases. a model hospital preparedness plan has been developed in most countries to be used by their health facilities in time of pandemic. hospital surge capacity (extra beds) has been planned in all countries but lao pdr and cambodia. similar to surveillance and response, only taiwan and viet nam had an explicit staff surge capacity plan. lao pdr and taiwan had additional plans to use volunteer in time of pandemic. in regard to case management, the focus was mainly on ahi cases. clinical treatment guidelines for ahi infection have been developed in all countries. training on clinical management of ahi cases has been conducted with patient isolation and antiviral treatment as the main instruments. in all countries there was a policy to provide antiviral prophylaxis to ahi contacts. however, there was no clear rationing policy on antiviral distribution in case of pandemic. all countries (except taiwan which has not reported any case) have provided free care to all ahi patients thus far. in the five countries where human cases have been reported, most infected patients arrived at hospital after their symptoms had developed for several days. in these countries, a patient generally seeks self medication or informal/private primary-care providers as his/her first contact point and only visit public health facilities when the symptoms are severe. this is compounded by the relative lack of health care facilities in lower resource countries like cambodia and lao and the high use of private care facilities in cambodia. there were active public health education efforts in all countries. in the countries with ahi cases, most of the messages and materials were related to the handling of livestock and basic health hygiene such as hand washing, protection when sneezing/coughing. the main strategy of public health education was to focus on the prevention of avian influenza transmission (e.g. use chicken as a mascot, etc). very few messages were on pandemic influenza. a number of simulation exercises have been conducted in all six countries. most of the exercises were table-top style where relevant officers discuss and manage a hypothetical pandemic situation in a round-table manner. for example, thailand had at least one table-top exercise at the central level and in each province. viet nam has conducted many simulations for ahi preparedness at national, provincial and district level as well as at airport and borders. there were also a few regional (multi-country) table-top exercises coordinated by the world health organization and one table-top exercise by the mekong basin disease surveillance network (mbds). only indonesia and taiwan had full-scale exercises involving real field activities. indonesia's full-scale exercise in bali in april was the first of its kind in the world. taiwan's full-scale exercise at its national airport focused on its response to the arrival by plane of a suspected h n case. most exercises reveal that management and coordination between various players, including non-health sector players, constitutes a major weakness in preparedness. a criticism common to all six countries is that most simulations exercises have focused on early containment but not on pandemic preparedness in later phases. the preparation for mitigation efforts at more advanced stages of a pandemic was quite limited in most countries. they have identified various channels for risk communication to the public. however, only taiwan had clear operation procedures to sustain service provision and resource mobilization when widespread pandemic occurs. the researchers also found that knowledge/skills for pandemic preparation at local level were more limited than central level staff. the rapid analyses in six asian countries show a strong link between the health system functions and pandemic preparation. in all countries, the health system context shapes how pandemic preparedness in the country is carried out. from the rsa we found that the interfaces/linkages between health system contexts and pandemic preparedness programmes are particularly strong in three areas: governance and stewardship, resources, and service provision. the arrangements and strength of governance and stewardship of pandemic preparedness programme follow those of the general health system. in well-established health systems, pandemic preparedness is integrated within existing mechanisms, notably within the national disaster preparedness framework. in countries with a weak healthcare system, new vertical programme had to be established to manage and coordinate pandemic preparedness and response. the nature of pandemic governance also depends on the existing political context. decentralized countries have greater challenges to deal with during both outbreaks and pandemics. in a decentralized system like in indonesia, the level of political commitment could affect the level of investment in pandemic preparedness in that region/area as seen in the contrasting difference between bali and jakarta. in jakarta, where political interest on pandemic is low, the planned table-top simulation exercise was postponed because of the lack of budget while in bali, a full-scale exercise was carried out with strong support from all sectors. the political and historical context also shapes the pandemic preparedness process. for example, the political crisis in thailand in resulted in frequent changes of minister of public health and several postponements of national pandemic preparedness committee meetings. in taiwan, pandemic preparation is high on national political agenda because of its previous history of sars outbreak and casualties as well as a perceived threat of bioterrorism. the level of resource available for pandemic preparedness depends on the level of economic and health system development of the country. the amount of financial investment in preparedness activities and stockpiling of drugs and equipments is dependent on the level of budget availability. countries with low financial resource need to rely on external funding for their pandemic preparedness activities. the series of h n outbreaks which have occurred in the region since combined to the heightened global interests in averting a pandemic have allowed many low resource countries to draw in financial resources to support their preparation especially for surveillance and early detection. however, there are questions about the sustainability of these external resources given the current global economic recession and other public health priorities in donor countries themselves. such resources might also be much more difficult to mobilize during pandemic time. similarly, the shortage of highly skilled workers in the general health system has been raised as a major limitation of the preparedness planning and response in many of these countries. this situation could be even more serious in pandemic time when a number of staff may become ill with the disease and some of them may be absent due to the fear of infection. health service provision for ahi control relies primarily on the existing provider system. the main strategy used in all countries but taiwan is to focus on early detec-tion and containment. investment was made into rapid response team and surveillance mechanisms with attention to the linkages between poultry infection and human cases. this strategy may be driven by several factors. the emergence of human cases of h n may have led each of the five countries to strongly assume that outbreaks of human-to-human transmission could start within their own country. moreover, the potential threat of the h n pandemic also drew external funding whose main interest may have been to rapidly contain avian influenza outbreaks within the region, hence investment in surveillance and case detection. besides, the lack of internal resources may have yield to limited investment in pharmaceutical interventions such as antiviral and vaccine stockpiling. the who pandemic classification system into various phases could have also influenced countries into investing first in preparedness for the earlier phases and to delay preparedness for the later phases, although phases will remain fluid during a pandemic as the h n / has demonstrated. investment in pandemic preparedness activities has contributed to the strengthening of health system functions in many countries specifically in regards to surveillance, laboratory capacity, monitoring and evaluation, and public communication. regionally, there has been active cooperation through the surveillance network in the mekong basin through the mekong basin disease surveillance network (mbds). these health system functions could be useful for other diseases beyond pandemic response. however, the low investment in clinical care in relation to other health services may be a big challenge for these countries, especially if a pandemic is to expand beyond the early containment phase. the outbreak of influenza h n / and its spread globally also raises many important questions on how prepared these asian countries are for global pandemic influenza. the underlying assumption that the pandemic would start from avian influenza virus mutation within the country led to heavy investment on surveillance and case detection mechanisms in the five developing countries. these mechanisms were designed primarily for ahi with reliance on poultry contact history in the surveillance and case detection operational guidelines and unlikely to be effective for early-detection and containment of pandemic influenza now that human-to-human transmission has been observed without an animal tracer. the pandemic response strategy and the surveillance and case detection protocols in these countries need to be transformed to accommodate this changing circumstance. it is also important to translate existing pandemic response and mitigation plans into operations particu-larly at the subnational level as local administration and communities need to be active and ready for these plans to be effective. limited stockpiles of the antivirals, covering % or less of the population in all countries other than taiwan, raise the issue of drug allocation when a large-scale highimpact pandemic occurs. the world health organization recommended countries to stockpile antivirals for % of their population but this is obviously not feasible financially for many developing countries [ , ] . similarly, it is already clear with the h n / outbreak that when the pandemic vaccine is developed its availability will be limited [ ] . explicit rationing or prioritization policy for the medicines and vaccines is necessary and should be developed to avoid ethical and political conflicts that may arise [ ] [ ] [ ] . the ongoing threat of pandemic influenza with humanto-human transmission also calls for a revision/reposition of public education campaigns that were shown to be focusing on animal to human transmission in many southeast asian countries. the message requires adjustment from current emphasis on animal handling hygiene to respiratory health hygiene and when to seek medical care. the current treatment strategy to rely on a referral hospital system may also need to be adjusted towards community level surge capacity and the use of volunteers to support the system in time of pandemic. simulation exercises with phase hypothetical scenarios could be useful as a test of the level of preparedness especially with actors from non-health sector. for the preparation to be effective and sustainable, the interventions need not only focus on the influenza related activities. our study shows that health systems provide important context towards the success of the responses. the effort to strengthen pandemic preparedness should also be done in such a way that also strengthens health systems. three areas of improvement based on our findings of strong linkages between pandemic preparation and health systems in governance and stewardship, health system resource, and service provision are highlighted here. firstly, the governance and stewardship of ahi and pandemic preparedness should be integrated into the broader disaster preparedness system. taiwan benefited from more resources from higher level of economic development but comprehensive and multisectoral responses with commitment from all levels also resulted from high political interest and a systematic approach to preparedness using disaster and bioterrorism response system. national ownership of the preparedness activities is particularly important especially in low resource countries where external funding is prominent. the allocation decision of pandemic related investment should be harmonised and aligned with national systems and priorities. secondly, the scarcity of health care resources particularly in rural areas was shown to hamper the preparation for the pandemic as well as the responses to other diseases. scaling up health system capacity such as health workforce and health care infrastructure is necessary and should be decided based on evidence together with effective planning. for example, the countries can benefit from the asiaflucap project's ongoing analysis of health system resource gaps to effectively respond to pandemic. nevertheless, investment in health workforce and health care infrastructure should avoid disease-specific focus and contribute to overall system strengthening [ ] . a number of tools and proposed actions for scaling up disease specific capacity that also promote health system strengthening are increasingly available [ ] [ ] [ ] . lastly, in service provision the preparedness strategy also needs to address the prominent role of the private sector. private providers are the first contact point for health care in many countries. in many countries where the linkage of information system between public and private sector does not exist, the surveillance system may not be able to detect the cases early enough before it has already spread. treatment success could also be lower and the fatality rate could be higher if the patients present themselves late to public health care system where antiviral medicines are prescribed. the pandemic and disaster responses could also tap into the capacity of private nonprofit network and volunteers to support the scaling up of necessary responses. better planning and coordination between public and private sector health providers and is necessary and should be strengthened. this study contains a number of limitations. first, the rapid nature of the analysis was useful for simplicity, speed, and limited cost but it also limits the extent and the depth of the analyses. this limitation is alleviated by the way the questionnaires and data collection procedures were designed. published and grey literature documents were reviewed prior to and after field visits to prepare and verify the data received from the interviews. second, there are potential biases from key informants' selection. these were mitigated by including resource persons from different health system levels and sectors to allow for the triangulation of results from various sources. additionally, the data collection including interviews was carried out by both external and local experts to balance the views and to provide systematic, robust, contextual understanding. third, the scope of the analysis is limited to pandemic influenza and the health systems. other competing health care needs and priorities were assessed to a limited extent in the analysis of health care context. relative importance of those needs could influence how health systems respond to pandemic influenza, which could add to the complexity of the analysis. additionally, a pandemic could create adverse social events beyond health impacts and interrupts essential services such as food logistics or water and electricity supply systems. our study did not explore multisectoral responses or the continuity of essential services beyond the health sector, which is important and deserves further careful evaluation. additional research should be conducted to shed more light into pandemic preparation in these asian countries. a number of research activities are now going on as part of the asiaflucap project. these include the analyses of health system capacity and resource distribution in the country, scenario development for identification of resource requirements at different stages of a pandemic, and stakeholder analyses to better understand the political context and relationship between actors. future research may include the implications of pandemic preparedness on health systems e.g. financial trend, health workforce burden, the economic analyses of resource needed to fill the capacity gaps, and so on. the study in late prior to the h n / epidemic shows that the health system context influences how the six countries have been preparing themselves for a pandemic. the level and form of pandemic preparedness depend on existing health systems arrangements particularly its governance, resource, and existing service provision patterns. the political and historical context of previous epidemics shaped the priority given to pandemic preparation in a country. countries with limited domestic resources rely heavily on external funding for pandemic preparation activities. the fragmentation of health information and referral systems in some countries particularly in relation to linkage with private sector providers constitutes a challenge in synergistic pandemic response. pandemic preparation in the six asian countries has contributed to improvement in health system surveillance, laboratory capacity, monitoring and evaluation and public communications. however, preparation for pandemic mitigation in countries with low health system resources is still rather limited. with the emergence of h n / , the previous preparation in the five developing countries based on the ahi model of poultry to human transmission became less relevant. if a pandemic is to expand beyond the early containment phase it will be a big challenge for these countries whether their health system will have enough capacity to effectively respond. a number of suggestions for improvement were presented to strengthen the pandemic preparation and mitigation as well as to overcome three areas of the underlying health system constraints -governance and stewardships, resources, and service provision. the heightened public interest and awareness on the ongoing pandemic could be mobilized towards more investment in health systems. world 'well prepared' for virus afp: swine flu: asia 'better prepared' to tackle outbreak world health organization: who checklist for influenza pandemic preparedness planning pandemic influenza preparedness in the asia-pacific region how prepared is europe for pandemic influenza? analysis of national plans progress and shortcomings in european national strategic plans for pandemic influenza pandemic influenza preparedness in africa is a profound challenge for an already distressed region: analysis of national preparedness plans pandemic influenza preparedness in latin america: analysis of national strategic plans. health policy plan summary report of the sars expert committee major issues and challenges of influenza pandemic preparedness in developing countries avian and pandemic influenza: progress and problems with global health governance. global public health meeting the challenge of influenza pandemic preparedness in developing countries coordination of avian and human influenza activities. a report produced for the un system influenza coordinator a toolkit for rapid assessment of health systems and pandemic influenza preparedness and response: systemic rapid assessment toolkit (sysra). london, london school of hygiene and tropical medicine world health organization: guide to rapid assessment and response (tg-rar) a framework and toolkit for capturing the communicable disease programmes within health systems tuberculosis control as an illustrative example world health organization: summary of probable sars cases with onset of illness from uk department of health: agreements secured for pre-pandemic vaccine for the uk prioritization strategies for pandemic influenza vaccine in countries of the european union and the global health security action group: a review priority setting for pandemic influenza: an analysis of national preparedness plans antiviral resistance during pandemic influenza: implications for stockpiling and drug use overcoming health-systems constraints to achieve the millennium development goals task force on human resources for health financing: what countries can do now: twenty-nine actions to scale-up and improve the health workforce scaling up in international health: what are the key issues? health policy & planning the asiaflucap project is funded by a grant from the european commission # this paper benefits from the comments received from the participants of the ubud workshop on health system resource for pandemic preparation between - february . we are grateful to the three reviewers -mahomed patel, oscar mujica, and hitoshi oshitani -who provided extremely helpful comments to improve the manuscript. excellent administrative support from nicola lord and wasamon sabaiwan is greatly appreciated. rc has received funding from f hoffmann-la roche, various governments, and the european commission. key: cord- -hayhbs u authors: gonzalez, jean-paul; souris, marc; valdivia-granda, willy title: global spread of hemorrhagic fever viruses: predicting pandemics date: - - journal: hemorrhagic fever viruses doi: . / - - - - _ sha: doc_id: cord_uid: hayhbs u as successive epidemics have swept the world, the scientific community has quickly learned from them about the emergence and transmission of communicable diseases. epidemics usually occur when health systems are unprepared. during an unexpected epidemic, health authorities engage in damage control, fear drives action, and the desire to understand the threat is greatest. as humanity recovers, policy-makers seek scientific expertise to improve their “preparedness” to face future events. global spread of disease is exemplified by the spread of yellow fever from africa to the americas, by the spread of dengue fever through transcontinental migration of mosquitos, by the relentless influenza virus pandemics, and, most recently, by the unexpected emergence of ebola virus, spread by motorbike and long haul carriers. other pathogens that are remarkable for their epidemic expansions include the arenavirus hemorrhagic fevers and hantavirus diseases carried by rodents over great geographic distances and the arthropod-borne viruses (west nile, chikungunya and zika) enabled by ecology and vector adaptations. did we learn from the past epidemics? are we prepared for the worst? the ultimate goal is to develop a resilient global health infrastructure. besides acquiring treatments, vaccines, and other preventive medicine, bio-surveillance is critical to preventing disease emergence and to counteracting its spread. so far, only the western hemisphere has a large and established monitoring system; however, diseases continue to emerge sporadically, in particular in southeast asia and south america, illuminating the imperfections of our surveillance. epidemics destabilize fragile governments, ravage the most vulnerable populations, and threaten the global community. pandemic risk calculations employ new technologies like computerized maintenance of geographical and historical datasets, geographic information systems (gis), next generation sequencing, and metagenomics to trace the molecular changes in pathogens during their emergence, and mathematical models to assess risk. predictions help to pinpoint the hot spots of emergence, the populations at risk, and the pathogens under genetic evolution. preparedness anticipates the risks, the needs of the population, the capacities of infrastructure, the sources of emergency funding, and finally, the international partnerships needed to manage a disaster before it occurs. at present, the world is in an intermediate phase of trying to reduce health disparities despite exponential population growth, political conflicts, migration, global trade, urbanization, and major environmental changes due to global warming. for the sake of humanity, we must focus on developing the necessary capacities for health surveillance, epidemic preparedness, and pandemic response. infectious diseases have swept the world, taking the lives of millions of people, causing considerable upheaval, and transforming the future of entire populations. every year pathogens cause nearly million deaths worldwide, mostly in developing countries. more than infectious diseases have emerged between the s and [ ] . also among the known arboviruses, only are known to be human pathogens, while the others only infect wild animals and/or arthropods. to anticipate an epidemic one must identify the risk, prepare an appropriate response, and control the disease spread by first identifying the vulnerabilities of the population and circumscribing the potential space into which a disease will extend. when the epidemic expansion risk is identified, adequate information must be communicated to decision makers. ultimately, an appropriate response will depend on biosurveillance, prevention, sustained data processing, communication, strategic immunization campaigns, resilience, and mitigation strategies. the viral hemorrhagic fevers (vhfs) are a diverse group of human illnesses caused by rna viruses including approximately species of the arenaviridae, filoviridae, bunyavirales, flavi viridae, and rhabdoviridae (table ) . despite the efforts placed on early detection, viruses like dengue, ebola, lassa, crimean-congo hemorrhagic fevers continue to threaten the health of millions of people, mostly in areas where demographic changes, and political and socio-economic instability interrupt vaccination campaigns [ ] . however, the threat of vhf to global health is increased by intercontinental travel and global trade. moreover, because of the high case fatality rate of some of these pathogens, such concerns extend to the potential use of these viruses by bio-terrorists [ ] . global expansion of several diseases is exemplified by the spread of yellow fever from africa to the americas, the spread of dengue fever across continents, and recently, the spread of ebola virus from the democratic republic of the congo to western africa. the concept of an epidemic, as a disease affecting many persons at the same time and spreading from person to person in a locality where the disease was not previously prevalent, was not enunciated until when john snow produced his admirable demonstration of the emergence of an infectious disease in an urban area: the emergence of a cholera epidemic in london. at that time, none could clearly comprehend the mechanisms of emergence and spread since the existence of microbes had just been demonstrated by louis pasteur in the late s and microbe transmission modes were more speculative than based on medical or scientific facts, until when robert koch demonstrated that bacteria can be transmitted and responsible for diseases. nowadays, it is extremely difficult to make a retrospective diagnosis of historical pandemics, there are currently species in the orthohantavirus genus. the pathogeny of most of them is unknown during times when clinical descriptions were rare or lacking accuracy, and the extent of an epidemic was extremely subjective. thus, it is common to note that the first outbreak described in the western world was that of the plague of athens for which thucydides rather precisely reported the symptoms; today this epidemic has often been attributed to typhus through its clinical picture and epidemic profile [ ] . the first historically recorded outbreaks due to viral agents date to antiquity when the roman armies were returning from distant countries bringing with them "exotic" diseases. indeed, the rise of a "new" virus is an extremely rare event. most often, in terms of pathogen emergence, a virus adapts through mutation and selection pressure to a human host causing disease. presumably, smallpox, measles, and influenza were among the plagues that struck the ancient latins in gusts of epidemics more or less severe. the antonin plague that extended from to ad in much of western europe, when the troops of emperor lucius verus returned from war against the parthians, is often attributed to a smallpox pandemic by historians. in the middle ages, it seems that smallpox made a return around ad to france, germany, belgium, and the british islands [ ] . the acute respiratory infections reported during the winter of - ad accompanying the return of the carolingian armies from italy have been attributed by historians to a flu epidemic. many soldiers of charlemagne died then. the disease returned regularly and fiercely in and ad to the western european peninsula [ , ] (table ) . from the plague (sensu lato, including all transmissible diseases) of antiquity, to the severe acute respiratory syndrome that emerged on the eve of the third millennium, pandemics have followed in the history of mankind. as noted by mirko grmek, a historian of medicine, it seems that one pandemic will drive in another. if several diseases circulate concomitantly, one of them will take precedence over the other, an epidemic over the previous, and it is more likely that a pandemic will prevail [ ] . plague temporarily replaced the leprosy that appeared in eurasia for over , years; during the first millennium, plague was manifested by successive pandemics that crossed continents. during the first half of the past millennium, syphilis started its expansions, crossed oceans, and became global. tuberculosis originated in europe more than , years ago, but it was only at the turn of the seventeenth century that it was considered a pandemic; smallpox was also manifest as epidemics and then was pandemic at its peak in the late nineteenth century, then smallpox persisted until the jenner area. although early medical records of smallpox are available (egypt, china, india), large and devastating epidemics were only identified in the late fifteenth century of the millennium. smallpox was introduced into the americas by spanish settlers in the caribbean island of hispaniola in and arrived in mexico in . on hispaniola island, one third of a million of the inhabitants died of smallpox in the following years. smallpox devastated the native amerindian population and was an important factor in the conquest of the aztecs and the incas by the spaniards [ ] . in , children died in goa, india, from a smallpox epidemic. in europe, smallpox was a leading cause of death in the eighteenth century, killing an estimated , europeans each year [ ] . during the twentieth century, it is estimated that smallpox was responsible for - million deaths. the last known natural case of smallpox occurred in somalia in [ ] . it is only at the end of the first millennium that all these pathologies were better understood and their infectious origins elucidated. the first pandemic of the twentieth century was attributed to the h n spanish flu that emerged in kansas in . however, this "flu pandemic" is now thought to have had subepidemic circulation earlier in france or germany or even prior emergence in china in or [ ] , and to be exascerbated by concurrent bacterial infections. although it burned out quickly by , it has been estimated that one third of the world's population was afflicted; million people died, half of them in the first weeks of the outbreak. since the s, the frequency and magnitude of dengue fever epidemics increased dramatically as the viruses and the mosquito vectors have both expanded geographically in pandemic proportions [ ] largely extending the pandemic to all the intertropical zone. in the early s, human immunodeficiency viruses (hiv- and hiv- ) spread as an acquired immunodeficiency syndrome (aids), a pandemic that continues to take its terrible toll at the global level. since the emergence of aids, organization updates, as of june only million people were accessing antiretroviral treatment and among them, seven of ten pregnant women received treatment. in , a severe acute respiratory syndrome, sars, inaugurated the twenty-first century as a first pandemic of the millennium, involving more than countries with secondary epidemic chains in asia, europe, north america, south america, and a total of cases [ ] . ultimately, one of the major characteristics that defines today's pandemics, apart from the introduction of the disease within several continents or the rapid expansion across the administrative borders of countries, is the initiation of locally active transmission of the pathogen. although, the first ebola virus disease outbreak of western africa was considered a pandemic and witnessed several exported cases with secondary epidemic chains in distant countries of the african continent (i.e., nigeria, mali), outside of africa, exported cases rarely sparked local transmission. emergence from a sporadic case to an outbreak, to an epidemic, and ultimately to a pandemic depends upon effective transmission among nonimmune hosts, host availability (density), characteristics of the vector (natural or human made) that would enable it to circumvent distances, and the pathogen infectiousness. all these dynamics are essential for an effective disease transmission and spread. an outbreak is a sudden increase in occurrences of a disease in a particular time and place, more localized than an epidemic. an epidemic occurs as the disease spreads to a large number of people in a given population within a short period of time. to spark an epidemic chain of transmission depends on factors like immune population density, virus infectiousness, promiscuity, vulnerability, etc., while the efficiency of such transmission depends on how many persons will be infected by one person (i.e., the reproductive ratio or r ). an epidemic event will therefore expand in space (beyond the first cluster of cases) and time (rapid spread). a pandemic is essentially spatial, and represents an epidemic of infectious disease that has spread through human populations across a large region, extensively across two or more continents, to worldwide. however, all these typologies harbor the same fundamentals: emergence from one index case, transmission from one host to another, and spatial expansion. altogether, an epidemic and a pandemic are respectively a local and a global network of inter connected infectious disease outbreaks (i.e., epidemic chains). ultimately, understanding how disease (i.e., pathogens) spread in the social system is fundamental in order to prevent and control outbreaks, with broad implications for a functioning health system and its associated costs [ ] . also, after the last case occurs at the end of an epidemic, the goal is to control the risk of transmission for a -day time period. this three-week period represents an incubation when the infected subject does not transmit the virus and remains asymptomatic. the " days" is based on experimental methods use in virology to detect virus replication: influenza virus infected eggs should hatch in days, there is a -day limit for an arbovirus to infect a living model (suckling mice, mice, rats, guinea pigs, cell lines). moreover, most viral infectious diseases have a maximal incubation period of days, with few exceptions (e.g., hiv, and rabies). ultimately, such -day periods multiplied by the potential of a carrier to travel will produce the risk area for the emergence of secondary cases (from a walking distance to the long distances covered by commercial jets). however, it is important to clarify that many vhf including ebola virus can be carried by an asymptomatic host for several months [ , ] . the mode of transmission profiles the epidemic pattern of a transmissible disease. it is extremely helpful when a disease emerges to rapidly surmise the mode of transmission and how to respond (e.g., water-borne disease, arthropod-borne disease, human-tohuman transmission). pathogen transmission can be interspecific or hetero-specific, direct or indirect. direct transmission occurs by close contact with infected biological products (e.g., blood, urine, saliva). indirect transmission occurs with intermediate hosts such as arthropod vectors (e.g., mosquito, tick) or mammalian vector/reservoir (e.g., rodent, chiropteran) or from infected environmental means (e.g., soil, water, etc.). mobility and transportation are the main factors for diseases dispersion, as an emblematic example, one can simply show how the - evd outbreak of western africa expanded due to the transportation of patients during their -day incubation periods, first by foot-paths, then by motorbike, then taxis and public transportation, finally becoming a global concern with patients traveling by boat or commercial airline [ , ] . host population density and promiscuity, crowded places (like schools, markets, mass transportation system) also play an important role in the efficiency of transmission as well as the level of herd immunity (e.g., annual pandemic flu), altogether this gives us the level of population susceptibility (i.e., vulnerability). environmental factors can also be major drivers of pathogen expansion, for example the emergence of nipah encephalitis. the nipah virus, when it emerged for the first time in malaysia in , was transported by its natural host, a frugivorous chiropteran. a year earlier, an immense forest fire affecting several indonesian islands had forced the escape of disease-carrying bats that took refuge in malaysian orchards, planted to nurture newly developed pig farms. both pigs and farmers became infected and nipah virus was discovered for the first time. another classical example, more associated with human environment and behavior, is the old story of the spread of dengue virus via the used tires carrying infected aedes aegypti eggs and transporting dengue across oceans and continents [ ] . understanding the mechanisms of transmission and expansion of disease vectors with respect to the typology (epidemic pattern) of a disease is the ultimate challenge for controlling and preventing disease. typologies from human-to-human transmission, zoonotic diseases, arboviruses, water-borne diseases, and others play different roles in the rate of disease spread and need to be clearly understood. finally, while an epidemic pattern is driven intrinsically by the virus and its vector, the host population, the mode of transmission, and even the human environment (e.g., population density, urbanization, agricultural practices, health system, public health policies) as well as physical environment (season, meteorology, climate changing, latitude, altitude) factor into the rate of disease spread. with respect to pandemic risk (the rapidity and area covered by disease), the main characteristics of a virus are found in its environmental persistence while remaining infectious. environmental persistence depends on: virus structure, enveloped viruses are more sensitive than the naked viruses; its mode of entry into the body of the susceptible subject (transdermal, oral, respiratory); its ability to diffuse out of the body for a sufficient period of time which will, in turn, enable transmission to a greater number of subjects (r ). altogether these intrinsic factors link to the infectivity of the virus, indeed, viruses transmitted by aerosol possess certainly the most efficient way to spark an epidemic that increases with population density and vulnerability as well as with the resistance of the virus to environmental factors outside the host cells. the cycle of transmission shapes the epidemic in time and spatial dispersion. for example, animal to human zoonoses are dictated by chance encounters between host (population density, animal farming, pets, hunting) and, eventually transmission such as that observed between human and nonhuman primates [ ] . vectortransmitted diseases (i.e., arthropod-borne diseases) depend on the vector ecology (ability to transmit, length of the intrinsic cycle of the virus, trophic preferences, vector density, seasonality, reproduction, breeding sites, food abundance for hematophagous arthropods). mobility of hosts/vectors that are part of the natural cycle will also play a role in the potential for disease expansion (e.g., mosquito-flying distance, cattle transhumance, human migration). also, other factors associated with the hosts will render a more efficient transmission: human behaviors like fear/social responses, nosocomial infections, super-spreaders); viruses having multiple natural hosts (vicariates) or vectors; vectors with multiple trophic preferences (e.g., biting cattle, birds, and primates); the incubation period in the vertebrate hosts as well as the intrinsic replication in the arthropod vectors will also intervene; ultimately subclinical infection is also an underestimated factor of virus dispersion and transmission that modifies the epidemiological pattern of disease. one can distinguish also a typology of communicable diseases that reflects the spatial and temporal mode of transmission including arthropod-borne transmission, human-to-human transmission, human-to-animal (and vice versa) transmitted diseases (i.e., zoo- predicting hfv pandemics noses) including vector and nonvector transmitted diseases, and some other types of environmentally transmitted diseases. all of them represent unique types of transmission and risk of spread with a variable path of time, and also dependent on multiple factors (environment, climate, behavior, etc.). we have to consider territories as spaces where disease can potentially expand and that can be characterized by the fundamental factors of emergence and spread: the vulnerability of the population, the level of favorable transmission factors, and the probability for the population to be exposed to the virus. vhf are exemplary for their epidemic patterns of expansion dependent on the above reviewed factors (i.e., fundamentals of emergence) and their epidemiological characteristics (i.e., virus, host, environments). for example, let us consider the control of arenavirus spread by their strong host-species association. on a geological time scale, arenaviruses such as the agent for argentinian hemorrhagic fever (ahf) coevolved with their natural rodent host and then spread according to the expansion of the rodent host. one host-one virus ultimately produces a localized endemic cycle, the distribution of the disease overlaps the distribution of the rodent host while enzootic patterns appear naturally limited to an ecosystem (e.g., local rodent populations, behaviors, and environmental factors). hantaviruses also appear as a global complex, resulting from the coevolution of virus and rodent hosts and a global dispersion of generally localized enzootic diseases [ ] [ ] [ ] . as for the pandemic risk associated with a natural virus reservoir, chiropterans are unique flying and migratory mammals that have been associated with filoviruses and other viruses of major public health importance [ ] , their potential as vectors will eventually favor the spread of these viruses into new territories. also because there is potential for a long coevolution, epidemiological patterns are also dependent on virus-host spillover, host vicariate, and other environmental factors (e.g., climate change and man-made changes in land use). other arboviruses such as yellow fever virus, dengue virus, as well as west nile, chikungunya, or zika viruses show a pandemic risk associated with the existing distribution of their respective arthropod vector, vector density, and ability to transmit virus. investigating the fundamental factors of transmission and favorable territories for disease emergence are necessary to evaluate the risk, respond to the epidemic, and control its expansion from an index case to a pandemic. ultimately, when the fundamentals are understood and epidemic/pandemic risk identified, suitable emergency funding needs to be identified and made available in endemic areas to insure political willingness and community participation. ultimately, a suitable response will improve biosurveillance, data processing, communication, strategic immunization campaigns, and research for future risk prevention. several emblematic vhf and their original "epidemiological engineering" are presented in herein. vhf such as ebola virus disease, lassa fever, rift valley fever, or marburg virus disease are highly contagious and deadly diseases, with potential to become pandemics. remarkably, vhf are essentially caused by viruses of eight families; arenaviridae, filoviridae, hantaviridae, nairoviridae, peribunyaviridae, phenuiviridae, flaviviridae, and more recently rhabdoviridae [ ] (table ) . hemorrhagic fever viruses (hfv) have been classified as "select agents" because they are considered to pose a severe threat to both human and animal health due to high mortality rate, human-to-human transmission, and, in some cases, the potential to be aerosolized and used as bioweapons [ ] . each of these hfv shares some common features that define the nosology of the vhf group, from virus structures to the clinical and epidemiological characteristics of their diseases. -hfv spread person-to-person through direct contact with symptomatic or asymptomatic patients, body fluids, or cadavers. -vhf can have a zoonotic origin, as when humans have contact with infected livestock via slaughter or consumption of raw meat, unpasteurized milk, bushmeat, inhalation or contact with materials contaminated with excreta from rodents or bats. -hfv can be vector-borne, i.e., transmitted via rodents, mosquitos, and ticks. -vhf are zoonotic diseases. accidental transmission from the natural host to humans can eventually lead to human-to-human transmission, human infection, and sporadic outbreaks. -with a few noteworthy exceptions (i.e., ribavirin), there is no cure or established drug treatment for vhf, while limited vaccines could be available, including yf, ahf, and rvf (the latter is for animals only). -vhf have common features: they affect many organs, they damage blood vessels, and they affect the body's ability to regulate itself. clinical case definitions describe vhf with at least two of the following clinical signs: hemorrhagic or purpuric rash; epistaxis, hematemesis, hemoptysis, melena, among other hemorrhagic symptoms without known predisposing host factors for hemorrhagic manifestations. in fact, during an epidemic, all infected patients do not show these signs and a specific case definition needs to be defined in accordance with the suspected or proven viral etiology of the disease [ ]. also, vhf pathogenesis encompasses a variety of mechanisms including: ( ) alteration of hepatic synthesis of coagulation factors, cytokine storm, increased vascular permeability, complement activation, disseminated intravascular coagulation. moreover, severe pathogenic syndrome is often supported by an ineffective immunity, high viral loads, and severe plasma leakage and co-infection with other pathogens [ ] . the present chapter will mainly focus on the factors that can specifically and eventually contribute to a pandemic risk and how did we learn from historical spread of the vhf. the yellow fever disease pandemic is thought to have originated in africa, where the virus emerged in east or central africa and spread to western africa. in the seventeenth century, it spread to south america through the "triangular" slave trade, after which several major outbreaks occurred in the americas, africa, and europe [ , ] . the yellow fever vaccine is a fantastic gift from pioneering vac- cinology; it is efficient, affordable for developing countries, and protects for at least a decade or even life-long. however, yf remains a particular concern at the global level and the number of cases has unexpectedly increased this past decade. nowadays, yfv causes , infections and , deaths every year, with nearly % occurring in africa. nearly a billion people live in an endemic area [ ] . although yfv is common in tropical areas of south america and africa, it has never been isolated in asia [ ] . ultimately, the pandemic risk is there, from the uncontrolled epidemic as for example in the inland remote area of the brazilian mato grosso state, to the recent burst of epidemics in west and central africa including angola, drc, as well as imported cases in kenya and china [ , ] . indeed, the risk of a pandemic exists if any imported case goes to an area where the fundamentals of emergence are present (i.e., aedes aegypti and a nonimmune human population). for years it has been stressed that yf coverage needs to be exhaustive in the endemic area, and the who international health regulations (ihr) need to be strictly respected when peoples are crossing frontiers to or from an endemic area [ ] . even though the virus was known to actively circulate in asia, north america, and africa years ago, a global pandemic of dengue fever began in southeast asia in the s [ , ] . dengue virus (denv) expansion was followed by the emergence of a dhf pandemic that occurred in the late twentieth century (see above, the "tire-mosquito larvae connection"). by the end of the century, dhf emerged in the pacific and the americas, and extended to all asian continents [ ] . lately, in the s, epidemic dengue fever occurs in africa, with a predominant activity in east africa, while sylvatic denv circulation was described in western africa [ ] . the different dengue virus serotypes spread also independently to all continents. while it is remarkable that infection with one serotype does not provide cross-protective immunity against the others, epidemics caused by multiple serotypes became more frequent, and highly pathogenic denv were identified [ ] . dengue fever to date has a global distribution with an estimated . billion people at risk. yearly, hundreds of thousands of dhf cases occur [ ] . altogether, the requirements for a dhf pandemic are globally present [ ] : the highly competent aedes aegypti and aedes albopictus denv vectors, the globally distributed denv serotypes and highly pathogenic strains, and finally, climate change that opens new breeding opportunities for these mosquitoes to expand and eventually transmit imported denv into new populations and territories [ ] . mankind will have to live with this pandemic until the new denv vaccines can be implemented. in , an unknown disease was reported by a group of laboratory workers in west germany and former yugoslavia [ ] . over the course of months, cases and seven deaths occurred. conclusions made by treating physicians at the time (and published shortly thereafter) highlighted the following: high fatality rate, risk of relapse; risk of sexual transmission [ ] . a connection was made to infected african primates, chlorocebus aethiops, when laboratory workers were exposed to their imported tissues. it took years to effectively connect marburg virus, marv, to a bat, rousettus aegyptiacus, as a natural marv reservoir in central africa [ ] . marv is considered to be extremely dangerous for humans, is classified as a risk group pathogen, and also is listed as a select agent; however, the pandemic risk cannot be assessed because only four epidemics have occurred. although marv expansion appears to be limited to a few countries in africa, the recent emergence (estimated at a few decades ago) of a second human pathogenic marburgvirus known as ravn virus, and the widely distributed old world rousette fruit bats (rousettus spp.) serving as reservoir for both viruses [ ] , are two factors that favor pandemic risk. although more than years after its emergence from a remote area on the ebola river in the central african rain forest, ebola virus (ebov) remained hidden in a cryptic natural cycle. then a series of outbreaks occurred in the large congolese rain forest of central africa [ ] . the epidemic risk was always considered to be localized and circumscribed [ ] . then, suddenly without warning, in the late months of , ebov emerged for the first time in a remote area of western africa and sparked an outbreak more massive than ever witnessed before. more than , people were infected, ten countries recorded cases (transmitted or imported), the pandemic risk raised fear, and who declared it as an inter national health emergency that requires a coordinated global approach [ ] . besides the lack of preparedness of national and international public health systems, the other major factor that played an immense role for the dispersion of evd in western africa was the extreme mobility of village populations. they followed the kissidougou forest foot-paths to the towns in guinea using motorbikes, cars, and other public transportation, then later evd traveled by plane to the global level. the evd epidemic went from outbreak to pandemic risk. like marburg virus, another member of the filoviridae, ebola virus, shares bats as a potential virus reservoir, human and nonhuman primates are highly sensitive to the virus, and inter-epidemic periods play an important role since the epidemic silences tend to diminish the attention of health services and increase epidemic risk. in this way, the first western african evd epidemic is exemplary for showing the hidden risks contained in the natural cycle of a virus, and the sudden emergence followed by an unprecedented velocity of spreading. in the absence of biosurveillance, a pandemic risk remains. hemorrhagic fever with renal syndrome, hfrs, appears first as a global concern of one virus family, several human pathogenic viruses of the genus orthohantavirus, multiple clinical presentations, and different epidemiological patterns [ ] . hantaviruses and hfrs were first described in asia [ ] ; nowadays, hantaviruses are the cause of zoonoses that are expanding worldwide. indeed, since when a previously unknown hantavirus was implicated in the first hantavirus pulmonary syndrome (hps) outbreak in the united states, several other hantavirus infections were reported in western europe, and then hantaviruses were described in south america. ultimately, after an early suspicion of the presence of the hanta viruses in africa [ ] , a novel hantavirus, sangassou virus, was isolated in in guinea [ ] . altogether we observed the emergence of the hantaviridae in the western hemisphere, from the old world to the new world, and recently discovered its first tentative steps on the african continent. with respect to the orthohantavirus genus, a real pandemic exists even when multiple viruses are involved. ultimately, as for the arenaviridae, hosts are specific and certainly the major vectors of virus dispersion. the arenaviridae includes different viral species grouped as old or new world arenaviruses [ ] , each is maintained by rodents of individual species as natural reservoir host and as vector for the viruses that are human pathogens. the rodent hosts are chronically infected without obvious illness and they pass virus vertically to their offspring. de facto, the distribution of the virus covers that of its natural hosts but is isolated in an ecosystem generally limited by natural barriers, e.g., mountains, river. a phenomenon in which rodent lineages are naturally infected by a virus and remain in such a limited environment is called "nidality" [ ] . this is what it is observed for argentinian hf, venezuelan hf, bolivian hf, and lassa hf. regarding the pandemic risk of any of these hf, arenaviruses because of their strict association with their natural hosts, like the hantaviruses, have their expansion potential limited by their natural hosts even though the latter are widely spread and could certainly be infected. such risk lies in an unexpected encounter between infected and noninfected populations under the pressures of (as yet unknown) factors that favor their migration from enzootic to non-enzootic areas. in that matter, lymphocytic choriomeningitis virus, another member of the arenaviridae, has a worldwide distribution through its domesticated natural host, the ubiquitous house mouse, mus musculus. although crimean-congo hemorrhagic fever, cchf, is a widespread disease endemic to africa, the balkans, western asia, and asian countries south of the th parallel north, it is generally transmitted by ticks to livestock or humans and therefore geographically limited to regions where tick vectors feed on humans. although the competent ixodid vector is limited, as is the abundance of their natural hosts, climate change modifies the distribution and abundance of tick hosts (i.e., tick abundance) [ ] . additionally the cchfv pandemic risk is limited by low mobility, geographical repartition, and seasonal activity, although its main natural hosts are widely dispersed from africa, to asia and europe [ ] . ultimately, human-to-human transmission occurs from close contact with the blood, secretions, or other biological fluids of infected persons but these remain rare events with a r < . altogether, a cchf pandemic risk remains hypothetical but underlined by the risk of human-to-human transmission [ ] . as for cchf, rift valley fever, rvf, is first a disease of cattle and illustrates a unique subcontinental zoonotic spread along the path of traditional herders. rvf became a transcontinental risk with trade and transportation when the virus spread from north east africa to western africa, and even to madagascar [ ] . if one considers its pandemic risk, with respect to rvf epidemiology as a mosquito-transmitted disease, two factors have to play concomitantly: the presence of infected cattle (i.e., nonimmune) and competent mosquito abundance, both considered hazards, while concretizing the risks from human vulnerability (nonimmune; mosquito bite; direct exposure to infected blood). in order to streamline the prevention and the actions to reduce epidemic risk, the various elements involved in an outbreak are here considered from a systemic point of view, considering the risk as the convergence of a hazard and vulnerability: -the presence of the threat (or "hazard" pathogen, i.e., vector, virus reservoir) is considered to be a necessary-but not sufficient-condition for the development of a disease. it is often known only in terms of probabilities, sometimes very low and therefore often subject to significant random variability in time and space. we often seek to evaluate the spatial and temporal differences of this probability, trying to measure its significance. sometimes, it only uses one character necessary to the presence of the pathogen or vector (e.g., the presence of water, a minimum temperature, a type of vegetation). -the susceptibility of the host (which is essentially linked to individual characters, genetic, biological, such as immune status or age) is individual, and often given by a probability. -direct exposure of the host to the hazard is an element of active vulnerability, depending on the behavior of the host that increases the likelihood of contact between host and hazard by exposing it to an environment conducive to his presence (e.g., travel and contacts, professional activities). it also includes all the known "risk" behaviors that increase the likelihood of direct exposure to the hazard. -passive vulnerability of the host, which is not directly dependent on the pathology, is not even necessary nor sufficient for pathology, but influences the exposure of the host to the hazard or to protection from the pathology. this protection consists of prophylaxis, access to care, availability of care. it is independent of the real presence of the hazard; the host can be vulnerable without being exposed to the threat. the vulnerability is often defined by several levels (individual, context). it is very often "spatial" as linked to phenomena of segregation or spatial concentration. this is an area primarily studied by geography. ultimately, this vision can differentiate what is active, often subject to high variability, random in time and space (the emergence or the presence of hazards is often difficult if not impossible to control) from what is passive, generally situated among more stable population levels (sensitivities, exhibitions, behaviors, and vulnerabilities). this allows for better public health preventive actions, and also to understand rationally crisis situations by preemptively targeting the most important elements of the system in terms of vulnerability, and secondly by optimizing risk reduction (elimination of vectors, vaccinations, quarantine, etc.). in all cases, these actions must be adapted to social contexts to have a real impact on risk behaviors and vulnerabilities that they generate, hence the increasing role of anthropology in the field of health. to prevent or reduce the epidemic risk, it is necessary to act on each component of this system: -reducing the susceptibility of the host (e.g., immunization, vaccination, prophylaxis). -reducing host exposure to the pathogen (e.g., vector control, quarantine, exclusion zone). -eliminating the pathogen directly (e.g., animal slaughter, disinfection, hygiene), or indirectly (e.g., suppress transmission). -reducing host vulnerability (e.g., socio-economic, behavioral, access to health care system). -reducing host exposure to emergency condition (e.g., realtime data collection, warning systems for emergency, crisis management, implementation of treatment). the rapid detection of emergence is the key to controlling the spread of an epidemic. it requires comprehensive monitoring to trigger alerts and all other risk-reducing actions, in particular, reducing the exposure of the host to the pathogen and, if possible, the elimination of the pathogen. in parallel to the monitoring and warning systems, protocols must always take into account local characteristics of political power and decision-making bodies that could otherwise render ineffective year-long action plans or warning systems (for example, the management of the chikungunya epidemic in reunion island was largely impacted by bottlenecks related to local political system) [ ] . biosurveillance and efficiency in data collection and management will be the technical keys for prevention (early detection of epidemic risk) and forecasting epidemic emergence and spread (i.e., analyzing the data in near real time taking into account the vulnerability of a given population). also, this can be achieved only by exhaustive capacity building (human and technical) mostly in the more vulnerable developing countries but also where the most advanced technology needs to be developed. networking biosurveillance systems are a major undertaking from regional to global, involving politics and diplomacy. taking in account the local characteristics of political structures and decision systems is fundamental. despite our current recognition of the risks posed by emerging and re-emerging infectious diseases to global public health and stability, reliable structured data remains a major gap in our ability to measure (and therefore manage) globally infectious diseases. who has long served as an information hub for infectious disease events worldwide; however, extracting quantitative data from who information bulletins (weekly epidemiological record and the more recent disease outbreak news alerts) proves to be a time-consuming effort with limited results in terms of operability, and exists more for the record and future analysis. the current proliferation of geospatial information tools (i.e., geographical information system, gis) and stepwise advances in data extraction capabilities have made it possible to develop robust, systematic databases facilitating anomaly detection (like clusters), infectious disease models (and model evaluation), and apples-to-apples comparisons of historic infectious disease events worldwide. however, biosurveillance capabilities-the key to global prevention and health securityremain inadequate to support true early detection and response. increased access to technology, rapidly developing communications infrastructures, smartphone usage for suspected-case reporting, and global networks of (formal and informal) disease surveillance practitioners provide an explosive opportunity to patch and improve surveillance networks. the challenge is to leverage all these developments, implement technical and capacity building where needed, before the next epidemic with global impact emerges. several organizations have developed systems to collect epidemic information and facilitate rapid response: who has the department of pandemic and epidemic diseases (ped) that develops mechanisms to address epidemic diseases, thereby reducing their impact on affected populations and limiting their international spread. among them some have self-explanatory titles: the battle against respiratory viruses (brave); early warning and response systems for epidemics in emergency (eware); emerging and dangerous pathogens laboratory network (edpln); international coordinating group for access to vaccines for epidemics (icg); global infection prevention and control network; (gipcn ); global influenza surveillance and response system (gisrs); global leptospirosis environmental action network (glean); meningitis environmental risk information technologies (merit); weekly epidemiological record (wer); emerging diseases clinical assessment and response network (edcarn). global commitment to these efforts will insure their readiness in times of need. most certainly and most importantly, any preparedness and response requires emergency funding [ ] . it has been estimated that if the ebola virus disease response started months earlier, it could have reduced the total number of deaths by % in liberia and sierra leone [ ] . we learned from this last evd epidemic that in march , the african union's minister of finance requested the african risk capacity (arc) agency to help member states to better plan, prepare, and respond to devastating outbreaks by developing new applications for financial tools, like insurance, that can significantly improve the speed of funds to affected countries and shorten the time between event and response. the agency is now developing an outbreak and epidemic insurance product primarily based on responsibly and timely budget reallocation; however, viruses do not wait. moreover, the world bank's pandemic emergency facility is designed to finance surge capacity and support international government partners to actively participate to the response. ultimately, epidemics are not one-off events, but rather demonstrate financial patterns similar to other natural catastrophes. as natural catastrophes, large epidemics can be insured by creating financial mechanisms to facilitate the movement of critical resources within affected countries and ultimately manage the spread of disease and minimizing macroeconomic impact [ ] . classical tools and strategies for predicting epidemics encompass human disease surveillance (e.g., public health and hospital statistics) and, sometimes, environmental surveys (e.g., climate, el niño, earthquake, tsunami); also more recently complying with one health concept, human and veterinary health as well environmental risk factors have been reunited in a comprehensive approach of public health risk (i.e., outbreak, epidemic risks). however, this heuristic approach of health remains limited to specific diseases and territories and does not apply as a global predictor of pandemics. first, historical data is the only available objective view of past epidemics and pandemics, needs to be collected, formatted, corrected, and analyzed. this will be the foundation of the different tools and strategies described below. in that matter, with respect to the depth of the past data available, time series of disease observation, modern tools such as internet search data have actually led to the development of several specific sites (e.g., google flu and dengue) [ ], whose search-term reports have correlated strongly with incidence estimates in several public health reports in europe, asia, and the u.s. however, even though such tools can complement classical disease surveillance, most of these sites are geographically limited and cannot be used for live monitoring of epidemic risk and for neglected tropical disease surveillance [ , ] . however, from such historical and live-collected data, health alert systems can be implemented, and prediction models can be developed. moreover, thanks to the spatial analyses, combining multiple data sources will provide the ultimate tools for livemapping an outbreak, which will lead to an efficient response when tools and strategy have been specifically identified (i.e., sufficient and available in-country heath system resources and funding; identifying variations in pathogen sequences that contribute to ro and pathogenicity; monitoring population movement; etc.). the amount of data being digitally collected and stored is exponentially accumulating. it is estimated that, as of september of , the world wide web reached . billion pages containing eight zettabytes of accessible data, and the accumulation of information is growing around % every year [ ] . this situation has generated much discussion about how to use the unprecedented availability of information and computational resources and the sophistication of new analytic and visualization algorithms for decision-making to reduce the impact of infectious diseases. in fact, it is argued that the paradigm of "big data" will change not only the way business and research is done, but significantly improve the understanding of factors leading to the emergence of infectious diseases. big data could lead to the implementation of a decentralized biosurveillance enterprise allowing organizations and individuals to take full advantage of a large collection of disparate, unstructured qualitative, and quantitative datasets. with the proper integration and the right analytics, big data could find unusual data trends leading to better pathogen detection systems, as well as therapeutic and prophylactic countermeasures. however, the impact of these analyses and forecasts depends not only on how the data is collected, ingested, disambiguated and processed, but also on how it is relayed in different operational contexts to users with different backgrounds and understandings of technology. while impressive in data mining capabilities, real-time content analysis of social media data misses much of the factual complexity. quality issues within freeform user-provided hashtags and biased referencing can significantly undermine our confidence in the information obtained to make critical decisions about the natural versus intentional emergence of a pathogen. risk factors associated with a health event in a population are often linked to environmental factors (fig. ) . they are also linked to spatial relationships between individuals, especially for infectious diseases. the geographical distribution of these phenomena reflects spatial relationships. beyond "classic" epidemiology mainly based on statistical analysis, using the location and spatial distribution is essential in the understanding of health events and analysis of their mechanisms. spatial analysis in epidemiology is a method to help determine the location (georeferenced) of risk factors. it allows one to identify the spatial and temporal differentiation in the distribution of events, using their location in time and space. when the location is available, with precision for each studied object (i.e., individuals or geographical units), it is possible to: -characterize the overall spatial distribution, using synthetic indices on the absolute position of an object, on the average spatial arrangement of objects or their values (grouping/ fig. mapping environmental factors that have a major impact on insect vector population (i.e., mosquitoes and ticks). this map of laos constitutes the basis of a risk map showing part of the hazards contributing to virus vector density that could be matched with human density and pathogen prevalence leading to a risk map (spatial risk) and eventually extended through seasonality (temporal risk). mean temperature and mean rainfalls are interpolated as climatic conditions, as environmental factors influencing the presence of mosquitoes dispersion, spatial dependence, variogram measure of autocorrelation space). -look for characteristics of the overall shape of the phenomenon (tendency, shape), and search for a theoretical spatial distribution, or for a process to model the observed spatial distribution. -look for unusual places (geographical centers and source sites; aggregates; exclusions; hot spots, cold spots), and to study the spatial relationships at the individual level. -conduct spatiotemporal analysis: search index cases, reconstruction of paths, diffusion models, models of extinction, etc. -spatial analysis allows the development of applications for modeling epidemics, preparing warning systems, as well as crisis management systems, risk prevention and analysis systems, and vaccination campaigns. many tools for biomonitoring and prevention of epidemic risk have been developed (fig. ) , as well as software tools to: (a) visualize spatial distributions. (b) synthesize and analyze position and spatial relationships between events (continuity, consolidation, attractionrepulsion, shape, centrality, displacement, diffusion processes). (c) to analyze the relationship between spatial distribution of attributed values and environmental characteristics of the phenomenon (environmental correlations). (d) to model the phenomena of emergence, dissemination, extinguishment of an epidemic. cluster detection, space-time analysis, and spatial integration with environmental and demographic data are widely used in such warning systems. multiple and complex factors are associated with the emergence and impact of pathogens in a given geographical area. therefore, public health analysts are confronted with the task to identify the likely, and unlikely, consequences and alternative critical outcomes of a given vhf outbreak. this requires the ability to monitor in near real time the dynamics of the geographical dissemination of these viruses in villages, cities, countries, continents, or the globe using new analytical techniques within the emerging field of genomicbased biosurveillance. this concept integrates microbial genotyping, next generation sequencing, metagenomics, big data and database analytics, and contextualized visualization to identify, characterize, and attribute known and unknown pathogens and generate estimates of how different contingencies will affect their impact [ ] . a genomic-based biosurveillance system includes powerful microbial genomic characterization to rapidly identify a pathogen [ ] . this characteristic makes a genomic-based biosurveillance a useful approach not only for public health but serves as a deterrence tool for intentional biological weapon development and deployment. the initial step consists of integration of signals generated by molecular-based assays and next generation dna sequencing and unbiased microbial characterization for pathogen source tracing, attribution and forensics. while each of these techniques has been discussed in the literature in detail [ ] , the integration of this information can yield a more extended view of the scale of a pathogen outbreak. the development of high-throughput the exemplary case of the highly pathogenic avian influenza virus h n in thailand. from the emergence of one imported case (red-filled circle), the pathway direction (arrowed green lines) of h n infection in farms (yellow points) is reconstituted, using dates of infection and distance between farms. results show local spread with time-to-time medium distance jumps dna sequencing technologies (i.e., dna and cdna forms of rna viral genomes) is allowing the genomic characterization of previously unknown pathogens without relying on prior reference molecular information [ , ] . this information is available within days, and even hours, of sample collection, and well before the development of animal infection models. because of their portability, this technology will become widely used in the next years in routine clinical settings. however, to be clinically and epidemiologically relevant, dna sequences must be rapidly and effectively translated into actionable information defining pathogen characteristics (i.e., virulence or drug resistance), it must point to a source of origin, and discriminate a natural event from a manmade release [ ] . while some government agencies are considering use of genomic information to develop next generation level- and level- detection/surveillance devices [ , ] , there is no reference database where researchers can retrieve standardized genomic signatures and motif fingerprints to develop primer-, probe-, and antibody-based detection technology using reference moieties. the impact of genomic-based biosurveillance in public health and biodefense will not be fully realized until addressing the current impracticality of transferring the terabytes of genomic data generated by dna sequencing devices to a centralized architecture performing analysis operations, as that might take hours or even days. therefore, a new paradigm could emerge from encouraging the development of decentralized algorithms that first determine in situ the presence of pathogen-specific genomic signatures or motif fingerprints, summarize and relay the results into an operational biosurveillance metadata format for contextualized decision support. the localized data management, time, and space required for spatial analysis is performed by geographic information systems (gis). these are computer systems that manage large volumes of data and easily use the location to perform spatial analysis. most gis are not limited to data management functions, but also integrate multiple analysis tools, data transformation, and cartographic representation. these are for the most part complex applications with enormous features. the "gis" designation covers a wide variety of software projects built according to different technical options, functionality, and diverse performances. a gis is essentially a management tool (structure, organization, entry, storage), an analytical tool (statistical and geographical treatment, spatial analysis), and a communication tool (data visualization, descriptive mapping, thematic mapping, atlas). it is also a tool that allows the use of a spatial model for the simulation of a process, such as the development of an epidemic. gis facilitates the interface between modeling and simulation program, and the geographic database, and can ultimately take over the whole of access to spatial information needed by the modeling program. the gis should thus be at the heart of organizing the collection and processing of monitoring data. to ensure the management of this system, it is important to set up a body specifying all the collection, validation, processing and dissemination of information and results (alerts, risk modeling, near real-time dissemination of results). this body must be proposed and validated by political authorities, preemptively, to avoid further blockage and to ensure effectiveness in situations of epidemic crisis. mathematical modeling is a mathematical formulation of a parameter or risk; it depends on identified or hypothesized risk factors whose coefficients are determined by a statistical or heuristic analysis from historical or observed data with the use of r , as a basic reproduction rate, to timely and spatially predict the spread-speed of an emerging outbreak. spatial-temporal modeling of health events can be seen as the final stage of the analysis. it is different from statistical modeling. despite using risk factors, it considers the epidemic phenomenon as a whole, taking into account the spatial relationships between agents (hosts, vectors, reservoirs, and pathogens), between individuals, and relationships between individuals and their environment. this model is thus useful for understanding and anticipating the epidemics, and can be generally used to classify individuals in different states (susceptible, infected, sick healed, immune) and to model the major phenomena that can change the state of an individual. however, when a model takes into account many phenomena, it can quickly become very complex. the vast majority of models are simplifications of assumed reality. two broad categories of methods are usually developed in modeling: -a deterministic approach, based on differential equations whose coefficients are adjusted from observed data, or monitoring data from epidemics. in this model, one can introduce stochastic types of components in the coefficients, studying the variability of observed data. taking no account of spatial relationships is difficult in these models, which deal in general populations, not individuals. -a nondeterministic approach, which is based on agents whose behavior is described by expertly determined rules (multiagent models). the status of each agent is calculated at each time step, from its behavior, environment, and relations between the agent and all other agents. these models take into account a more realistic description of the phenomenon, near the complex system finely describing reality. they allow us to consider spatial relationships in each time step. these models require intensive calculation, and their use is made possible by development of the power of computer calculations. let us first honestly address the fundamental questions about epdimeics and preparedness: what did we learn from all the past epidemics, what will we remember in times of need? are we prepared for the worst of these hypothetic pandemics abundantly illustrated in the cinema and unfortunately sometimes overwhelmed when reality goes beyond fiction? certainly, we are not "globally" prepared, unfortunately, at that scale, the immense natural and human disparities do not permit it, but we do our best in our own societies. the concept of disease emergence, born only at the end of the twentieth century, is a societal marker, our desire to be on alert, understand and predict epidemics. ultimately, there are a few, but necessary and difficult goals to reach for the prevention and control of any epidemic, also these goals are part of the development of our societies, as well as for education, they become part of the wellbeing for all: first, beyond understanding transmission, is needed a clear understanding of the epidemiological pattern and the spread of a given disease, before it is too late; then, which is certainly one of the more complex and costly things to achieve, is having an efficient health system to respond to an epidemic and an operational network to respond at the regional and global levels; and last but certainly not a least, having identified funding for any public health emergency will be crucial to changing our world. perhaps, in a shrinking global community, after too many ebola virus disease outbreaks, we will learn and be prepared for future epidemic challenges? the progress made, mostly by computer sciences in the overall analysis of health data, should serve as a tool in the prevention of major epidemics. let us ultimately use our predictions of pandemic risk to meet and unite beyond the current frontiers of political and social wills. epidemic predictions in an imperfect world: modelling disease spread with partial data vie et mort des epidémies biological warfare and bioterrorism the history of the peloponnesian war (english trans les maladies en europe: équilibre et ruptures de la pathocénose faut-il encore avoir peur de la grippe galen and the antonine plague author(s) histoire de la pensée médicale en occident-tome , de la renaissance aux lumières smallpox and its eradication (history of international public health, no ). world health organization the smallpox pandemic of smallpox: , years from plagues to eradication: a dermatologic ailment shaping the face of society strategies for mitigating an influenza pandemic dengue, urbanization and globalization: the unholy trinity of the st century sars: an emerging global microbial threat predicting epidemic risk from past temporal contact data ebola control: effect of asymptomatic infection and acquired immunity shedding of ebola virus in an asymptomatic pregnant woman understanding the emergence of ebola virus disease in sierra leone: stalking the virus in the threatening wake of emergence perspectives on west africa ebola virus disease outbreak aedes alpobictus and the world trade in used tires, - : the shape of things to come? men, primates, and germs: an ongoing affair seewis virus: phylogeography of a shrew-borne hantavirus in siberia coevolution of rodent and viruses: arenaviruses and hantaviruses the arenavirus and rodent coevolution process: a global view of a theory bats worldwide carry hepatitis e virus-related viruses that form a putative novel genus within the family hepeviridae a novel rhabdovirus associated with acute hemorrhagic fever in central africa federal select agent program: select agent and toxins list pathogenesis of the viral hemorrhagic fevers viruses, plagues, and history: past, present and future yellow fever fact sheet n° . world health organization yellow fever in africa: estimating the burden of disease and impact of mass vaccination from outbreak and serological data the changing epidemiology of yellow fever and dengue resurgence of yellow fever in angola international health regulations in practice: focus on yellow fever and poliomyelitis yellow fever in africa: a disaster waiting to happen dengue/dengue hemorrhagic fever: the emergence of a global health problem delaporte ( ) rapp. au ministre de la marine the global epidemiology of infectious diseases, global burden of disease and injury series epidemiology of arthropod-borne viral disease the xxth century dengue pandemic: need for surveillance and research emergence of epidemic dengue/dengue hemorrhagic fever as a public health problem in the americas zur Ätiologie einer unbekannten, von affen ausgegangenen menschlichen infektionskrankheit isolation of genetically diverse marburg viruses from egyptian fruit bats virological and serological findings in rousettus aegyptia cus experimentally inoculated with vero cellsadapted hogan strain of marburg virus ebola virus circulation in. africa: a balance between clinical expression and epidemiological silence ebola and marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for africa the ebola epidemic: a global health emergency hantavirus infections : endemic or unrecognized pandemic hantaviruses: history and overview serological evidence for hantaan-related virus in africa sangassou virus, the first hantavirus isolate from africa, displays genetic and functional properties distinct from those of other murinae-associated hantaviruses past, present, and future of arenavirus taxonomy natural nidality in bolivian hemorrhagic fever and the systematics of the reservoir species driving forces for changes in geographical distribution of ixodes ricinus ticks in europe seroepidemiological studies of crimean-congo hemorrhagic fever virus in domestic and wild animals crimean-congo hemorrhagic fever virus: new outbreaks, new discoveries a systematic review of rift valley fever epidemiology - the chikungunya epidemic on la réunion island in - : a cost-of-illness study global health risk framework: pandemic financing: workshop summary african risk capacity. executive perspective: outbreak and epidemic insurance, new solution to an old problem. the rockefeller foundation from the ebola river to the ebola virus disease pandemic: what have we learned? using web search query data to monitor dengue epidemics: a new model for neglected tropical disease surveillance evaluation of internetbased dengue query data: google dengue trends biosurveillance enterprise for operational awareness, a genomic-based approach for tracking pathogen virulence bioinformatics for biodefense: challenges and opportunities biosurveillance of emerging biothreats using scalable genotype clustering optimizing biosurveillance systems that use threshold-based event detection methods biodefense oriented genomic-based pathogen classification systems: challenges and opportunities biosurveillance observations on biowatch generation- and other federal efforts: testimony before the subcommittees on emergency preparedness, response, and communications and cybersecurity, infrastructure protection, and security technologies, committee on house homeland security, house of representatives congress. house ( ) committee on homeland security. subcommittee on emergency preparedness response and communications., united states. congress. house. committee on homeland security. subcommittee on cybersecurity infrastructure protection and security technologies., united states. government accountability office: biosurveillance observations on biowatch generation- and other federal efforts: testimony before the subcommittees on emergency preparedness, response, and communications and cybersecurity, infra structure protection, and security technologies, committee on house homeland security, house of representatives acknowledgments w.a. valdivia-granda has been funded by the department of homeland security and the department of defense. we are greatfull to sarah cheeseman barthel, director, data acquisition & management metabiota, inc., for her review and input of the section on "global surveillance and data collection." key: cord- -r w milu authors: olaseni, abayomi o.; akinsola, olusola s.; agberotimi, samson f.; oguntayo, rotimi title: psychological distress experiences of nigerians during covid- pandemic; the gender difference date: - - journal: social sciences & humanities open doi: . /j.ssaho. . sha: doc_id: cord_uid: r w milu this study examine the psychological distress experience of nigerians during the covid- pandemic, across gender. from march , , to april , , this descriptive survey used a snowballing sampling technique to select -nigerians with an online semi-structured questionnaire detailing the impact of event scale-revised, generalized anxiety disorder – item scale, patient health questionnaire and insomnia severity index. gender had an insignificant difference in the level of insomnia (χ ​= ​ . ; df ​= ​ ; p ​> ​ . ), however, . % of males had sub-threshold of insomnia, . % experienced moderate insomnia and . % had severe insomnia; % females reported sub-threshold of insomnia, . % had moderate insomnia while . % had severe insomnia. also, gender had an insignificant difference in the measures of depression (χ ​= ​ . ; df ​= ​ ; p ​> ​ . ); . % males reported minimal depression, . % had mild depression, . % had moderate depression; . %– . % males had moderate to severe depression while, . % of the females had minimal depression, . % reported mild depression, . % had moderate depression, . %– . % had moderate to severe depressive symptoms. posttraumatic stress symptoms (ptss) has no gender difference among respondents (χ ​= ​ . ; df ​= ​ ; p ​> ​ . ); % of males reported partial ptss, . % presented clinical ptss, and . % males had severe ptss; while . % of females had severe ptss, % reported partial ptss and . % had clinical ptss. respondents reported insignificant gender differences on anxiety (χ ​= ​ . ; df ​= ​ ; p ​> ​ . ), while % reported moderate anxiety and % exhibited severe anxiety during the covid- pandemic in nigeria. findings revealed that nigerians experienced psychological distress during covid- pandemic. the government and stakeholders should initiate tele-mental health services to serve as alternative to traditional treatment to manage present and future pandemic psychological implications among nigerians. a great threat of a novel viruscoronavirus otherwise known as covid- pandemic rocked the entire world in the wake of the year . covid- which was first reported in december in wuhan china, declared as public health emergency of international concern in january and later a pandemic in march by the world health organisation (who) (web news, ; world health organisation, ). the threat is so strenuous that the entire world was placed on lockdown in the matter of social restriction such as on international and national transport links, market or business transaction, school and organisation activities, and all related social and religious gatherings. being a novel disease that is highly contagious, spreading fast across the world, and the fact that there is yet to be an established cure for it, the covid- pandemic has created a lot of panic in every part of the world. also, information and misinformation about such factors as those associated with the transmission of the virus, period of incubation, and impact on the socio-economic, political and psychological livelihood of people in the society put the general population at risk of mental health distress. in nigeria, there is no empirical finding (to the best knowledge of the investigators) establishing the impact of covid- pandemic on the mental health of the general populace. however, several studies especially in asia and europe (bao et al., ; brooks et al., ; kang et al., ; shigemura et al., ) have reported serious psychological distress experiences of members of the society in response to the covid- pandemic. considering its grave impact, the covid- pandemic has been likened to natural disasters , mass dispute, and war outbreaks (fiorillo & gorwood, ) . the present pandemic is, however, more devastating because unlike during a natural disaster or war outbreak whereby people can relocate or build a sophisticated defence system to minimize or escape any foreseeable negative impact, there is nowhere to run to escape the impact of covid- pandemic (olapegba et al., ) . the effect is far-reaching beyond a specific geographical location as the political and socio-economic structure of the whole world is disrupted and crashing, thus putting people more at risk of experiencing psychological distress (raviola et al., ) . it has also been argued that in periods of disease outbreaks, anxiety in the community can rise after the first death of a patient is being reported, also misinformation from media and increasing number of new cases can predispose people to serious psychopathology . kang et al. (kang et al., ) also opined that the present covid- pandemic will drastically increase global stress and mental health burden. according to xiang (xiang et al., ) , the experience of the ongoing covid- pandemic is triggering tension and a timely understanding of mental health is very essential for the government, health agencies and the public. recent studies affirm the high and huge level of psychosocial consequences of outbreaks like covid- on individuals, the general public, and the international community (hall et al., ; wang et al., ) . for instance, in the period of sars outbreak, many that were examined on the psychological consequence showed substantial psychological complications that were found to be related with young people and exacerbated blaming of self (sim et al., ) , while those older people who were females and highly schooled, displayed higher anxiety feelings for sars positivity, while the less educated had a moderate anxiety rate; those with known contact history with the infected individuals, perceived they have symptoms of sars and have more tendency to indulge in preventive measures against the disease (leung, ) . furthermore, the means of containing the pandemic such as; selfisolation, quarantine, social distancing, and treatment of infected persons can further pose a detrimental effect of psychological distress (fiorillo & gorwood, ; world health organisation, ) . specifically, the loneliness effect of reduced social interactions is a risk factor for several psychological disorders such as; anxiety, drug use, insomnia, major depression, and suicidal ideation especially among vulnerable populations like the elderly and those with health challenges. according to rubin et al. (rubin & wessely, ) , excessive quarantine tends to give rise to anxiety significantly, for multiple reasons; even the elevated anxiety may also trigger and initiate the implications for some related mental health issues. barbisch et al. (barbisch et al., ) had earlier pointed out the implication of confinement on the psychological well-being of the public, by identifying hysteria, rejection and dejection feelings, obsessive-compulsive symptoms and mood challenges as conditions that can lead to complicated health issues in the victims and the public. despite the devastating effect that dealing with highly contagious and threatening disease expose healthcare workers to in sub-saharan africa, a concern has been raised that the government in the region has not paid enough attention to the psychological distress implications of a pandemic such as a coronavirus on her healthcare workers (higgins, ) . in nigeria, it has been opined that despite financial aid and infrastructural support being received from both local and international organizations, the government pays little or no attention to the necessary psychological well-being of healthcare professionals on the frontline of combating coronavirus pandemic (guardian, ; web news, ) . concerning the aforementioned, it is noteworthy that seeking to devise a better approach to addressing the imminent and present psychological problems of people who witnessed the covid- outbreak is a necessity. this, therefore, calls for objective assessment of levels and patterns of possible psychological distress among the general population to inform necessary interventions. as at the time of data collection for this study, no study (to the best of knowledge of the investigators) existed that investigated the psychological impact of covid- on the general population in nigeria, therefore this study becomes very relevant. consequently, this study represents the first one examining the psychological impact of covid- among the general population in nigeria. this study aims to establish the prevalence of common psychological distress among the general public, and identify the specific pattern of occurring psychopathology among nigerians during the pandemic. to address the aim of this study, the following objectives were raised: . to examine the prevalence of insomnia outcomes among residents of nigeria among residents in nigeria during the covid- pandemic. . to investigate the prevalence of depression symptoms across categories of male and female residents in nigeria during the covid- pandemic. . to assess the prevalence of posttraumatic stress symptoms across male and female residents in nigeria during the covid- pandemic. nigeria during the covid- pandemic. this study utilised a cross-sectional descriptive survey research design that entailed collecting quantitative data on more than one case at a single point in time or simultaneously in survey research. the main variables of interest are depression, generalized anxiety, insomnia, and posttraumatic stress. this design was found applicable to describe the psychological distress experiences of nigerians during the covid- pandemic. a snowballing sampling technique was used in this study because data collection was conducted during a nationwide lockdown in response to the covid- pandemic which made it very difficult to physically access people at the time of data collection. an online semi-structured questionnaire was developed by using google forms, with a consent form appended to it. the link of the questionnaire was sent through emails, whatsapp, and other social media to people on the contact of the investigators. the prospective respondents were then encouraged to roll out the survey to as many of their colleagues as possible. thus, the link was forwarded to people apart from the first point of contact and so on. five hundred and two ( ) nigerians aged between years and years (m ¼ . , sd ¼ . ) participated in the study. the participants comprised ( . %) males, ( . %) females, while ( . %) did not disclose their sex. in terms of ethnic affiliations, the majority of the participants ( . %) identified with ethnic groups in the southern region of nigeria, while . % indicated they were from ethnic groups in northern nigeria, the remaining . % did not disclose any specific nigerian ethnic affiliation. in terms of religious affiliation, the majority ( . %) are christians, . % are muslims, while only . % practiced other religions, and . % of the respondents identified themselves with traditional religion. data on the marital status of participants showed that . % were married, . % unmarried, and . % were separated. finally, categorization based on the highest level of education, only . % of the participants had secondary school education, . % reported incomplete tertiary education, . % completed tertiary education, and the remaining . % had postgraduate education. data were collected via an online self-reported questionnaire designed by the investigators. the questionnaire contained five sections. the first section consisted of information assessing demographic attributes such as sex, age, religion, and marital status of participants. the second section contained the -item impact of event scale-revised (ies-r). the scale was developed to measure the subjective response to a specific traumatic event, especially in the response sets of intrusion, avoidance, and hyperarousal, as well as total subjective stress ies-r score. the ies-r is not meant to be diagnostic. the total ies-r score was divided into - (normal), - (mild psychological impact), - (moderate psychological impact), and > (severe psychological impact). weiss (weiss et al., ) affirmed the validity and reliability of the scale. cronbach's alpha . was established as the reliability coefficient for the scale in this study. in section three of the questionnaire is the generalized anxiety disorder -item (gad- ) scale (spitzer et al., ) consisting of questions assessing generalized anxiety disorder, focusing on the frequency of symptoms during the preceding -week period. the gad- requires approximately - min to administer and for each symptom queried provides the following response options: "not at all," "several days," "over half the days" and "nearly every day" and these are scored, respectively, as , , or . a score ranging from to is obtainable by respondents. scores of , , and are taken as the cut-off points for mild, moderate and severe anxiety, respectively. cronbach's alpha . was established as the reliability coefficient for the scale in this study. the fourth section contained the patient health questionnaire (phq- ). the phq- is a nine-item depression scale that has the potential of being a dual-purpose instrument to establish the diagnosis of a depressive disorder, as well as the grade of symptom severity (kroenke et al., ) . statements measuring depressive symptoms such as "little interest/pleasure in doing things" were rated from (not at all) to (nearly every day) by respondents as applicable to them over the past two weeks. phq- score can range from to . the scale has strong psychometric properties and has been widely used. cronbach's alpha . was established as the reliability coefficient for the scale in this study. the fifth section contained the insomnia severity index, a -item selfreport questionnaire assessing the nature, severity, and impact of insomnia. participants were required to rate their sleep condition in the last weeks as described by each item of the scale. questions on the isi cut across the severity of sleep onset, sleep maintenance, and early morning awakening problems, sleep dissatisfaction, interference of sleep difficulties with daytime functioning, noticeability of sleep problems by others, and distress caused by the sleep difficulties. the scale is responded to on a -point likert scale with a score ranging from to ; thus, yielding a total score ranging from to . the total score is interpreted as follows: the absence of insomnia ( - ); sub-threshold insomnia ( - ); moderate insomnia ( - ); and severe insomnia ( - ). previous studies have reported adequate psychometric properties for both the english and french versions (bastien et al., ) . cronbach's alpha . was established as the reliability coefficient for the scale in this study. this was an online study. participants with access to the internet were invited to participate in the study. participants with age more than years, able to understand english and willing to give informed consent were included. a link to the survey on google form was sent to all participants. on receiving and clicking the link, the participants got auto directed to the information about the study. a detailed informed consent form was attached at the beginning of the online questionnaire and consent was a prerequisite to continue in the survey. therefore, only individuals who gave their consent participated in the study. the data collection was initiated on march , and closed on april , . the sampling technique employed allowed the investigators to collect data from across various states of nigeria. five hundred and two ( ) correctly filled questionnaires were recovered through the google form and processed for statistical analysis. the collected data was analyzed using the spss package (version ) and graphpad prism (v . . ). the analyzed data respond to the four research questions stated in the early paragraph. the analyses include prevalence estimate analysis, and chi-square analysis was therefore presented. this phase presents the results and interpretation of data collected on the prevalence of psychological distress among five hundred and two ( ) residents in nigeria during the outbreak of the pandemic. the prevalent rate of psychological distress outcomes was reported among residents of nigeria across the six geopolitical zones. based on the exploratory process, outcomes of the evaluated psychological constructs were presented in the chart below (see charts - ). chi-square contingency chart (see chart ) revealed that there was no significant difference in the reported severity of insomnia among female and male residents in nigeria during pandemic (χ ¼ . ; df ¼ ; p > . ). however, prevalence estimates analysis revealed that majority of the male respondents ( . %) had no clinical insomnia, . % of the male participants reported sub-threshold level of insomnia, . % of the respondents had moderate insomnia symptoms, while . % of the male respondents presented severe clinical insomnia during the covid- pandemic. it was further reported that majority of the female respondents ( %) had no clinical insomnia symptoms, % reported subthreshold level of insomnia, . % had moderate insomnia symptoms, while . % of the female respondents presented severe clinical insomnia during the covid- pandemic. further analysis that aimed to reveal the prevalence of depression symptoms across categories of male and female residents in nigeria was tested using a contingency analysis of the graphpad prism (see chart ). chi-square contingency chart (see chart ) revealed that there was no significant difference in the reported severity of depressive symptoms among female and male residents in nigeria during pandemic (χ ¼ . ; df ¼ ; p > . ). however, prevalence estimates analysis revealed that majority of the male respondents ( . %) had minimal depressive symptoms, . % reported mild depressive symptoms, . % of the respondents had moderate depressive symptoms, . % had moderately severe depressive symptoms, while . % of the male respondents presented severe depressive symptoms during the covid- pandemic. it was further reported that majority of the female respondents ( . %) had minimal depressive symptoms, . % reported mild depressive symptoms, . % had moderate depressive symptoms, . % had moderately severe depressive symptoms, while . % of the female respondents presented severe depressive symptoms during the covid- pandemic. based on the study objectives, the analysis that aimed to reveal the prevalence of posttraumatic stress symptoms across male and female residents in nigeria was tested using a contingency analysis of the graphpad prism (see chart ). chi-square contingency chart (see chart ) revealed that there was no significant difference in the reported severity of posttraumatic stress symptoms (ptss) among female and male residents in nigeria during pandemic (χ ¼ . ; df ¼ ; p > . ). however, prevalence estimates analysis revealed that the majority of the male respondents ( . %) had no pts symptoms, % reported partial pts symptoms, . % presented clinical pts symptoms, while . % of the male respondents presented severe pts symptoms during the covid- pandemic in nigeria. it was further reported that the majority of the female respondents ( . %) had severe pts symptoms, % reported partial pts symptoms, . % had clinical pts symptoms, while % of the female respondents presented no pts symptoms during the covid- pandemic. further objective to explore the prevalence of anxiety symptoms among residents in nigeria during covid- pandemics was tested using prevalence estimate analysis of the graphpad prism (see chart ). chart revealed that there was no significant difference in the disparity of anxiety symptoms among residents of nigeria during the covid- pandemic (χ ¼ . ; df ¼ ; p > . ). based on chart , it was revealed that the majority of the residents in nigeria insignificantly had moderate anxiety symptoms during the covid- pandemic. in other words, % of the participants in the study had moderate anxiety symptoms (i.e. incapacitating level of anxiety), while approximately % of the residents exhibited severe anxiety symptoms in nigeria. the outbreak of deadly disease is not a new occurrence in nigeria; the country has faced so many outbreaks of emerging and reoccurring diseases such as malaria, avian influenza, ebola virus, hiv/aids, meningitis, lassa fever, tuberculosis, monkeypox and many more (nigeria centre for disease control, ) and yet, it thrived above all these outbreaks. for a country that has no recent serious prior experience with natural disasters such as tsunami and earthquake (hansen, ) , and infectious disease such as sars, the country and its occupants seem overwhelmed with the covid- pandemic. the novel covid- pandemic has brought along with it, innovation and changes that nigerians are not used to which can lead to psychological distress. nigerians are distinct people with a rich social culture such as; partying, hanging out and routine dropping off and picking up of children at school, termed "school runs", is a social activity and opportunity of networking for most parents. therefore, the lockdown, physical and social distancing, closure of schools and the imposition of the use of face/nose mask could serve as stressors among this population. also, amidst the fear and risk of contagion of the covid- , the changes in the day to day activities of so many nigerians would have caused the prevailing psychological distresses. the overall prevalence of insomnia indicated was % among the general public in nigeria ( . % severe insomnia and . % moderate insomnia), a little less than a quarter ( %) indicated experience of moderate depression to severe depression and a quarter ( %) of the population indicated experiencing symptoms of severe posttraumatic stress and . % indicated experiencing symptoms of clinical posttraumatic stress. on april , , the nigeria centre for disease control reported that nigeria has recorded confirmed cases of covid- and deaths in states and the federal capital territory (nigeria centre for disease control, ), this figure seems quite low in comparison to the figures reported in china and the global recorded death. the low reported confirmed cases (as at the time of data collection) may have culminated in the lower prevalence of depression reported (moderate depression . %, moderately severe depression . % and severe depression . %) among nigerians as against higher reported prevalence of depression due to covid- pandemic among chinese citizens (gao et al., ) . the researchers reported the prevalence of depression among general chinese citizens has . % and reported prevalence of depression among hospitalized patients in wuhan, china has . % (gao et al., ) . confirming the output of our study, clinical psychological scientists at the university of washington have requested the need to prepare for a possible clinical depression epidemic because of covid- (the conversation, ) . consistent with our study findings of the prevalence of psychological distress among the public in nigeria, wang, et al. (wang et al., ) reported prevalence of moderate or severe psychological impact of the covid- outbreak among the public in china and bo et al. (bo et al., ) reported that before discharge, most clinical stable covid- patients suffered from significant posttraumatic stress symptoms. importantly, the prevalence of posttraumatic stress symptoms during covid- was lower among chinese citizens; sun et al. reported . % posttraumatic stress symptoms and % in china hardest-hit areas (liu et al., ) , while the public in nigeria reported higher experience of posttraumatic stress symptoms ( %). the difference in prevalence between the two populations can be attributed to the direct experience of the covid- devastation by the chinese population at the early stage of the outbreak and the nigerian population observation of the event through mass media. the several misleading information on the social media relating to the covid- from its inception and the increase in confirmed cases in nigeria could have heightened the experience of posttraumatic stress symptoms of the nigerian population. adult females and even children (female) provide unpaid care in families (sandoiu, ) in nigeria, which ranges from cooking, washing, taking care of kids, and general cleaning of the house. due to the lockdown, stay at home mandate of the federal government and cleaning of surfaces mantra, most female household chores have been doubled or tripled in most cases and this can be distressing. there has been an upsurge in the issues of domestic violence against women and the girl child, which prompted amina mohammed (un deputy secretary-general) to call on all governments, civil society, and individuals to consider gender-based violence as a dominant issue of all domestic plans on covid- response (united nations, ). so many women in nigeria, especially those in abusive marriages and relationships have no escape because of the restriction of movements and lockdown in most states of the country (daniels, ) . against this backdrop, it was expected that females should indicate the higher experience of psychological distress but our study found no substantial variation between male and females' experiences on psychological distresses during covid- pandemic, though articles and studies have contrary opinions. women in eight countries across africa (nigeria not included) and asia were reported to have consistently self-reported higher sleep problems than men based on series of roles they play in families (stranges et al., ) , female more than their male counterpart were confirmed to be susceptible to insomnia (zhang & wing, ) and high posttraumatic stress symptoms (liu et al., ) . similar to our findings of % experience of insomnia (moderate to severe), a korean population reported an overall prevalence of insomnia symptoms of . % which included difficulty in initiating sleep, difficulty in maintaining sleep and early morning awakening but the symptoms were more prevalent in female than in male (la et al., ) . the similarity of the genders on their psychological distress during the covid- based on the peculiarity of the population can be attributed to a deep culture that has made women in nigeria believe that it is socially acceptable to be hit and discipline (standard, ; trust, ) , hence, they might have adapted to the situation at a significant level that it does not cause them psychological distress. in conclusion, our findings expose the prevalence of insomnia, depression and posttraumatic stress symptoms among nigerians during the covid- pandemic. though this study recorded no significant difference between the gender (male and female) experiences of insomnia, depression, posttraumatic stress symptoms and anxiety, the study result reported a relevant prevalence of outcomes of psychological distress among the general public in nigeria. the government of nigeria should make available, if not for all, psychological health services for survivors of covid- . the study does not involve larger numbers of nigerians to ascertain the generalizability of the current findings. it is also possible that outcomes would vary if measured over a thousand or more participants. some socioeconomic factors should have been included in this study to ascertain the comorbid factors that could aggravate psychological distress in the current pandemic among nigerians. finally, the issue of response bias, which is prevalent in self-report surveys could have influenced the result and considered a limitation to this study. considering the findings of this study, the following are suggested to enhance psychological wellbeing among nigerians during the pandemic period: . tele-psychotherapy means of managing psychological distress among the public should be adopted by stakeholders during a lockdown and infectious disease outbreak like this. this intervention has been found to be effective in treating disorders such as; anxiety, depression, suicide attempts, trauma-related problems, insomnia, etc in the face of a pandemic that strains health care resources (augenstein, ; national quality forum, ) . especially when face-to-face appointments are risky. . federal and state governments should initiate a bill honoring the telemental health services to manage present and future pandemic psychological implications. . healthcare stakeholders needed to collaborate with psychotherapists in the management of pandemic or disease outbreak to regulate residents' emotions and promote people's psychological wellbeing in society. . experts should start an awareness campaign on basic means of overcoming psychological distress on media and in communities generally in nigeria to foster mental healthiness. opportunities to expand telehealth use amid the coronavirus pandemic -ncov epidemic: address mental health care to empower society is there a case for quarantine? perspectives from sars to ebola. disaster medicine and public health preparedness validation of the insomnia severity index as an outcome measure for insomnia research posttraumatic stress symptoms and attitude toward crisis mental health services among clinically stable patients with covid- in china the psychological impact of quarantine and how to reduce it: rapid review of the evidence women are suffering domestic violence because of covid- the consequences of the covid- pandemic on mental health and implications for clinical practice mental health problems and social media exposure during covid- outbreak children are dying of preventable diseases all the time in africa the kikwit ebola outbreak: lessons hospitals and physicians can apply to future viral epidemics. general hospital psychiatry of the deadliest natural disasters ebola fight in africa is hurt by limits on ways to get out the mental health of medical workers in wuhan, china dealing with the novel coronavirus validity of a brief depression severity measure gender differences influence over insomnia in korean population: a cross-sectional study the impact of community psychological responses on outbreak control for severe acute respiratory syndrome in hong kong prevalence and predictors of ptss during covid- outbreak in china hardest-hit areas: gender difference matter ecological disasters and mental health: causes, consequences, and interventions creating a framework to support measure development for telehealth. th street, nw, suite a preliminary assessment of novel coronavirus (covid- ) knowledge and perceptions in nigeria development of a comprehensive, sustained community mental health system in a coronavirus: the psychological effects of quarantining a city how covid- affects women's sexual and reproductive health public responses to the novel coronavirus ( -ncov) in japan: mental health consequences and target populations psychosocial and coping responses within the community health care setting towards a national outbreak of an infectious disease a brief measure for assessing generalized anxiety disorder why fewer men are beating their wives accessed sleep problems: an emerging global epidemic? findings from the indepth who-sage study among more than , older adults from countries across africa and asia prevalence and risk factors of acute posttraumatic stress symptoms during the covid- outbreak in wuhan covid- could lead to an epidemic of clinical depression, and the health care system isn't ready for that cultural beliefs fuel domestic violence. archived from the original on september un backs global action to end violence against women and girls amid covid- crisis immediate psychological responses and associated factors during the initial stage of the coronavirus disease (covid- ) epidemic among the general population in china psychologist advocates increased palliatives to cushion lockdown effect the impact of event scale: revised advice and guidance from who on covid- timely mental health care for the novel coronavirus outbreak is urgently needed sex differences in insomnia: a meta-analysis supplementary data to this article can be found online at https:// doi.org/ . /j.ssaho. . . key: cord- - qvvkvk authors: shammi, mashura; bodrud-doza, md.; islam, abu reza md. towfiqul; rahman, md. mostafizur title: strategic assessment of covid- pandemic in bangladesh: comparative lockdown scenario analysis, public perception, and management for sustainability date: - - journal: environ dev sustain doi: . /s - - -y sha: doc_id: cord_uid: qvvkvk abstract: community transmission of covid- is happening in bangladesh—the country which did not have a noteworthy health policy and legislative structures to combat a pandemic like covid- . early strategic planning and groundwork for evolving and established challenges are crucial to assemble resources and react in an appropriate timely manner. this article, therefore, focuses on the public perception of comparative lockdown scenario analysis and how they may affect the sustainable development goals (sdgs) and the strategic management regime of covid- pandemic in bangladesh socio-economically as well as the implications of the withdrawal of partial lockdown plan. scenario-based public perceptions were collected via a purposive sampling survey method through a questionnaire. datasets were analysed through a set of statistical techniques including classical test theory, principal component analysis, hierarchical cluster analysis, pearson’s correlation matrix and linear regression analysis. there were good associations among the lockdown scenarios and response strategies to be formulated. scenario describes how the death and infection rate will increase if the bangladesh government withdraws the existing partial lockdown. scenario outlines that limited people’s movement will enable low-level community transmission of covid- with the infection and death rate will increase slowly (r = . , p < . ). moreover, there will be less supply of necessities of daily use with a price hike (r = . , p < . ). in scenario , full lockdown will reduce community transmission and death from covid- (r = . , p < . ). however, along with the other problems gender discrimination and gender-based violence will increase rapidly (r = . , p < . ). due to full lockdown, the formal and informal business, economy, and education sector will be hampered severely (r = . ). subsequently, there was a strong association between the loss of livelihood and the unemployment rate which will increase due to business shutdown (p < . ). this will lead to the severe sufferings of poor and vulnerable communities in both urban and rural areas (p < . ). all these will further aggravate the humanitarian needs of the most vulnerable groups in the country in the coming months to be followed which will undoubtedly affect the bangladesh targets to achieve the sdgs of and other development plans that need to be adjusted. from our analysis, it was apparent that maintaining partial lockdown with business and economic activities with social distancing and public health guidelines is the best strategy to maintain. however, as the government withdrew the partial lockdown, inclusive and transparent risk communication towards the public should be followed. recovery and strengthening of the health sector, economy, industry, agriculture, and food security should be focused on under the “new normal standard of life” following health guidelines and social distancing. proper response plans and strategic management are necessary for the sustainability of the nation. graphic abstract: [image: see text] electronic supplementary material: the online version of this article ( . /s - - -y) contains supplementary material, which is available to authorized users. performed is , which is tests/ million (iecdr ; worldometer ) . the number is one of the lowest in the world (table ) . it is predictable that during a pandemic, a humanitarian crisis may arise in a developing country like bangladesh. in most incidents, it will be the combined effects of a variety of shortages that will likely culminate in the worst outcomes (truog et al. ). this can lead to a shortage of basic needs including foods, goods, and services such as job loss, economic and financial loss, food insecurity, famine, social conflicts, and deaths. besides, an impact on the psychosocial and socio-economic and health and well-being of the citizens may be affected which we had shown in our previous study . while predicting all the subsequent impact of the covid- pandemic is challenging, early strategic planning and groundwork for the evolving and established challenges will be crucial to assemble resources and react in an appropriate timely manner. moreover, as the gob has lifted the lockdown without flattening the curve of the pandemic what should be the socio-economic management strategy for the government at this stage. this article, therefore, focuses on the public perception of comparative lockdown scenario analysis and the strategic management regime of covid- pandemic in bangladesh. as there is no such prediction on how long the situation prevails, the absence/lack of management strategy for an epidemiological and socio-economic emergency response might be a tool to assess the forthcoming situation under a set of specific scenarios. therefore, the objective of this study is to analyse long-term strategic management of the pandemic in three different lengths of scenarios in a resource-limited setting of the so-called lockdown of the country. the outcome can play a crucial role to formulate emergency response strategy to tackle the covid- considering the impact of current socio-economic lockdown for flattening the curve of covid- infection in bangladesh, this study identifies three scenarios of lockdown based on literature review, the lockdown situation in bangladesh, and the global lockdown practices in different countries. a total of statements were used to develop the questionnaire to understand the scenario-based impact assessment and management of covid- outbreak in bangladesh. we had taken expert suggestions, consultations, and cross-validation of statements for getting perceptions from a different group of people. we have used google form to prepare the questionnaire and conduct the survey online. an online database of target bangladeshi participants was prepared by reviewing different online social platforms of different expert groups in bangladesh, considering their current activities, responsibilities, and engagement related to covid- response in socio-economic sectors, planning, and policymaking. the prepared questionnaire with an introductory paragraph outlining the objective of the study was then shared through email, facebook, messenger, linkedin, and whatsapp with selective and relevant people considering the purposive sampling method. the questionnaire survey was conducted from april to april . a five-point ( - ) scenario-based likert scale was employed to test whether each respondent understands the statements described ranging from strongly disagree to strongly agree. the target population was general bangladeshi citizens age years and older. the inclusion of the respondents was different social groups like university faculty and scholars, government officials, non-government officials, development workers or practitioners, doctors, engineers and technologists, youth leaders and students, businessmen and industry officials, banking and finance corporates, researchers, and others. the answers to the survey questionnaires were the voluntary basis. a total of responses were recorded during the survey. according to the survey findings, the ratio of male to female participants was (n = ): (n = ). the composition of age groups was % ( - years old), % ( - years old), and % ( - years old), respectively. however, the average age of the respondents (n = ) was . years (sd ± . ). % of the youth leader was mostly students as they are the dynamic group in the society, also involved in covid- response, volunteer social works, job seeking, research and reporting activities. rest of the % participants belonged to various professions of doctors, civil service officials, development practitioners, non-government officials, expert panels, and university scholars. the descriptive statistics (e.g. frequencies, percentages, and student t test) were used to understand the participant's characteristics. applying the statistical package for the social science (spss) v. . , datasets were analysed via a set of statistical tools such as principal component analysis (pca), hierarchical cluster analysis (hca), pearson's correlation coefficient (pcc), multiple regression analysis (mra), and classical test theory (ctt) analysis. pca is one of the population data reduction techniques that indicate each potentiality of variables and their significance level in a huge sample size. before conducting the pca, kaiser-maier-olkin (kmo) and bartlett's sphericity tests were applied to confirm the necessity of this analysis. the results of the kmo > . (the kmo value was . in this research) and the significance of bartlett's sphericity test at p < . verified our datasets to be fitted for the pca ). the number of factors chosen was based on the kaiser's normalization principle, where the only factors with eigenvalues > . were regarded. from ctt analysis, cronbach's alpha was employed to test the consistency and reliability of the factor loadings in this study. cronbach's alpha validation values ranged from . to . (the cronbach's alpha reliability value was . indicating that these statements are appropriate in social science study (table ) (devellis ). the hierarchical cluster analysis (hca) is a crucial means of identifying relationships among all socioenvironmental variables. the hca assists to classify a population into different groups based on the similar characteristics of a set of the dataset that may show causes, effects, and or the source of any undetected socio-environmental crisis. furthermore, hierarchical clustering was adopted to determine the possible number of clusters. the one-way anova test was conducted to confirm the significant differences in the variance at p < . . participants were informed of the specific purpose of the study. participants' consent was taken before the survey and they remained anonymous. the survey was completed only once, and the survey could be completed/terminated whenever they wished. the survey content and procedure were reviewed and approved by the department of public health and informatics, jahangirnagar university. reductions of covid- pandemic have been linked with the cessation of public transport, educational institutions, the closing of entertainment and business centres, and the prohibition of public meetings. averagely, cities that carried out control measures of lockdown within the first week of the outbreak reported fewer cases compared to the cities which started control later (tian et al. ) . vietnam, the communist country bordering china with a population of million, has been an under-reported low-cost success story of the pandemic, which has had just coronavirus cases and no deaths due to strong public health systems, good governance and transparent communication, strict quarantine approach, and contact tracing. from the first-known international cases on january , vietnam quarantined anyone who arrived from the high-risk area and closed its porous -km border with china to all but essential trade and travel. in february, it quarantined more than , people in the son loi village due to infections. it also closed all schools, colleges, universities, and all other educational institutions beginning in february. on march , the vietnamese government suspended all foreign entries (wef a). it also decided early on to impose a -day quarantine on anyone arriving in vietnam from a high-risk area. on april , vietnam eased its lockdown effort. unfortunately, in the european region such as worst-affected italy, france, and uk, the region in the americas such as the usa and now brazil experienced most deaths due to the failure to understand the disease and keep continuing their activities such as travelling and tourism which spiked the death rates, or delayed lockdown efforts (table ). the case of new zealand is interesting in the sense that it pursued an eradication tactic historically based on a mitigation model and focused on slower arrival of the virus, followed by a range of measures to flatten the curve of cases and deaths (cousins ) . the measures include increased testing, screening, strict quarantine of the infected person, contact tracing, and surveillance. the same measures have been adopted by south korea, taiwan, and many successful countries. luo ( ) , of singapore university of technology and design (http://www.sutd.edu. sg) forecasted using a data-driven model that by may , % of the infection case will end, while % will end by july for bangladesh. however, the forecast does not seem to be valid considering the present context in bangladesh. at this background, a scenario-based assessment under different assumptive situation considering the socio-economic and cultural attitude of the country could better identify the impacts. the later section of the article mainly focused on the different scenario and their possible management and their way forwards. in our study, we have considered global lockdown practice, country situation analysis, and expert suggestions to set three scenarios for impact analysis and possible management strategies which are: lockdown scenario : withdraw the existing partial lockdown (ls ) lockdown scenario : continue the existing partial lockdown (ls ) lockdown scenario : full lockdown/shutdown with an exit plan (ls ) a total of scenario-based statements were set, and perception-based statistical analysis was performed. the descriptive statistics are presented in table , which exhibits the percentage, mean, and standard deviation (sd), describing the responses of participants to the related scenarios for all statements from each of the respondents and the direction of each statement in the studied survey datasets. sect. . - . discusses the impacts of different lockdown scenarios. considering the withdrawal of existing partial lockdown, the results of ctt analysis and the corrected inter-item correlation analysis reveal that eight statements have low corrected item-total correlation values (< . ). this includes, people will start moving towards table (continued) table (continued) regular life (ls s : . ); massive movement and a mass gathering of people will be started again (ls s : . ); community transmission of covid- will increase due to people's movement and mass gathering (ls s : . ); and the number of infected populations will increase (ls s : . ). bangladesh is entering into this scenario without having any signs of flattening the infection curve. from pearson correlation analysis, a strong significant positive relationship was observed between people will start moving towards regular life (ls s ) and the formal and informal economic activities will be started (ls s ) (r = . , p < . ) ( table ) . linear regression analysis reveals that the community transmission of covid- will increase due to people's movement and mass gathering (ls s ) as people will start moving towards regular life (ls s , p < . ), and crime will rise and more people will die (ls s , p < . ) exhibited a statistically significant high correlation with the number of infected populations will increase (ls s ) ( table ). in addition, more unemployment and loss of livelihood (ls s ) and more people will die (ls s ) statistically pose a significant positive impact on an irreversible loss to the economy (p < . ) of bangladesh. from ctt analysis, continue the existing partial lockdown (ls m : . ); limited people's movement will enable low-level community transmission of covid- (ls s : . ); infection and death rate will increase slowly (ls s : . ); increased facilities to the healthcare system for covid- treatment will be able to provide health services to the infected peoples (ls s : . ). from pearson correlation (table ) , a significant positive relationship was found between the limited people's movement will enable low-level community transmission of covid- (ls s ) with the infection, and the death rate will increase slowly (ls s ) (r = . , p < . ). also, there will be less supply of basic products for daily use (ls s ) which posed a significant relationship with the price of most of the basic products will be higher than usual (ls s ) (r = . , p < . ). from the linear regression model (table ) , the association between dependent statements limited people's movement will enable low-level community transmission of covid- (ls s , r = . , p < . ) with poor people will suffer from food and the nutritional deficiency (ls s ), and gender-based violence will increase (ls s ). based on management scenario , massive awareness and enforcement of proper lockdown and quarantine initiatives were strongly associated with limited people movement will enable low-level community transmission of covid- (ls s , p < . ). from the ctt analysis, among statements, the corrected inter-item correlation analysis showed that only one statement has low corrected item-total correlation values (< . ). this adds existing with increased facilities for covid- in the health system will be able to provide health services to the infected people (ls s : . ). the highest interitem correlated value is the loss of livelihood and the unemployment rate will increase due to business shutdown (ls s : . ), while the lowest value is the number of infections and death will be limited (ls s : . ). in the case of management of scenario , inter-item correlated values are more than . . the high inter-item correlation was observed in the synergy with government, law enforcement agencies, and private sector initiatives (ls m : . ) and long-term planning and implementation of policies regarding covid- , psychosocial, and socio-economic loss (ls m : . ). according to the results of the pearson correlation, there was a statistically significant correlation among scenario where gender discrimination will increase due to covid- outbreak with gender-based violence will increase rapidly (r = . , p < . ). besides, extremely limited people's movement will reduce the risk of community transmission of covid- with the number of infection and death will be limited (r = . , p < . ). for management purposes, synergy with government, law enforcement agencies, and private sector initiatives with coordinated emergency relief support (r = . , p < . ). also, microfinance support to small and medium enterprises is required for recovery (ls m , p < . ). for management strategies of scenario , deep analysis of the situation should be carried out and go for full lockdown with relief support to the poor and most vulnerable are urgently needed for decision-making in the county due to the rapid community transmission of covid- (p < . ). first of all, the government should come up with a comprehensive strategic plan accompanied by non-governmental and social organizations and law enforcement to analyse the spread of the virus, identifying the most vulnerable hosts, properly tracked the movement of general people, precise estimation of economic losses from different financial and industrial sectors, educational diminutions and professional and informal employment disruption to picture an integrated scenario of the current situation and future predictions by which the revival of the negative aspects of the country could be managed. there must be two types of the strategic plan on under the category of the emergency response plan (short-term) by ensuring basic supplies to all citizens who are in real needs, motivate and/or force the people to abide by the covid- guidelines by the gob and who, prepare a complete but robust list of vulnerable population in terms of covid- spreading, co-morbidities, and economic stress, activate all the local wings of the gob such as local government representatives at the village level, and construct a covid- response task force to monitor and handle the country situation through application of information and communication technologies (ict). the government should implement those plans with proper timing, transparency, and resources. the gob has already been taking a lot of initiatives to tackle covid- pandemic, but there seems lacking proper risk assessment and weak coordination among stakeholders from medical to social welfare. another plan must be focused on the reconstruction or rebuild (long-term) and must follow the guidelines of the sendai framework. the sendai framework for disaster risk reduction - recognizes health at the heart of disaster risk management (drm) at the global policy level (wright et al. ). this sendai framework has given the rise of the health-emergency disaster risk management (health-edrm) framework an umbrella term used by who ( ). health-edrm thus refers to the "systematic analysis and management of health risks, posed by emergencies and disasters, through a combination of ( ) hazard and vulnerability reduction to prevent and mitigate risks, ( ) preparedness, ( ) response and ( ) recovery measures" (djalante et al. ). this also includes build back the healthcare sector, industrial sector, education, agriculture, research, environment, and finance. however, deep research complied with massive surveillance could help in making decisions whether the lockdown must be further carried on or not and this must have to be based on evidence. miscommunication and miscalculation of the strategy may trigger worsen the situation. communicating the disease risk in the local language is also necessary to increase awareness about the diseases. moreover, in sects. ( . . - . . ) we have analysed emergency management issues including short to medium-term measures as well as long-term management strategies of covid- pandemic lockdown scenarios in bangladesh based on our research outcomes. "lockdown" is an unfamiliar word or term to the people of bangladesh. according to scenario , a partial lockdown is a hoax. people recommended to use a more familiar term "curfew" (legal section ) to maintain strict and there is no alternative to reduce covid- transmission. in bangladesh, section of the penal code prohibits assembly of five or more people, holding of public meetings, and carrying of firearms and this law can be invoked for up to two months (minlaw/gob ). this law could have been a much more effective strategy to contain the infection. in total, . % of the participants agreed that community transmission of covid- will increase due to the people's movement and mass gathering, . % agreed to continue the existing partial lockdown, whereas approximately % of respondents agreed that deep analysis of the situation is required and go for full lockdown with the relief support to the poor and the most vulnerable. overall, the participants had a positive view about lockdown scenario to possibly spread out of covid- at the community level. many people expressed their disappointment towards the extreme corruption of the healthcare sector and that it has collapsed before the covid- pandemic. respondents advocated the government to consider biomedical waste management for reducing further environmental transmission and that efficient incinerator to be built for hospital waste management. however, the responders also suggested the government to sustain the retail and wholesale kitchen market/bazaar of any area maintaining the health guideline and social distancing. this approach could have positive feedback as already experience in different upazilas in bangladesh with the help of local administrative authorities, magistrates, and police forces. after the days of the partial lockdown, the federation of bangladesh chambers of commerce and industries recommended the opening of the industrial sectors with some guidelines (fbcci ). moreover, the fbcci taskforce demanded the covid- incentive financial package in a more gettable way from the gob. it could be a very crucial decision to be taken considering the covid- contagions and the business development to protect the exports. to maintain livelihood, industrial workers resumed their work from april . however, the gob weakened the lockdown and resumed the industrial activities without proper guidelines or the scientific basis for such a risky decision. the question is why the gob was in hurry to weakening the lockdown and withdraw it without eradicating the disease? predictably, there might be a strong business/financial association to withdraw the lockdown when life and livelihood matters for the poor and middle-class people and to run the country's economy. although gob provided healthcare guidelines and social distancing during work, the infection rates surged significantly among the workers in the industrial zones. most of the covid- clusters are majorly distributed in dhaka city, chittagong city, narayanganj, cumilla, gazipur, and the peripheral cities (iedcr ; tbs news b). finally, this study confirms that the withdrawal of the partial lockdown will not become positive in terms of covid- management in bangladesh, because still, we do not have enough evidence even after the days of lockdown that the transmission is reducing from the peak. overall, the participants had a positive view about lockdown scenario to stop/slow down the spreading out of covid- pandemic in bangladesh. in total, . % of respondents in this study agreed that existing health facilities will not be able to provide adequate services to the number of covid- patients due to limited community transmission, while . % strongly agreed that there will be a need for emergency food and financial support to the poor communities. about . % strongly agreed that emergency relief to the poor communities in both urban and rural areas should be provided ensuring transparency. around million people, or . % of the population, live below the poverty line and based on the current rate of poverty reduction, bangladesh is projected to eliminate extreme poverty by (chaudhury ). yet, as covid- pandemic hit the country within weeks poverty rate in bangladesh rose to . % as % of family incomes fell (the financial express a). so, it was the choice between life versus livelihood (hussain ) . the poor community always lacks food and nutrition due to the injustice and corruption by the local or regional level of political stakeholders in bangladesh. by nature, people of bangladesh are quite unaware and kind of ignorant or does not like to abide by rules. moreover, the public is not confident somehow with the administrative decisions, policies, and their implementation of covid- emergency response such as lockdown on their livelihoods. there was also a lack of coordination among the different government stakeholders to tackle emergency healthcare and crisis management in the field. for instance, people usually made different excuses to go outside and a regular crowd was common in the kitchen market, streets, and small bazaars. only the government, semi-government, autonomous institutes/organizations, and educational institutions were maintaining the rules/guidelines. this situation is well visualized in different mass media that people are in movement for relief, road blockage, corruption by the government representatives, mismanagement in relief distribution, biases to party supporters, bureaucratic administrators to look after the response activities, and so on. likewise, the potential danger of covid- pandemic from the very beginning has been overlooked by the people due to the presence of misinformation in the social and mass media that it was general flue, and that the virus cannot infect in a humid country like bangladesh. so, the government should try to implement a stringent policy of risk communication and media communication during this emergency to the most vulnerable communities. the vulnerable groups such as disable and disadvantaged persons, young children and orphans, and aged citizens should be taken under protection for their well-being (undp a). right now, doctors, bankers, grocers, police, and armed forces are the most vulnerable profession to the covid- infection. until may , % doctors, % nurse and % frontline healthcare workers were covid- -infected. of the infected, police personnel had so far died, while more than others are in either isolation or in quarantine (the daily star ). although the extension of partial lockdown was not a solution in bangladesh, it could have been an effective option continued to slower the infection rate. the lockdown should have been partially continued with necessary financial support for the vulnerable. it would have been a crisis for a short time, but it would be a saviour for the future (shammi and bodrud-doza ). however, to run the economy, the hotspots of the infection and the cluster areas could remain lockdown, while economic activities could have maintained by strongly abiding public health guidelines and social distancing. moreover, for the next couple of years, it will be extremely hard for the country especially as far as the financial issues are concerned to achieve the current development as well as sdg targets and reaching to middle-income countries (undp a). gob should declare the delayed beginning of its th five-year national plan due to the covid- pandemic as a large part of it seems to be irrelevant at this stage, according to his proposals (the financial express b). increasing surveillance as well as the reallocation of the budget, the distribution of direct cash, and private sector engagement could be some of the options to alleviate the crisis. in total, . % of the respondents in this study agreed that due to full lockdown, the formal and informal business, economic and education sector will be hampered severely. . % agreed that the poor and vulnerable communities both in urban and rural areas will be affected severely. for management purposes, % of the respondents thought that coordinated emergency relief support is required. overall, the respondents had a positive viewpoint about lockdown scenario due to the covid- outbreak in bangladesh. if we have no other options, a strategic plan and policy should be taken for the revival of the health sector, economy, and education. it is speculative that a full lockdown might end up with famine and starvation. according to the world bank report ( ) prolonged and broad national lockdowns will bring a negative growth rate of the economy in bangladesh and other south asian countries in due to the covid- pandemic. this negative growth rate will continue in with growth projected to hover between . and . %, down from the previous . % estimate. a more serious issue that will arise due to the progress of the pandemic is the rate of suicide as a long-term effect on the vulnerable population due to fear and economic hardships (mamun and griffiths ) . preventing suicide and counselling mental health issues are therefore be considered by the authority (gunnell et al. ) . moreover, the authority should take proper steps to meet the basic emergency services and maintain the basic supply-demand of the daily needs of urban and rural people by transporting the crops and vegetable production from the farms. due to the lockdown, the farmers should not face any crop loss and they should be also brought under the financial and other stimulus plans so they can continue their productions for the future. if the needed government should give them free seeds, fertilizers, electricity for irrigations, and water and other incentives such as no-interest agricultural loans for future food security. the government already declared a financial recovery package with a clear disparity towards the agricultural sector. the financial stimulus package mainly focused on large and export-oriented businesses such as the readymade garment sector (rmg). it seems that this package has arrived a little earlier without any participatory strategic assessment. a strong collaborative need-based assessment is required to tackle the short-term and long-term needs to properly distribute the stimulus package. in this emergency response, the local government must have to come forward with full strength and capacities to implement the work plan for the gob. for overall relationship assessment for effective management of policy implications, governance, and developmental effects, pca (fig. ) , cluster analysis (fig. ) , and pearson correlation (table and supplementary table ) significantly show the relationships. pca showed a significant level of controlling factors in bangladesh covid- pandemic and how these statements are associated with the various scenarios (table ) . nine principal components (pcs) were originated based on standard eigenvalues (surpassed ) that extracted . % of the total variance as outlined in table . however, before pca applying in the tested data, the kaiser-meyer-olkin (kmo) and bartlett's tests of sphericity were conducted to appropriateness for this study. the findings of the kmo value in this research were . (> . ), the confidence level of bartlett's sphericity (bs) test was zero at p < . , suggesting the tested data were fit for pca analysis. the scree plot was used to identify the number of pcs to be retained to the understanding of the inherent variable structure (fig. ) . the loading scores were classified into three groups of weak ( . - . ), moderate ( . - . ), and strong (> . ), respectively (liu et al. ; islam et al. ) . the pc (first) explained . % of the variance as it covered a significance level of strong positive loading of the lockdown scenarios and management in bangladesh (ls s : . and ls s : . ). similarly, moderate positively loaded of the lockdown scenarios in bangladesh (ls s : . ls s -s : . - . ). the pc (second) explained . % of the total variance and was loaded with moderate positive loading of lock drown scenarios (ls s - : - . and ls s : . ). the pc (third) elucidated . % of the variance and was strong positively loaded of massive awareness and enforcement of proper lockdown and quarantine initiatives (ls m : . ) and provide emergency relief to the poor communities both in urban and rural areas ensuring transparency (ls m : . ). furthermore, management scenario and scenario were observed moderate positive loading of pc (ls m : . ; ls m : . , ls m : . and ls m : . ). the pc (four) accounted for . % of the total variance and was strong positively loaded of poor people who will suffer food and the nutritional deficiency (ls s : . ) and moderately loaded in scenario (ls s -s : . - . and ls s : . ). the pc (five) explained . % of the variance and was strong positively loaded of deep analysis of the situation and continue this existing partial lockdown (ls m : . ) and with moderately loaded in the management scenario (ls m : . and ls m : . ). pc (six) accounted for . of the total variances and were strong positive loading of existing with increased facilities for covid- in the health system will be able to provide health services to the infected peoples and number of infection and death will be limited (ls s : . and ls s : . ) and with moderately loaded of very limited peoples movement will reduce the risk of community transmission of covid- (ls s : . ). pc (seven) explained for . % of the variance and was strong positively loaded with gender-based violence will increase (ls s : . ) and gender discrimination will increase (ls s : . ). pc (eight) was responsible for . % of the variance and was strong positively loaded with people will start moving towards regular life and formal (ls s : . ) and informal economical activities will be started (ls s : . ) and moderate positively loaded of massive movement and a mass gathering of people will be started again (ls s : . ). cluster analysis (ca) further recognized the total status of scenario variations and how these scenarios influence the socio-economic and development impacts (fig. ) . all the statements were categorized into five major classes: cluster (c ), cluster (c ), cluster (c ), cluster (c ), and cluster (c ). c consisted of five sub-clusters of c -a, b, and c; c -a composed of an irreversible loss to the economy and more people will die (ls s -ls s ) c -b comprised of community transmission of covid- will increase due to people's movement and mass gathering and panic will rise in the mass communities (ls s -s ). c -c is comprised of the possibility of the full lockdown of the whole system again and no basic services will be available (ls s and ls s ). c consisted of three sub-clusters of c -a, and b. c -a consists of continue the existing partial lockdown and deep analysis of the situation and go for full lockdown with relief support to the poor and most vulnerable (ls m -m ) c -b consists of people will start moving towards regular life and massive movement and a mass gathering of people will be started again (ls s -ls s ). c consisted of three sub-clusters of c -a, b, and c. c -a contained an existing increase in the health facilities involving private sectors and implement inclusive sustainable quick plan and policies to revive the economy and employment (ls m -m ). c -b consisted of lack of support and improper management will lead to the psychosocial and socio-economic crisis and long-term planning and implementation of policies regarding covid- , psychosocial, and socio-economic loss (ls s and ls m ), while c -c composed of continuous situation analysis of disease outbreak and implement the full lockdown with relief and basic support for human survival and loan support for business and economic recovery (ls m -m ). cluster consisted of three sub-clusters of c -a due to full lockdown, the formal and informal business, economic, and education sector will be hampered severely, loss of livelihood and unemployment rate will increase due to business shutdown, and poor communities in both urban and rural areas will be affected severely (ls s - ); c -b supply and access to basic daily products in urban areas will be reduced drastically, the extreme need for relief and financial support in the urban and rural communities will increase, and people will be involved with conflict and crime to access the basic needs (ls s - ); and c -c there will be less supply of basic products for daily use and price of most of the basic products will be higher than usual (ls s -s ). c -d indicates poor people living from hand to mouth will be severely affected and the formal education system will be hampered. c consisted of two sub-clusters of c -a, b, and c. c -a contained gender-based violence will increase and gender discrimination and violence will increase ls s and ls s . c -b comprised of limited people's movement will enable low-level community transmission of covid- and infection and death rate will increase slowly (ls s -s ). c -c contained limited people movement will reduce the risk of community transmission of covid- and the number of infections will be limited ls s -s . the covid- pandemic has the most effects on vulnerable populations, ranging from good health and well-being (sdg ) to quality education (sdg ) worldwide. disruptions in the routine health care, poverty, and access to food and nutrition will culminate into unavoidable shocks and health system collapse which will increase child mortality and maternal deaths as well as many unwanted deaths (roberton et al. ) . the crises in achieving clean water and sanitation targets (sdg ), weak economic development and the absence of decent jobs (sdg ), overall inequality (sdg ), and above all, no poverty (sdg ), and food insecurity (sdg ) will be aggravated in many developing countries. the world bank reports that about million people will be forced into poverty by the crisis (wef b). according to undp ( b), revenue losses in developing countries are estimated to reach $ billion. the losses would be consequences of the education, human rights, and, in the most extreme cases, fundamental food security and nutrition, with an estimated % of the global population not having access to social protection. wider socio-economic effects will likely continue for several months to years across the world which will also significantly impact the economy of bangladesh. global food security will be hampered as one-third of the world's population is in lockdown (galanakis ) . both the import of important goods and exports related to the readymade garment sector and others likely will be affected for income and employment. financial protection during outbreak matters. at the initial stage of the covid- epidemic, out-of-pocket expenditure posed a substantial financial burden for the poor populations with severe symptoms, even for those under coverage by the social health insurance scheme (wang and tang ) . people marginally above the poverty level particularly low-income families, daily and informal low wedge earners, ethnic community groups, people with disabilities, and returnee migrant workers are already started falling below the poverty line due to loss of income and employment. brac an international bangladeshi ngo survey report confirmed to increase a % rise in poverty amidst the covid- pandemic (brac ). the intake of foods, vegetables, and herbs can boost the immune system against the infection disease, while it can stimulate the transmission through the food chain (galanakis ) . again, the lack of food will rise to malnutrition, hunger, and famine. approximately , million people worldwide will be suffering from acute hunger projected by the un world food programme (wef c). ready-made garment (rmg) sector is going to suffer a serious shortfall as until march , orders of rmg products from garment factories worth us$ . billion was cancelled. this is the sector where almost million low-income people-of whom over % are women-work and another similar number of people indirectly depend on the downstream and upstream services required by the rmg value chain (dhaka tribune a). as the lockdown continues to ensure public health and safety, many rmg workers already lost their jobs and did not receive their salary of the previous months, some of them have been sacked already. food security and social and economic recovery package of the government should focus on immediate response during the lockdown period and outbreak and post-lockdown support mechanisms. in this condition, middle-income families are relying on their savings available. the negative coping mechanism includes skipping meals and nutrition and distressing the whole family. in the prolonged lockdown scenario, they need government and other support measures to continue their lives under lockdown. due to lockdown, the agricultural products in the urban areas are selling at a high price, while the farmers are not getting the fair price of the product in agricultural districts. it was due to the proper decisions and policy of the gob that aman paddy was timely harvested ensuring the safety of migrant workers. otherwise, it would have likely imposed a bigger social and economic implications such as heavy rainfall triggering natural flash flooding. moreover, due to the lockdown transport of animal, poultry and fish feed are hampered. likewise, due to the closure of local restaurants and hotels, the market demand for eggs and chicken had lowered. all this will likely impose further impacts on food production and crop supply chains. to protect the country from famine, the bangladesh government should consider the stimulus package for the farmers with % agricultural loan to continue cropping and agricultural production. receiving education has stopped for most of the students in bangladesh. the government of bangladesh postponed all academic and public exams until the indefinite period, considering the growing public concern. distance learning education of the national curriculum through air transmission in the national tv had started though. while urban children can attend virtual classes through the internet, rural and marginalized children are deprived due to limited resources. students from marginalized backgrounds particularly with disabilities will lose out more on their education. considering this, gob should prepare special educational package including counselling for marginalized and disadvantaged students. the severe infection of covid- pandemic has devastated the healthcare systems across the globe from a shortage of n masks, and personal protective equipment (ppes) for the healthcare workers and putting occupational health risk, allocations of ventilators, icus, and hospital beds to a patient who can benefit most from treatment while letting the older persons to death. the peaked disparity between supply and demand for healthcare properties raised a normative query of equitable resource allocation during the covid- pandemic (emanuel et al. ). thousands of healthcare workers have already been infected worldwide (gan et al. ) , and the administrative and managerial departments are likely to place increased burdens and stresses on the frontline healthcare workers (willan et al. ). bangladesh has no exceptional scenario. on may , gob lifted its partial lockdown after days of general holidays. the gob claimed the withdrawal of lockdown as a test for next days from may to june , but it was decided without having the designated committees' opinion rather only considering the economic considerations. the gob is planning to divide areas around the country that are affected by the covid- into three zones based on colour as red, yellow, and green indicating the severity of cluster infections and to prevent the disease spread (the daily star ). at present bangladesh is at number considering the infections and mortality from covid- (worldometer ) . the overall attack rate among the bangladeshi population is . / million and more than % positive cases have been identified in the recent days reported in the who situation report on th may (who c). among the countries of india, pakistan, nepal, bhutan, sri lanka, thailand and vietnam, bangladesh is at the bottom in terms of the number of covid- tests done per million population (newage ) . the maldives and bhutan are on the top of the list with each conducting , tests per millions of people (tbs news c). the testing laboratories are situated in the urban metropolitan areas and often due to fear and social stigma the patients do not want to test. moreover, the incidences of a false negative in one laboratory while positive in another laboratory had been reported in mass media. in addition, the mortality rate from covid- infection remains a puzzle which just cannot be explained by the gdp of the country, strength of healthcare governance and availability of equipment like icu or ventilators. the trend of screening and testing ( / million population) and contact tracing the covid- patients in bangladesh is not quite enough to conclude that the curve is flattening, or the peak of the curve has reached. thus, at this point, the database does not seems to be robust and it could be chaotic from the epidemiological point of view. after the lockdown is withdrawn, it was speculated that the number of infections will increase as the life and livelihood needed to sustain. on st may , bangladesh recorded deaths from covid- and new infections (iedcr ). at this stage, gob should increase the icu numbers and strengthen the healthcare departments by recruiting more doctors, nurses, and technicians. rapid testing, screening and diagnosis should be increased which was the advice of who from the beginning. along with isolation, clinical management, and infection prevention and risk communication should be continued to the public. the gob should engage public and private hospital authorities for the treatment of covid- infected patients and resume treatment of other critical-care patients who are being deprived of any treatment at present. moreover, as the infection from dengue is also rising government should take special emphasis for dengue treatment and management also. in fig. we have outlined the overall impact and management analysis of the three scenarios: scenario , scenario , and the scenario after the withdrawn of partial lockdown. community health workers can support pandemic preparation earlier to the epidemics by increasing access to the healthcare services and the healthcare products within the communities. they can communicate disease risks and increase awareness in the comparative lockdown scenarios with impact and management analysis for bangladesh due to covid- pandemic respected area in cultural language whereas reducing the weights of the formal healthcare systems. community healthcare workers can also contribute to pandemic preparedness by acting as community-level educators and mobilizers, contributing to surveillance systems, and filling health service gaps (boyce and katz ) . it is critical to detect cluster surveillance of covid- to better allocate resources and improve decision-making as the outbreaks continue to grow in different districts of bangladesh to improve resource allocation, faster testing stations, stricter quarantines and city/block lockdowns as well as travel bans (desjardins et al. ) . it is predictable that environmentally the decrease in air pollution reduces preventable communicable and non-communicable diseases such as covid- (dutheil et al. ) . likewise, ma et al. ( ) mentioned that the warmer season and lockdown activities were the keys to reduce exposure to novel coronavirus on humans in china. although the relationship between the infection rate and climatic variables is not confirmed in bangladesh, as the partial lockdown failed and continued, the number of infections over the past days indicates that gob should have ensured proper implementation of the lockdown scenario with limited public movement in the hotspots, resulting in lower community transmission of the virus and a slower death rate, while continuing economic activity with strict guidelines. gob was looking forward to exiting from partial lockdown beginning of may, yet no specific exit plans were executed by the government which should be scientifically rational and practically achieved. the exit plans from the lockdown should have been well communicated to the public ensuring transparency. without ensuring safety and security the partial lockdown was withdrawn. public transportation started on may without maintaining any health guideline (tbs news d). coordination among the different stakeholders of the government is necessary, along with increased surveillance and resource allocation to the needy ones, to ensure supply of daily necessities, control price hikes, and reduce the loss of livelihood and unemployment. moreover, very recently cyclone amphan hit bangladesh on may , living the coastal districts flooded and in the mayhem. preliminary losses were estimated to be worth bdt , crores (dhaka tribune b). at this stage detection of covid- hotspots by increased testing facilities all over the country must be ensured. the poor and vulnerable communities always lack food and nutrition due to injustice and corruption by local political stakeholders. the vulnerable groups, such as disabled and disadvantaged persons, young children and orphans, and elderly citizens, should be taken under protection for their well-being. they should be provided with food and nutrition for the time being. covid- pandemics cause environmental, economic, and social attributes which have only partially been described in bangladesh. to fight this pandemic, it requires remarkable tasks and partnership development in the local and global level. the world must prepare for the likelihood that mitigation measures might fail because lockdown periods in different countries took different times to prevent or suspend the spread of covid- (gautam and hens ) . collective responsibility is required from the public as well to protect themselves by abiding general health guideline, maintaining hygiene and social distancing, and avoiding going to crowded places and meetings. extremely coordinated and effective planning and strategies for both the ongoing and afterwards response are required from the gob to manage this pandemic and take it as a new "standard of normal". considering the global hard-hit economy, depression, unemployment, job loss, shortfall of rmg export and incoming remittances, the socio-economic and development impacts along with the food insecurity as well as rising poverty due to covid- at the community level need to be coordinated in bangladesh. at present, as the lockdown is withdrawn, both lives and livelihoods are in danger which is a long-debate that is going on. along with the pandemic disease, the upcoming seasons of natural disasters from cyclones, tidal floods, flash floods, and landslides of monsoon seasons should be considered to prepare for the emergencies. all these will further aggravate the humanitarian needs of the most vulnerable groups in the country in the coming months to be followed. as the health sector is the most strained at present, it will affect the targets of sustainable development goals of . in addition, quality education will be hampered in the country. the government of bangladesh has already mobilized a noteworthy stimulus package to support the affected industries and community which needs to be coordinated over a longer period of - months and may be incorporated in the upcoming th -year plans with substantial revising. however, this package should also include research and innovation, recovery of education. there is no alternative to strengthen the health care facilities and preparedness for the potential humanitarian crisis. moreover, humanitarian support should reach the most vulnerable communities which need to be targeted, outlined, and delivered. finally, economic implications should be subjected to the spatial and geographical locations based on the vulnerabilities. hotspots identified in the delta plan can be considered here. the long-term strategic plan can be integrated into perspective plan and bangladesh delta plans , for better strategic management. whatever will be the lockdown scenario, the basic supports to the mass people must be ensured and that is not so easy without strong strategic planning and multisectoral collaboration for sustainability including supports from the private sectors and international bodies. community health workers and pandemic preparedness: current and prospective roles covid- situation report new zealand has no new coronavirus cases and just discharged its last hospital patient. here are the secrets to the country's success covid- : preparedness, decentralisation, and the hunt for patient zero at current pace, bangladesh to end extreme poverty by . the economic times new zealand eliminates covid- rapid surveillance of covid- in the united states using a prospective space-time scan statistic: detecting and evaluating emerging clusters scale development: theory and applications coronavirus: bgmea says orders worth $ . billion cancelled so far cyclone amphan: bangladesh may face losses worth tk , cr building resilience against biological hazards and pandemics: covid- and its implications for the sendai framework covid- as a factor influencing air pollution? environmental pollution fair allocation of scarce medical resources in the time of covid- federation of bangladesh chambers of commerce & industries the food systems in the era of the coronavirus (covid- ) pandemic crisis preventing intra-hospital infection and transmission of coronavirus disease in health-care workers. safety and health at work sars-cov- pandemic in india: what might we expect? environment global implications of bio-aerosol in pandemic suicide risk and prevention during the covid- pandemic. the lancet psychiattry what are the real choices? tbs news bangladesh covid- update national preparedness and response plan for covid- characterizing groundwater quality ranks for drinking purposes in sylhet district, bangladesh, using entropy method, spatial autocorrelation index, and geostatistics simultaneous comparison of modified-integrated water quality and entropy weighted indices: implication for safe drinking water in the coastal region of bangladesh potential association between covid- mortality and health-care resource availability. the lancet global health application of factor analysis in the assessment of groundwater quality in a blackfoot disease area in taiwan response to the covid- epidemic: the chinese experience and implications for other countries when will covid- end? data-driven prediction. singapore university of technology and design effects of temperature variation and humidity on the death of covid- in wuhan, china. science of the total environment first covid- suicide case in bangladesh due to fear of covid- and xenophobia: possible suicide prevention strategies penal code : section bangladesh worst coronavirus fighter in the region assessing global preparedness for the next pandemic: development and application of an epidemic preparedness index early estimates of the indirect effects of the covid- pandemic on maternal and child mortality in lowincome and middle-income countries: a modelling study. the lancet global health retrieved from https ://tbsne ws.net/thoug hts/lockd ownwithd raw-or-not-withd raw- ?fbcli d=iwar oanmr goirz omt a fhrle xytyh utc i j yocfj v dba -wapgs mfjm covid- pandemic, socioeconomic crisis and human stress in resource-limited settings: a case from bangladesh. heliyon icu space limited, critical covid- patients at risk half the country's covid- infection in dhaka city alone bangladesh lowest in covid- testing in south asia social distancing in public transport yet another cruel joke covid- pandemic: govt plans to divide country into red, yellow, green zones economic ramifications of covid- in bangladesh covid : sanem proposes -year recovery plan for bangladesh an investigation of transmission control measures during the first days of the covid- epidemic in china the toughest triage-allocating ventilators in a pandemic undp bangladesh situation analysis: support to the national response to contain the impact of covid- covid- : looming crisis in developing countries threatens to devastate economies and ramp up inequality combating covid- : health equity matters strengths, weaknesses, opportunities and threats (swot) analysis of china's prevention and control strategy for the covid- epidemic viet nam shows how you can contain covid- with limited resources why we cannot lose sight of the sustainable development goals during coronavirus doubl e-acute -hunge r-un-warns ?fbcli d=iwar jlhk fiove fpyf jwcdv qqovv j qsa xwx t gqv-iwnmy cri d ydidr o health emergency and disaster risk management framework who coronavirus disease (covid- ) dashboard who bangladesh covid- situation report no who bangladesh covid- situation report no challenges for nhs hospitals during covid- epidemic bangladesh must ramp up covid- action to protect its people, revive economy covid- coronavirus pandemic health emergency and disaster risk management: five years into implementation of the sendai framework covid- containment: china provides important lessons for global response publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations the authors would like to acknowledge all the frontline doctors, healthcare workers, emergency responders, security, and armed forces fighting this pandemic.funding this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. key: cord- - oehzarg authors: skoloudik, david; mijajlovic, milija title: neurosonology during the covid‐ pandemic (editorial commentary from the chairs of the ultrasound panel of the ean) date: - - journal: eur j neurol doi: . /ene. sha: doc_id: cord_uid: oehzarg the covid‐ pandemic is seriously affecting the lives of billions of people around the world, especially in the healthcare systems.( ) although the impact of pandemic on health services are mostly negative, there is still a chance to use this situation as an opportunity for positive changes. neurosonological examination involves direct contact between the patient and the sonographer, often for several tens of minutes. prof. david skoloudik (orcid id : - - - ) the covid- pandemic is seriously affecting the lives of billions of people around the world, especially in the healthcare systems. although the impact of pandemic on health services are mostly negative, there is still a chance to use this situation as an opportunity for positive changes. neurosonological examination involves direct contact between the patient and the sonographer, often for several tens of minutes. thus, this examination should be included in procedures with a potentially high risk of covid- transmission. this article is protected by copyright. all rights reserved nevertheless, the correct assessment of neurosonological examination is not only a question of image evaluation as in the other neuroimaging methods but it is "state-of-art" highly dependent on sonographer experience . thus, the hands-on courses are necessary to provide adequate education and practice to neurosonographers. the covid- pandemic has also seriously affected these educational activities. it is an urgent challenge for authorities (esnch, european academy of neurology scientific panel on neurosonology and neurosonology speciality group of the world federation of neurology) to create a suitable, safe, effective and modern system of neurosonology education able to protect participants, but to continuously deliver up-to-date neurosonology information. facing covid- pandemic, currently various new digital educational concepts are developed for distance learning and we should therefore share these broad experiences for future courses, but this is yet another demanding task for neurosonology community. it is an ultimate goal to increase the use of interactive videoconferencing in the remote neurosonology education as well as in the delivery of acute stroke care, known as telestroke/teleneurosonology, also feasible and very efficient during the crisis. among the first steps, sonographers should complete infection-control and protection training using these interactive remote modalities. major goal of all relevant recommendations of neurosonology societies or authorities is to protect both patients and sonographers but keeping a high attention on stroke as an emergency condition always strictly adhering to treatment guidelines for patients to ensure appropriate stroke care. the introduction of published recommendations into the clinical practice may also mitigate negative effects of new pandemics in the future. world health organization coronavirus disease (covid- ) pandemic. available at www.who.int/emergencies/diseases/novel key: cord- - pm pj p authors: brooks, oliver t. title: what if they threw a pandemic and nobody came? date: - - journal: j natl med assoc doi: . /j.jnma. . . sha: doc_id: cord_uid: pm pj p nan author affiliation: chief medical officer, watts healthcare corporation, los angeles, ca, usa w e are at present in the throes of a sars-cov- pandemic, the coronaviruis that causes the disease process covid- , characterized by fever, cough and shortness of breath that may lead to death. a pandemic is defined as "an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and usually affecting a large number of people". the classical definition includes nothing about population immunity, virology or disease severity. by this definition, pandemics can be said to occur annually in each of the temperate southern and northern hemispheres, given that seasonal epidemics cross international boundaries and affect a large number of people. however, seasonal epidemics are not considered pandemics. a true influenza pandemic occurs when almost simultaneous transmission takes place worldwide. the who declared a sars-cov- pandemic on march , . president trump declared the united states in a sars-cov- state of emergency on march , . so where are we as physicians now and what should we do? the first response is well-known by now; we are right here and we know it is the same in any outbreak: identify, isolate and quarantine. treat those that need medical intervention. the cdc recommends social isolation of at least feet/ m. simple enough. now what? we need the country to not join the "party": this is where i will diverge from referenced information (except two more). everyone at this point knows that there is a plentitude of credible information being updated daily from the cdc, the who, state and local health departments, and so on. allow me to speak more personally. i am the second nma president to serve during a pandemic. the nma president in during the spanish flu epidemic was dr. george w. cabaniss. i do not know what the challenges were then, but i but i am sure they were legion. the message i would like to convey is that in times of high stress, in this case a pandemic, management of this, by we physicians, is what we were trained to do. in the end, medical school and any subsequent training was to provide you with the tools to face medical adversity, aka illness. dr. lasalle lefall, my now deceased and world-renowned professor and chief of surgery at howard university college of medicine taught us "equanimity under duress" (my reference is my colleagues). i see now that this applies not only to the hemorrhaging from a nicked femoral artery in the or, but to a challenged healthcare system and population during a pandemic. we are on the frontlines, treating covid- cases as we speak. we are also still managing face to face our pregnant women; those needing an appendectomy; those with acute chest pain; the suicidal. essential care and pathology do not go away during a pandemic. however, as we are learning from covid- , chronic disease management before a pandemic is also crucial during a pandemic. studies are showing that those with certain comorbidities (chronic lung disease, moderate to severe asthma, serious heart conditions, those immunocompromised including cancer treatment, severe obesity (body mass index [bmi] ) and (particularly if not well controlled) diabetes, renal failure, or liver disease are at higher risk for severe illness. we must reduce these populations of patients with these and other comorbidities. most of these comorbidities are avoidable; we need to ensure our patients "avoid" them. leaving treating illness behind, we have been forced to evolve with our training to understand that there is the next level; that is not just healing the sick and reducing comorbidities, but keeping the healthy well. wellness as a primary focus is just as important as secondary medicine; we all know this but it gets magnified during a pandemic. the consensus is that those that are healthy are less more likely to have mild disease: proper sleep, diet, and personal behaviors lead to better outcomes. it is unclear which is easier to manage as physicians, getting patients well or keeping patients well; it does not matter because we are ª published by elsevier inc. on behalf of the national medical association. https://doi.org/ . /j.jnma. . . charged with managing both. if we treat the sick and keep others healthy, we will succeed, as best we can in mitigating the effects of a pandemic. we as physicians need to know more about covid- than anyone else, as we pledged an oath (of hippocrates or imhotep) to be ready for anything related to health and wellness, e.g. a pandemic. no one else being called upon to act at this took such an oath (except perhaps the police or military). when the whole of society has closed down, shuttered their windows, locked their gates, and gone home to be with their loved ones, we will be the ones that the national guard will allow to pass onto the highways, with one flash of our md id badge. this is our responsibility, to be there when no one else is: to prepare, to have answers, to calm, to treat, to heal, to be responsible. my title was a bit misleading; there will always be pandemics, and those affected by them, but if the popu-lation is healthy, the response is robust, and the knowledge disseminated is accurate, widespread and implemented, we can blunt the effects of pandemics going forward. let us hope that, just like with a war, it will be poorly attended and over fast. clinical features of patients infected with novel coronavirus in wuhan a dictionary of epidemiology key: cord- -x djkzqn authors: hao, fei; xiao, qu; chon, kaye title: covid- and china’s hotel industry: impacts, a disaster management framework, and post-pandemic agenda date: - - journal: int j hosp manag doi: . /j.ijhm. . sha: doc_id: cord_uid: x djkzqn this exploratory study reviews the overall impacts of coronavirus disease (covid- ) pandemic on china’s hotel industry. a covid- management framework is proposed to address the anti-pandemic phases, principles, and strategies. this study also suggests that covid- will significantly and permanently affect four major aspects of china’s hotel industry—multi-business and multi-channels, product design and investment preference, digital and intelligent transformation, and market reshuffle. the effect on human health has been the most devastating and observable of all the effects of coronavirus disease . however, the unfolding economic catastrophe resulting from this pandemic sets apart the latter from any disaster in living memory (huang, ) . since the outbreak of covid- at the end of , industries have been plagued by uncertainties, and this scenario is especially evident in the tourism and hospitality industry. as an industry based on human mobility and close interaction, the tourism and hospitality industry is the co-creator and main receiver of the pandemic and its ramifications (gallen, ) . china's (referred to as the chinese mainland in this paper) hospitality industry was the first to be hit by the devastating impact of the covid- . however, it has been presenting early signs of performance recovery since the end of march . the overall effects of covid- on china's hotel industry are depicted in the first section of the study. depicted later in this study, the anti-pandemic experience and strategies of china's hotel industry would respectively help the hotel industry in other parts of the world to forecast the disastrous scenarios and industry recovery and undertake effective anti-pandemic actions (valle, ) . in this regard, to the best of our knowledge, this is the first study to explore the covid- management framework in the context of china's hotel industry; the framework addresses phases, principles, and strategies of the industry's anti-pandemic journey. this study contributes to practical implications by recommending the hotel industry to gain on the major trends that may follow the fundamental and permanent changes that covid- is expected to bring to the industry; this discussion may shed light on the industry activation and revitalization during the post-pandemic era. china was the first country affected by the health crisis, and thus its hotel industry has encountered severe challenges (china hospitality association, ; china tourism research institute, ; sun et al., ; zhang et al., ) . these challenges have affected every stakeholder in the hotel industry. owing to travel bans and social distancing norms, there has been a decline in tourists' willingness and access to travel. this has led tourists to cancel travel plans and hotel bookings, which has eventually affected the job and income security of hotel employees. the consequential shortage of labor and cash has led to the postponement of hotel renovation projects, decelerating the expansion of domestic hotel groups (elena, ) . in order to survive, many hotel owners, especially individual hotel owners, have temporarily shut down or transferred their properties. this scenario has led to a sharp decline in the market value of stocks in the hotel sector. in other words, the pandemic has been devastating hotel firms' market and performance. the sudden outbreak of covid- swept through chinese lunar new year-the most important festival in china, casting a dark shadow over the until then thriving hotel industry. during the lunar year, the occ used to be about % and %, respectively, in major cities and tourist and fourth-and fifth-tier cities (lanjing finance, ) . however, during this period, the pandemic led to a sharp decline in the occ of major hotels. several industry associations and consulting agencies have investigated the overall loss of china's hotel industry. as per the china hospitality association ( ), china's hotel industry lost over billion yuan (approximately us$ . billion) in revenue, and . % hotels in china were closed for an average period of days in january and february . as per str ( ), from january to , the occupancy (occ) of the hotels dropped from around % to % and remained under % in the following days. almost % of the hotels were shut down temporarily in february. zhang et al.'s ( ) study on hotels revealed that the overall occ dropped by % in two weeks between january and and, subsequently, remained at around % until the end of february. in major cities, hotels' revenue per available room (revpar) declined by over in february (zhang et al., ) . as the pandemic intensified, the financial loss of china's hotel industry continued to the first quarter and its impact was evident in the financial reports of several hotel firms. for instance, concerning domestic brands, in the first quarter of , the second largest hotel group in the world and the largest in china, jinjiang international, reported a net profit of million yuan (approximately us$ . million), a yoy decrease of . % (zhang, ) . the world's th largest and china's nd largest hotel group, huazhu temporarily closed few of its hotels, with the numbers declining from a peak of , hotels in mid-february to in the subsequent month (elena, ) . the quarterly revenue of the btg hotel group ( th largest in the world and rd in china) was million yuan (approximately us$ . million), which indicated a . % yoy decrease (real estate opinion network, ) . the occ of dossen international group, the th largest hotel group in the world and the th largest in china, fell by % and its revenue dropped by % yoy (wu, ) . likewise, china's th largest hotel group, the sunmei group, closed , hotels, on the back of an average occ of only . % during february and a revenue loss surpassing million yuan during january and february (approximately us$ . million) (y. . international hotel brands were not immune to the effects. ihg closed down out of hotels in china during february, and its occ dropped by % to under % during the same period (k. . meanwhile, hilton closed about hotels in china by february , (lanjing finance, . similarly, marriott's revpar in greater china by more than % and that of accor fell by . % in china (jerry, ). the hotel market started witnessing positive signs after the pandemic slowed down in mid-march. during the qingming holiday, the tourism packages featured one-day short excursions, and there was a relatively low hotel demand during the period. however, the five-day labour day holiday was the first peak season since the outbreak. according to the ministry of culture and tourism, during this period, the total number of domestic tourists reached million passengers, and the domestic tourism revenue reached about . billion yuan (approximately us$ . billion). according to data adopted from str that based on sample properties including , room in china (shown in figure ) , hotels have undertaken a devastating hit of covid- , especially during january to march . among seven different hotel scales, the luxury and independent hotels have suffered the most from the negative impact, whilst midscale chains and economic chains were least affected. the long-term recovery of china's hotel industry seems to be promising, yet not without challenges. several organizations forecasted about hotel's performance in . hilton forecasted a - -month recovery period and revenue losses of around us$ million (lanjing finance, ). zhang et al. ( ) forecasted that the industrywide occ in will drop to approximately . %; however, if there is a rebound in the pandemic in china, then the decline could be around . % (zhang et al., ) . as per the china hospitality association ( ), in the second quarter of , occ will rise gradually; the yoy revenue will decline to about . %, with a revenue loss amounting to billion yuan (approximately us$ . billion). the third quarter of will witness a gradual recovery of domestic business activities, a pick-up in exhibitions and business meetings, and the peak season during the summer holiday in july and august. this scenario will contain the decline in yoy revenue at around %, with a revenue loss of around billion yuan (approximately us$ . billion u.s. dollars). in the fourth quarter, the hotel industry may embrace a compensatory consumption growth, especially during the national day golden week, eventually making up for the revenue loss. notably, business recovery will still be influenced by the global situation. owing to the economic recession, shortened vacations, and customers' pervasive post-disaster panic, it is less likely that a retaliatory growth will occur after a slowdown in the pandemic. the potential impacts of disastrous events on hospitality and tourism will increase in both magnitude and frequency with an increase in the hypermobility of tourism and interconnectedness of the global economy (hall, ) . in the context of covid- and the progressively disaster-prone world, the hospitality industry must develop a framework for understanding and implementing disaster management strategies (chan et al., ) . since the beginning of the st century, there has been an increased sensitivity and awareness for crisis and disaster in the hospitality and tourism sector (laws et al., ) . in most occasions, the terms crisis and disaster have been used alternately or simultaneously without considering their distinction (evans & elphick, ; lettieri et al., ). however, based on the distinction of faulkner ( ) , an organization faces a crisis due to internal failures, while it confronts a disaster due to uncontrollable external factors. in this regard, covid- should be defined as a disaster; it indicates a situation where sudden devastating events, neither absolutely predictable nor avoidable, affect enterprises, challenging their operational routine, structure, and survival (faulkner, ) . theories from different disciplines shed light on the disaster management literature. the general disaster management literature is predominantly based on the engineer-oriented all-hazards theories (lettieri et al., ). however, from the tourism and hospitality perspective, most disaster management studies are guided by management-oriented theories. for example, jia et al. ( ) adopted the crisis management theory emphasizing on the proficient dissemination of information and communication between various stakeholders. nguyen et al. ( ) used the collaborative planning theory to investigate hotel-stakeholders' attitude, consequences, and obstacles of collaboration. socio-psychological theories were also applied in the disaster management literature in the context of hospitality and tourism. for instance, wang and wu ( ) , by applying the theory of planned behavior, developed an iceberg model that presents the influences of underlying beliefs and psychological factors on crisis planning and implements actions with an emphasis on cultural diversity. furthermore, inter-disciplinary system theories were also implemented. for example, brown et al. ( ) developed an integrated disaster management framework of economic, social, human, physical, natural, and cultural capital using the complex adaptive systems theory. similarly, faulkner ( ) and ritchie ( ) used the chaos theory to obtain a more complex and comprehensive understanding of disaster management in tourism encounter. this study adopts the chaos theory to address the complex nature of the disaster, turbulence in tourism encounter, and the dynamics of changes. several frameworks present a holistic understanding of a disaster situation and provide suggestions for coping with the disaster at each phase (wang & ritchie, ) . drawn from broader disaster management studies and peculiarities of the tourism and hospitality industry, faulkner ( , p. ) proposed a generic framework that has been widely adopted to scrutinize and develop tourism disaster management strategies. this framework sets out the following three components-phase in disaster process, elements of disaster management responses, and principal ingredients of the disaster management strategies. specifically, phases in disaster process comprise pre-event, prodromal, emergency, intermediate, recovery, and resolution. the united nations ( ) developed a framework for general disaster risk reduction; it comprises core components of disaster management such as context, risk factors, awareness, risk assessment, knowledge development, public commitment, preparedness, early warning, response, recovery, and measures. ritchie ( ) and sawalha et al. ( ) modified the framework of the united nations ( ) and developed their disaster management strategies and actions for the hospitality and tourism context. lettieri et al. ( ) identified the mitigation, preparedness, response, signaling, recovery, and learning phases. with a focus on factors and resources at the individual, organizational, and environmental levels, wang and ritchie ( ) developed an onion model for strategic crisis planning; it comprises the onion system, the key influencing factors, and strategic crisis management. nguyen et al. ( ) explored a disaster management framework emphasizing the collaboration of public-private stakeholders. despite the existence of the aforementioned frameworks and models, there is a growing demand for a context-specific model for covid- because of the following reasons: existing frameworks are not realigned to the health-related disaster; hotels play a vital role in supporting disaster relief and resilience (dobie et al., ) , but hotels' csr during disasters has been largely ignored in existing frameworks; existing frameworks fail to present the phases, principles, and strategies of disaster management in a chronological manner, which comprise a crucial instruction for actors. effective disaster management strategies of enterprises can minimize potential hazards and accelerate the recovery process (ritchie & jiang, ) . the disaster management strategy and actions are highly related to the nature of the disaster (hall, ) . therefore, we consider a similar context based on the disaster management measures taken by the hospitality and tourism industry during the severe acute respiratory syndrome (sars) outbreak; these measures are reviewed and presented in table . drawn from the review, the process of disaster management is deployed to various phases featuring specific events, principles, and strategies. lessons learned in the post-disaster phase are documented, analyzed, and standardized as valuable experience in order to prepare actors for the next disastrous event in the pre-disaster phase, and thereby a closed loop is formed to improve the actors' disaster-response ability continuously. based on a review of the anti-sars experience and the chinese hotel industry's anti-covid- experience, we develop a framework comprising phases, principles, and strategies for the anti-covid- battle. the framework also considers all hotel stakeholders (e.g., investors, property owners, customers, employees, communities, and the government). a covid- management framework is proposed in figure . the underlying rationale of the framework hinges on the following aspects. first, it considers the whole process of disaster management. second, it focuses on hotels (at the property and firm/brand levels) as main actors. third, in the proposed model, the first section-phases in the anti-pandemic process-depicts major events that have affected or may affect china's hotel industry during the six pandemic phases. fourth, the second section-principles-presents four fundamental principles that can help hotel firms focus and to guide their actions during different disastrous phases. fifth, in line with the proposed principles, the third section-anti-pandemic strategies-presents major strategies that have been or should be implemented by the hotel industry to alleviate the catastrophic effects of covid- . this study adopted the six phases of disaster management proposed by faulkner ( ) , as it fits in the context of covid- and the advancements in health-related disaster management (henderson & ng, ) . in the pre-event phase, prerequisite actions are taken beforehand to evade or alleviate disastrous impacts. in the prodromal phase, we observe the warning signs of an impending disaster; this is followed by the emergency phase wherein urgent actions are taken to safeguard people and properties. subsequently, this leads to an inflexion point; it is followed by the intermediate phase focusing on restoring normalcy to key community services and activities. the recovery phase is the continuation of the previous phase, which focuses on facilitating a series of self-reflection and self-healing measures. finally, in the resolution phase, the normal routine is restored and the system is optimized to strengthen its disaster resistance capability. notably, the boundaries between the six phases are blurred in practice. in the context of covid- , the pre-event phase began on november , when the first infected case of china was found in wuhan (j. , and lasted until january , . on december , , the wuhan municipal health commission reported a cluster of cased infected by a novel coronavirus. on january , , the who alerted about the outbreak of pneumonia in wuhan (world health organization, ). some hotel brands generated the pandemic response mechanism before the outbreak based on the anti-sars experience in . the prodromal phase covered the period from january to january , . increasing evidence indicated that the outbreak was imminent. tourists became more suspicious and started to cancel non-essential travel plans. hotels were engaged in dealing with growing cancellations and addressing concerns about the upcoming epidemic. for instance, dossen acknowledged that it received more than % room cancellation messages during the prodromal phase (wu ( ) . china's hotel industry entered the emergency phase in january , , which lasted until the mid-march . on january , , wuhan city was locked down, and provinces and regions across the country launched public health emergency response on the next day. the chinese government issued a series of travel restrictions to prohibit cross-province and cross-city mobility. covid- started to spread nationally, infecting , people and causing , deaths until march , . china's hotel business suffered a disastrous decline and dropped to the freezing point almost overnight. the intermediate phase was from mid-march to april . the pandemic was gradually brought under control as a result of china's unprecedented lockdown. subsequently, chinese authorities commenced easing travel restrictions. during this phase, the hotel industry started showing some early signs of performance recovery. the hotel industry shifted its focus from anti-pandemic to business restoration measures. by the end of march, the average occ of china's hotels was to . % (china hospitality association, ). leading hotel brands gradually restored normalcy in operations; for instance, the occ of huazhu was restored to % (jin, ) . both the revenue and occ of dossen hotels surged to %, and their employees' return to work rate reached % (d. . concerning hotels in the str database, at the beginning of april, % of the hotels restored operations, and % luxury and upper-upscale properties were reopened (str, ). although china started recovering from the disaster in mid-march, the pandemic had spread globally to over countries by this period. the health crisis had evolved into an economic crisis. there was also an increased risk in the resurgence of covid- in china due to the imported cases. the global outbreak of covid- was expected to significantly impact china's hotel industry during the second half of . on march , , china closed its border to foreign citizens temporarily to avert a second wave of covid- . a vast majority of nations and regions also closed their borders and reduced the number of international airlines. the overnight rate of china's inbound passengers dropped dramatically, compelling upper-scale hotels targeting international business travelers to seek new markets and segments. however, the hotels' occupants included stuck travelers, hubei citizens who could not return to their rented apartments, people who were required or volunteered to undertake self-quarantine, relatives of non-covid patients admitted in hospitals, material supply transportation teams, and government officials overseeing anti-pandemic actions (guan, ). with expectations of controlling the outbreak by april (ho, ) , china gradually loosened the domestic travel restrictions. however, the recovery of the inbound tourist market remains hard to predict. according to lanjing finance ( ), the china tourism research institute projected that the market recovery will start from the second quarter of this year, with the recommencement of business travel, local leisure trips, short-distance sightseeing (one-day tour) and weekend leisure, mid-range sightseeing and leisure (intra-provincial tourism), and long-distance tourism (cross-provincial domestic travel); therefore, hotels should focus on business travelers and local demands. further, the china hospitality association ( ) predicted that in the fourth quarter of , the hotel industry may undergo a compensatory consumption growth, eventually making up for the revenue loss. given the above, it is prudent to state that china's hotel industry has already entered the long-term recovery phase, which started in may and is expected to continue until the end of . the resolution phase is expected to last for more than years after the termination of the pandemic. during the post-covid- period, a set of prerequisite strategies will be undertaken for industry activation and enhancements. according to zhang et al.'s ( ) prediction, although the business sector will witness a faster recovery, the spending power will remain the same. the meetings, incentives, conferences and exhibitions (mice) sector will recover slowly, which will contribute toward the avoidance of crowd gathering. the leisure sector will embrace a short-term retaliatory consumption, after months of travel restriction, and witness a rise wellness and technology trends (zhang et al., ) . j o u r n a l p r e -p r o o f hotel firms must set forth appropriate principles corresponding to different phases of disaster management (chan et al., ; faulkner, ; ritchie & jiang, ) . this study proposes four principles for the different phases of the pandemic. in the pre-event and prodromal phases, it would be crucial to evaluate the potentially devastating effects of the pandemic and their probability of occurrence (faulkner, ) . based on the disaster assessment, hotel firms can better prepare for different scenarios and adjust the anti-pandemic strategies promptly and effectively. in the emergency phase, the hotel firms must ensure the safety of employees, customers, and property. many hotel brands actively participated in the anti-pandemic battle to accommodate medical crew, infected patients with mild symptoms, stranded travelers, and quarantined citizens. in the intermediate phase, when the tension and fear of the pandemic lessens to some extent, the hotel firms must switch from an anti-pandemic to self-save mode to cope with the ensuing economic crisis. during the long-term recovery and resolution phase, hotel firms must focus on activating and revitalizing their business. actions taken during the long-term recovery and resolution phase will increase resource investment and optimize operations in the affected area, and thereby lead to improvement over the pre-pandemic situations. the uncertainty brought by covid- has led to fear and severe volatility in the global hotel industry. in this regard, the hotel consumption and anti-pandemic strategies undertaken by china's hotel industry can help the hotel industry in other parts of the world to better prepare for different disaster scenarios and prepare an appropriate action (valle, ) . major anti-pandemic strategies adopted by china's hotel industry are discussed in detail in the following subsections. as in all disaster situations, the first step involves the formation of an efficient and responsible disaster management team and the appointment of a team leader (faulkner, ) . several hotel groups, including dossen, btg, ihg, huazhu, jinjiang, wanda, and new century, established a disaster management team in the prodromal or emergency phase, in order to undertake leadership, command, and action. concerning communication, the covid- scenario calls for innovative communication that can facilitate smooth and responsive exchange of information and decision-making (moorhouse, ) . in china, mobile applications, such as enterprise wechat, dingtalk, tencent conference, zoom, feishu, and welink, have gained popularity for office automation, remote conference, and online training (juzhang data, ; li et al., ) . using a combination of online office technologies, tools, and platforms, hotel brands have established an effective remote command and management system to deploy employees and arrange meetings. during disasters, high performance employees are considered valuable assets for the firm; these employees contribute toward firms' performance recovery once the disaster is pacified. therefore, hotel firms should strive to retain employees during the pandemic. for hotels located in the center of the pandemic and involved in the anti-pandemic battle, it is critical to ensure the physical health, psychological well-being, position and income of the front-line staff. hotels at the periphery of the pandemic must reduce non-essential labor costs flexibly by socializing service production, sharing labor with the related service industry, adopting intelligent devices to replace manual labor, and laying off laborers with low-performance efficiency and poor working attitude. some hotels share staff with industries facing a labor shortage, such as food delivery organizations or mask manufacturers. hotels also employ outsourced labor for some service procedures (e.g., food delivery and laundry) to enhance cost-efficiency. there is an emerging trend to retrain staff to multitask in order to improve work flexibility and optimize human resource allocation. besides, hotels can also take advantage of the low business season to train staff online, support staff development, encourage employees to take annual leave, and reduce workdays and hours (mckercher, ). restoring customer confidence is critical to tide through a crisis. in this regard, it is interesting to note that several hotel brands initiated the free cancellation service (until end of april) and re-booking assistance, extended the loyalty program membership, and increased the benefits of membership to reassure customers. for instance, domestic hotel companies, such as jinjiang, huazhu, new century, and the atour group, extended their loyalty programs' membership by months; several international firms, including hilton, hyatt, and accor, extended such membership programs even up to an year . hotel brands have taken strict hygiene and sanitary measures to secure their customers' accommodation environments; these measures include conducting complete disinfection; controlling food hygiene; distributing masks; offering online medical consultation; detecting the health of customers and employees; and shutting down laundry rooms, gyms, and other public areas and facilities. for instance, btg homeinns hotels upgraded its worry-free service to include special cleaning standards and anti-pandemic cleaning measures (d. . tujia homestay promoted a standardized disinfection procedure covering contact points (luo, ) . hotels must explain about their protective measures to the customer, and thus restore customers' confidence (valle, ) . a good example is huazhu's hanting brand; it not only launched post-epidemic cleaning operations in its , hotels but also publicly invited customers to supervise the entire process of deep cleaning on-site and broadcasted the procedure online to reassure customers of the hotel's safety (meadin, ) . hotels have also been implementing technological solutions to provide contactless service and assure customers of service safety (all-china federation of industry and commerce, ). during the pandemic, hotel groups (such as dossen, huazhu, and new century) increased the implementation of intelligent contactless services, including self-check-in, remote check-in, face-scanning, voice control of room service, robotic room service, and the zero-second check-out. these services aimed to avoid human contacts and minimize their customers' stay in public areas, and thereby contributed toward reducing the risk of covid- transmission and cross-infection (guan, ; yunji technology, ) . hotels also collaborated with the online travel agencies (otas) to launch accommodation projects that guaranteed hygiene. by april , , over , hotels from cities had joined the 'rework and stay safe' project initiated by qunar.com. of these hotels, there has been an expansion of contactless service hotels equipped with self-check-in machines and robotic room services. alibaba business travel also launched the worry-free accommodation service for the first batch of business travelers from reinstatement enterprises in more than cities (guan, ). hotel industry associations also issued guidelines to monitor pandemic prevention. china hospitality association and hvs released a compilation of cases on the preventive measures and operation of hotels in the asia-pacific region. this compilation serves as a reference for hotel practitioners on measures taken by hotels during the sars outbreak. china hospitality association, national green hotel working committee, and meituan published the convention on pandemic prevention in china's hotel rooms to instruct hotel practitioners. besides, the china hospitality association, alibaba, and cornell china established guidelines for food and beverage merchants during covid- ; these guidelines directed the anti-epidemic work of catering practitioners . during the peak pandemic period, the rapid increase in the number of infected cases led to a shortage of hospital beds. there was a need to find hospital extensions to quarantine and treat infected patients. additionally, the wuhan government had to arrange accommodation for the covid- medical staff deputed in the province as well as the construction workers involved in the construction of covid- hospitals. at this time, the china's hotel industry displayed solidarity with people and carried out social responsibilities. by providing existing infrastructure and services, many hotels voluntarily participated in providing accommodation and meals to the medical staff, construction workers, and patients. in the first quarter of , government agencies designated huazhu hotels (a total of two million room nights) as medical crew dormitories and quarantine stations (elena, ) . in hubei, more than dossen hotels were voluntarily designated as anti-pandemic hotels, which hosted more than , person-times of medical staff from hospitals. on january , , dossen started encouraging franchised hotels in china to restore operations and provide free accommodation, meals, and transportation for the front-line medical staff (wu, ) . jinjiang's midscale brand vienna also provided , free rooms to the medical staff (chang, ) . hotels also worked closely with authorities to accommodate stranded tourists from hubei province and serve as quarantine stations. moreover, by the end of march, some non-locals who returned to the province to resume work were quarantined for days. several hotels in major cities were designated as quarantine stations for the returning non-local workforce. meanwhile, with the global spread of covid- , inbound travelers were also required to undergo the same quarantine process. to minimize the spread of disease, hotels nearby major international airports served as quarantine stations for inbound travelers. hotel firms should focus on policies issued by related government agencies and seek financial aids from authorities (china hospitality association, ; mckercher, ; sun et al., ) . various government agencies issued supporting policies to avoid layoffs and firm bankruptcies by supporting their cash flows in the short-term and enabling them to repay their long-term debts. the supporting policies predominantly include labor cost reduction policies (flexible employment policy, returning unemployment insurance, deferring social security payments, alleviating the burden of housing fund, and subsidizing staff training), tax deduction or deferral policies (reducing or exempting land use or real estate tax, postponing tax payment, simplifying tax payment and refund procedures, and deducting tax for donation expenditure), rent reduction policies, funding support policies (low-cost financial support, various financial services, green channels, and fast and easy access to loan), and energy cost reduction and exemption policies (china hospitality association, ). besides, the local government also provided subsidies to hotels that served as hospital extensions, medical crew dormitories, and quarantine stations. hotels must also apply self-save strategies to revitalize the cash flow, reduce non-essential costs, enhance operating capabilities, monitor cash flow predictions, and make dynamic adjustments promptly based on the ever-changing pandemic situation. based on existing facilities and services, many hotels developed new functionalities and customer values such as hospital outplacement and quarantine station. they must also employ efficient methods and systems to reduce operating costs, such as by strategically closing, partially closing, or reducing the number of properties and facilities, postponing non-essential building and system maintenance, minimizing fixed costs, and cutting non-essential services. hotels must also engage customers online and develop sales strategies such as advance sale, package sale (combining airfare, accommodation, local tours, and food and beverage), and flexible daily pricing strategies, based on the current situation. furthermore, as a community with a shared purpose, hotel brands must collaborate with their parent firms to overcome financial hurdles. many international and domestic hotel chains reduced management and franchise fees, waived marketing and system fees, and offered discounted supplies and pandemic prevention materials (zhang et al., ) . in addition, some hotel brands, such as dossen, huazhu, and vienna, provided health insurance to franchisees and a substantial loan amount for market renovation and establishing new hotels (chang, ; jin, ; wu, ) . ota giant ctrip also recommended otas to collaborate toward reducing hotel supplier commissions and advertisement fees, exempting management fees for months, and providing loan service to individual hotels (traveldaily, ). hotels must establish a responsive and efficient standard operating procedure (sop) to enhance the effectiveness of disaster management capabilities in addressing disasters, including natural disasters and emergencies (e.g., epidemics, explosions, fires, violence, robbery, critical illness, and death). hotels with an experience in a specific category of disaster will obtain a better understanding of the disaster and become well-prepared to cope with a similar situation in the future. hotels should organize and maintain a team of expert consultants to respond to the pandemic, establish an expert consultation mechanism, and compile and update the guidelines for the hotel's response to the pandemic. the insurance companies who have a long-standing cooperation with the hotel industry should optimize products and services to adjust to the pandemic situation and help hotels hedge against possible losses . covid- will significantly and permanently affect several major aspects discussed in the following subsections. even before the pandemic, the hotel industry was facing fundamental challenges. hotels faced increasing pressure to become more customer-centric, digital, agile, and sustainable (valle, ) . as a blessing in disguise, the health and economic impacts of the pandemic significantly changed the supply-demand balance of the hotel industry, requiring hotel firms to re-evaluate the current business model and set out a new agenda to enhance competitiveness. in this way, disaster can be a trigger or catalyst for a robust and more adaptable hotel industry (faulkner, ) . figure shows the four aspects and their connections and logical relationships. the traditional hotel business model focusing on catering and accommodation has been severely challenged by covid- , which has driven proactive companies to restructure and develop a more diversified business scope and distribution channels. some of the changes will last through the post-pandemic era. therefore, the hotel industry must renew services by deconstructing and reconstructing existing products, marketing strategy, distribution channels, delivery methods, and consumption points (gallen, ) . the hotel industry will embrace reforms facilitating multi-business and multi-channel platforms. for example, hotels can maximize their space and utilize it for accommodation, catering, retail, and public activities as well as for the off-line demonstration of online shopping. wanda hotels and resorts uses its public space to demonstrate consumption scenarios and exhibits commodity (chen, ) . atour generates profits through commodity displays and e-commerce, in addition to room income, and thus e-commerce income has become an important source of atour's income (socialbeta, ). many igh hotels launched a food delivery service (k. . jinling hotels and resorts extended its business scope and broadened the operating income structure by setting up a food retail platform, which integrates the commercial scale production of classic dishes, an online sales system, and the cold chain logistics system. jinling received an order from the local government to provide food to its non-local covid- medical crew; the hotel produced , pork bales and , brined ducks within hours and delivered the products on time (hu et al., ) . hotels should also endeavor to update channels to contact, attract, and sell to customers (valle, ) . china's hotels depend heavily on otas as their primary e-commerce channel; these otas are based on the public domain-a huge customer base is shared by various ota platforms through bidding. in the past decade, all businesses, including hotel otas, had benefited from the rapidly increasing number of users on the public domain. in recent years, the saturation of users in the public domain increased the costs of acquiring user growth, which, in turn, increased the expenses of the ota platform. in , the private domain concept changed hotels' e-commerce ecosystem, allowing direct contact with the user pools attached to the brand/hotel. the growth of private domain has been promoted by the emerging social media channels in china, such as the wechat group, online flagship stores, vlog, and live-streaming. private domain forms a close loop where users can be converted into consumers at lower costs, and these converted users will also share a stronger bond with the brand. in china, the emerging mobile applications for hotel marketing via private domain include paipai (developed by ctrip), dianping (developed by meituan), xiaohongshu, tiktok, and wechat public account (shao, ) . triggered by the pandemic, in the chinese mainland, the live streaming sale has become one of the most popular marketing and sales channels across industries. live streaming sales have achieved phenomenal success (ni & wang, ) . hotels should seize the opportunity to use live streaming to display products, interact with customers, and promote sales. for instance, fliggy made more than , live broadcasts in over countries and regions and attracted million users during february and march (xu, ) . liang jianzhang, the chairman of the board of ctrip, turned himself into a key opinion leader (kol) and conducted seven live broadcasts since march, which drove a total of million yuan (approximately us$ . billion) gross merchandise volume (jenny, ) . in april, through live streaming, , advanced sales packages of a shanghai hotel were sold in half an hour; since then, the hotel has sold nearly , packages (ministry of culture and tourism of the people's republic of china, ). china's hotel industry has evolved rapidly in the past years. while most hotels were poorly managed and state-owned independent properties in the s, a diverse and thriving brand landscape emerged in s. these successful brands emerged not only the upscale sector but also in the economy and the upper-midscale ones. recently, personalized, innovative, and non-standard hotel brands, such as muji and atour, have emerged as a trend. during the pandemic, some hotels exhibited their high competitiveness and good financial performance through excellent product design and investment preference. for instance, the -room upscale shilifangfei hotel (a member of huazhu's vue brand) achieved its key performance indicators for the entire financial year by the first quarter; this success was attributed to its attractive brand storytelling, keen market positioning, space utilization, highly educated customer community, rapid innovation, and iterative operational capabilities (sammi, ) . covid- brought about enduring changes in customer preferences and consumption behaviors. hence, hotels should identify customer needs and develop state-of-the-art products. for example, customers' concern for hygiene, health, and sustainability will continue during the post-covid- era (valle, ) . new hotel products should allow customers to maintain a healthy and balanced lifestyle, exercise at will, work effectively, ensure social distancing, and reduce close contact. thus, functional private space, such as a private office, fitness center, and recreation space and facilities, plays an important role within a hotel room (k. . homestays are also suggested to launch accommodation products with abundant private space, such as a balcony, private kitchen, and a washing room to reduce unnecessary interpersonal contact (luo, ) . owing to the epidemic's severe damage, future hotel investment and asset renewal will be more concerned with the return on investment and control of cash flow, and thus strive to maximize the value of a property and operating value (lanjing finance, ). china's rapid development in the past years has led to an unusual growth in the number of luxury hotels. having experienced significant losses during the pandemic, hotel investors will become more rational and return-driven in regard to their future projects. the preference of investors will change from big and comprehensive to small and exquisite (qu, ) , and the return-optimization formula for hotels will focus on maximizing revenue per square meter per minute (gallen, ) . covid- pandemic has enhanced the need for intelligent services in both the supply and demand sides of the industry. changes in consumer demand are the fundamental drivers of digital transformation. in the current scenario, customers have developed a renewed preference for contactless service supported by the digital platform and intelligent technology; these services are expected to continue after the pandemic. several large-scale chain brands have hastened the digital transformation to sustain competitiveness in the post-pandemic world (china hospitality association, ). hotels' investment in digital customer relationship management has endowed customers service with configurability and traceability; this is based on which hotels can predict the individual preference, provide customized services, improve membership conversion, and increase customer loyalty via various engagement schemes. through big data and revenue management, hotels can analyze the composition, demand, travel distance of the target consumer, and carry out precision marketing. the digital and intelligent tools will eliminate human error, increase service efficiency, stabilize service quality, and thus enhance customer satisfaction and improve hotel performance in the increasingly competitive business environment. in china, several technology companies (e.g., puietel, resthour, xiezhu, and yunji) with independent innovation capabilities have emerged to provide technical support to hotels. industry giants such as ctrip, alibaba, xiaomi, baidu, and iflytek have also shown high interest in developing artificial intelligence (ai) applications for hotels. for example, flyzoo hotel, which is developed and operated by alibaba, is widely recognized as the leader of smart hotels in china. based on the internet of things, flyzoo adopted intelligent technologies such as smart control (e.g., access, lights, speakers, curtain, air conditioner, and tv), self-check-in and checkout, room service and food delivery robots, kiosks, face recognition, voice applications, and mobile payment. the digital, intelligent, and contactless service will reduce interpersonal contact and the risk of cross-infection, and thus boost customer's confidence in the service environment. the implementation of digital and intelligent technologies can also improve a hotel's operational efficiency and achieve significant cost reductions. the pandemic has also accelerated the ad hoc implementation of video conferencing, cloud collaboration, and teleworking. in the post-covid- era, hotels will be more agile and effective in attracting generation-y and z customers and employees if they continue to implement digital and smart solutions (valle, ) . given that the hotel industry is a labor-intensive industry relying on standardized manual inputs and operations, the implementation of digital and intelligent technologies, specifically process automation, will automate a considerable proportion of repetitive administrative work and replace human labor. the digital and intelligent tools ensure uninterrupted hotel operations on the business side and service provision on the customer side. hotel firms require an integrated management-marketing-service digitalization plan and extend the loop from marketing to operation management. hotels can develop a digitalized operation system that connects the management scenarios with service scenarios throughout the lifecycle of a hotel. the pandemic will also significantly influence the market composition of china's hotel industry in the post-pandemic world. after the revitalization of the hotel business, rampant hotel brand expansion may take assume a different pattern (dassen, ) . china's hotel industry comprises of almost % independent hotels (about , ) and only approximately % of the hotels are operated by hotel chain brands (oyo, ). owing to the pandemic, individual hotels are likely to suffer more severely than the other actors; this is because the former are intrinsically susceptible to disaster (zhou, ) . they suffer from disorganized operation and management; unstable service quality; poor hygiene condition; high turnover rate; weak customer loyalty; unprofessional cost control; and even unqualified fire, sanitation and public security (china hospitality association, ; djeebet, ; jin, ; k. sun, ; wu, ; zhou, ) . however, during the pandemic, the branded hotel chains emerged more competitive due to their advantages in the business model, refined sop, disaster management mechanism, and proficient operation. the pandemic promoted the reshuffling of the small-and medium-sized hotels, and it is expected to push them to upgrade to high quality branded hotel chains. the rebranding of individual hotels will provide the hotel industry a major opportunity to shift from the new property market to the stock property market (lanjing finance, ). china's hotel industry will see an increase in the ratio of branded properties and a focus on leading hotel brands. the pandemic helped hotel firms visualize this opportunity to promote the brands that can integrate individual hotels with the strong sales and marketing system of the hotel brands while maintaining the unique features of individual hotels, such as oyo, voco (launched by ihg), h hotel (huazhu), aaroom (sunmei), qingzhu (meituan), oyu (yilong) (zhou, ) . hotel firms should seize the opportunity to increase market share, while individual hotels can actively cooperate with major firms to achieve transformation and upgradation. in addition to summarizing the overall impacts of covid- on china's hotel industry, the importance and originality of this study are that it develops a covid- management framework comprising anti-pandemic phases, principles, strategies. it also offers original insights into major trends of china's hotel industry during the post-pandemic era, including the emergence of multi-business and multi-channels, product design and investment preference, digital and intelligent transformation, and market reshuffle. based on the disaster management literature and the experience and trends of china's hotel industry, the study aims to enable hotel practitioners reeling under the pandemic to live better for today and plan well for tomorrow. this study can inspire hotel firms globally to understand the disaster evolution scenarios, adopt effective anti-pandemic strategies, and strive for industry activation and revitalization. the covid- management framework can be adopted for managing health-related disasters in a broader context, which enhances the generalizability of this study. although china's hotel industry was the first receiver of the pandemic's ramifications, it took timely measures to cushion the economic loss and secure its employees and customers. the industry undertook social responsibilities and actively participated in the anti-pandemic battle during a comprehensive and elongated lockdown. after witnessing positive signs, the industry adopted a series of innovative measures to revitalize performance. the effect of covid- remains uncertain as the economic ramifications in the global hotel industry are existentially threatening. against this background, the experience of china's hotel industry will provide systematic, albeit limited, solutions to hotel firms abroad who are suffering from the health and economic crisis. besides, the pandemic will fundamentally change the economic environment of china's hotel industry. in this regard, the study provides scenarios and suggestions in the post-covid- hotel industry context in china, which will shed light on industry transformation and upgradation. the limitations of this study mainly lie in the lack of empirical exploration and the unpredictability of the pandemic. hence, future studies must use more accurate prediction models and methods. surveys about customers' post-pandemic travel willingness and consumption preference will help academics and practitioners to foresee the rehabilitated service ecosystem. there can be a deterioration in the performance of hotels serving as quarantine stations, hospital extensions, and medical crew dormitories. this decline may occur when occupants have negative connotations with the place due to their unpleasant memories about the virus, horror, suffering, and death. the performance may also boost as a result of its corporate social responsibility activities during the time. longitudinal studies can be conducted to explore their performance and examine whether it could have been improved with better marketing strategies. the future studies can empirically investigate the influences of technology adoption on customers' experience, engagement, satisfaction, loyalty, and the hotel brands' and properties' performances during the post-pandemic era. additionally, it would be worthwhile to investigate the benefits of live streaming marketing. the future research can also analyze the post-pandemic hotel franchising, merging, and acquisition strategies. towards diversification: the pandemic situation forces the hotel industry to innovate and transform exploring disaster resilience within the hotel sector: a systematic review of literature tourism and natural disaster management process: perception of tourism stakeholders in the case of kumamoto earthquake in japan after the pandemic, the high-quality development path of chinese accommodation brands. symposium conducted at the rejuvenation · rebirth china cultural tourism and hospitality industry digital summit is there any investment opportunity in the severely damaged chinese hotel industry? the impact of covid- on china's lodging industry research on the qingming holiday tourism market japanese tourism and the sars epidemic of how to manage the covid- impact: tips and recommendations from hotel industry experts what is the impact of covid- on the global hospitality industry? hotels as critical hubs for destination disaster resilience: an analysis of hotel corporations' csr activities supporting disaster relief and resilience the q revpar of huazhu hotel dropped by more than half, and the revpar of deutsche hotel dropped by % models of crisis management: an evaluation of their value for strategic planning in the international travel industry towards a framework for tourism disaster management the response of tourism businesses vis-à-vis the economic ramifications of sars-cov- . aiest crisis events in tourism: subjects of crisis in tourism responding to crisis: severe acute respiratory syndrome (sars) and hotels in singapore covid- could be under control by end of april, china's top respiratory expert says in the post-pandemic era, the 'digital viability' of the hotel industry coronavirus: for china, the economic pain has only just begun the role of the hotel industry in the response to emerging epidemics: a case study of sars in and h n swine flu in in hong kong the ihg greater china picked up, the global occ is between % to % a framework of knowledge management systems for tourism crisis management the anti-epidemic journey of china's hospitality industry. symposium conducted at the rejuvenation · rebirth | china cultural tourism and hospitality industry digital summit sars: lessons in strategic planning for hoteliers and destination marketers the most downloaded remote office apps in china, million people are using them the effects of sars on the korean hotel industry and measures to overcome the crisis: a case study of six korean five-star hotels fosun and china lodging's hotels accelerate their opening, the hotel industry welcomes the spring crisis management in tourism disaster management: findings from a systematic review. disaster prevention and management crisis management during the sars threat: a case study of the metropole hotel in hong kong five major online office apps hard core pk the survival of hotels during disaster: a case study of hong kong in the post-pandemic trend and opportunities of non-standard accommodation. symposium conducted at the rejuvenation · rebirth | china cultural tourism and hospitality industry digital summit coronavirus: china's first confirmed covid- case traced back to the epidemic accelerated transformation of the hotel industry. symposium conducted at the rejuvenation · rebirth | china cultural tourism and hospitality industry digital summit a tourism crisis recovery checklist hanting stores adopted 'deep cleaning standards' to help hotel travel recovery adaptations to a face-to-face initial teacher education course 'forced'online due to the covid- pandemic public-private collaboration for disaster risk management: a case study of hotels in matsushima coronavirus: can live-streaming save china's economy? big data report of china's individual hotel owners qiu you: after the oandemic, investors will prefer 'small and refined' mid-range hotels affected by the pandemic, the first quarter revenue of btg hotel decreased by . % yoy to million yuan tourism disaster planning and management: from response and recovery to reduction and readiness a review of research on tourism risk, crisis and disaster management: launching the annals of tourism research curated collection on tourism risk, crisis and disaster management crisis and disaster management in jordanian hotels: practices and cultural considerations. disaster prevention and management the hotel operation during the pandemic: challenges and opportunities. duocaitou and donglixuetang atour tells you: how to seize the new middle class with the fourth space scene chinese mainland hotel industry shows early signs of performance recovery revitalization and future of the hospitalityindustry. symposium conducted at the rejuvenation · rebirth | china cultural tourism and hospitality industry digital summit the anti-epidemic and post-epidemic international group's hotel development. paper presented at the rejuvenation · rebirth | china cultural tourism and hospitality industry digital summit perspective crisis: the impact of covid- on hotel industry and its response. huamei consulting ctrip released the 'tongpao' plan, measures invested billion in support funds living with risk. a global review of disaster reduction initiatives. new york: international strategy for disaster reduction the tourism industry and the impact of covid- scenarios and proposals. global journey consulting a theoretical model for strategic crisis planning: factors influencing crisis planning in the hotel industry top-down or outside-in? culturally diverse approaches to hotel crisis planning who timeline: covid- after the anti-epidemic battle, the hotel group's large-scale brand output. symposium conducted at the rejuvenation · rebirth | china cultural tourism and hospitality industry digital summit travel live-streaming helps the 'spring seed' of the travel industry the 'anti-pandemic power' of the hotel industry in the robot 'big data jinjiang hotel's net profit for the first quarter of was million yuan , individual hotels are dying in loneliness? where is the new journey? international hospitality management. key: cord- -wl mlk authors: bozkurt, ozan; sen, volkan; irer, bora; sagnak, levent; onal, bulent; tanidir, yiloren; karabay, emre; kaya, coskun; ceyhan, erman; baser, aykut; duran, mesut berkan; suer, evren; celen, ilker; selvi, ismail; ucer, oktay; karakoc, sedat; sarikaya, ege; ozden, ender; deger, dogan; egriboyun, sedat; ongun, sakir; gurboga, ozgur; asutay, mehmet kazim; kazaz, ilke onur; yilmaz, ismail onder; kisa, erdem; demirkiran, engin denizhan; horsanali, ozan; akarken, ilker; kizer, onur; eren, huseyin; ucar, murat; cebeci, oguz ozden; kizilay, fuat; comez, kaan; mercimek, mehmet necmettin; ozkent, mehmet serkan; izol, volkan; gudeloglu, ahmet; ozturk, bilgin; akbaba, kaan turker; polat, salih; gucuk, adnan; ziyan, avni; selcuk, berin; akdeniz, firat; turgut, hasan; sabuncu, kubilay; kaygisiz, onur; ersahin, veli; ibrahim kahraman, halil; guzelsoy, muhammet; demir, omer title: nation‐wide analysis of the impact of covid‐ pandemic on daily urology practice in turkey date: - - journal: int j clin pract doi: . /ijcp. sha: doc_id: cord_uid: wl mlk objective: to present a nation‐wide analysis of the workload of urology departments in turkey week‐by‐week during covid‐ pandemic. methodology: the centers participating in the study were divided into three groups as tertiary referral centers, state hospitals and private practice hospitals. the number of outpatients, inpatients, daily interventions and urological surgeries were recorded prospectively between ‐march‐ and ‐may‐ . all these variables were recorded for the same time interval of as well. the weekly change of the workload of urology during pandemic period was evaluated; also the workload of urology and the distributions of certain urological surgeries were compared between the pandemic period and the same time interval of the year . results: a total of centers participated in the study. the number of outpatients, inpatients, urological surgeries and daily interventions were found to be dramatically decreased by the third week of pandemics in state hospitals and tertiary referral centers; however the daily urological practice were similar in private practice hospitals throughout the pandemic period. when the workload of urology in pandemic period and the same time interval of the year were compared; a huge decrease was observed in all variables during pandemic period. however, temporary measures like ureteral stenting, nephrostomy placement and percutaneous cystostomy have been found to increase during covid‐ pandemic compared to normal life. conclusions: covid‐ pandemic significantly effected the routine daily urological practice likewise other subspecialties and priority was given to emergent and non‐deferrable surgeries by urologists in concordance with published clinical guidelines. the first case in turkey was this article is protected by copyright. all rights reserved reported at march and the peak of daily cases and deaths were seen during the th week of the pandemic curve in our country. the workload of hospitals has increased considerably during the pandemic process and many healthcare measures were taken by governments and hospital systems. most of the hospitals turned to pandemic or quarantine hospitals and had to serve only covid- patients. some detailed recommendations were published for the triage of urological surgeries during the covid- pandemic. - like other surgical subspecialties; cancellation of elective surgeries and utilization of solely emergent surgeries and non-deferrable oncologic surgeries that delay may cause negative impact on survival have been performed in urology clinics according the triage recommendations. also, urological outpatient clinics have been adapted to new social distancing rules in covid- pandemic; the number of appointments was limited and only emergent patients could be treated in most of the urology clinics in worldwide as in our country. , , in this report, we aimed to present a nation-wide analysis of the workload of urology departments in turkey week-by-week during covid- pandemic and to compare the outcomes with the same time interval of the year . the study was approved by the local ethics committee. an announcement of the study was sent to all urology clinics across turkey via e-mail and social media. all of the centers that agreed to participate in the study were included in the study. this article is protected by copyright. all rights reserved all of these variables were also recorded week-by-week at the same time interval of the year . other surgical and diagnostic approaches were not analyzed as guidelines regarding covid- pandemic suggested the postponement of nearly all surgeries for female urology, andrology and some other elective surgical operations. , [ ] [ ] [ ] the centers were divided into three groups as tertiary referral centers, state hospitals and private practice hospitals. the weekly change of the workload of urology throughout the pandemic period was evaluated; also the workload of urology and the distributions of certain urological surgeries were compared between the pandemic period and the same time interval of the year . all statistical analyses were performed with the statistical package for the social sciences (spss, inc., chicago il), version , software for windows. shapiro-wilk test was used to determine whether the data was normally distributed, since p values were found to be greater than . , it was decided that the data were normally distributed. after the descriptive statistics were made, the data for the period and pandemic period were compared with the paired-samples t test. the results were given as mean ± standard deviation and n (%). p< . was considered statistically significant. a total of centers from all geographical areas participated in the study. of these centers; ( . %) were tertiary referral centers, ( . %) were state hospitals and ( . %) were private practice hospitals. the number of outpatients, inpatients, urological surgeries and daily interventions were found to be dramatically decreased by the third week of pandemics in state hospitals and tertiary referral centers; however the daily practice were similar in private practice hospitals throughout the pandemic period. urooncological surgeries were decreased week by week in tertiary referral centers; a huge decrease was observed for the stone surgeries at the third week of the pandemics in tertiary referral centers and state hospitals; however the number of emergent/trauma surgeries was relatively similar in both centers during the pandemics. the weekly analysis of workload of urology and urological surgeries by categories were given in this article is protected by copyright. all rights reserved when the workload of urology in pandemic period and the same time interval of the year were compared; a huge decrease was observed in all variables during pandemic period (table ) . in a detailed analysis of the three groups of centers; a significant decrease was detected in outpatients, inpatients, daily interventions and urological surgeries in tertiary referral centers and state hospitals; however the decrease was not statistically significant in private practice hospital in terms of inpatients and daily interventions ( although the total numbers of temporary measures like nephrostomy placement ( to ; - . %) and percutaneous cystostomy ( to ; - . %) for certain instances decreased; the rate of these procedures for emergent-trauma surgeries has been found to increase during pandemic period ( % to . % and . % to . %; respectively). urologists took active role in fighting against covid- with all of the centers participating in this study; . ± . , . ± . , . ± . pandemic outpatient clinics were performed by urologist in tertiary referral centers, state hospitals and private practice hospitals, respectively. this article is protected by copyright. all rights reserved the radical prostatectomy and definitive therapies can be deferred; small renal masses can be safely observed with active surveillance, and the treatment of localized kidney cancers (ct b and ct tumors) can be delayed to - months without adverse affects in outcomes; however radical nephrectomy should be performed in priority in locally advanced kidney cancers this article is protected by copyright. all rights reserved (ct +); the risk of a delay in the treatment of upper tract urothelial cancer (utuc) is depended on the stage and grade of cancer, especially in high-grade utuc a delay up-to months was found associated with disease progression, so keep in mind nephroureterectomy in these patients; avoid from delaying radical orchiectomy in testicular cancer patients; avoid from a delay in penile cancer treatments including surgeries. was also detected in all of the oncologic surgical procedures during pandemic period in our study (- . %). as stated above, most of the urooncological surgeries are usually performed in tertiary referral centers in our country; so the highest decrease has been observed in these centers whereas no significant change was observed in private practice hospitals in terms of urooncological surgery. the lowest decrease in urooncological surgeries was detected in radical cystectomy operations in the present study as most of the above-mentioned reports and guidelines offer prioritization of radical cystectomy. , we detected a sharp decrease within rd and th week of the pandemic in our country for all urological as well as urooncological cases as government and healthcare authorities suggested lock-down measures for the spread of sars-cov- ; and those low case load continued until the end of our study period which reflects the end of lock-down measures in our country. an interesting finding of this study was that the ratio of almost all urooncological surgeries was similar between the pandemic period and routine daily practice despite a significant decrease in total numbers. we did not deeply analyze the surgical indications, but surgery for higher risk cases for all cancer types might have been prioritized in most involved centers. tur-bt was the mostly utilized urooncological surgical procedure for both the pandemic period and normal life conditions in our country in concordance with previous reports. cancellation of elective surgeries for urolithiasis, benign prostatic hyperplasia and urethral strictures were recommended in pandemic period. if there is an obstruction in upper urinary tract, this article is protected by copyright. all rights reserved the ureteral stenting or nephrostomy tube placement are recommended instead of definitive treatments. , , the eulis collaborative research working group published the results of a survey related with routine practice of endourologists in stone diseases during the covid- pandemic. they pointed that the majority of the participants ( . %) have used to perform temporary interventions like jj placement or percutaneous nephrostomy, rather than the stone removal operations. gul et al reported that complicated ureteral stone diseases have increased in pandemic period; consequently the rate of nephrostomy placement has also increased. in pandemic patients were primarily treated by state hospitals and tertiary referral centers in our country, so the elective cases were cancelled by these hospital types whereas most private practice hospitals did not treat covid- patients. our findings demonstrated that workload for urological diseases dramatically decreased during covid- pandemic. however, the workload of hospitals dramatically increased during the covid- pandemic and most of the hospitals had to turn to pandemic or quarantine hospitals and serve this article is protected by copyright. all rights reserved only covid- patients. a total of pandemic outpatient clinics by -hour shifts were done by urologists in our study. so, we detected that urologists also took active role in the front-line management of covid- patients in our country. participation of mainly tertiary referral centers in comparison with state and private practice hospitals constitute one of the limitations of the present study. most state hospitals also turned to pandemic hospitals and did not serve for routine practice. participation of more state hospitals would better reflect daily practice. however, results demonstrated that most of the urology workload was met by tertiary referral centers in our country. conclusions: covid- pandemic led to a serious challenge to healthcare systems. like the worldwide results; the number of outpatients, inpatients and daily interventions have decreased, elective surgeries mostly deferred and a priority has given to emergent and high-grade malignancy surgeries in our country. we believe that the results of the present study will help in organization of human resources and triage of urology clinics for further possible mass casualty events. conflict of interest: none declared. this article is protected by copyright. all rights reserved world health organization. coronavirus disease (covid- ) situation report - considerations in the triage of urologic surgeries during the covid- pandemic covid- and urology: a comprehensive review of the literature changes in urology after the first wave of the covid- pandemic european association of urology guidelines office rapid reaction group: an organisation-wide collaborative effort to adapt the european association of urology guidelines recommendations to the coronavirus disease the early impact of covid- pandemic on surgical urologic oncology practice in turkey: multi-institutional experience from different geographic areas changes in urology after the first wave of the covid- preserving operational capability while building capacity during the covid- pandemic: a tertiary urology centre's experience influenza: the mother of all pandemics accepted article this article is protected by copyright. all rights reserved . duley mg. the next pandemic: anticipating an overwhelmed health care system risks from deferring treatment for genitourinary cancers: a collaborative review to aid triage and management during the covid- pandemic delaying radical cystectomy after neoadjuvant chemotherapy for muscle-invasive bladder cancer is associated with adverse survival outcomes evaluating the effect of time from prostate cancer diagnosis to radical prostatectomy on cancer control: can surgery be postponed safely? a delay in radical nephroureterectomycan lead to upstaging impact de la pandémie de covid- sur l'activité chirurgicale au sein des services d'urologie de l'assistance publique -hôpitaux de paris management, surgical considerations and follow-up of patients in the covid- era endourological stone management in the era of the covid- urolithiasis practice patterns following the covid- pandemic: overview from the eulis collaborative research working group the increased risk of complicated ureteral stones in the era of covid- pandemic acknowledgements: none declared. key: cord- -w zqxwdh authors: kanekar, amar; sharma, manoj title: covid- and mental well-being: guidance on the application of behavioral and positive well-being strategies date: - - journal: healthcare (basel) doi: . /healthcare sha: doc_id: cord_uid: w zqxwdh the raging covid- pandemic has been a great source of anxiety, distress, and stress among the population. along with mandates for social distancing and infection control measures, the growing importance of managing and cultivating good mental well-being practices cannot be disregarded. the purpose of this commentary is to outline and discuss some research-proven positive well-being and stress reduction strategies to instill healthy coping mechanisms among individuals and community members. the authors anticipate that usage of these strategies at the individual and the community level should greatly benefit the mental well-being not only in the current covid- pandemic but also in any future epidemics at the national level. covid- is an unprecedented pandemic affecting people all over the world. as of august , covid- (caused by the novel coronavirus) has caused , , cases and , total deaths in the united states [ ] and , , cases and , deaths worldwide [ ] . the pandemic is still raging havoc at the time of writing this article. pandemic by definition means when a disease or a condition spreads across countries and continents [ ] . the covid- pandemic with its uncertainty has imposed great mental distress on the general public, its patients, and healthcare providers [ ] . the pandemic and its constant reporting in the media have increased distress-related psychological problems such as anxiety, depression, and insomnia [ , ] . at present, there is no established treatment for covid- or any vaccine for specific protection against it. the testing for covid- is not widely available and lacks desirable sensitivity and specificity [ , ] . the testing of its antibodies is also not quite accurate or readily available. hence, the current public health measures include preventing person-to-person transmission of the disease by separating people. among the approaches that are being used are ( ) isolation in which infected persons are separated from non-infected individuals; ( ) quarantine and fever surveillance of contacts who have been exposed but are not yet symptomatic; ( ) community containment in which social distancing and movement of the general public is restricted by efforts such as "stay at home orders" (community-wide quarantine) [ ] . such measures further compound the emotional distress being experienced by individuals. the pandemic also has an important economic aspect to it with millions of people losing their employment, which is a great source of emotional distress [ , ] . the fear associated with this pandemic is responsible for the activation of the hypothalamuspituitary-adrenal (hpa) axis [ ] . the hypothalamus liberates the corticotrophin-releasing hormone (crh) in response to emotional distress, which in turn, activates the pituitary gland to liberate the adrenocorticotropic hormone causing the liberation of cortisol from the adrenal cortex. cortisol, a glucocorticoid hormone, affects the body in several ways. for example, it affects the sleep/wake cycle, it affects the glucose metabolism, it regulates the blood pressure, and it boosts energy so one can handle stress [ ] . all these effects eventually drain the body's energy resources in the long run and also compromise immunity and mental resilience [ ] . although the centers for disease control and prevention (cdc) have provided some guidelines to reduce stress and initiate coping [ ] , the need of the hour seems to be planning and having resources and techniques for long-term mental health flourishing and better emotional health management. recent reports from the world health organization calls for global action to invest in and strengthen mental health services to avert an impending mental health crisis [ ] . mental health denotes emotional, psychological, and social well-being [ ] . positive mental health and positive psychology have an imminent role to play during this unprecedented public health crisis. although there is enough evidence-based literature on the application of positive mental health techniques at individual level for stress reduction or life fulfillment, its application in a pandemic scenario is minimally explored [ , ] . the purpose of this commentary is to address the unexpected and uncertain situation experienced due to this pandemic (which is to cause anxiety, alarm, panic) and a deep sense of ongoing fear by providing readers with research-proven techniques and strategies for generating and maintaining momentary and lifelong happiness, fulfillment, and entitlement to positive being and positive living. some of the strategies such as nurturing and maintaining social connections (while maintaining physical distancing), mindfulness and momentary living, goal commitment, and resilience [ ] will be explored, particularly from its applicability to the current covid- pandemic. the authors will additionally explore the science of gratitude development and maintenance as a strong strategy in this pathway. happiness strategies classically outlined in lyubomirsky's book "the how of happiness" revolve around (a) living in the present, (b) managing stress (which is outlined later in this article), and (c) investing in social connections [ ] . similarly outline strategies of broadening your thinking, raising your positivity-ratio, and disputing negative thinking and fear (which is obvious during pandemics) greatly assist in maintaining well-being at its highest levels [ ] . mindfulness meditation practice daily helps in quieting one's mind and prevents the constant internal mental chatter. this is additionally proven to focus your attention on the present moment and a lot of existing research has proven the efforts of its practice in maintaining and nurturing improved mental health. [ , ] . for example, the student population has greatly benefitted from a mindfulness course in terms of improved well-being, decreased stress, and increased resilience [ ] . similar benefits were noted in diverse populations such as older adults [ ] , adolescents [ ] , and educators [ ] . a systematic review [ ] and another meta-analysis [ ] found that mindfulness-based stress reduction (mbsr) was effective in reducing stress, depression, anxiety, and distress and in improving the quality of life of healthy individuals. the role of religion and prayer in reducing stress cannot be overemphasized such that studies have proven that prayer plays a significant role which is no less than meditation and other mind-body techniques in reducing stress [ ] . social connections (some of which are explained later) have shown proven associations between long-term well-being [ ] [ ] [ ] , and this could be practiced in a 'lockdown' environment by way of telephonic, message, and video-contact with family, friends, and colleagues. the role of dispositional and/or trait gratitude in mental well-being is a comparatively recent development in positive psychology [ , ] . there are some possible mechanisms of applying gratitude for generating positive mental well-being leading to prolonged life satisfaction and flourishing in life such as: (a) savoring positive life experiences, particularly in eras of pandemics such as spending time with your kids, having healthy meals or pursuing hobbies while being indoors could be joyful; (b) building positive emotions, which help in creative activities such as writing, playing an instrument, painting, and singing, and finally (c) engaging in social connections via electronic means and video-chats with family and friends, which assist in generating social bonds leading to improved relationships, elevated self-esteem, and overall psychological well-being [ ] living indoors and not going outdoors due to 'lockdowns' in a pandemic provides an individual level opportunity for self-introspection and assessing and reframing current and planned events through a positive lens and engaging in active problem solving [ ] . building and maintaining gratitude through actions of kindness, being thankful that one is living, and enjoying all the benefits that life offers also helps in coping with stressful situations by building lifelong resilience [ ] . there are several determinants of positive mental health such as hardiness, sense of coherence, social support, optimism, and self-esteem [ ] that are important in the context of covid- . according to the hardiness theory [ ] , three attributes can enhance our coping. the first one is "control" that pertains to one's belief that one can influence the environment. in the case of covid- , the control can come from taking all the precautionary measures that are under one's control. if one has lost his or her job, one needs to still maintain a sense of control and continue trying for alternatives. adhering to such measures will help one endure the adverse effects of distress and have better mental health. the second attribute in hardiness is that of "commitment", which pertains to one's deep involvement in whatever one does. with covid- , if one is confined to the home one can get involved in creative activities such as writing, cooking, drawing, and other activities that keep one busy. searching for a job if one has lost one's job with commitment will also lower distress. such commitment to everyday activities will help cope with stress and achieve better mental health. the third and final attribute of hardiness is that of "challenge", which pertains to one's ability to undertake change, confront new activities, and seek avenues for growth. the covid- pandemic provides ample opportunity for the challenge, which if harnessed appropriately, can foster positive mental health. the second theory that is of relevance to covid- is the sense of coherence theory [ , ] . the three components of the sense of coherence are comprehensibility, manageability, and meaningfulness. comprehensibility pertains to the ability to see the stressor that one faces as making some sense in the context of its structure, consistency, order, clarity, and predictability. with covid- , the comprehensibility of the stressor is lost and replaced with uncertainty, which results in distress. the second component of manageability pertains to the ability to believe that the resources under one's control are sufficient to meet the demands posed by the stressors. with covid- , one may at times feel that one is overwhelmed, but once again reminding oneself that the problem is temporary and the solution is inbuilt in the problem will go a long way in lowering distress and fostering positive mental health. the final aspect of the sense of coherence is that of meaningfulness, which pertains to the belief that life makes sense, and that the stressors in life are worthy of putting efforts into dealing with. it requires accepting stressors in life as challenges instead of feeling that they are burdensome. this type of attitude in dealing with covid- -related crises of any kind is vital not only in dealing with emotional distress but also in succeeding in life. the third theory that is of relevance in the covid- pandemic is that of social support, which is the help obtained through social relationships [ , ] . social support was classified into four kinds: ( ) emotional support that requires the provision of understanding, caring, love, and fosters reliance; ( ) informational support that requires the provision of information, counsel, and guidance; ( ) instrumental support that requires the provision of tangible help; ( ) appraisal support that provides evaluative help. during these times of covid- pandemic, all these types of social support are very much needed. one needs emotional support to buffer emotional distress; one needs informational support to keep abreast with latest developments on the disease, resources, and opportunities; one needs instrumental support in the form of tangible resources, and one needs appraisal support on various facets of dealing with the pandemic and its influence on one's life. another theory linked to good mental health is that of optimism [ ] , which requires one to expect the best possible outcome in any situation and is a learned behavior [ ] . optimism, in the covid- context, will operate through enhancing one's efforts to avoid the disease by increasing one's attention to information regarding its threat, directly improving coping, and building a positive mood. a final theory that is popular in the mental health field and common parlance is that of self-esteem [ , ] . a favorable attitude of oneself or confidence in one's self-worth is very important for mental health and must be maintained during the covid- pandemic no matter what the circumstances are. the concept of 'death anxiety'-the anxiety and psychological distress among human beings due to thoughts related to fear of death in the current covid- pandemic-has been growing recently such that 'coronaphobia' has been quite evident as a construct predicting generalized anxiety along with death anxiety across the population [ ] . fortunately, this anxiety can be measured [ ] and techniques used to manage it. although some of the strategies as suggested by the world health organization such as minimizing news feeds and promoting social media usage could be beneficial [ ] , emerging research suggests the role of positive self-talks and cognitive behavior therapy as effective modalities to modify or attenuate the 'death anxiety' [ , ] . thought interference, particularly annoying thoughts related to fear of death due to covid- can be very disturbing for individuals, and these strategies promote the 'problem-centered' coping style [ ] for stress reduction and, along with the behavioral strategies mentioned earlier, could be highly effective. the covid- pandemic continues to dominate the public health field. the authors believe that although the initial panic caused by the pandemic has mitigated to some extent its effects (such as anxiety, stress, fear, and uncertainty) will continue to linger for months ahead. there were a number of theories discussed in this commentary such as the hardiness, sense of coherence, and the social support theory. these theories when applied to a pandemic scenario, such as the current covid- scenarios, greatly helps us shape our understanding of the impact that this pandemic is having on anxiety, fear, and stress. social support theory guides us in managing and coping with these mental health conditions. future research should be aimed at the application of these theories in improved understanding of the role they play specifically in the covid- pandemic, and how the constructs of these theories could be modified to enhance mental health and well-being among covid- affected individuals. social support theory-based constructs could be utilized in developing and implementing interventions in preventing and promoting mental health in covid- affected individuals. additionally, the behavioral and positive well-being strategies outlined and discussed in this commentary provide guidance not only to individuals and community members at the frontline of this pandemic but also to people staying at home due to 'stay at home' orders. it behooves us to make use of as many behavioral strategies in our repertoire in these unprecedented and precarious times. funding: there were no funding sources we would like to acknowledge for this article. the authors declare 'no conflict of interest'. coronavirus disease : cases in the us rolling updates on coronavirus disease (covid ) covid and its mental health consequences public mental health crisis during covid- pandemic progression of mental health services during the covid- outbreak in china antibody testing for covid antibody detection and dynamic characteristics in patients with covid isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus ( -ncov) outbreak the socioeconomic implications of the coronavirus pandemic (covid ): a review covid- , unemployment, and suicide psycho-neuroendocrine immune interactions in covid- : potential impacts on mental health practical stress management workplace responses to covid- associated with mental health and work performance of employees in japan substantial investment needed to avert mental health crisis pandemic fear" and covid- : mental health burden and strategies the how of happiness: a scientific approach to getting the life you want top-notch research reveals the -to- ratio that will change your life mobile mindfulness meditation: a randomized controlled trial of the effect of two popular apps on mental health effects of mindfulness meditation on mindfulness, mental-wellbeing and perceived stress exploring the impact of mindfulness on mental well-being, stress and resilience of undergraduate social work students predictors of improvements in mental health from mindfulness meditation in stressed older adults enhanced well-being through mindfulness: supporting the gifted adolescent journey the impact of mindfulness on the wellbeing and performance of educators: a systematic review of the empirical literature mindfulness-based stress reduction as a stress management intervention for healthy individuals: a systematic review mindfulness-based stress reduction for healthy individuals: a meta-analysis spirituality and prayer on teacher stress and burnout in an italian cohort: a pilot, before after controlled study social capital as a resource for mental wellbeing among older people: a systematic review longitudinal associations between social connections and subjective well-being in the english longitudinal study of ageing greater good science center a meta-analytic review of the relationship between dispositional gratitude and mental well-being. personal how does trait gratitude relate to subjective well-being in chinese adolescents? the mediating role of resilience and social support the resilience workbook: essential skills to recover from stress, trauma and adversity foundations of mental health promotion personality and resistance to illness unraveling the mystery of health: how people manage stress and stay well social support and health optimism, coping, and health: assessment and implications of generalized outcome expectancies learned optimism. how to change your mind and life measures of self-esteem society and the adolescent self-image incremental validity of coronaphobia: coronovirus anxiety explains depression, generalized anxiety and death anxiety measuring anxiety related to covid- : a turkish validation study of the coronavirus anxiety scale. death stud looking after our mental health the role of self-talk in predicting death anxiety death anxiety in the time of covid- : theoretical explanations and clinical implications disease perception and coping with emotional distress during covid- pandemic: a survey among medical staff key: cord- - z h authors: perea del pozo, eduardo; aparicio‐sánchez, daniel; hinojosa ramírez, fátima; pareja ciuró, felipe; durán muñoz‐cruzado, virginia; sánchez arteaga, alejandro; dios barbeito, sandra; padillo ruiz, francisco javier title: a prospective cohort study of the impact of covid world pandemic on the management of emergency surgical pathology date: - - journal: br j surg doi: . /bjs. sha: doc_id: cord_uid: z h nan ( ⋅ %) ** ( ⋅ %) ( ⋅ %) ** ( %) ( %) ( ⋅ %) ( ⋅ %) ( %) ( %) ( %) ( %) ( ⋅ %) ( ⋅ %) ( %) ( ⋅ %) ( ⋅ %) ( ⋅ %) ** ( %) ( %) ( %) ( %) ( %) ( ⋅ %) ( %) ( %) ( ⋅ %) ( ⋅ %) ( %) hospiral re-admission ( ⋅ %) ( ⋅ %) ( ⋅ %) ( %) ( ⋅ %) ( %) ( ⋅ %) ( %) ( %) ( ⋅ %) ( %) ( %) ( %) ( %) ( ⋅ %) ( ⋅ %) ( ⋅ %) ( %) ( ⋅ %) ( %) ( %) ( %) ( ⋅ %) ( ⋅ %) ( %) ( ⋅ %) ( ⋅ %) ( ⋅ %) department for surgical pathology (n = ), a significant decrease in the total number of its patients was observed during pandemic period ( , % less than in ). the mean waiting time in the emergency department, was significantly shorter during pandemic ( ⋅ ± ⋅ hours vs ⋅ ± ⋅ hours; p = ⋅ ), probably related to the decrease in the no-covid activity in the emergency department during confinement status. both groups showed similar demographic data. emergency pathologies, were classified as complicated or uncomplicated . an increase in preoperative complicated diagnosis was observed during pandemic ( % vs ⋅ %; p = ⋅ ). overall comparation showed that there was an increase in the complications rate during pandemic ( ⋅ % vs ⋅ %; p = ⋅ ) with an increase of ⋅ days in icu stay. nevertheless, mortality was lower in patients operated during pandemic ( ⋅ % vs %) ( table ) . the worse results during covid- pandemic were founded in acute appendicitis with an increase in complicated appendicitis ( % vs ⋅ %, p = ⋅ ), hospital stay ( vs days, p = ⋅ ) and surgical site infections ( % vs ⋅ %, p = ⋅ ). interestingly, a % reduction in the number of diagnosed cases of appendicitis was observed during pandemic period when compared with the previous year. this could be explained by the fact that these patients have received conservative management by primary care physicians, since no data exists that would cause one to believe that the real incidence of acute appendicitis is lower . during the period of the pandemic some groups have proposed conservative management for this pathology to reduce the need for emergency room visits and operating rooms . this treatment is controversial and should be limited to cases of uncomplicated appendicitis, as a recurrence rate of % to % per year has been documented. a decrease in the indication for surgical treatment of cholecystitis was observed. also, a longer evolution of the disease at home (average of days), before surgical evaluation at the hospital was observed. this determined a more conservative attitude in the management of these patients. when operated, the percentage of the laparoscopic approach remaining at %, similarly to the previous year. in the comparative analysis of the remaining subgroups, it was only noted that in the peritonitis group, the median stay in the icu was significantly longer in the covid group ( ⋅ ± ⋅ days vs ⋅ ± ⋅ days, p = ⋅ ). the general analysis of the data suggests that, due to confinement measures and the risk of nosocomial infection in hospital centers, patients have chosen to go to primary care centers, avoiding a visit to the hospital as much as possible when they did not consider it necessary. thus, pandemic due to sars-cov- virus has had a negative impact on emergency surgical pathology due to an increase in the days of preoperative evolution and therefore more evolved forms of these pathologies. this has caused an increase in hospital stays and morbidity, without affecting mortality. covid- and emergency surgery global guidance for surgical care during the covid- pandemic the management of intra-abdominal infections from a global perspective: wses guidelines for management of intra-abdominal infections antibiotics alone as an alternative to appendectomy for uncomplicated acute appendicitis in adults: changes in treatment modalities related to the covid- health crisis the author declare that there are no conflicts of interest regarding the publication of this paper. key: cord- -vnazexhj authors: pelargos, panayiotis e.; chakraborty, arpan r.; adogwa, owoicho; swartz, karin; zhao, yan d.; smith, zachary a.; dunn, ian f.; bauer, andrew m. title: an evaluation of neurosurgical practices during the covid- pandemic date: - - journal: world neurosurg doi: . /j.wneu. . . sha: doc_id: cord_uid: vnazexhj objective to understand how the covid- pandemic has affected the neurosurgical workforce. methods a survey consisting of twenty-two questions assessing respondent’s operative experience, location, type of practice, subspecialty, changes in clinic and operative volumes, changes to staff, and changes to income since the pandemic began was distributed electronically to neurosurgeons throughout the united states and puerto rico. results there were respondents throughout the united states and puerto rico representing all practices types and subspecialties. nearly all respondents reported hospital restrictions on elective surgeries. most reported a decline in clinic and operative volume. nearly % of respondents saw a decrease in the work hours of their ancillary providers, and almost half ( . %) of respondents had to downsize their practice staff, office assistants, nurses, schedulers, etc. overall, . % of survey responders had experienced a decline in income, while . % expected a decline in income in the upcoming billing cycle. more senior neurosurgeons and those with a private practice, whether solo or as part of a group, were more likely to experience a decline in income as a result of the pandemic as compared to their colleagues. conclusion the covid pandemic will likely have a lasting effect on the practice of medicine. our survey results describe the early impact on the neurosurgical workforce. nearly all neurosurgeons experienced a significant decline in clinical volume which leads to many downstream effects. ultimately, analysis of the effects of such a pervasive pandemic will allow the neurosurgical workforce to be better prepared for similar events in the future. downstream effects. ultimately, analysis of the effects of such a pervasive pandemic will allow the neurosurgical workforce to be better prepared for similar events in the future. procedures, triaging of urgent cases, deploying telemedicine for office visits, and altering the traditional workflow of every day practice. for many, productivity has decreased, and neurosurgeons' practices and income have been affected. to better understand the ways the covid- pandemic has affected the neurosurgical workforce, we conducted an electronic survey of practicing neurosurgeons in various settings. specifically, we sought to understand how the pandemic has impacted case and clinic volume, compensation, changes in clinic structure, employment of support staff, and attitudes towards these changes. categorical variables were summarized using counts and proportions and were compared among grouping variables such as subspecialty and geographic region (high volume vs low volume) using the fisher's exact test. cochran-armitage trend test was used to assess the relationship between number of years in practice and the reduction in income during the covid- pandemic. high volume regions were defined as those states, districts, or territories with greater than , cases of covid- and low volume regions were defined as those with less than or equal to , cases, as reported by the united states centers for disease control and prevention on may , . all tests were two-sided, and a p value less than . was considered statistically significant. statistical analysis was performed using sas (version . , sas institute, cary, nc) . demographics the first email was opened by , aans and csns members with opening the survey link. the second email was opened by , members with opening the survey link. in total, there were respondents from all states as well as from the district of columbia and puerto rico. the overall response rate was . %. all practice types and subspecialties were represented ( figure ). there were survey responders from low volume regions and from high volume regions; survey responders declined to give the location of their practice. most respondents were in practice for greater than twenty years ( . %), while the remainder were evenly distributed in terms of years of practice: - years ( . %), - years ( that care was not negatively affected and . % were unsure ( figure ). there was no significant difference between effects to neurosurgery care when comparing respondents by their years in practice, type of practice, or sub-specialty. most respondents ( . %) reported a decline in their clinical volume: . % experienced - % decline, . % experienced - % decline, . % experienced - % decline, and . % experienced - % decline. twenty-four respondents ( . %) closed their practice completely during the pandemic, while . % of respondents experienced no change in clinic volume and . % reported an increase in their clinic volume ( figure ). neurosurgeons in practice greater than years ( . % vs. . % for all others, p=. ), those in solo private practice ( . % vs. . % for all others, p=. ), and those whose primary sub-specialty is spine ( . % vs. . % for all others, p= . ) were significantly more likely than their counterparts to completely close their outpatient clinics during the pandemic (figure ). of those who continued to see patients in clinic, most continued to do so remotely, as . % increased their use of telemedicine. similarly, most respondents ( . %) reported a decline in their operative volume: . % experienced - % decline, . % experienced - % decline, . % experienced - % j o u r n a l p r e -p r o o f decline, and . % experienced - % decline. thirty-three respondents ( . %) stopped operating completely during the pandemic, while . % reported no change in their operative volume and . % reported an increase in their operative volume ( figure ). several groups were found to be more likely than their counterparts to stop operating completely during the pandemic period. those in practice greater than years were more likely to stop operating during the pandemic than those in practice less than or equal to years ( . % vs. . %, p<. ). neurosurgeons in solo private practice were more likely to stop operating than their peers in other practice types ( . % vs. . %, p=. ). spine surgeons were more likely to stop operating than colleagues in other sub-specialties ( . % vs. . %, p<. ) ( figure ). further, the reduction in operative volume differed significantly (p=. ) between regions with high volumes of covid- cases compared to regions with low volumes of cases (table ) . while there were generally fewer restrictions placed on outpatient surgery centers, . % of respondents decreased their use of the outpatient surgery center, while nearly one-tenth ( . %) continued to operate at the same or greater volume. most respondents ( . %) did not perform surgeries at outpatient surgery centers prior to or during the pandemic. slightly more than half of respondents ( %) reported working with residents or fellows. of those, . % felt that the education of their residents and/or fellows has suffered as a result of the pandemic, and . % felt that adequate adjustments were made to the educational program so that their education would not suffer. just over sixty percent of respondents noted a decrease in resident and fellow clinical work hours during this period. j o u r n a l p r e -p r o o f similarly, nearly % of respondents saw a decrease in the work hours of their ancillary providers. only . % of respondents reported increasing the work hours of their ancillary providers to make up for the decrease in clinical hours worked by residents and fellows. almost half ( . %) of respondents had to downsize their practice staff, office assistants, nurses, schedulers, etc., due to the pandemic, while . % did not have to make any changes to their staff. the pandemic has also had an effect on the academic pursuits of neurosurgeons. of the respondents who participate in research, nearly half ( %) stated that they were unable to enroll patients into clinical trials during the pandemic period. many respondents also had to downsize or close their research laboratories ( %) or were unable to hire laboratory staff ( . %). further, many experienced delays in publication of scholarly papers ( . %), and . % were unable to obtain or experienced delay in obtaining grant funding. a small group applied for emergency grant funding to study covid- associated neurosurgical issues ( . %) (figure ) . exposure to covid- only . % of respondents reported their practice being affected due to themselves or a partner being exposed to or contracting covid- resulting in quarantine. further, only . % of respondents were asked by their hospital to provide non-neurosurgical medical services to covid- patients. just over % said they would be willing to provide non-neurosurgical medical care to covid- patients on a voluntary basis if needed, while . % said they would not be willing to provide non-neurosurgical medical care, and another . % stated they were j o u r n a l p r e -p r o o f not comfortable or qualified to provide these services. neurosurgeons in practice less than years were significantly more likely to be willing to provide non-neurosurgical care to covid- patients than those in practice greater than years ( . % vs. . %, p=. ). neurosurgeons, and % of peripheral nerve neurosurgeons experienced or expected to experience a decline in income. these differences across subspecialties were statistically significant (p=. ). overall, there was no statistical difference found in income changes between responders practicing in high volume versus low volume states (p=. ) ( table ) . nonetheless, nearly two-thirds of participating neurosurgeons felt that care for their patients suffered during this period and these effects were similar for all neurosurgeons regardless of their seniority, type of practice, sub-specialty, or practice location. overall, nearly three-fourths of neurosurgeons experienced greater than % decline in outpatient clinic volume with just over % of respondents closing their outpatient clinics during the pandemic. these changes in clinic volume were similar in all states and regions regardless of the volume of covid- cases. this decline in clinic volume creates a major access problem for our patients and an ethical dilemma in deciding which patients are "emergent" enough to be seen or to have surgery. those in solo private practices were disproportionately affected as nearly % closed their outpatient clinics in response to the pandemic, a statistically significant percentage compared to other practice types. given that many solo practices are located in areas which are already underserved, this may serve to perpetuate the patient access problem. while this survey did not specifically address the types of patients or cases that were delayed, it may be worth further study to determine which elective or semi-elective cases are universally considered "urgent" or "emergent". for example, should surgery for a patient with newly diagnosed glioblastoma be delayed for a number of weeks based on the fact that it is not truly emergent? the pandemic has also brought out new ways in which we practice neurosurgery. nearly % of those that responded to our survey said that they increased their use of telemedicine. j o u r n a l p r e -p r o o f the reduction in operative volume was higher than previously reported during the early pandemic period. nearly three-fourths of respondents had experienced a decline of greater than % in operative volume with . % stopping surgery completely. while the reduction in operative volume was not significantly different across neurosurgeons with different experience or type of practice, there was a statistically significant decline in operative volume in regions with higher cases of covid- . further, spine surgeons were more likely to stop operating completely during the pandemic period. this decrease in inpatient operative volume did not translate to a proportional increase in outpatient surgery center use as only . % of respondents continued to operate at the same or greater pace at the outpatient surgery center, while more than double that decreased their use of the outpatient surgery center during the same period ( . %). the pandemic not only affected neurosurgeons and their patients, but it had similar effect on neurosurgery trainees and ancillary providers. over sixty percent of respondents noted a decrease in resident and fellow clinical work hours, and nearly % expressed concern that their education suffered as a result. the shortfall in work by residents was not compensated for by increased use of ancillary providers as less than % reported an increase in their ancillary providers' work hours. rather, . % of survey responders saw a decrease in their ancillary providers work hours and almost half had to decrease their practice staff. these limitations in residents and ancillary providers may have led to a larger role for the staff neurosurgeon in call coverage and inpatient hospital work which may have further limited patient access. given the decline in clinic and operative volumes, it can be expected that most neurosurgeons would experience a decline in income during the pandemic. overall, % of respondents experienced or expected a decline in income during the pandemic while the remaining % did not. neurosurgeons who practiced in a private practice setting were more j o u r n a l p r e -p r o o f likely to experience a decline in income than those who were hospital-employed (p<. ). those who were hospital-employed were more likely to experience a decline in income than those in an academic setting (p<. ). this may be reflective of the fact that there are often other non-clinical components of the compensation plan of the academic neurosurgeon which were less likely to be affected by covid- (i.e. research, teaching, etc.). there was a greater decline in income of more senior neurosurgeons during the pandemic period. this likely reflects the fact that senior neurosurgeons have well-developed elective referral bases and mature practices that are more likely to be strongly affected by any limitation in elective work. it is also possible that the more senior neurosurgeons were more vigilant about practicing social distance measures. it is also important to consider that while the incoming revenues significantly declined, practice expenses (payroll, insurance, office expenses, etc.) continue unchanged, which led . % of the respondents in our study to downsize their practice in an effort to limit these expenses. this, in turn, may lead to issues for patient access in the future. overall, about two-third ( . %) of respondents were willing to assist in the non- neurosurgical care of covd- patients if needed. neurosurgeons that have been in practice more than years stated they were less willing to provide non-neurosurgical medical care than their counterparts in practice fewer than twenty years. most neurosurgeons, however, were not asked by their hospital to assist in the non-neurosurgical care of these patients, as only . % of respondents reported being asked by their hospital to do so. was also sent to non-board-certified neurosurgeons; therefore, it reasonable to expect that the survey was sent to the majority of practicing neurosurgeons in the united states and puerto rico. as with any survey, there is the opportunity for response bias. our selected population was not random, and it is quite possible that neurosurgeons most affected by the pandemic were non- responders due to their increased responsibilities working on the front lines caring for covid patients. additionally, due to the rapid progression of the pandemic, the survey could not be validated as a psychometric analysis tool prior to distribution. therefore, the results should be interpreted more in a descriptive fashion. the covid pandemic will likely have lasting effects on many aspects of the practice of medicine. our survey sheds light on the particular vulnerabilities of different practice types and subspecialties to disasters of this nature. nearly all neurosurgeons have seen a significant decrease in clinical volume. this was most pronounced for more senior surgeons who have well established elective practices and more likely for those who subspecialize in spine. as expected, this decrease in volume has led to decreased income for neurosurgeons and their practices which in many cases has led to restructuring of the practice itself. in the future, this may lead to j o u r n a l p r e -p r o o f reduced patient access. there is little doubt that the lessons learned will shape our clinical practice patterns, compensation models, and preparedness for future pandemics or disasters. there are no conflicts of interest to report as pertained to this work. the authors would like to acknowledge the support and collaboration from the csns workforce committee. without their assistance in survey distribution, this work would not have been possible and certainly would not have been as complete. finally, the authors appreciate and acknowledge the willing participation of survey respondents nationally in this difficult time. most respondents experienced a greater than % decline in their clinic volume, while over % of respondents closed their clinic altogether during the pandemic. figure . change in clinic volume by years in practice, type of practice, and subspecialty during the covid- pandemic. those in practice greater than years were significantly more likely to close their clinic than the remainder of their colleagues ( . % vs. . %, p=. ). those in solo private practice were significantly more likely to close their clinic than those in other practice types ( . % vs. . %, p=. ). those whose primary sub-specialty was spine were significantly more likely to close their clinic than those in other sub-specialties ( . % vs. . %, p=. ). most respondents experienced a greater than % decline in their operative volume, while over % of respondents stopped operating altogether during the pandemic. j o u r n a l p r e -p r o o f figure . change in operative volume by years in practice, type of practice, and subspecialty during the covid- pandemic. those in practice greater than years were significantly more likely to completely stop operating than the remainder of their colleagues ( . % vs. . %, p<. ). those in solo private practice were significantly more likely to completely stop operating than those in other practice types ( . % vs. . %, p=. ). those whose primary sub-specialty is spine were significantly more likely to completely stop operating than those in other sub-specialties ( . % vs. . %, p <. ). j o u r n a l p r e -p r o o f ( ) q has the covid epidemic affected your academic and research pursuits? select all that apply. have not been able to enroll patients in clinical research trials ( ) downsized or closed research lab ( ) unable or delayed in obtaining grant funding ( ) i have applied for emergency covid grant funding for study of covid associated neurosurgical issues ( ) delay in publication of scholarly papers ( ) unable to hire laboratory staff ( ) i do not participate in any clinical or laboratory research ( ) j o u r n a l p r e -p r o o f q has your practice been negatively affected because you or one of your partners was exposed to or contracted covid resulting in quarantine? o yes ( ) o no ( ) q have you been asked by your hospital to provide non-neurosurgical medical services to assist with covid patients (i.e. critical care, medical care, ventilator management, er triage, etc.)? s. -investigation, data curation, writing (original draft and revisions), visualization bs -writing (original draft and revisions) owoicho adogwa m.d.-data curation, writing (review and editing) zhao ph.d. -validation and formal analysis, visualization smith m.d. -writing (original draft and revisions), writing (review mba -conceptualization, methodology, investigation, data curation, writing (original draft and revisions), writing (review and editing), project administration and supervision key: cord- -vlxewj k authors: hooker, claire; leask, julie title: risk communication should be explicit about values. a perspective on early communication during covid- date: - - journal: j bioeth inq doi: . /s - - - sha: doc_id: cord_uid: vlxewj k this article explores the consequences of failure to communicate early, as recommended in risk communication scholarship, during the first stage of the covid- pandemic in australia and the united kingdom. we begin by observing that the principles of risk communication are regarded as basic best practices rather than as moral rules. we argue firstly, that they nonetheless encapsulate value commitments, and secondly, that these values should more explicitly underpin communication practices in a pandemic. our focus is to explore the values associated with the principle of communicating early and often and how use of this principle can signal respect for people’s self-determination whilst also conveying other values relevant to the circumstances. we suggest that doing this requires communication that explicitly acknowledges and addresses with empathy those who will be most directly impacted by any disease-control measures. we suggest further that communication in a pandemic should be more explicit about how values are expressed in response strategies and that doing so may improve the appraisal of new information as it becomes available. behavioural responses-both practicing recommended behaviours (such as putting on a mask) and the refusal to do so are reactions to perceive loss of control (jetten et al. ; wong ) . "self-determination" is used in relation to communities as much as to individuals, which may provide new understandings or representations for relations between individual and communal self-shaping in the context of pandemics (eichler ) . given the extensive and growing data that reveals values and ideologies as often the strongest determinants of people's attitudes to health protection behaviours (e.g., dryhurst et al. ; seale et al. ) , we suggest that rich accounts of self-determination, autonomy, and/or freedom beyond "thin" versions of liberty (e.g., to travel or not wear masks) will have much to offer pandemic ethics in future research. in this paper we make a modest beginning on exploring what adding a "values perspective" to risk communication might look like by examining one risk communication principle, "communicate early and often," in the very first stages of the pandemic. our argument is that use of this principle could have minimized some of the negative impacts seen in australia and the united kingdom in february and march . we contend that a hitherto undiscussed reason for why this principle is effective is because it conveys value for people's self-determination, even as this is threatened by both disease and the measures needed to control the disease. we discuss how proactive communication might have improved community preparedness but also suggest that being more explicit about this value should have involved better acknowledgement of, and empathetic engagement with, those who were most directly impacted by control measures at that time. as a result, the australian government could have better addressed stigma, racism, and xenophobia during late january and february and mitigated or avoided food and hygiene product stock-outs in early march. we conclude with a brief discussion of how communication of values might have avoided the loss of trust and misunderstandings associated with the misnamed strategy of achieving "herd immunity" when discussion of this emerged in the united kingdom. we conclude by suggesting that the communication of values can improve the quality of pandemic response and can increase the degree of trust placed in responding authorities. when people face the heightened fear of a novel, uncontrolled, and uncertain risk such as the pandemic of sars-cov_ , self-determination in multiple dimensions is compromised and well-being is reliant on the knowledge and decisions of experts and governments (siegrist and zingg ) . risk communication must connect as much as possible with people's sense of selfdetermination, even (perhaps especially) in contexts where individual liberties may become limited. how c a n t h i s b e d o n e ? t h e p r i n c i p l e s o f r i s k communication-for example communicating early and often, being open and transparent, and not dismissing concerns as "panic"-are all means of affording some sense of control in people facing a situation of high concern and uncertainty. transparency is a core recommendation for pandemic risk communication (van der weerd et al. ) , because it enables citizens' knowledge and confidence (earle, siegrist, and gutscher ; siegrist and zingg ) that the response strategy will occur as expected. because values and moral commitments are intrinsic to all pandemic responses, we argue that true transparency requires that pandemic risk communication is explicit about the values that guide it. further, we suggest that part of the task of managing a pandemic is to cultivate public convergence (kahan ) on the guiding values. this is important because a pandemic response, and communicating about it, are not actually separable: action is, in itself, a very powerful form of communication (amabile and kabat ) , as we discuss below. we suggest that conveying respect for selfdetermination involves early, proactive communication with those who are directly affected by any response strategy. this will involve addressing issues of fairness or justice, since these are present in virtually all ethical frameworks for pandemic response (australian government department of health ; kinlaw, barrett, and levine ; n e w z e a l a n d n a t i o n a l e t h i c s a d v i s o r y committee-kāhui matatika o te motu ; thomas, dasgupta, and martinot ) and have also been shown to strongly influence peoples' perceptions of, and responses to, risk (siegrist, connor, and keller ) . the earliest representations of the new coronavirus in media coverage of the disease in australia and the united kingdom conformed to what priscilla wald has identified as "the outbreak narrative," in which a disease emanating from a non-white, non-western nation is eventually contained as a result of the scientific and technologic prowess of democratic western societies (wald ) . through january and february , health risk communicators from who and government health authorities balanced communication of the potential seriousness of the new disease (clun ; the sydney morning herald ), with caution about acting too strongly or too soon. nonetheless several elements in news media coverage of the novel coronavirus disease in this period together tended to frame the disease as unlikely to significantly threaten australia or the united kingdom (the guardian ). these included comparisons with sars, mers, and ebola, and associations of the new disease with chinese political authoritarianism, which somewhat signalled that these diseases were unlikely to cause widespread disease in western nations (boseley ) . the discourse of "technology as saviour" (hooker, king, and leask ; wald ) , in the form of early and frequent expectation that a vaccine and effective treatment would be rapidly developed by scientists, was prominent (garcia ; mannix ) . media coverage identified that mortality was strongly associated with the elderly and those with comorbidities. media commentators have noted that this reporting often portrayed the elderly, and those with significant health issues, as a passive, vulnerable minority, even one that was expendable or burdensome (ashimoni ). these representations have continued to raise considerable concern (see, for example, people with disability australia (pwda) et al. ) and provides an important context for later discussions of "herd immunity." ii. "communicate early and often" in this discursive media environment, we argue that earlier, proactive communication signalling that nations outside china might become affected and about the possibility of a pandemic was needed. early communication could have supported earlier sense-making, encouraged citizen engagement, and provided potential convergence towards a response strategy. by - february, the who and other health authorities were considering the possibility of a pandemic increasingly likely (callaway ). yet in australia there was little proactive public communication at this time-indeed, australian government websites only contained advice pertinent to travellers. the australian health sector emergency response plan for novel coronavirus (covid- ) was released on february (grattan ) but was accompanied by little transparent communication about what was being done or which elements of the plan were receiving attention. this created a "risk communication vacuum" (leiss ) . in this vacuum, messages came from sources not privy to government planning. one was virologist dr ian mackay, who recognized and attempted to fill the space by publishing an opinion piece in the sydney morning herald (mackay ) . this advised australians to prepare for a pandemic and suggested that australians moderately stock up on basic consumer items and medicine, urging people to "prepare, but do not panic." a steeply-increasing, sometimes harmful, and prolonged period of stockpiling of basic supplies like hand sanitizer, toilet paper, and flour swiftly followed in australia, fed by escalating public anxiety. we contend that earlier and values-oriented communication could have reduced the anxiety that was later expressed in stockpiling behaviours by enabling longer and more moderated preparation for what could be ahead. respect for citizens' complex selfdetermination within the context of potential outbreaks could be conveyed in the cautious communication of concrete scenarios concerning what people might consider in their own family preparation (for example, of how to manage if somebody became sick). this period of sense-making and preparation can allow proactive communication of values around which people might shape their responses, such as providing support for neighbours (e.g., new zealand national ethics advisory committee-kāhui matatika o te motu ). proactive early communication with supermarket managers could have limited or avoided stockpiling (poloyo ) . in attempting to avoid early overreactions, which unintentionally communicates a lack of trust in the public, government effectively intensified a problem, rather than reducing it. early communication centred on ideas of selfdetermination (acknowledging individual and communal aspects of this) could have helped address the challenge that most pandemic response measures affect people unequally (howse et al. ; vaughan and tinker ) . racism and stigmatization have been a feature of almost every epidemic in history (wailoo ) , with anti-asian prejudice and sinophobia widespread during the outbreaks of sars in (leung ) . explicitly confronting this through communication is crucial, not only to reduce violence and injustice but because these issues are entangled in epistemic judgements, as occurred in debates in australia during february, concerning racism in relation to containment measures. as reports of racism and a range of sinophobic behaviours (including avoidance of chinese businesses, suburbs, and people) began to appear in the media from the end of january (vrajlal ; young ), a range of containment measures that primarily, but not exclusively, affected chinese people were enacted. a number of wealthy, independent secondary schools in australia had unilaterally acted to temporarily exclude students who had recently travelled in china (most of whom were chinese), including imposing segregated quarantine, in contravention of commonwealth government health advice (hooker, silva, and anderson ). on february , the australian government announced that foreign national travellers from mainland china would not be allowed entry into australia; australian citizens (most of whom were chinese) returning from china were quarantined in offshore detention facilities notorious for their use with refugees. while it is now generally agreed that early border measures to limit transmission of disease into australia were effective, at the time, school exclusions, selective border controls, and travel-related quarantines in immigration detention camps were questioned as unnecessary and were sometimes perceived as forms of racism (bedo and mcphee ; hooker, silva, and anderson ) . to convey respect for people's self-determination, leaders should reflexively examine how their actions might also be interpreted as disrespectful and discriminatory. actions such as containment (border control) measures are strong forms of communication (sandman and lanard ). while we do not suggest that this was not an important measure at the time, communication needed to address (particular through pre-established two-way channels) those likely to be directly affected by containment measures-in this case, chinese and other asian australians. the predictable harms of stigmatization needed to have been explicitly acknowledged alongside the scientific rationale (major et al. ). risk communication handbooks should urge authorities to be open and honest about the potential for discrimination, in the same way they are encouraged to be explicit about uncertainty. early communication proactively addressing the potential for stigmatization and racism might have not only limited some of the direct racism experienced by asian australians and u.k. nationals but helped to clarify judgements around containment measures by ensuring they were not confused with forms of racism. we note that sometimes violent racism is continuing in australia at the time of writing (fang, yang, and zhou ) . perhaps the most intractable feature of covid- in its early stages was the persistent framing of pandemic response strategies as a choice between "the economy" and "saving lives." this frequently contested (hamilton et al. ; zeballos-riog ) framing exemplified the tendency toward values-based polarization in views about the best response to covid- (kahan ) . early communication with the groups most likely to be affected by any given containment strategy could help with this seemingly incommensurable choice. we discuss how improved communication might have contributed to the pandemic response in the united kingdom when this was first announced on march , the day after the who formally declared a pandemic. a crucial period for communication about covid- in australia and the united kingdom were the first two weeks of march : the period in which the reality and likelihood of a pandemic was dawning, exponential growth feared in both countries (churley ) , and news of crisis from iran and italy were fresh. this period of adjustment was critical for sense-making amid uncertainty, through which convergence on a response strategy could occur. in the united kingdom there was reportedly heated disagreement between members of the scientific advisory group for emergencies over what response strategy to pursue. such disagreement is a predictable but highly confounding feature of emergency response (christensen and painter ) . these differences were epistemic-they involved different appraisals of the evidence available and different assumptions about "herd immunity"-but they were fundamentally driven by different values. how the term "herd immunity" was constructed and interpreted in relation to covid- is worthy of a study in itself. the indirect protection of susceptible individuals resulting from high levels of immunity across a population (d'souza and dowdy ), "herd immunity" is a concept associated most with vaccination (hanage ; macintyre ) . for the first two weeks of march, the u.k. government pursued a "mitigation" (wickham ) strategy with little social restriction under the belief that there was ultimately little the government can do to stop the virus (shipman and wheeler ); social distancing restrictions would incur a high economic cost, be unsustainable for a long period, and would produce a more severe second wave of infection in winter (wickham ) . this approach assumed that reaching "herd immunity" through widespread infection would resolve the pandemic (the times ). this strategy fitted with prime minister boris johnson's values of limiting state intervention and government spending (wickham ) ; we note that it also fitted with the cluster of values termed "hierarchical individualism" in cultural cognition theory (kahan ) . within twenty-four hours of johnson's announcement of this policy on march , outrage was rising as the strategy's scientific credibility was disputed by epidemiologists and others (sandle and boyd ) , who pointed out that the "mitigation" strategy would result in an overwhelmed national health service and that achieving high exposure across the population should not be anticipated to achieve long lasting population immunity and thus conclude the pandemic. the mitigation strategy was perceived as a callous sacrifice of lives, with the media widely reporting that top government aide dominic cummings had told a private meeting that the government's strategy was "herd immunity, protect the economy and if that means some pensioners die, too bad" (buchan ) . a "crisis of trust" (smyth ) followed. even though modelling from imperial college, london (ferguson et al. ) , indicated how swiftly the nhs would be overwhelmed, and convinced the u.k. government to introduce a "suppression" strategy (wickham ) from monday march , doubts remained. the government was urged to "come clean" about the sources of the information on which the mitigation strategy was based (smyth ) , and media investigations followed. earlier communication in this case, where valuesdriven disputes existed between experts (kahan ), likely would not have prevented political crisis, but it would have allowed more time for sense-making processes in scientific, medical, and public communities. we recommend a commitment in pandemic planning documents to sharing sources, models, and evidence at the time of deliberation, and with it, the questions advisors are asking (such as, will the same number of deaths occur regardless of strategy over the long term?) earlier public discussion of these questions might at least have somewhat disrupted simplistic framing and use of "herd immunity," by enabling early and public scientific challenge from epidemiologists, as occurred from mid-march (armitage and hawke ; barr ; macintyre ). we note that the simplistic expectation that "herd immunity" would end the pandemic remains widespread (e.g., hasan ). earlier communication that explicitly discussed values might have enabled better public sense-making about the "mitigation" and "suppression" strategies. because each strategy invoked values differently and prioritized different values, we suggest that better communication is needed to explain how values such as being "proportionate" (australian government department of health ) are expressed in these strategies. because the costs of different strategies tend to fall on different members of the community, valuesexplicit communication could more effectively engage with the concerns and needs of those most affected when a strategy is selected. this paper offers some early thoughts for why the principles of risk communication should include the recommendation to be explicit about values. we are not suggesting that better communication alone can prevent or resolve either epistemic or political disagreements in pandemic management nor alleviate every anxiety nor uncertainty. but we do suggest that, given that disagreements about pandemic responses are very often driven by different value commitments, a "values turn" in risk communication (feinberg and willer ) is likely to produce significant benefits, including clearer communication, with greater impact. with regard to the principle of communicating early, we have shown that this is a means of conveying respect for peoples' threatened sense of self-determination, understood broadly. we suggest that this communication of value offers a richer explanation for why early communication, especially where directed with empathy at those most affected by response measures, is important. values-based risk communication will enable a more effective pandemic response. when self-descriptions contradict behavior: actions do speak louder than words what is herd immunity and could it slow the spread of coronavirus covid- around the world? abc news effective risk communication how coronavirus exposes the way we regard ageing and old people. the conversation australian health management plan for pandemic influenza what is herd immunity and is it a possibility for the uk? the independent stranded chinese students confused and angry over australia's coronavirus travel ban who declares coronavirus a global health emergency the guardian coronavirus: downing street denies claim dominic cummings wanted to protect economy over elderly. the independent time to use the p-word? coronavirus enters dangerous new phase crisis an d emerg ency ris k co mmuni catio n m an ual the politics of sarsrational responses or ambiguity, symbols and chaos? it is a shock to realise everything is not going to be ok. the times health system responds to virus threats. the sydney morning herald best practices in public health risk and crisis communication risk communication-principles, tools, and techniques. paper presented at the presentation for the united states nuclear regulatory commission evaluation and effective risk communication what is herd immunity and how can we achieve it with covid- ? covid- school of public health expert insights risk perceptions of covid- around the world trust, risk perception and the tcc model of cooperation reconciling indigenous peoples' individual and collective rights: participation, prior consultation and selfdetermination in latin america coronavirus has fuelled racism against asian-australians, but why isn't official data showing it? abc news moral reframing: a technique for effective and persuasive communication across political divides impact of non-pharmaceutical interventions (npis) to reduce covid- mortality and healthcare demand risk perception and communication unplugged: twenty years of process political liberty: integrating five conceptions of autonomy an introduction to risk communication we thought we had three years": uq team to fast-track coronavirus vaccine. the sydney morning herald government triggers emergency plan for covid- pandemic, and considers economic assistance. the conversation the guardian. . the guardian view on herd immunity: yes it was "part of the plan open letter from australian economists: don't sacrifice health for "the economy". the conversation . i'm an epidemiologist. when i heard about britain's "herd immunity" coronavirus plan, i thought it was satire. the guardian coronavirus and the threat to south asian democracy. the interpreter journalists' views about reporting avian influenza and a potential pandemic: a qualitative study coronavirus fears can trigger anti-chinese prejudice. here's how schools can help. the conversation chronic disease, health equity and covid- together apart: the psychology of covid- bioethical inquiry cultural cognition as a conception of the cultural theory of risk ethical guidelines in pandemic influenza: recommendations of the ethics subcommittee of the advisory committee of the director the chamber of risks: understanding risk controversies the yellow peril revisited: the impact of sars on chinese and southeast asian communities risk communication in public health risk communication: a handbook for communicating environmental, safety, and health risks busting the myths about covid- herd immunity, children and lives vs jobs. nhmrc centre for research excellence integrated systems for epidemic response. blog you and i may get coronavirus-and live with it: here's how to prepare for a pandemic. the sydney morning herald public health with a punch: fear, stigma, and hardhitting media campaigns csiro to begin testing coronavirus vaccines within weeks. the sydney morning herald national ethnic disability alliance (neda), et al. . statement of concern -covid- : human rights, disability and ethical decisionmaking a toilet paper run is like a bank run. the economic fixes are about the same. the conversation four questions for risk communication: a response to roger kasperson coronavirus: boris johnson warns "many families will lose loved ones" because of virus. the mirror containment as signal: swine flu risk miscommunication. peter sandman risk communication website covid- is rapidly changing: examining public perceptions and behaviors in response to this evolving pandemic crisis communication and the public health coronavirus: ten days that shook britain-and changed the nation for ever trust, confidence, procedural fairness, outcome fairness, moral conviction, and the acceptance of gm field experiments the role of public trust during pandemics: implications for crisis communication perception of risk ministers urged to come clean on model for british response. the times keep coronavirus risk in perspective the theory of self-determination ethics in a pandemic: a survey of the state pandemic influenza plans ethics and risk communication the times. . the times view on boris johnson's handling of the coronavirus crisis: no immunity effective health risk communication about pandemic influenza for vulnerable populations chinese-australians facing racism after coronavirus outbreak stigma, race, and disease in th century america monitoring the level of government trust, risk perception and intention of the general public to adopt protective measures during the influenza a (h n ) pandemic in the netherlands heated" debate between scientists forced the psychology behind why some people refuse to wear face masks communicating risk in public health emergencies: a who guideline for emergency risk communication (erc) policy and practice this is racism": chinese-australians say they've faced increased hostility since the coronavirus outbreak began top economists are deriding the "false choice" between saving lives from coronavirus and maximizing economic growth publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations acknowledgments no funding or conflicts of interest are associated with this manuscript. the authors wish to gratefully acknowledge the very useful feedback provided by two reviewers of this article.author statement all authors contributed to the study conception and design. media analysis and the first draft of the manuscript was written by claire hooker. both authors edited and discussed subsequent versions of the manuscript. claire hooker completed the revisions in response to reviewers. all authors read and approved the final manuscript. key: cord- -czuw t i authors: radic, aleksandar; lück, michael; ariza-montes, antonio; han, heesup title: fear and trembling of cruise ship employees: psychological effects of the covid- pandemic date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: czuw t i the current covid- pandemic has evolved to unprecedented proportions. this research aimed to gain a deeper understanding of the psychological effects of the covid- pandemic on cruise ship employees stuck at sea. using an inductive qualitative approach, a synchronous online focus group was conducted with nine cruise ship employees who were stuck at sea during covid- pandemic. the findings revealed that covid- pandemic has managed to erase the feeling of joy from cruise ship employees who were stuck at sea while exposing weakness of cruise line companies such as poor human resource management leadership. moreover, covid- pandemic demonstrated that it is of paramount importance that cruise line companies create a comprehensive strategy in assisting their employees who are experiencing an anxiety disorder and depression. the managerial implications are outlined. up until , cruise tourism was the fastest-growing sector within the tourism industry [ ] ; however, on march , members of the cruise line international association (clia) voluntarily suspended their cruise ship operation due to the covid- pandemic, and on april a no sail order issued by the centers for disease control and prevention (cdc) suspended all cruise operations until september [ ] . the cruise line international association ( ) [ ] outlines that . million jobs worldwide will be in danger due to the suspension of cruise operations caused by the covid- pandemic. furthermore, major cruise lines are experiencing enormous financial losses [ ] , and fears from the covid- cruise tourism crisis have induced a devastating crash of major cruise lines stocks [ ] . thus, new ocean-going ships that are on order until with a total value of . billion usd$ [ ] , are at risk due to the shrinking liquidity of the extremely fragile cruise line industry. due to this poor liquidity and being on the verge of bankruptcy: • carnival corporation has laid off and furloughed employees from their miami-based office [ ] , laid off from their uk-based office [ ] , and tapped into various financial agreements, raising . billion usd$ in liquidity [ ] ; • royal caribbean cruises ltd. has laid off or furloughed approximately % of their employees in the united states [ ] and raised over $ . billion usd$ in liquidity [ ] ; • norwegian cruise line holdings ltd. furloughed about % of its workforce including shore side employees and roughly , shipboard workers [ ] , and raised close to . billion usd$ in liquidity [ ] . with suspended cruise ship operations and without revenue, cruise line companies are draining their funds at a fast rate. balboa [ ] predicts that from may , carnival corporation can sustain itself for more months, royal caribbean cruises ltd for more months and norwegian cruise line holdings ltd for more months. with such predictions, at least , crew members worldwide [ ] are in danger of losing their jobs. studies on well-being and life satisfaction of cruise ship employees are scarce; however, studies that are related to the psychological effects of being unemployed and isolated at sea due to the covid- pandemic are to the authors' best knowledge non-existent. thus, the purpose of this research is to obtain a deeper understanding of the psychological effects of the covid- pandemic on cruise ship employees stuck at sea. to accomplish this task, the following research question is addressed: "what are the psychological effects of the covid- pandemic on cruise ship employees stuck at sea?" this study is exploratory in nature and the present work addresses a major research gap. the aim of this research will be addressed by utilizing an inductive approach to data collection and an online synchronous focus group with cruise ship employees stuck at sea during the covid- pandemic. hence, to answer the research question and to fulfill the aim of this study, the specific objectives were to: (a) explore if cruise ship employees are experiencing certain worries, fears and sleep disturbances; (b) investigate how the lack of onboard social cohesion and lack of family and friends social support is affecting cruise ship employees; (c) assess components associated with perceived stress of cruise ship employees; and (d) evaluate the state of hope and sense of belonging of cruise ship employees. in light of the current covid- pandemic, the results of this study provide valuable contributions to the theory of cruise tourism. cruise tourism is a socio-economic system based on maritime transport with a sole purpose of creating tourism experiences founded on interaction between people, organizations, and geographical entities [ ] [ ] [ ] [ ] [ ] . as such, cruise ship employees have a crucial role in delivering quality service [ ] in a multi-sensory cruise experience [ ] . thus, the service quality and cruise experience are heavily dependent on the well-being and life satisfaction of cruise ship employees. looking at cruise ship employees' well-being, radic et al. [ ] argue that cruise ship employee well-being is a synthesis of happiness and pleasure. similarly, the life satisfaction of cruise ship employees can be understood as an individual's psychological aspects rooted in their hedonic satisfaction [ ] . considering the well-being and life satisfaction of cruise ship employees, bardelle and lashley [ ] outlined how a large number of crew members are experiencing homesickness and sadness while working on a cruise ship. while investigating onboard experiences of cruise ship employees, bolt and lashley [ ] found considerably stressful constraints that place pressure on cruise ship employees. furthermore, larsen at al. [ ] found how life satisfaction of cruise ship employees was strongly influenced by respect, social atmosphere, and quality of food and living quarters. hence, in a recent study on occupational health and safety of cruise ship employees, radic [ ] concluded how work-related injuries have profound negative effects on the well-being of cruise ship employees, creating a perception of unattractive and unfavourable working conditions among crew members. interestingly, cruise ship employees who resigned from cruise line companies to start a new beginning with a land-based job, exhibit a certain degree of nostalgia with a romanticized feeling about well-being and life satisfaction while being onboard [ ] . however, while being onboard, cruise ship employees are exposed to prolonged harsh working conditions in the form of constant time pressure and heavy workload coupled with the everlasting uncertainty about their next contract assignment [ ] . moreover, unfavorable working conditions combined with the inability of psychological detachment from the work creates a negative impact on cruise ship employees' well-being [ ] . thus, cruise industry news [ ] argues how poor well-being of cruise ship employees can affect their mental health, which leads to high employee turnover, absenteeism, and increased expenses due to health care costs. hence, it appears that cruise ship employees are trapped in what moore [ ] calls "misery machines". peculiar work and life conditions of cruise ship employees affect their well-being to the point of the alarming rise of suicide rates in recent years [ , ] . the shipowners' club [ ] briefly outlines that cruise ship employees' mental and physical health and relationships at home and onboard were evidently affected by the covid- pandemic. in summary, although aforementioned studies have provided a glimpse of cruise ship employees' well-being and life satisfaction, currently there exists a research gap on the psychological effects of a pandemic, in particular the covid- pandemic on cruise ship employees stuck at sea. because of the observational nature of the study, and in the absence of any involvement of therapeutic medication, no formal approval of the institutional review board of the local ethics committee was required. nonetheless, all subjects were informed about the study and participation was fully on voluntary basis. the study was conducted in accordance with the helsinki declaration. this research is explorative as it analyzes new and unprecedented areas of the covid- pandemic. the goal of this study is to explore the psychological effects of the covid- pandemic on the cruise ship workforce stuck at sea. taking into consideration that the covid- pandemic has led to a health and epidemiological type of crisis in cruise tourism, this novel situation needs to be explored in-depth, and qualitative research with an interpretivist paradigm was adopted. interpretivism argues that social phenomena should be studied from the perspective of involved social actors [ ] . communication and social relationships are comprised of diverse expositions and individual responses, and, as such, interpretivist-qualitative lenses provide a meticulous understanding of the connection between implication and action [ ] . furthermore, the interpretivist paradigm creates opportunities for accessing diverse expressions and points of view since this paradigm seeks to raise the voices of the community in the appraisal process [ ] . this study took an inductive approach and a qualitative method where an online synchronous focus group was conducted. the synchronous online focus group is a peculiar situation where the moderator and somewhere between four to nine participants are in an online chat room where everyone simultaneously types comments that are visible to all group members [ ] . possible participants were invited to take part in the research via the crew center facebook group that connects cruise ship employees. participants for this study were chosen using a convenience sampling method. to participate in the synchronous online focus group, the participants had to meet the following criteria: ( ) being stuck at sea on a cruise ship during the interview; ( ) being on a cruise ship since march , the day when members of the clia voluntarily suspended their cruise ship operation; ( ) being without a contract and not being paid while being stuck at sea; and ( ) not knowing their repatriation date. data were collected from nine cruise ship workers employed by four major cruise lines and who were on nine different cruise ships during the covid- pandemic. these cruise ship employees are members of various onboard departments. given the aim of examining the psychological effects of the covid- pandemic on cruise ship workforce stuck at sea, cross-sectional research was conducted. the major strength of a cross-sectional design is convenience, as such studies are quick to complete and relatively inexpensive [ ] , and they provide a picture of a situation related to a particular population within a specific time [ ] . in this study, a synchronous online focus group was conducted via the well-known text and voice messaging cross-platform whatsapp. this option ensured participants' anonymity since they are not visible to the group and the recent popularity of chat emoticons buffered the disadvantage of not having visual cues [ ] . the study was conducted on may and the online synchronous focus group lasted min. one of the authors who works on the cruise ship and was stuck at sea since march when members of the clia voluntarily suspended their cruise ship operation, acted as a moderator. at the end of the discussion, the moderator downloaded the entire script. written data were coded using open and axial coding techniques grounded in procedures outlined by strauss and corbin [ ] . online synchronous focus groups are not without shortcomings, however, rigor was achieved by following higginbottom's [ ] recommendations, carefully recruiting participants based on their experience and knowledge. validity was enhanced by facilitating a lavish data set as recommended by morse [ ] . reliability was ensured by following richard et al.'s [ ] recommendations with a skilled and experienced researcher (one of the authors) acting as moderator, which was instrumental in overcoming the disadvantages of lack of non-verbal cues, minimizing disturbing conduct of some of participants, and minimizing various errors and biases. in summary, an inductive approach and a qualitative method with an online synchronous focus group are commonly used for topics that are not well understood so the new insights could be discovered. this study aims to explore the psychological effects of the covid- pandemic on cruise ship employees stuck at sea. its explorative nature made online a synchronous focus group a suitable method for this study. furthermore, as an exploratory study on the psychological effects of the covid- pandemic, the portrayal of the sample as part of a specific entity is not a considerable worry as the method aims to investigate the aspects and provide a structure instead of variables estimation and their description. respondents from the synchronous online focus group were cruise ship employees who were on board since march ; they were without a contract and not being paid, and they did not know their repatriation date. the respondents' age ranged from to years; five respondents were from asia, followed by three respondents from europe, and one respondent from south america. the sample was evenly distributed in terms of gender, with five females and four males. looking at the participants' working departments, the sample had seven respondents from the hotel department, one participant from the marine and technical department, and one participant from the entertainment department (table ) . the maritime labour convention [ ] "seafarers' bill of rights" was extended to cruise ship seafarers in , and under the "seafarers' bill of rights", cruise line companies are obliged to provide for their crew members repatriation at the end of their contract. however, on april , due to the covid- pandemic, the cdc issued a no sail order, which has prohibited cruise line companies to use any form of commercial transportation for crew member repatriation purposes [ ] . the cdc's no sail order in combination with poor liquidity of cruise line companies due to the covid- cruise tourism crisis has created an unprecedented event leaving , cruise ship employees stuck at sea for months without any certainty when they will be repatriated to their homes [ ] . consequently, like song and li [ ] argue, the uncertainty of what future might hold can lead to anxiety. during the discussion, all participants have outlined that they are experiencing certain worries while being stuck at sea. my contract was until july . the company unilaterally stopped it on march and since then (today is may) they are holding me onboard without pay. my family needs financial support and i am unable to provide them financial support because my company doesn't want to pay for the charter flight, and the cdc is not allowing the company to send me home with a commercial flight. (cruise ship employee no. ) cruise ship employees' worries are related to not being able to provide financial support to their families, not being able to see their family and friends, and ultimately they are left with a feeling that they do not have any control of their life. they are experiencing negative economic and social effects of being unemployed and isolated at sea due to the covid- pandemic. thus, the aforementioned conditions can lead to anxiety, where house and stark [ ] define anxiety as a comprehensive adaptive reaction when the individual is facing an unknown danger. moreover, due to the covid- pandemic, government-issued isolations will have an enormous negative effect on mental health for many, especially on those individuals who are peripheral members of the society, because they are more likely to face financial deprivation and lower quality of life [ ] . although cruise ship employees come from various countries around the globe, the majority of them are from undeveloped or developing countries [ ] , thus, cruise ship employees' mental health will be most likely affected by the covid- pandemic. the anxiety of cruise ship employees stuck at sea is growing as they fear an uncertain future and an economic mega-crisis that lies ahead. increased anxiety and fear-associated traits within human behavior are related to the fearful stimuli and increased activity in the amygdala. it is well documented that fear spreads extremely fast and that no one is immune to fear [ ] . during the discussion, all respondents outlined that their biggest fears were related to not being able to see their family, not being able to go home, not getting paid, the uncertainty of what future holds, and knowledge of forthcoming financial deprivation. i fear that my son won't recognize me when i come home. i am already months onboard. i have to wear a mask while i talk to my son, and he always asks me to remove my mask because he can't see me. i can't hold off my tears when he tells me this. (cruise ship employee no. ) seafaring is an occupation that carries hardship [ ] , and the covid- cruise tourism crisis illustrated that cruise ship employees feel afraid, lonely, unprotected, and financially enslaved. living in fear is what makes one "being a slave" [ ] and since cruise ship employees are low paid, mobile, and under "maltese contract," "cyprus contract," or "swiss contract", they fit well in what mann [ ] describes as wage slaves. nevertheless, cruise ship employees come onboard with hopes that their work efforts will in return provide them and/or their family considerable financial benefits [ ] . furthermore, the covid- cruise tourism crisis has shattered, both in ethical and aesthetic nature, cruise ship employees' dreams and ideals of a brighter future. however, kierkegaard [ ] argues how such destruction leads only to the remolding of dreams and ideals on new grounds. sleep is a process that incorporates neurobiological, neurochemical, and psychological systems [ ] . moreover, an optimal period of quality sleep plays an important function as a safeguard for individuals' mental health and everyday performance [ ] . abysmal sleep quality can lead to quite a few psychological disorders including depression, anxiety, and paranoia [ ] . thus, sleep disturbances are one of the symptoms of anxiety [ ] . gillespie [ ] discusses how isolation and coronavirus anxiety lead to insomnia. during the discussion with the participants, every single one of the participants described in an individual way how their quality of sleep was poor. i am constantly tired although i am not working. with too much pressure on my shoulders, too much free time to think about all the possible things that can go wrong, locked inside my cabin, when night comes i can't fall asleep. i force myself to sleep, only to wake up every - h. looking at my watch asking myself when will this agony come to an end. (cruise ship employee no. ) a clear sign of cruise ship employees' growing anxiety is their sleep pattern. as days onboard become weeks, and weeks become months, cruise ship employees experience insomnia and when they fall asleep, nightmares wake them in distress. sleep disturbances are a common factor in anxiety disorders where complaints related to insomnia and even nightmares are fundamental in defining generalized anxiety disorder and even posttraumatic stress disorder [ ] . worries, fears, uncertainty, isolation in small cabins, lack of opportunity to share one's concerns, and loud noise from maintenance were just some of the factors that have led to sleep disturbance and anxiety of cruise ship employees. moreover, due to the cdc's no sail order [ ] , cruise line companies are failing to meet obligations related to cruise ship employees' living conditions, recreational areas and amenities set in the maritime labour convention [ ] "seafarers' bill of rights". depression is a profound medical illness that negatively affects how an individual feels, thinks, and acts, which ultimately leads to sadness and/or a deprivation of delight in previously pleasurable activities [ ] . seafarers are susceptible to diverse mental health disorders including depression [ ] . bearing in mind that social isolation is a robust contributor to depression [ ] , cruise ship employees that are stuck at sea for months [ ] due to the covid- pandemic are at risk to aggravate depressive symptoms. during the discussion, all respondents clearly outlined some traits of depression. this hopelessness, confusion, sadness, and longing. some of us have finished our contracts two months ago and since then we are not paid. there are people on board who are here for more than months. it's very hard for all of us and none of psychologist and none of that nonsense talk will help us. just look at the people who have committed suicide in the last days. i think there were or suicides by crew members who were stuck at sea. this is terrible. people are on the edge and most of the people are broken beyond repair. (cruise ship employee no. ) prolonged isolation, despair, deterioration of well-being, and impossibility to return to their homes so they can be reunited with their loved ones have seriously affected how cruise ship employees feel, think, and act. although evidence on seafarers' depression and suicide rates are scarce and fragmented [ ] , while being stranded at sea due to the covid- pandemic, four crew members have died under unclear circumstances and not related to the covid- virus [ ] . cruise ship employees who embark on the cruise ship in pursuit of a brighter future found themselves in what kulzer et al. [ ] describe as a world where fear survives. cruise ship employees are facing a transformational experience that rogell et al. [ ] pronounce as the journey of a lifetime. humans are social beings that are constructing the hierarchical structure of society to obtain and maintain resources [ ] . to comply with the maritime labour convention [ ] "seafarers' bill of rights", cruise line companies are in obligation to provide recreational facilities and amenities for socializing purposes of their crew members. however, the cdc's no sail order [ ] has specifically forbidden the usage of recreational facilities and amenities for socializing purposes. consequently, the cdc's no sail order [ ] has created both objective and subjective social isolation. subjective social isolation from both family and friends is associated with higher depressive symptoms [ ] . participants have made a clear statement that it is impossible to socialize due to the cdc's no sail order [ ] . by some law, we should have recreational space and space for socializing like crew bar or similar space. the cdc forbids the usage of crew gym, crew bar, or anything where we can group for socializing. i come from a society where we live in small and large groups caring for each other. this is also how we behave while we are on the ship. now we can't do that, so i fell very lonely, sad, and depressed. cruise ship employees socialize with one another in specially designated bars, while they are at the gym, on the rare occasion when they go ashore, and some of the crew members even engage in casual intimacy [ ] . however, while being stuck at sea due to the covid- pandemic, cruise ship employees feel alone, isolated, depressed, and detached because they are unable to enjoy onboard socialization due to the cdc's no sail order [ ] . the liminality of the cruise ship and rigid managerial hierarchical structure erase a clear line between private life and workplace of crew members [ ] , thus, while being stranded at sea, cruise ship employees have lost all points of reference except daytime and nighttime. human beings are social animals [ ] in need of relatedness to friends and family. however, cruise ship employees understand that to the cruise line companies they are nothing more than a number on their identification card, thus, for the cruise ship employees' perceived social support and relatedness to friends and family needs satisfaction is of paramount importance [ ] . furthermore, the quality of family interactions is of utmost importance for understanding the development process of depressive symptoms in adolescents [ ] . depressive symptoms decrease significantly with those individuals who enjoy strong family and spousal support [ ] . during the discussion, participants used every opportunity to stress how much they are missing their friends and family at home. under normal circumstances cruise ship employees leave their family and friends at home and the mental pressure of such decision weighs heavy on them. crew members cope with such hard decisions by psychologically preparing themselves that their sacrifice will provide them and/or their families with considerable financial benefits [ ] . however, in a case when cruise ship employees are stuck at sea due to the covid- pandemic, where the majority of them are not getting paid or are paid a minimal salary, the uncertainty of when they will go home, if they will find another job and what would be a new reality when they eventually go home, is crushing them. human functional brain networks is a system that organizes various assignments such as planning, anticipating, analyzing (executive control network), reflecting on previous experience (default mode network), determining the importance of the current environment (salience network), and focusing attention to the issue at hand (ventral attentional networks) [ ] . on april , cruise ship seafarers went to sleep with hopes that they will soon go to their homes and loved ones, however, they woke up on april in a completely different world where the cdc's no sail order [ ] was not allowing them to use any form of commercial transportation for repatriation purposes. thus, since that point in time, cruise ship employees have been under chronic stress, due to situations where salience brain network activity (scanning the environment for threat) has taken control and executive control brain network (analyzing current conditions) has been deactivated. fear is a mind killer [ ] , and being afraid of something suppresses the ability to think straight [ ] . as a consequence, sep et al. [ ] conclude how extrapolation of fear is a frequent indication of anxiety and trauma-related disorders. during the discussion, participants clearly outlined how they feel agitated due to the uncertainty of what the future holds. the covid- cruise tourism crisis managed to erase the feeling of joy from cruise ship employees, thus, it does not come as a surprise when they speak in an almost passive participant voice about their relentless complaints against diminished control of their own life. it appears as though fear of what might come has spread across the cruise ships. thus, melancholy prevents cruise ship employees from feeling any positive emotions. as the uncertainty of future events keeps on suffocating cruise ship employees, they grow agitated, confused, and depressed. for inexperienced seafarers, cruise ships appear as delightful ocean-floating hotels with never-ending entertainment, and a wonderful way to obtain monetary gain while being able to visit exotic places. however, cruise ship employees work and live on board for a prolonged period of time, and during their stay on board, they are often exposed to various stressful events that affect their life satisfaction [ ] . in light of the covid- pandemic, cruise ship employees that are stuck at sea are experiencing particularly high levels of stress that may develop mental health disorders such as anxiety and depression. during the discussion, all participants but one expressed how they feel stressed and nervous. i feel stressed and furious. if the president of the imo, cdc, or whatever had a kid or spouse stuck on a ship would they not do everything to get them home? it's common sense to allow crew members to go to their homes. did you know that crew members committed suicide in the last days? do you know why they did it? because they couldn't cope with stress, so what do you think will happen if this drags for another two months or until july when the no sail order comes to an end?! governments around the world need to step up and help their citizens who are crew members, and the cdc needs to come forward towards an agreement with an international organization and various governments. (cruise ship employee no. ) while being stuck at sea, cruise ship employees are caught in no man's land between: ( ) cruise companies on verge of bankruptcy that are trying to consolidate their liquidity; ( ) a distant cdc administration who are inhumanly insisting on noncommercial transportation for crew members' repatriation purposes; and ( ) quite a few government bureaucracies who are not allowing their crew members to come back home. due to the fear of uncertainty, stress builds up and it appears that on the high seas no one can hear crew members' silent screams of existential despair. lastly, as reconstructions in fear neurocircuitry influence anxiety disorder, chronic stress manifestation reorganizes fear neurocircuitry, triggering structural degeneration in the prefrontal cortex and hippocampus, thereby restricting dominance over the stress response [ ] . the covid- pandemic changed the world, and each human being has changed in their own way. when it comes to cruise ship employees, the covid- cruise tourism crisis showed that major cruise line companies do not have a contingency plan in case of a health and epidemiological type of crisis and that many governments do not have coherent leadership. consequently, cruise ship employees found themselves alone in a chaotic situation. during the discussion, the majority of participants shared the opinion that they cannot cope with all the things that are happening in the world during the covid- pandemic. every question we asked we get an answer "we don't know" or "we are not sure". we are really worried about our future and our mental health because this is a situation without a solution. we are not getting paid, we can't buy drinks, the gym is closed, and there are no activities that would relax us here onboard. when you want to buy morning coffee you need to wait in line for h, because the ship is understaffed. of course all of us are very stressed in this situation. today security called us in cabins to ask for the names of people who were protesting yesterday. it is serious retaliation and this is against human rights. it feels like none of us have a right to say our opinion. we just want the world to hear us because all of us just want to go home to be with our families. (cruise ship employee no. ) cruise ship employees who are stuck at sea have found themselves in a peculiar situation that they cannot change because they depend on multilateral dialog and agreements between cruise line companies, the cdc, airlines, and various governments. as uncertainty crawls in every pore of cruise ships, causing waves of stress, depression, anxiety, and panic, cruise ship employees are in need to create a common sense from what appears to be a hopeless situation. the covid- pandemic is having an overwhelming effect on all life aspects of cruise ship employees, including mental and physical health. thus, as frankl [ ] concludes, when a person finds themselves in a situation that they cannot change, the only thing the person can do is to embrace the opportunity to change themselves. while cruise line companies are dealing with the covid- cruise tourism crisis, their leadership needs to look further and make contingency plans on how to prevent the next pandemic crisis and pending climate change crisis. cruise line companies' leadership should, therefore, ask themselves how the covid- cruise tourism crisis did happen in the first place, and diligently work to change everything that went wrong. the covid- pandemic has created a unique opportunity for cruise line companies to revise their corporate culture, reinvent their business models, enhance their human resource management, develop and embrace the risk and crisis management strategies, and adopt sustainable development. based on the respondents' answers, there are mixed opinions if there are positive ways how cruise line companies can get out of the covid- cruise tourism crisis. we should not only look into the cruise companies and what they are doing. have faith and hope. talk to each other about what's good. somebody out there anywhere in the world is battling for their life in this pandemic. come to think of the other perspective. after all of this darkness and rain, there will be light and rainbow and a brighter future. one day all of this will be the history which we will tell to our grandchildren. it would be a story of how we coped with a crisis and survived. all this will probably help us to be better people. (cruise ship employee no. ) to those people who are saying that we need to wait, put yourselves in our shoes, that is come on the ship that has a covid- outbreak. this is day of our isolation excluding the days when we were at sea before we started isolation. almost . months without contact with other people. we are only asking for one thing, send us back home to our families. (cruise ship employee no. ) the covid- pandemic has exposed the unsustainable business model of cruise line companies. although under normal circumstances working conditions onboard do not dehumanize cruise ship employees, the covid- pandemic has certainly shown that for cruise line companies and the cdc, cruise ship employees do not matter in some profound way. the aforementioned condition is rooted in a systemic failure of cruise line companies' leadership to understand what is happening with the covid- pandemic, aggravated by the capitalism of the neoliberal era. thus, as cruise line companies claim they are doing their best for the crew members' repatriation, there is a dividing perception among cruise ship employees in regards to positive ways how cruise line companies can get out of the covid- cruise tourism crisis. while some cruise ship employees see the light at the end of tunnel as the cdc's no sail order [ ] expires on september , others think that the long-awaited september and the light at the end of the tunnel is nothing more than what Žižek [ ] (pp. xi-xii) describes as: "probably the headlight of another train approaching from the opposite direction". on february , princess cruises confirmed that people on the ship diamond princess had tested positive for covid- [ ] and on march , the world health organization officially declared covid- a pandemic. at that time, there were , people infected, dead and , recovered including nearly people aboard four cruise ships [ ] . shortly after that on march , members of the clia voluntarily suspended their cruise ship operations, followed by the cdc's no sail order issued on april , which suspended all cruise operations until september [ ] . lastly, on may , there were around , cruise ship employees stuck at sea without any certainty in regards to their repatriation to their homes [ ] . all respondents but one were quite skeptical about the leadership of cruise line companies and their energetical pursuit to do everything in their power to get them home. no, i don't think that office people are doing everything in their power to get us home. crew members should be respected way more than they have been. if the company continues this horrible management of their crew members, the day will come when no one will work for them and they will fail as a company. everything starts at the top. horrible leadership! i have lost all faith in this company. i am just tired of all the lies and their failure to care about people. true colors came out in tough times. this is no way to treat anyone. so sad! (cruise ship employee no. ) while being stuck at sea, cruise ship employees' doubts in regards to cruise line companies' leadership capabilities and their sincere efforts in pursuing crew members' repatriation are boiling up. thus, as despair, anxiety, depression and stress accumulate across various cruise ships, it appears that trust in cruise line companies' leadership is diminishing, and as walker [ ] points out, some crew members are organizing protests, while others go even further by performing a hunger strike [ ] . thus, while cruise line companies' leadership is battling the covid- cruise tourism crisis, and they are looking into ways to tap into liquidity so they can stay afloat and avoid bankruptcy, they must not neglect their obligations outlined in the maritime labour convention [ ] "seafarers' bill of rights". all participants expressed an opinion that even when cruise line companies get bad publicity, they hope that they will find a way to solve the covid- cruise tourism crisis yes, they are doing their best. i don't understand why media is bad mouthing cruise lines and they can't understand that some countries are not accepting their crew members coming from cruise ships. beside me, my sister is working on a cruise ship and we are from trinidad and tobago, and my sister's boyfriend who also works on a cruise ship is from nicaragua. all of us are not allowed by our countries to come back home. however, all you read is how cruise companies are bad and no one is accusing countries like ours who are not allowing us to come back home. this is hypocrisy! i can tell you that our company is looking after us while we are on board. (cruise ship employee no. ) crew ship employees believe that sometimes they are being used by media who are attracted to stories related to the covid- pandemic and cruise tourism since, as pooley [ ] said, "if it bleeds, it leads." nevertheless, the covid- pandemic should awaken cruise line companies' leadership to the realization that exploitation of crew ship employees should be abandoned and replaced by social bonds between cruise line companies' leadership and cruise ship employees. the bad publicity of the cruise line companies' leadership during thecovid- pandemic is a direct result of poor leadership skills, poor human resource management, nonexistent contingency plans, nonexistent crisis management, and nonexistent crisis communication strategies. lastly, as cruise line companies' leadership are delaying crucial decisions and continue to weigh the costs of crew members' repatriation using charter flights and/or cruise ships while meeting the cdc's no sail order [ ] , they are putting hardship on their crew ship employees. onboard working conditions under normal circumstances do not dehumanize cruise ship employees, however, the covid- pandemic has managed to erase the feeling of joy from cruise ship employees while exposing the weakness of cruise line companies such as poor human resource management strategies, nonexistent contingency plans, and nonexistent crisis management. accordingly, this study attempted to answer the question: what are the psychological effects of the covid- pandemic on cruise ship employees stuck at sea? the results of this study revealed that cruise line companies have poor human resource management strategies and that they did not have a contingency plan to manage this health and epidemiological type of crisis. moreover, cruise line companies do not have a strategy for managing various negative psychological effects of the covid- pandemic on cruise ship employees who are stuck at sea. thus, since cruise line companies have to develop a comprehensive contingency plan for managing onboard covid- outbreaks as a mandatory requirement set by the cdc's no sail order [ ] , cruise line companies have to look further and develop strategies for managing anxiety, depression and stress of cruise ship employees during a pandemic and/or crisis. cruise line companies need to embrace the philosophy defined by mitroff [ ] as "thinking about the unthinkable". regarding the worries, fears and sleep disturbances experienced by cruise ship employees stuck at sea, it appears that they are related to fears of not being able to see their family and friends, not being able to provide financial support to their families or significant other and the feeling that they have lost control of their lives. anxiety within cruise ship employees stuck at sea was inflated due to the fear of an uncertain future and economic recession. these findings are in line with shigemura et al. [ ] who argue that during a pandemic, worries and fears surge the anxiety levels in particularly healthy persons, and boost the manifestations of those with pre-existing mental disorders. as days become weeks and weeks become months, cruise ship employees experience sleep disturbances. the sleep disturbances of cruise ship employees stuck at sea were related to the combination of worries, fears, and anxiety, which ultimately affected their sleep quality. this finding is in line with alvaro et al. [ ] who in their systematic review on sleep disturbances, anxiety, and depression point to causality between anxiety and sleep quality due to a specific condition where anxious individuals experience difficulties to fall asleep and they wake up frequently during their sleep. during the covid- pandemic, cruise ship employees experience a lack of onboard social cohesion and lack of family and friends' social support, which leads to the development of depression. without an opportunity to socialize with fellow crew members due to restrictive social distancing, each cruise ship employee was left alone to face their worries and fears of uncertainty. fear is an adaptive defense mechanism essential for survival with several biochemical processes as a response to potential threats [ ] . moreover, despair, a decline in well-being, combined with a loss of hope that the day of final repatriation is in sight has seriously affected how cruise ship employees feel, think, and act, causing the development of depression. these findings are supported by garcia [ ] who argues how chronic or disproportionate fear can harm individuals' mental health and as it progresses it can lead to the development of various psychiatric disorders. hence, as melancholy sweeps over cruise ship employees, their silent screams of existential despair go unheard by cruise line companies, the cdc, airlines, and national governments. uncertainty of what the future holds, distress, and neurosis coupled with not being able to cope with the covid- pandemic were the main components associated with the perceived stress of cruise ship employees. unbearable uncertainty of what the future holds paralyzes cruise ship employees as they are preoccupied with the day of their final repatriation and loss of their only source of income. peculiar conditions of cruise ship employees who are stuck at sea leave them with limited, if any strategies to manage their negative emotions. thus emotion regulation strategies described by diefendorff et al. [ ] such as: (a) connecting with others so one could feel good; (b) working or keeping oneself busy; (c) enjoying pleasurable activities to improve one's mood; (d) doing one's best to solve a problem; are not applicable to cruise ship employees who are stuck on the sea due to the cdc's no sail order [ ] . hence, cruise ship employees speak in an almost passive participant voice about their relentless complaints against diminished control of their own life. these findings are in line with stein [ ] who points out how the uncertainty of what the future holds, coupled with distress, and an inability to cope with the covid- pandemic creates worries and anxiety among many people, leaving them with nothing but dread and despair. this study showed that a state of hope and sense of belonging of cruise ship employees is hitting an all-time low. cruise line companies' leadership failed on multiple levels of human resource management, as they reached the point of being perceived by cruise ship employees as inauthentic and untrustworthy. moreover, cruise line companies' leaderships' poor crisis communication strategies left the cruise ship employees almost without any hope in regards to their repatriation. the covid- pandemic demonstrated that for cruise line companies and the cdc, cruise ship employees do not matter in some profound way. even though it appears that hope has abandoned the cruise ship employees, there is a glimmer of a sense of belonging as cruise ship employees are willing to defend the image of cruise line companies under the ruthless judgment of mainstream media. hence, as crises create opportunities, the covid- pandemic has provided a unique opportunity for cruise line companies to revise their corporate culture and enhance their human resource management strategies. the covid- pandemic demonstrated that it is of paramount importance that cruise line companies create a comprehensive strategy in assisting their employees who are experiencing anxiety disorder and depression. in the case of a pandemic and/or crisis, cruise ship companies need to employ onboard psychologists who could assist employees with anxiety disorder and depression. the anxiety of cruise ship employees could be solved by fairburn's [ ] cognitive behavior therapy. cognitive behavioral therapy (cbt) is a well-established psychological treatment with robust effectiveness in treating depression and anxiety disorders [ ] . onboard leaders have to be approachable and they have to recognize crew members who are experiencing anxiety and depression. during the open conversation with cruise ship employees, onboard leaders have to be authentic and emphatic as they listen to worries, fears, and troubles of their crew members. it is a duty of onboard leaders to explain to cruise ship employees that it is normal to feel worried and anxious as uncertainty and loss of control are two key factors associated with stress and anxiety. additionally, onboard leaders have to be supported by shore-side cruise line companies' leaders with appropriate video content and digital cbt. in their study on the mental health burden of covid- , da silva lopes and jaspal [ ] concluded that digital cbt can address all aspects of stress management and the management of worry and fear. furthermore, murphy et al. [ ] suggest that delivering enhanced cbt remotely by video-calls delivers strong results in treating anxiety disorder. practical aspects of cbt that onboard leaders can perform every day are: engaging crew members in the novel ways of protection against covid- ; showing crew members reasons and positive ways to overcome despair; arranging outdoor activities that do not violate the cdc's no sail order [ ] (e.g., walks on the open decks, yoga and breathing classes with prescribed social distance); and engaging crew members in solving problems such as contacting their embassies for potential charter flights and final repatriation and sharing the information with shore-side leaders related to individual countries lockdown measures. cruise line companies need to be transparent in their communication with cruise ship employees by providing them with accurate information in a timely manner. cruise ship employees understand that during the covid- cruise tourism crisis, cruise line companies' leadership is struggling to keep companies afloat, while at the same time preventing potential takeovers by protecting the stock value. however, lack of information and/or inaccurate information can only boost the crisis. the covid- pandemic demonstrated poor crisis communication of cruise line companies, since the main source of information and loudest spokespeople during the covid- cruise tourism crisis was social media and mainstream media. it appears that cruise line companies neglect the fundamentals of crisis communication strategies, which is, as per fink [ ] , managing the perception of reality by framing the public opinion. although some cruise line companies created the slogan (e.g., "we will be back"), unfortunately, the slogan failed to capture a feeling of security so that cruise ship employees' reaction was cold. onboard leadership needs to understand who their crew members are and what they want to hear. in particular, cruise line employees are interested in: (a) their repatriation home; (b) financial support while they are away from home; and (c) their employment status. thus, onboard leadership must communicate to them such information with empathy and compassion. the cruise industry will certainly experience an exponential drop in employment due to the covid- pandemic; however, this issue of unemployment will affect cruise ship employees' family members as well. while being stuck at sea, cruise ship employees who are not getting paid cannot engage in activities such as searching for another job, looking into ways to increase their visibility on the labor market, rearranging their family finances by decreasing expenses, and outsourcing alternative resource for existential purposes. to soften the negative impact on cruise workers, cruise ship companies should provide a minimum basic salary for at least months to all cruise ship employees who were affected by the covid- pandemic, as well as support laid-off cruise ship employees in finding another job or allowing them to return to work if cruise line companies resume their operation. due to its qualitative nature, this study cannot be generalized. it would be interesting to conduct similar research with additional online synchronous focus groups over time, to elicit in-depth information evolving during the course of the covid- pandemic. the second limitation is the cross-sectional time horizon utilized in this study; thus, there is space for potential causality and reciprocal relationships among components [ ] . future studies should use a longitudinal time horizon to understand the complexities of the psychological effects of the covid- pandemic on cruise ship employees stuck at sea. moreover, a quantitative follow up study that is built on findings from this study would help improve our understanding of the psycholotablgical effects of the covid- pandemic on cruise ship employees stuck at sea. lastly, future studies can address the shortcomings of this study to gain a deeper understanding of the psychological effects of the covid- pandemic on cruise ship employees stuck at sea. funding: this research received no external funding. the authors declare no conflict of interest. towards an understanding of a child's cruise experience. curr. issues tour cruise ship no sail order extended through recollection of the sea cruise: the role of cruise photos and other passengers on the ship using a choice experiment (ce) to value the attributes of cruise tourism assessing the 'poverty of cruise theory' hypothesis using twitter data for cruise tourism marketing and research economic impact of cruise activity: the case of barcelona managing context to improve cruise line service relationships. cornell hosp connected at sea: the influence of the internet and online communication on the well-being and life satisfaction of cruise ship employees the effect of internet use on well-being: meta-analysis pining for home: studying crew homesickness aboard a cruise liner working onboard -job perception, organizational commitment and job satisfaction in the cruise sector. tourism manag occupational and health safety on cruise ships: dimensions of injuries among crew members new kids on the ship: organisational socialisation and sensemaking of new entrants to cruise ship employment talent management and the cruise industry identity construction in transient spaces: hospitality work on-board cruise ships succeeding in literature reviews and research project plans for nursing students researching interpersonal relationships: qualitative methods, studies, and analysis participatory evaluation in youth and community work: theory and practice conducting focus groups for business and management students orthopaedic basic science: foundations of clinical practice cross-sectional study basics of qualitative research: techniques and theory for developing grounded theory sampling issues in qualitative research critical analysis of strategies for determining rigor in qualitative inquiry online focus groups: a valuable alternative for hospitality research? no way off. , crew members remain in cruise ship limbo for months locus of control and trait anxiety in aged adults: the mediating effect of intolerance of uncertainty anxiety in medical patients adaptive anxiety job demands-job resources (jd-r) model, work engagement, and well-being of cruise ship employees contributory to stress and fatigue of filipino seafarers the state, race, and 'wage slavery' in the forest sector of the pacific north-west united states fear and trembling; penguin classics: london waking up to the importance of sleep: why that extra shut eye is key to medical student wellbeing the effects of improving sleep on mental health (oasis): a randomised controlled trial with mediation analysis management of chronic insomnia disorder in adults: a clinical practice guideline from the american college of physicians management of chronic insomnia disorder in adults sleep and anxiety disorders american psychiatric association screening of anxiety and depression among seafarers using machine learning technology the effect of modified jazz dance on balance, cognition, and mood in older adults seafarers' depression and suicide power talk: communication styles, vocalization rates and dominance social isolation, depression, and psychological distress among older adults all hands on deck: employee engagement on cruise ships family support and conflict: prospective relations to adolescent depression the relationship between family support; pain and depression in elderly with arthritis why does propaganda work? fear-induced repression of the executive control brain network time-dependent effects of psychosocial stress on fear contextualization and generalization: a randomized-controlled study with healthy participants have a healthy lifestyle or organize work-creating healthy shipboard work environments can anxiety damage the brain? man's search for meaning the courage of hopelessness; penguin random house medical news today stuck-at-sea-protest-erupts-on-royal-caribbeans-majesty-of-the-seas grins, gore and videotape: the trouble with local tv news crisis leadership: planning for the unthinkable public responses to the novel coronavirus ( -ncov) in japan: mental health consequences and target populations a systematic review assessing bidirectionality between sleep disturbances, anxiety, and depression pandemic fear" and covid- : mental health burden and strategies neurobiology of fear and specific phobias linking emotion regulation strategies to affective events and negative emotions at work covid- and anxiety and depression in cognitive behavior therapy and eating disorders an oasis in the wilderness understanding the mental health burden of covid- in the united kingdom dalle grave, r. challenges and opportunities for enhanced cognitive behaviour therapy (cbt-e) in light of covid- crisis communications: the definitive guide to managing the message games researchers play: extreme-groups analysis and mediation analysis in longitudinal occupational health research key: cord- - ym rsq authors: monto, arnold s; fukuda, keiji title: lessons from influenza pandemics of the last years date: - - journal: clin infect dis doi: . /cid/ciz sha: doc_id: cord_uid: ym rsq seasonal influenza is an annual occurrence, but it is the threat of pandemics that produces universal concern. recurring reports of avian influenza viruses severely affecting humans have served as constant reminders of the potential for another pandemic. review of features of the influenza pandemic and subsequent ones helps in identifying areas where attention in planning is critical. key among such issues are likely risk groups and which interventions to employ. past pandemics have repeatedly underscored, for example, the vulnerability of groups such as pregnant women and taught other lessons valuable for future preparedness. while a fundamental difficulty in planning for the next pandemic remains their unpredictability and infrequency, this uncertainty can be mitigated, in part, by optimizing the handling of the much more predictable occurrence of seasonal influenza. improvements in antivirals and novel vaccine formulations are critical in lessening the impact of both pandemic and seasonal influenza. outbreaks of seasonal influenza are perennial occurrences in the temperate zones. their impact on morbidity and mortality is highly variable but in some years can occur at levels that nearly disrupt the functioning of healthcare systems [ , ] . during such seasonal outbreaks, questions usually center around the severity and how well the vaccine is protecting. but, regardless of disruptions, their impact is quickly forgotten. by contrast, pandemics of influenza occur much less often but are viewed as more threatening because of their relative unfamiliarity and potential for catastrophic impact. even a century later, much of the concern stems from recognition of the sheer number of deaths attributable to the influenza pandemic. while estimates of death have varied greatly, recent scholarship, largely based of previously omitted data from lower-income countries, such as india, has revised global estimates upwards [ ] now, the estimate of million deaths is generally used as an overall global estimate, constituting nearly % of the world's population at the time [ ] . pandemics are caused only by type a viruses. the current classification of a subtypes was developed in based on molecular evidence indicating that the previous nomenclature needed revision with, in addition, the inclusion of neuraminidase (na) [ ] . table shows the terminology used pre- and the current terminology. years listed are either the start of virologically confirmed pandemics or consensus dates reflecting when it was thought that a new subtype had emerged based on serology [ ] [ ] [ ] [ ] . influenza viruses were first isolated in the s, and the etiology and timing of previous activity were based on testing of sera from individuals who had lived through the period in question. this approach, termed "seroarcheology, " resulted in occasional controversy. most identified the influenza as caused by a viruses and postulated that a viruses had started to circulate in , with no recognized pandemic occurrence. persons who lived through the pandemic were found to have antibodies against "swine" influenza viruses, now designated as a(h n ). the more recent reconstruction of that virus confirms the overall validity of the seroarcheologic technique [ , ] . the most remarkable epidemiological feature of the pandemic was the unexpectedly high mortality among those aged - years [ ] . theories to explain this pattern abound but most involve an aberrant immune response [ ] . one recent hypothesis postulates that prior infection of children in the pandemic rendered them particularly susceptible by immunologic imprinting to reinfection in when they were in their late s [ ] . current evidence suggests that older individuals may have actually been protected in . this is in contrast to the traditional belief in the w-shaped epidemic curve, in which the high mortality in the elderly was a result of the erroneous inclusion of seasonal disease from the early months of [ ] . figure shows the age-specific mortality in philadelphia where the pandemic shut down the city and peaked at a weekly annualized rate of deaths per population [ , , ] . another often overlooked but constant feature of all pandemics is the high mortality in the very young experiencing their first influenza infection [ ] . these observations indicate that understanding the positive and negative effect of prior influenza exposure is critical [ ] . other observations of relevance to planning efforts are indications of the usefulness of nonpharmaceutical interventions in mitigating community impact [ ] . the susceptibility of pregnant women was well documented; it should not have been such a surprise during the influenza pandemic when it was rediscovered [ ] . sudden death has often been emphasized as a feature of , but it took, on average, or more days for death to occur [ ] (figure ). this stresses the need for health systems to have the surge capacity necessary to handle patients with the more typical prolonged illness regardless of the severity of a pandemic. a proportion of the deaths were associated with bacterial complications. the global increase in antibioticresistant organisms is another major vulnerability [ ] . most pre- lists of influenza pandemics included one in despite lack of documentation of global outbreaks ( table ). in that year, seasonal vaccine became ineffective and it was thought that a new subtype named "a prime" had emerged [ , ] . this understanding was important in developing the doctrine of original antigenic sin. it is now understood that an intrasubtypic reassortment occurred in , which resulted in a major antigenic change of the a(h n ) viruses [ ] . a new subtype, a(h n ), actually emerged in when gene segments coding for b these strains were identified by serology, but the specific identification is in dispute. some have the virus as h n but without a different subtype identified starting in , a year when there was not a clear pandemic [ ] [ ] [ ] [ ] . hemagglutinin (ha), na, and an internal component moved from an avian virus into the circulating a(h n ) virus through genetic reassortment [ , ] . the resulting a(h n ) virus, which was called "asian influenza" since it emerged from china, totally replaced the a(h n ) viruses. since this was the first true pandemic since , there was immediate concern about its potential impact and great relief when it was found to resemble seasonal influenza with morbidity highest in children and mortality at the extremes of age [ , ] (figure ). in the united states, the virus emerged in the spring of , but outbreaks intensified only after schools in the southern united states opened in august, underscoring the importance of children in dissemination [ ] . although vaccine was available in the united states late in the first wave, it had to be reformulated because of subpotency and standardization issues, concerns still being addressed [ ] ( figure ). with little vaccine available, attention was paid to other ways to reduce transmission. a controlled experiment conducted at the veterans administration hospital in livermore, california, demonstrated reduced transmission from the use of ultraviolet lights [ ] . that tantalizing observation has been used recently to strengthen the suggestion that small-particle aerosol transmission of influenza viruses is of importance. the a(h n ) period lasted only years until mid- . in july of that year, a major outbreak in hong kong signaled that another reassortment event had occurred [ ] . avian influenza genes, one coding for ha and the other an internal component, replaced the existing counterparts in the circulating a(h n ) virus; the na gene was not replaced [ , ] . emergence of a(h n ) and a(h n ) viruses and later events led to the concept that "novel" influenza viruses are most likely to come from east asia. at the time, it was conjectured that reassortment (or "shift") of avian and human influenza viruses occurred in a nonhuman "mixing vessel" because humans were believed not to have the right cellular entry receptors for avian influenza viruses. pigs have receptors for both human and avian influenza viruses, and since influenza viruses replicate in these animals they were considered to be the mixing vessel [ ] . this was further supported by the observation that humans, poultry, pigs, and wild birds live in close proximity in east asia, providing ample opportunity for reassortment to occur there. the a(h n ) pandemic exhibited the same patterns of morbidity and mortality as the earlier a(h n ) pandemic. in terms of reasons for emergence of a pandemic variant after only years, it is of interest that the last outbreak of a(h n ) in - was extensive, as measured by pneumonia and influenza (p and i) mortality. this indicates that a considerable percentage of the population still remained susceptible to a(h n ) [ , ] . however, the new a(h n ) virus completely replaced the previous subtype, and its variants, more than years later, have been responsible for the greatest proportion of mortality from influenza viruses. the first a(h n ) pandemic wave occurred in the united states in midwinter - at a time typical of seasonal influenza but which in some parts of the world was delayed. there has been speculation that the delay was a result of protection from the unchanged na. even in the united states, contemporaneous studies showed reduction in infection in those with higher anti-na titers, indicating an independent protective effect beyond anti-ha [ ] . the role of anti-na remains an issue in present-day efforts to improve vaccine [ ] . in january , an outbreak of severe influenza occurred at the us military's fort dix, new jersey. the causative virus was surprisingly found to be a variant of swine influenza, now recognized to be an a(h n ) virus [ ] . since previous serologic studies had shown that the pandemic was probably caused by swine influenza (table ) , there was strong concern that the fort dix outbreak could herald another severe pandemic [ ] . in the united states, vaccine production was begun after liability concerns of the manufacturers had been addressed. even though no further human outbreaks were detected, mass vaccinations were begun and stopped only when a relationship between the vaccine and guillain-barré was identified. this "affair" has been studied extensively in terms of potential pitfalls in pandemic response and decision making [ ] . in the following year, a different a(h n ) virus, one that had been circulating before , was identified [ ] . transmission of this virus, termed "russian influenza" since the reports first came from the far east of the soviet union, was unexpected because the virus had not been detected for years. infections were widespread, generally mild, and limited to younger individuals; residual protection was nearly complete in older individuals [ ] . this event has never been considered a true pandemic because so much of the world's population was not susceptible and because of the uncertain origin of the virus. the re-emerged a(h n ) virus remained in persistent circulation worldwide along with a(h n ) viruses and continued to evolve until it disappeared in . before this, when a new a subtype began circulating, it completely replaced the previous one. the concept that avian influenza viruses could not directly infect humans ended in when avian a(h n ) viruses spread directly from poultry to humans, causing a small but highly important outbreak in hong kong. this event, which raised global concern, resulted in the deaths of of patients with documented infection [ , ] . once control measures, especially culling of poultry, were put into place, new cases abruptly stopped. no further human cases were detected until, in , when, in conjunction with die-offs of poultry, the spread of a(h n ) to humans occurred, mainly in southeast asia [ ] [ ] [ ] . most human infections were the result of contact with poultry, but examples of limited human-to-human transmission were documented [ ] . because human cases were often severe and resulted in respiratory failure and death, there was high global concern that a pandemic of this virus would be severe if sustained human-to-human transmission occurred [ ] . the nature of the threat, arising in animals but directly of concern to humans, highlighted the generally poor coordination and often rigid separation between animal and human health authorities at national and international levels, as well as a general lack of national planning. the adoption of new international health regulations in , which was strongly influenced by the emergence of sars (severe acute respiratory syndrome) and the re-emergence of a(h n ) in , constituted a major step forward [ ] . in the united states, there was particular attention directed to nonpharmaceutical interventions, a result of the recognition that pandemic-specific vaccines would be available relatively late and that influenza-specific antiviral drugs, while important, would be limited in quantity. there were discussions as to whether the use of antivirals might be able to contain human transmission of an emerging virus at the source; these plans were mainly predicated on the emergence occurring in asia [ , ] . continuing concern about outbreaks of avian influenza was interrupted when the first pandemic of the st century unexpectedly started in mexico in [ ] . as a result of intrasubtypic reassortment, the a(h n ) variant involved was antigenically highly distinct from previously circulating influenza a(h n ) viruses [ ] . the previous prevailing dogma was that pandemic influenza was the result of the emergence of a new virus subtype. however, the subsequent global spread indicates that a pandemic is better defined by the global population's immunological susceptibility and antigenic distance of the new virus from other influenza viruses, rather than rigid applications of virologic rules involving antigenic shift [ ] . the a(h n ) virus was associated with lower attack rates in older individuals, presumably because of prior exposure to older a(h n ) viruses. its spread in north america in the spring extended quickly to other parts of the world, highlighting the importance of air travel in accelerating dissemination. in the united states, the spring wave slowed with the beginning of school summer vacations only to pick up again as schools opened in the autumn, reconfirming the importance of children in transmission. this most recent pandemic has been extensively documented. severe disease developed in a small proportion of healthy adults, many of whom had no underlying conditions, which was reminiscent of but at a much smaller scale [ ] . particularly vulnerable groups included indigenous populations, well-documented in canada in the first spring wave [ ] . this was not observed in the second wave, most likely related to modifications in response, including careful employment of antivirals. the association of severity with pregnancy was another clear reminder of the pandemic. a newly observed risk was morbid obesity [ ] . the new pandemic virus completely replaced the prior circulating seasonal a(h n ) but cocirculation of the influenza a(h n ) virus continued. a societal issue of considerable importance, which is essential to address for future pandemics as well as for seasonal influenza planning efforts, was the perception promoted by some that the pandemic was a "fake" pandemic [ , ] . the claim, amplified by social media, was that the public health response was a conspiracy by governments and the world health organization (who) to benefit the sale of influenza vaccines. the overall pattern of mortality, which was less extensive than in th-century pandemics, was an important component [ ] . but perhaps the more fundamental observation is that the accusations were consistent with a broader erosion of trust within society. the need to focus on communications and trust building in all phases of a pandemic is an essential lesson for improving planning for pandemics and responding to seasonal influenza. during the past years since , each of the influenza pandemics has presented both common and unique challenges. none has been predictable in terms of timing, location of onset ,or the causative influenza virus. those that started in and had the most similar morbidity and mortality patterns, with severe complications and deaths that were highest at the extremes of age. the practical consequences for planning are the need to direct interventions to cover such groups while recognizing that other groups may also be at a higher than usual risk [ ] . the age groups most at risk may be the same as in seasonal influenza but may not. questions about "severity" are to be expected early, but determining such levels is particularly challenging. the impact on morbidity and mortality may differ, and perception of severity may also differ widely depending on place and time. during the start of events, the information available to health authorities is often limited and highly uncertain. nonetheless, severity assessments are likely to be important for justifying the use of nonpharmaceutical interventions, such as closing schools and restricting population movement. such actions, which apparently had an effect in , are socially disruptive and likely to be divisive. reducing impact may benefit from using more resources early while communicating the uncertainties involved and the consequences of inaction. since , vaccine has always been available late, often after the first wave. in , the current system of virus sharing through frameworks already established at who worked well but vaccine was still not available widely nor equitably. new technologies, such as a universal vaccine, may eventually change this situation but not in the near term. the prepandemic use of vaccines containing known potential pandemic viruses, often with adjuvants, has been proposed, but there are significant uncertainties in choosing what viruses might go into such a vaccine or for taking the inherent risks [ , ] . preparing for, and responding to, a pandemic is a complex phenomenon, combining science, societal beliefs, practical operational considerations, and political will. some countries and regions have continued to update plans, but others have not. this is a reflection, in part, of uncertainties following the pandemic but also what has been termed "pandemic fatigue. " the latter issue has been made worse by the repeated recognition of the pandemic potential of different avian influenza virus variants that have infected humans [ ] [ ] [ ] . given this context, it is important to recognize that seasonal influenza occurs every year and many of the essential control measures for pandemics are based on those used for seasonal influenza. it is critical to avoid viewing pandemic and seasonal influenza as unrelated. seasonal influenza is a cause of significant morbidity and mortality, and the vaccine supply used for seasonal influenza sets, in a real-world sense, the production capacity for a pandemic. some countries that will want access to pandemic vaccine do not consider seasonal influenza as a priority. this will limit their capacities to vaccinate their most vulnerable subpopulations in a pandemic, even if vaccine is available. this situation is especially true of lower-resource countries, and continued efforts to document the impact of seasonal influenza and, concomitantly, to develop the health system capabilities needed to support a pandemic response remain high priorities. determining the possible reduction in seasonal severe disease from the use of vaccine can be evaluated in a vaccine probe study in which the vaccine is given under controlled conditions to young children in underresourced areas, similar to studies that documented the need for pneumococcal vaccine [ ] . the need for all countries to have and use vaccine in a pandemic is an issue of the equitable distribution of resources on both a national and global scale. scientific advances have positioned the world to respond better to both seasonal and pandemic threats of influenza. however, to make the most of such advances before the next pandemic will still require consistent attention and both scientific and political leadership. potential conflicts of interest. a. s. m. reports consulting fees from sanofi, seqirus, and roche, outside the submitted work. k. f. has no potential conflicts to disclose. both authors have submitted the icmje form for disclosure of potential conflicts of interest. conflicts that the editors consider relevant to the content of the manuscript have been disclosed. chasing seasonal influenza-the need for a universal influenza vaccine update: influenza activity in the united states during the - season and composition of the - influenza vaccine epidemic influenza: a survey updating the accounts: global mortality of the - "spanish" influenza pandemic a revision of the system of nomenclature for influenza viruses: a who memorandum viral infections of humans: epidemiology and control pre-epidemic antibody against strain of asiatic influenza in serum of older people living in the netherlands immunological interrelationships of hong kong, asian and equi- influenza viruses in man recycling of asian and hong kong influenza a virus hemagglutinins in man initial genetic characterization of the "spanish" influenza virus characterization of the reconstructed spanish influenza pandemic virus aberrant innate immune response in lethal infection of macaques with the influenza virus genesis and pathogenesis of the pandemic h n influenza a virus the epidemiology and clinical impact of pandemic influenza us bureau of the census. special tables for mortality from influenza and pneumonia influenza in : recollections of the epidemic in philadelphia antibodies against the current influenza a(h n ) vaccine strain do not protect some individuals from infection with contemporary circulating influenza a(h n ) virus strains nonpharmaceutical influenza mitigation strategies, us communities, - pandemic the unidentified pandemic disease the influenza pandemic: insights for the st century influenza a prime: a clinical study of an epidemic caused by a new strain of virus the total influenza vaccine failure of revisited: major intrasubtypic antigenic change can explain failure of vaccine in a post-world war ii epidemic multiple reassortment events in the evolutionary history of h n influenza a virus since on the origin of the human influenza virus subtypes h n and h n avian-to-human transmission of the pb gene of influenza a viruses in the and pandemics morbidity and mortality characteristics of asian strain influenza mortality from influenza - and - epidemiology of asian influenza: with special emphasis on the united states some problems in the standardization and control of influenza vaccine in the mechanism of spread of asian influenza origin and progress of the - hong kong influenza epidemic pigs as "mixing vessels" for the creation of new pandemic influenza a viruses the age distribution of excess mortality during a hong kong influenza epidemics compared with earlier a outbreaks national influenza experience in the usa effect of neuraminidase antibody on hong kong influenza naction! how can neuraminidase-based immunity contribute to better influenza virus vaccines? swine influenza a at fort dix influenza a virus recycling revisited the swine flu affair: decision-making on a slippery disease. washington: us government printing office the russian flu: its history and implications for this year's influenza season tecumseh study of illness. xiii. influenza infection and disease, - characterization of an avian influenza a (h n ) virus isolated from a child with a fatal respiratory illness risk of influenza a (h n ) infection among poultry workers, hong kong, - re-emergence of fatal human influenza a subtype h n disease genesis of a highly pathogenic and potentially pandemic h n influenza virus in eastern asia world health organization international avian influenza investigative team. avian influenza a (h n ) in patients in vietnam probable limited person-to-person transmission of highly pathogenic avian influenza a (h n ) virus in china the threat of an avian influenza pandemic world health organization. international health regulations strategies for containing an emerging influenza pandemic in southeast asia containing pandemic influenza at the source critically ill patients with influenza a(h n ) in mexico antigenic and genetic characteristics of swine-origin a(h n ) influenza viruses circulating in humans what is a pandemic? preliminary estimates of mortality and years of life lost associated with the a/h n pandemic in the us and comparison with past influenza seasons canadian critical care trials group h n collaborative. critically ill patients with influenza a(h n ) infection in canada who working group for risk factors for severe h n pdm infection. risk factors for severe outcomes following influenza a (h n ) infection: a global pooled analysis report of the review committee on the functioning of the international health regulations ( ) in relation to pandemic (h n ) . (fineberg report). available at response to the pandemic: effect on influenza control in wealthy and poor countries novel framework for assessing epidemiologic effects of influenza epidemics and pandemics investing in immunity: prepandemic immunization to combat future influenza pandemics a universal influenza vaccine: the strategic plan for the national institute of allergy and infectious diseases human infection with influenza h n human infection with a novel avian-origin influenza a (h n ) virus h influenza viruses pose a potential threat to human health vaccines as a tool to estimate the burden of severe influenza in children of low-resourced areas key: cord- - i zj b authors: khurana, sonal; haleem, abid; luthra, sunil; huisingh, donald; mannan, bisma title: now is the time to press the reset button: helping india’s companies to become more resilient and effective in overcoming the impacts of covid- , climate changes and other crises date: - - journal: j clean prod doi: . /j.jclepro. . sha: doc_id: cord_uid: i zj b covid- is the pandemic caused by one of the coronaviruses. this virus was not known before the outbreak in wuhan, china, in december . by january of it was declared to be a global human health crisis. the deaths and illnesses caused by the virus caused extensive fear and anxiety among people in all societies. the pandemic slowed economic activities nearly to a halt. the challenges of how companies should respond to the disruptions in their supply chains and how they can build more resilient systems, must be systematically addressed. the authors of this paper highlighted essential factors which can help companies to overcome this crisis and other types of crises, by learning from the approaches taken in india, which has a unique and diverse economic system. the analytical hierarchy process (ahp) technique was used to identify the essential factors which can help companies to improve their resilience so they can recover during and after the covid- pandemic era and potentially in other similar complex crises. the results of the ahp evaluation were prioritized by performing a sensitivity analysis to prioritize the essential factors. the “role of governance” was found to be the most important factor that can be used to help in rebuilding industries and societies and in helping them to become more resilient to future severe shocks. the results of this research were used to develop recommendations for company managers, practitioners and policy-makers. the authors hope that this advice will help india to become a stronger nation with more resilient companies, which are better prepared to anticipate and to respond to future crises. we hope people in other nations will also benefit from the finding presented in this paper. it is widely known that the covid- pandemic does not differentiate between nationality, gender, religion, wealth or the economies and markets it affects. dramatic challenges have impacted businesses in every country. in this context, india was not spared. in recent years, j o u r n a l p r e -p r o o f micro, small and medium-scale enterprises (msmes) were recognised by the indian government as the backbone of the economy, as, they provide about % of india's economy (ministry of msme website, ) . the msme sector is a highly dynamic sector of the indian economy. it provides extensive employment opportunities and contributes socially and economically to india's stability. approximately million workers were employed by msmes in india in (ministry of msme website, ). with the importance msmes have in india, revision in the definition of msmes has been needed for a long time. this revision came at the time of the pandemic when the industries were in dire need of the help from the government. the revised categorisation of msmes can help them to grow in size as they derive benefits from being msmes. this is an important step as their survival has been dramatically challenged by the covid- virus that was first detected in wuhan, china in november . it has people in the entire world in the first half of because of which, the covid- virus outbreak was declared a pandemic and a public health emergency of international concern on january (euro surveillance editorial team, ). till july, , there has been . million cases of covid- and more than , people have lost their lives (world health organization, ) . figure depicts the global deaths due to covid- . the data is till nd may, and the graph shown in figure does not constitute deaths from cardiovascular diseases or cancer, which according to world economic forum, are the top causes of deaths in the world. the covid- pandemic hangs over societies' futures, like a spectre. this pandemic has brought economic activity to a standstill, and has resulted in dramatic declines in global trade and growth . the international labour organisation (ilo) described the pandemic as the most serious challenge since second world war; it has forecasted that the pandemic will infect . billion workers, or % of the world's workforce (livemint, a) . the loss of livelihood, social isolation, and fear of contracting the virus have created fear and anxiety among the people which has led to mental illnesses and other types of severe illnesses. even though, covid- was, at first considered to be a physical health crisis, it has given rise to mental health risks as well as it expands globally into a severe pandemic (united nations organisation, ) . the physical and mental health illnesses have caused increased risks of the survival to millions of people. therefore, focus should be on incorporating the approaches which would be able to restore the environment and to improve the health of humans which are vital for sustainable development of society (song et al., ) . the impacts evolving from pandemic are documenting that this pandemic is causing extensive social, psychological and economic damage. (laing et al., ) . the estimation by the ilo stated that in india, more than % of the workers work in the informal sector and they are at risk of moving deep into poverty because of the pandemic, which will adversely affect overall societal development (i.l.o., ). this pandemic has increased the urgency to incorporate all three aspects of sustainability, social, environmental, and economic goals into all dimensions of supply chain management including coordinating inter-organisational business practices to ensure improvement in performances of all of the firms in all supply chains (hussain et al., ; khurana et al., ) . moreover, in the current economic scenario, the success of any firm should be based, not only on profitability, but also on its capacity to contribute to the future of people and planet (bubicz et al., ) . this pandemic has disrupted millions of supply chains, filled hospitals with millions of sick and dying people, closed schools; and highlighted the urgency to consider the social aspects of sustainability along with ways to increase productivity of companies, i.e. to make them covid- resilient (p.i.b., a) . although the "human dimension" is urgent, it must be balanced with the ecological and economic dimensions of all countries. the united nations secretary general antónio guterres made an announcement in mid-march that overcoming covid- would be the main focus of the world and climate change has to take a backseat. many international policymaking conferences on environmental issues have been postponed till . but, unless improvement stimulus support also includes policies focussing on climate change mitigation, there is a high probability that firms will return to their high polluting practices when the pandemic fades (spratt and armistead, ) . adversities bring opportunities for making holistic improvements. thus, this time must be utilized by companies to modify their business models, policies, procedures and practices in the short and long-term so that they become more sustainable, equitable and resilient (ivanov and dolgui, ) . the pressures from stakeholders for equity should act as a catalyst for company leaders to transition their companies to have sustainable performance at all levels. therefore, it is urgent to recognise and bring to the forefront the factors, which can help companies to reduce their losses, incorporate sustainable practices and to increase their resilience to this crisis and to future crises (amankwah-amoah, ). the covid- has given every country many new lessons, which if implemented will help the countries to reduce the negative impact of this crisis and of future pandemics. the lesson to be learnt is that economic development of the country is more important than economic growth of the country. as societal reactions to this pandemic have shown, many businesses have been closed leading to loss of livelihood. many people who have lost their jobs are suffering from mental illnesses and others have developed fear because of uncertainties for their future (nicola et al., ) . therefore, the challenge which needs to be addressed is how to save the lives of people from being killed by the virus or dying due to lack of work, money and food. this can be done by upgrading the healthcare system of the country. for this, one of the obstacles to overcome lies in improving the numerous supply chains of the country (farooque et al., ) . all aspects of supply chains are interlinked. disruption of supply chains cause businesses to close which in return lead to loss of livelihood which affects the mental and physical health of individuals and of society, overall. as people switch to drugs and alcohol, the abuse at home increases. therefore, how companies cope with the problems associated with supply chain disruptions due to this and other pandemics needs to be addressed. previous research on covid- has been performed in the context of medical science. but, a production and operations management perspective of the pandemic is missing (kumar et al., ) . therefore, to proceed on this journey and address these issues, the authors of paper had the objective to identify the factors, which would help to rebuild resilient industries and societies in the post covid- era. consequently, the objectives of the research were: j o u r n a l p r e -p r o o f • to identify the factors which are important in helping india's companies to become more resilient and effective in overcoming the impacts of covid- , climate changes and other crises; • to rank the priorities of the identified factors, which are important in helping companies to recover from such shocks; and • to perform sensitivity, analyses to test the strength of the identified factors under different weighting categories. the main objective of the authors of this paper was to develop a holistic view of sustainable supply chains. because, as this pandemic has made us realise, that a holistic, resilient plan for protection, followed by revival and growth are urgently required otherwise many companies will fail (p.i.b, b). survival of companies in the post pandemic era would depend on their commitment towards the various aspects of sustainability. failure of the company would lead to the loss in the economy of the country. the remaining parts of the paper consist of the following sections: section contains the introduction; section contains the literature review to identify the factors which are important in helping to rebuild companies and societies during and in the post-covid- pandemic era. it depicts the gaps observed in the existing literature; section sketches out the research methodology used in the paper; section outlines the results of the analysis performed by ahp process; section discusses the technique to test the strength of the rank of factors obtained by the above process; section compiles the findings of this research; section highlights implications of the findings of this paper, for company leaders and for researchers; and section summarises the conclusions and highlights urgently needed future research. the authors of this paper hope that the recommendations will help india's and other societies and they will make speedy, equitable, sustainable recoveries during the pandemic and in the post pandemic era. j o u r n a l p r e -p r o o f the st occurrence of covid- in india was documented on january (mohfw, ). like the time when the disease is spreading at a faster rate, it has become essential to save the lives and livelihood of people. therefore, the systematic literature review was performed to review relevant literature that can provide guidance in making urgently needed corporate and societal changes and which can help in building a theoretical foundation for future research on socio-economic vulnerability to pandemics and other crises such as climate changes, which are integral to the pandemic. during the period of january -july, , the covid- pandemic has evolved; it has changed the world, it has dramatically affected human society, which underscores the urgent need to build resilient industries and societies that are able to withstand such shocks in the future. coronavirus has brought the economy to a halt and has changed the lives of societies globally. devastating the operation of businesses, covid- has affected almost all supply chains; be it manufacturing, service, healthcare or agriculture. it will take a long time for the industries to recover the losses incurred by them by supply chain disruptions and societies to recover from the loss of family members who died from the virus due, in part to due weaknesses or fissures in the healthcare supply chains (govindan et al., ) . the prioritisation of economic growth at costs to human health and environmental impacts are among the short and long-term consequences of covid- . however, the main priority in today's scenario has been to save the lives of individuals. this can be accomplished, in-part by creating awareness amongst them to follow social distancing measures and maintaining proper hygiene . but, the pandemic should be used as an opportunity to improve the health care system of the country. improving the health care system would provide benefits now and in the future since the future is dependent on the health of the country which is the new wealth of the country. the present time should be used in investing in cleaner production and sustainable consumption methods and improving in labour intensive sectors which currently often puts the health of workers at risk (song et al., ) . investing in such approaches will help in improving the sustainability of the society which will help to ensure that the needs of the present and future generations are secured. a fiscal stimulus is required to restart the engine of the economy. according to the federation of indian chambers of commerce and industry (ficci) "bharat self sufficiency fund" should be constituted for promoting research and innovation to build a strong and resilient nation and to constitute self-sufficient industry clusters with completely developed value chains inside the country (p.i.b, a). the extensive spread of the pandemic has created psychological suffering and increased frequencies of severe mental illnesses (bao et al., ) . strategies should be formulated that address the food and other needs of the people, and measures for preventing spreading of the disease (rajkumar, ) . a roadmap reassuring the people for meeting the needs of the vulnerable must be prepared because india has a very large informal economy in the workforce. those at the bottom must be at the top in the order of priority. india also stands low in the list of the countries which have the proper equipment in public hospitals (paital et al., ) . therefore, it is difficult for a country like india to contain the spread of the disease. therefore, it becomes more important to work on building a stronger resilient nation and the industries which are capable of withstanding such shocks. reorientation of development models and consumerism driven lifestyles is required in the wake of covid- pandemic so that economic development is attained post covid- pandemic (p.i.b, b). therefore, the measures taken by the government to prevent the spreading of the disease should become a part of life for every individual in order to stay healthy in the post covid world. the silver lining to the crisis for the country like india is that it comes at a time when there is disruption happening in technology. technologies are going through an enormous amount of change. moreover, the survival of the businesses will depend on their digital transformation . adoption of sustainable technologies will become an increasingly important ingredient, among others, to support business recoveries, now and when confronted with future pandemics. company leaders must also be part of the holistic plans to ensure human, ecological and economic health of cities and communities (amankwah-amoah, ). the initial variables which influence the preparedness of companies to recover during the post-covid- pandemic period was identified based upon: a. the literature review, b. obtaining the opinion of academic experts, c. reviewing newspaper articles and reports of reputed organisations, d. obtaining advice from scientists working in eminent organisations, e. building upon information from governmental policy-makers. j o u r n a l p r e -p r o o f that phase was followed by conducting a brainstorming session amongst the experts and the authors via videoconferencing. the experts were selected based on their research expertise in related fields. the experts, who were a part of the brainstorming process, later helped in prioritizing the variables. the details of the expert's responses are included in subsection . . . better recommendations usually come later with the brainstorming sessions (danes et al., ) . the experts' expertise and the second and third author's previous research on related issues under the guidance of the fourth author helped in identifying the appropriate variables and their respective groupings. this was followed by another brainstorming session amongst the experts and the authors to select and group the variables. the brainstorming session helped the authors to finalise the analytical framework. during the process of proposing and discussing the variables, the expertise of the experts and authors practical experience and in-depth understanding of the field of operations and supply chain were very beneficial. a total of forty-two variables were included in the final list. these variables were grouped into nine key factors and related subfactors. table lists identified key factors, which were selected as essential for helping industries to rebuild in the post covid- pandemic period and hopefully contribute to more sustainable societies, globally in the context of the likelihood of more pandemics in the near future due to climate changes. these factors can help business leaders to take concrete solutions that can improve their business' capacity to comply with the 'new norms' that respond to present and future pandemics, in the context of climate changes and other challenges. climate changes are also evidencing the very serious risks to sustainable societal futures, globally. climate changes will not only affect agriculture, fisheries and forestry but also industries such as transportation upon which all societies in developing and developed countries are totally dependent (song et al., ) . roles of governance roles of governance is paramount for the revival of industries in post-covid- • provide economic stimulus packages to provide low-cost money to industries to help them to restart • targeted social security programmes for those below the poverty line • close cooperation of government and industry to improve efficiency and resilience of production and supply chain management issues • measures are to be adopted to ensure demand for locally produced products, i.e. produced in india • strong and quick decision-making and effective implementation of the selected approaches • new norms for personal hygiene and sanitation • new healthcare norms facilitate the barrierfree movements of goods and services so that timely delivery can be accomplished within the country. the focus should be to overcome intracountry barriers. • shift management • flexible production size • workers safety and health to be the paramount agenda • transparency • welfare scheme and its effective implementation . environmental issues drastic reduction in pollution level is observed, i.e. the planet revives with no humans into play • new environmental assessment models and norms • pollution is made from industrial production and mankind consumption level has been reduced. • newer energy sources, renewable sources of energy • energy-efficient devices to be used . capacity building capacity building helps in easy incorporation of the technology • industries must focus on realignment, retraining and re-skilling of their employees • digitisation, automation and artificial intelligence will have to be accelerated in every stream. hands-on training on automation and artificial intelligence is required so that the future of societies is secured. jobs under mgnrega (mahatma gandhi national rural employment guarantee act) should be increased so that the workers who have returned to their home towns can also obtain employment. . change management stakeholders to be prepared mentally and trained to take the new normal • the morale of the workers should be boosted by giving them assurance that their health is the priority of the company; by removing the fear of the disease and by providing them a liveable wage, even when the company is temporarily 'closed.' • training for the "new normal" • psychological issues and management • awareness to be created amongst individuals on the importance of maintaining hygiene • safety of the consumers is to be ensured . organisational change management • organisational should coalesce as a team these factors can be used to challenge us to make dramatic changes in business models, corporate social responsibilities, designs for improved produce-services, improved life-long educational systems, and dramatically improved political systems and health-care systems from the local to the global levels. all of these changes must be envisioned and implemented from holistic, integrative, preventative perspectives. the indian government's priorities are: a. preventing the disease from spreading, b. ensuring provision of food and basic amenities for the poor and c. restarting the engine of the economy. lockdown and social distancing are being used as a means to break the chain of transmission of the disease and simultaneously improve the health infrastructure of the country . the challenge that the government is facing today is of unimaginable magnitude as india has the second-largest population in the world (paital et al., ) . timely, governmental interventions have contained the spread of the disease. nevertheless, the focus should be on rebuilding a more robust, resilient, equitable, sustainable nation which can prevent, anticipate or reduce the impacts of such shocks without affecting the economy (alicke et al., ) . the source of the coronavirus has not been identified as yet, and scientists are in the process of developing a vaccine to cure the same (vieira et al., ) . it is still not known whether this disease will be completely wiped off or it will re-emerge on a seasonal basis, and if it does, will it lead to the same kind of destruction as it has caused during the present time . however, the need of the hour is to help to make industries more resilient, sustainable and equitable so that they are able to face such kind of pandemic in the future. the steps followed in the present study are shown in the research flowchart, as depicted in initial variables have been identified by studying the literature, newspaper articles, the reports of reputed organisations and taking the opinion of the experts. recognition of important factors to rebuild the industry post-covid- was performed using the ahp approach. after the preliminary survey, forty-two variables were selected as highly relevant for seeking to make needed changes in industry and society. this method is built upon four hierarchy decision process levels (see figure ) which are explained below. after developing the hierarchical structure, pair-wise comparisons of the elements of the hierarchy were performed. in all comparisons, the comparative significance of a pair of elements in relation to a higher-level criterion was calculated, considering the decision-making objective. viewpoints from the experts were taken through a scientifically designed questionnaire and specified in terms of clear numeric values. in spite of the carefully designed system, the evaluation scale of ahp was not able to quantify the ambiguity due to human judgement. it is certain that there is a high degree of uncertainty in making decisions on matters related to covid- , and thus was difficult to quantify the suggestions for the company experts and from other stakeholders. but, a solution has to be provided to help the industries in restarting their work and in building resilient societies. even though there are weaknesses with ahp analyses, they are helpful when the objective is to rank the elements and the alternatives. in such cases, ahp is the most reliable method for determining the relative significance of criteria and alternatives. methods involving pair-wise comparisons can be rigid when criteria and alternatives are very closely interrelated (such as in the present case). therefore, it was important to consider all of the relevant elements of the decision problem. on the other side, mcdm methods that depend upon on the direct rating of criteria and alternatives, require less effort on the part of the decision-makers, but determining the weight coefficients for interactions is less precise (calabrese et al., ) . in comparing these methods, ahp is more appropriate to determine weight coefficients as it helps the decision-makers to obtain a better understanding the relative importance of interactive j o u r n a l p r e -p r o o f alternatives and criteria. in the ahp technique, attention is on two elements at a time and therefore, it provides a more accurate evaluation (konidari and mavrakis, ) . since the research for this paper pertained to a complex problem that had the risk of inconsistency, ahp provided the flexibility of its consistency thresholds compared to other methods that require perfect consistency for calculating weights. the threshold of ahp can be reduced or increased based on the decision-makers (ishizaka and siraj, ) . the ( ) calculating eigenvector (λ max ) for every matrix of the order n ( ) cr can be computed with the help of the following formula: ( ) where "n" is the order of the matrix and "ri" is known as the random consistency index. table gives the ri values for matrices of the order - . the experts involved in the ahp survey were selected based on their expertise in the related field. the questionnaire was mailed to the experts to ask about their opinion. a reminder mail was sent to the experts after one week. ten experts of the related field, with a minimum of ten years of experience were chosen for the study. six professionals from the industry, two academic experts and two medical doctors were invited to participate in filling the questionnaire to provide their assessment of the comparative significance of factors and sub-factors. the industrial experts were either managers or owners of msmes who had experience in running their enterprises. one of the experts had experience in managing workers and in taking care of their welfare for more than years. two of the experts were heads of parts supply departments. two experts dealt with managing inventory of parts. the final expert was the owner of an enterprise. two academic leaders who had more than twenty years of experience in research and in teaching supply chain management at their institutes and in providing training to the employees of msmes were also involved in the analytical process. one of the experts from academia was a member of the covid- committee of the government. one medical doctor was heading the cghs dispensary of north delhi and the other medical doctor was a very experienced doctor at the apollo hospital. the questionnaire was mailed to each of the experts. they were asked to make pair-wise evaluations of the critical factors which would help in restarting the businesses and in building resilient industries, which can face future shocks in the indian context. the experts were selected based on their work and experience in the related field. due to the current unprecedented situation of the covid- pandemic, the questionnaire was mailed to the respective experts to obtain their responses safely. table shows a brief description of the experts who participated in the analyses. after scrutinising data obtained from the questionnaires and applying the ahp approach, the key factors were identified. table presents information about ranking the significance of various factors based on the weight obtained by applying the ahp technique. (tables a to a ) depicts the local priority weights of varied factors that were produced to determine the relative significance of these factors and their sub-factors for helping to successfully rebuild the industries in the post covid- pandemic era in india. the rank of specific factors presented in table , depicts that global rank based upon on the value of global weights obtained by using the ahp methodology. global weights are attained by multiplication of the relative weight of factor category values with the relative weights of each specific factor. table suggests that the 'role of governance' has more weightage and thus influences the other factors. govindan et al. ( ) have referred in their paper that slight variations in relative weights leads to significant variations in final rankings. these weights were given from an individual perspective; thus, the sensitivity analysis was used to test the strength of the rankings obtained under the different weight categories. the 'role of governance (rg)' factor received the top priority with the ahp methodology. in order to determine the stability of the priority given to the factor 'role of governance (rg)' this factor's value was changed by . increments from . to . . this helped the researchers to ascertain the robustness of the results obtained by the ahp methodology (thanki et al., ) . table reflects the changes in the relative values of the other categories of factors when the value of the factor, "role of governance" was changed from . to . . figure shows that the changes in the weights of the other factors when the weight of the factor, "role of governance" was incrementally changed from . to . . it can be seen from table and figure that weighting of the other factors were minimally influenced by the changes of the j o u r n a l p r e -p r o o f weight of the "role of governance", thereby indicating robustness of the ranking obtained. this permitted the authors to generalize the results obtained. numbers on the horizontal axis in figure present the factors obtained by the procedure reviewed in section . . values of other factors after changing rg values from . to . table presents the ranking of the sub factors when the weight of the factor "rg" value was changed by . increments from . to . . etc etc etc etc it it it it rg rg rg rg rg rg rg scl scl scl scl ip ip ip ip ip ip cm cm cm oc oc oc oc oc at . of the factors "role of governance", factor scl holds the first rank and ip holds the last rank. from . to . ; rg attains the first rank and the ranks of other critical factors vary. according to the un department of economic and social affairs (desa), the covid- pandemic, has disrupted global supply chains and international trade. this is likely to decrease the economy, globally by almost % in (kumar et al., ) . the current research was designed to identify and to rank the essential factors which would help industries to rebuild in the post-covid- pandemic era in india. the ahp approach removes any unbalanced scale of judgment, doubt, and inaccuracy amongst the pair-wise comparisons performed (borade et al., ; thanki et al., ) . appendix a (a to a ) shows the results obtained by the ahp approach. it has been documented from table for their immediate working capital requirements and to help those who are at the bottom of the value chain. a targeted social security programme for these individuals has to be developed and implemented using a roadmap for helping to make the needed changes while ensuring health and safety of the workers, and others in the reverse and forward supply chains. it may happen that industries put environmental sustainability initiatives behind social sustainability issues in the wake of the pandemic. the pandemic could also cause a reversal in the trend toward more sustainable societies as governments take steps to loosen environmental law enforcement policies to favour the short-term survival of businesses. but the pandemic has given us dramatic, new insights of the significance of delivering a proactive response and of the urgent need to take timely actions. the industries and their competitors will be differentiated in the post covid world by their commitment to implementing sustainability issues and on their willingness and commitment to actualize such holistic, proactive practices (amankwah-amoah, ). the experts in this research predicted that during the post covid- era, much manufacturing will be shifted back from china to india. therefore, the "made in india programme," should be given a push by providing domestic and foreign manufacturers policy and fiscal incentives for manufacturing the products locally. the idea of building back better in terms of living in harmony with nature should be utilized rather than going back to the 'old' normal (the hindustan times, a). have obtained the next highest weight, which underscores the importance of fulfilling the essential needs of the citizens. healthcare equipment has to be supplied on a priority basis so that timely treatment can be provided and the lives of the individuals can be saved. keeping this in mind, specific industries have to be supported to resume operations. however, they will have to follow the mandatory protocols of social distancing and to maintain proper hygiene. the focus should be on the manufacture of products which are important in dealing with the situation. technology giants such as apple and tesla have drawn in their expertise and their supply lines to source supplies and to produce essential products in the usa rather than to depend upon global supply chains. (cankurtaran and beverland, ) . health care systems need an uninterrupted supply of medical equipment, testing equipment and protective equipment. therefore, restructuring of the existing industrial units is required so that they can produce the products which are required to respond to the urgent needs by making changes in their existing plants (elavarasan and pugazhendhi, ) . also, the covid- pandemic has helped to improve the environmental sustainability of the supply chain. but, that is not necessarily helpful enough in addressing the challenges of restarting businesses post covid- . that requires direct emphasis on re-establishing economically, ecologically, socially, sustainable and resilient supply chains (kumar et al., ) . it preparedness obtained the weight of less than half the weight obtained by the factor "role of governance". survival of the businesses post-covid- era will depend on their digital transformation. several useful technologies of industry . and industry . can help to provide the much-needed help to properly control and manage covid- pandemic . technological strategies can provide essential support in dealing with the pandemic state of affairs. technology can aid health care facilities and can help in uniting the society to function as j o u r n a l p r e -p r o o f one (elavarasan and pugazhendhi, ) . it can play crucial roles in every sector of the country. it-enabled services should be used to benefit all during and after this crisis. firms like microsoft and facebook have joined hands with the world health organisation for organising #buildforcovid , a global hackathon for developing a software for addressing issues related to the pandemic (cankurtaran and beverland, ) . additionally, more than million people of india have already downloaded the "aarogya setu" mobile application. this app is one of the most important tools in fighting covid- and one of the lifelines for common people during this global pandemic (p.i.b, c) . it informs the people of their potential risks of infection and the steps to be followed to stay healthy. it-enabled services should also be utilised to provide telemedicine services, especially in rural parts of india. this will bring much-needed relief to people who are finding difficulty in accessing medical services. however, digital transformation requires proper it and security tools to prevent cyber-attacks (pwc report, ). this was followed in priority by "change management". it is a means to transform the company's goals into reality. the main objective is to implement the plan of action for accomplishing change and in helping people to adapt to the changes (alicke et al., ) . stringent public health measures have to be implemented to curtail the spread of covid- (rajkumar, ) . strategies have to be formulated to reduce the fear of the disease. "organisational culture" received the next highest priority. corporate leaders should evaluate the flexibility of their organisation in making decisions for addressing market changes (bernauer and slowey, ) . the covid- pandemic and lockdown lessons should serve as a warning for industries and governments to plan for anticipating, preparing for and in effectively responding to future shocks. emphasis should be given on implementation of industry . technologies. assurance should be provided to the employees that their safety and health are considered to be extremely important to the company . "capacity building" has received the next highest weight. taking cognizance of the situation, it has become necessary to upgrade the skills of the workers. training on industry . technologies should be provided. short term courses and diplomas in such technologies should be provided to prepare the workers to work in companies of the future. industry protocols" in this context, the covid- pandemic has given us the opportunity to envision and hopefully to implement an economic system that focuses on the , un sustainable development goals. firms which operated during the pandemic are perceived in a very positive way; this will help to enhance their reputations among their customers. take for example, the j o u r n a l p r e -p r o o f decision made by brewdog, a firm in uk, to utilize its idle transportation capacity for distributing food to children of lower economic strata, helped to enhance brewdog's reputation among its customers. many firms have taken similar steps in times of crisis to keep their work going (cankurtaran and beverland, ) . this type of altruistic behavior is beneficial for those who receive help and for enhancing the reputation of the company in the post pandemic era. transformation of economic and socio-economic systems should support to help to make them environmentally sustainable and socially equitable, while continuing to be economically sound. the ahp approach was followed by performing sensitivity analysis that was used to analyse the robustness of the results obtained by the ahp methodology. this analysis showed that the "role of governance" factor category influences and impacts many other factor categories. thus, an integrative, holistic, multi-factorial approach is needed to make the needed transitions. covid- is the most severe pandemic that the whole world has encountered recently. recognising essential factors helps in identifying those factors which have received more weight. given the possibility of future pandemics as stated by who chief, and the higher probability of adverse environmental events due to increasingly severe consequences of climate changes, it has become necessary to identify factors which can help to restart the industries so that they are more resilient and also that they can help societies to become more resilient. the objective of the authors of the paper was to integrate this research with earlier related research on design thinking. design thinking was chosen because it focussed upon disruptive thinking and on reframing; therefore, it provides relevant insights pertaining to restarting companies in the context of crises. this term was first used by herbert simon ( ) in reference to the unique mental tools used by researchers in solving problems. the special features of design thinking such as creativity and innovation, capability to visualize, scope of ambiguity and failure, mixing analysis with intuition along with the approach of brainstorming were found to be beneficial for addressing the " wicked problems" associated with the covid- pandemic (head and alford, ) . issues brought up by the pandemic are considered to be "wicked" as they are defined as the problems in which they are not defined properly, there is no proper information, there are no agreements on ideas between the customers and the decision-makers and where the consequences of the decisions taken are not even clear (cankurtaran and beverland, ) . the pandemic has produced a number of wicked problems for industries which, suddenly met with lack of markets and no future for their products. therefore, the 'new normal,' will require deploying decision thinking responses to emerging and multifaceted challenges imposed by the covid- pandemic. the current research can help the government in reviewing its policies formulated for msmes and society as a whole so that they can be benefitted and motivated to rebuild their businesses. it is very important for the government to review the cyber security law so that the policies favouring msmes can be incorporated (alicke et al., ) . the big lesson that the pandemic has taught us is the need for self-reliance and how each village, district, state and the country as a whole needs to become self-sufficient. it can happen if domestic capabilities are given a boost to help in prevention of the disruption of the supply chains in the future. disruption in the supply chains can be prevented by evaluating automotive alternatives to reduce the number of workers on the shop floor. it is also very important to transfer new knowledge across supply chains and training supply chains that must be nurtured, strengthened and supported. it is paramount to communicate about the best practices as the situation evolves and help the suppliers to implement them (pwc report, ). the effects of covid- emphasize the significance of using sustainable, holistic policies, procedures and technologies that will become vital for businesses to sail through the present and future pandemics, as they co-work with governmental leaders to implement the goals related to ecologically sustainable, economic development of cities and communities. the pandemic has highlighted the need of having flexibility in the existing norms, which could improve the ease of the survival of businesses in the short-term. but the survival of businesses in the long-term will depend on their commitment to incorporate an array of aspects of sustainability in their policies, business plans, product-service system designs, as well as how they work with all stakeholders in their supply chains, as well as with their consumers and their neighbours. the authors of this paper underscore the necessity for investing in the health care systems of the country. the most important factor in preventing the spread of the disease is to empower citizens j o u r n a l p r e -p r o o f with the right information and keep social distancing and maintain personal hygiene. social distancing is necessary until the time an effective vaccine is developed to eradicate the disease. also, lessons from past outbreaks revealed that social distancing measures, communication and international cooperation can help in curbing the spread of the disease. many researchers from the past pandemics infer that steps related to social distancing, cancelling public gatherings, isolating the sick, and wearing masks were the most effective measures to slow the spread of pandemics (peeri et al., ; vaka et al., ) . but cushioning the effect of covid- will require the companies to draft innovative ways to ensure the health of workers while simultaneously protecting the environment and their economic viability. though it is tough to sell environmentally friendly policies, incentives by the government and demands from consumers and other stakeholders will help the companies to draft and implement the guidelines ensuring the incorporation of all three aspects of sustainability. the present research is a contribution of the authors towards society as a whole in encountering the pandemic by identifying the essential factors which can be used to help to rebuild the nation, especially the industries in the post lockdown era. guidance from academicians, industry experts and medical doctors was used to identify, evaluate and prioritise the groups of factors which are most likely to be effective in rebuilding the systems by making changes to the 'new normal'. the present paper was designed and prepared to help to re-instil confidence that we, as the citizens of india, should have faith in ourselves in the transition to the future. taking cognizance of the present work can help in understanding that the factors highlighted to help many to become 'corona warrior,' if followed properly. the 'corona warriors' can help in confronting the pandemic and in assisting in creating a restructured society in which there will be a "new normal," as depicted in figure . j o u r n a l p r e -p r o o f global societies are facing multiple challenges in seeking to combat the covid- pandemic, which is 'among the most critical challenges,' we have had to address in a long time. some of the consequences of this pandemic are that many manufacturing organisations were forced to stop their operations and this forced leaders of some firms to explore implementation of sustainable solutions which can help them in building resilient industries and sustainable societies which are able to withstand such shocks in the future. the current study was designed to identify and to prioritise the essential factors that affect in the rebuilding of more robust, resilient, equitable, sustainable industries in the post covid- era. categories of nine major factors with forty-two variables were selected, based on the advice of j o u r n a l p r e -p r o o f the experts. it was followed by using the ahp approach, which was used to develop priorities to the forty-two variables. the ahp approach was used to identify and prioritise the factors which can contribute effectively to make needed changes. based upon the calculations, it was found that the factor 'role of governance' received the highest weight. the "role of governance," is critical in developing and implementing policies to revive the economy by rebuilding the industries. but there are also many other aspects that must be addressed to effectively transit to a more resilient, equitable and sustainable society in the face of disruptions from the current pandemic and to respond effectively in building a society that is fully engaged in seeking to reverse climate changes. although, the authors of the paper have tried to contribute by identifying the factors which can help in building resilient industries, still the paper has limitations which provide opportunities for further research. the findings were primarily based on the review of literature, reports of international organisations and opinion of the experts. the priorities for future action were based upon the opinions of experts obtained with the help of the questionnaire mailed to them. due to the social distancing norms that had to be followed, the entire procedure was conducted via mail. it would have been better to conduct the procedure of getting the questionnaire filled by 'face-to -face' interactions with the experts. additionally, the selection of experts from various sectors of the industries was not uniform; thus increasing the probability that the findings of the study may be somewhat biased towards a particular industrial sector. also, the ahp technique has a limitation of inaccuracy associated with the expert's judgements. thus, the fuzzy ahp, which can provide freedom to experts to express their viewpoints with natural languages, should be addressed in our future research. additional research should be performed on individual companies to obtain more comprehensive insight into the issues they must face due to this pandemic's disruption in their supply chains, their employee's health and their customer's capacity to 'buy' or to rent their products and services. this will help, to obtain a more generalized overview. additionally, the effects of short and long-term governmental and corporate policies on different industrial sectors, needs to be examined. awareness should be created on maintaining personal hygiene. the fight against the covid- pandemic begins with regular hand-washing and wearing masks that are practices which have been found to be useful in slowing the spread of the virus. on these and other levels india has been a leader in addressing the challenges of the covid- pandemic. the objective of the authors of this paper was to provide researchers with a challenge to take these suggestions and help to facilitate their implementation at the local, regional and national levels for the short and long-term future of india and other countries. also, companies that exhibit their dedication towards sustainability issues in the wake of and in the post covid- era will be respected for their holistic responses to the challenges and for their stronger relationships with their key stakeholders. supply-chain recovery in coronavirus times-plan for now and the future stepping up and stepping out of covid- : new challenges for environmental sustainability policies in the global airline industry -ncov epidemic: address mental health care to empower society covid- , extractive industries, and indigenous communities in canada: notes towards a political economy research agenda analytical hierarchy process-based framework for vmi adoption incorporating social aspects in sustainable supply chains: trends and future directions integrating sustainability into strategic decision-making: a fuzzy ahp method for the selection of relevant sustainability issues using design thinking to respond to crises: b b lessons from the covid- pandemic the sequential order and quality of ideas in electronic brainstorming restructured society and environment: a review on potential technological strategies to control the covid- pandemic note from the editors: world health organization declares novel coronavirus ( -ncov) sixth public health emergency of international concern circular supply chain management: a definition and structured literature review barriers analysis for green supply chain management implementation in indian industries using analytic hierarchy process a decision support system for demand management in healthcare supply chains considering the epidemic outbreaks: a case study of coronavirus disease (covid- ) areas of academic research with the impact of covid- wicked problems: implications for public policy and management exploration of social sustainability in healthcare supply chain ilo: as job losses escalate, nearly half of global workforce at risk of losing livelihoods are multi-criteria decision-making tools useful? an experimental comparative study of three methods viability of intertwined supply networks: extending the supply chain resilience angles towards survivability. a position paper motivated by covid- outbreak industry . technologies and their applications in fighting covid- pandemic determinants for integration of sustainability with innovation for indian manufacturing enterprises: empirical evidence in msmes multi-criteria evaluation of climate policy interactions covid- impact on sustainable production and operations management the economic impact of the coronavirus what google tells us about lockdown impact in india's biggest cities? online detail question and answers on covid- for general public the socio-economic implications of the coronavirus and covid- pandemic: a review government working on a separate scheme to address delayed payments issues of msmes¬ shri nitin gadkari b, b. pib' s daily bulletin on covid- shri sanjay dhotre takes stock of the state of it services in the country inter nation social lockdown versus medical care against covid- , a mild environmental insight with special reference to india the sars, mers and novel coronavirus (covid- ) epidemics, the newest and biggest global health threats: what lessons have we learned? considerations for a secure working environment covid- and mental health: a review of the existing literature application of ahp for process parameter selection and consistency verification in secondary steel manufacturing coupled human-environment system amid covid- crisis: a conceptual model to understand the nexus governance, technology and citizen behavior in pandemic: lessons from covid- in east asia the sciences of the artificial ( st ed) improving natural resource management and human health to ensure sustainable societal development based upon insights gained from working within 'big data environments' covid- climate lessons: unprepared for a pandemic, can the world learn how to manage the bigger threat of climate disruption? breakthrough-national centre for climate restoration an investigation on lean-green implementation practices in indian smes using analytical hierarchy process (ahp) approach india looks at china, south korea, and germany for best practices, technology to contain virus once lockdown ends, govt plans make in india boost united nations policy brief: covid- and the need for action on mental health a review on malaysia's solar energy pathway towards carbon-neutral malaysia beyond covid' pandemic covid- : the forgotten priorities of the pandemic world health organization, . who director-general's opening remarks at the media briefing on covid- - the authors look forward, with optimism, that global societies will be able to 'conquer' the pandemic and will emerge with new norms, new lifestyles, and new tools in anticipating and in dealing with future crises. key: cord- -xnr xq authors: mansuri, farah m.a. title: situation analysis and an insight into assessment of pandemic covid- date: - - journal: j taibah univ med sci doi: . /j.jtumed. . . sha: doc_id: cord_uid: xnr xq nan the world is seeing a catastrophic pandemic of sars-cov or of the disease covid- , in first quarter of st century with the emergence of novel corona virus. after starting in wuhan city of china in dec' it has spread over countries so far, with varying degree of severity and fatalities. nearly . million of world population have been confirmed as cases of covid- and above thousand deaths were reported by april , . the intensity of pandemic varies from country to country and the worst affected ones are italy, spain and france regarding the fatality ratio. it is learnt that % of total global cases and . % of total global deaths due to covid- are reported in european region. , regional statistics of world health organization depicts that eastern mediterranean region (emro) stands fourth in the rank of prevalence of confirmed cases of covid- after europe, americas and western pacific, with a total number of thousand cases and deaths. among emro countries, iran contributes the highest proportion % of cases as compared to that of . % cases recognized in the ksa. correspondingly, % of deaths due to covid- in emro region were documented in iran. , the case fatality rate (cfr) would be a misleading indicator without knowing the complete natural course of the disease and the number of total cases due to limited diagnostic and research facilities at the moment. nevertheless, case fatality rate in covid- documented to be . % as mean (in age > as high as . %), as compared to % of sars-cov and % of mers-cov. , in current scenario, nature of the virus and its ability to affect populations, is still unclear. but we should not forget the example of hiv/aids, spanish flu and hong kong flu pandemics, where resurgence, mutation of virus, unusual trend, deceptive figures of pandemic and certain misconceptions further deteriorated the scenario and hampered with peoples' response to control strategies. likely clinical diagnosis of covid- is based on clinical symptoms ranging from high fever, dry cough, shortness of breath to acute respiratory distress syndrome. few asymptomatic cases were also identified in family clusters. it was evaluated that % of the cases were mild, % required oxygen therapy while % were critical with multiple organ failure and septic shock. for its laboratory diagnosis, cdc has developed a new laboratory test kit, called as "cdc -ncov real-time reverse transcriptase (rt)-pcr diagnostic panel." it is intended for use with upper and lower respiratory specimens collected from persons suspected of covid- . this test is said to be % sensitive. till date no specific pharmacological therapy has been identified. patients have been treated with symptomatic therapy of oxygen, antiviral preparations, while hydroxychloroquine also shows some promising results lately. in an epidemiologist's perspective, definitely two aspects are to be investigated to characterize the pandemic; one is transmission rate and the other is clinical severity. transmission can be studied by calculating basic reproduction number r , rate of infection in household, schools or workplace, travel history of suspected cases, and outpatient reporting of cases. if r is calculated less than , the pandemic is unlikely to occur, if less likely and if more than then a pandemic is certain. the covid- has r of . e . , that is higher than of sars. the other indicator besides transmission rate, is severity of the pandemic, that can be studied by ratio of cases to hospitalization, ratio of deaths to hospitalization and ratio of intensive care unit admissions to total admissions. it is imperative to identify pandemic severity index to tackle the situation accordingly. pandemic severity index should be assessed in the early phase of the outbreak by taking into account transmissibility, seriousness of clinical course and impact of pandemic on health care and societies. the pandemic severity index is categorized as none [ depending on covid- overall mortality ratio it can be classified as having category pandemic severity index. in the absence of vaccines and any known treatment against covid- , the mainstay of the control strategies for communities at large, is non-pharmacological measurements namely 'suppression' and 'mitigation' strategies. suppression is aimed at reversing pandemic growth to low levels for indefinite time, whereas mitigation measures to flatten the pandemic curve or to slow down its progression. the public health actions taken to prevent the transmission of virus include social distancing of the entire population, home isolation of mild cases, household quarantine of their family members, travel restrictions, school closures, working from home and partial or complete lockdown. at individual level, wearing of mask, frequent hand washing and sneezing and coughing etiquette are encouraged. though standard guiding principles have been laid down by international health agencies but countries taking steps according to their own feasibility and requirements. besides these community measures, availability of skilled health work force, enough diagnostic kits, medical and protective supplies and preparedness of health systems would play an important role in containment of pandemic. we drew sufficient evidence that despite technological advancements and public health awareness, the average basic reproduction number r in covid- pandemics is evidently increased up to . as compared to of early th century pandemics. moreover, the fatality ratio reported being . % in covid- , . % in h n flu, as compared to > . in spanish flu. whereas, pandemic severity index was and in last century pandemics as compared to in this millennium. this disparity in fatality and pandemic severity index may be due to several factors such as higher virulence of virus and availability of better preventive or therapeutic health care services etc. the path to assess new infections is to be explored further under the guidance of global frameworks and, there is a dire need to conduct research through syndromic surveillance and proper case control studies to find out associated risk factors and fulminant or less fulminant outcomes. equally important is integration of data sources and data types to identify severity pyramid in order to be prepared for the future. because the question at present is when and which next pandemic confronts us rather than will it happen altogether or not. at present, overestimation of the pandemic can not be ruled out unless evidence-based data is gathered and robust analysis is performed accordingly. we may conclude that though our community and technical efforts have been improved to tackle the emergent infections but the viruses also getting adversely smarter in its virulence and causing higher severity in terms of fatality ratio and reproduction number. time has come to win the battle with a holistic armamentarium against these deadly pandemics by bringing a balance between economic stability and health related timely disclosures. we got to be ready to address all components of health, including physical, social, mental, and spiritual wellbeing and try to maintain harmony in life at its best. this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. world health organization. coronavirus disease (covid- ); . situation report the reproductive number of covid- is higher compared to sars coronavirus features, evaluation and treatment coronavirus (covid- ) pathogenicity and transmissibility of -ncov-a quick overview and comparison with other emerging viruses novel framework for assessing epidemiologic effects of influenza epidemics and pandemics nonpharmaceutical interventions for pandemic influenza, national and community measures ): e . how to cite this article: mansuri fma. situation analysis and an insight into assessment of pandemic covid- there is no conflict of interest. key: cord- -mb dnf authors: shanahan, lilly; steinhoff, annekatrin; bechtiger, laura; murray, aja l.; nivette, amy; hepp, urs; ribeaud, denis; eisner, manuel title: emotional distress in young adults during the covid- pandemic: evidence of risk and resilience from a longitudinal cohort study date: - - journal: psychological medicine doi: . /s x sha: doc_id: cord_uid: mb dnf background: the coronavirus disease (covid- ) pandemic and associated lockdown could be considered a ‘perfect storm’ for increases in emotional distress. such increases can only be identified by studies that use data collected before and during the pandemic. longitudinal data are also needed to examine ( ) the roles of previous distress and stressors in emotional distress during the pandemic and ( ) how covid- -related stressors and coping strategies are associated with emotional distress when pre-pandemic distress is accounted for. methods: data came from a cohort study (n = ). emotional distress (perceived stress, internalizing symptoms, and anger), covid- -related stressors, and coping strategies were measured during the pandemic/lockdown when participants were aged . previous distress and stressors were measured before covid- (at age ). results: on average, participants showed increased levels of perceived stress and anger (but not internalizing symptoms) during the pandemic compared to before. pre-covid- emotional distress was the strongest predictor of during-pandemic emotional distress, followed by during-pandemic economic and psychosocial stressors (e.g. lifestyle and economic disruptions) and hopelessness, and pre-pandemic social stressors (e.g. bullying victimization and stressful life events). most health risks to self or loved ones due to covid- were not uniquely associated with emotional distress in final models. coping strategies associated with reduced distress included keeping a daily routine, physical activity, and positive reappraisal/reframing. conclusions: in our community sample, pre-pandemic distress, secondary consequences of the pandemic (e.g. lifestyle and economic disruptions), and pre-pandemic social stressors were more consistently associated with young adults' emotional distress than covid- -related health risk exposures. during spring . young adults face many normative transitions (arnett, ; shanahan, ) , which are known to be stressful , including in their educational and professional development (e.g. important exams, entry into the labor market, financial pressures, and uncertainties), social and romantic relationships, and changes in their living situation (e.g. living away from family for the first time). these normative changes and pressures could be compounded by covid- -related stressors and disruptions (e.g. declining labor market and inability to socialize with friends or romantic partners). despite these potential stressors, young adults have a relatively low risk of health complications from covid- , are competent in using social media to connect with others, and typically do not have caregiving duties (e.g. for children or elderly parents). thus, they also have the potential to experience resilience (i.e. adaptive or better-than-expected outcomes despite the presence of significant risk/adversity, masten, ; werner, ) during the covid- pandemic. during-and pre-pandemic emotional distress assessed in our study includes perceived stress, internalizing symptoms, and anger. in addition, pre-pandemic stressors typically associated with such distress, including social isolation, victimization experiences, and stressful life events, were measured. we also assessed low self-rated health to gauge participants' pre-pandemic health status. during-pandemic putative stressors assessed included one's own health risk status and that of loved ones. in addition, we assessed stressors related to secondary consequences of the pandemic (e.g. economic and lifestyle disruptions); and also hopelessness, low trust in societal responses to the pandemic, and frequent covid- -related news-seeking as factors that could be associated with increased emotional distress. we also assessed potentially adaptive coping strategies that could mitigate during-pandemic distress. data were collected in switzerland's largest city, zurich, which is located approximately h by car/train from northern italy, the first epicenter of the european covid- outbreak. following italy, switzerland was among the first european countries affected by covid- , ranking among the most affected countries worldwide in march , with one of the highest per-capita rates of covid- infections (salathe et al., ) . the swiss national lockdown policies were strictest from march to april . schools, universities, and all non-essential stores were closed, social distancing measures were enforced, social gatherings of more than five people were prohibited, working from home was implemented whenever possible, and public transport was considerably reduced (swiss federal office of public health, ). borders with neighboring countries were mostly closed. by the end of data collection ( april ), switzerland (with a population of . million) had reported cases of covid- and deaths (worldometer, ) . however, the case reports represent underestimates as testing was sometimes limited to at-risk individuals. universal health care and unemployment benefits are available in switzerland, and the government subsidized furlough schemes to prevent widespread unemployment during the pandemic. data came from the zurich project on the social development from childhood to adulthood (z-proso), a prospective-longitudinal study. the cohort comprises participants who entered first grade in one of public primary schools in zurich in . the initial target sample of schools was selected using random sampling procedures (slightly oversampling disadvantaged school districts). the original study consists of eight assessment waves, at ages , , , , , , , and (in ) , respectively (for additional details on the sample and attrition, see, eisner, malti, & ribeaud, ; eisner, murray, eisner, & ribeaud, ) . in april , all age participants (then aged ) were invited to participate in a covid- online study. the current analysis uses stressor and emotional distress data from the age and covid- assessments (see online supplementary fig. s ). out of eligible participants from the age assessments, could not be reached due to invalid contact information/ unclear status. out of cases contacted, participants responded ( . % of age sample). due to this attrition, sampling weights were used in all analyses to allow generalizations back to the original recruitment population from (for the creation of these weights, see nivette et al., ) . at age , participants completed surveys (lasting ∼ min) at a university research laboratory. participants received a ∼$ cash compensation for their time. at age , data collection began during week of the swiss national lockdown ( april ) and ended days later. the online survey took ∼ - min to complete; participants were entered into a lottery to win one of prizes of ∼$ . participants provided written informed consent to participate in the study at ages - and online informed consent at age . ethical approval was obtained by the ethics committee of the faculty of arts and social sciences of the university of zurich. the authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the helsinki declaration of , as revised in . below, we list the measures, and their sources and time frames. individual items of all non-demographic measures, and their scales, scoring, and cronbach's α can be found in the online supplement (table s ) . perceived stress during the past weeks was assessed using four items from the perceived stress scale (cohen, kamarck, & mermelstein, ) . internalizing symptoms were assessed using items from the social behavior questionnaire (murray, obsuth, eisner, & ribeaud, b) addressing depressive and anxiety symptoms in the past weeks and two additional items assessing suicidal ideation and self-injury. anger during the past weeks was assessed using three items from the promis® emotional distress -anger -short form (pilkonis et al., ) . perceived stress was correlated with internalizing symptoms and anger at r = . and . , respectively; internalizing symptoms were correlated with anger at r = . . nevertheless, each construct captures somewhat different aspects and stages of emotional distress. for example, perceived stress may precede the manifestation of internalizing symptoms, whereas anger/irritability is an expression of emotional distress but is typically not wellcaptured in anxiety and depression scales (vidal-ribas, brotman, valdivieso, leibenluft, & stringaris, ) . therefore, we examined the correlates of each of these indicators separately. lilly shanahan et al. family socioeconomic status (ses) was assessed using the international socioeconomic index of occupational status (isei, ganzeboom, degraaf, treiman, and de leeuw, ) ; the highest isei recorded for each household between child ages and was used. education/occupation (age ) was based on participants' highest educational degree and their current educational/occupational status. categories included ( ) college-track credentials or higher educational degree (high), ( ) vocational/compulsory education, currently in education/training or employed (medium), ( ) completion of compulsory school degree or preparatory vocational bridge year but currently not in education, employment, or training (neet, bynner and parsons, ) (low). migration background indicated whether both parents were born abroad (v. at least one parent born in switzerland). living alone was coded positive if participants did not share a household with another person at age . antecedent risk factors (age ). perceived stress, internalizing symptoms, and anger at age were assessed as for age , except with a -month time frame. perceived social exclusion was assessed with six items (bude & lantermann, ) . low social support from adults was assessed using four items created by the study team. bullying victimization during the past year was assessed with four items (murray et al., a) . low generalized trust was measured with three items (inglehart et al., ) . low self-rated health was measured with one item. stressful life events assessed potentially stressful events since the age assessment. a cumulative sum score was created to capture the overall stressor load from life events. concurrent risk factors. health risks during covid- were measured by asking respondents whether they or a loved one (e.g. family member, partner) had an occupation or a pre-existing health condition that increased their health risks during the covid- pandemic. we also assessed symptoms of covid- , positive covid- test, hospitalization because of covid- , and death of a loved one from covid- . based on these items, six binary variables indicated the presence or absence of occupational risk, health risk, and actual illness of a loved one or oneself. lifestyle disruptions were assessed by having participants rate the degree to which covid- had disrupted their lives (e.g. daily routines, work, education, and family). economic disruption was assessed by asking participants whether they had financial problems due to the current situation. loss of occupation/education assessed job loss, suspension of educational program, or problems with one's business during the covid- outbreak. hopelessness was assessed with one item. low trust in society's responses to covid- was measured using six items assessing the degree to which respondents distrusted the government's responses to, other people's responses to, and media coverage about the covid- crisis. frequent covid- news-seeking was assessed by asking respondents how often during the day they sought news or information about covid- . coping. we assessed several coping strategies, including emotional support-seeking, self-distraction, acceptance, and positive reappraisal/reframing, with one item each, adapted from carver ( ) . in addition, several coping strategies that may have been particularly important during the covid- lockdown (keeping a daily routine, physical activity/exercise, helping others, and seeking professional mental health support) were assessed. relative change in well-being. respondents rated the extent to which they currently felt worse or better compared to before the covid- pandemic using a -point scale. based on this scale, we coded a categorical variable: feeling worse ( - ), feeling approximately the same ( - ), and feeling better ( - ). open-ended comments. in a final open-ended comments section, participants were invited to share any additional thoughts about the covid- crisis and their current well-being. paired sample t tests were used to compare absolute levels of preand during-pandemic emotional distress. regression analyses were performed in separate steps to examine the antecedents and concurrent correlates of during-pandemic emotional distress. first, we analyzed associations of pre-and during-pandemic stressors/risks with during-pandemic levels of emotional distress. for this purpose, each pre-and during-pandemic correlate was entered separately while adjusting for sociodemographic characteristics only. second, we analyzed whether pre-and duringpandemic stressors and risk factors were associated with change in individual differences in distress. for this purpose, the lag of the outcome at the previous time point was added to examine predictors of covid- distress 'net' of pre-pandemic distress. third, all demographic variables and all significant concurrent correlates from the previous step were entered into one model, keeping only significant predictors. fourth, in a separate model, the same step was repeated for all antecedent predictors. thus, the third and fourth steps resulted in trimmed models of final concurrent and antecedent correlates. attrition analyses showed that, compared to the first assessment at age , respondents in the age covid- survey were more likely to be female and from a non-migrant background ( p < . and p = . , respectively). the percentage of missing data in each assessment was low. nevertheless, we used multiple imputation to address any potential bias (enders, ; schafer & graham, ) . we specified an imputation model with all variables used in our study; imputed data sets were generated. multiple regression analyses were then performed in mplus (muthén & muthén, ) to examine the antecedents and correlates of distress during covid- . we estimated linear models (in which all outcome variables were continuous) using the maximum likelihood robust estimator. parameter estimates were averaged across the imputed data sets and standard errors were pooled following rubin's rules (rubin, ) . table shows the descriptive statistics for all study variables. paired sample t tests revealed that young adults' mean perceived stress levels and anger were higher during the pandemic compared to the pre-pandemic assessment ( p < . ). the mean of internalizing symptoms decreased ( p < . ). only a minority of participants worked in an occupation that increased their risk of contracting covid- , had a health condition that increased their risk of covid- complications, or had experienced symptoms of or were diagnosed with or hospitalized for covid- . most participants had a loved one working in an at-risk occupation or with a health condition that increases their risk of complications, but only a minority of participants psychological medicine had a loved one who had either been diagnosed or hospitalized with covid- or had died from it. on average, participants rated the covid- crisis as somewhat disruptive to their lifestyle (i.e. daily routine, work, education, and family). approximately one in seven participants reported economic disruption. more than one in five reported frequent news-seeking in relation to . online supplementary table s shows descriptive variables by sex, revealing, for example, that females reported higher levels of pre-and also during-pandemic emotional distress compared to males on all indicators. females also reported higher levels of during-pandemic lifestyle disruptions and hopelessness than males. figure shows associations between each correlate and each outcome, adjusting for sociodemographic variables; these coefficients of concurrent correlates of during-pandemic emotional distress could be compared to those from other cross-sectional work (for exact coefficients and p values, see online supplementary table s ). females were at higher risk of each of the three emotional distress indicators. having a migrant background was associated with more perceived stress. in addition, pre-pandemic social stressors, stressful life events, low generalized trust, poor self-rated health, and concurrent pandemic-related stressors (i.e. during-pandemic lifestyle and economic disruptions, loss of occupation/education) and other risks (e.g. hopelessness and low trust in responses) were associated with during-pandemic distress. frequent news-seeking was associated with perceived stress and anger. health risks to self and loved ones during the pandemic generally had small or no associations with distress. figure shows results of the analyses in which all models depicted in fig. were adjusted for previous distress (i.e. adjusted for the outcome variable at age ; for exact coefficients and p values, see online supplementary table s ). thus, the coefficients for risk factors depicted indicate risk of greater increases in perceived stress and anger during the pandemic assessment compared to before relative to others in the sample (or fewer decreases in internalizing symptoms relative to others as internalizing symptoms decreased on average). those with previous emotional distress were at considerably increased risk of during-pandemic emotional distress; internalizing symptoms had the highest stability among the distress indicators. with the inclusion of previous emotional distress the size of the coefficient for female sex was reduced by about half. the inclusion of previous distress reduced the size of some associations between pre-pandemic stressors (e.g. low social support) and during-pandemic distress, but pre-pandemic bullying victimization, stressful life events, perceived social exclusion, and low self-rated health still predicted pre-to during-pandemic increases in emotional distress. many during-pandemic/lockdown stressors, including lifestyle and economic disruptions and loss of education or employment, were associated with greater increases in emotional distress. in addition, hopelessness was associated with during-pandemic distress. indeed, after pre-pandemic distress, during-pandemic stressors and hopelessness were the strongest correlates of during-pandemic distress. health risks to or actual covid- illness of loved ones were associated with increases in perceived stress; being in the health risk group was associated with internalizing symptoms, and having had symptoms or a diagnosis of or having been hospitalized for covid- was associated with anger. all other associations between the health risk variables and emotional distress were not significant. table shows associations from the final multivariate models which aimed to understand which correlates explained unique variance in during-pandemic emotional distress when taking into account pre-pandemic emotional distress and other significant correlates at the same time point. pre-pandemic distress and lifestyle and economic disruptions and hopelessness during the pandemic were most strongly associated with during-pandemic perceived stress, internalizing symptoms, and anger. prepandemic bullying victimization and cumulative stressful life events were also uniquely associated with during-pandemic emotional distress. some correlates were associated with a single emotional distress outcome only. for example, migration background and a loved one's covid- health risks or actual illness were (weakly) associated with increases in perceived stress only. furthermore, low pre-pandemic generalized trust, low concurrent trust in society's responses, and frequent covid- -related news-seeking were associated with increases in anger only. with the inclusion of during-pandemic lifestyle disruptions and hopelessness, the sex coefficient was reduced considerably (to nonsignificance for perceived stress and internalizing symptoms). table shows that there were no correlates associated with internalizing symptoms only. coping strategies online supplementary table s shows descriptive statistics for all coping variables. there are several possible processes that may underlie associations between young adults' use of coping strategies and emotional distress: first, individuals who are distressed by the pandemic/lockdown may more frequently use certain coping strategies (resulting in positive coping-distress associations). second, frequent use of other coping strategies may work more preventatively or instantaneously (resulting in negative copingdistress associations). consistent with the first process, table shows that several coping strategies, specifically seeking social support, engaging in distractions, and seeking professional help, were used more frequently by those with more pandemic/lockdown distress. consistent with the second process, frequent use of several other coping strategies, specifically keeping a daily routine, positive reappraisal/reframing, engaging in physical activity, acceptance, and keeping in contact with family and friends, was associated with reduced distress (the latter two were associated with reduced internalizing problems only). given that coping strategies were assessed at the same time as the emotional distress measures, additional processes, including bidirectional processes, may also be consistent with these findings. we directly asked participants whether they were doing better, approximately the same, or worse during the pandemic compared to before; . % reported feeling approximately the same (or just slightly worse or better), . % reported feeling notably better, and . % reported feeling notably worse. the continuous feeling worse item was correlated with increased emotional distress during covid- , as measured by the differences (covid- score minus the age score) for the respective outcomes (r = . , p < . ; r = . , p < . ; and r = . , p < . for associations of sociodemographic and risk variables with changes in emotional distress from the pre-pandemic to the during-pandemic/lockdown assessment (i.e. adjusted for pre-pandemic distress). models that used stressors and health risks as predictors were adjusted for all sociodemographic variables. risk factors were each entered one at a time (i.e. a separate model for each risk factor). standardized regression coefficients (β) and % cis were applied. for exact coefficients, cis, and p values, see online supplementary table s . the future (of the pandemic, society, and their personal educational or professional future). the stress-inducing characteristics of the covid- pandemic and associated lockdownwhich include uncertainty, ambiguity, loss of control, social isolation, and worries about one's own health and that of loved onescould induce or increase stress and stressrelated mental health problems, including internalizing symptoms and anger (reger et al., ) . although most young adults are at low risk of physical health complications from covid- , they may be distressed by the pandemic's secondary consequences, including the lockdown and associated social standstill and economic decline. indeed, these secondary consequences of the pandemic could be especially troubling for young adults as they attempt to tackle many of life's key transitions (e.g. educational, professional, social, and romantic relationships, arnett, ; shanahan, ) , but are now frustrated in these efforts. this study leveraged a prospective-longitudinal cohort study to examine several important issues relating to the pandemic/lockdown and young people's mental health, including the roles of previous distress and stressors in during-pandemic emotional distress, which can only be examined with a combination of pre-and during-covid- assessments. the largest risk factor for emotional distress during covid- was previous emotional distress. stability of stress and psychopathology is a well-known phenomenon (copeland, shanahan, costello, & angold, ) and should be considered for the identification of those in need of duringpandemic mental health services. in addition, pre-pandemic social stressors (e.g. bullying victimization, stressful life events, and feelings of social exclusion) predicted during-pandemic emotional distress. it is possible that the effects of pre-covid- social stressors may be exacerbated during the pandemic/lockdown (e.g. by limited opportunities for social contact). among during-pandemic stressors, the secondary consequences of the pandemic/lockdown, including lifestyle and economic disruption, and feeling hopeless, were most strongly associated with emotional distress. this is consistent with previous work reporting that economic disruptions are accompanied by declines in mental health (forbes & krueger, ) . economic downturn changes young adults' future outlook, including their visions and hopes for their professional and economic future (gassman-pines, gibson-davis, & ananat, ) . despite the availability of certain safety nets in switzerland (e.g. unemployment benefits and furlough schemes), young adults, who are relatively new to or just transitioning into the job market, may be more likely to fall through the gaps in these safety nets. economic disruptions also tend to be associated with tensions in interpersonal relationships, which can further impact mental well-being (conger, ge, elder, lorenz, & simons, ) . surprisingly, health risks to self or others during the covid- pandemic were only weakly associated with emotional distress. this could be due to the fact that only a small percentage of participants was exposed to the most traumatic aspects of the pandemic (e.g. death of a loved one or own hospitalization due to . furthermore, young adults with work-related potential exposure to the virus may not perceive themselves as being at risk of serious covid- -related complications, and/or could have found a sense of meaning or purpose in contributing to society during the pandemic (which could increase resilience). in addition, the swiss lockdown was effective at 'flattening the curve', and at no point during march or april were hospitals or intensive care units in zurich overwhelmed. flattening the curve may not only reduce risks to physical health, but could also have positive downstream effects on mental health. female young adults had a higher risk than males of pre-and also during-pandemic distress, which is consistent with previous work reporting that females are generally more prone to internalizing-spectrum symptoms . indeed, with the inclusion of previous distress, the size of the female sex coefficient in the prediction of during-pandemic distress was halved. it was further reduced considerably (to nonsignificance for perceived stress and internalizing symptoms) with the inclusion of during-pandemic lifestyle disruptions and hopelessness (which had higher levels for females than males). young adults with a migration background were also at increased risk of during-pandemic perceived stress, perhaps because of separation or isolation from loved ones due to closed borders, greater likelihood to work in jobs affected by the pandemic, or worries about loved ones in heavily affected countries. together, our findings suggest several targets for prevention/ intervention. first, females, migrants, and young adults with higher pre-pandemic emotional distress, social exclusion, and an accumulation of stressful life events may need additional mental health supports and services during pandemics and lockdowns. second, during times of unexpected disruption, educational and professional development institutions and responsible government agencies should aim to establish clear communication with young adults and make supportive measures availableperhaps especially for young adults in the final stages of their educational and professional development. third, supplemental income measures could alleviate distress among economically vulnerable young adults who are not covered by unemployment or furlough payments. finally, educating young adults about select coping strategies could counteract emotional distress during a pandemic. indeed, our findings show that keeping a daily routine, engaging in physical activity/exercise, positive reappraisal/reframing, and additional coping strategies were associated with lower distress. the association of positive reappraisal with less emotional distress is consistent with another recent study (veer et al., ) . importantly, positive reappraisal (i.e. changing thought patterns about events that cannot themselves be changed) is a skill that can be practiced and improved (beck, ) through avenues such as internet-based applications (donker et al., ) and online cognitive behavior therapy (axelsson et al., ) . regular physical activity is known to be an effective antidepressant (harvey et al., ) . switzerland did not institute home confinement, allowing individuals to exercise outside, which may have alleviated distress. although we cannot infer causality from our cross-sectional analyses of coping and emotional distress, our results suggest actionable targets for prevention/intervention, even within the restraints of lockdowns, although these will need to be evaluated in future research. future longitudinal during-pandemic study designs will also need to further illuminate whether increased use of certain coping strategies (e.g. emotional support-seeking) will result in decreased emotional distress over time. almost one in five young adults reported feeling better during than before the pandemic, a finding consistent with another recent study (de quervain et al., ) . this phenomenon is worth exploring considering the pre-pandemic trends of increasing stress and internalizing symptoms among contemporary western youth in recent decades (keyes, gary, o'malley, hamilton, & schulenberg, ; twenge, cooper, joiner, duffy, & binau, ) , and the need for measures to reverse these trends. participants whose well-being improved during the pandemic tended to appreciate the opportunity to decelerate their life. additional work is needed to pinpoint the specific reasons for improved well-being during pandemic/lockdown conditions with the goal of applying these to post-pandemic life. in the openended comments, several participants suggested that being removed from workplace or educational pressures, more time with family, partners and close friends, spending time on hobbies, and the opportunity to sleep more contributed to better wellbeing during the pandemic; these and additional potential causes of better during-pandemic well-being warrant future systematic investigation. our study has the important strength of including both pre-and during-covid- assessments, but it also has limitations. first, symptoms of post-traumatic stress disorder were not assessed but may have increased in individuals directly or indirectly exposed to covid- at-risk occupations, health risks, hospitalizations, or death of loved ones. second, the pre-pandemic assessment occurred approximately years before the covid- crisis, and some of the changes observed here could have been due to typical age-related development or other stressors preceding the pandemic. third, most stressors and life events assessed during the pandemic were covid- -specific. other ongoing stressors in participants' lives could have also increased their distress during covid- . fourth, coping and emotional distress were measured at the same assessment, during the pandemic, meaning that the directions of effects underlying their association are uncertain. for example, it is not clear whether distressed individuals had recruited additional emotional support or whether co-ruminating with others about covid- -related stressors increased emotional distress. fifth, those acutely affected by covid- (or whose loved ones were acutely affected) may not have participated in the survey. sixth, our assessments took place in weeks and of the lockdown in switzerland; findings could change with prolonged social distancing and lockdown measures, and in places where the lockdown is less successful in flattening the curve. finally, while our sample was generally representative of young adults in the zurich area, findings may not generalize to regions with different lockdown strategies; different rates of covid- cases, hospitalizations, and deaths; or different social systems and safety nets. in our sample of young adults, economic and social factors were more strongly and consistently associated with distress during the covid- crisis than exposure to virus-related health risks. indeed, previous distress and covid- -related economic and lifestyle disruptions and hopelessness were among the strongest correlates of young adults' distress during the lockdown, followed by pre-pandemic victimization experiences and accumulation of stressful life events. keeping a daily routine, physical activity and exercise, and positive reappraisal/reframing were associated with less distress, and young adults whose well-being improved during the pandemic/lockdown tended to comment on a positive deceleration of their lives. despite its many downsides, the pandemic/lockdown may have given some young people the opportunity to take stock of their lives and to improve their long-term well-being. emerging adulthood: a theory of development from the late teens through the twenties effect of internet vs face-to-face cognitive behavior therapy for health anxiety: a randomized noninferiority clinical trial cognitive therapy: nature and relation to behavior therapy -republished article the psychological impact of quarantine and how to reduce it: rapid review of the evidence soziale exklusion und exklusionsempfinden social exclusion and the transition from school to work: the case of young people not in education, employment, or training (neet) perceived social isolation makes me sad: -year cross-lagged analyses of loneliness and depressive symptomatology in the chicago health, aging, and social relations study you want to measure coping but your protocol's too long: consider the brief cope a global measure of perceived stress economic stress, coercive family process, and developmental problems of adolescents childhood and adolescent psychiatric disorders as predictors of young adult disorders the swiss corona stress study smartphones for smarter delivery of mental health programs: a systematic review trends in mood and anxiety symptoms and suicide-related outcomes among u.s. undergraduates, - : evidence from two national surveys large-scale criminological field experiments: the zurich project on the social development of children a practical guide to the analysis of non-response and attrition in longitudinal research using a real data example multiple imputation as a flexible tool for missing data handling in clinical research the life stress paradigm and psychological distress the great recession and mental health in the united states mental health outcomes in times of economic recession: a systematic literature review a standard international socio-economic index of occupational status how economic downturn affects children's development: an interdisciplinary perspective on pathways of influence exercise and the prevention of depression: results of the hunt cohort study world values survey: all rounds-country-pooled data file version recent increases in depressive symptoms among us adolescents: trends from ordinary magic: resilience processes in development validation of a brief self-report measure of adolescent bullying perpetration and victimization evaluating longitudinal invariance in dimensions of mental health across adolescence: an analysis of the social behavior questionnaire mplus user's guide non-compliance among young adult with covid- -related public health measures: insights from a longitudinal cohort study item banks for measuring emotional distress from the patient-reported outcomes measurement information system (promis (r)): depression, anxiety, and anger suicide mortality and coronavirus disease -a perfect storm? multiple imputation for nonresponse in surveys covid- epidemic in switzerland: on the importance of testing, contact tracing and isolation missing data: our view of the state of the art pathways to adulthood in changing societies: variability and mechanisms in life course perspective new coronavirus: protect yourself and others age, period, and cohort trends in mood disorder indicators and suicide-related outcomes in a nationally representative dataset mental resilience in the corona lockdown: first empirical insights from europe. preprint the status of irritability in psychiatry: a conceptual and quantitative review immediate psychological responses and associated factors during the initial stage of the coronavirus disease (covid- ) epidemic among the general population in china risk, resilience, and recovery: perspectives from the kauai longitudinal study key: cord- - lx w h authors: nikolopoulos, konstantinos; punia, sushil; schäfers, andreas; tsinopoulos, christos; vasilakis, chrysovalantis title: forecasting and planning during a pandemic: covid- growth rates, supply chain disruptions, and governmental decisions date: - - journal: eur j oper res doi: . /j.ejor. . . sha: doc_id: cord_uid: lx w h policymakers during covid- operate in uncharted territory and must make tough decisions. operational research - the ubiquitous ‘science of better’ - plays a vital role in supporting this decision-making process. to that end, using data from the usa, india, uk, germany, and singapore up to mid-april , we provide predictive analytics tools for forecasting and planning during a pandemic. we forecast covid- growth rates with statistical, epidemiological, machine- and deep-learning models, and a new hybrid forecasting method based on nearest neighbors and clustering. we further model and forecast the excess demand for products and services during the pandemic using auxiliary data (google trends) and simulating governmental decisions (lockdown). our empirical results can immediately help policymakers and planners make better decisions during the ongoing and future pandemics. first spotted in wuhan in china, the ongoing covid- pandemic has triggered the most severe recession in nearly a century and, according to the oecd's latest economic outlook , it has been causing enormous damage to people's health, jobs, and well-being. covid- has affected almost all countries in the world and, has practically put the entire planet on hold for more than months. at the time this paper was being revised, the number of confirmed global cases was more than million; the number of deaths crossed the mark of , in late june -standing at , as of - - - - (who, . unfortunately, the number of cases and deaths is still exhibiting significant growth in many countries, with the americas (most notably the usa and brazil) been in the pandemic's epicenter . our generation has never met anything remotely similar to this pandemic. despite hiv/aids been associated with far more deaths , the speed with which covid- can kill even-perfectly-healthy humans (sometimes within just a few days), and the unprecedented disruption in work and social life that it has brought (getting workers furloughed for months, and the vulnerable part of the population in strict isolation for weeks), makes this pandemic unique. furthermore, due to this pandemic and the associated global healthcare crisis, supply chains have faced significant disruptions in the upstream, while hoarding and panic buying caused equally significant disruptions to the downstream. the balance of supply and demand was further impacted by the travel restrictions and lockdowns implemented by several countries worldwide. due to these disruptions, shortterm real time forecasts (daily and weekly) about the pandemic and its effect on the supply chain have become a very important managerial and policy-making imperative. mid-and long-term forecasts are essential too for supply chain planning (at monthly, quarterly and annual frequency). however, research on these is more likely to be conclusive after the first wave of the pandemic is over, when more -and more reliable -supply chain data becomes available. an accurate forecast of the evolution of new cases enables the more effective management of the resulting excess demand across the supply chain. common sense and recent experience suggest that the acceleration and progression of covid- across countries drives changes in immediate actual needs (healthcare and food) and in consumer behavior (for example panic buying and overstocking at home ). such changes put an enormous strain to the respective supply chains. for instance, when consumers start panic buying dry pasta, eventually, the whole supply chain involving eggs, flour, wheat, is affected. a phenomenon, which is likely to be significantly exacerbated by the well-known implications of the bullwhip effect (wang & disney, ; chen et al., ; lee et al., ; kahn, ) . therefore, forecasting during the pandemic becomes essential for effective governmental decision making, for managing supply chain resources, and for informing very difficult political decisions as, for example, imposing a lockdown or curfews. yet, forecasting the evolution of the pandemic i.e. the growth in the number of cases per country, or even to greater spatial detail, is a complex task because of the limited history of pandemic data and the multidimensionality of the problem. for instance, there are several, and at times unknown, factors that affect the contagiousness and the severity of the disease. to that end, forecasting in real time and while new data becomes available is a complex exercise for both government and supply chain managers (beliën & forcé, ; nikolopoulos, ) . epidemiologists have been applying traditional models for outbreak prediction (nsoesie, marathe, & brownstein, ; yang et al., ) . applied mathematicians, decision scientists, and operational researchers have been employing time-series, and machine-learning techniques. as a result, for covid- , since the onset of the crisis, a few statistical and regression-based forecasts have been available online (al-shammari et al., ; team ihme covid- & murray, a , b ). yet, and despite the contribution of these models for predicting the progress of the virus and its impact on the supply chain, their proliferation generates confusion. the most profound manifestations of this confusion have been the different approaches taken by companies and governments to deal with the pandemic, e.g. timings and extents of lockdown, processes of reopening the economy etc. and the differing, and often confusing, views about the onset of a second wave. this has been exacerbated by the wider recognition that different countries and, even, different regions are structurally diverse. thus, using a single forecasting model may not accurately predict how the pandemic evolves. as a result, there is an emergent and urgent need for, on the one hand, more of these models (petropoulos, makridakis, assimakopoulos, & nikolopoulos, ) and, on the other, a methodology that enables decision makers to select the one, which is likely to be the more applicable in their own context. to address this need, in this article we forecast the growth of the pandemic at the country-level and evaluate time-series, epidemiological, machine-learning, and deep-learning techniques. furthermore, we propose a new hybrid forecasting method tailored to the task that is using cross-country information. to achieve generalizable results, we use data from a diverse set of countries (uk, usa, india, germany, and singapore), and perform a rolling forecasting evaluation consisting of daily and weekly forecasts. our research can easily be extended into all the countries affected by the pandemic. we further use these forecasts in order to estimate the excess demand for products and services during the pandemic. therefore, this study provides a methodological contribution as it illustrates how to perform such a forecasting exercise. a prerequisite for this is that that data from the academic and policymaking community becomes available in accessible formats . for the remainder of this paper in section we review the literature while in section we present our empirical forecasting competition. in section we provide models for estimating the excess demand and source code of our forecasting models is freely available upon request. respective supply chains disruptions. in the final section we provide our conclusions and implications for practice. in section . , we provide a targeted review on different techniques and methods used for the forecasting of the evolution of a pandemic. after that, in section . , we provide a review of the literature on forecasting the demand and supply in a supply chain in view of the evolution of a pandemic. in the last sub-section, we present our research questions and our methodological approach. forecasting methods for pandemic evolution can be divided into time-series methods, compartmental epidemiological models, agent-based models, metapopulation models, and approaches in metrology (nsoesie et al., ) . a recent addition to this long list is machine learning (ml) and deep learning (dl) methods (yang et al., ) . soebiyanto, adimi, and kiang ( ) proposed the use of arima models for one-step ahead forecasting of influenza weekly cases. andersson et al. ( ) proposed the use of regression methods for the prediction of the peak time and volume (of cases) for a pandemic and provided promising empirical evidence to that end from seven outbreaks (in sweden). shaman &karspeck ( ) used the kalman filter based sir epidemiological model to forecast the peak time of influenza and claimed that the peak can be predicted - weeks in advance. an extensive evaluation of multiple time series methods for forecasting the evolution of an epidemic (hantavirus) with data from cdc was performed by yaffee et al. ( ) in which they compared casual methods with time-series univariate methods and found that univariate methods were better at prediction than causal models. for covid- , petropoulos and makridakis ( ) applied ets (hyndman, koehler, snyder, & grose, ) models for predicting the evolution of the number of cases at a global scale. they reported very successful results in terms of real accuracy both for their point forecasts and the prediction intervals they provided. this is an open-access article in plos one that has already drawn significant attention with , views up to - - while available online for only months, providing evidence of the interest and importance of such quantitative studies for academia and practice. finally, there has been a series of studies focusing on predicting deaths in the usa and european countries for the next few months of the first wave of the covid- pandemic ( team, ihme covid- & murray, a , b . furthremore, researchers and software companies have also rapidly during the covid- pandemic developed live-simulators which make use of simulation models integrating governmental decisions (e.g. lockdown) and have been made available online via freely accessible websites and portals. we focused only on peer-reviewed and preprints in the literature review. for portals for live-prediction, reference is made in the introductory section. https://www.cdc.gov/hantavirus/index.html https://exchange.iseesystems.com/public/isee/covid- -simulator/index.html#page supply chain disruptions have been known to cause significant challenges and can affect organization performance (hendricks and singhal ) . famous incidents, such as the tsunami that hit japan in and the financial crisis of have illustrated how the interconnectedness and global nature of the supply chains can amplify even the smallest of "glitches" (hendricks and singhal ) . as a result, there have been several studies that attempt to explain the antecedents of resilient supply chains, both at the network (kim, chen et al. ) and the organization levels (bode, wagner et al. ). pettit, croxton, and fiksel ( ) and pettit, fiksel, and croxton ( ) offer a good review of the literature on supply chain resilience that predates covid- . the severity of the business disruption of covid- pandemic has challenged much of our previous understanding of what constitutes a resilient supply chain. recent reports have clearly indicated that this crisis has led to the rapid deterioration of several business and economic indicators, including productivity and global gdp (harris, ) . in addition, a few studies also estimated the impact of covid- on the labor demand, a . % decrease in the demand of working hours (castro, duarte, & brinca, ) . these impacts are due to the imposition of travel and trade (baveja, kapoor, & melamed, ) restrictions and the shutting down of work places. as a result, araz, choi, olson, and salman ( ) asserted that covid- is, probably the most severe disruption to the global supply chain in the last decade. ivanov ( ) , who considered the pandemic and the respective supply chain risks, provided a simulation model for global supply chain disruption and predicted the severity of covid- 's impact on supply chain performance. similarly, team ihme covid- and murray ( a) predicted that covid- will place unprecedented stress on hospitals, icus, and ventilators, and that the overall demand will be beyond the healthcare system's current capacity. in a follow up study, team ihme covid- and murray ( b) predicted the impact of covid- on hospitals and deaths for europe and us and suggested measures to temporarily increase the supply of critical products and services. govindan, mina, and alavi ( ) presented a decision support system to manage the demand for healthcare supplies based on physicians' knowledge and fuzzy inference system (fis). they claimed that the use of their propositions leads to efficient and accurate managing of the supply chain disruptions in case of an outbreak. finally, hobbs ( ) assessed the implications of covid- on the food supply chains and reported that demand and supply shocks created during a pandemic are due to a shift in consumer behaviors. for instance, the sudden panic buying shift to ready-meals caused demand shocks, which then led to labor shortages, and disruptions of the transportation network. furthermore, restrictions on cross-border goods movement led to further supply side shocks to the food supply chains. as a result, it would be reasonable to conclude that covid- will have long-lasting effects on consumer habits and supply chains. https://forio.com/app/jeroen_struben/corona-virus-covid -seir-simulator/index.html#decisions.html https://metasd.com/ / /interactive-coronavirus-models/ https://metasd.com/ / /community-coronavirus-model-bozeman/ in summary, covid- has put some significant and unprecedented strain on global supply chains across most product categories. past literature on forecasting and on supply chain disruption has been able to provide some indication of the factors that can lead to it. however, and at the same time, it has exposed some of the challenges associated with identifying and responding to significant changes in the demand patterns during a pandemic. the ability to forecast excess demand during the pandemic early could, however, has significant implications for both supply chain managers and policy makers. the former can benefit from early warnings about where resources will be needed and the latter from a data driven approach to government interventions, e.g. by prioritizing critical supply chains. considering the targeted literature presented, our research aims to address the following research questions: what are the best models for forecasting the evolution of the pandemic at the country-level? r : how can we forecast the excess demand for products and services during the pandemic, before even actual supply and demand data become available? we need to emphasize that we address the aforementioned research questions during the pandemic and not after it, and thus the urgency and importance of our ongoing research. this caveat constitutes a contribution by itself, as it evidences the ubiquitousness, responsiveness, and the timeliness of or research. we deploy an exploratory methodological approach in order to find the best forecasting methods (the 'horses for courses ' -petropoulos et al., ) -as we do not prescribe which methods/models we expect to perform better via a set of formal hypotheses. then via a series of simulations we forecast the excess demand of products and services, i.e. the excess demand that is driven from the growth of covid- cases. our analysis covers a major part of the current wave of the pandemic, the period from the january to april . from a methodological standpoint, we contribute to the stream of phenomenon-based research as we engage in a very early phase of a scientific inquiry, observing, researching, and providing solutions for a developing a novel phenomenon (von krogh, rossi-lamastra, &haefliger, ). we further contribute both to the fields of operations research (or) and supply chain management (scm). for the former, we provide an exhaustive empirical investigation that identifies the most accurate method for forecasting growth rates during a pandemic. we do so during the phenomenon and before the start-growthmaturity-decline sequence is complete. we contribute to the latter, the field of scm, by providing an input (the demand forecasts for the new cases and the selected products), which is essential to decision-making algorithms that involve stock-control, replenishment, advance purchasing, and even rationing , i.e. situations that require a mean forecasted demand over the lead-time. we further provide simulations for the excess demand for products and services during the pandemic. https://uk.reuters.com/article/us-health-coronavirus-britain-supermarke/panic-buying-forces-british-supermarketsto-ration-food-idukkbn m finally, we contribute to the theory of predictive analytics, as we propose new data-driven predictive methodologies. we do so by building on theory from non-parametric regression smoothing on nearest neighbors (härdle, ) , and by using machine-learning clustering approaches. we capitalize on the experience of those countries where the outbreak of the pandemic came earlier to forecast the evolution of the pandemic. we also contribute to policymaking as we take into account the impact of political decisionsspecifically the enforcing of a lockdown/curfew -on both the evolution of the pandemic and the resilience of the affected supply chains. following the influential empirical forecasting evaluation at the global level of petropoulos and makridakis ( ), we perform our empirical forecasting analysis at the country-level. this is also the most common geographical level for decision-making during the pandemic. although at the time of writing there was data from countries we decided to focus our study on five of these. we did so for both brevity and for providing a clearer illustration of the benefits of the methods we used. the countries we selected are: germany, india, singapore, the united kingdom, and the usa as they cover a wide range of national systems and government responses. more specifically:  germany because it is the country with the best response in europe. this is despite neighboring with badly affected countries and being very close to the epicenter of the outbreak in europe: italy. germany is also of interest as it followed a very aggressive testing policy early on, trying to identify each and every case as early as possible. as of / / a total of , cases with , deaths have been confirmed, bringing the deaths per capita at / m of population, much lower than most g countries.  india because it is the most populous country in the world still affected by the pandemic (with a population more than m, second largest in the planet). on this basis we did not include china because it is considered to have completed the first wave in april . as of / / a total of , cases has been reported (third-most in the world) with , deaths.  singapore because it is the country with one of the most advanced healthcare systems in the planet , a claim supported profoundly during this pandemic as well. despite singapore not employing extremely strict lockdown measures, it had a very aggressive testing approach, deployed a very effective tracking mobile application and has been in the forefront of technology adoption and development e.g. it developed a wearable device to obtain better results than those achieved by https://en.wikipedia.org/wiki/national_responses_to_the_covid- _pandemic , views to date in just over months https://www.who.int/whr/ /en/ https://www.tracetogether.gov.sg/ the mobile app . as of / / a total of , cases has been reported and a total of only deaths, with , confirmed recoveries. this performance equals to a mortality rate at . %, which is less than long term average for the seasonal flu ( . % ) for which both a vaccine and a first-line antiviral treatment is available, rendering this country's response arguably the best in the planet. this is despite singapore being one of the first hit by the pandemic, right after china and taiwan.  the uk because it has been the most-affected country in europe and the one with the most deaths per capita at deaths per m of population (worst among countries with population over m). as of / / the uk had reported a total of , cases and , deaths. the uk is also of interest as it has the largest public healthcare system in europe (and nd largest singlepayer healthcare system in the world). it also followed a different approach early in the pandemicaiming for "herd immunity" rather than virus containment .  and finally, the usa because it has been the most-affected country in the world by the outbreak (up to the time of this submission). as of / / it had reported a total of , , cases and , deaths. we collected all data on covid- cases and respective healthcare and socio-economic variables from credible international publicly available sources (listed in appendix a). we used a set of models (from more than methods ), ranging from simple to complex, and from timeseries and epidemiological, to machine-and deep-learning. we produced forecasts for the growth rates at various stages of the pandemic for each nation. in total we produced forecasts times for daily data and times for weekly data. we identified the top-three methods per country that exhibit the smaller mean absolute scaled error (mase), and used the equal-weighted combination of these methods for the follow-up simulations in section . we used the simple average of forecasts, as it is a simple and effective method for combining forecasts (makridakis & winkler, ) . we used mase as our primary accuracy metric (hyndman & koehler, ) because it is scale-independent and widely accepted metric for forecast evaluations (makridakis, spiliotis, & assimakopoulos, ) . in table we provide a list of competing models. for details on these popular methods, the interested reader may revisit either the article on the latest forecasting competition (the m competition -makridakis, spiliotis & assimakopoulos, ) or the free online forecasting textbook from hyndman and athanassopoulos . for the more advanced machine-and deep-learning methods we provide a brief description in appendix a. time-series naïve, moving averages (four models , , , ), ses, ets, arima, theta, tbats, ann_ar, g&m ( )-damped trend (gardner & mckenzie, ) , holt -trend, ns-hw (non-seasonal holt-winters), arfima, garch( , ) (six models, wih: ged, sged, norm, snorm, std, sstd), arimax, naïve-d with drift (ten models with step of . the new proposition is data-driven and designed to use historical data from several countries to produce better forecasts for a target country. this is a classic adaptation of a nearest neighbor approach (kyriazi & thomakos, ; härdle, ) . we have named it partial curve nearest neighbor forecasting (pc-nn) because it tries to find similarities in between parts of curves (from the start of the time series of a pandemic in a country until the date the forecast is made, as depicted in figure ). the method involves the following steps: i. collecting the data for a period of t days on daily cases growth for a set of n countries. iv. comparing the daily changes curve of country (a) to those of other countries. to do so in a simple and effective manner, we normalized the data and we calculated the euclidean distance between curves as the squared root of the sum of squared differences between the selected country's curve (e.g. india) and those of others. based on the values of the , we selected the nearest neighbors. vi. finally, using the pc-nn groups identified in step v for a country a and the ( th period naïve forecasts for these countries, the ( th period forecast is produced for country a using a simple average of all pc-nn's naïve forecasts. in the case of pc-nn we can either use equal weightings for the three neighbors (pc-nn ew), or uneven/triangular ones (pc-nn uw). this would mean that a % weighting is given to the nearest neighbor and % to the other two. for future research, we would recommend employing the next actual values of the neighbors instead of a naïve forecast. we further extend this approach by using a multivariate dataset and a clustering algorithm. we performed the clustering with data on socio-economic, climate, and covid- related factors and grouped them according to whether they are facing, or they are about to face similar challenges. we used the k-means clustering algorithm to find the clusters of the countries. the countries that are in the same cluster will probably face a similar situations and challenges related to covid- in the future, especially if they adopt similar policies. we consider this a very important feature of this forecasting method as it allows the clustering. the policy implication here is that there may be policies that some can learn from some but not from others. we call this method hereafter: clustering and partial curves and nearest neighbor forecasting (cpc-nn). we use similar notations for the variations of this latter extension too: cpc-nn , cpc-nn ew, cpc-nn uw, cpc-nn , and cpc-nnall. we produced forecasts for the growth rates at various stages of the pandemic for each of the five nations. in total we conducted this process times for daily data and times for weekly data for the period of january to april . we derived the time series of percentage daily changes in covid- cases from the daily new case series. we calculated the daily percentage growth with the following equation. we used the forecasting methods listed in table for forecasting for all the countries across all time periods. we used the death and recovery rates as the independent variables for the multivariate forecasting methods. we calculated the mean absolute scaled error (mase) and the symmetric mean absolute percentage error (smape) for each iteration (makridakis, spiliotis, & assimakopoulos, ; shankar, ilavarasan, punia, & singh, ) . we calculated the relative errors by dividing with the corresponding error from the naïve method (davydenko & fildes, ; punia, nikolopoulos, singh, madaan, & litsiou, ) . we report in table the relative (to naïve) medians for: mase (relmdmase), and smape (relmdmape) . since we are interested in finding the overall 'winner' across the competing methods, we need to evaluate the methods across the five countries simultaneously. to do so, we produced forecasts for all competing the reader may revisit the theory of the k-means at https://stanford.edu/~cpiech/cs /handouts/kmeans.html we do find similar results when we are using the medians of me and rmse, as well as the averages of them. average errors can be used in parallel with median errors to help identify in which countries we do face more extreme errors (when avg>>md). methods, for each period and country. we then calculated the medians of the forecasting errors across all countries. we observe from table that the performance of the naïve method was very difficult to beat for the weekly data: only splines (cv) did better. this led us to develop models using the pc-nn/cpc-nn method. in table and in the next subsection we demonstrate that these models do outperform all other methods for weekly data, but at a computational cost. given that many policy decisions are taken weekly, a weekly frequency and forecasting horizon becomes very important for planning. for instance, the uk revised its social distancing measures based on forecasts and actual data for the pandemic every weeks. for the daily data the picture is very different, with many methods outperforming the naive method. the garch( , ) model with sged with . ranks first and ma with . for mase ranks second. on the other hand, for smape, garch( , ) model with sged with . ranks first and ets with . ranks second. the two epidemiological models did not perform well. however, for the weekly data at country level (table ) , the average of top-three methods performs significantly better than the naïve forecast. most of the relative errors are less than . indicating the large performance improvement over naïve by the proposed methodology, and the respected anticipated benefits of combinations . one key conclusion from table , is that the level of error is not the same across all countries and for some it is easier to forecast than others. for example, for singapore the error on the weekly data is . and the one for daily . . at the other end, for the uk the error on the weekly data is . for the usa . (on the daily ones). therefore, a key conclusion is that forecasting at the country level is more likely to lead to effective local guidance and would need to consider different underlying time series. a second key conclusion is that different methods perform better in different countries. for example, for germany naïve and two variants of naïve with drift are the top-performing models; while for the usa the two variants of pc-nn and cpc-nn uw are the top-performing ones. thus, the forecasting evaluation needs to be performed in every country separately: this is a consistent result with the 'horses for courses' doctrine (petropoulos et al., ) as well as the makridakis forecasting competitions . in we first produce forecasts with the five models for pc-nn for the weekly data following the steps prescribed in . . . then we proceed at implementing the five models for cpc-nn by using the k-means algorithm for clustering the multivariate data we collected. the data consists of the variables listed in table . travel restrictions when no ban ( ) we performed the clustering at each step of the rolling forecasting evaluation because we expect clusters to change with the evolution of the pandemic in different countries. figure table . forecasting performance of the pc-nn & cpc-nn models on weekly data. this concludes our investigation for r , as we have identified many models and combinations that perform better than the standard forecasting benchmarks at multiple frequencies. in this section, we advance our work towards addressing the second research question (r ), which aims at exploring how we can forecast the excess demand for products and services during the pandemic. in normal conditions, the demand for some of these products and services is relatively non-volatile and, as a result, does not exhibit complex patterns. it is, thus, not very difficult to forecast. this is especially so for products in more mature markets such as pasta, rice, toiletries. however, during a pandemic, we expect the purchasing behaviors will become significantly more volatile because of consumer biases on the potential for scarcity (chandon and wansink, ) . in such cases, customers become less able to evaluate both their own inventory of supplies and the risk of scarcity of the products they are planning to panic. this leads to "panic buying" (tsao et al., ) , which was particularly prevalent in the covid- pandemic (gray ). we consider the excess demand for the quantity of different products and services including groceries, electronics, automotive and fashion. we start by considering the following equation as our benchmark model. where is the quantity of the excess demand at time t. is the growth rate of incidents of covid- that took place at time t-b with b being the respective lag. we assume that the effect on the quantity demanded will take place after society becomes aware of the evolution of the infectious disease. parameter a captures the effect of cov on if a government decides to impose measures to reduce the spread of the virus, it could force a lockdown. the lockdown could generate further anxiety and as a result further change in consumer behavior. to capture this effect, we introduce a dummy, which takes the value of one ( ) after the date that the government imposed lockdown and zero ( ) before. ( ) for the estimation of the demand quantities, we use as a proxy the searches for products from the google trends (jun, yoo, & choi, ) of four different sectors (groceries, electronics, fashion, automotive) for the five countries we research. we decided to use auxiliary data as confirmed supply chain demand data will not be available for the months to come and as such no demand modelling would be possible until then. this is not an option for policymakers however and to that end we believe we provide here an essential set of tools to inform decision making. for the values of variable covid- in equation ( ) we use the average of the top- forecasts prepared in section . we then use ordinary least squares to estimate the coefficients in equation ( ). we model the excess demand over and above normal stable demand. we make the implicit assumption that the products we are looking at follow a relatively stable average demand in the long-run. since we are focusing on the impact of the covid- on the supply chains of these products we assume that the pandemic leads to an intermittent demand pattern over and above the mainstream (nikolopoulos, ) . to estimate a, we need the demand of the relevant products and the growth of the confirmed covid- cases. since demand patterns and data are not available yet, we extracted the google search trends for certain goods to get an estimation of how the demand changed on a daily basis during the covid- pandemic as shown in we used several consumer products per sector, which allowed us to get a more holistic trend. we chose sectors that have different underlying supply chains. we extracted google trends data for a -day window, starting from the beginning of february and ending on the th of april . we estimated parameter a by running regressions between the daily growth and the daily search trend, resulting in table . table . estimation of parameter a. ***, **, and * indicate statistical significance at the %, % and % levels respectively. robust standard errors presented in the parenthesis. to consider the impact of imposing lockdowns, we use the same data from google trends and add the variable we further investigate the impact of moving the lockdown over the weeks to create alternative scenarios (figure ). we consider four scenarios: a) no lockdown, b) lockdown from week , c) lockdown from week , and d) lockdown from week . we focus on the more critical products, that of product category -groceries, as these are essential during the pandemic. we provide the simulations for groceries (p ) for the remaining four countries in appendix c. our results show that the onset and the amount of the excess demand are dependent upon the type of product and the timing of the lockdown. demand for groceries (p ) and electronics (p ) becomes excessive, whereas that for fashion (p ) and automotive related items (p ) reduces ( figure ). these trends have been confirmed by articles in the daily press. furthermore, figure , shows that for groceries, the earlier the lockdown is imposed, the higher the excess demand. finally, the longer the lockdown lasts the higher the cumulative excess demand. we find similar results for india, the uk, the usa and singapore (appendix c). our results therefore point to various directions for both the process of forecasting and the management of the supply chain. first, we demonstrate that the process of forecasting during the pandemic needs to be dynamic and to take into account the changes in the external circumstances. research that focuses on responses to humanitarian crises data (van der laan, van dalen et al. ) has also argued for a flexible approach to forecasting. as more information becomes available and decisions about the response to the pandemic are being taken, the approach to forecasting needs to be readjusted. therefore, our results extend those for the management of more localized humanitarian crisis by illustrating the implications for forecasting at the time of a global pandemic. furthermore, our results illustrate the challenge of making forecasts and making supply chain decisions for products where consumers need to make judgments about their own immediate needs. in the case of groceries, previous research indicates that when consumers make estimates about their own inventory levels (e.g. the amount of toilet paper they have at home), they do so with unrealistic assumptions and limited data (chandon and wansink ) . as a result, they are very likely biased and influenced by the external environment. our results forecast that similar effects are at play with other product categories such as electronics, where consumers have to make evaluations about the capability of their own equipment and the potential for scarcity, e.g. the combined effect of fear of failure of one's own laptop and the potential for stockouts. therefore, we can make two recommendations because of our results. the first for policy makers and relates to efforts to secure high volumes of inventory for products in those categories (p and p ) before the lockdown. our analysis shows that this should not be based only on data of actual needs, but should take into account consumers', often biased and at times irrational, behavior. the second recommendation is for supply chain managers of companies in the product categories we analyzed above. in addition to the preparations for fluctuations in demand, particularly in view of a lockdown, our results indicate that the approach to forecasting needs to continuously adjust to take into account the changing needs. this would imply changes to the forecasting models as well. this concludes our investigation for r , as we have identified ways to forecast the excess demand for products and link that to governmental decisions. this paper has examined urgently and extraordinarily the predictability of covid- growth in five countries and modeled the dependent short-term supply chain disruptions. we evaluated existing state-of-the-art and proposed new data-driven methods for forecasting pandemic evolution while working with limited, volatile, and constantly revised data. countries have different healthcare systems, run the covid- tests in different places (hospitals, gps, community centers, airports), apply different policies (track and trace, lockdowns, legislation, etc.), test with different devices and protocols, and report differently new cases and deaths (including or excluding deaths at home or in care homes). all these complicate and limit the extent of accuracy that can be achieved from forecasting models. there is, therefore, an immediate need for a homogenous credible database to enable more accurate and comparable forecasting by the academic community, policy makers and supply chain professionals. nevertheless, forecasting remains an essential part of many decision-making processes, and as such, this motivates us further for this research endeavor. we also modeled the excess demand for products and services during the pandemic via using auxiliary data (google trends) as actual supply & demand data are not yet publicly available: our models rightly predicted the panic buying effect and respective excess demand for groceries and electronics during the current wave of covid- . many operational decisions are affected by our research including those associated with planning, production, shipping, stock-control (prak et al., ) , ordering, and allocating of resources (nikolopoulos et al., ) . they are all decisions where an accurate forecast is an essential input and as such, our study is relevant. furthermore, the results of our research can inform government decisions. we show that the earlier a lockdown is imposed, the higher the excess demand will be for groceries. furthermore, the longer the lockdown lasts the higher the cumulative excess demand and thus the higher the need for planning for production and inventory. consequently, a policy recommendation for the governments will be to secure high volumes of inventory for such products before the lockdown; and if not possible, consider radical interventions such as rationing. during a health emergency response, leaders need to make a numerous critical decisions for the supply chain, and for prevention strategies (fisher et al. ; glasser et al. ). the decisions occur in a rapidly changing environment and they might be misinformed or biased. consequently, forecasting becomes an essential tool for helping and providing guidance for the utility and timing of prevention strategies. however, the use of infectious disease forecasts for decision-making is challenging because most existing infectious diseases require different methods for different countries. each forecasting model has limitations. furthermore, data may not be reliable because it may have been recorded during the emergency situations. as a result, comparing forecasts at the country level remains challenging, potentially limiting the development and utility of forecasts. despite these limitations, covid- forecasts provide indications and quantify the needs that appear in an emergency, and thus more research should be directed towards identifying the best forecasting models for all geographical contexts and temporal frequencies. the decision tree is supervised machine learning algorithm used for the classification and regression application. we used the continuous variable, regression decision tree with classification and regression tree (cart) algorithm. the caret package from r is used for the implementation of the method (kuhn, ) . the parameter optimization was performed using grid search. random forest was developed by (breiman, ; ho, ) and it generates multiple random samples and perform the bagging of decision tree applied on random sample of data, thus called random forest. the algorithm is implemented using caret package in r (kuhn, ) and grid search was used to search best combination of parameters. the literature is referred for optimal implementation of the random forest fore forecasting (fischer & krauss, ; . ann have three layers for data modeling, namely, an input layer, an output layer, and hidden layers. the inputs and outputs are modeled through ∑ ( ∑ ) , where s and s are connection weights, p is the number of input nodes and q is the number of hidden nodes. the output from the ann is a non-linear function that maps the inputs to outputs with the help connection weights. ann were applied for the forecasting using death rate and recovery rate as the input and cases growth as the output variable in r. the lstm networks are state-of-the-art sequencing modeling methods which comes under deep learning. the sequence modeling feature of lstm can be used for time-series forecasting specially to model non-linear time series variations. the lstm were implemented using keras library in r (chollet, ) . the work of was followed for implementation and hyperparameter optimization of the lstm networks. ridge regression is an advanced regression technique that allows to perform l regularization i.e. adding penalty equals to square of coefficients along with minimizing the sum of squared error between actual and forecast. the linear ridge regression was implemented using ridge library in the r. svm are the machine learning techniques that is based on classification and regression algorithms and can be used for the forecasting purposes using regression method. svm were implemented using e package in r. the "linear" kernel were used along with "eps-regression" type from the parameters for the implementation of the method. the splines are used to fir a smoothing function to the data just like the regression. different smoothing splines can be fitted to the data using different non-linear functions and best one can be selected for the purpose of forecasting. we have used the sigmoid, logistics functions to fit the data. the functions smooth.spline and nls (non-linear least square estimates) were used from the base package of the r. **, **, and * indicate statistical significance at the %, % and % levels respectively real-time tracking and forecasting of the covid- outbreak in kuwait: a mathematical modeling study. medrxiv predictions by early indicators of the time and height of the peaks of yearly influenza outbreaks in data analytics for operational risk management. decision sciences, forthcoming stopping covid- : a pandemic-management service value chain approach (ssrn scholarly paper no supply chain management of blood products: a literature review understanding responses to supply chain disruptions: insights from information processing and resource dependence perspectives random forests measuring sectoral supply and demand shocks during covid- how biased household inventory estimates distort shopping and storage decisions quantifying the bullwhip effect in a simple supply chain: the impact of forecasting, lead times, and information deep learning with long short-term memory networks for financial market predictions forecasting trends in time series modeling and public health emergency responses: lessons from sars a decision support system for demand management in healthcare supply chains considering the epidemic outbreaks: a case study of coronavirus disease (covid- ) toilet roll mania boosts sales of andrex maker kimberly-clark financial times applied nonparametric regression covid- and productivity in the uk. durham university business school random decision forests. document analysis and recognition the effect of supply chain glitches on shareholder wealth food supply chains during the covid- pandemic another look at measures of forecast accuracy a state space framework for automatic forecasting using exponential smoothing methods predicting the impacts of epidemic outbreaks on global supply chains: a simulation-based analysis on the coronavirus outbreak (covid- /sars-cov- ) case ten years of research change using google trends: from the perspective of big data utilizations and applications inventories and the volatility of production supply network disruption and resilience: a network structural perspective caret package distance-based nearest neighbour forecasting with application to exchange rate predictability information distortion in a supply chain: the bullwhip effect averages of forecasts: some empirical results the m competition: , time series and forecasting methods we need to talk about intermittent demand forecasting forecasting branded and generic pharmaceuticals integrating industrial maintenance strategy into erp forecasting peaks of seasonal influenza epidemics forecasting the novel coronavirus covid- horses for courses' in demand forecasting the evolution of resilience in supply chain management: a retrospective on ensuring supply chain resilience ensuring supply chain resilience: development of a conceptual framework on the calculation of safety stocks when demand is forecasted deep learning with long short-term memory networks and random forests for demand forecasting in multi-channel retail from predictive to prescriptive analytics: a data-driven multiitem newsvendor model. decision support systems forecasting seasonal outbreaks of influenza forecasting container throughput with long-shortterm-memory networks modeling and predicting seasonal influenza transmission in warm regions using climatological parameters forecasting covid- impact on hospital bed-days, icu-days, ventilator-days and deaths by us state in the next months forecasting the impact of the first wave of the covid- pandemic on hospital demand and deaths for the usa and european economic area countries product substitution in different weights and brands considering customer segmentation and panic buying behavior demand forecasting and order planning for humanitarian logistics: an empirical assessment clustering, forecasting and cluster forecasting: using k-medoids, k-nns andrandom forests for cluster selection phenomenon-based research in management and organisation science: when is it rigorous and does it matter? coronavirus disease (covid- )-situation report- the bullwhip effect: progress, trends and directions an experiment in epidemiological forecasting: a comparison of forecast accuracies of different methods of forecasting deer mouse population density in montana modified seir and ai prediction of the epidemics trend of covid- in china under public health interventions the following publicly available data sources has been used. confirmed, recovered and deceased cases were obtained from johns hopkins university, this data set is derived from multiple sources, including who and national governmental organisation and is updated on a daily basis: (https://data.humdata.org/dataset/novel-coronavirus- -ncov-cases) key: cord- -i whxt authors: horby, peter title: improving preparedness for the next flu pandemic date: - - journal: nat microbiol doi: . /s - - - sha: doc_id: cord_uid: i whxt pandemic influenza remains the single greatest threat to global heath security. efforts to increase our preparedness, by improving predictions of viral emergence, spread and disease severity, by targeting reduced transmission and improved vaccination and by mitigating health impacts in low- and middle-income countries, should receive renewed urgency. g iven its potential to cause an acute global health crisis with many millions of deaths, pandemic influenza can rightly be considered the greatest single threat to global health security. yet despite this threat, influenza has recently been eclipsed in the popular and scientific consciousness by less common infections, such as those caused by ebola and zika viruses. the centenary of the influenza pandemic, which is estimated to have killed million people, is an opportune time to remind ourselves that the greatest risks often lay in the mundane. much like we need reminding that driving is far more dangerous than flying, familiarity can breed contempt. the appearance of a human influenza pandemic depends on the emergence of a novel virus that can readily infect and transmit between people. the mostly likely source of a pandemic virus is the pool of influenza viruses that infect animals such as wild birds (the natural reservoir of influenza a viruses), domestic poultry and pigs. the scale of pig and poultry farming has increased massively over the past years, with the estimated global number of pigs and chickens having increased roughly twofold and fivefold, respectively, from the early s until now (from million to around billion pigs; and billion to billion chickens) . swine influenza is endemic in pig populations, with co-circulation of multiple subtypes and the intermittent introduction of new strains from avian or human sources, whilst poultry populations are affected by an increasing variety of influenza viruses. human infections with a diverse range of zoonotic influenza viruses are now being detected ( fig. ) , some of which are associated with a high case fatality rate, and some of which have mutations that confer resistance to the major classes of influenza antiviral drugs. although it is hard to be sure as surveillance and genetic sequencing capabilities have been increasing, we seem to be experiencing a notable increase in the genetic exchange and diversification of animal influenza viruses . determining which of these viruses will cause the next pandemic, when it will happen and how bad it will be remains incredibly challenging. however, there are warning signs to be heeded and areas in which our preparedness could be strengthened to make sure that we are best placed to identify and swiftly confront the next influenza pandemic. influenza is probably one of the most studied viruses, yet fundamental gaps exist in our ability to predict the transmissibility and virulence of novel influenza viruses. the recent lifting by the us national institutes of health of their moratorium on funding of so-called 'gain-of-function' experiments (laboratory experiments where viruses are genetically altered to assess the effect on properties such as transmissibility and virulence) is good news, as it allows us to explore the limits of evolution and the genotypic predictors of phenotype . however, there are limits to the predictive value of laboratory experiments and animal models, and when a new pandemic virus does emerge, which inevitably it will, the most important measure will be the disease severity per infected person. this information is crucial for understanding the potential impact of the pandemic and appropriately calibrating the political and public health response. estimating the severity per infected person requires robust and real-time data on the number of people infected and the proportion within this group that develop severe disease . such data are surprisingly hard to gather and interpret because care-seeking and care-giving behaviour can change as awareness of a pandemic and pressures on healthcare change. this is an area that requires investment in methodologies and tools for gathering the necessary input data, including potential modifying factors such as care-seeking behaviour, and feeding that data into analytic frameworks for estimating the severity per infected person. mathematical models of disease transmission have become a routine tool for evaluating and predicting the behaviour of epidemics. these models are attractive to public health officials as they provide a quantitative answer to many questions, but most importantly to: "how bad is this and how bad might it get?" a promising approach to even faster and more reliable characterization of outbreaks is 'modeldriven data collection' , which tells us "how much data to collect and when to collect it" in order to improve the predictive power of the models and to maximize the efficiency of data collection . this concept should be tested by developing and piloting modeldriven data collection systems for seasonal or zoonotic influenza, to see what and how much data are needed to provide estimates of the severity per infected person that are sufficiently reliable to be actionable. the world population is around four times the size it was in , and the mobility of this population is massively increased . if a potential pandemic influenza virus acquires the ability to readily transmit between humans, it will spread with alarming speed and essentially become unstoppable. aeroplane transportation is the greatest facilitator of rapid global spread , yet airport screening has limited ability to prevent importation and at best can lead to a short delay (less than two weeks) in the onset of local transmission , . at a national level, measures to limit local transmission, such as school closure, can have some effect in reducing community transmission and can mitigate pressures on the healthcare system by reducing peak incidence. the effect is, however, dependent on timing and coordination and therefore requires access to real-time surveillance data, such as absenteeism , . the simultaneous use of face comment masks and hand hygiene together, targeting both aerosol and contact transmission, can reduce spread under laboratory conditions, although the effectiveness of these measures as a community-wide intervention is unproven . whilst neuraminidase inhibitors (nais) have been demonstrated to be effective in reducing symptomatic influenza and intra-household transmission when used prophylactically, there are no data on the effectiveness or cost effectiveness of nai use in reducing community-wide transmission . therefore, the stockpiling of nais by individual countries could permit prophylactic use that may reduce the local impact of a pandemic, but at the global level nais are not likely to have a significant role in reducing pandemic influenza transmission. around half of the world's population lacks full access to essential health services . it is therefore not surprising that the burden of influenza is greater in low-and middleincome countries (lmics) than in highincome countries. in the pandemic, the estimated death rate in africa was - times that of other regions , whilst mortality rates for influenza-associated acute lower respiratory tract infection in children younger than years are three times higher in low-income countries than in high-income countries . the influenzaassociated death rate in the elderly is also likely to be substantially increased in lmics compared to higher-income countries . this burden of influenza in lmics is often unrecognized, particularly in rural areas , . any assessment of our ability to mitigate the health impact of the next influenza pandemic must consider what will be available for the large and vulnerable populations living in lmics. the therapeutic efficacy of nais is a matter of some debate, but can probably be summarized as a proven but modest effect on the duration of symptoms in patients with mild influenza, and a probable but unproven small reduction in severe outcomes such as pneumonia and death. given the weak evidence of an impact on severe outcomes, the nai oseltamivir has recently been 'downgraded' to the complementary part of the who essential medicines list, only to be used for critically ill patients hospitalized with influenza . it is, therefore, hard to see nais having a significant global impact on the rate of hospitalization or death in any future pandemic. in addition to the weak evidence of an impact on severe outcomes, the existence of viral genetic variants that confer considerable resistance to nais make it clear that new antivirals for influenza are needed. there are candidates in clinical development but progress is slow, and companies have favoured evaluating new candidate drugs in patients with uncomplicated influenza, since this is the bigger market. what is needed is a large influenza clinical trials network that can evaluate multiple candidates and combination therapies (including antiviral combinations and host-directed therapies) in an adaptive platform trial, as has been achieved for cancer, for example with the i-spy platform trial . however, at this time, interventions other than antivirals can probably offer more health benefit globally. the two simple interventions that can save lives are antibiotics and oxygen. secondary bacterial infections, largely due to streptococcus pneumoniae, are thought to have made a substantial contribution to influenzaassociated pneumonia and death in (ref. ). despite the widespread availability of antibiotics, only around half of children with pneumonia in lmics receive care from a healthcare provider who can give appropriate antibiotics . although oxygen therapy is considered an essential medicine, reliable access to oxygen is absent in much of the world due to technical and cost challenges . the other intervention likely to have a major impact is pneumococcal conjugate vaccines (pcvs). these vaccines have been shown to reduce the risk of influenza-associated pneumococcal disease , and an analysis in china suggests that routine pcv immunization prior to a pandemic would have a major impact on mortality and would be cost saving . globally, only % of children received three doses of pcv in , although coverage is actually higher in low-income than highincome countries due to support from agencies such as gavi, the vaccine alliance . effective, safe and affordable interventions, such as antibiotics, oxygen and pcvs, will save lives during an influenza pandemic and are available now. such interventions should be made available to all. whilst current influenza vaccines meet an important need and their wider use should be promoted, traditional influenza immunization approaches and the predominant egg-based production methods seriously limit their value as a tool in pandemic preparedness. there has certainly been progress in the speed of development and breadth of candidate vaccine viruses, and in the diversification and expansion of production capacity -global pandemic influenza vaccine production capacity is at its highest level ever, and may be sufficient to immunize % of the current global population with two doses, or % with one dose . nevertheless, the time frame to produce and evaluate new vaccines against novel antigenic variants and to switch vaccine production is still too slow to have a substantial impact on the first wave of a pandemic. only time will tell if the notional pandemic vaccine production capacity will ever be realized, and a pandemic vaccine will find its way into people's arms in time. substantial efforts are ongoing to optimize the use of existing vaccine technologies and to develop novel approaches, including, most importantly, work to realize the aspiration of a broadly protective, universal influenza vaccine. these efforts are of major global importance and must continue to be supported. if we do not keep our eye on the ball and continue to aggressively pursue improvements in pandemic influenza comment preparedness across the whole range of disciplines, including basic science, vaccinology, clinical evaluation and therapeutics, public health and health service delivery, we will be culpable of neglecting the obvious risks in favour of the more exotic and dramatic. whilst the recently updated world health organization public health research agenda for influenza has some value, it does not constitute a strategic plan of action. as we have seen being recently developed for other high-threat pathogens, such as the viral haemorrhagic fevers and middle east respiratory syndrome coronavirus, what is needed is a blueprint for action against pandemic influenza that is comprehensive, detailed, endorsed, funded and monitored. ❐ peter horby , notice announcing the removal of the funding pause for gain-offunction research projects vaccine trialist group the author declares no competing interests. key: cord- - b u kt authors: chern, alexander; selesnick, samuel h. title: dissemination of information during public health crises: early covid‐ data from the laryngoscope date: - - journal: laryngoscope doi: . /lary. sha: doc_id: cord_uid: b u kt objectives: during a public health crisis, it is important for medical journals to share information in a timely manner while maintaining a robust peer‐review process. this review reports and analyzes the laryngoscope's publication trends and practices during the covid‐ pandemic, before the covid‐ pandemic, and during previous pandemics. methods: comprehensive review of two databases (pubmed and the laryngoscope) was performed. covid‐ manuscripts (published in the laryngoscope during the first months of the pandemic) were identified and compared to manuscripts pertaining to historic pandemics (published in the laryngoscope during the first years of each outbreak). keywords included “laryngoscope”, “flu”, “pandemic”, “influenza”, “sars”, “severe acute respiratory syndrome”, “coronavirus”, “covid‐ ”, and “sars‐cov‐ ”. data were obtained from the laryngoscope to characterize publication trends during and before the covid‐ pandemic. results: from march , to june , , the laryngoscope had covid‐ submissions. as of july , , ( . %) were accepted, ( . %) under review, and ( . %) rejected. during the first months of the pandemic, covid‐ manuscripts were published. the mean number of days from submission to online publication was , compared to in and in . a total of manuscripts concerning previous pandemics were published during the initial years of each outbreak. conclusions: the laryngoscope rapidly disseminated quality publications during the covid‐ pandemic by upholding a robust peer‐review process while expediting editorial steps, highlighting relevant articles online, and providing open access to make covid‐ ‐related publications available as quickly as possible. laryngoscope, severe acute respiratory syndrome coronavirus (sars-cov- ) has rapidly spread across the world since first identified in december in wuhan, china. the disease caused by the virus, termed coronavirus disease (covid- ) , has since been declared a pandemic; as of july , , there have been over . million cases and over , reported deaths worldwide. clinical sequelae range from mild upper respiratory infection symptoms to a progressive life-threatening pneumonia, multi-organ failure, and even death. the sars-cov- virus targets endothelial cells via angiotensin-converting enzyme receptors and causes distinctive vascular changes (i.e., severe endothelial injury and widespread thrombosis with microangiopathy) that are thought to underlie the acute respiratory failure and multi-organ dysfunction associated with the disease. , as the covid- pandemic poses unprecedented challenges and significant threats to the worldwide population, clinicians have urgently needed answers to questions that can help guide clinical care and decision-making. consequently, a vast amount of research has emerged on covid- ; according to one analysis, the scientific community has released over , covid- related scientific articles within the first months of the initial outbreak, with topics ranging from epidemiology to new detection methods and interventions. scientific and clinical progress depends on effective transmission of research findings to members of the scientific and medical communities, who go on to share these discoveries to a broader audience. during a public health crisis such as the covid- pandemic, it is important for medical journals to share information in a timely manner while simultaneously maintaining a robust peerreview process. this ensures the publication of highquality content and prevents spread of misinformation, which can ultimately have detrimental effects on patient care. this review describes publication trends and practices of the laryngoscope that have enabled the journal to combine urgency and scientific rigor for rapid dissemination of quality publications. our research objectives were to report and analyze publication trends and practices of the laryngoscope during the covid- pandemic, before the covid- pandemic, and during previous pandemics. comprehensive review of two databases (pubmed and the laryngoscope journal website) was performed on july , to identify the laryngoscope publications pertaining to the covid- pandemic and historic respiratory pandemics of the th and st century. [ ] [ ] [ ] [ ] the highlighted content: covid- section of the laryngoscope journal website provides all published covid- manuscripts. the laryngoscope issue archive provides historic and present-day issues. entries from these sections of the website were searched to identify relevant manuscripts published during the first months of the covid- outbreak ( / / - / / ) and first years of each historic outbreak. , historic pandemics and relevant dates included the influenza pandemic ( / / - / / ), - a pubmed literature search was performed using pertinent date ranges for each pandemic to verify the aforementioned review of the laryngoscope website. search terms "flu", "pandemic", "influenza", "sars", "severe acute respiratory syndrome", "coronavirus", "covid- ", and "sars-cov- " were each combined with "laryngoscope". publication titles, abstracts, and manuscripts were reviewed to identify those related to historic pandemics. relevant publications from both databases were compiled, with duplicates removed, for analysis. internal submission and publication data from the laryngoscope during the early covid- pandemic ( / / - / / ) were obtained from the laryngoscope to identify covid- submissions during this time. covid- submissions were categorized by topic, publication type, and publication status (as of / / ) to characterize submission trends and publication speed. internal publication metrics (time from submission to acceptance, acceptance to online publication) prior to the covid- pandemic ( and ) were obtained to anchor the reader to the typical publication speed of the laryngoscope. outcomes of interest extracted from the database search and internal data from the laryngoscope included ) number of covid- publications during the first months of the covid- pandemic, ) number of publications pertaining to historic respiratory pandemics of the th and st century during the first years of each pandemic, ) covid- submission trends (i.e., number of submissions, topic, publication type, and status of publication) during the first months of the covid- pandemic, and ) publication speed before and during the covid- pandemic. since the laryngoscope was founded in , these pandemics were all caused by viruses with similar respiratory disease presentations and transmission modalities (i.e., aerosols or respiratory droplets) as sars-cov . the most severe of these pandemics was the so-called "spanish flu" ( influenza pandemic), which caused - million deaths from - . milder influenza pandemics occurred subsequently; the - and pandemics were estimated to have our comprehensive search of two databases, pubmed (use of relevant keywords and date ranges) and the laryngoscope journal website (review of publication entries in prior issues published during relevant date ranges), yielded a total of articles pertaining to historic pandemics published by the laryngoscope within the first years of each pandemic. these included two case series on otolaryngologic manifestations of the disease during the influenza pandemic, , as well as reports pertaining to safe tracheostomy for patients and the impact of the pandemic on otolaryngologists during the sars outbreak of . in summary, remarkably little was published regarding prior pandemics by the laryngoscope. from march , to june , , a total of manuscripts concerning covid- were submitted to the laryngoscope. there were submissions in march, in april, in may, and in june. as of july a total of covid- publications have been published during the first months of the pandemic ( / / - / / ). mean number of days from submission to acceptance was , acceptance to online publication , and submission to online publication . prior to the covid- pandemic in , mean numbers of days from submission to acceptance was , acceptance to publication , and submission to online publication . in , mean number of days from submission to acceptance was , acceptance to publication , and submission to online publication (fig. ) . otolaryngologists have been uniquely impacted by the covid- pandemic and are often closely involved in the management of patients suffering from the disease. covid- often presents with otolaryngologic symptoms, including cough, sore throat, dyspnea, dysgeusia, and most notably, anosmia. , otolaryngologists have been frequently called upon for their expertise in airway management (e.g., performing and managing tracheostomies for patients with covid- that require chronic invasive mechanical ventilation). the high rates of community and nosocomial spread have also led to a wide variety of innovations (e.g., novel personal protective equipment) centered around reducing risk of sars-cov- virus transmission during surgery. , these innovations have been valuable for those involved in patient care during the pandemic; healthcare personnel, specifically those who routinely participate in aerosol-generating procedures (e.g., endotracheal intubation, nasal endoscopy) such as otolaryngologists and anesthesiologists, reportedly suffered a high rate of infection and death during the initial outbreak in wuhan, china. , the large impact that covid- has had on otolaryngology practice has led to a notable influx of submissions to the laryngoscope during the first months of the pandemic. overall, the publication trends and practices of the laryngoscope have enabled the journal to transparently bring its audience the best possible information available in an expedited manner. several trends in the data are noted. the proportion of original reports per month has dramatically increased over the first months of the covid- pandemic, consisting of . % of all submissions in march, to . % of all submissions in june; this can be attributed to the time required to collect adequate data for a high-quality research study. for comparison, original reports typically represent approximately % of all articles published in non-pandemic time. on the other hand, the proportion of contemporary reviews per month has significantly decreased over time, from . % of all submissions in march to . % of all submissions in june. contemporary reviews are typically submissions that address rapidly evolving topics, such as novel diagnostic or therapeutic advances for a public health crisis. in the early stages of a public health crisis, there are less data to collect for a meaningful research study suitable for an original report. the low acceptance rate ( . %) of covid- manuscripts can be attributed to several factors. as mentioned previously, there is typically a paucity of rigorous data during initial stages of a pandemic, which facilitates the submission of level studies (e.g., case series without an internal control). as time passes and more rigorous studies can be performed, those types of descriptive studies published early on are no longer novel and will no longer be published. moreover, with time, there are duplications of ideas and findings; these can vary geographically because the covid- pandemic affected different regions at different times. physicians from communities that were affected at a later time point may wish to publish their experience, which may simply echo the experience of earlier researchers. these submissions would not be accepted by the laryngoscope. it is also important to note that a large number of current submissions (i.e., from may and june) are still under review. the overall acceptance rate of the journal during the first months of the pandemic can be assessed more accurately once most manuscripts have undergone peerreview. given the high prevalence of anosmia in patients with covid- , manuscripts pertaining to anosmia comprised a large proportion of all submissions ( . %). the large impact that covid- has had on otolaryngology practice worldwide has resulted in a considerable proportion of all submissions relating to impact and changes in clinical practice ( . %). many of these submissions attempted to describe various challenges that otolaryngologists have faced, as well as guidelines and recommendations to address them. the high transmission rates sparked more manuscript submissions over time that addressed procedural and surgical innovations; these were often centered around reducing viral spread during surgery. these submissions reflect the remarkable ingenuity of otolaryngologists when facing this contagion threat to their patients, co-workers, and themselves. moreover, as otolaryngologists became more familiar with the covid- disease process and how it may affect their patients, the proportion of submissions addressing other otolaryngologic symptoms and manifestations of covid- also increased over time. there were substantially more publications by the laryngoscope during the early stages of the covid- pandemic ( during the first months) compared to the other major pandemics of the th and st century (total of during the first years of each outbreak). this phenomenon cannot be attributed to lack of otolaryngologic symptoms during prior pandemics-influenza is a contagious respiratory illness that certainly manifests with otolaryngologic symptoms, including cough, shortness of breath, sore throat, nasal congestion, and rhinorrhea. we would also not expect that curiosity and zeal for clinical research were diminished in the physicians of earlier pandemics. although the laryngoscope was a well-known journal during prior pandemics, it is possible that authors sent their pandemic-related research to other otolaryngology journals. publishing speed during the covid- pandemic by the laryngoscope has also been considerably faster when compared to the non-pandemic times ( and ) . we report the publishing speed in and to anchor the reader in the usual publication rate prior to the covid- pandemic. the time from submission to online publication for non-covid- article in ( days) or ( days) is approximately - times the time from submission to online publication for a covid- manuscript ( days) during the first months of the outbreak. of note, the peer-review process for covid- submissions is not accelerated and is treated the same as any other submission; reviewers are not instructed to complete their peer-review more quickly. the speed of publication can be attributed to specific editorial steps are taken by the laryngoscope to ensure rapid dissemination of novel information during the covid- pandemic. all submissions pertaining to covid- are flagged to ensure eventual prompt distribution to reviewers. the time from acceptance to publication online is accelerated to enable the effective spread of new information by working closely with the postproduction team of the journal publisher. relevant manuscripts leapfrog other accepted, non-covid- papers in queue for publication. once published, covid- articles are highlighted in a section prominently located on the journal webpage. furthermore, the laryngoscope has made these articles accessible to all without an institutional subscription, personal subscription or fees. the covid- pandemic highlights the need for rapid scientific communication of essential information on the disease to facilitate optimal patient care. historically, medical journals have played a key role in dissemination of peer-reviewed science; however, the conventional peer-review process and post-production process can take a significant and prohibitive amount of time, delaying time from submission to publication for months-and sometimes for a year or more. clinicians and public health authorities require actionable information as soon as possible to slow down, contain, and eventually stop the disease. for example, a number of recent publications address methods and outcomes for tracheostomy in patients with novel methods for performing tracheostomy to mitigate aerosolization, as well as patient and healthcare worker outcomes (i.e., transmission amongst patients and healthcare workers) can realistically benefit clinicians worldwide, especially those who may be less experienced or practice in an area where a severe worsening of the pandemic is imminent. laryngoscope : chern and selesnick: covid- publications from the laryngoscope the urgency of a public health crisis may also prompt inadvertent spread of misinformation. recently, two worldrenowned medical journals, the new england journal of medicine and the lancet retracted two high-profile papers on treatments in patients with covid- . , one of the studies reported the results of clinical trials of two antimalarial drugs used for treatment of covid- (chloroquine and hydroxychloroquine). this retracted study claimed that these drugs were not associated with improved outcomes and were, in fact, associated with higher mortality in patients. although no strong evidence exists supporting the use of such antimalarial medications for treatment of covid- , the study wase based on faulty data and had a global impact, halting trials of the drugs by the world health organization and other entities. one of the coauthors of the studies admitted he was rushed to publish research during the covid- pandemic, which prevented him from verifying the source of the data. there were several limitations to our historical comparison. the dissemination of information by journals during the mid-late th century (i.e., the pre-digital age, when manuscripts were submitted with multiple hard copies) took place more slowly compared to today, where digital transmission of information occurs almost instantaneously through the internet. a more generous window for publication during earlier pandemics was provided in our analysis for a fairer comparison to publication during the covid- pandemic ( years vs. months after initial outbreak). during the early-mid th century, the laryngoscope also did not have the global reach that it does today. this is particularly important when considering previous pandemics that predominantly affected other parts of the world and did not have as large of an impact on the united states. authors may have chosen to publish their work in other more familiar, well-known journals of that time, which may partially explain the paucity of historic pandemic publications in the laryngoscope. publication data (e.g., number of submissions and acceptances, time from manuscript receipt to acceptance) of the laryngoscope during historic pandemic years were not available for comparison to current covid- publication data. future directions include post-pandemic bibliometric studies conducted to inform the scientific community on effective strategies for mobilization of scholarly efforts during a public health crisis. characterizing how the scientific community responds to emergencies may be beneficial in creating and adjusting anti-epidemic or antipandemic strategies. the laryngoscope was initially founded by max goldstein of st. louis "in an effort to speed the dissemination of the rapidly expanding body of knowledge in otolaryngology". the laryngoscope continues to hold to this core tenet to this day by publishing exceptional quality and timely manuscripts during what is arguably the most severe public health crisis of the past century-the covid- pandemic. during a public health crisis such as the covid- pandemic, it is important for medical journals to share essential information in a timely manner while maintaining a robust peer-review process. compared to pre-pandemic times, the laryngoscope has combined urgency and scientific rigor to rapidly spread quality publications by upholding a strict peer-review process while expediting all editorial steps, highlighting relevant articles in a prominent section online, and providing open access capabilities to make publications available as quickly as possible. clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study endothelial cell infection and endotheliitis in covid- covid- : the vasculature unleashed preprinting a pandemic: the role of preprints in the covid- pandemic asked questions about sars severe acute respiratory syndrome (sars) highlighted content: covid- brief history of the triological society and the laryngoscope who. influenza and covid- -similarities and differences hemorrhage in epidemic influenza a study of the aural complications of the recent influenza epidemic with special reference to the clinical picture safe tracheostomy for patients with severe acute respiratory syndrome the impact of severe acute respiratory syndrome on otorhinolaryngological services at the prince of wales hospital in hong kong internal database from the laryngoscope author guidelines covid- in otolaryngologist practice: a review of current knowledge anosmia and ageusia: common findings in covid- patients utility of tracheostomy in patients with covid- and other special considerations the covid- airway management isolation chamber (camic) for ears minimizing contagion risks of covid- during trans oral robotic surgery high risk of covid- infection for head and neck surgeons covid- pandemic: effects and evidence-based recommendations for otolaryngology and head and neck surgery practice the oxford levels of evidence cdc. the difference between flu and covid- novel percutaneous tracheostomy for critically ill patients with covid- outcomes after tracheostomy in covid- patients retraction: cardiovascular disease, drug therapy, and mortality in covid- retraction-hydroxychloroquine or chloroquine with or without a macrolide for treatment of covid- : a multinational registry analysis (the lancet two elite medical journals retract coronavirus papers over data integrity questions a tribute to max goldstein, md, founder and editor of the laryngoscope key: cord- - jxdnm l authors: lee, sang m.; lee, donhee title: lessons learned from battling covid- : the korean experience date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: jxdnm l background: the covid- pandemic has swept the world like a gigantic tsunami, turning social and economic activities upside down. methods: this paper presents some of the innovative response strategies implemented by the public health system, healthcare facilities, and government in south korea, which has been hailed as the model country for its success in containing covid- . korea reinvented its public health infrastructure with a sense of urgency. results: korea’s success rests on its readiness, with the capacity for massive testing and obtaining prompt test results, effective contact tracing based on its world-leading mobile technologies, timely provision of personal protective equipment (ppe) to first responders, effective treatment of infected patients, and invoking citizens’ community and civic conscience for the shared goal of defeating the pandemic. the lessons learned from korea’s response in countering the onslaught of covid- provide unique implications for public healthcare administrators and operations management practitioners. conclusion: since many epidemic experts warn of a second wave of covid- , the lessons learned from the first wave will be a valuable resource for responding to the resurgence of the virus. the recent spread of the coronavirus (covid- ) has thrown the world into total chaos. covid- has caused not only a health and social crisis of immense proportions forcing people to deal with the fear of infection and the physical, emotional, and financial damage from government recommended physical distancing, but it has also caused a global economic turmoil [ , ] . the virus started spreading in wuhan, china in late december , and became a shocking pandemic by mid-march ; by this time, it had already caused several hundred deaths, disrupted the global economy, and forced countries to close their doors to visitors [ ] [ ] [ ] . the world health organization (who) defined covid- as "an infectious disease caused by a newly discovered coronavirus" [ ] . who declared the novel coronavirus outbreak a global pandemic, the highest category for infectious diseases, on march , officially notifying the global community that a health crisis is upon us [ , ] . major infectious diseases that have occurred during the past years include severe acute respiratory syndrome (sars: ), novel influenza virus (h n : ), middle eastern respiratory syndrome (mers: ), avian influenza ( and ), and covid- ( ), most of which were originally reported in china. particularly, covid- has potent infectivity, implying that it spreads quicker and its mutations are more complex than other infectious diseases. as the numbers of confirmed cases and deaths began to rise exponentially, halting the coronavirus became a global issue. in addition to the immediate health concerns, the covid- pandemic disrupts and destroys global supply chains along the associated systems of purchasing, manufacturing, logistics, and sales [ ] . this study attempts to present directions for potential changes in the crisis response systems of public healthcare worldwide, by analyzing covid- pandemic response cases, both successes and failures, in korea. more specifically, this study has the following objectives: ( ) to analyze korean experiences with cases where healthcare facilities failed to prevent previous infectious diseases from spreading, and how these failures served the government in devising effective approaches to encounter the covid- pandemic, ( ) to dissect cases that showed innovative and successful response measures to deal with the covid- pandemic, and ( ) to elaborate on suggestions for crisis management based on the lessons learned from these covid- response cases in korea. the rest of this paper is structured as follows. in section , we present a review of relevant literature on global infectious diseases and covid- as well as several real cases of korean healthcare providers in managing the covid- pandemic. section presents the innovative response strategies deployed in korea (k-response model) to fight the pandemic. in section , we summarize the important lessons learned from the korean experience. we conclude the study in section by discussing implications of the study results, limitations of the study, and future research needs. infectious diseases refer to those "caused by pathogenic microorganisms, such as bacteria, viruses, parasites, or fungi; the diseases can spread, directly or indirectly, from one person to another" [ ] . these diseases can infect people by contact with other humans, animals, or other reservoirs infected by a pathogen or toxic substance. additionally, communicable diseases refer to those that directly or indirectly spread between humans or between humans and animals. thus, an infectious disease pandemic is an epidemic that has the potential to be easily transmitted and to affect the global population due to its highly infectious nature [ ] . since the second world war, the world has seen many innovative developments in vaccines and antibiotics; such advances have ensured that communicable and infectious diseases are reasonably controlled [ ] . an important study by the institute of medicine, "emerging infections: microbial threats to health in the united states," shed some light on the issues involved with novel infectious diseases [ ] . soon thereafter, the who passed the resolution "global health security: epidemic alert and response" in [ ] , which enabled the collection of information and enforcement of actions through cooperative work by inter-governmental agencies, non-governmental institutions, private organizations, and governments around the world. in , the sars outbreak in china quickly spread fear of a pandemic that could cross borders and affect countries worldwide. particularly, china failed to promptly and transparently disclose epidemic information. the chinese government reported the outbreak to the who several months after the first confirmed case of sars, thus delaying effective response measures by world organizations. immediately, the who raised the alert that the sars outbreak was of high risk, subsequently issuing a travel advisory notice (e.g., advising a travel ban to places where the epidemic had occurred) aimed at suppressing the spread of the disease. as a result of this experience with sars, many countries worldwide recognized the importance of a global infectious disease governance system, which should stretch beyond the governance of each country [ ] . in , the international health regulations were revised and expanded to include not only communicable diseases but also other possible threats (i.e., biological terrorism and events that induce international public health crises). nevertheless, other highly contagious diseases have continued to emerge throughout the last two decades. in the presence of healthcare emergencies, such as the infectious and coronavirus outbreaks discussed above, public healthcare should be available throughout the country not only with rapid response but also based on an equitable basis [ , , ] . the sense of equity involves a person's perception of the input and output relationship which should not create tension or displeasure as a result of cognitive dissonance [ ] . rousseau [ ] defined equity as a function of customer's perception in a service encounter experience. equity is realized when a person believes his/her outcome concerning resources invested is in harmony with that of others [ ] . equity theory has become the theoretical foundation for service recovery as it helps create possible recovery approaches for service failures through recognition, procedures, and mutual interaction involving customer complaints [ , ] . it is important that people perceive that a service is being provided equitably. especially in a crisis such as the covid- pandemic, it is imperative for people to perceive that urgent public healthcare is being provided equitably [ ] . such perceived equity inspires people to be transparent about their activities (e.g., infection status, contacts, self-quarantine, etc.) that are the first line defense against the disease. this study examines the successes and failures of the korean healthcare organizations in their efforts to contain covid- , from an equity perspective relating to healthcare services. korea has a history of responding poorly to infectious diseases (e.g., sars, h n , and mers). in , saudi arabia was the first country to experience the mers outbreak. korea was the most detrimentally affected country by the virus as many korean global firms have operations in saudi arabia. in korea, the first mers case was confirmed in and its rapid spread resulted in a significant number of casualties which heightened anxiety that swept throughout the country. furthermore, the serious blow caused to the national economy clearly revealed the weakness of korea's infection crisis management system [ , ] . the korean government's limited response capacity regarding mers and its poor communication to its citizens weakened people's trust in the government's infection crisis management policies to the point where many started believing that the national epidemic prevention system could easily collapse [ ] . there were confirmed cases of mers among those who traveled to the middle east, of whom died in . the causes of the high mortality rate could be attributed to the limited capacity of the healthcare delivery system for handling the new virus, shortage of epidemic prevention equipment for medical first responders, and the moral hazard among patients [ , ] . after painful experiences in dealing with past diseases, the korean government was determined to establish an effective infrastructure to deal with future epidemic emergencies, with kcdc as the control tower. the new infrastructure includes an increased number of negative-pressure isolation wards, real-time systems for data and transparent information collection and analysis, and modernization of the healthcare system. since the mers crisis, the korean government has reinvented a national healthcare delivery system equipped with advanced digital technologies and expanded the facilities specifically designed to deal with infectious diseases (e.g., the creation of negative pressure wards) [ , ] . thus, kcdc was well prepared to respond effectively to epidemic emergencies when the covid- crisis occurred. when covid- began to spread, the korean government raised the response level to serious (the highest) on february and promptly established the central disaster and safety countermeasure headquarters, headed by the prime minister to bolster government-wide responses to the virus with kcdc as the command center [ ] . according to the korea economic daily [ ] , the rapid spread of covid- around the world, especially in china, italy, and in the united states, and the subsequent spike in the number of deaths, has brought global attention to the prevention model and early response operational strategy implemented by daegu city, the epicenter in korea. daegu took aggressive actions with speed to prevent the collapse of its healthcare system without placing the city in a lockdown [ ] . the city government performed aggressive screening, testing, and quarantining of patients in the communities that were confirmed to have, or suspected of having, infected citizens. according to kcdc [ ] , daegu city did not implement this approach at the onset of the covid- outbreak in korea ( february ). daegu and the north gyeongsang province (where daegu is located) were heavily criticized for the exponential growth rate of infected patients as ground zero. this region accounted for % of the confirmed cases in korea, caused primarily by the shincheonji church gatherings (worship services where people sat on the floor shoulder-to-shoulder) and the mass infections that occurred among the first medical responders while providing care services. the city government performed screening tests of the entire congregation of the shincheonji church, isolated severely ill patients, and secured enough quarantine beds for those in need of treatment and isolation. to achieve this, daegu operated a public-private partnership (ppp) network (composed of the emergency response advisory group, the daegu medical association, and three infectious disease management support groups), which served as the control team for the covid- epidemic [ ] . the ppp collaboration network deployed several response strategies against covid- . first, private hospitals were converted into isolation hospitals. a group chatroom for the control team was created, through which experts held discussions about the situation throughout the night. through these discussions, the daegu dongsan hospital and the ministry of defense were contacted and asked to secure as many beds as possible at the daegu armed forces hospital and daejeon hospital. at that time ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) , there were only about available negative pressure wards in daegu, and some confirmed patients died while waiting to be admitted into a hospital. second, the entire congregation of the shincheonji church was tested, and those who had symptoms were identified. on the night of february , % of confirmed cases of covid- were members of the shincheonji church. the daegu secured information on the members of the church, identified them, and ordered symptomatic patients to remain in self-quarantine for two weeks. a leading physician at the kyungbook national university stated that "the rate of confirmed cases reached % among patients who showed symptoms; so, if we had not prompted early isolation of those shincheonji church members who showed symptoms, daegu might have been in the same situation as europe or the united states" [ ] . third, members of the daegu medical association provided care to those patients in self-quarantine via video calls using outgoing-call-only smartphones provided by daegu city, hence eliminating the previously existing void in the response system. these response activities represent innovative strategies implemented in the initial stage of the covid- invasion (e.g., aggressive testing, almost immediate test results, contact tracing of infected persons, and prompt treatment of severely ill patients). the mortality rates in new york, usa ( . %) and in madrid, spain ( . %) are much higher than that in daegu, korea ( . %) as of june (see table ). these high mortality rates indicate that their patient monitoring and healthcare facilities operations were not systematic. it is evident that "the most potent operational strategy amid the lack of a cure is not search and destroy, but identification and isolation of symptomatic citizens" [ ] . fourth, drive-through screening centers were developed for the first time in the world, supported by a world-leading ict infrastructure [ ] . the yeungnam university medical center, in the vicinity of daegu, had admitted a covid- patient on february , which resulted in the closing of the emergency room (er) and prompted self-isolation of its medical staff. based on this experience, the medical center decided to establish a drive-through screening center, which eliminated the risk of shutting down er and self-quarantining first responder medical staff. moreover, the existing screening center was inefficient in handling the large crowd of people needing testing in a small space. thus, this was another innovation in need that led to the strategy of developing drive-through testing centers. laura bicker, a bbc correspondent in seoul, referred to the drive-through testing centers as "such a clever idea and so quickly set up". sam kim, an economics reporter at bloomberg, mentioned that korea "once again proved to be among the world's innovative nations," and ian bremmer, president of the eurasia group, a think tank in the us, stated that "innovation drives resilience" [ ] . innovative operation strategies are critical in fighting such a formidable global pandemic as covid- . finally, creative applications of the national ict infrastructure and rapid development of mobile apps by young entrepreneurs have helped analyze the details about confirmed patients and their contacts (e.g., locations, people contacted, and travel patterns before their infection confirmation). kcdc [ ] collected and released relevant information (e.g., regions, pockets of high infection density, and places visited) on covid- patients in real-time. such transparency regarding the handling of covid- patients encouraged citizens to voluntarily participate in physical distancing and personal hygiene. this is another strategy that has helped korea effectively manage the crisis when compared to other nations such as italy and the us. in korea, after kcdc disclosed the movements of the first covid- patient in daegu on february, all the places the patient had visited were immediately shut down and disinfected; moreover, the government analyzed security footage (e.g., cctv from the entrance of the church) to help identify and isolate anyone who might have come into contact with the patient. local governments sent out emergency alert text messages to provide real-time updated information so that the population of other provinces and cities could be advised not to visit the infected locations. table summarizes the current (as of june ) state of the cities with the greatest number of confirmed cases among countries most affected by covid- , and the innovative operational strategies implemented by daegu to respond to the covid- pandemic. daegu, the epicenter of covid- cases, is currently in the process of being transformed into a smart city. it is noteworthy that the city/area where an explosive outbreak of covid- cases occurred had higher mortality rates than that of the country as a whole. table summarizes statistics of the number of confirmed covid- infection cases, deaths, and mortality rates among the top % of countries, including italy, china, and south korea, as of september . the table also indicates average statistics for the entire countries. figure shows the mortality rates of the top countries for covid- infection, including south korea, as of september (including the average for the entire countries as a group). the bars in the figure show the number of deaths per , population. in the early phase of the coronavirus spread, south korea recorded the second highest number of infected persons after china. however, as shown in tables and and figure , korea initiated aggressive strategies for testing and contact tracing based on its well-established public health infrastructure. thus, the country has been able to flatten the curve of infected cases which resulted in relatively low rates of deaths/infected cases and mortality (deaths/ , population) [ ] . source [ ] . the crisis caused by a pandemic can lead to issues of equity in the public healthcare service [ ] . particularly, failures in providing equitable public healthcare and in community participation in the decision making process should not be repeated. thus, it is necessary to analyze the successes and failures experienced in the current situation (i.e., the first wave) as a preparation for the possible mortality: deaths/ k population ( september ) the crisis caused by a pandemic can lead to issues of equity in the public healthcare service [ ] . particularly, failures in providing equitable public healthcare and in community participation in the decision making process should not be repeated. thus, it is necessary to analyze the successes and failures experienced in the current situation (i.e., the first wave) as a preparation for the possible onslaught of the second wave of the pandemic. to conduct an in-depth analysis of the causes and consequences of the covid- virus spread in korea, we examine the operational procedures and strategies implemented by several healthcare facilities. many seriously ill patients with the virus were diagnosed or infected in er. even in a normal day, er operates at the disaster level [ ] . the covid- pandemic severely tested the agility, flexibility, and resilience of er operations at every hospital. the following five cases are investigated based on the information released by kcdc [ ] . hospital a is an -bed tertiary general hospital located in seoul with employees. the hospital provides care to an average of inpatients and outpatients daily. the first covid- case in this hospital was confirmed on february , and was consequently quarantined for two weeks until march. a careful contact tracing of the patient resulted in additional confirmed cases within the hospital. the first confirmed case in the hospital was a patient aide who helped patients move from the ward to the lab. prior to the diagnosis, it was found that this aide had helped patients. after the diagnosis of the first confirmed case, the hospital's er and outpatient clinics were closed and quarantined. hospital b is a -bed general hospital with employees located in seoul. it was closed for two weeks, from to march, due to a patient's dishonesty. the patient was a resident of daegu city but falsified his home address when hospitalized. after being diagnosed with covid- , the patient was isolated. the hospital shut down its outpatient center, some wards, and er. the particular concern which this patient caused was the fact that the person had visited the artificial kidney unit, contacting many high-risk patients. although there was no additional positive case found, the hospital was quarantined for two weeks. hospital c is a psychiatric hospital (housed on floors - in a high-rise building) in daegu with inpatients and employees. the first positive diagnosis of covid- was made on march, after which the number of confirmed cases increased at an alarming rate. this case happened because the first patient was originally at a convalescent hospital (located on floors - in the same building) where the first positive case was tested on march and spread quickly to patients. when the first case was confirmed at the convalescent hospital, the building management firm failed to disinfect the entire building and consequently the virus spread to hospital c. hospital c conducted virus tests on its own employees but did not screen all patients because all the employees were tested negative. there were infected patients as of april and the hospital was closed. kcdc conducted a thorough investigation of hospital c and found that the mass infection occurred because of the failure to screen all patients [ ] . further, due to the nature of the psychiatric hospital (i.e., closed wards in confined spaces), the infection spread rapidly, and subsequently the number of infected cases increased at an accelerated rate. hospital d is a -bed general hospital located in seongnam city, in the vicinity of seoul, with employees, including specialists in specialty areas. the hospital serves an average of patients daily. one patient was discharged after treatment in the hospital and returned to receive outpatient care. the same patient became very ill and was brought to er and diagnosed with covid- infection on march. consequently, a mass infection of the virus occurred among healthcare providers within the hospital ( confirmed cases). hence, the hospital was closed from march to april ( days). hospital d provided incomplete information to kcdc, as a person in need of isolation was omitted from the list [ ] . hospital e implemented proactive measures to suppress the spread of covid- . all patients and their respective caregivers were required to fill out a paper-based health questionnaire upon admission. however, there were concerns about having the patients complete the questionnaire, which might take too much time while they were crowded in a limited space. in order to reduce crowding and minimize hospital-acquired virus infections, a mobile health questionnaire was delivered by the hospital. the questionnaire asked patients to precisely list all travel to foreign countries, visits to regions or facilities with confirmed cases, and any symptoms of fever or respiratory difficulties. hospital e reported that (https://www.yuhs.or.kr/en/), between and march, an average of people submitted the mobile health questionnaire each day. on average, the questionnaire took min s to complete ( . s for each of items). further, hospital e sent the mobile health questionnaire to visitors scheduled for outpatient services or testing at am on the day of the appointment via kakaotalk (korean sns) or text message. once the patient had completed the questionnaire, a quick response (qr) code was generated. if the patient had self-reported covid- -related flagging, a red qr code was assigned, and no flagging was noted with a black qr code. only visitors who had the red qr code were issued with proper stickers and allowed to enter the hospital. the patients with the red qr code were required to undergo an additional evaluation at the hospital entrance. based on this evaluation, they were either directed to a designated safe care facility or were not allowed to enter the hospital for treatment. moreover, visitors who were not able to use a mobile questionnaire or were not aware of this requirement were provided with the paper-based questionnaire at the entrance. the implementation of this mobile questionnaire was an effective measure to reduce hospital-acquired infections, among the patients and between employees and patients (hospital press release; https://www.yuhs.or.kr/en/). table presents a summary of problem causes and response strategies employed by the sample hospitals. during a pandemic crisis, the government should encourage people to take preventive measures for their own safety, and share information transparently, including that on the risk involved. after failing to effectively manage the mers outbreak in the past, korea improved its public health infrastructure and expanded its relevant medical facilities. this experience enabled the korean government and healthcare providers to develop innovative response strategies to covid- . drive-through and walk-through testing centers were implemented for the first time in the world. these systems have been heralded as a creative response model to the pandemic, and they have been benchmarked and copied by countries worldwide [ , , ] . the compelling motivation for these systems was rooted in the challenging problems experienced by some screening centers. these centers were overwhelmed by an onslaught of patients with suspected covid- symptoms. the average waiting time for a screening was as high as six hours or even longer in some cases, consequently raising serious cross-infection concerns [ ] . a drive-through screening center can process suspected patients through several steps (e.g., completion of the patient questionnaire, physician's examination, sample collection, and education) without them getting out of their automobiles, hence shortening the testing duration to less than min per patient [ ] . these testing systems lower the risk of infection, minimize contact between test recipients and healthcare providers, and save time. in a regular screening center, the room must be disinfected and ventilated after treating each patient. drive-through centers, on the other hand, do not require such procedures, thus not only diminishing the risk of contamination but also greatly increasing the number of daily cases handled. for example, a regular screening center could process two cases per hour ( daily cases), whereas a drive-through center can process up to six cases per hour ( daily screenings) [ ] . furthermore, the people being tested preferred the drive-through system because the waiting time for the test is far less and the queue time is spent in the comfort and safety of their own cars [ ] . the most challenging task in controlling the spread of covid- is making sure incoming international travelers are not carriers of the virus. thus, kcdc set up walk-through outdoor screening booths (eight for each of the two international terminals). all incoming passengers are tested as they walk through the station at the rate of min per person, screening more than passengers per day. one of the most important aspects of suppressing the spread of the pandemic is the battle against time. performing aggressive testing in a short period of time to identify and isolate confirmed patients is the most critical operational strategy for flattening the curve of infection cases [ ] . the screening systems discussed here represent innovations developed due to the desperate need to contain covid- at the most critical point of time, the beginning of the rapid spread stage [ ] . on march , the korean government established residential treatment centers to treat confirmed covid- patients while maintaining their quarantine. in this residential system, each room is occupied by one person as a rule, and all residents must conduct self-monitoring twice daily and are on constant monitoring and treatment by health professionals residing in these centers. such centers' primary aim is to triage and categorize patients into four levels (mild, moderate, severe, critical), and the secondary aim is to manage patients with mild conditions. this system helps ensure that hospital beds are provided for covid- patients needing critical inpatient care. the resident treatment centers are managed independently by each local government. the primary goal of these centers is to prevent the spread of the virus by treating, isolating, and medically monitoring infected patients. while it is not necessary to send patients with mild symptoms to hospitals, it is still necessary to isolate them as they have the potential to widen the spread of the disease. thus, these patients are the major targets of residential centers. to achieve their strategic objectives, these residential centers need to make their operations flexible and dichotomous, encompassing both hospitals and centers. hence, their provision requires accurate triage of confirmed patients, active participation by residents, and strict compliance with the care policies and regulations within the center. these residential treatment centers represent an innovative model of care that has helped prevent the spread of the infection to the community while addressing the shortage of hospital beds. "untact" means no human-to-human contact in service encounters [ ] . during the covid- pandemic, korea has been able to provide untact services to its population based on innovative applications of digital technologies. this operational strategy has contributed a great deal to suppressing the spread of covid- through an advanced healthcare system (e.g., drive-through screening centers). one of the best examples of such untact services is the self-diagnosis app and the self-quarantine protection app [ ] . on february , the central disaster management headquarters of korea announced that it was going to use a self-diagnosis app to monitor the virus infection status of all incoming travelers through a special entry procedure in order to strengthen infection management. this app monitors the symptoms once a day and provides a quick consultation by medical staff for everyone who enters the country. after this app became mandatory, permission to enter korea has been granted to only those (citizens and foreigners alike) who provided their personal information (e.g., name, passport information, nationality, and actual address) in the app. anyone entering korea must consent to use the app and download it themselves as a special entry procedure. the results of the self-diagnosis feature (i.e., fever, cough, and/or sore throat) are submitted to the corresponding public health center and kcdc. moreover, this app provides important information to the user about screening centers (i.e., the closest available area/location for inspection and contact information), the sns channel of kcdc, and consultation call centers. untact technology-based approaches are currently making a substantial contribution to address the challenges regarding patient management, shortage of healthcare staff, and lack of resources needed to provide a diagnosis. additionally, aimed at healthcare providers, a dashboard was developed by the korea university medical center and softnet to automatically send information about patients' (self-assessed) body temperature, symptoms recorded on the app, pulse and blood pressure (taken with a bluetooth blood pressure cuff) to healthcare providers [ ] . the application of such innovative apps involves a trade-off between the concern of staying safe from the virus and personal privacy [ ] . nonetheless, these measures have proven to be essential for preventing the spread of the pandemic through prompt and convenient reporting of symptoms among all travelers to korea. the crisis caused by a pandemic requires a robust response system to prevent global health, economic, and social disasters. the key lesson learned from the korean experience in managing the covid- crisis is the importance of innovative response strategies at the onset of the pandemic. based on the review of some of the experiences of sample hospitals and the practices that have been proven effective, an innovative pandemic management system should include the following strategies. the pandemic response cannot be made by one independent organization. there should be a collaborative public-private partnership that can utilize the synergistic capabilities of governments, private enterprises, healthcare institutions, university research centers, and volunteer organizations (e.g., daegu's collaborative network: emergency response advisory group + daegu medical association + daegu center for infectious disease control and prevention). such a collaborative innovation partnership is imperative to generate creative strategies, operational plans, and detailed work procedures. when a collaborative system is established, especially with many volunteer entities, it is difficult to seamlessly execute strategies and actions in a timely fashion in the face of the rapidly spreading pandemic. thus, an explicitly designed governance system with clearly defined roles, responsibilities, and authorities is as important as the strategic plans. in the exponential increase stage of the pandemic infection, healthcare facilities in the ground zero area could be overwhelmed by severely ill patients, causing the collapse of the system. for effective response management, healthcare facilities in the affected area (cities and surrounding counties) should be integrated as an emergency response system. then, the various healthcare facilities can be dichotomized based on their scale and core competencies so as to designate some as intensive care facilities where severely ill patients are quickly assigned for treatment and others as safe facilities where patients with non-virus related illnesses are treated [ ] . fighting a pandemic requires much more than simply testing and treating infected patients. it is essential to secure a sufficient quantity and quality of medical supplies, protection of frontline health professionals, and secure supply chains. it is imperative to develop an effective logistics system for timely delivery of medical supplies (e.g., testing kits, medications, ventilators, additional er facilities, ambulances, helicopters, etc.). the healthcare delivery system is bound to collapse if frontline healthcare providers are infected because of insufficient or ineffective personal protective equipment (ppe) such as face shields, masks, and body covers (for head, hands, shoes, and body). in addition, stable and emergency supply chains are necessary to ensure timely supply of all medical and other supplies in order to provide urgent care to the patients on an on-demand basis in the face of the pandemic crisis [ ] . the spread of a pandemic is not even throughout a country or region. while a national pandemic management center is necessary (e.g., kcdc) to develop nation-wide guidelines and strategies, each region of the country has its own unique patterns of virus infection. thus, each local area government or virus control center should be allowed to establish its own strategies to control the spread of the pandemic. as the virus spreads throughout the community at a rapid pace, the need for mature civic consciousness usually grows proportionately. the current physical distancing campaign is a good example. many countries incurred enormous damage due to citizens not abiding to recommended guidelines to prevent the spread of the pandemic (e.g., social distancing, shelter-in-place, personal hygiene, etc.), awakening the need for social co-consciousness and citizen engagement [ ] . therefore, policymakers of the central government should develop definite policies regarding the devolution of control and direction, which are required of all citizens during the critical phase of a pandemic. the covid- pandemic has brought a total upheaval to the way people live, businesses operate, and governments function. the pandemic has infected more than million people, brought profound sadness to people who lost their loved ones ( , deaths as of september ), and hundreds of millions lost their jobs around the world in a matter of several months. we must learn from our experience of failure, and some successes, so that we can be better prepared to prevent and manage future pandemics. there are several lessons that have now been learned and identified as important elements for managing a pandemic from the covid- experience in korea. at the time of the mers outbreak, the ministry of public safety and security of korea sent out tips to the entire population on how to prevent the virus via an emergency text message. however, this only occurred during the early days of the outbreak, and the government's crisis management system-which should have directed efforts to manage the epidemic-failed to function properly [ ] . consequently, despite having a response system for infectious diseases, the government failed to effectively execute early responses and was criticized for aggravating the damage caused by mers. this inefficacy of early responses resulted in human casualties, public anxiety, and substantial economic damage, all of which revealed the weakness of the government's infection crisis management system [ ] . this failure not only made the korean government recognize the vulnerability of the national epidemic prevention system but also provided an opportunity to learn from the failure [ ] . leadership was recognized as a key contributor to the successful containment of the sars outbreak in korea in . previous studies show that leadership has played a significant role in the effective implementation of proactive measures and facilitation of inter-agency communication in the face of an epidemic [ ] . more specifically, during the current pandemic outbreak, the national crisis management capacity which was strengthened due to the lessons learned from mers helped execute necessary response steps at the critical early stage of the pandemic spread. an emergency leadership team should be established with experts in the relevant fields to develop specific strategies for prevention, response measures, and medical treatment procedures to contain the pandemic. the international media have been reporting korean strategies and practices for controlling covid- as a model [ , ] . most korean provincial governments have been effectively containing the spread of the pandemic without shutting down business operations such as restaurants, coffee shops, retail stores, and even golf courses [ , ] . particularly, the international media praised korea's testing capacity with its innovative drive-through and walk-through stations, rapid processing for results (less than min), and the korean government's information management that did not require a lockdown enforcement like wuhan, china. the new york times [ ] reported that, if south korea succeeds in containing the infection as it has, it will set an example for the world to follow. johnson et al. [ ] also noted that korea's advanced diagnostic capability was proven to be the enabler of its massive testing of more than , a day, while the u.s. was testing a mere persons (reported on february ). moreover, health korea news [ ] reported that the mortality rate of covid- patients was only . % among , infected patients during the early stage of covid- spread. it is evident that the korean government's quick response capacity, information disclosure transparency, and implementation of innovative models to protect patients and healthcare providers were the key factors for early success in containing the pandemic. korea had a bitter experience with mers which helped the government to learn from failures and then establish a proven infrastructure to handle the spread of pandemics. a set of best practices, what is now known as "the k-response model," is based on standardized proven systems that can be applied by all healthcare providers, including testing procedures, contact tracing, isolation by self-quarantine, hospitalization, treatment procedures of severely ill patients, and release after being cured. the control tower in central government and in each local government should proclaim a standardized preventive system (e.g., closing all large audience events such as sports, theaters, shopping centers or educational institutions; limiting the number of people in any group gathering to or less, with social distancing of feet or more; the stay-at-home policy; closing all business operations for - weeks, including all personal services such as hair salons, massage parlors, physical therapy centers, dental offices, etc.) [ ] . the operating systems and strategies that the korean government implemented to contain covid- have proven to be effective. the ebola outbreak in west africa in caused more than , deaths with a % mortality rate. the affected governments' approaches to combatting the virus failed to foster trust among the citizens, causing fear, and inaccurate information led to a considerable amount of time spent on tracing the actual movements of those infected [ ] . a previous study analyzed the outbreak of novel infectious diseases since , focusing on global pandemic management systems [ ] . this study stressed the importance of transnational monitoring and information sharing about the spread of diseases (e.g., disease symptoms and infected areas). another study investigated the outbreak of sars and pinpointed the chinese government's failure to provide effective early response to the pandemic, either concealing or underreporting, as the reason for the global spread of the disease [ ] . the korean government, in response to the current covid- pandemic, has been reporting the number of confirmed cases, the number of deaths, and the actual movements of confirmed patients in real-time. such government efforts for transparency and urgency regarding the pandemic have gained the public's attention regarding the risk involved. such government efforts also gained the trust of citizens and helped people comply with issued guidelines. the government also announced disinfection measures and schedules for locations where confirmed patients made contact with others on a daily basis. this information indirectly advised the general public not to visit those hot spots. in addition, local governments sent out text messages to all citizens upon confirmation of a new infection case in their region and other helpful safety tips about the virus. such real-time information sharing about the pandemic has been possible because of the advanced mobile technology infrastructure and the public's high mobile device usage in korea. as covid- began to spread throughout the country in february , various apps were developed rapidly by young entrepreneurs (e.g., apps showing confirmed patients' locations, the closest place where masks and gloves can be purchased, assistance tips for self-quarantine, etc.). currently, several european countries (e.g., uk and italy) are also attempting to utilize a gps tracking system to locate confirmed patients and to inform disinfection and prevention activity areas using smartphone apps. a team of medical researchers at oxford university in england published a report suggesting that communicable diseases can be controlled effectively if many utilize digital contact tracing [ ] . based on the current covid- situation in korea, while the government's response capacity is crucial to prevent the disease from spreading, mature civic consciousness is essential to ensure social compliance with the imposed measures. in korea, people did not engage in panic buying during the early days of the pandemic outbreak. for example, when there was a shortage of masks, instead of the profiteering behavior of some hoarders, many people began to donate some of their daily allotted masks to the community for those in need. mass media also encouraged beneficence through public emotions showing a strong spirit of community and unity. people recorded their daily lives in sns, including health status and places visited, to help prevent the infection from spreading to others around them. some people even traveled only on foot to prevent spreading the disease in the community. furthermore, people complied with the five-day rotating purchase system for masks, which was instituted by the government to ensure a fair distribution to everyone in the face of mask shortages. the global media has praised koreans for their voluntary civic engagement and compliance with government guidelines to contain covid- . the washington post [ ] reported that korean citizens canceled major events and most religious services were held online at the outset of the pandemic breakout. daegu, the epicenter of a massive spread of the virus, was able to manage the situation without a lockdown, as people in other parts of the country voluntarily refrained from visiting the city. moreover, the bbc news [ ] stated that south korea was able to manage the spread of covid- without implementing a complete lockdown or strict measures against people's movement. koreans voluntarily wore masks everywhere outside of their homes and were tested for covid- , demonstrating mature community and civic consciousness. responding together and responsibly to the threat of covid- have now become a battle cry for koreans [ ] . contrastingly, there were cases where civic duty was not practiced. there were incidents where people lied about their addresses, pretending to be from an area of mass infection, to receive priority care. there were also cases where people under the required self-quarantine violated the isolation guidelines and roamed around the community restaurants and coffee shops, thus spreading the infection [ ] . there was a major relapse of the virus infection after two weeks of almost no daily infection had been reported in korea. during april- may , over young party goes visited several night clubs in seoul during the social distancing enforcement period. these clubs are known for their loud music, dancing, and drinking in a rather confined space. these clubs often restrict entry only to young people, enforced by a reverse carding system (usually only under years of age). among those who visited the clubs, more than infected people were identified by june . however, there was a social stigma issue (regarding the sexual orientation of many regular customers of the clubs) involved which made contact tracing difficult for those who visited the clubs. it was reported that many club goers falsified their names or addresses (e.g., cell phone numbers). to suppress the spread of a dangerous pandemic, a spirit of unity and shared purpose is required. korean people realized the potentially devastating chain of infection that could sweep through their communities and the country as a result of the misguided actions of a single person. in addition to the government's control measures, the public's strict adherence to government guidelines and voluntary participation in implementing certain rules (e.g., mask rationing) based on a sense of community have played a major role in suppressing the spread of covid- [ , [ ] [ ] [ ] . in response to the covid- pandemic, physical distancing has been encouraged based on the recommendation of the who [ , , ] . as people refrain from engaging in outside activities, many businesses (e.g., restaurants) start to experience financial difficulties. the drive-through covid- screening model has been applied to other businesses, and a new drive-through shopping model emerged. for example, south korea's large seafood markets are utilizing their parking lots to provide drive-through services, where customers can order sushi meals from their cars as they approach the market and vendors fulfill the order immediately. department stores are delivering pre-ordered products to customers at the valet parking service lot. in addition, services such as drive-through book-lending and agricultural product sales have flourished [ ] . most of package and food delivery services have transitioned from personal service to the "untact" method that minimizes direct human-to-human contacts. classes and lectures in elementary, middle, and high schools and colleges have transitioned to online platforms. video conferences and home-offices have also become the common method of running operations. automobile repair services now provide a "special pick-up and delivery" option to ensure that their services are untact, helping those customers who have hesitated to visit a service center due to covid- . diebner et al. [ ] pp. - stated that digital delivery has become a necessity for "most customers who are confined at home" and "that app downloads and new sign-ups have grown between - %" during the covid- pandemic. as covid- has been reported to infect people via contact with infected people's droplets [ , ] , untact services utilizing innovative technology applications have flourished and are expected to expand continuously. when a pandemic outbreak occurs, identifying the source of infection and suppressing its spread are the most important steps. amidst the covid- crisis, healthcare institutions are like battlefield military units that are fighting an enemy with necessary weapons, albeit in the form of much-needed medical supplies. in response to the pandemic emergency, many organizations have shifted to remote-working to ensure operational continuity and employee safety. however, many business firms that cannot operate remotely (e.g., manufacturing plants, construction sites, sports events, etc.) had to completely shut down business. enterprises are scrambling to make fast adjustments to their disrupted supply chains [ ] . educational institutions were ordered to shift the teaching mode from the classroom to the online educational environment. these are "new normal" in the covid- crisis [ ] . this study reviewed the cases of innovative responses, as well as failures, to the explosive spread of covid- in korea since the first confirmed case on february . based on the review of these cases, we summarized the lessons learned from korea's covid- experiences. the knowledge gained from the struggle against the virus provides new insights about required strategies for managing the pandemic. our study suggests that the healthcare policy makers and related organizations must be transparent in demonstrating to the citizens that emergency healthcare services are being provided on an equitable basis throughout the country. based on these experiences, policy makers should develop strategies that include the government's response capacity, information sharing, mature sense of unity and community, and application of advanced technologies in the time of urgency. the results of this study provide several theoretical and practical implications. first, the covid- outbreak taught the world that massive and rapid testing is essential to identify infected patients and infection clusters to prevent the pandemic from spreading. the identified patients can be either treated promptly (severely ill cases) or quarantined. second, we showed that the spread of an epidemic can be effectively suppressed only through well prepared public health infrastructure; coordinated and exhaustive efforts of the central/local governments, disinfection and prevention authorities and healthcare providers; and the spirit of unity and community of citizens (e.g., adhering to the government guidelines regarding social distancing, stay-at-home, avoiding large gatherings of people, etc.). third, innovative operational strategies should be established based on past experiences (e.g., the mers failures) in order to ensure success in managing the pandemic. in korea, the primary cause of the early spread of covid- was related to a mass gathering within a confined indoor space (e.g., worship services of religious organizations). the koreans learned quickly about the perils of such undisciplined activities and their consequences in terms of the uncontrollable spread of the pandemic [ ] . moreover, the korean government enforced an aggressive covid- screening program to promptly identify and trace contacts made by infected people and treat seriously ill patients while strictly isolating them from the general population. furthermore, these measures cannot be implemented successfully without active cooperation of the citizens. from the outset, the government asked all citizens to refrain from participating in group gatherings or events, both indoors and outdoors, that could pose a threat to others, and strongly encouraged the practice of physical distancing. moreover, the government also placed a legal liability on agents who proceeded with non-recommended events. a mature civic consciousness is needed to voluntarily comply with government guidelines. a crisis is said to be a combination of danger and opportunity. president john f. kennedy analyzed the word "crisis" in chinese and pointed out that the word consists of two characters, one representing danger and the other representing opportunity [ ] . winston churchill's famous quote was also in the same vein, "a pessimist sees the difficulty in every opportunity; an optimist sees the opportunity in every difficulty" [ ] . these quotes serve as reminders that every crisis encompasses opportunities for creating a better future. the koreans have learned this lesson from their experience with the covid- pandemic. therefore, we might view the crisis from the perspective of "crisis = danger + opportunity" based on response efforts. the covid- crisis shows how each country organizes the delicate balance between achieving efficient results (avoiding high rate of mortality) and intrusion on personal privacy and economic security. this means that there is a trade-off relationship between two important factors in life: health and economy. for example, much of the offline education system will most likely transition to the online environment, causing a trade-off relationship between students' face-to-face education needs and a safer/cheaper mode of delivery. the measures undertaken by the korean government to avoid repeating the same mistakes incurred during the mers outbreak (i.e., re-organization of the kcdc, the healthcare delivery system, and disinfection and prevention systems, as well as the expansion of healthcare facilities) were shown to have a significant impact on the effectiveness of the implemented response strategies in the face of the covid- pandemic. therefore, developing an effective public healthcare infrastructure and new operational strategies based on past experiences could turn a crisis into an opportunity for preventing such virus infections [ ] . we are confident that the fear of covid- that is currently sweeping the globe will soon be overcome and hope that this costly experience will serve the world well in preparing for the next pandemic. this study has reviewed the response strategies of korea in dealing with the covid- pandemic outbreak. korea's pandemic management approach, known as the k-response strategy, has been effective in containing covid- as the country learned a bitter lesson from the pains of mers and reinvented its public health infrastructure as a preparation for the next pandemic. we do hope that the operational strategies of korea discussed in this study would help prepare effective crisis management systems in other nations. this study, however, has some limitations. first, the scope and experience of the covid- cases discussed in this study are specific to korea. thus, the results of the study have limited generalizability to other situations or countries with different cultures and social systems. future research that includes various cases from around the world would further reinforce the findings of our study. second, the covid- pandemic is still causing havoc around the world and its end is difficult to predict. furthermore, the world will surely encounter new coronavirus pandemics in the future. the results of our study are limited to the discussion of covid- that we are battling today. thus, new pandemics will require different research approaches, although the lessons learned from the current pandemic will certainly be of much value. covid- and commercial pharma: navigating an uneven recovery the path to the next normal who declares covid- a pandemic sustainable covid- mitigation: wuhan lockdowns, health inequities, and patient evacuation covid- pandemic: what can the west learn from the east world health organization (who). coronavirus united nations office for the coordination of humanitarian affairs) reimagining medtech for a covid- world a study on improvement of national disaster management system through the mers outbreak in korea changes of global infectious disease governance in s: rise of global health security and transformation of infectious disease control system in south korea the covid- crisis" as an opportunity for introspection: a multi-level rreflection on values, needs, trust and leadership in the future testing on the move south korea's rapid response to the covid- pandemic. transportation research interdisciplinary perspectives korea's foreign minister explains how the country contained covid- feeling connected after experiencing digital nature: a survey study untact": a new customer service strategy in the digital age hospitals consider universal do-not-resuscitate orders for coronavirus patients. the washington post developing an environmental health sciences covid- research agenda: results from the niehs disaster research response (dr ) work group's modified delphi method who. infectious diseases. . available online what is a pandemic? emerging infections: microbial threats to health in the united states epidemic alert and response governance, and global public health in the wake of sars maintaining places of social inclusion: ebola and the emergency department a theory of cognitive dissonance psychological contracts in organizations: understanding written and unwritten agreements inequality in social exchange a model of customer satisfaction with service encounters involving failure and rrecovery customer evaluations of service complaint experiences: implications for relationship marketing a study on the national crisis management system in the case of the new infection diseases: focusing on school infection prevention activities available online the korea economic daily. daegu, the initial response was fast. it was different from south korea's health minister on how his country is beating coronavirus without a lockdown daegu operated a public-private partnership network drive-through screening center for covid- : a safe and efficient screening system against massive community outbreak corona 'drive through' topic covid- pandemic data sources covid- pandemic in mainland china covid- pandemic in italy. available online covid- pandemic in spain. available online covid- pandemic in south korea covid- pandemic in the united states special report: how korea trounced u.s. in race to test people for coronavirus. reuter covid- pandemic data sources healthcare service justice and community engagement in crisis situation: focusing on failure cases in response to covid- emergency department resilience to disaster-level overcrowding: a component resilience framework for analysis and predictive modeling south korea's drive-through testing for coronavirus is fast-and free. national public radio needs to do today to follow south korea's model for fighting coronavirus time community treatment center. weekly dong-a civic capital and social distancing: evidence from italians' response to covid- . vox cepr policy portal uncertainties of international standards in the mers cov outbreak in korea: multiplicity of uncertainties factors influencing the response to infectious diseases: focusing on the case of sars and mers in south korea south korea controlled its coronavirus outbreak in just days. here are the highlights from its -page playbook for flattening the curve worldwide confirmed coronavirus cases top million a faulty cdc coronavirus test delays monitoring of disease's spread. the philadelphia inquirer korean government's response to corona addressing contact tracing challenges-critical to halting ebola virus disease transmission implications of sars epidemic for china's public health infrastructure and political system quantifying sars-cov- transmission suggests epidemic control with digital contact tracing south korea shows that democracies can succeed against the coronavirus coronavirus: what could the west learn from asia? lessons from south korea's covid- outbreak: the good, bad, and ugly. the diplomat effectiveness of workplace social distancing measures in reducing influenza transmission drive-thrus booming in korean society amid virus scare adapting customer experience in the time of coronavirus kennedy presidential residential; library and museum author contributions: all authors have conceptualization, writing, and read of the manuscript. all authors have read and agreed to the published version of the manuscript.funding: this research received no external funding. the authors declare no conflict of interest. key: cord- -l icp w authors: koonin, lisa m.; pillai, satish; kahn, emily b.; moulia, danielle; patel, anita title: strategies to inform allocation of stockpiled ventilators to healthcare facilities during a pandemic date: - - journal: health secur doi: . /hs. . sha: doc_id: cord_uid: l icp w during a severe pandemic, especially one causing respiratory illness, many people may require mechanical ventilation. depending on the extent of the outbreak, there may be insufficient capacity to provide ventilator support to all of those in need. as part of a larger conceptual framework for determining need for and allocation of ventilators during a public health emergency, this article focuses on the strategies to assist state and local planners to allocate stockpiled ventilators to healthcare facilities during a pandemic, accounting for critical factors in facilities' ability to make use of additional ventilators. these strategies include actions both in the pre-pandemic and intra-pandemic stages. as a part of pandemic preparedness, public health officials should identify and query healthcare facilities in their jurisdiction that currently care for critically ill patients on mechanical ventilation to determine existing inventory of these devices and facilities' ability to absorb additional ventilators. facilities must have sufficient staff, space, equipment, and supplies to utilize allocated ventilators adequately. at the time of an event, jurisdictions will need to verify and update information on facilities' capacity prior to making allocation decisions. allocation of scarce life-saving resources during a pandemic should consider ethical principles to inform state and local plans for allocation of ventilators. in addition to ethical principles, decisions should be informed by assessment of need, determination of facilities' ability to use additional ventilators, and facilities' capacity to ensure access to ventilators for vulnerable populations (eg, rural, inner city, and uninsured and underinsured individuals) or high-risk populations that may be more susceptible to illness. d uring a pandemic caused by respiratory pathogens, such as influenza or sars-cov- (the virus that causes coronavirus disease , or covid- ) , large numbers of people in the united states may require critical care that includes mechanical ventilation, resulting in a surge on hospitals and increased demand for ventilation equipment. although the current supply of approximately , * ventilators in us acute-care hospitals would likely be adequate to support patient care needs during a pandemic with mild to moderate severity (similar to the h n pandemic), a pandemic with greater severity would probably result in many more patients requiring ventilatory support. in this severe scenario, there will likely be insufficient capacity to ventilate all those who need this treatment. assuming that ventilators would be effective in reducing morbidity and mortality during a future severe pandemic, researchers estimate that approximately , to , additional ventilators will be needed. to support this need, scientists estimate that with robust planning, if us hospitals could increase space and the number of trained and qualified staff to care for ventilated patients during a pandemic, approximately , to , additional patients could be ventilated at the peak of a pandemic. another study of more than , hospitals found a significant increase in the number of adult intensive care beds between and , but this growth was seen mostly in large urban teaching facilities, rather than in rural areas or smaller, less-resourced hospitals, which often serve residents with little or no other access to care. in addition, there has been an increase in the number of rural hospitals closing each year. during a public health emergency, federal, state, or local stockpiled ventilators should be deployed in a way that optimizes the effectiveness, efficiency, and equity of this scarce resource. for over a decade, policymakers and researchers have explored the pros and cons of stockpiling mechanical ventilators in hospitals and other locations. , currently, caches of ventilators are held in reserve in healthcare facilities (largely acute-care hospitals) and in public health stockpiles at the federal, state, and local levels. , in addition to having ventilator equipment and ancillary supplies, it is critical for healthcare facilities to have sufficient staff and space to care for as many patients as possible who require ventilation. , legal experts have advised that hospitals, public health entities, and clinicians have an obligation to develop comprehensive, vetted plans for mass casualty incidents involving large numbers of critically ill patients. considering these critical factors (ie, sufficient staff, supplies, and space), jurisdictions should plan for how they would allocate stockpiled ventilators to their relevant healthcare facilities. researchers have proposed that allocation decisions for a limited supply of stockpiled ventilators to healthcare facilities should not use a pro-rata or ''first come-first served'' model, but rather they should base allocation on a detailed assessment of facilities' capacity to absorb and use additional ventilators and to ''ensure the efficient, effective, and ethical distribution of stockpiled ventilators'' to facilities that can best use them during an emergency. during a public health emergency, the expectation is for facilities to first use ventilators and ancillary supplies that they have on site (or stored elsewhere); then, if needed, facilities may request support from state or local health departments. if state and local health departments are unable to meet the demand, additional requests for federal stockpiles may be made. if additional ventilators are available from state or federal resources, health departments would be responsible for allocation and deployment to the facilities that can demonstrate they can effectively use them in their jurisdiction. in , as part of a pandemic influenza readiness assessment exercise, the centers for disease control and prevention (cdc) assessed all public health emergency preparedness jurisdictions (n = ) to ask about their readiness to respond to a pandemic. within the medical countermeasures module, jurisdictions were asked to identify the key considerations they would use to determine ventilator allocation to hospitals during a pandemic. of the jurisdictions queried, ( %) responded. several key findings from the response included that ( ) almost two-thirds ( %) of the jurisdictions had conducted a hospital-based assessment between and to determine their mechanical ventilation capabilities, and ( ) ( %) jurisdictions (in aggregate covering . % of the us population at the time) had not determined when or how they would train healthcare systems to operate ventilators from stockpiles. { in addition, jurisdictions were asked about the key parameters that they would consider when evaluating to which facility they would allocate stockpiled ventilators ( figure ). the most frequent parameter cited was the availability of trained and qualified staff, although this item as well as the number of icu beds and availability of sufficient equipment and space were all cited by more than % of jurisdictions. patients who need mechanical ventilation will be critically ill and will require trained clinicians to provide comprehensive intensive care. the ability to absorb additional ventilators will depend on having sufficient trained and qualified staff to operate ventilators and care for patients, as well as adequate bed space, and availability of essential equipment and supplies needed to care for critically ill *this estimate was produced in ; more recent estimates are not available. therefore, this number may not accurately reflect the number of full-featured mechanical ventilators currently in us acute-care hospitals. { unpublished data, centers for disease control and prevention. patients (eg, oxygen, suctioning, airway management, monitoring equipment). , as part of a conceptual framework for allocating federally stockpiled ventilators during a large-scale public health emergency, figure illustrates the steps in planning and allocating ventilators during a pandemic emergency. the strategies in this document focus on step e-''states determine allocation to individual hospitals''-and provide information to operationalize these concepts. by applying ethical principles throughout the process of pre-pandemic planning and allocation of ventilators during a pandemic, states can, in an equitable and transparent way, allocate scarce resources. cdc has developed guidance on ethical principles for use of ventilators during a pandemic, which includes as a main principle the ''duty to plan.'' these principles necessitate multiple preparedness efforts, including planning at state, local, and facility levels. a number of articles have been published describing recommended ethical and clinical principles for triaging and allocating ventilators to individual patients. , [ ] [ ] [ ] [ ] in addition to surveillance and epidemiologic data, the same ethical principles relevant to allocating ventilators to individuals during times of scarcity can also inform decisions about how to allocate ventilators to facilities. in a pandemic, if resources are scarce, plans and protocols will need to shift from an individual patient care outcome perspective to a population-based focus and must be grounded in a principled allocation of resources that attempts to ensure equity and fairness. specific ethical principles can inform a jurisdiction's plans for allocation of ventilators. these include: duty to plan: as previously mentioned, public health officials have a duty to prepare for allocating stockpiled ventilators in the face of scarcity. however, it may not be possible to develop a plan that will meet all patients' needs in future scenarios. transparency: state and local planners should share planning guidelines with hospitals and other facilities, partners, and stakeholders and seek public comment and incorporate public values into planning efforts. public health officials should prepare to explain to the public the rationale and purpose of ventilator allocation decisions. distributive justice: during an emergency when there are insufficient services and/or equipment to meet the needs of all, efforts should be focused on allocation to facilities that can save the greatest number of lives. balancing distributive fairness and efficiency is extremely difficult even with advance planning. , , duty to care: once a provider-patient relationship is formed, providers have the obligation to care for their patients, and the care they provide should be aligned with what a ''reasonable physician'' would provide under the circumstances during an emergency. if ventilators are insufficient to meet the needs of all those who would benefit from them, then plans should include other means of providing curative and palliative care for these patients. healthcare facilities in a community that collaborate using a ''systems approach'' to plan for a pandemic may be able to develop community-level plans that designate specific facilities for patient care during a pandemic to improve outcomes. duty to steward resources: allocation consideration should include sending limited resources, like venti-lators, to facilities that can make the best use of the equipment. equity: to achieve fairness, the same allocation framework should be used to allocate stockpiled ventilators to all facilities in a jurisdiction, taking into consideration facilities' needs and available supply. the concepts of equity and consideration for vulnerable populations should be included in ventilator allocation plans. as a part of pandemic preparedness, public health officials should identify and query healthcare facilities in their jurisdiction that care for critically ill patients on mechanical ventilation to learn about their current inventory of these devices and their ability to absorb additional ventilators. information about the types of patient populations served (including facilities' ability to care for critically ill neonatal and pediatric patients and adults including pregnant patients) should be collected. healthcare coalitions that work with these facilities may be able to assist public health partners in conducting these assessments and coordinating system-level collaboration in a jurisdiction. to familiarize facilities and their staff, pre-pandemic training and discussions about use of specific models of stockpiled ventilators and ventilator allocation scenarios can be conducted. draft plans can be developed to serve as a starting point when need arises. planning should incorporate stakeholder and public input based on scenarios in which there are insufficient ventilators, staff, and ancillary supplies during a time of critical need during a pandemic. the principles of crisis standards of care should be incorporated in planning and decision making. allocation decisions must be made carefully because reallocation will be difficult once ventilators have been distributed. one modeling study of ventilator stockpiling dynamics in a large state found that the peak of the pandemic would likely affect different areas of the state almost simultaneously, making redistribution of ventilators challenging. at the time of an event, verifying information previously gathered about facilities' needs and capacity to absorb additional ventilators will be critical. allocation of stockpiled ventilators may include acute care hospitals or other settings such as long-term care facilities. these allocation decisions will likely need input from state and local leaders and legal and ethical experts, as well as engaged and informed community stakeholders. in summary, decisions on how to strategic allocation of stockpiled ventilators in a pandemic allocate ventilators during a pandemic response should be informed by the following factors (see figure ): assessment of need: during a response, jurisdictions must assess demand and need for ventilators based on available surveillance data (eg, the number of patients with respiratory failure resulting from infection who currently need and will benefit from mechanical ventilation). assessment should factor in the number of ventilators currently available for use by each facility, including any additional ventilators to which the facility may have access (eg, cached equipment, ventilator surge contracts, sharing agreements). determination of ability to absorb additional ventilators: jurisdictions must confirm and assess any available information on each facility's ability to absorb and use additional ventilators to care for critically ill patients and quantify the number of additional ventilators each facility can realistically absorb. this estimate should be based on having enough trained and qualified staff, adequate space, and necessary equipment needed for caring for additional patients on mechanical ventilation. ensuring access to ventilators for vulnerable or highrisk populations: this element refers to the geographic location or catchment area served by the facility within the jurisdiction and/or the ability to serve vulnerable and high-risk populations within this area. b consider whether each facility serves as a referral hospital or regional hospital or serves a high-density population area, rural area, or underserved populations. b determine how to distribute a limited supply of ventilators to serve the largest number of people at risk or in need. following ethical principles: use ethical principles to guide the development and implementation of ventilator allocation plans. examples of questions to consider include: b will the allocation plan use scarce resources in a manner to save as many lives as possible? b does the allocation plan apply criteria consistently across all hospitals and facilities? b if ventilators are insufficient to meet the needs of all those who would benefit from them, what are plans for providing care for patients who cannot access them? b how do stakeholder and public input and values factor into decisions? b are allocation decisions transparent? the strategies portrayed in figure are designed to assist planners in preparedness and allocation of ventilators during a pandemic. ideally, planning ahead would provide jurisdictions with a baseline assessment of the ability of healthcare facilities in their jurisdiction to absorb and deploy additional supplies of ventilators. at the time of a pandemic response, the impact of disease (severity of illness, transmission), the effectiveness of mechanical ventilation at preserving life given the specific pandemic pathogen, and the population subgroups most affected who may need mechanical ventilation will all factor into allocation decisions. using ethical principles to assess need, determine ability to absorb additional ventilators, and ensure resources to the most vulnerable populations, state and local public health officials can equitably allocate stockpiled ventilators during a pandemic. having strategies for allocating scarce resources like ventilators in advance may improve decision making, with the understanding that plans will need to adapt to the realities presented during a pandemic response. mechanical ventilators in us acute care hospitals estimates of the demand for mechanical ventilation in the united states during an influenza pandemic assessing the capacity of the us health care system to use additional mechanical ventilators during a large-scale public health emergency hospital-level changes in adult icu bed supply in the united states a conceptual framework for allocation of federally stockpiled ventilators during largescale public health emergencies strategies for providing mechanical ventilation in a mass casualty incident: distribution versus stockpiling stockpiling ventilators for influenza pandemics strategic national stockpile: overview and ventilator assets clinical review: allocating ventilators during large-scale disastersproblems, planning, and process stockpiling ventilators for influenza pandemics legal preparedness: care of the critically ill and injured during pandemics and disasters: chest consensus statement ethics subcommittee of the advisory committee to the director. ethical considerations for decision making regarding allocation of mechanical ventilators during a severe influenza pandemic or other public health emergency ethical considerations: care of the critically ill and injured during pandemics and disasters: chest consensus statement allocation of ventilators in a public health disaster priority setting of icu resources in an influenza pandemic: a qualitative study of the canadian public's perspectives pandemic ventilator rationing and appeals processes who should receive life support during a public health emergency? using ethical principles to improve allocation decisions system-level planning, coordination, and communication: care of the critically ill and injured during pandemics and disasters: chest consensus statement institute of medicine; board on health sciences policy committee on guidance for establishing standards of care for use in disaster situations guidance for establishing crisis standards of care for use in disaster situations: a letter report murray and nadel's textbook of respiratory medicine key: cord- -nu q l authors: iskander, john; strikas, raymond a.; gensheimer, kathleen f.; cox, nancy j.; redd, stephen c. title: pandemic influenza planning, united states, – date: - - journal: emerg infect dis doi: . /eid . sha: doc_id: cord_uid: nu q l during the past century, influenza pandemics occurred. after the emergence of a novel influenza virus of swine origin in , national, state, and local us public health authorities began planning efforts to respond to future pandemics. several events have since stimulated progress in public health emergency planning: the avian influenza a(h n ) outbreak in hong kong, china; the anthrax attacks in the united states; the outbreak of severe acute respiratory syndrome; and the reemergence of influenza a(h n ) virus infection in humans. we outline the evolution of us pandemic planning since the late s, summarize planning accomplishments, and explain their ongoing importance. the public health community’s response to the influenza a(h n )pdm pandemic demonstrated the value of planning and provided insights into improving future plans and response efforts. preparedness planning will enhance the collective, multilevel response to future public health crises. influenza pandemics occur when an animal influenza virus to which humans have no or limited immunity acquires the ability, through genetic reassortment or mutation, to cause sustained human-to-human transmission leading to community-wide outbreaks ( ) . the existence of a pandemic is currently determined by the extent of disease spread, not by the lethality of the disease caused by the novel virus ( ) . during the twentieth century, influenza pandemics occurred in , , and . the pandemic, known as the "spanish flu" pandemic, was unique in that the highest number of deaths was among young, healthy persons. excess mortality in the united states during the pandemic was estimated at , deaths ( ) . the pandemics in and , although associated with death rates greater than those for seasonal influenza epidemics ( ), were far less devastating than the pandemic. before , public health planning for pandemics primarily occurred in response to detection of a novel influenza virus. this reactive mode continued despite the framework outlined in by us surgeon general l.e. burney for responding to the next pandemic. that framework involved recognition of the pandemic (i.e., surveillance), manufacture and distribution of vaccine, and identification of research needs ( ) . large-scale infectious disease response planning may have been hampered by the tacit assumption that the government's public health resources were better directed to other priorities. in january , a novel swine-origin influenza virus emerged among soldiers at fort dix, new jersey ( ); soldier died, and an estimated were infected. the emergence of influenza virus of swine origin at fort dix led to the decision to mount a national immunization program ( ) . the following events occurred subsequent to this decision: congress funded vaccine production and liability indemnification of manufacturers, vaccine was produced, a mass immunization campaign commenced, and . million persons were vaccinated in the united states ( ) . initial fears that the virus would cause a pandemic did not materialize: sustained transmission did not occur outside of fort dix. the vaccination campaign began in october and was halted in december because of initial reports of a rare association between the so-called "swine flu" vaccine and guillain-barré syndrome; the association was later confirmed ( ) . an influential policy review of the "swine flu affair" (i.e., the campaign to immunize the us population against a possible epidemic) identified several critical needs for future planning: ) a more cautious approach to interpreting limited data and communicating risk to the public, ) greater investment in research and preparedness, ) clearer operational responsibilities within the federal government, ) clear communication between planners at all levels of government, ) strengthened local capacity for plan implementation, and ) improved mechanisms for program evaluation ( ) . in november , separate from the fort dix outbreak, a strain of human influenza a(h n ) virus reemerged in the former soviet union, northeastern china, and hong kong, china, even though the virus had not circulated since . this strain primarily affected young persons, and caused mild illness ( ) . the virus was found to be closely related to a a(h n ) strain but dissimilar to the strain, suggesting that this outbreak strain had been preserved since ( ) . the confluence of fears of a possible pandemic in followed by the reemergence of a new strain of circulating seasonal influenza virus in led to focused pandemic planning efforts in the united states. the primary purpose of this article is to describe us pandemic planning during - , just before the onset of the influenza a(h n ) pdm pandemic in april . we believe that understanding the historical and policy context within which the a(h n )pdm pandemic occurred is helpful in assessing the implications of pandemic planning for responses to future pandemics and for ongoing infectious disease preparedness efforts. we conducted searches of the medical literature and key websites (e.g., www.pandemicflu.gov) for peer-reviewed manuscripts and published governmental plans relevant to pandemic planning during - . we also consulted authors' personal files and the internet for records of speeches, national and international conference proceedings, and other unpublished original source documents. in addition to published survey data concerning local and state response planning ( , ), we sought unpublished data from the association of state and territorial health officials, the national association of county and city health officials (naccho), and the council of state and territorial epidemiologists (cste). a historical overview of key milestones in us pandemic planning is provided in the table. in , a federal interagency working group on influenza was formed at the request of the deputy assistant secretary for health in the department of health, education, and welfare, partly in recognition of the need for greater cooperation across government "silos." the interagency group included representatives from the center for disease control (cdc; renamed centers for disease control and prevention in ), the national institutes of health, the food and drug administration (fda), and the department of defense. under cdc leadership, the work group drafted the first us pandemic plan, which was released in and included recommendations for annual influenza immunization of persons at high risk, strengthening of surveillance, expanding research, and establishing a planning and policy mechanism ( ) . the plan was revised in to include a new recommendation to develop means to distribute and use influenza antiviral drugs (r.a. strikas, pers. comm.). even before completion of the pandemic plan, participants of a conference on influenza, held by the secretary of the department of health, education, and welfare, recommended continued federal support for influenza vaccination, particularly to increase vaccination levels of persons at high risk, to improve pandemic preparedness. in addition, cdc implemented a federally funded seasonal influenza immunization program, which purchased . and . million vaccine doses for the - and - influenza seasons, respectively, of which ≈ million and > . million doses, respectively, were administered. initial plans were to purchase - million doses of vaccine. however, budget constraints limited vaccine purchases and ended the program after ( , ) . the next major event leading to further us pandemic planning was legislation creating the national vaccine program office (nvpo), which was given a mandate to coordinate federal vaccine-related activities. at the options for the control of influenza ii meeting held in , a consensus report identified the core components of pandemic preparedness: surveillance, vaccines, antiviral drugs, nonmedical/personal hygiene measures, communications, and enhanced annual seasonal influenza vaccination programs ( ) . in , nvpo formed the federal interagency group on influenza pandemic preparedness and emergency response (grippe). the group, which included nonfederal consultants and representatives from cdc, fda, the national institutes of health, and the department of defense, drafted a pandemic planning framework that was published in ( ) and updated by federal staff in ( ) . the grippe-initiated planning documents emphasized the need for enhancements to influenza surveillance, vaccine production and distribution, antiviral drugs, influenza research, and emergency preparedness. perhaps the most consequential outcome of grippe was the creation of a core group of public health experts dedicated to pandemic planning. global events helped accelerate interest in pandemic planning. in , hong kong recorded the first outbreak of avian influenza a(h n ) virus infections in humans. virus was transmitted from infected chickens directly to humans, and of persons with confirmed infection died. in late , > . million chickens were culled throughout hong kong as part of successful efforts to stem the outbreak ( ) . this event, combined with the reemergence of a(h n ) virus, led to concerns that the next pandemic would be caused by spread of a(h n ) virus through asia into africa and europe. in the united states, despite the crucial role of state and local authorities in implementing pandemic plans, a cste survey indicated that < % of state health departments perceived the need for a state-specific plan ( ) . through a cooperative agreement between cdc and cste, a state and local planning effort was begun in the fall of . the state project steering committee included the grippe co-chairs and representatives from cdc, nvpo, cste, and the association of public health laboratories. a meeting of > state and local health officials convened in september in atlanta and identified "pillars" deemed most critical for state and local pandemic preparedness efforts: ) surveillance, ) vaccine delivery, ) communication and coordination, and ) emergency response. from this meeting and subsequent subgroup meetings dedicated to the pillar areas, critical elements of draft state and local guidelines were developed by january . four states (connecticut, missouri, new mexico, and new york) and local area (east windsor township, new jersey) were selected by the state project steering committee-primarily on the basis of the identification of a key project leader within each jurisdiction-and funded to pilot test the draft guidelines; additional state, maine, volunteered to test the draft guidelines without cste support. these states conducted pilot tests during february and march and submitted results to cste. findings were discussed on april - , , at a meeting in atlanta. the major outcomes from pilot testing were the following recommendations: ) a fifth pillar area, guidance for use of antiviral drugs, should be added to the guide; ) the format of the guidelines should be more in concert with the national plan ( ) ; and ) all states should receive the revised guidelines to enable development of state-specific plans (r.a. strikas, pers. comm.). these issues were discussed at the association of state and territorial health officials/nac-cho annual meeting in september and incorporated into the state and local pandemic influenza planning guidelines (r.a. strikas, pers. comm.), which were then further revised. california, maryland, minnesota, and south carolina were funded through cste to develop state plans and submitted their model plans in april . a national pandemic influenza steering committee was subsequently formed; it was comprised of immunization ( ) . throughout this process, all states received the same nominal level of funding support, which was typically used to convene a statewide stakeholders meeting. elements critical to the planning process included technical support provided by the national steering committee and the identification of a key public health professional within each state who assumed responsibility for leading and coordinating planning efforts. arkansas, arizona, and oregon concurrently developed plans of their own accord; west virginia, tennessee ( ), and pennsylvania ( ) had already developed plans. ultimately, funds were sought for every state to develop a plan. at this early stage in the planning process, the importance of disseminating information to the broader public health community was recognized. on february , , and july , , cdc presented satellite videoconferences on influenza pandemic preparedness for states and local areas, which were viewed by > , and ≈ , participants, respectively. state and local public health staff engaged in development of pandemic plans participated in the broadcasts. at a meeting of state and local planners sponsored by cste and cdc in atlanta on september - , , detailed discussions were held regarding ) a scenario of how an influenza pandemic might affect states in ; ) how states should enhance surveillance; ) how vaccination priorities should be determined, and ) other national and federal pandemic planning issues, such as infection control, patient triage, and antiviral drug usage (r.a. strikas, pers. comm.). after the september , , terrorist attacks on the united states, public health preparedness emerged as a priority of the federal government. in , bioterrorism emergency funding support was provided to all states to assist in the nation's response to the anthrax attacks. the reemergence of avian influenza a(h n ) infections in humans fundamentally altered the scale of pandemic preparedness. as the a(h n ) virus spread to more countries in east and southeast asia during - , concern grew among senior policymakers and public health experts that the world was on the verge of an influenza pandemic. a(h n ) infection in humans primarily resulted from exposure to ill poultry and had a case-fatality rate of ≈ %. substantial federal funding was provided for federal-level planning, procurement of countermeasures (e.g., vaccines and antiviral drugs), development of countermeasures, and state and local pandemic preparedness efforts ( ) . state health departments eventually received $ million to prepare for an influenza pandemic. additional high-level policy engagement by the us federal government included the national strategy for pandemic influenza, which was announced in november ( ) , and the white house's national implementation plan, which was published in may and addressed federal planning and response strategies: international transport and border control; protection of human and animal health; and security and continuity of operations issues ( ) . in , the biomedical advanced research and development authority (barda) was established within the department of health and human services in response to the growing need for a centralized effort to coordinate research, development, and procurement of countermeasures against potential natural or intentional public health emergencies ( ). barda preparations for a possible a(h n ) pandemic included development of a stockpile of influenza vaccines produced by using strains circulating in poultry and wild birds in asia ( ). in addition, the us government began to purchase influenza antiviral medications for the strategic national stockpile sufficient to treat % of the us population. additional investments were initiated to procure ventilators and personal protective equipment, such as respirators. the us government also initiated an advanced development agenda for vaccines, therapeutics, and diagnostics. barda co-invested with industry to modernize vaccine production methods, with the -year aim of creating the capacity to produce sufficient vaccine to protect the entire us population within months of the onset of an influenza pandemic ( ) . the us government invested in modernizing diagnostic technologies for public health laboratories. in september , fda approved specific pcr tests for a panel of influenza diagnostics to be used in cdc reference laboratories in the united states and department of defense laboratories around the world. this diagnostic test panel will detect and identify a(h n ) infections and distinguish novel influenza virus infection from infection with seasonal a, b, and a(h ) and a(h ) influenza viruses. barda and cdc awarded contracts in november for development and evaluation of clinical point-of-care rapid diagnostics to identify seasonal influenza viruses and a(h n ) viruses ( ) . beginning with its first published pandemic plan in ( ) , the world health organization globally promoted pandemic planning among member states, with continued planning efforts thereafter ( ) . the international partnership on avian and pandemic influenza was formed to coordinate support for developing countries' efforts to control the spread of a(h n ) virus and to prepare for an influenza pandemic. this international body convened a series of meetings beginning in january ; these efforts generated hundreds of millions of dollars in pledges to support global pandemic preparedness and promoted a level of visibility and readiness that would not otherwise have been possible. in addition to direct financial assistance, the us government provided technical assistance to help countries develop capacities for rapid response, laboratory diagnosis, and surveillance. the federal government recognized that the foundation for domestic pandemic response rests with state and local governments; thus, the department of health and human services strategy and the white house strategy and implementation plan called for major efforts in planning, exercising, and refining state and local preparedness. the pandemic and all-hazards preparedness act called for a review of comprehensive state pandemic preparedness plans. the federal government reviewed and scored the plans and released the results to the public in january ( ); preparedness levels varied across states and across the domains that were scored. in , as part of its local health profile survey, naccho queried local health departments about emergency preparedness and planning activities they had undertaken during the past year ( ): % of , responding health departments said they had developed or updated pandemic influenza preparedness plans, and % said they had participated in tabletop drills or exercises. in addition, % had updated their written response plan on the basis of a postexercise after-action report, % had participated in a functional drill, and % had participated in a full-scale drill or exercise. a total of % of local health departments had reviewed existing state legal authorities for isolation and quarantine, and % had assessed the emergency preparedness competencies of staff. only % of local health departments did none of the above. the pandemic planning pillars-surveillance, vaccine and antiviral drug delivery, emergency response, and communication-are a solid foundation for pandemic preparation. although state pandemic plans may have different structures, reliance on these pillars has remained more or less constant across jurisdictions and over time. the major contemporary developments in these core areas are summarized below. surveillance, including rapid detection of human infection with novel influenza viruses, remains a cornerstone of pandemic response. this need has been recognized since the early stage of state-and local-based planning ( ) . improvements in diagnostic technology have enabled confirmation of infection with novel influenza viruses within hours rather than weeks. human infection with a novel influenza virus became a nationally notifiable disease in , and since then, an increased number of infections have been detected ( ). virologic surveillance is also used to determine which seasonal viruses are circulating and thus provides information for seasonal vaccine strain selection. systems to measure the effect of seasonal influenza (i.e., pediatric deaths, hospitalizations, and syndromic surveillance) have also been enhanced. these systems have been further adapted to measure the effect of pandemic influenza ( ) . the need to maintain ongoing surveillance for novel influenza viruses (e.g., viruses of swine or avian origin) in humans and animals exemplifies the one health concept ( ) . in recognition that vaccine might be in short supply during the early phase of a pandemic, federal vaccine allocation guidelines were published in ( ) . these guidelines laid the groundwork for the pandemic vaccine priority-group recommendations put forth during the a(h n )pdm pandemic ( ) . antiviral medications are critical to a pandemic response, particularly in the interval between recognition of the pandemic and the availability of vaccine. plans for using these countermeasures have stressed the need for early treatment of affected persons and assumed that the drugs would be scarce. it was recognized at the cste meeting that close coordination between emergency response staff and public health authorities is needed to develop and implement effective state and local influenza response plans. this recognition has strengthened over time. although, states were initially not allowed to use bioterrorism funds awarded in to support pandemic planning, key emergency management concepts, including the all-hazards approach and unified incident command, were eventually integrated into planning efforts ( ) . communication, more than ever, is a fundamental component of any response effort. timely, transparent, and proactive communication is critical, particularly in the early stages of a confirmed or suspected outbreak, when factual information is limited and the public demand for information and guidance is high. continuous media coverage and the evolving role of social media ( ) must be used to enhance communication to and from the public, particularly concerning new or evolving recommendations for disease control. pandemic planning since had a direct and obvious effect on the response to the influenza a(h n ) pdm pandemic; however, pandemic preparedness has been a feature of public health since the late s. coordinated state and federal planning processes have been a consistent feature of that planning. the pillars of pandemic planning response have remained conceptually constant: surveillance; vaccination and delivery of other medical countermeasures; emergency response coordination; and communications. although the a(h n )pdm pandemic spread globally within a matter of weeks, a -like pandemic did not materialize. nonetheless, this most recent pandemic resulted in ≈ , deaths in the united states, ≈ % of which occurred in persons < years of age ( ) . in the wake of this pandemic, the challenge in preparedness is to sustain the interest of private and public sectors in planning for a large-scale outbreak that may have a much more severe effect at a time that cannot be predicted. recent assessments of state level epidemiology capacity revealed potentially critical gaps in personnel and training needed for a rapid response to an epidemic ( ) . there will be a need for continued commitments to support state, local, and national planning for the next infectious disease emergency. a comprehensive, coordinated, and effective response cannot be built at the time of a crisis. for future planning and response efforts, sufficient resources are required to sustain the public health response infrastructure developed during the past decade. an effective response to a pandemic requires at least distinct elements. first, material resources, such as vaccines, antiviral drugs, and personal protective equipment are essential. second, a commitment to planning, exercising, and refining plans is necessary. third, a sufficiently large and robustly trained workforce is the basis of any response. fourth, a commitment to improvement is crucial. this concept extends from continuously improving plans and training to ensuring that scientific advances are incorporated into procurement and planning. one of the main lessons from the history of influenza is to expect the unexpected. plans and training should be flexible and designed to respond to various levels of disease severity or newly identified pathogens. benefits from pandemic preparedness will enhance our collective public health response to the next infectious disease crisis. dr iskander is a senior medical consultant in the office of the associate director for science, cdc. world health organization. pandemic influenza preparedness and response: a who guidance document us department of health and human services. about pandemics pandemic versus epidemic influenza mortality: a pattern of changing age distribution influenza pandemic: preparedness plans of the public health service swine influenza a outbreak from the national institute of allergy and infectious diseases of the national institutes of health, the center for disease control, and the bureau of biologics of the food and drug administration: a status report on national immunization against influenza guillain-barré syndrome following vaccination in the national influenza immunization program preparing for avian influenza: lessons from the "swine flu affair historical perspective-emergence of influenza a (h n ) viruses preparing for pandemic influenza: the need for enhanced surveillance influenza pandemic preparedness interagency work group on pandemic influenza. a plan for pandemic influenza. department of health, education, and welfare influenza immunization program review and update of influenza grant programs pandemic planning: conclusions and recommendations influenza pandemic preparedness plan for the united states influenza pandemic preparedness action plan for the united states: update outbreak of avian influenza a(h n ) virus infection in hong kong in influenza pandemic planning: review of a collaborative state and national process continuation guidance for cooperative agreement on public health preparedness and response for bioterrorism-budget year five, program announcement national strategy for pandemic influenza national strategy for pandemic influenza: implementation plan ) of the vaccines and related biological products advisory committee report to congress: pandemic influenza preparedness spending planning for the next pandemic of influenza world health organization. who strategic action plan for pandemic influenza us government departments, agencies, and offices. assessment of states' operating plans to combat pandemic influenza national association of county and city health officials update: influenza a (h n )v transmission and guidelines-five states surveillance for influenza during the influenza a (h n ) pandemic-united states confronting zoonoses through closer collaboration between medicine and veterinary medicine (as 'one medicine') us department of health and human services and us department of homeland security. guidance on allocating and targeting pandemic influenza vaccine use of influenza a (h n ) monovalent vaccine: recommendations of the advisory committee on immunization practices (acip) influenza pandemic preparedness pandemics in the age of twitter: content analysis of tweets during the h n outbreak estimating the burden of pandemic influenza a (h n ) in the united states assessment of epidemiology capacity in state health departments-united states key: cord- - ex c tj authors: dai, bibing; fu, di; meng, guangteng; liu, bingsheng; li, qi; liu, xun title: the effects of governmental and individual predictors on covid‐ protective behaviors in china: a path analysis model date: - - journal: public adm rev doi: . /puar. sha: doc_id: cord_uid: ex c tj the outbreak of the covid‐ pandemic has plunged the world into a crisis. to contain the crisis, it is essential to build full cooperation between the government and the public. however, it is unclear which governmental and individual factors are the determinants and how they interact on protective behaviors against covid‐ . to resolve this issue, this study built a multiple mediation model and found government emergency public information as detailed pandemic information and positive risk communication had more important impacts on protective behaviors than rumor refutation and supplies. moreover, governmental factors could indirectly affect protective behaviors through individual factors such as perceived efficacy, positive emotions, and risk perception. these findings suggest that systematic intervention programs for governmental factors need to be integrated with individual factors to finally achieve effective prevention and control of the covid‐ pandemic among the public. this article is protected by copyright. all rights reserved. covid- has plunged the world into a crisis, and its effect on people's physical and mental health, economic development and social stability cannot be underestimated (van gelder et al. ). china is not only one of the first countries to experience the outbreak of covid- infection, but also one of the few that have largely contained it. this could not be separated from the strict governmental supervision and people's effective protective behaviors (li, chen, and huang ). therefore, drawing on its experience in pandemic prevention and control can help accelerate the world's progress in defeating the pandemic. the protective action decision model (padm) was developed to explore people's actions to natural hazards and disaster events. padm believes that various sources of information cause people's attention, exploration, and comprehension to generate threats perceptions, protective actions perceptions, and stakeholder perceptions, and finally form decisions about how to take self-protective actions (lindell and perry ; lindell ) . based on this framework, the current study proposes an information-perception/consideration-action mediation model to elucidate protective behaviors during a pandemic. in this model, government emergency public information is considered to be the sources of information, the individual's emotional and cognitive perception and consideration are considered to be the extension of perceptions in the padm model. additionally, protective behaviors, including preventive (i.e. wearing masks, disinfectants) (kim et al. ) , avoidant (i.e. stringent quarantine, avoiding public places) (bayham et al. ) , and management of disease behaviors (i.e. seeking professional protection or treatment information, paying for preventive and therapeutic drugs) (hagan, maguire, and bopping ) , are considered to be the actions (bish and michie ) . one important issue that should be explored is how this government emergency public information can persuade the public to adopt recommended protective behaviors to control the spread of the covid- pandemic. government emergency public information should enhance the public's courage and determination, raise their risk awareness, and adopt effective protections to fight the pandemic (paek et al. ) . the chinese government implemented several effective emergency public information measures through detailed pandemic information, positive risk communication, and rumor refutation (chon and park ; li, chen, and huang ; xu et al. ) . detailed pandemic information means the released statistical information, such as confirmed cases, dynamic suspected cases, recovered cases, and deaths both in accumulative numbers and daily updates, as well as tracked information including travel history, and trains or flights taken by specific confirmed or suspected patients. during covid- , the detailed pandemic information has become the foundation of the current south korean policy actions to combat covid- successfully (moon ). some researchers believe that detailed information can increase people's risk perception and promote protective behaviors (qazi et al. ; french ) . positive risk communication conveying positive educational information can result in more appropriate manners (fewtrell and bartram ) . according to china's fight against covid- (china daily ), the achievements in the fight against the virus and stories of frontline medical workers, volunteers reported by the mainstream media could inspire people to participate in the pandemic. rumors increase the uncertainty of public information and trigger conspiracy theories and pseudoscientific claims (dredze, broniatowski, and hilyard ; sharma et al. ) . one important challenge to control the ebola haemorrhagic outbreak was numerous rumors (lamunu et al., ) . timely refutation of rumors can help the government reduce public confusion, perceived risk and panic, build trust, and promote proper protective behaviors (difonzo and bordia ; greenhill and oppenheim ) . in addition, medical supplies during a pandemic are desperately needed (who ) . for example, during the west africa ebola epidemic, evidence suggests that earlier supplies modestly reduced mortality (walker and whitty ) . the efforts to add supplies such as the lifesaving medicines and trained clinicians could increase the public trust and promote people to seek clinical care (who ebola response team ). during this covid- pandemic, the rapid construction of huoshenshan hospital made people concern more about the pandemic and feel they have "warriors" in this battle (bbc news ). perceived efficacy, positive emotions, and risk perception are important individual factors affecting protective behaviors (prati, pietrantoni, and zani ) . first, perceived efficacy plays a key role in positively predicting protective behaviors (balkhy et al. ; rubin et al. ; seale et al. ). according to the protection-motivation theory (rippetoe and rogers ) , perceived efficacy is made up of self-efficacy and response efficacy. self-efficacy refers to individuals' confidence in their abilities to carry out protective behaviors, and response efficacy refers to individuals' belief of the effectiveness of protective behaviors in coping with a health threat. people with higher perceived efficacy are more likely to take precautionary behaviors and seek control in avian influenza pandemic (de zwart et al. hypotheses, this study tries to test two hypotheses. the first is that government emergency public information would promote people to comply with protective behaviors directly. the second is that government emergency public information would contribute to protective behaviors through increasing people's perceived efficacy, positive emotions, and perception of risk. participants and data collection. this cross-sectional design research was approved by the institutional review board of the institute of psychology, chinese academy of sciences, and followed the declaration of helsinki. data collection was conducted from - - to - - . all the participants were recruited online from provinces in china. after reading and signing the informed consents, we asked participants to rate government, personal, and behavior factors with items on a -point likert scale, which were displayed in table preventive behaviors items, one avoidant behaviors item, and two management of disease behaviors items. in the present study, these items were chosen to reflect the main components of these variables in the context of covid- pandemic and most of them had good or accepted reliabilities. a total of , participants finished the survey. data of , participants ( . %) entered final statistical analyses after deleting the invalid data, where participants gave a wrong response on a question used to detect whether they answer the questionnaire carefully. participants' demographic information is displayed in table . comparison of the sample's demographic characteristics to the corresponding census data suggested that the sample over-represented youth, higher education population and students. this article is protected by copyright. all rights reserved. data analysis. data were analyzed using spss version . , amos version . , and mplus . . t-test and one-way anova were used to explore whether there were gender, age, and education differences in protective behaviors. descriptive statistics were performed to describe the sample characteristics of each factor. pearson correlation analyses were performed to examine whether associations between factors conformed to the prerequisites for path analysis. path analysis was conducted to test the model. the squared multiple regression correlation coefficient was estimated to identify the variance in protective behaviors which was explained by proposed factors. bootstrap resampling was employed to test the significance of direct and indirect variable effects (mackinnon, lockwood, and williams ) . we analyzed how gender, age, and education background impact on protective behaviors. t-test showed that gender had a significant effect on protective behaviors, t ( ) = . , p < . . females showed more protective behaviors (m ± sd = . ± . ) than males (m ± sd = . ± . ). one-way anova showed that age had a significant effect on protective behaviors, f ( , ) = . , p < . . post hoc test indicated that participants from to years (m ± sd = . ± . ) showed significantly fewer protective behaviors than participants from to years (m ± sd = . ± . ), p < . . no significant differences were found between other age groups, ps > . . one-way anova showed that education background had a significant effect on protective behaviors, f ( , ) = . , p < . . post hoc test indicated that participants with high school or lower education background (m ± sd = . ± . ) had significantly more protective behaviors than participants with university bachelor's degree (m ± sd = . ± . ), p < . . no significant differences were found between other groups, ps > . . means and standard deviations for the predictors of protective behaviors, as well as the correlation coefficients between them are displayed in table . only the association between risk perception and supplies was not significant (r = . , p > . ). associations between other factors and protective behaviors reached significance (ps < . ). furthermore, all the proposed governmental and individual factors were positively correlated with preventive, avoidant, and management of disease behaviors (ps < . ). these three protective behaviors were also positively correlated with each other significantly (ps < . ). therefore, path analysis could perform based on the current model. mediational model. the model-data fit was evaluated using  ,  /df, root mean square error of approximation (rmsea), standardized root mean square residual (srmr), normed fit index (nfi), comparative fit index (cfi), and goodness of fit index (gfi). the rmsea and srmr should be less than . . regarding nfi, cfi, and gfi, values no less than . indicate a good model fit, whereas values above . indicate an excellent fit (cohen et al. ) . because protective behaviors may be associated with a variety of demographic factors, the hypothesized model was performed adding gender, age, and education as control variables, which was a common statistics method considering the confounding effects of personal (table ). in addition, to further examine whether the mediating effect was significant, the indirect effects were computed using the bias-corrected bootstrapping method; if the % confidence interval (ci) did not include , it meant that the mediating effect was significant (mackinnon, lockwood, and williams ) . table the current study has several limits and future directions. first, the sample in the current study is not representative of all demographic categories. a large number of participants were young college students and with a bachelor's degree or higher although age and education had no significant effects on protective behaviors. thus, the applicability of the findings to other samples needs to be further explored. second, previous study found that people's perceptions of authorities are different across countries and are correlated with their protective actions to pandemic (wei et al. ). all participants of the current study were from china, and a cross-country comparative study is needed to expand the applicability of the current findings. third, cronbach's alpha coefficients for the detailed pandemic information, perceived efficacy and protective behaviors have accepted reliabilities rather than good reliabilities in the present study, which may be caused by their limited number of items or omission of important items (e.g., hand washing as an important protective behavior item). future research should adopt questionnaire with more items or adding important items to improve their reliabilities. in order to combat the covid- pandemic effectively, governments should take effective measures in combination with governmental and individual factors. the suspected numbers, infected numbers, critically ill numbers, and death toll in different regions are officially announced every day. (strongly disagree) to (strongly agree) the confirmed patient's recent movements are officially published as soon as possible. (strongly disagree) to (strongly agree) positive risk communication a lot of information about medical staff and supplies are brought from other areas to the frontline is officially announced. (strongly disagree) to (strongly agree) rumor refutation fake news is officially refuted in time. (strongly disagree) to (strongly agree) supplies medical staff are sufficient in your current country or region. (strongly disagree) to (strongly agree) medical supplies are sufficient in your current country or region. (strongly disagree) to (strongly agree) living supplies are sufficient in your current country or region. (strongly disagree) to (strongly agree) mental health support is sufficient in your current country or region. (strongly disagree) to (strongly agree) patients are treated on time during the pandemic. (strongly disagree) to (strongly agree) perceived efficacy i believe the pandemic will be fully controlled in the foreseeable future. (strongly disagree) to (strongly agree) i am confident that the pandemic will be overcome. (strongly disagree) to (strongly agree) to cope with the pandemic, i can discriminate between true information and rumors about covid- . (strongly disagree) to (strongly agree) when i return home from outside, i disinfect myself with alcohol spray or sanitizer. (strongly disagree) to (strongly agree) avoidant i will not go out until the pandemic is over unless i have to. (strongly disagree) to (strongly agree) management of illness as soon as covid- preventive and treatment medications appear on the market, i will pay for them immediately. (strongly disagree) to (strongly agree) i usually get medical information and prevention measures about covid- . (strongly disagree) to (strongly agree) note. all the estimates provided in the table are standardized estimates. * p < . , ** p < . , *** p < . . eppm and willingness to respond: the role of risk and efficacy communication in strengthening public health emergency response systems unresolved issues in risk communication research: the case of the h n pandemic measured voluntary avoidance behaviour during the a/h n coronavirus: cement mixers become celebrities in china lockdown demographic and attitudinal determinants of protective behaviours during a pandemic: a review this article is protected by copyright. all rights reserved report: china's fight against covid- predicting public support for government actions in a public health crisis: testing fear, organization-public relationship, and behavioral intention in the framework of the situational theory of problem solving applied multiple regression/correlation analysis for the behavioral sciences monitoring of risk perceptions and correlates of precautionary behaviour related to human avian influenza during - in the netherlands: results of seven consecutive surveys rumors influence: toward a dynamic social impact theory of rumor zika vaccine misconceptions: a social media analysis public support for government actions during a flu pandemic: lessons learned from a statewide survey a social-cognitive model of pandemic influenza h n risk perception and recommended behaviors in italy analyzing situational awareness through public opinion to predict adoption of social distancing amid pandemic covid- stockpiling supplies for the next influenza pandemic effects of components of protection-motivation theory on adaptive and maladaptive coping with a health threat public perceptions, anxiety, and behaviour change in relation to the swine flu outbreak: cross sectional telephone survey the community's attitude towards swine flu and pandemic influenza zika virus pandemic-analysis of facebook as a social media health information platform the role of public trust during pandemics remote control: how the media sustain authoritarian rule in china covid- : reducing the risk of infection might increase the risk of intimate partner violence effective health risk communication about pandemic influenza for vulnerable populations tackling emerging infections: clinical and public health lessons from the west african ebola virus disease outbreak perceived stakeholder characteristics and protective we thank all the participants for their commitment in the present study. we particularly thank lux li for his kindly help with proofreading and thank both reviewers for helping us improve the quality and clarity of our manuscripts. this study was supported by grants from the national natural science note. * p < . , ** p < . . key: cord- -zt o co authors: sovacool, benjamin k.; furszyfer del rio, dylan; griffiths, steve title: contextualizing the covid- pandemic for a carbon-constrained world: insights for sustainability transitions, energy justice, and research methodology date: - - journal: energy research & social science doi: . /j.erss. . sha: doc_id: cord_uid: zt o co abstract the global covid- pandemic has rapidly overwhelmed our societies, shocked the global economy and overburdened struggling health care systems and other social institutions around the world. while such impacts of covid- are becoming clearer, the implications of the disease for energy and climate policy are more prosaic. this special section seeks to offer more clarity on the emerging connections between covid- and energy supply and demand, energy governance, future low-carbon transitions, social justice, and even the practice of research methodology. it features articles that ask, and answer: what are the known and anticipated impacts of covid- on energy demand and climate change? how has the disease shaped institutional responses and varying energy policy frameworks, especially in africa? how will the disease impact ongoing social practices, innovations and sustainability transitions, including not only renewable energy but also mobility? how might the disease, and social responses to it, exacerbate underlying patterns of energy poverty, energy vulnerability, and energy injustice? lastly, what challenges and insights does the pandemic offer for the practice of research, and for future research methodology? we find that without careful guidance and consideration, the brave new age wrought by covid- could very well collapse in on itself with bloated stimulus packages that counter sustainability goals, misaligned incentives that exacerbate climate change, the entrenchment of unsustainable practices, and acute and troubling consequences for vulnerable groups. the global covid- , or coronavirus disease, pandemic has overwhelmed our societies, shocked the global economy, thrown energy markets into disarray and overburdened struggling health care systems and other social institutions around the world. unlike earlier modern disease outbreaks such as severe acute respiratory syndrome (sars), swine flu (h n ), or ebola, the covid- virus is very easily transmitted by person-to-person contact. further, it has no known preexisting immunities, it is spread by people that do not appear to be sick, and the ratio between infections and fatalities is very high, particularly for older people and people with preexisting medical conditions. in medical terminology, society is undergoing a global pandemic with an immunologically naïve population. when addressing a group of sustainable development and medical professionals in april , columbia university professor jeffrey sachs estimated that the virus that causes covid- (i.e. sars-cov- ) could infect half the world's population within the next few years [ ] . although the global response to covid- may not be fully commensurate to the severity of the challenge, it has nevertheless disrupted longstanding notions of human resilience, disease preparedness, and even global health governance [ ] . national and subnational responses to the disease have often been far-reaching and at times transformative, including not only mandatory lockdowns, quarantines and restrictions on travel but key interventions such as evacuations, the distribution of hygiene and sanitation kits, and the suspension of all public visitors. some countries have utilized mass surveillance (as well as tracking and contact tracing apps) to monitor symptoms within their populations, funded community participation in the development and distribution of personal protective equipment, or participated in the design of intersectoral and transnational cooperation and aid packages. more than $ trillion in fiscal support measures had been announced by governments globally as of june to mitigate the economic impact from the pandemic, particularly impacts from the lockdown measures implemented to prevent spread of the disease [ ] . these relief packages amount to nearly % or more of gdp in germany, japan and the united states, with the united states alone signing a massive $ trillion covid- emergency bill and stimulus package in march [ ] . the european union set up a € billion coronavirus response investment initiative to provide liquidity to small businesses and the health care sector [ ] . the united kingdom also has invested heavily, launching a furlough program where the government paid the wages of . million affected workers (one quarter of the workforce) at a cost of more than £ billion with an additional £ billion in loans to businesses [ ] . initial assessments of the economic consequences of the pandemic are sobering, with estimations of a global gdp contraction of . % in [ ] , global trade shrinking by % [ ] and as many as million people losing their jobs [ ] . although the impacts of covid- on health systems and national economies are heavily covered in the media, and oft debated in the public, the implications of the disease for energy and climate policy are more prosaic. this special section of energy research & social science seeks to offer more clarity on the emerging connections between covid- and topics such as energy supply and demand, energy governance, future low-carbon transitions, social justice, and even the practice of research methodology. it features articles that ask, and answer: what are the known and anticipated impacts of covid- on energy demand and climate change? how has the disease shaped institutional responses and energy policy frameworks, especially in places such as africa where covid- is negatively affecting ongoing efforts to achieve access to modern energy? how will the disease impact ongoing patterns of innovation, social practices and future transitions, including not only adoption of renewable energy but also the electrification of mobility and mobility-as-a-service? how might the disease, and social responses to it, exacerbate underlying patterns of energy poverty, energy vulnerability, and energy injustice? lastly, what challenges and insights does the pandemic offer for the practice of research, and for research methodology? although ostensibly never intended as measures to reduce energy consumption, air pollution, or climate change directly, responses to the virus have had substantial connections with energy demand and greenhouse gas emissions. the most prominent drivers of these have been mandatory lockdowns or quarantines for households (people are only permitted to leave for essential reasons) and the related severe restrictions on travel. in late april , more than half of the entire global population ( %) was under some form of a coronavirus lockdown, with their movement actively restricted and controlled by their respective governments. the share of energy use that was exposed to containment measures reached % [ ] . as the top panel of fig. indicates, the largest lockdowns were in india, china, and the united states. one article calculated that more people were in lockdown due to covid- than were alive during world war ii [ ] . as the other panels of fig. indicate, more than countires had travel restrictions in place due to coronavirus in late march and the number of commerical flights has plummeted dramatically. abu-rayash and dincer (this volume [ ] ) add that road transport is also down significanty given the large number people forced to stay at home. they further show that in canada not only did civil aviation activities drop by % compared to business-as-usual in late , but also military aviatation activities were down by a significant % in . they also projected that for , greenhouse gas emissions for the canadian transport sector will be nearly % lower than than in . covid- has not only affected travel and the energy involved in providing it, but also global energy supply chains and the viability of energy firms. writing in this volume [ ] , hosseini argues that the most affected renewable energy sector has been solar energy and remarks that indeed, "the covid- pandemic has struck the renewable energy manufacturing facilities, supply chains, and companies and slowed down the transition to the sustainable energy world". the causes behind such shifts are manifold: governments have understandably redistributed public funding to combat the disease in a way that leaves less available for renewable energy incentives and tax credits. various renewable energy technology suppliers have placed staff on furlough and also adopted austerity measures and reduced operating capacity. projected installations are down significantly over earlier forecasts; one investment bank in the united states predicted residential-solar installations to fall by % year-over-year in the second quarter of and by % in the fourth quarter of . this reinforces the projections provided by irena that total new solar pv capacity additions in will be roughly on par , but this is as much as % below earlier expectations stated by several industry organizations [ ] . the off-grid renewable energy sector could face even more dire circumstances, with the world bank noting that the pandemic has seriously disrupted electrifications efforts, meaning that sdg (that encompasses universal energy access by ) is now unlikely to be met [ ] . it is in this context that mark mccarthy akrofi and colleagues (this volume [ ] ) caution that the pandemic could "reverse the enormous progress that off-grid energy companies have made to bring power to some million people in the last decade." solar pv alone is responsible for employing about % of the entire african workforce but solar firms and enterprises are already being forced to cut jobs, lay off staff, and confront declining liquidity. due to a strong dependence on imported solar pv technology from china, where manufacturing has declined due to the pandemic, dramatic reductions on future installed solar capacity are also projected for countries such as india [ ] . covid- is affecting global fossil fuel markets as well. hosseini (this volume [ ] ) adds that the coronavirus has disrupted global oil markets far more than any geopolitical event has (such as an embargo from opec), weakening the ability of oil suppliers to control markets and driving down natural gas spot prices into the $ /mmbtu (million british thermal units) range. although geopolitical tensions between saudi arabia and russia played an early role in the oil price collapse [ ] , demand destruction due to covid- has indeed been the driving force. jefferson (this volume) [ ] writes "in the run-up to the collapse of crude oil prices in early it was primarily a division between russia and saudi arabia within opec which appeared to be the main force at work, but then the covid- pandemic took over, followed by us oil prices turning negative in april , as may contracts expired and traders had to offload stocks with ongoing storage becoming extremely limited." he further states that despite the stimulus and recovery packages being offered by many nations, "there will be many oil sectors incurring losses, from us shale oil and canadian tar sands producers, to many standard crude oil exporters incurring problems with production equipment access and costs, or experiencing lack of competitiveness in key markets." recent data from the international energy agency confirms this point, noting severe reductions in global demand for oil and natural gas (see fig. ). although not representative of all countries and regions, the special section does feature some deep and nuanced assessments of the particular impacts the pandemic is having on national energy supply or demand. nima norouzi and colleagues (this volume) [ ] intimately trace the impacts of the virus where it first emerged in wuhan, china, looking at how it impacted not only national energy demand, but also precipitated steep declines (and future uncertainty) in patterns of electricity consumption and oil consumption, industrial productivity and energy markets. they specifically propose a methodology for analyzing such patterns during periods in which historical data becomes inaccurate because of a crisis event such as covid- . azzam abu-rayash and colleagues (this volume) [ ] closely analyze the impacts of the pandemic on electricity demand in ontario, canada, where they calculate declines in electricity consumption during april of about % or , gw and note distinct changes in demand patterns due to quarantine and travel restrictions. this corresponds with some positive externalities as well, including greenhouse gas emission reductions of , tons of co equivalent attributed to covid- with a monetary value of $ , for the month of april . fig. shows a similar trend in europe, with significant (and positive) reductions in air pollution noted across france, italy, and spain, largely from the curtailment of road transport. abouzar estebsari and colleagues (this volume [ ] ) offer a well-reasoned explanation for why related reductions in electricity demand occurred, having analyzed patterns of electricity demand in spain, italy, belgium and the united kingdom (countries with more severe covid- movement restrictions) as well as the netherlands and sweden (countries with less restrictive measures). they found that during the second week of april only in sweden demand remained more or less the same (actually rising slightly) relative to a reference week in . significant reductions were experienced in spain ( %), italy ( . %), belgium ( . %), the uk ( . %) and even the netherlands ( . %) due to covid- . the ramifications of covid- extend well beyond the avoided energy consumption and emissions associated with travel and household lockdowns; they are also drastically shaping the strength (or erosion) of some energy institutions and policy frameworks. for instance, the pandemic is having a particularly pronounced effect on institutions and policy frameworks in africa, even though it is not (at the time of this writing) a major center of infections or death. mulualem gebreslassie (this volume) [ ] writes that the closure of energy intensive businesses and industries in africa has meant a positive shift in that states can now provide scarce energy services to homes or national health care systems. as they conclude, the pandemic "may even convince the african continent to rethink and clear the way for investing more in clean and reliable energy resources and make business processes easy for those who are interested to enter the renewable energy sector." mark mccarthy akrofi and colleagues (this volume [ ] ) add that african states are already rushing to intervene and stimulate recovery but do not specifically address how stimulus packages will influence the clean energy transition. further research therefore needs to examine how government stimulus can strengthen the renewable energy sector via various aid packages, economic incentives, and monetary and fiscal incentives-efforts müller et al. note are all broadly consistent with many national policy frameworks across the continent [ ] . as already stated, the pandemic has significantly disrupted lives, businesses, and economies. furthermore, it could culminate in lasting effects on social norms and practices. to contextualize this claim, consider that the global response to covid- has necessitated unprecedented levels of coordination and information sharing with the intent of ultimately curtailing outbreaks and minimizing harm [ ] . this has occurred at multiple levels of society at once across many different types of institutions-making it what the nobel laureate elinor ostrom would have called "organizational multiplicity" and a "polycentric" phenomenon [ , ] . fig. displays the variety of messages received about covid- merely by the lead author, including those from the mass media (covid- dominated headlines in the uk for weeks), companies and travel providers, national government, grocery stores, universities, restaurants, social groups and charities, and even churches. this phenomenon parallels what scholar eve kosofsky sedgwick terms the "christmas effect" [ ] to describe the way that major parts of western society come together and speak "with one voice" for the christmas holiday. for it is annually during the christmas season that churches build nativity scenes and hold a greater number of masses; state and federal governments establish school and national holidays; the media run major advertising campaigns; and social events and domestic activities align. whenever society combines institutional inertia in this manner, it can exert profound and lasting influence over patterns of behavior, transcending individual firms and people. although certainly not festive, the "coronavirus effect" may be just as effective as the "christmas effect." such messages and strategies of communication underscore an immense amount of coordination across diverse and heterogeneous actors and organizations. the resulting messages were persistent, coming repeatedly and daily. they were prominent, in many times coming from sources people trust. they were multifaceted, coming from many sectors beyond health care including not only those in fig. , but also the mayor of london sadiq khan, banks, libraries, political groups, airlines, friends, and family. one of the authors even had his "smart printer" send an automated email about ink delivery during the pandemic, as well as six emails from his dentist about dental hygiene during the pandemic. and the messages were personal, often prescribing very specific actions or recommendations (about washing, essential travel, social distancing, self-quarantining, and mask wearing) connected to personal health and calling for immediate changes in behavior and practice. given the coronavirus' ability to achieve this "christmas effect," hundreds of millions of people immediately adopted the new behavior of "social distancing," with fig. showing its adoption in india, the united states, the united kingdom and singapore. when making the predictions mentioned in the introduction, jeffrey sachs even remarked that "we should expect to change our behaviors not just during this pandemic but perhaps forever." indeed, wisdom kanda and colleagues (this volume [ ] ) argue that in the context of sustainability transitions, the pandemic is causing "disruptive" change not only by potentially accelerating transformations in incumbent socio-technical systems, but also by also affecting emergent innovations and niches. in the mobility sector, they discuss how in finland and sweden the virus has weakened the push for mobility-as-a-service efforts (given they involve sharing rides, not ideal in an environment of social distancing) but had less impact on the push for electric vehicles (given they permit individualized, private transport). they therefore suggest that the impacts of covid- on mobility practices and transitions are important research streams moving forward. caroline kuzemko and colleagues (this volume [ ] ) take an even broader and more holistic view of the ways the pandemic can place pressure on sustainability transitions in the near-term and the longterm. they argue that covid- can alter the scope and pace of energy systems change with declining electricity demand and prices, the disruption of supply chains, and possible rebounds associated with recovery and stimulus packages. it could also shift financial investment flows away from incumbent industries and carbon intensive fuels. the pandemic is changing multi-scalar policy and politics by calling into question longstanding conventions about globalization and interconnectivity, as well as freedom of movement and geopolitical tensions between groups such as the united states and china or the united states and the world health organization. the pandemic is lastly transforming social and political practices, especially those related to telework/working from home as well a preferred modes of travel given the near-term focus on social distancing. here they warn that the lasting imprint of the pandemic is uncertain, with the potential that it entrenches unsustainable practices (such as driving a car) perhaps as great as its ability to introduce more sustainable practices (such as walking). they raise the critical question of whether there will be an acceleration of pre-pandemic drivers for sustainability across the dimensions they consider or whether momentum for sustainability will be lost as pandemic recovery plans are rolled out. kester et al. recently refer to this as the "dialectic" nature of future sustainability transitions, given they can reinforce dominant practices as much as they can reform existing ones [ ] . even electric mobility, an innovation kanda and colleagues noted may ultimately be less affected by the pandemic, has unclear and highly differentiated impacts on sustainability as noted in table . this means the adoption of electric vehicles is neither good nor bad in sustainability terms, it instead depends on how such innovations are governed and managed across areas such as vehicle use, daily life, social identity and systemwide environmental effects. the covid- pandemic has equally compelling linkages with energy crises, energy poverty, energy vulnerability and energy injustice. kathleen brosemer and colleagues (this volume [ ] ) write that the pandemic will only "illuminate and compound existing crises in energy sovereignty." it is worsening already terrible inequalities in health care access among the navajo nation in the united states, where hospitals were overburdened before covid- outbreaks with caring for indigenous peoples harmed from coal mining and extraction as well as increases in kidney disease and cancer that resulted from many years of living next to abandoned uranium mines. the pandemic is compounding environmental injustices as covid- most affects those with preexisting medical conditions, and yet decades of poor environmental and air quality leave minority groups at heightened risk of having those conditions. it is undermining the ability of energy firms to guarantee the provision of energy access and modern energy services in times of austerity and uncertainty. it is lastly serving as a mechanism for powerful incumbent interests to usurp various regulatory processes that back their own narrow interests at the expense of the public good. one particular example is enbridge "taking advantage of divided public attention and a fraught financial situation during the covid- crisis to push forward permit applications" for a major change in the routes of one of their pipelines. such attempts at regulatory manipulation are not limited to north america; kalyani writes how vested interests in india were using the pandemic as an excuse to increase employment in the coal and gas sectors, even though these sectors operate contrary to india's stated climate policies [ ] . paolo mastropietro and colleagues (this volume [ ] ) add that "the covid- pandemic and the consequent lockdown exacerbated energy poverty and insecurity worldwide." however, they also note that the collective response from policymakers has been to attempt to safeguard vulnerable citizens by an array of protection measures including: • disconnection bans; • energy bill deferral and payment extension plans; • enhancement of energy assistance programs; • energy bill reductions or cancellations; • support measures for commercial and small industrial activities; • creation of funds and other support measures to suppliers. after reviewing the global prevalence of these measures, they conclude that two are "best" at minimizing vulnerability: direct energy assistance programs and bans on disconnections, the latter being the most widespread measure introduced by governments during the pandemic. matthew henry and colleagues (this volume [ ] ) take an equally useful global analytical lens, reinforcing the recent call for a "just transition." this debate about a "just transition" is ongoing across many countries and provinces, with at least national commissions, policies, or task forces in place across canada, china, czech republic, germany, ghana, indonesia, new zealand, scotland, south africa, spain, the united states and vietnam. as table indicates, a "just transition" is backed by powerful coalitions and groups around the world. as henry and colleagues note, a just transition intends to ensure that as global society decarbonizes, it does not leave anyone behind. efforts must be made to offer income support for workers during the full duration of transition, to tailor local economic development tools for affected communities, and to offer realistic training or retraining programs that lead to decent work. they worry, however, that both the covid- pandemic and the global fall in oil prices could complicate ongoing attempts to realize a just transition-especially since the pandemic has resulted in the loss of more than , clean energy jobs and halted momentum in the push for solar energy and wind energy. they conclude however that the covid- crisis represents "a unique opportunity to adopt just transition principles into community and economic recovery efforts." the insights offered by this special section are not just topical or thematic. they also relate to the very art and craft of undertaking research, with some interesting insights for research design and research methodology. both jefferson (this volume [ ] ) and kanda and colleagues (this volume [ ] ) note how scholars, especially those designing energy programs (such as the global energy assessment) or utilizing table the differentiated impacts of electric mobility and electric vehicles on sustainability. strengthens sustainability weakens sustainability vehicle uptake evs substitute for conventional cars and motorcycle. evs increase car-based mobility by drawing people away from active and public modes of transport. evs used more in intermodal (active and public transport) systems and in combination with measures to discourage car use. evs encourage excessive driving and are bought as second or third (luxury) cars. evs increase the use of car sharing/ride sharing schemes. evs increase the preference for private, single-occupancy driving practices. evs are a wakeup call to address private vehicle use if alternatives are available -public transport, shared services etc. evs, through their cheaper variable costs, enable longer distances, thus supporting urban sprawl. they also compete with public transport and shared services. evs allow for more family time as commutes are part of office hours. evs allow office hours to be extended to include commuting time. expression of gender evs and ev marketing break with gender distinctions through alternative design, comfort and ease of operations. evs and ev marketing reinforce stereotypical car images of masculinity (large, sporty, pickup trucks) or femininity (small, quiet, early generation evs). evs and ev marketing point to new stereotypes around responsible and sustainable car use. evs and ev marketing reinforce stereotypical car discourses of joy and notions of freedom. evs break with class distinctions, as low variable costs enable more mobility for all. evs reinforce class/wealth distinctions as high capital costs imply that only rich can afford them and their benefits. evs, through their broad deployment, signal a need for more efficient low-carbon propellants, alternative modes of transport, less mobility and spur pro-environmental behavior in other sectors evs have lower emissions, which lead to rebound effects: more miles travelled, heavier vehicles, more private vehicles. this is especially relevant if the ecosystem around evs fails to materialize, e.g. no battery recycling, only dump charging, nonrenewable electricity, etc. oil independence evs minimize and signal lower oil/gas consumption, which reduces dependency among households and non-oil producers on oil companies and oil producing countries. evs cause a reduction in demand for oil, which reduces the oil price and makes fueling conventional vehicles cheaper. lower oil prices also reduce oil sector investments and thereby limit production to a smaller group of oil producing countries (those with low variable costs) and counterintuitively increasing oil dependence on a smaller group of countries. evs are designed and promoted by sustainably oriented firms with a focus on innovation and entrepreneurship. evs are co-opted and marginalized by transnational conglomerates with little desire for social change. source: authors modification from kester et al [ ] . selected organisations and movements supporting a "just transition" in . conceptual frameworks (such as the multi-level perspective) need to better account for epidemics and pandemics as landscape shocks. the persistence, prominence, multifaceted and personal nature of effective messaging about the virus (discussed in section ) also remind us about the importance of recognizing culture [ , ] whenever researchers engage in communication or outreach. fig. even shows the adapting to local culture of messages about social distancing and wearing masks. for instance, images about the virus in the western state of colorado (in the united states) feature skis and cowboys-symbols well embedded in local culture. lucha libre in mexico has played a relevant role in its culture since the late s, mainly due to its masked wrestlers, who have incorporated their own family traditions, beliefs and fears into the design of their masks [ ] . the louvre abu dhabi similarly adapted their messages about the pandemic to feature culturally appropriate attire for women, e.g. abayas on images of women performing social distancing. michael fell and colleagues (this volume [ ] ) suggest that the pandemic represents not only an existential threat to society, but also a threat to the practice of research, given that it calls into question the internal and external validity of our findings in the academy. this includes both the validly of research done before the pandemic (given that society may never be the same after) and the future robustness of any research conducted during the pandemic (a situation of extreme anxiety and stress far removed from "normal" life, potentially making findings less stable over time). they argue that covid- changes the context for research as it creates an environment that may be unprecedented and highly unusual compared to future years. they note the pandemic is reconfiguring demographics in rapid and unforeseen ways, with advanced morbidity and mortality and differentiated effects across age, gender, or ethnicity. they argue (much as we have in section ) that the pandemic is altering behaviors and daily routines; changing perceived personal and cognitive constraints and feelings; putting pressure on exiting social norms and identities; and materially changing homes and workplaces. taken together, these features of covid- may demand that we rethink in meaningful ways the design of future studies, how we determine demographically representative samples, how we collect data, how we interpret findings, and how we translate those findings into recommendations. such considerations are timely and relevant given the explosion of covid- publications that have appeared since the start of the pandemic. nearly , papers on the pandemic were published between february and may alone, and , of these were released through the preprint servers biorxiv, medrxiv and arxiv [ ] . chen and colleagues (this volume [ ] ) further these themes in their work on acceptance of and willingness to pay (wtp) for home energy management systems (hems) during the covid- pandemic in new york, usa. they note that the pandemic is having a distinct effect on survey participants with social-psychological variables, such as attitude toward hems and social norms, arising as important factors for explaining technology adoption intention. they also affirm some of the points raised by fell et al. about the unique situation survey respondents have found themselves in. many reported feeling "anxious" and others suggested that they felt they had a high chance of getting infected by coronavirus themselves-a salient message considering that the survey was conducted in new york, one of the global epicenters of the disease. the authors indicate that they hope that their survey results offer a "foundation for researchers to conduct larger-scale energy studies by considering the opportunities to build transdisciplinary collaborations through integrated methods and matching datasets." this might include future work on cultural differences in social distancing, how energy burdens are framed and distributed, what constitutes healthy built-home environments, and other social-psychological factors including perceived fairness or social networking. marius schwarz and colleagues (this volume [ ] ) offer additional insights regarding the impacts of the pandemic on research methodology that are perhaps obvious but nonetheless highlight important and perhaps persistent trends. they argue that covid- is opening up new ways of doing research, of being an academic, of collecting data and attending conferences. they argue "the pace with which researchers adopted digital formats for conferences, lectures, and meetings showed that currently available tools can substitute many of the physical interactions at work. it also showed that academics are willing to use digital tools for scientific exchange." the pandemic has showcased that academics and those in higher education can quickly and creatively change how they deliver lectures and are accessible to students; how they give guest seminars and discuss findings; even how they may interview for jobs, do research interviews, and host online workshops. they hope that "going digital" in many of these formats and contexts will continue, given the generally positive nature of the energy or carbon savings involved [ ] . they further suggest that such digital modes of interaction could come to substitute for physical modes in how academics work in groups, hold team meetings, and socially network. situated at the nexus of the covid- pandemic, energy systems, and climate change, this special section has revealed the complex, and often shifting, contours of how the disease is shaping global patterns of energy consumption, policymaking, and governance. it is altering the desirability of some emerging innovations and sustainability transitions, and heightening concerns over energy vulnerabilities and injustices. it is even challenging in fundamental ways how future energy and climate researchers go about their work. as table reveals, these intersections can be weighty and protean, but they are also perilous and precarious. for every noted positive intersection with some aspect of stainability or doing research, or benefit, we see an almost equally salient negative intersection, or risk. take one of these examples: lowering demand for, and prices of, fossil fuels. is this a blessing-foretelling that fossil fuels are becoming unviable-or a curse-cementing fossil fuels as cheap and abundant sources of energy to be utilized for many years to come? potently, it is the aspect of energy justice and vulnerability that particularly has more negative intersections (risks) than positive ones (benefits). covid- , as various authors presented in this special section, represents a strategic opportunity to work in parallel on designing and implementing economic and social recovery programs and advancing the global climate agenda towards a just transition. what is also evident from the special section is the multi-scalar and multifaceted nature of social responses to the pandemic, which have created a "christmas effect" or "coronavirus effect" of: • instructing people how to immediately alter and change their routines and practices in response to a crisis (e.g., social distancing, wearing masks, quarantining, and handwashing); • bolstering the strength and resilience of infrastructure and institutions (e.g., of hospitals and medical research institutions); • building capacity to monitor and manage emergency measures (e.g., trace infections, test people); • properly financing social responses in ways commensurate to a grand challenge (e.g., donations to national health services or the world health organization); • restoring economic activity gradually and via approaches that are backed by science (e.g., mandatory lockdowns and partial reopening, deployment of government rescue and stimulus funds); • harnessing innovation and rapidly developing critical new technologies (e.g., new therapeutics and vaccines); • utilizing a variety of trusted institutions and individuals to convey information and messages (e.g., the cdc, major news outlets, doctors and medical professionals); • while undertaking these steps, protecting the vulnerable (e.g., those with preexisting conditions, the unemployed and/or the indigent). although the impacts from the pandemic have so far been far from equitable or welcomed by the majority of people, this list of actions does offer a possible recipe for how future energy and climate planning could proceed as well, if policymakers and planners see the opportunity to transform social practices and institutions as much as the pandemic has. this could help achieve a "christmas" or "coronavirus" effect for energy and climate policy that encompasses: table the dialectic or dualistic impacts the covid- pandemic can have on energy and climate sustainability and research. energy and climate impacts of the virus -sharp reductions in travel related energy consumption and carbon emissions -immediate reductions in electricity consumption -depression of fossil fuel markets (particularly coal, oil and gas) -immediate reductions in global air pollution -redistribution of scarce energy resources in african nations to homes or national health care system -acceleration of african stimulus packages for low-carbon transitions -disruption of clean energy jobs -disruption of clean energy supply chains -risk of real and substantial rebounds in consumption accelerated by stimulus and recovery packages -disruption of off-grid energy markets and eroded progress on energy access programs -potentially bolstered trends in the electrification of private transport -shifted financial and investment flows away from carbon intensive assets -transformed social and professional practices in ways that are less energy intensive (e.g., working from home, walking, cycling) -undercutting of demand-side innovations such as ridesharing or mobility-as-a-service -dis-incentivizing mass-transit and public transport due to social distancing norms -calling into question the increasing interconnectivity and globalization of socio-technical systems -accelerating a geopolitical divide between the united states and other actors (e.g. china, world health organization) connections with energy justice an vulnerability -implementation of a variety of emergency protective measures including bans on disconnection and targeted assistance packages -increased attention to the principles of a "just transition" and the need for stimulus packages to be low-carbon and equitable • instructing people how to immediately reduce their carbon footprints (e.g. using energy efficient technologies in their homes, eating less meat, avoiding air travel [ ] ); • bolstering infrastructure, institutions and industrial strategy (e.g.. incentives for clean energy manufacturing and deployment including wind turbines, solar panels, electric vehicles [ ] ); • building capacity to mitigate, monitor and manage emergency measures (e.g., tracking plans for universal energy access and sdg , deployment of micro grids, bans on disconnection [ ] ); • properly financing social responses in ways commensurate to the challenge (e.g., substantially increase funding for national and multinational climate and development organizations or green investment banks, investment for deployment of low-carbon technologies and infrastructure [ , ] ); • restoring economic activity gradually and via approaches that are backed by science (e.g., development pathways synchronized to the ndcs of the paris accord or the findings of the ipcc, investment of economic stimulus funds in low-carbon technologies, green new deals [ ] [ ] [ ] ); • harnessing innovation and the development of new technologies (e.g., the next generation of transport fuels, energy storage, smart grids or hydrogen fuel cells) [ ] [ ] [ ] ; • utilizing trusted institutions and individuals to convey persistent and repeated information, messages and narratives in ways that resonate with audiences (e.g., major news outlets, the ipcc, governments, major corporations, churches, restaurants and celebrities sent persistently through various media channels) [ ] [ ] [ ] [ ] ; • while undertaking these steps, protecting the vulnerable (e.g., households in energy or mobility poverty, marginalized groups or indigenous peoples) [ ] [ ] [ ] [ ] . if such actions were taken in concert, progress on energy and climate would likely outpace all previous targets and milestones, rather than remaining chronically underfunded, underperforming and continually lagging behind expectations. both of these core findings-that covid- matches its promise of change with precariousness about the direction it goes, and that covid- responses offer a possible template for future energy and climate action-remind us that we remain at a critical but fragile crossroads. as much as we see great progress in efforts toward ameliorating the covid- crisis, we also see the same types of hindrances that have plagued progressive energy policy and climate action. specifically, lack of attention to warnings about a potential crisis, delayed responses to building evidence of crisis onset, nationalism at the expense of the global good, politics overshadowing social welfare, marginalized populations (e.g., people of low socio-economic status, or people in low and middle income countries) experiencing adverse consequences at higher rates, conspiracy theories and fatigue of mitigation measures. as fig. both comically and tragically seeks to depict, climate change is akin to a perpetual pandemic, but one that multiplies threats in steeper and more severe ways than covid- or its economic consequences. markard and rosenbloom have the right of it when they write that unlike the pandemic, "climate change, in particular, threatens the very basis for continued human prosperity and requires an equal, if not greater, societal mobilization" [ ] . hence, the opportunities emerging from the pandemic for energy systems and climate policy can be secured or squandered. without careful guidance, governance and consideration, the brave new age wrought by covid- could very well collapse in on itself with bloated stimulus packages, misaligned incentives, the embedding of unsustainable practices, and acute and troubling consequences for vulnerable groups. ssdn: epidemiology and economics of covid covid- gives the lie to global health expertise world economic outlook: the great lockdown trump signs $ trillion coronavirus stimulus bill jobs and economy during the coronavirus pandemic uk furlough scheme spending exceeds billion pounds trade set to plunge as covid- pandemic upends global economy more people are now in 'lockdown' than were alive during world war ii analysis of mobility trends during the covid- coronavirus pandemic: exploring the impacts on global aviation and travel in selected cities an outlook on the global development of renewable and sustainable energy at the time of covid- an agenda for resilience, development and equality, international renewable energy agency covid- intensifies the urgency to expand sustainable energy solutions worldwide covid- energy sector responses in africa: a review of preliminary government interventions challenges to just energy transitions in a post covid india a crude future? covid- s challenges for oil demand, supply and prices when pandemics impact economies and climate change: exploring the impacts of covid- on oil and electricity demand in china analysis of electricity demand amidst the covid- the impact of different covid- containment measures on electricity consumption in europe covid- and energy access: an opportunity or a challenge for the african continent? is green a pan-african colour? mapping african renewable energy policies and transitions in countries editorial, communication, collaboration and cooperation can stop the coronavirus polycentric systems for coping with collective action and global environmental change beyond markets and states: polycentric governance of complex economic systems what opportunities could the covid- outbreak offer for sustainability transitions research on electricity and mobility? covid- and the politics of sustainable energy transitions novel or normal: electric vehicles and the dialectic transition of nordic automobility the energy crises revealed by covid: intersections of indigeneity, inequity, and health emergency measures to protect energy consumers during the covid- pandemic: a global review and critical analysis just transitions: histories and futures in a post-covid world culture and low-carbon energytransitions the cultural barriers to a low-carbon future: a review of six mobility and energy transitions across countries the role of lucha libre in the construction of mexican male identity validity of energy social research during and after covid- : challenges, considerations, and responses scientific research on the coronavirus is being released in a torrent coronavirus comes home? energy use, home energy management, and the social-psychological factors of covid- covid- and the academy: it is time for going digital a systematic review of the energy and climate impacts of teleworking it starts at home? climate policies targeting household consumption and behavioral decisions are key to low-carbon futures harnessing innovation policy for industrial decarbonization: capabilities and manufacturing in the wind and solar power sectors of china and india sdgs in action: a novel framework for assessing energy projects against the sustainable development goals the politics of climate finance: consensus and partisanship in designing green state investment banks in the united kingdom and australia the misallocation of climate research funding the green new deal in the united states: what it is and how to pay for it canada's green new deal: forging the socio-political foundations of climate resilient infrastructure? a post mortem of the green deal: austerity, energy efficiency, and failure in british energy policy critical perspectives on disruptive innovation and energy transformation innovating innovation-disruptive innovation in china and the lowcarbon transition of capitalism are low-carbon innovations appealing? a typology of functional, symbolic, private and public attributes credibility, communication, and climate change: how lifestyle inconsistency and do-gooder derogation impact decarbonization advocacy climate change strategic narratives in the united kingdom: emergency, extinction,effectiveness using stories, narratives, and storytelling in energy and climate change research greenberg energy policy and research: the underappreciation of trust advancing an energy justice perspective of fuel poverty: household vulnerability and domestic retrofit policy in the united kingdom mobility justice in low carbon energy transitions justice, social exclusion and indigenous opposition: a case study of wind energy development on the isthmus of tehuantepec energy justice discourses in citizen deliberations on systems flexibility in the united kingdom: vulnerability, compensation and empowerment a tale of two crises: covid- and climate the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. key: cord- -sa aeu w authors: mansuri, farah muhammad asad; zalat, marwa mohammed; khan, adeel ahmed; alsaedi, esraa qabl; ibrahim, hanan mosleh title: estimation of population’s response to mitigation measures and self-perceived behaviours against covid- pandemic date: - - journal: j taibah univ med sci doi: . /j.jtumed. . . sha: doc_id: cord_uid: sa aeu w abstract objectives since march , a rapid increase has been observed in the prevalence of the covid- pandemic, which has essentially resulted from increased disease transmission and intensified testing and reporting. the international guidelines for the prevention and treatment of the covid- pandemic have been frequently updated. such guidelines assist the governmental regulatory bodies in taking optimal measures and safeguarding their citizens against the pandemic. we conducted a short survey with a saudi cohort to understand the awareness about covid- and estimate the responses for mitigation strategies. methods an electronic survey was conducted, and the first responses were analysed for publishing an initial report. the questionnaire comprised items and was divided into three sections, namely demographic, awareness, and response to mitigation strategies and participants’ self-perceived behaviours regarding covid- . the perceptions of the participants were compared with their responses to mitigation measures. results in our study, . % understood the meaning of pandemic, while . % correctly identified that the elderly belonged to a high-risk group for the covid- infection. as many as . % agreed that staying at home was one of the mitigation strategies. nearly % preferred self-medication. higher educational level (or: . , % ci: . - . ) and longer working hours were found to be significantly associated with a positive response to mitigation measures with p< . and p<. , respectively. conclusions we report better understanding and appropriate response to mitigation measures towards the covid- pandemic among the general population in saudi arabia. nevertheless, the tendency towards self-medication was reported by one-third of the responders. the covid- outbreak was declared a worldwide pandemic by who on march , with a -fold increase in the number of cases reported outside china, over a couple of weeks. it has affected more than . million people in countries in the world. out of the total global burden, a little above thousand confirmed cases and deaths were reported in emro by april . saudi arabia, with cases and deaths, is the third country in the region to be affected by the novel coronavirus or sars-cov- (severe acute respiratory syndrome-cov- ). the overall case fatality rate (cfr) among all countries is . %, but the highest is in italy at . %. , the covid- pandemic may become a category pandemic, depending on its reproduction number (r ) and overall fatality ratio thus far. , furthermore, there is an absence of a specific treatment method or vaccine against the novel coronavirus disease, which has enough potential of a pandemic. in such a situation, non- pharmaceutical interventions are the mainstay, such as community mitigation strategies and suppression to slow down the transmission, particularly among the high-risk population. , an exploratory survey was conducted in the united states of america in , to study the expected public reaction to social distancing and other non-pharmaceutical interventions that may be used during a pandemic. a total of questions were developed to cover the information on the acceptability of mitigation measures and about the problems that the public would face while complying with the recommended measures towards preparedness to a pandemic. it was found that % knew what the term 'pandemic' meant, while % had never heard of this term. in addition, it was reported that % intended to stay at home, away from work, while % said that they would be able to take care of sick persons in their household. the results of the same survey, published later in , reported the ability to comply with isolation recommendations and difficulties faced by low-income and urban populations. of the respondents, % reported that they might lose their job or business because of staying away from work for - days, during an expected event of an influenza outbreak. in saudi arabia, a cross-sectional study was conducted in , which showed high levels of concern and widespread utilisation of precautionary measures against mers-cov by most participants. the results revealed that gender and knowledge were the predictors of the level of concern. for the current pandemic, mitigation measures have been implemented from the questionnaire comprised questions and was divided into three sections, namely demographic, awareness, and response to mitigation strategies and participants' self- perceived behaviours regarding covid- . the questions were developed by consulting and reviewing currently available international guidelines [annex: report of systematic literature reviews pages - ]. the tool was designed in english and translated to arabic by a bilingual co-investigator and back-translated by another bilingual expert. the questions have undergone necessary modifications and corrections to ensure their clarity and ease of understanding. the questionnaire has been tested on persons. the reliability coefficient test (cronbach's alpha) was high for all questions. the results of the pilot study were consistent with the study results; therefore, it was included in the main survey. in this survey, we estimated an optimal sample size of participants by using openepi software version . (https://www.openepi.com/samplesize/sspropor.htm). invitations to participate in the survey were sent to individuals, and an accepted minimal response rate of % was used while keeping a % margin of error. this quick survey was the first phase of a longitudinal mixed method study funded by taibah university. approximately . % of the participants were younger than years of age, and . % were females. they were mostly residents of makah ( . %), madinah ( . %), and riyadh ( . %). nearly half of the participants were of saudi nationality ( . %), and most of them were university graduates or above ( . %). the majority ( . %) reported that they have travelled in or out of sa, more than two weeks ago. the mean number of family members in the house was . ± . persons, with approximately two children per household, on an average. while % of the participants were working inside the health sector, . % were working outside the health sector, and nearly a third of them were not working (including homemakers/retired). further, % were government employees, and % were working in the private sector. of the respondents, . % reported that their overall work duration was ≤ years, and . % were working for more than years, with an average of . ± . work hours/day. table shows the socio-demographic and occupational characteristics modelled by using multivariate logistic regression for independent association with response to mitigation measures. only educational level showed a significant independent association with response to mitigation measures (or: . , % ci: . - . , p= . ). however, nationality, residence, and gender did not show any independent association with response to mitigation measures. among occupational characteristics, longer working hours (or: . , % ci: . - . , p= . ) were independently associated with higher odds of positive response to mitigation measures, but neither with a type of occupation nor the work sector. it was also found that participants identified children younger than five years of age as the only high-risk group, which was significantly associated with response to mitigation measures (p= . ). most participants ( %) were aware that senior citizens are more at risk; however, the other high-risk groups, such as those with co-morbidities, like smokers, asthmatics, and diabetics ( - %) were not that well known to a majority of the population. thus, this information must be provided to the people to protect the high-risk groups from the infection. this is akin to the findings of the study conducted among healthcare providers in the qassim region, which reported that approximately % of the participants knew that people with co- written consent was obtained from all the participants at the start of the online survey, after clarification was provided regarding the study's aim and the privacy of personal data. authors contributions: fam conceived and designed the study, conducted research, and provided research materials. collected and interpreted data. eqa wrote the introduction and collected data. hmi obtained ethical approval and wrote results. all authors wrote the manuscript, contributed to data extraction, critically reviewed and approved the final draft, and are responsible for the content and similarity index of the manuscript. the authors would like to thank all participants of this study for sharing their knowledge, perceptions, and experiences. as the corresponding author, i had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. only heard the term pandemic • understand the meaning of pandemic • heard but don't know what it is • don't know at all which of the following are at a greater risk of coronavirus infection?* • elderly of age > ys this study was approved by the taibah university college of dentistry research ethics committee. informed consent was obtained from all participants electronically before participating in the research. all procedures of the research were according to the world medical association (wma) declaration of helsinki on ethical principles for medical research involving human subjects taibahu university key: cord- - nkrrqqw authors: patrick, jennifer r.; shaban, ramon z.; fitzgerald, gerry title: influenza: critique of the contemporary challenges for pandemic planning, prevention, control, and treatment in emergency health services date: - - journal: australas emerg nurs j doi: . /j.aenj. . . sha: doc_id: cord_uid: nkrrqqw the h( )n( ) influenza pandemic was a major challenge to health services around the world. previous experiences with severe acute respiratory syndrome (sars) and avian influenza a (h n ) prompted initiation of formal pandemic planning. essential and desirable features of pandemic plans include preparation for surveillance, investigation of cases, treatment modalities, prevention of community spread, maintenance of essential services, research and evaluation, and implementation, testing and revision of the plan. the experience of h( )n( ) influenza pandemic for emergency departments and their staff was problematic. the pace of the pandemic, coupled with untested pandemic plans, presented a unique range of challenges. in this paper, the contemporary challenges with respect to pandemic influenza prevention, control, and treatment are examined. the lessons learned are critical to our response to future pandemics, which are inevitable. the experience with severe acute respiratory syndrome (sars) and avian influenza a (h n ), as well as knowledge of influenza pandemics last century, prompted initiation of formal pandemic planning. pandemics evolve rapidly, and are complex and unpredictable. in , after the sars experience, the world health organization (who) identified the essential and desirable features of pandemic plans, which included: (i) preparation for surveillance; (ii) investigation of cases; (iii) treatment modalities; (iv) prevention of community spread; (v) maintenance of essential services; (vi) research and evaluation, and implementation; and (vii) testing and revision of the plan. this paper will critique the current literature with respect to contemporary challenges for pandemic influenza prevention, control and treatment. influenza viruses are myxoviruses, with three main genera, influenza a, b and c, which are capable of causing infection in humans. , only influenza a causes epidemics or pandemics in humans. , one antigen (haemagglutinin or h) on the outer coat of the virus anchors the virus to cells, and another (neuraminidase or n) helps it both enter and exit cells. influenza a subtypes are named according to which subtypes of h and n they possess. these antigens alter over time by a process of drift, or repeated minor mutations that occur over time, or shift, or major change in the antigens, which occurs when two different influenza viruses are simultaneously in a host and recombine. [ ] [ ] [ ] [ ] influenza may be transmitted by aerosols, large droplets, and direct and indirect contact. the relative importance of these modes is considered debatable. the virus can survive on non-porous surfaces for up to h and on unwashed hands for min. both seasonal and pandemic h n influenza outbreaks failed to demonstrate significant airborne transmission over long distances, but aerosol transmission may occur in confined spaces, especially when a large airborne infectious burden is present. , what is pandemic influenza, and what is the difference between it and seasonal influenza the who and the department of health and ageing (doha) state an epidemic occurs when there are more cases of a disease than is normal and a pandemic is declared when a worldwide epidemic occurs. , the who monitors influenza globally and is the body that declares the commencement and end of pandemics. influenza pandemics occur when a virus to which people have little or no immunity develops, and efficient human-to-human transmission exists. , pandemics may persist for months, years or decades, have rapid transmission, disease occurrence is outside usual seasonal patterns, and attack and mortality rates across age groups are unpredictable. the declaration of a 'pandemic influenza' has major effects on resource allocation within government and non-government health agencies. it also has profound effects in the function of societies, including disruption and closure of schools and workplaces, as well as restrictions on travel and social gatherings. however, the criteria by which an outbreak of an infectious disease may be declared a pandemic are neither fixed nor well defined. , they depend on a variety of factors including the relative incidence of an outbreak across jurisdictions, the severity of the infection, and cross-border or transnational cooperation with respect to the epidemiology of the disease. if a pandemic is defined merely by the spread of a new influenza virus strain around the world, the effects of having the formal declaration in place may disproportionately affect the function of society in the event of a mild illness. criteria also need to be developed for declaring a pandemic 'over'. in the case of pandemic h n , countries around the world ceased epidemiological tracking of the infection when it became ubiquitous. thus there is a need to establish international consensus on the formal definition and criteria for pandemic influenza to allow appropriate response to an outbreak, and to determine when declarations of pandemic may be lifted. pandemic plans require large-scale surge capacity in healthcare systems and the community. surge capacity is the ability to manage a sudden, unexpected increase in patient volume (i.e., numbers of patients) that would otherwise severely challenge or exceed the current capacity. pandemics have health, economic, political, and social impacts. , internationally, healthcare systems have few surplus resources. a us study identified that regardless of planning, few health services had staff, equipment, and facilities to implement them. there is no reason to believe that australia was in any better case. in australia, doha developed the australian health management plan for pandemic influenza (ahmppi) which was tested though exercise cumpston in and exercise sustain in . australian jurisdictional plans complement and augment the ahmppi. [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] exercise cumpston gave recommendations on the ahmppi. these included calling for streamlined decision making processes, flexible response according to disease severity and local resources, improved communications, public health education, a national surveillance framework, clarification of quarantine, border control, and emergency legislation, and involvement of primary care providers in planning. two years later, exercise sustain identified the differences between pandemic and disaster responses, and stressed the impossibility to plan for all eventualities given the unpredictability of new viruses. it addressed local community empowerment, recommending planning with community leaders and groups. social distancing was identified as an important prevention strategy. development of a productive relationship between the media and public health agencies, with an emphasis on timeliness, transparency, and honesty was explored, with health professionals considered to have most credibility for message delivery. australian state and territory pandemic plans additionally recommend the establishment of flu clinics, separate influenza triage, and designated 'flu hospitals' to facilitate quarantine and allow eds and general practitioners to maintain their core business. these plans aimed for staff protection, including priority vaccination for at-risk staff, pre-and post-exposure prophylaxis, the use of personal protective equipment and access to pandemic stockpiles, with those exposed or ill expected to self-isolate. [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] other identified needs include extra funding, pre-defined triggers for plan implementation and deactivation, anticipatory training of key personnel and suspension of non-essential and/or non-emergency hospital functions during the crisis. ventilators, medications and personal protective equipment were to be stockpiled. increased cleaning, security and crowd management capacity was identified in the plans, along with the need to increase morgue and laboratory capacity. more non-medical staff are required for administration, communication, transportation, security, cleaning and garbage disposal, and for crowd control. surge capacity applies across the entire community, with health, government and community groups required to act cooperatively. when individual hospitals reach capacity they need to have means to move patients and/or services to other hospitals or centres. [ ] [ ] [ ] healthcare worker illness needs to be planned for with use of agency, retired staff, and volunteers. seasonal influenza seasons have highlighted a lack of surge capacity in emergency departments (eds). the literature shows that pandemic planning and management are complex, expensive and difficult. in spite of exercises cumpston and sustain , australian pandemic plans were criticised during the h n influenza pandemic for most of the reasons identified as problematic during those exercises. [ ] [ ] [ ] remedying these problems goes beyond their recognition, and requires sustained and systematic investment on the part of government, the health system, health professionals, and the general public. overwhelming evidence exists that it is not possible to prevent pandemics, and when they occur they can cause substantial morbidity, mortality and social disruption. , when the h n influenza isolate was identified in mexico, their borders were closed at great economic cost to the country. however, the virus had already spread. air travel allows rapid and efficient spread during the incubation period when people are asymptomatic, rendering border closure and controls such as thermal scanning inefficient as a means of prevention. surveillance, identifying the onset, nature and size of the outbreak and populations affected is fundamental to pandemic control, identifying spread and trends, determining at-risk populations, allowing for targeted interventions, and monitoring of their effectiveness. surveillance of influenza-like illness (ili) in mexico allowed for identification and early warning of pandemic h n influenza , although there can be little doubt that the virus was circulating for some months prior to formal identification. it is difficult to clinically differentiate patients with influenza from those with other viral respiratory infections. rapid antigen point-of-care testing, was shown to have low accuracy for known pandemic h n influenza , and reverse transcriptase polymerase chain reaction (rt-pcr) provided the best method of testing. obligatory testing of all with respiratory disease ceased during the sustain phase of the pandemic, as positive diagnosis would not change treatment or isolation, and it would have been a pointless expense to keep testing. the literature shows testing was problematic and expensive. immunisation is a primary tool for pandemic influenza control, however it takes time to develop and manufacture vaccines. , in the interim, community mitigation strategies including social distancing, cough and sneeze etiquette, and frequent thorough hand hygiene may be used. , atrisk groups need targeted information and intervention. contact tracing of healthcare worker and patients' contacts has been recommended to identify those with risk factors for severe disease who may benefit from antiviral prophylaxis. a recent study in australia of the knowledge and attitudes the general public held towards pandemic h n influenza found low levels of public anxiety, a high degree of belief in government preparedness, vaccination and quarantine as effective public health measures, antiviral medication as moderately effective, and a low level of belief in hand hygiene as a preventative measure. quarantine was cited as being problematic with respect to work and food shopping. the literature shows that hand hygiene education and vaccination development are required for pandemic influenza control. social distancing is effective in infection control as a form of isolation. at the commencement of the pandemic, health department officials advised people with ili to present to their local ed causing overwhelming presentations by those with ili and those fearful they may have had contact. , , in a pandemic, general practitioner and hospital waiting rooms are a potential site for cross infection to already unwell people if people present with a highly infectious illness. this happened during the sars outbreak in canada in . the literature indicates that these patients are best treated in other sites. overcrowded living conditions contribute to rapid influenza spread. this contributed to the disproportionately high impact of pandemic h n influenza in indigenous communities in the northern territory. school closures have been used as a means of social distancing. however a western australian survey of parents whose children were in schools closed during the h n influenza pandemic revealing that % of these students participated in out of home activities including sporting events, shopping, outdoor recreation and parties while their schools were closed. this paper questions the efficacy of school closure in preventing infection spread, highlighting that students were congregating elsewhere. an example of effective isolation practice was seen during the simultaneous outbreak of pandemic h n influenza and seasonal (h n ) influenza which was contained on two australian cruise ships. the conditions encouraging contagion on the ships included living and socialising in partially enclosed close proximity, and people from both hemispheres (i.e., opposite flu season) coming together. prior to the outbreak, the ship procedures already included point-of-care testing, antiviral medication and isolation for ili patients. however, not all ill passengers sought medical care, presumably because they had mild illness or were unwilling to be isolated while holidaying. after disembarkation, passengers discovered their need to be quarantined via media reports, word of mouth, from ship staff or public heath staff. almost all complied with quarantine requirements, and only one case of infection passed from a passenger to another person was found, with no further community spread. thus, an epidemic on board ships was prevented from contributing to the pandemic. many people continue to work when they are ill. in the tropics influenza is under-recognised and under-diagnosed, which can cause people to inadvertently infect families, colleagues and patients. studies have shown that many healthcare workers either go to work or intend to work when they have influenza. [ ] [ ] [ ] one hospital in the usa experienced high levels of infection in their eds at the peak of h n influenza pandemic, with no commensurate increase in sick leave. this finding was reflected in a recent australian study. thus, the literature indicates that healthcare workers need further education on this matter. australian healthcare guidelines recommend contact and droplet precautions for influenza control. contact precautions include surface cleaning, hand hygiene, the use of gloves and gowns, single-use equipment wherever possible, and masks and eye protection when splashes may occur. additionally, droplet precautions add patient isolation or cohorting and minimising patient transfers. particulate respirators, eye protection, and impervious gowns and gloves, are advised for all aerosol-generating procedures, which should be performed in a negative pressure room if available. , , , australian guidelines recommend surgical masks for those entering an infectious area, coming within m or m of an infectious patient. where tolerated, masking the patient is more effective than masking the health care workers. personal protective equipment is vital to healthcare workers who cannot be protected in any other way prior to effective vaccine development. in , slow distribution of personal protective equipment from the national stockpile to frontline workers was a problem, with general practitoner practices running out of stock and being unable to replace it early in the pandemic. while the cdc recommends the use of respiratory protection of at least the equivalent of n masks for health care workers managing patients with ili, canadian research has found n masks are no more protective in influenza than normal surgical masks. inconsistencies in recommendations between authorities must be resolved to improve staff compliance and confidence. thus the literature calls for better distribution of personal protective equipment during an influenza pandemic and identifies research is required into appropriate mask usage. public education is vital to stop influenza spread. materials used must target the audience and be culturally appropriate. in the hunter new england area, focus groups identified challenges and potential solutions for limiting pandemic influenza in indigenous communities. these included having a local resource person with an understanding of the disease, provision of clear, simple, culturally appropriate information, access to health services and knowledge of how obtain these without infecting others, sensitivity to the importance of family and cultural gatherings, and aboriginal people having a say in how support is provided. pregnant women were targeted and encouraged to take precautions against acquiring infection and accept vaccination. doha developed a website which gave detailed advice for individuals, households, healthcare providers, businesses and communities, and provided a telephone hotline. this allowed people to receive the best possible advice in a timely fashion. the media are vital to spreading public health messages, but can be sensationalist, ill-informed, and may desensitise the public to the issue through information overload or precipitate 'moral panic'. , a single, knowledgeable, authoritative voice has the best chance of conveying information effectively. while vaccination is vital to halt the spread of pandemics, time is needed for development and production. an american study found that most of the people they surveyed would not accept a new, not fully tested vaccine approved under emergency use authorization. healthcare worker immunisation rates in australia are reportedly between % and %. reasons include low perception of personal risk, poor knowledge of how immunisation works, doubts about vaccine efficacy and/or safety, self-perceived contraindications, and inconvenient access. in spite of the hong kong experience of sars, a study conducted prior to and repeated during the outbreak of pandemic h n influenza reported no significant increase in intention to receive immunisation, with participants citing fears of side effects and doubts of efficacy. this was echoed in a more recent australian study with widespread perception that the pandemic h n influenza vaccine was rushed into production and not comprehensively tested. , low acceptance was also reported in greece. in the usa there was low public willingness to accept vaccination under an emergency order. when released in australian, presentation in multi-dose vials posed a problem, with insurance companies initially refusing to cover administering general practitioners. the use of multi-dose vials for mass immunisation was part of the ahmppi, and known associated risks can be minimised by adherence to clear guidelines on their use. alternative vaccination sites, including retail outlets and workplaces, have been proposed to increase public uptake of influenza vaccination. british columbia has proposed regulatory changes to allow pharmacists to administer vaccines. treatment for pandemic influenza is a matter of conjecture until the actual virus is identified and the clinical profile emerges. most pandemic h n influenza cases required simple supportive treatment including rest, fluids, and antipyretics, however advanced oxygenation therapy including high-frequency oscillation ventilation, nitric oxide or extracorporeal membrane oxygenation was required for some with severe disease. stockpiled ventilators were too old or too simple to provide complex ventilation strategies. [ ] [ ] [ ] [ ] debate occurred about the efficacy of oseltamivir for the treatment and prevention of pandemic h n influenza . the cochrane review concluding it merely shortened the duration of symptoms by h if given within h of disease onset, and thus should only be given to those sufferers with known risk factors for severe disease - especially as side effects include gastrointestinal symptoms and headaches, with rare cases of delirium and psychosis (most frequently in children and adolescents), raised liver enzymes, and allergic reactions. guidelines recommend oseltamivir administration within h of disease onset. adherence to this would have seen many treated for a disease they did not have in the h n influenza pandemic, as overwhelmed pathology services saw extended time lags between specimens being sent for testing and the arrival of results. generally speaking, humanity was better prepared for the h n influenza pandemic than for any other pandemic in history. while the disease itself was less virulent than expected, it confirmed the unpredictability of pandemic influenza, and its ability to cause significant impacts on health systems and the community. the h n influenza pandemic highlighted unresolved challenges identified in both exercise cumpston and exercise sustain , which we as a profession and society must address. public health challenges include developing means of increasing acceptance of influenza vaccination by both the general public and healthcare workers, provision of targeted education for the indigenous population and other at-risk groups, improving public knowledge of social distancing and personal hygiene measures in the prevention of transmission, and improving dissemination of information during a pandemic, especially via the media. we can use the evidence to refine pandemic plans and promote community well-being during an influenza pandemic. jennifer r. patrick and gerard j. fitzgerald have no competing interests or conflict of interests to declare. ramon z. shaban is editor-in-chief of the australasian emergency nursing journal but had no role in the editorial review of this manuscript whatsoever, and has no other competing interests or conflict of interests to declare. world health organization. who checklist for influenza pandemic preparedness planning department of health and ageing. pandemic influenza -types of influenza microbiology and infection control for health professionals s principles and practice of infectious diseases a/h n influenza virus the basics communicable disease control handbook asid (hic-sig) position statement: infection control guidelines for patients with influenza-like illnesses, including pandemic (h n ) influenza , in australian health care facilities. emja influenza in the acute hospital setting clinical management of human infection with pandemic (h n ) : revised guidance department of health and ageing. pandemic influenza world health organisation swine flu --lessons learnt in australia calibrated response to emerging infections health care facility and community strategies for patient care surge capacity working group on australian influenza pandemic prevention and preparedness. exercise sustain overview world health organisation. who consultation on priority public health interventions before and during an influenza pandemic hospital infectious disease emergency preparedness: a survey of infection control professionals department of health and ageing office of health protection. australian health management plan for pandemic influenza department of health and ageing. national pandemic influenza exercise -exercise cumpston report. canberra australian capital territory health management plan for pandemic influenza communicable disease control unit. victorian health management plan for pandemic influenza department of health south australia. pandemic influenza: a summary of health's operational plan special counter disaster plan: human pandemic influenza hospital response to pandemic influenza, part : emergency department response nsw human influenza pandemic sub plan queensland department of the premier and cabinet tasmanian action plan for human influenza pandemic national strategic plan for emergency department management of outbreaks of novel h n influenza. american college of emergency physicians surge capacity: a proposed conceptual framework pandemic influenza and critical infrastructure dependencies: possible impact on hospitals flu outbreak overwhelm eds highlight lack of surge capacity australia's influenza containment plan and the swine flu epidemic in victoria pandemic (h n ) influenza outbreak in australia: impact on emergency departments the general practice experience of the swine flu epidemic in victoria -lessons from the front line challenges and opportunities in pandemic influenza planning: lessons learned from recent infectious disease preparedness and response efforts what mexico taught the world about pandemic influenza preparedness and community mitigation strategies communicable disease control an introdction. melbourne: ip communications new influenza a(h n ) virus infections: global surveillance summary pandemic (h n ) influenza community transmission was established in one australian state when the virus was first identified in north america summary of the australasian society for infectious diseases and the thoracic society of australia and new zealand guidelines: treatment and prevention of h n influenza (human swine influenza) with antiviral agents poor clinical sensitivity of rapid antigen test for influenza a pandemic (h n ) virus detection of influenza a(h n )v virus by real-time rt-pcr the community's attitude towards swine flu and pandemic influenza h n influenza -managing the 'moral panic hospitals inundated as swine flu panic spreads flu planners fear ers flooded with the not-so-sick sars outbreak in the greater toronto area: the emergency department experience disproportionate impact of pandemic (h n ) influenza on indigenous people in the top end of australia's northern territory household responses to pandemic (h n ) -related school closures outbreaks of pandemic (h n ) and seasonal influenza a (h n ) on cruise ship influenza in the tropics self-reported anticipated compliance with physician advice to stay home during pandemic (h n ) results from the queensland social survey incidence and recall of influenza in a cohort of glasgow healthcare workers during the - epidemic: results of serum testing and questionnaire will they just pack up and leave?'' -attitudes and intended behaviour of hospital health care workers during an influenza pandemic which health care workers were most affected during the spring h n pandemic australian guidelines for the prevention and control of infection in healthcare centers for disease control & prevention. interim guidance on infection control measures for h n influenza in healthcare settings, including protection of healthcare personnel infection prevention and control in health care for confirmed or suspected cases of pandemic (h n ) and influenza-like illnesses preventing the spread of influenza a h n to health-care workers outbreak of swineorigin influenza a (h n ) virus infection -mexico surgical mask vs n respirator for preventing influenza among health care workers: a randomized trial hospitals and the novel h n outbreak: the mouse that roared reducing the risk of pandemic influenza in aboriginal communities centers for disease control & prevention. pregnant women need a flu shot public willingness to take a vaccine or drug under emergency use authorization during the h n pandemic influenza vaccination among healthcare workers influenza vaccination of health care workers in hospitals--a review of studies on attitudes and predictors willingness of hong kong healthcare workers to accept pre-pandemic influenza vaccination at different who alert levels: two questionnaire surveys toll of second swine flu wave could be high low acceptance of vaccination against the pandemic influenza a(h n ) among healthcare workers in greece insurance row threatens swine flu vaccinations h n and the use of multi-dose vials in mass vaccination alternative vaccination locations: who uses them and can they increase flu vaccination rates? ministry of health services british columbia. proposed changes allow pharmacists to give injections the experiences of health care workers employed in an australian intensive care unit during the h n influenza pandemic of : a phenomenological study critical care doctors want escalated pandemic planning novel h n influenza: the impact on respiratory disease and the larger healthcare system preparing for pandemic (h n ) neuraminidase inhibitors-the story behind the cochrane review what can we learn from observational studies of oseltamivir to treat influenza in healthy adults? neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis module name=product% info&searchkeyword=oseltamivir+phosphate &previouspage=∼/search/quicksearch. aspx&searchtype=&id= #an-adversereactions key: cord- -hpnkou authors: pitlik, silvio daniel title: covid- compared to other pandemic diseases date: - - journal: rambam maimonides med j doi: . /rmmj. sha: doc_id: cord_uid: hpnkou in december , the first cases of a new contagious disease were diagnosed in the city of wuhan, the capital of hubei province in china. within a short period of time the outbreak developed exponentially into a pandemic that infected millions of people, with a global death toll of more than , during its first months. eventually, the novel disease was named coronavirus disease (covid- ), and the new virus was identified as severe acute respiratory syndrome coronavirus (sars-cov- ). similar to all known pandemics throughout history, covid- has been accompanied by a large degree of fear, anxiety, uncertainty, and economic disaster worldwide. despite multiple publications and increasing knowledge regarding the biological secrets of sars-cov- , as of the writing of this paper, there is neither an approved vaccine nor medication to prevent infection or cure for this highly infectious disease. past pandemics were caused by a wide range of microbes, primarily viruses, but also bacteria. characteristically, a significant proportion of them originated in different animal species (zoonoses). since an understanding of the microbial cause of these diseases was unveiled relatively late in human history, past pandemics were often attributed to strange causes including punishment from god, demonic activity, or volatile unspecified substances. although a high case fatality ratio was common to all pandemic diseases, some striking clinical characteristics of each disease allowed contemporaneous people to clinically diagnose the infection despite null microbiological information. in comparison to past pandemics, sars-cov- has tricky and complex mechanisms that have facilitated its rapid and catastrophic spread worldwide. on january , , the genome of a new coronavirus, now known as severe acute respiratory syndrome coronavirus (sars-cov- ), was posted on the internet. it had been isolated days before from patients developing varying degrees of pneumonia in wuhan, the capital of hubei province in china. immediately thereafter, a growing number of scientists worldwide became deeply involved in analyzing its molecular details. one of the major tasks that they focused on was synthetizing the proteins encoded by the viral rna and deciphering their structure and function. acutely aware of the pandemic potential of sars-cov- , some of these scientists immediately alerted selected vaccine producers, with the hope of triggering a swift process for vaccine design and development. , once the protein amino acid composition and the post folding structure of close to proteins in sars-cov- were defined, multiple computational searches were launched by a number of institutions, looking to repurpose extant drugs aimed against the newly discovered molecular targets. in parallel to this accelerated research, there was a marked and frightening spread of this new coronavirus throughout wuhan to a widening area in china, and it was subsequently exported to a rapidly growing list of countries worldwide. , this paper reviews the microbiological, clinical, and epidemiological characteristics of the coronavirus disease (covid- ) pandemic, as well as its socio-economic impact. in addition, covid- is compared to previous pandemics in human history. in the early days of the pandemic great effort was invested into understanding the life cycle of sars-cov- , so as to provide a basis for discovery of an effective vaccine to prevent covid- and/or a safe and efficacious drug to cure it, or at the least, to ameliorate its symptoms, shorten its duration, and/ or block its mechanism of transmission. being a virus, sars-cov- must invade host cells, hijack the cell's biologic machinery for reproduction, and, finally, release multiple daughter virions. research uncovered six steps in the life cycle of sars-cov- : ( ) attachment and entry; ( ) uncoating; ( ) guide ribonucleic acid (grna) replication; ( ) translation in the endoplasmic reticulum and golgi apparatus; ( ) assembly; and ( ) virion release. , the external surface of sars-cov- has multiple protruding elements called spike proteins which, after manipulation by host cell enzymes (furin and tmprss ), function as anchors for attachment to the host cells. , the cell surfaces of the upper and lower respiratory tract are covered with angiotensinconverting enzyme- (ace ) receptors, which are physiologically involved in blood pressure regulation. however, these receptors are also present in many other organs and tissues, helping to explain some of the extra-respiratory manifestations of covid- . once attached to the external membrane, sars-cov- covers itself with a portion of the host cell membrane and becomes an intracellular endosome. this structure undergoes partial uncoating allowing the release of grna into the cytoplasm of the host cell. the released strands of grna attach to host ribosomes, rna-dependent rna polymerase (rdrp), and together activate the grna replication mechanism. other released strands of grna undergo translation into structural, nonstructural, and coat proteins. the different basic blocks of the reproduced virus are finally assembled into multiple virions that are expelled to the extracellular space of the host. these released daughter virions are now ready to infect other cells or, even worse, other hosts. once these mechanisms had been clarified, multiple hypotheses relating to specific actions of different drugs were proposed. for example, chloroquine, hydroxychloroquine, and azithromycin all inhibit the uncoating of the invading endosomes. on the other hand, the antivirals remdesivir and favipiravir inhibit grna replication by rdrp. additional drugs, not only antivirals, have also been identified to tar-get the complex mechanisms of the intracellular viral cycle. the first human coronavirus was described by june dalziel almeida in . she had observed a viral structure seen under electron microscopy while being involved in a study investigating causes of the common cold. a paper submitted by almeida and her team described a crown-shaped structure supposed to be a new type of virus causing common colds. this paper was rejected as the editors claimed that "these microscopic observations resulted from distorted influenza viruses." , since this pioneering observation, around species of viruses in the subfamily coronaviridae have been described, the majority of which were found in animals, primarily though not only in bats. only some of the animal coronaviruses had been associated with a specific animal disease such as a severe type of bronchitis in poultry. on the other hand, many of these coronaviruses were isolated from healthy animals, again predominantly bats. based on current knowledge, there are seven species of human coronaviruses. four of them ( figure , table ) cause a mild upper respiratory tract infection manifested as a runny nose. occasionally, they involve the lower respiratory tract. the remaining three human coronaviruses are associated with a wider spectrum of disease severity. relatively frequently they cause severe pneumonia and other serious complications ( figure , table ). as indicated in figure , five of the seven human coronaviruses have well established intermediate hosts, based on both epidemiologic and genomic data. in the case of covid- , preliminary data suggest that several species of pangolins are the suspected intermediate host. pangolins are mammals covered by keratin scales. in china the pangolin is seen as an edible animal mainly, but traditional medicine in this country also attributes multiple curative properties to a powder obtained by mashing their scales. , although the transmissibility of both severe acute respiratory syndrome (sars) and middle east respiratory syndrome (mers) is lower than that of covid- , the case fatality ratio is many times higher for mers and sars than for covid- (table ) . however, the number of covid- cases have markedly outnumbered the number of cases in both sars and mers. while clinical manifestations for the two last-mentioned infections were generally limited to the respiratory tract, although with higher degrees of disease severity, it is remarkable that there has been a wide spectrum of heterogeneous clinical manifestations in covid- cases. from a pathophysiological perspective, this phenomenon is explained by the ubiquitous presence of ace receptors throughout multiple organs and blood vessels. at a clinical level, some typical covid- manifestations described during the pandemic include "silent anoxia," a discrepancy between an extremely low oxygen level as measured by pulse oximeter and the simultaneous lack of dyspnea; signs of cardiac involvement including myocarditis, myocardial ischemia, and myocardial infarction ; hepatitis ; reddish discoloration of the toes mimicking frostbite or chilblains ; intravascular coagulation including pulmonary embolism ; encephalitis ; and acute renal failure (see also table ). recently a condition similar to kawasaki syndrome was described in a growing number of teenagers (as opposed to toddlers with classical kawasaki syndrome); it has been proposed to name the syndrome "pediatric multisystem inflammatory syndrome." the mechanism of this complication is an overreaction of the immune system. a comparison of the leading clinical identifiers of recognized pandemic diseases is provided in table . the simplest definition of a pandemic is a contagious infectious disease that has spread to multiple geographic areas or continents. the term "contagious" implies that the infection can be transmitted person-to-person, either directly or indirectly. various degrees of controversy emerge between members of the medical and scientific communities when defining a new disease as pandemic. according to the world health organization (who), "a pandemic is the worldwide spread of a new disease." however, even this condensed and crisp definition, not infrequently, leaves room for discussion. a convention, held at the beginning of the h n pandemic under the umbrella of the national institutes been published, mainly during this last decade. [ ] [ ] [ ] [ ] [ ] [ ] [ ] many web sites [ ] [ ] [ ] [ ] [ ] [ ] and review articles have also reviewed the history of pandemics. interestingly, there is a significant discordance in the inclusion or the exclusion of specific infectious diseases causing pandemics. table provides a chronological list of the major known pandemics reviewed in this article. [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] obviously, written testimony on possible pandemics is lacking with regard to prehistoric times. however, it is important to recall that during the preagricultural era, the nomadic population of homo sapiens on earth was relatively small. consequently, we can assume that pandemics were relatively rare at that time. the known history of pandemics is based on the discoveries of documentation by ancient historians and other sources. table provides an overview of the known pandemics throughout history. [ ] [ ] [ ] [ ] [ ] [ ] [ ] due to the lack of consensus on the definition of a pandemic, there are some cases in which there is a discrepancy regarding the categorization of an epidemic as a pandemic. for example, the sars epidemic in - had all the characteristics of a potential dire pandemic, but fortunately its spread was interrupted by yet unexplained mechanisms. some pandemics such as aids have been widespread both in time and in vast geographic distribution. current knowledge marks the s as the beginning of the human immune deficiency virus (hiv) epidemic, when zoonoses from pan troglodytes troglodytes to humans occurred in africa. , similarly, the cholera and plague pandemics had a zoonotic origin. , figure provides some illustrative examples of the human (panel a) and zoonotic (panels b and c) factors contributing to the spread of pandemics, and devices developed to help avoid their spread (panels d, e, and f). intriguingly, and according to databases managed by both johns hopkins university and the european centre for disease prevention and control, plots of the daily global numbers of covid- infected persons during the second trimester of reveal an undulating and ascending pattern that is difficult to explain. however, they also show a progressive and steady decrease in mortality for that same period. this last observation merits a logical explanation, but there has not been enough research to date to provide one. the cumulative number and type of mutations detected during the first months of do not explain the reduced severity of sars-cov- . table also demonstrates the predominance of rna viruses as the cause of most pandemics, with the only exception being the variola virus, which is composed of dna. relatively few pandemics were caused by gram-negative bacteria. yellow fever epidemics occur mainly in africa and south america. the disease is transmitted by several species of mosquitoes, mainly by aedes aegypti. the disease life cycle has two possible scenarios: ( ) the sylvatic cycle, where the hosts are various types of animals, primarily monkeys; and ( ) the urban cycle, where the reservoir is human beings. outbreaks occur mainly during the rainy season. water accumulation, on land or in various objects, facilitates development of vector mosquitos. other viruses transmitted by aedes aegypti include dengue virus, zika virus, and chikungunya virus. for close to half a century, several ebola virus outbreaks have occurred in western and central africa. the long-term reservoir of this virus is a species of bats. due to massive deforestation, there have been episodes of viral spillover to humans and animals, including gorillas and chimpanzees. subsequently, human-to-human transmission occurred as the result of close contact with patients or bodies at burial ceremonies, and some convalescing patients continued to transmit the virus for some time after recovery. due to the high contagiousness of ebola, many health care workers were also infected. currently, there is an effective vaccine to prevent ebola (table ) as well as a drug composed of three types of antibodies (table ). in general, annual seasonal influenza in postpandemic years is caused by variants of the corresponding virus from the prior pandemics. influenza viruses involved in seasonal flu accumulate antigenic changes in a progressive fashion resulting in annual seasonal epidemics. an accepted parameter for the impact of annual influenza activity is the excess number of deaths. , interestingly, in , a reemergence of human h n viruses identical to those circulating before was attributed to an accidental "escape" of an old frozen laboratory specimen. epidemics and pandemics have had a very strong impact on human history. diseases like smallpox, measles, and plague decimated entire populations in several regions of europe, the middle east, and asia. at the end of the fifteenth century, the european conquistadores of the americas brought diseases with them that were unknown to the native population. due to the local lack of immunity to these newly imported viruses, smallpox and measles spread rapidly, causing fear and frustration among the natives due to the lack of natural resistance and a very high mortality rate; local communities were decimated and sometimes entire settlements were wiped out. this tragedy facilitated the conquest of the land and the massive conversion of indian tribes to christianity across the americas. beginning in the last decade of the twentieth century, the aids pandemic intensified its spread on all continents, inflicting the greatest damage in africa at the social, economic, and political levels. some of the manifestations of this megacatastrophe were the significant shortening of life expectancy, massive destruction of family units, and orphanhood. in addition, the profound immune suppression caused by hiv led to a rampant increase in the incidence and prevalence of tuberculosis and other infectious diseases. combined, these factors had a disastrous effect on the political structure of most african countries. , across history, pandemics have differentially infiltrated battling armies and in this way tipped the outcome of battles and war. during the last decades and as a valuable complement to the written documentation on ancient bacterial pandemics, paleomicrobiological studies relating primarily to the plague (yersinia pestis) have contributed greatly to the reshaping of our understanding of its epidemiology. there was much confusion and controversy regarding the epidemiology of plague in the multiple pandemics that occurred several centuries ago, until the studies of french investigators, drancourt and raoult and colleagues, which revolutionized several contentious concepts established by other investigators. their work centered on the skeletal remains of common graves from various epochs. [ ] [ ] [ ] [ ] by examining the bacterial dna in the pulp of relatively preserved teeth, they found genomic evidence for not only yersinia pestis but also for bartonella quintana, a bacterium transmitted by lice. , since yersinia pestis is also found in body lice, the investigators developed a laboratory rabbit model and exposed the animals to human lice infected with specific bacteria. additional epidemics investigated by the same scientists were found to be caused by bartonella quintana alone or combined with rickettsia prowazekii. these and other studies supported the theory that infected lice were key spreaders of yersinia pestis, sometimes found in polymicrobial infections. with regard to smallpox, several well preserved mummies have been found in egypt and other countries. some mummies, such as that of the egyptian pharaoh, ramses v, provided dermal evidence that they had terminally suffered from smallpox. however, genomic evidence for the actual virus has been found only rarely in mummies. this can be explained by the poor long-term preservation of viruses. other diseases documented by paleomicrobiological methodologies include tuberculosis, leprosy, and multiple parasitic infections. the past years have seen rapid development of genetic sequencing technologies for rna and dna. from the beginning, rna/dna research has been characterized by both exaggerated promises and inflated expectations regarding the importance of human genetic traits that predispose for both infectious and non-infectious diseases. unfortunately, to date, no human genetic markers predisposing to sars-cov- infection, nor the severity of covid- , have been found-although recent isolated exceptions to this statement can be found. for example, there may be a predisposition to covid- among humans with blood group a as opposed to other blood groups. in sharp contrast to human genomics, mapping viral rna mutations of sars-cov- has enabled a fairly accurate reconstruction of its transmission ( figure b ) and helped to determine its phylogenetic origins (figure and figure a ). , viral sequencing of samples obtained from covid- patients, and being able to mark its different mutations, has provided a much clearer and more accurate picture of viral transmission as opposed to results obtained by contact tracing. for example, a study of disease importation to continents, countries, or regions has surprisingly uncovered several shuffled patterns in the genomic data. when considering importation of the first covid- cases to the western united states, the initial investigation based on contact tracing indicated that those cases were epidemiologically unrelated. however, after sequencing multiple virus isolates, the researchers concluded that they were not only closely related, but probably also began with one patient of origin. a series of questions must be answered when attempting to determine the primary source of a pandemic virus like sars-cov- . as it is a coronavirus, the most probable source is a virus that originated in bats. to confirm this theory, genomic profiles of coronaviruses previously isolated from bats must be compared with coronavirus profiles isolated from patients. if these sequences are identical, then it can be assumed that the primary source is a bat. however, if the virus has been preserved in panel b, each circle represents a coronavirus isolated from a patient. different colors indicate a virus mutation. a genome sequencer device (machines in the figure) is used to determine the location and type of mutation: auuu, a segment of the viral genome adenine uracil uracil uracil; aucu, same segment of the genome after mutation cytosine replacing middle uracil; or gucu, same segment of the genome following another mutation: guanine replaced adenine. in the refrigerators of a virology laboratory, there exists a very real possibility of viral "escape" from the laboratory to the community. in this scenario, especially if the laboratory is located in the proximity of the epidemic epicenter, a laboratory origin of the pandemic virus would be a strong alternative. additional tests such as antibody testing of the personnel working in the suspected laboratory should provide further assistance in elucidating the true origin and pathway of the virus. other possible trajectories should also be investigated. for example, if early infections occurred in persons who had close contact to bats or other animals, such as animals raised on farms or held and sacrificed at wet markets, this would clearly point to a specific zoonotic link. another possibility is that the new virus was engineered for investigational purposes or with malicious criminal intentions. by looking at the structural details of the virus, molecular biologists have ruled out and published the arguments against this last-mentioned possibility. the covid- pandemic exemplifies the difficulties encountered when attempting to quantify the important numerical parameters of the disease. first of all, when trying to count the number of infected cases, this parameter is significantly underestimated, primarily because the proportion of people who are asymptomatic or suffering from mild disease are not yet known. secondly, the initial shortage of laboratory kits has limited the number of people who can be ideally tested. the same problem arises when attempting to calculate the basic reproduction number, i.e. the number of persons who were infected by a certain patient. in this case, it is not easy to draw a line to those who should be considered a contact. a similar bias can interfere with calculation of the case fatality ratio, i.e. the proportion of infected persons who have died of covid- . in addition to underdetection of mainly asymptomatic patients, some deaths due to covid- complications passed under the radar since the patients had not been tested for the virus. last but not least, the sensitivity and specificity of viral tests are not %, resulting in occasional false negative or false positive results. a complementary method to assess pandemic-related mortality is to measure excess deaths compared to previous years during the same season. in order to retrospectively estimate the number of infected persons, serologic tests are performed that measure the presence of specific igm and igg antibodies to sars-cov- . currently, there are many ongoing seroprevalence studies of anti-sars-cov- antibodies; however, the picture remains incomplete regarding the significance of these findings as markers of previous infections. in , a cholera outbreak erupted in the densely populated neighborhood of soho, london. john snow, a physician who lived in the vicinity, mapped the houses of the many affected persons with cholera. he discovered a water pump in the center of the mapped area that had been used by all infected persons for obtaining drinking water. on his advice, municipal authorities removed the pump handle, resulting in an immediate end to the epidemic, with no further cases. it was subsequently learned that human excrement pits had drained into and contaminated the water supply. this brilliant epidemiological investigation led to john snow being considered the "father of epidemiology." in the s a major epidemic of cholera occurred in peru. vibrio cholera contaminated the ballast water in ships that had arrived from india. massive contamination of large quantities of live fish occurred when the ballast water was discharged into the sea near the shore. fish were subsequently caught from this area, and thousands of peruvians developed cholera after consuming raw fish (ceviche), a popular traditional food. the epidemic was terminated abruptly when the health authorities recommended to discard the head and branchia (gills) when preparing the fish for consumption. following the spread of the covid- pandemic, the health authorities of most countries imposed a lockdown with various intervals of delay from the first detected case(s) so as to contain the local spread of the virus. subsequently, they also imposed the use of respiratory masks to reduce airborne transmission by infected persons and to prevent contagion among the uninfected population. data from several countries have shown that the earlier and more stringent the lockdown was applied, the better the efforts in containing the pandemic. vaccines are human-made molecular tricks aimed at cheating the immune system of the host, to make it "believe" that it has encountered a microorganism-causing disease (professor myron levine, personal communication). table lists the current availability of approved vaccines for pandemic diseases. paradoxically, some of the newer diseases such as aids and those caused by coronaviruses still lack an approved effective vaccine. on the other hand, smallpox, a very old but already eradicated disease, was (to the best of our knowledge) the first disease for which several types of "natural" empiric vaccines were used, initially by the chinese in ancient times, and subsequently by edward jenner in england in the eighteenth century. , interestingly, vaccination with smallpox vaccines was implemented several centuries before the discovery of viruses in general, and variola and vaccinia viruses in particular. as recently summarized by the who, there are currently at least different covid- vaccination research projects underway in the quest to prevent covid- . essentially, six groups of vaccines are being explored, three of which first require the isolation of viral particles. these virions are either: ( ) weakened (attenuated); ( ) killed by hot or chemical substances (inactivated); or ( ) fragmented viruses followed by isolation of small pieces of the virus (subunits). a second class of vaccine starts with genetically engineered pieces of either rna or dna, which subsequently are embedded in either: ( ) plasmids (dna); ( ) lipids (rna); or ( ) an adenovirus vector. in all cases, particles are diluted in a solution for initial animal testing (preclinical trials) and subsequent testing in humans (clinical trials). clinical trials are performed in three phases, each one having an increasing number of volunteers. phase i ( - volunteers) examines safety and immunogenicity. phase ii (> volunteers) examines safety, immunogenicity, and dose adjustments. phase iii (more than , volunteers) primarily examines infection prevention following exposure. if all three phases are successful, then the vaccine undergoes regulatory approval and subsequent mass production under strict quality control. the main problem with the need to develop a vaccine against a new pandemic microbe is that the process is lengthy and mined with multiple obstacles. , in the past, the elapsed time from vaccine development to approval and production could take up to years. however, in order to efficiently and rapidly cope with an emerging pandemic, ideally, the scientific world must be prepared with predefined "templates" to facilitate accelerated vaccine development. if a proposed vaccine causes serious side effects or alternatively is not sufficiently immunogenic, the development process should be restarted from the beginning. in some cases, when a clinical evaluation of a vaccine reaches phase iii, the number of newly infected cases drops rapidly, making it difficult to test the actual efficacy of the vaccine in preventing infection. in the quest for a covid- vaccine, there have been a few initiatives to recruit volunteers who would be challenged with the virus after being immunized. however, for this scheme to work, it is essential to have a very efficacious drug available for treating the infection, should the vaccine fail. in general, with regard to the efficacy of antiviral treatments, viral infections can be divided into three groups: ( ) infections lacking an effective antiviral therapy (e.g. sars, yellow fever, measles); ( ) infections in which antivirals do not cure the infection, but which do produce varying degrees of clinical improvement (e.g. influenza, aids, covid- ); and ( ) infections that can be cured by antiviral therapy (e.g. ebola, hepatitis c). table provides an overview of the treatments used for different pandemic diseases. despite an increase in antibiotic resistance, there remain multiple choices for treatment of bacterial pandemics. for example, the main pillar of medical treatment for cholera is the emergency replacement of large amounts of fluid lost as a result of diarrhea and vomiting, with antibiotics playing a secondary role in its treatment. the fatality ratio of untreated cholera is around %. however, prompt administration of appropriate amounts of fluids either orally or intravenously decreases the case fatality ratio to %. the overwhelming death toll from covid- has sparked a myriad of projects to identify drugs that can be repurposed on a fast track to for special treatment of patients with severe disease. in the meantime, the only drug that has shown some beneficial results in a double-blind randomized clinical trial compared to placebo is the antiviral remdesivir, which has been approved by the us food and drug administration and other regulatory institutions. the administration of convalescent plasma from recovering patients with covid- is now being examined at different sites, including new clinical trials, but conclusions regarding this therapy are still pending. the economic impact of past pandemics is hard to examine due to the lack of robust data. however, a retrospective look at the first months of the covid- epidemic reveals a catastrophic impact on the economies of most countries having to cope with significant numbers of cases. the harshest economic impact generally occurred in varying degrees in wealthier countries. one of the most important parameters for quantifying economic damage is the gross domestic product forecast, although different countries use other economic metrics. according to the majority of prognoses, the damage was expected to be greatest during the second quarter of . the primary reason for the severe economic impact of covid- has been the leading and widely justified slogan, "health before wealth." another parameter that has significantly contributed to the economic crisis worldwide is the swift increase in job losses. quantification of financial activities in selected populations may add important data to more accurate evaluation of the world economy as a result of the covid- pandemic. for example, listing the purpose of out-of-home visits (residential, parks, workplace, grocery stores, pharmacy) may contribute to a composite financial evaluation of representative family units. , despite the rapid and advanced progress in many medical disciplines since the end of the nineteenth century, the covid- pandemic has sadly demonstrated vast limitations worldwide in successfully coping with it. there is no doubt that the unexpected and yet fully unknown behavior of sars-cov- has strongly contributed to its pandemic status. for example, the high proportion of infected but totally asymptomatic persons has made containment challenging, to say the least. in some cases, the proportion of infected persons feeling absolutely well can approach almost %. for example, a covid- outbreak occurred on a cruise ship departing ushuaia in the province of tierra del fuego, argentina, and navigating to the antarctic peninsula. sampling the entire population on board revealed that a vast majority had contracted the infection, but % of them were asymptomatic patients. another tricky characteristic of the virus is that infected patients expelled virus particles through their respiratory tract, primarily during the early phases of the incubation period before they became symptomatic. selected examples from prior pandemics should illuminate our vision for the future. smallpox went from being a totally empiric vaccine to global eradication of the disease. however, aids, which is caused by a zoonotic retrovirus that translates its rna to dna and enters the human genome, presents an almost impossible challenge in approaching a total cure for the disease, although combinations of antivirals are able to halt or reverse the progression of the disease. this retrospective analysis and comparison of covid- with prior pandemic diseases can contribute to the improvement of a rationale and scientific approach to future epidemics or pandemics. the most important take-away point should be an understanding of the high degree of preparedness that is needed, including various protocols for social distancing that are adapted to the different transmission modalities of the involved microbes. in addition, multiple innovative protocols aimed at a robust accelerated vaccine development process are needed. disease-causing viruses, or colonizing species in the animal kingdom, should be evaluated for potential spillage to human beings. for those specific viruses, it is imperative to delineate seminal protocols that can be launched in emergency situations. recently, the new york times launched two very recent dynamic applications that allow tracking the daily status of therapies and vaccines for covid- . , readers can visit these sites to access updates regarding ongoing developments related to covid- vaccines and treatments. finally, the conclusion of this paper, at this point in time, is to stress the importance of ongoing refinement of interactions between government leaders, scientists, and economists, at both the national and international levels, so as to better grapple with the current (and any future) pandemic, as it unfolds. genomic epidemiology of novel coronavirus -global subsampling clinical characteristics of coronavirus disease china the trinity of covid- : immunity, inflammation and intervention moderna's work on a covid- vaccine candidate inovio urgently focused on developing covid- vaccine: because the world can't wait. inovio website. , inovio pharmaceuticals a sars-cov- protein interaction map reveals targets for drug repurposing european centre for disease prevention and control. covid- pandemic the architecture of sars-cov- transcriptome novel drugs targeting the sars-cov- /covid machinery covid- infection: origin, transmission, and characteristics of human coronaviruses structural variations in human ace may influence its binding with sars-cov- spike protein characterization of the receptor binding domain (rbd) of novel coronavirus: implications for development of rbd protein as a viral attachment inhibitor and vaccine physiological and pathological regulation of ace , the sars-cov- receptor network-based drug repurposing for novel coronavirus -ncov/sars-cov- she discovered coronaviruses decades agobut got little recognition studies on the structure of a coronavirus-avian infectious bronchitis virus mossman k. bats and coronaviruses zoonotic origins of human coronaviruses epidemiological analysis of covid- and practical experience from china probably pangolin origin of sars-cov- associated with the covid- outbreak crossref . tobin mj. basing respiratory management of covid- on physiological principles cardiovascular disease and covid- covid- and liver disease chilblain-like lesions on feet and hands during covid- epidemic covid- and its implications for thrombosis and anticoagulation neurological manifestations and complications of covid- : a literature review kidney disease is associated with in-hospital death of patients with covid- kawasaki-like disease: emerging complication during the covid- pandemic world health organization (who) pandemics: a very short introduction pandemics: a brief history plagues & history: past, present and future viruses: a scientific american library book a planet of viruses the evolution and emergence of rna viruses pandemic: a brief history of influenza, the plague, cholera, and other infectious diseases that have changed the world; how they started, how they ended, and the lessons learned by humanity of the worst epidemics and pandemics in history. live science website outbreak: of the worst pandemics in history how of history's worst pandemics finally ended. history website visualizing the history of pandemics. visual capitalist website the worst outbreaks in u.s. history a history of aids: looking back to see ahead crossref . sharp pm, hahn bh. the evolution of hiv- and the origin of aids plague: history and contemporary analysis attenuated sars-cov- variants with deletions at the s /s junction the influenza pandemic: years of questions answered and unanswered severe influenza: overview in critically ill patients paleomicrobiology of humans the history of epidemic typhus a personal view of how paleomicrobiology aids our understanding of the role of lice in plague epidemics human lice in paleoentomology and paleomicrobiology advancements in next-generation sequencing analysis of protein-coding genetic variation in , humans the effects of blood group types on the risk of covid- infection and its clinical outcome phylogenetic analysis of ncov- genomes where it went from there stunned the scientists a pneumonia outbreak associated with a new coronavirus of probable bat origin genomic characterization and epidemiology of novel coronavirus: implications for virus origins and receptor binding the proximal origin of sars-cov- a systematic review of asymptomatic infections with covid- evaluation of covid- rt-q pcr test in multi-sample pools preliminary prediction of the basic reproduction number of the wuhan novel coronavirus -ncov diagnosis of the coronavirus disease (covid- ): rrt-pcr or ct? excess mortality estimation during the covid- pandemic: preliminary data from portugal diagnostic performance of covid- serology assays cholera and the water supply in the south districts of london ucla department of epidemiology, fielding school of public health new insights on the emergence of cholera in latin america during : the peruvian experience impact of complete lockdown on total infection and death rates: a hierarchical cluster analysis the jenner society and the edward jenner museum: tributes to a physicianscientist smallpox vaccines for biodefense draft landscape of covid- candidate vaccines the race for coronavirus vaccines: a graphical guide the covid- vaccine development landscape the sars-cov- vaccine pipeline: an overview remdesivir for the treatment of covid- -preliminary report deployment of convalescent plasma for the prevention and treatment of covid- economics in the age of covid- the economic impact of covid- covid- : in the footsteps of ernest shackleton coronavirus drug and treatment tracker coronavirus vaccine tracker. the new york times key: cord- -upzxscux authors: adeoti, adekunle olatayo; marbus, sierk title: the european respiratory society course on acute respiratory pandemics: how to plan for and manage them date: - - journal: erj open res doi: . / . - sha: doc_id: cord_uid: upzxscux learn about the @erstalk course on acute respiratory pandemics http://ow.ly/xge i acute respiratory infectious diseases are more likely to cause future pandemics, as droplet generation and potential transmission of infectious agents could constitute a major public health threat [ ] . the exposure and associated risk of infections are not limited to the individuals' immediate environment, as some cases could cross boundaries and constitute global health challenges of international concern [ ] . a gap in emergency preparedness in the event of an outbreak was apparent during pandemics like those of severe acute respiratory syndrome coronavirus (cov), influenza virus a (h n ), ebola virus and middle east respiratory syndrome cov [ , [ ] [ ] [ ] . it is apparent that conducting clinical research in response to swiftly emerging disease outbreaks could be challenging and is often delayed [ ] . moreover, transmission of such infections during pandemics may be widespread in healthcare settings, especially with the increased demand on medical personnel and associated morbidity, resulting in a reduction in the available workforce. hence, it is imperative to create awareness among medical personnel, and train them on how to prepare for pandemics and conduct research in order to reduce mortality and morbidity during epidemics. the first european respiratory society (ers) course on acute respiratory pandemics was organised to train and improve participants' knowledge on how to plan for and manage pandemics [ ] . course members shared an interest in infection prevention and control but had different backgrounds, ranging from medical specialists to general practitioners, epidemiologists and researchers. participants from three continents, namely africa, europe and asia, were involved in the -day training programme held in amsterdam, the netherlands, from november to , (figure ). seasoned faculty members were carefully selected based on their research work, skills and experience in the area of outbreak investigation, communications, planning and management of pandemics. emphasis was laid on the practical workshops, which simulated pandemic scenarios with the aim of stimulating course participants to respond appropriately in cases of a pandemic. the aim of this course report is to give a short overview of some of the key lectures, highlights and take-home messages. • creating awareness, training medical personnel and planning an appropriate response at all healthcare levels is essential for pandemic preparedness. • integrating research into pandemic preparedness plans is often forgotten but is crucial for timely clinical research during and after pandemics. • during a pandemic, communication and collaboration between all stakeholders should be optimised for effective outbreak control. on the first day of the course, an overview of the european union seventh framework pandemic preparedness project prepare was given. prepare is a european research framework designed to harmonise large-scale clinical research studies on infectious diseases in order to provide real-time evidence for clinical management and timely healthcare interventions during a pandemic (www.prepare-europe.eu). the three outbreak research modes identified in the prepare programme are preparation, mobilisation and response, thereby differentiating the levels of research preparedness in case of an outbreak. the one health approach, which is a multidisciplinary collaborative approach to solve global and health challenges for humans, animals and the environment was also advocated by p. penttinen of the european centre for disease prevention and control (ecdc) to enable effective control of outbreaks [ ] . a public health preventive stance and outbreak investigation measures were stressed by v. prikazsky from ecdc during an interactive lecture in which he focused on the need for proper epidemiology in the investigation and sampling in case of an outbreak as well as factors responsible for vaccine failure. the key contributors on the second day stressed the importance of adequate communication during epidemics. crucial aspects of communication during an epidemic include finding out who your audience is, getting to know their social and cultural background, and delivering understandable, tailored and specific messages. taking the audience's comments into account, acknowledging risks and modifying your next messages are important for effective communication during an epidemic. the world health organization (who) risk communication course is worth taking as an e-module on the who website to improve communications skills in this setting [ ] . in another lecture, the need to escalate medical provision within the hospital and the value of a checklist for pandemic preparedness was emphasised [ ] . this checklist will help hospitals set up regulations and protocols on essential issues such as communication, surge capacity, logistics, case management, surveillance and scale-up of laboratory services. during outbreaks of severe acute respiratory infections, intensive care units (icus) are often fully occupied; l. derde gave an overview on the icu perspective on conducting research and management in critical cases during a pandemic. special attention was paid to children during pandemics by p. fraaji, as they may be worst hit due to their relatively low immune response to infectious agents. furthermore, j. buchanan stated the vital role played by an effective primary healthcare facility in the event of an outbreak. she also stressed the need for training and retraining of healthcare personnel in the use of personal protective equipment as basic as gloves and facemasks. on the final day of the course, ethical aspects of pandemics, in general and in research, were covered. these dealt with the ethical challenges, especially as regards to balancing social and individual benefits from research in an emergency situation against the potential harms and risks to individuals and the community at large (www.prepare-europe.eu). in addition, study participants may be more vulnerable because of public panic or fear; thus, the principles of autonomy, justice and beneficence may be subordinated to that of non-maleficence. a fast-track review by an ethical committee, which should include local representatives, is necessary to conduct timely research during such periods. the high point of this course was the workshop simulating a pandemic scenario due to a new cov strain. during this workshop lead by g. carson, the knowledge acquired on the ers course was put into practice. the participants were divided into six groups representing stakeholders from every healthcare level: clinicians, laboratory healthcare workers, researchers, government, and local and national public health personnel. each stakeholder had to adapt their strategy and management plan depending on new information given while the scenario evolved. there were live active inserts by skype from who, public health england and the us centers for disease control and prevention as the scenario escalated, to add realism. at the end of the workshop, situational reports were given by each stakeholder, underscoring the need for integrated care, effective communication skills, early research and information management in the event of an outbreak. important take-home messages were the need to improve communication between stakeholders and establish effective collaboration in outbreak control, as well as early efforts to integrate research activities in the event of a pandemic. factors associated with death or hospitalization due to pandemic influenza a(h n ) infection in california infection prevention and control of epidemic-and pandemic-prone acute respiratory infections in health care. geneva, world health organization emerging and reemerging diseases in the world health organization (who) eastern mediterranean region -progress, challenges, and who initiatives clinical review: sars -lessons in disaster management diagnostic preparedness for infectious disease outbreaks talking to the people that really matter about their participation in pandemic clinical research: a qualitative study in four european countries ers training course: acute respiratory pandemics: how to plan and manage mers-coronavirus: from discovery to intervention who checklist for influenza pandemic preparedness planning acknowledgements: we thank the organising committee, a. simonds, p. penttinen, l. sigfrid and g. carson. the course was funded by european union seventh framework research grant prepare (workpackage create). key: cord- - abweqko authors: kersebaum, dilara; fabig, sophie-charlotte; sendel, manon; sachau, juliane; lassen, josephine; rehm, stefanie; hüllemann, philipp; baron, ralf; gierthmühlen, janne title: the early influence of covid- pandemic-associated restrictions on pain, mood, and everyday life of patients with painful polyneuropathy date: - - journal: pain rep doi: . /pr . sha: doc_id: cord_uid: abweqko introduction: the sars-cov- pandemic requires special attention on its psychological effects and the impact on patients with chronic pain. objectives: this study aimed at examining the influence of the covid- pandemic-associated regulations initiated by the german government on pain intensity and characteristics, emotional well-being, and everyday life of patients with painful polyneuropathy. methods: forty-three patients (well assessed with questionnaires before the pandemic and without change of their health status between baseline and current assessment) were investigated with validated, self-reported questionnaires and covid- -specific items weeks after the regulations came into effect. results: pain intensity remained stable or even improved like the neuropathic pain symptom inventory total score (t : . ± . vs t : . ± . , p = . ). only . % reported a pandemic-associated pain worsening. rumination scores of the pain catastrophizing scale were lower during t compared to before the pandemic regulations (t : . ± . , t : . ± . ; p = . ). interestingly, pain ratings for the last days were higher in patients with a changed social life compared to those without (− . ± . vs . ± . ; p = . ). quality of life was decreased and helplessness increased in those with higher pain ratings. conclusion: results suggest a shift of attention from the chronic pain condition towards the imminent threat of a global pandemic. as the impacts of the pandemic are persistent and evolving, the development of the measured parameters in the forthcoming weeks will be of great interest. on january , , a strain of coronavirus (sars-cov- ) that had not been detected in humans before has been identified to be responsible for the occurrence of several recent cases of acute respiratory distress syndrome in wuhan city (hubei province, china). to date, the disease caused by sars-cov- (coronavirus disease , covid- ) has evolved into a pandemic. with , , cases (according to the respective case definition and testing rate of each country) and at least , fatal outcomes by finalization of this article, the covid- pandemic poses vast challenges for international healthcare systems. the world health organization (who) has published technical guidelines concerning covid- . the regulations taken by each country to contain and manage the outbreak in the spring of were individual but had one thing in common: an extensive impact on private, professional, and public life, as well as education, economy, and patient care, leading to social distancing, existential fear through loss of income or unemployment, and a feeling of uncertainty with unforeseeable long-term effects. previous infectious disease outbreaks have been shown to be associated with increased rates of depression, anxiety, and generalised fear. , a study examining the long-term psychiatric morbidities among sars survivors found posttraumatic stress disorder and depressive disorders to be the most prevalent longterm psychiatric conditions. this is also expected for the current pandemic, and the who has published recommendations to support mental and psychosocial well-being in different target groups during the outbreak. chronic pain, affecting up to % of the world's population, occurs in comorbidity with depression and concerns multiple fields, eg, social life and economy. the biopsychosocial approach of pain describes pain and disability as a multidimensional, dynamic integration among physiological, psychological, and social factors that reciprocally influence each other. it has been reported that pain interference is influenced by social isolation, and therapeutic interventions aimed at increasing social connection can potentially reduce the impact of pain on engagement with activities. consequently, chronic pain patients might exceptionally be affected by the pandemic due to medical concerns and the change of social life. it was therefore our hypothesis that in a group of patients with painful polyneuropathy, the emotional well-being and consequently the experienced pain intensity would deteriorate due to the pandemic and social isolation. this study aimed at the examination of this hypothesis in the early phase of the pandemic in germany (for exact regulations of the german government, see appendix , available at http://links.lww.com/pr /a ). patients with confirmed painful polyneuropathy who had been wellcharacterized clinically and with questionnaires for a former study were contacted by telephone and asked about possible participation in a new study (fig. ) . in case of consent, the patient information and agreement were sent along with a set of standardized questionnaires relating to pain, emotional well-being, sleep, and physical activity as well as pandemic-associated questions about changes in daily life due to the pandemic. to account for possible spontaneous changes in the above-mentioned parameters on overall state of health in the time between first assessment in the context of the former study and the current study, patients were asked to rate their overall health status for the time point before the corona pandemic (the time until the end of february ) compared to the time point of assessment for the former study on a seven-staged patient global impression of change likert-scale with very much improved, moderately improved, minimally improved, unchanged, minimally worse, moderately worse, and very much worse. the exact date of the patients' last visit was noted on the patient global impression of change questionnaire. for the analysis, only patients who reported an unchanged or minimally worsened or improved health status were included to exclude patients with a change of health status before the pandemic due to other reasons (fig. ) . all contacted patients had probable (presence of a combination of symptoms and signs of neuropathy including any or more of the following: neuropathic symptoms, decreased distal sensation, or unequivocally decreased or absent ankle reflexes) or confirmed (presence of an abnormality of nerve conduction or validated measure of small fiber neuropathy with class evidence with corresponding symptoms) neuropathy according to tesfaye et al. and neuropathic pain was diagnosed according to the neupsig algorithm. only patients with probable or definite neuropathic pain according to the neupsig algorithm were included in the analysis. patients with any additional painful comorbidity that could influence questionnaire results were excluded from participation in the study. the questionnaires were sent to the patients on april rd, ie, approximately weeks after the governmental regulations became effective (eg, prohibition of private events of any kinds). by then, we expected potential measurable changes that might have occurred as a consequence of the regulations. governmental regulations were stable during the time when the patients received and completed the questionnaires. all patients provided written informed consent to participate in the study. the study was performed in accordance with the declaration of helsinki, approved by the local ethics committee (az d / ) and registered at the german clinical trials register (drks ), also accessible through the who internationals clinical trials registry platform. demographic data (ie, age, sex, average pain intensity, pain relief, comorbidities, pain medication, pain location, and cause of neuropathy) of the patients were collected. pain presence, frequency, current analgesic medication, and pain relief were assessed with the brief pain inventory (bpi). originally developed for the measurement of cancer-related pain, the bpi is today validated in many languages and widely used for the assessment of chronic pain diseases and for acute pain conditions. pain severity, impact on daily function (not assessed in this study), pain location, pain medications, and the amount of pain relief in the past hours and the past week are assessed either selfreportedly or through an interview. pain intensity was calculated with the bpi pain severity subscale ranging from (no pain) to (maximum intensity). the scale was then interpreted to mild ( - ), moderate ( - ), and severe pain ( ) ( ) ( ) ( ) . an interpretation of this numeric scale into mild, moderate, and severe is common. because the bpi user guide does not recommend specific cutoff points, we chose this categorization because the intensity " " is usually considered to be the threshold for inclusion in pain studies. the neuropathic pain symptom inventory (npsi), a selfadministered questionnaire specifically developed to evaluate the severity of neuropathic pain, consists of items plus temporal items that are rated on a scale from to ( none, maximal imaginable intensity). higher scores indicate more severe neuropathic pain. the patient reported outcomes measurement information system (promis) short form v . -pain interference a is a self-reported, -item measure for the assessment of consequences of pain on life's relevant aspects. there are response options to each item, ranging from to ( not at all, very much). after the raw score is calculated by summing the score of each question, it is converted into a t-score through a conversion table, resulting in a standardised score with a mean of and an sd of . values . are considered abnormal. higher scores indicate a higher symptom/disease burden. ). their scoring works similarly to the above-mentioned system for the pain interference measure. the pain catastrophizing scale (pcs) was used to assess pain catastrophising traits. it consists of statements describing different thoughts and feelings that may be associated with pain. these statements are to be rated on a -point likert scale (ranging from "not at all" to "all the time"), a total score is obtained by scoring all the items. higher scores indicate greater pain catastrophizing. the factor iv -item scale of the international personality item pool's (ipip) is a representation of the goldberg markers for emotional stability. the patient is supposed to rate each item corresponding to the level of accordance with his own personality (ranging from very inaccurate to accurate). for the first questions, corresponds to "very inaccurate" and to "very accurate," whereas for the remaining, it is reverse. a sum score is calculated. for the interpretation of individual scores, the mean and sd for a sample of persons (same sex and particular age range) is calculated. scores within one-half sd of the mean can be interpreted as "average", and outside that range as "low" or "high". quality of life was measured with the eq- d- l, , one of the most frequently used instruments for the evaluation of healthrelated quality of life. besides a visual analogue scale (eq vas) where the patient is asked to rate the overall health state on a to scale, there is a descriptive system containing different dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that are to be rated on a five-point likert scale (ranging from to ). patients are asked to choose the most appropriate level in each dimension. through weighing of the items, an index score between and was calculated, a higher score indicating a better quality of life. only the change in scores was considered for this study. in items, patients were asked about changes in their daily life due to the regulations (appendix , available at http://links.lww. com/pr /a ). the items refer to ( ) whether the patient lives alone and/or has pets ( ) social interactions ( ) medical care ( ) activities of daily life ( ) physical activities (usual amount of days they spent walking at least minutes a day) in the past week and whether there had been changes due to the regulations. ( ) handling of the covid- news, habits of media consumption ( ) influence of restrictive regulations on pain, sleep, mood, and fear of future ( ) current state of employment and existential fear for part of the analysis, patients were divided into groups according to whether they experienced social change or not (see below). the analysis of the collected data was performed using ibm spss statistics for windows (version . ). intraindividual data of first and second assessments were compared using wilcoxon signed rank test. intergroup comparisons were calculated with differences in questionnaire results between first and second assessments for patients with and without social changes and with and without a pain increase using the mann-whitney u-test. "social change" was defined in case a patient had not lived socially distanced before february and personal social contacts were discontinued due to the pandemic-associated regulations. patients who had lived socially distanced before the pandemic already, ie, had no contact to friends and family or stated that their social life remained unchanged during the pandemic regulations, were considered for the "no social change" category. these categories were based upon questions in the pandemic questionnaire (question number and , see appendix , available at http://links.lww.com/pr /a ). chi-square test was used for statistical calculation of categorical variables between first and second assessments. values are presented as mean sd, and p , . was considered statistically significant. patients were included in the analysis (fig. ) . the time of assessment was . sd months (range - months) after the assessment that had been performed for the former study. patient characteristics such as sex, age, pain intensity, and comorbidities are shown in table . at the time of the second assessment ( t ), ( . %) patients reported having suffered from polyneuropathy-induced pain for to years and ( . %) patients for more than years. most patients (n , . %) were diagnosed with idiopathic polyneuropathy. the polyneuropathy of patients ( . %) was caused by diabetes mellitus. patients ( . %) suffered from medication-induced polyneuropathy ( of those caused by chemotherapy) and patients ( . %) from autoimmune-induced polyneuropathy. there was one patient each with one of the following diagnoses: polyneuropathy caused by alcohol abuse, poems syndrome, and vitamin b deficiency. none of the patients currently received chemotherapy or any other cancer treatment at either point in time. the analgesic medication is listed in table , and pain locations are shown in table . the number of coanalgesics did not differ significantly between t and t (t , t ). patients reported a general pain relief due to medication of . % at t and . % at t (p ns). despite the multitude of measures, we did not perceive any complaints by the patients. the feedback was overwhelmingly positive, and the patients communicated their satisfaction with the early inspection of this matter and their curiosity. / ( . %) returned the completed questionnaires. except for the npsi total score, which indicated an improvement of the extent of the neuropathic pain, the total scores and subscores of pain questionnaires did not change between the baseline assessment and the follow-up (table ). however, grading of bpi scores into mild, moderate, and severe showed more patients suffering from moderate pain and less patients suffering from severe pain upon follow-up (p . , table ). in line with this finding, only ( . %) patients indicated a deterioration of their pain intensity within the first weeks of the pandemic regulations ( table ) . pain catastrophizing scale rumination score decreased from baseline to follow-up, ie, patients spent less time occupied with thinking about their pain. looking specifically at patients with stable or improved pain within the first weeks of the regulations, they showed a lower pcs rumination score, ie, they seemed to be less occupied with their pain ( table ) . by contrast, a higher pcs helplessness score was found in those with a deterioration of pain ( table ). in addition, patients with a deterioration of pain reported a lower quality of life upon eq d ( table ). neither the promis pain interference score nor the eq- d assessment (eq- d index) resulted in significant changes in the overall patient cohort. interestingly, in contrast to pain intensity, a remarkable number of patients reported a worsening of their mood ( / , . %) and sleep ( / , . %) due to the pandemic in the pandemicrelated questionnaire (appendix , available at http://links.lww. com/pr /a ). however, this worsening was not mirrored by reports upon self-reported, validated questionnaires ( table ) . a set of pandemic-associated changes are shown in table . the results of the remaining items of the covid-associated questionnaire, that have been collected to characterize the study cohort, are shown in appendix (available at http://links.lww. com/pr /a ). there was no significant change measurable concerning the number of days the patients spent walking more than minutes in the past week (t : . . ; t : . . ; p ns). out of , ( . %) still reported to go out for walks and / ( . %) reported to do some exercise at home. more than % of the patients used to exercise regularly outside home before the pandemic, which was not possible anymore due to the regulations (appendix , available at http://links.lww.com/ pr /a ). patients ( . %) reported having experienced disadvantages in medical care due to the pandemic. those disadvantages affected doctors' appointments (n , . % of all patients who have answered the question), drug supply (n , . % of all patients who have answered the question), and postponed surgical interventions (n , . %, details in appendix , available at http://links.lww.com/pr /a ). patients who did not report any medical disadvantages due to the pandemic showed a lower npsi total score (t : . . vs t : . mean . sd; p . ). they also showed an increase in the ipip-emotional stability score (t : . . vs t : . . ; p . ) and an increase in the promis anxiety score (t : . . vs t : . . ; p . ). through the covid-related items, patients ( . %) described a changed social life during the pandemic. patients with a steady social life presented an improvement or a trend towards an improvement of pain intensity upon several pain scales in the first weeks of the pandemic regulations ( table ) , whereas patients with a social change showed higher pain ratings compared to those without a social change on bpi average pain rating within the last days (fig. and table ). patient reported outcomes measurement information system depression, anxiety, pain interference, sleep, and fatigue scores, and quality of life did not differ between those with and without a change of social environment. the pcs rumination score was higher in patients with a change of social environment compared to those without ( table ). two weeks after the onset of the pandemic-associated regulations, only . % of patients reported a worsening of pain intensity, whereas . % stated to be worried about the course of the pandemic. accordingly, mean pain intensity remained stable or even improved, whereas pcs rumination score decreased. patients who experienced a change of social life consequently to the regulations had increased pain ratings, reported less quality of life, and demonstrated more pain catastrophizing thoughts. overall, however, the effect of the pandemic regulations on pain intensity was-contrary to the expected-at best mild, although the regulations significantly impacted daily life. given that the patients would undergo the often-reported, common patterns of disaster response, a possible explanation is our early assessment. the present results would then mirror the so-called "heroic" stage which would be characterised through provisional adjustment. accordingly, a disillusionment on the further time course would be expected, characterised by resentment and uncertainty. we therefore hypothesize that collecting data at forthcoming dates is likely to reveal more distinct changes. eccleston et al. state that the pandemic will have consequences for patients with chronic pain conditions, discussing that this might also be due to diversion of resources and the circumstance that many healthcare professionals specialising in pain are directly relevant for the acute response to the pandemic. accordingly, nearly half of our study cohort reported to have experienced medical disadvantages since the pandemic. those who did not, however, displayed a decrease in neuropathic pain and a higher ipip emotional stability score (probably feeling confident as they did not experience the medical disadvantages that had been predicted to occur). the overall decrease of the npsi total score and pcs rumination score suggests that patients spent less time thinking about their pain, in line with the bpi scores that showed more patients suffering from moderate pain and less patients suffering from severe pain. we presume this might be due to the circumstance that the emergence of a pandemic (associated with anxiety, overflowing information, and dramatic changes in public and private life) poses a "distraction" from the chronic pain condition. , , comparing the results for patients with and without a worsening of pain, those without had lower scores upon several pcs items (eg, rumination). patients with a worsening of pain showed higher pcs helplessness scores and indicated to have a lower quality of life-implying that a certain predisposition to catastrophize might be linked to higher pain perception. a connection between increased behavioural expressions of pain and catastrophizing and a contribution of a tendency to "catastrophize" during painful stimulation to more intense pain experience have been described earlier. thus, coping mechanisms might be distinctive tools for the management of pain during the pandemic. in addition, patients with a social change reported higher or stable pain ratings, whereas patients without a social change even presented a trend towards an improvement of the pain. results of stable or even improved pain intensity can again be explained by distraction from pain, whereas increased pain intensity in those with social change is in line with findings by karayannis et al. who showed that the impact of pain is reduced in individuals who have the feeling of being included and engaged with others. a link of chronic and temporary loneliness with increased physical pain had been shown for fibromyalgia patients. the lower pcs rumination scores in patients with a steady social life stress the importance of maintaining contact with the family and social entourage in times of pandemic-associated regulations. , although the majority of our cohort reportedly remained in contact through telephone, personal interaction clearly is irreplaceable. thus, social integration also seems to be important for the handling of pain during the pandemic. wide-ranging psychological consequences of comparable events leading to quarantine and isolation (eg, anxiety through financial loss, , depressive disorders ) have been reported. during the initial phase of the sars-cov- outbreak in china, the psychological impact was rated as moderate to severe by more than half of the respondents, and a high prevalence of low mood ( . %) has been described. although nearly half of our patients indeed reported a worsened mood due to the regulations in our specific covid- -related items, we did not observe an influence on psychological parameters upon selfreported questionnaires, possibly due to above-mentioned short time interval between regulations and assessment and because these questionnaires have not been validated specifically under pandemic regulations. quality of life weeks after the onset of the regulations has not been affected significantly in our overall study population. this again is explainable through the assessment time. the examined time frame was accompanied by an immense public esprit of cohesion and "being in this together," possibly contributing to a certain appeasement of worries and fears. in addition, more than half of the study population ( . %) indicated to be confident that the situation would improve in the coming weeks and only patients reported existential fears. it will be of great interest to examine pain intensity, emotional well-being, and quality of life amid the upcoming fake news, conspiracy theories, and economic pressure. this work draws its relevance from the fact that chronic pain is a prominent health issue that reportedly affects up to one-fifth of the world's population with a bidirectional influence of similar magnitude of pain and mental illness. bearing in mind that depression has been reported to be one of the leading contributors to the global disease burden , and contributes to pain deterioration, patients with a chronic pain condition clearly require special attention amid the expected psychological impact of the pandemic. one limitation of this study is that the first assessment was part of former studies and thus not directly before the pandemic regulations. thus, we cannot fully conclude that the observed changes are really a consequence of the pandemic regulations or due to a memory bias of patients. however, to minimize this bias, we have included only patients who reported a stable disease between first and second assessments. in addition, treatment medication might have influenced the outcome. we acknowledge that the comparison of patients with and without social change is underpowered (with only patients without social change), but nonetheless found the comparison to be of interest. however, it is important to recognize that this study is exploratory due to the unique situation and needs confirmation in targeted studies. in the current assessment, . % indicated that their pain worsened due to the pandemic, as opposed to . % that stated to be worried about the course of the pandemic. a significant decrease of ruminating on pain and of the npsi score in painful neuropathy patients was observed weeks after the onset of regulations, suggesting that pain stands back amid the very real threat of a devastating pandemic. with the whole public and private life orientated towards tackling the exceptional situation and the media continuously reporting about various aspects of it, the population's attention is focused on the pandemic and is most likely to be in the "heroic" phase. consequently, it remains to be of interest how pain and mental health of the patients will evolve in the forthcoming weeks with persisting, exceptional impacts on public and private life. this study was supported by grünenthal gmbh deutschland with no involvement in experimental design, conduction, or interpretation of the study. dilara kersebaum reports grants from grünenthal gmbh, during the conduct of the study; sophie-charlotte fabig reports grants from grünenthal gmbh, during the conduct of the study as well as personal fees from grünenthal gmbh outside the submitted work; manon sendel reports grants from grünenthal gmbh, during the conduct of the study; personal fees from sanofi genzyme, personal fees from grünethal, personal fees from akcea, outside the submitted work; dr. sachau reports grants from grünenthal gmbh, during the conduct of the study; non-financial support from alnylam pharmaceuticals, non-financial support from pfizer, personal fees from grünenthal gmbh, outside the submitted work;. josephine lassen reports grants from grünenthal gmbh, during the conduct of the study; dr. rehm reports grants from grünenthal gmbh, during the conduct of the study; dr. huellemann reports grants from grünenthal gmbh, during the conduct of the study; grants from bmbf, grants from medoc , grants from zambon, the submitted work german federal ministry of education and research (bmbf): verbundprojekt: frühdetektion von schmerzchronifizierung (nochro) ( gw c) agentur brigitte süss, grünenthal pharma ag schweiz, grünenthal b.v. niederlande, personal fees from pfizer pharma gmbh asahi kasei pharma corporation, abbvie deutschland gmbh & co. kg, air liquide sante international frankreich, alnylam germany gmbh, lateral pharma pty ltd gierthmühlen reports grants from grünenthal gmbh, during the conduct of the study; personal fees from tad pharma, personal fees from glenmark, certkom, personal fees from pfizer, grünenthal, sanofi pasteur, novartis, outside the submitted work development of a promis item bank to measure pain interference imaging how attention modulates pain in humans using functional mri effectiveness and safety of tapentadol prolonged release (pr) versus a combination of tapentadol pr and pregabalin for the management of severe, chronic low back pain with a neuropathic component: a randomized, double-blind, phase b study comorbidity between pain and mental illness-evidence of a bidirectional relationship the psychological impact of quarantine and how to reduce it: rapid review of the evidence development and validation of patientreported outcome measures for sleep disturbance and sleep-related impairments the patient-reported outcomes measurement information system (promis) developed and tested its first wave of adult self-reported health outcome item banks md anderson. brief pain inventory (bpi) | md anderson cancer center pain assessment: global use of the brief pain inventory effects of valdecoxib in the treatment of chronic low back pain: results of a randomized, placebocontrolled trial grand challenges in global mental health training manual for mental health and human service workers in major disasters die bundesregierung. coronavirus-neue leitlinien. available at managing patients with chronic pain during the covid- outbreak: considerations for the rapid introduction of remotely supported (ehealth) pain management services covid- situation update worldwide, as of neuropathic pain: an updated grading system for research and clinical practice a broad-bandwidth, public domain, personality inventory measuring the lower-level facets of several five-factor models. personality psychology in europe the development of markers for the big-five factor structure the price of pain: the economics of chronic adolescent pain us department of heath, education, and welfare public health service alcohol, drug abuse, and mental health administration . ecdeu assessment manual for psychopharmacology development and preliminary testing of the new five-level version of eq- d (eq- d- l) mental health strategies to combat the psychological impact of covid- beyond paranoia and panic chronic pain has arrived in the icd- -iasp interpreting individual ipip scale scores mental health status of people isolated due to middle east respiratory syndrome the impact of social isolation on pain interference: a longitudinal study how item banks and their application can influence measurement practice in rehabilitation medicine: a promis fatigue item bank example postoperative pain in patients undergoing a transcutaneous active bone conduction implant (bonebridge) the experience of sars-related stigma at amoy gardens long-term psychiatric morbidities among sars survivors evaluating psychosocial contributions to chronic pain outcomes effects of attention on the intensity and unpleasantness of thermal pain anxiety, depression and sleep disorders in patients with diabetic neuropathic pain: a systematic review painrelated cerebral activation is altered by a distracting cognitive task item banks for measuring emotional distress from the patient-reported outcomes measurement information system (promis®): depression, anxiety, and anger pain catastrophizing a critical review wen soon s. psychosocial and coping responses within the community health care setting towards a national outbreak of an infectious disease the pain catastrophizing scale: development and validation theoretical perspectives on the relation between catastrophizing and pain eq- d value sets : inventory, comparative review, and user guide diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments the german ethics council. solidarity and responsibility during the coronavirus crisis immediate psychological responses and associated factors during the initial stage of the coronavirus disease (covid- ) epidemic among the general population in china global burden of disease attributable to mental and substance use disorders: findings from the global burden of disease study loneliness, daily pain, and perceptions of interpersonal events in adults with fibromyalgia world health organization. country & technical guidance -coronavirus disease (covid- ) world health organization. mental health and psychosocial considerations during the covid- outbreak the authors are indebted to the subjects who participated in the study for their consent and cooperation. the authors thank their student assistant swantje jendral for her committed, outstanding support of this study. key: cord- -jr x emx authors: de castro, leonardo; lopez, alexander atrio; hamoy, geohari; alba, kriedge chlare; gundayao, joshua cedric title: a fair allocation approach to the ethics of scarce resources in the context of a pandemic: the need to prioritize the worst‐off in the philippines date: - - journal: dev world bioeth doi: . /dewb. sha: doc_id: cord_uid: jr x emx using a fair allocation approach, this paper identifies and examines important concerns arising from the philippines’ covid‐ response while focusing on difficulties encountered by various sectors in gaining fair access to needed societal resources. the effectiveness of different response measures is anchored on addressing inequities that have permeated philippine society for a long time. since most measures that are in place as part of the covid‐ response are meant to be temporary, these are unable to resolve the inequities that have led to the magnitude of morbidity and mortality associated with the pandemic. these cannot improve the country’s readiness to deal with pandemics and other emergencies in the future. transition to a new normal recognizes the possibility that other infectious diseases could come and endanger our health security. our pandemic experiences are proving that having an egalitarian society will serve the interests not only of disadvantaged sectors but also of everybody else, including the privileged. response measures should thus take the opportunity to promote equity by giving importance to the concerns of the underprivileged and vulnerable while giving preference to initiatives that can be sustained beyond the period of the current pandemic. how dire is the situation in this country compared to the rest of the world? as of august , , the philippines was nd in the list of countries with the highest number of covid- cases throughout the world and it had the highest number of cases among members of the association of southeast asian nations, even though its population is less than half that of second placed indonesia. the philippines also had the highest number of covid- cases per million in the region, and the th highest number of active cases as well as the nd highest total number of deaths in the world. additionally, the country had the highest number of deaths per million population among southeast asian countries as of august , . in light of these statistics, it is quite frustrating that the philippines could only manage to be ranked a lowly th in the number of tests done per million population. perhaps this is partly due to the economic reality that the country's gross domestic product at purchasing power parity (ppp) per capita in was only $ , -rated th worldwide and only th among southeast asian countries. the rankings using the above covid- parameters have deteriorated even after the country was placed under the longest quarantine period in the world. the prolonged lockdown is understood to be the reason why filipinos are experiencing a "recession for the first time since the - asian financial crisis". before the pandemic started to show its effects in the country in january , the unemployment rate was recorded at . percent. it quickly rose to . percent in april , meaning that there were . million filipinos in the labor force who were out of a job -a record high for the country. the impact of covid- has been of such magnitude that social, cultural, economic, educational, political, and health institutions have been shaken. the steps taken to address this impact have forced the government to acquire loans since march this year amounting to us$ . billion, a figure that has worried economists because of what it means for the country's debt to gdp ratio. as the government experiments with ways of jumpstarting a process of recovery for the filipino people, we have to be very clear about the nature of the issues that we need to address as we put together initiatives based on a vision of the future that we can widely share. this paper uses a fair allocation approach to identify and analyze ethical concerns arising in the context of the covid- pandemic. fair allocation is taken to refer to "arrangements that allow equal geographic, economic and cultural access to available services for all in equal need of care." the arrangements can be systemic or politically driven; they can be the product of neglect or indifference. the approach shares the view that "all systematic differences in health between different socioeconomic groups within a country can be considered unfair and, therefore, classed as health inequities, [and these]. . . are directly or indirectly generated by social, economic and environmental factors and structurally influenced lifestyles. while highlighting the existing access or lack of access in the context of very closely intertwined social and health indicators, this paper uses equity and equality interchangeably: "in the public health community the phrase social inequalities in health carries the same connotation of health differences that are unfair and unjust. hence, the paper's fair allocation approach examines the covid- related events and response measures on the basis of the principle that the pandemic experiences cannot be seen in isolation as strictly health phenomena: "health equity cannot be concerned only with health, seen in isolation. rather it must come to grips with the larger issue of fairness and justice in social arrangements, including economic allocations . . . . indeed, health equity as a consideration has an enormously wide reach and relevance." this approach considers the impact of how health-related resources have been allocated or distributed and looks at the issues over a period that precedes the onset of the covid- emergency and extends beyond the expected end of the current pandemic. what this avoids is a narrower view that looks at the covid- emergency as a disease-focused phenomenon that started with the transmission of the virus to humans and will end when a medical solution is discovered in the form of a cure for the disease or employment and fair wage, and economic aid. the difficulties often lie in terms of geographic, economic and cultural access. the resources referred to are not readily recognized by non-medical people as having a huge impact on health although they have long been accepted as social determinants of vulnerability to diseases. , it is perhaps for this reason that the lack -or unfair allocation -of pertinent resources has been insufficiently addressed or pushed down the priority order in government decision-making. this paper examines an extensive inventory of reported experiences and explores their consequences and ethical implications as they arise from the inequities. it also investigates the interconnected and overlapping health, educational, and cultural fronts in the development of the pandemic and the impact that these have on existing social and economic inequities. by examining the way that pertinent resources are accessible to different stakeholders, a fair allocation approach highlights how closely the experiences of various socio-economic and political sectors are bound inextricably together. this is very useful because of the nature and character of the pandemic that we are going through. in the context of the covid- pandemic we are forced to accept that the kind of life that each sector of the country's population experiences is a function of the kind of life that every other sector is experiencing. during better times, we manage to live as if we have separate lives whose mutual and interdependent connections we can downplay or entirely overlook. this happens because the interconnection is not easily perceived even when it is comprehensively present. perhaps it is partly because we have been conditioned to accept the inequities as an inescapable part of reality in a resource-challenged country. the pandemic has put the interconnectivity among various sectors under the spotlight through the impact of sars-cov- . by infecting more than million people of various demographics throughout the world, the virus has manifested its ability to penetrate barriers regardless of nationality, age, ethnic origin, or socio-economic circumstances. there is an undeniably real risk of acquiring infection regardless of who we are and what demographic category we belong to. given the ease of transmission of the virus across the global population, no one can be left untouched by the pandemic's consequences. even statistical outliers such as billionaires who can pass the time away in secluded vacation spots have to be dependent on other people who maintain their yachts, produce and prepare their food, look after their psychosocial and medical needs, and provide such other services as they might require during their prolonged period of seclusion. the ability of these people to provide services can easily be affected by the pandemic. this paper proceeds by identifying specific inequities in the philippines and beyond, exploring how these are being experienced in the context of the pandemic, and examining how problems are being addressed through specific measures in the evolving covid- response. each section focuses on an area of inequity and discusses the implications of measures being implemented not only for the short term but also for the post-pandemic period. the paper goes on to anticipate the ethical requirements for the post-pandemic new normal and to make broad recommendations for an ethical framework that ought to govern our transition to the new normal. facilities but also on a more general access to prevention and basic treatment. if we begin to give thought to considerations of ethics and fairness only when we encounter shortages in the filling of prescriptions or the use of hospital facilities then we are likely to be acting merely to limit, or to make up for harm already inflicted on people because of their unmet healthcare needs. our effort to respond justly to people's emergency health care needs may be too late already at that point. but, using timely preventive measures, or simply well-directed dissemination of information, health problems that send people to emergency rooms can be avoided in the first place. these can even be addressed much earlier by attending to social determinants of health. there is nothing new about this observation, but the reiteration is timely because the emergency we are facing makes it easier to focus on basic principles of public healthcare. the effort to promote healthcare fairness, guided by the principle of prioritization of the worst off, has to be planned across various stages leading up to emergencies. steps taken to promote fairness at the time of an emergency can easily be a merely remedial measure that ought to have been preempted by proper allocation initiatives way before the existence of an emergency. this paper discusses the fairness of allocation measures in relation to the dispensing of adequate information, the provision of isolation and quarantine facilities, the availability of healthcare services and providers, and the criteria for triage in the hospital setting. it is important for this paper's approach that healthcare is understood to be a two-way effort that involves people caring and people being cared for. this relationship between the "carer" and the "cared for" involves both parties thinking about the situation and making decisions together. the process stems from the autonomy of human beings or their right to self-determination. patients in healthcare settings, as well as non-patients who are the intended beneficiaries of public health initiatives, simultaneously have the status of being cared for and being "carers." they are carers in the sense of having to be decision-makers insofar as the care that they need and deserve is concerned. by virtue of their being carers, they need to have access to information that may initially be available only to those who are regarded as having the primary role as carers (healthcare professionals and authorities). this means that information understandable to carers also has to be rendered understandable to the cared for. this is important in the context of public health and health promotion where healthcare providers may need reminding that dispensing care and information is an effort that they jointly carry out with the recipients. the pandemic emergency does not necessarily clothe them with authority to perform their tasks with arrogance and disdain for the ignorance and lack of medical sophistication that they may occasionally encounter in the cared for. this also means that the perspective of the cared for has to be understood -and respected -by the carer. in this way, the cared for is afforded an opportunity to exercise self-determination. strictly speaking, the cared for does not shift perspectives. what happens is that the perspective of the cared for is taken into consideration by the healthcare provider because the process of caring, on this account, is being done by the carer on behalf of the cared for. the carer and the cared for are partners in the activity. the relationship between them is not hierarchical but complementary, as healthcare providers or researchers need to be reminded when seeking informed consent from patients or research subjects. in this section of the paper, the neglect of these principles, especially the prioritization of the worst off, in public healthcare decision-making is examined in relation to three problems within the philippines in the context of the covid- pandemic: paternalistic decision-making complicated by false information, failure to be mindful of literacy levels, and failure to account for language and other barriers. the first problem is paternalistic decision-making or deciding without consulting stakeholders. the philippine government has needed to act swiftly to contain the spread of the disease. it has had to enforce quickly crafted rules that could not wait for extended rounds of consultations and confidence building. quite understandably, the existence of a pandemic emergency compels decision-makers and government officials to act unequivocally and resolutely. however, emergencies also tend to trigger a highly paternalistic stance that can have the effect of reducing human beings to mere recipients of information. failing to heed instructions for dealing with the pandemic, people may be shunted aside for being obstacles to the implementation of a necessary emergency response. yet, firm and decisive action is not necessarily incompatible with a compassionate and lawful consideration for the rights of citizens regardless of their level of education and health literacy. emergencies should inspire creativity in finding ways to implement laws and rules decisively without showing disrespect for fellow human beings who may not have the means or opportunity to understand the full import of new laws and rules. the arrogant display of power by authorities under these circumstances reflects a paternalistic stance that can deteriorate into a disregard for the interests of the cared for whom they need to protect in the first place. these paternalistic regulations can pertain to decisions to lock down communities without prior consultation or information dissemination, sending patients home even if they have covid- symptoms without giving prior information about the treatment protocol, etc. for example, persons from an urban poor community in quezon city were arrested for violating rules enforced during the enhanced community quarantine (ecq) that took effect in quezon city in april . those arrested explained that they were given false information about the distribution of goods to people who could not go out because of the lockdown. disappointed that the relief goods did not reach them, they wandered off to an area where distribution of relief goods was supposed to be taking place. the philippine national police rejected their explanation so they were arrested. desperately needing food and cash, and possibly exposed to sars-cov- , they were hauled off to jail and told that they were lawbreakers who could not be set free unless they posted bail. , in the aftermath they must have been more exposed to the infection that authorities should have protected them from. the fact that these people were misled into wandering off because of false information was bad enough. the real situation was made even worse because of the treatment that they got for actions motivated by desperation and ignorance. by acting decisively but with insufficient regard for individual sensitivities, authorities could be missing an important opportunity to process issues of fairness in the allocation of resources in the dispensing of full, accurate, and understandable information about the covid- pandemic. local media have reported situations reflecting a failure to appreciate pertinent information by people who have needed information the most but were probably not engaged in a meaningful conversation that considered their perspectives and vulnerabilities. paternalistic decision-making as illustrated here violates the equality between the carer and the cared for, in the carer (officers) failing to factor into decision-making the specific context of the cared for (those arrested). by not being sensitive to the situation of the economically deprived, the authorities failed to give due consideration to the interests of the worst off. in addition, the authorities may have failed to recognize their own deficiencies in disseminating accurate information in an effective and appropriate manner. com/ / /the-phili ppines-coron avirus-lockd own-is-becom ing-a-crack down/ studies abroad have shown that lower income groups have a harder time comprehending health information. , there is a direct relationship between socioeconomic status and the level of health literacy. this is a reason why a lot of filipinos have failed to grasp the full significance of the existence of the covid- pandemic and the importance of cooperating with measures to control and limit its spread. the failure to account for stakeholders' literacy levels violates the prioritization of the worst off. understanding this specific context should result in the provision of more assistance to those in more need of health and educational services, not in the easy targeting for police apprehension. prioritization of the worst off should also apply to the removal of language barriers, the third decision-making problem addressed in in this section. in the philippines, filipino is the national language, and both filipino and english are the official languages. however, as many as languages are spoken in the country. the oecd mentions in the pisa that: "some % of -year-old students in the philippines speak a language other than the test language (i.e. english) at home most of the time." notable efforts have been made by the university of the philippines (up) to translate english medical terms related to covid- into the filipino language. a up professor, eilene antoinette narvaez, has come up with a compendium of filipino terms regarding covid- , and the university's department of linguistics is connecting community translators with one another across the country. the up college of education has written a dictionary of covid- -related terms in both english and filipino for children, and this dictionary contains links to videos of the filipino sign language of the terms. apart from the language or dialect that is being used, the level and the manner of discourse is also important. viewed as a matter of fair allocation, the dissemination of information has to be seen in these terms. communication that is not carried out at the level of understanding pertinent to its divergent audiences or that is not cognizant of their specific information needs can only serve the interests of a select population and thereby contributes to inequity. this inequity arises especially because these divergent audiences are likely to be among the worst off financially and educationally, and deserve to be prioritized. in this country -as in many others -information infrastructures can be fully developed in affluent areas but not in others; access to interesting and high-quality information can be expensive; and training and equipment for the effective use of pertinent technology may not be equitably available." while the capability of new information and communication technology to level the playing field for all citizens has been much heralded, it may also have the reverse effect of exacerbating existing inequalities if access is not widely distributed and benefits are merely integrated into already existing socioeconomic structures. in addition to translation initiatives, telehealth practice illustrates what can be done to address an otherwise crippling lack of access to vital health-related information. advocates of telehealth have been taking the opportunity to highlight how the practice can help address inequities in access to health information and to healthcare more broadly. even before the onset of the covid- pandemic, they were already promoting the use of digital means to address healthcare issues faced by vulnerable sectors. telehealth has been demonstrated to help close the gaps in healthcare service delivery as a way of ensuring that national health- has certainly accelerated the acceptance of telehealth as a means to improve healthcare. aside from providing healthcare access to remote patients, the practice of telehealth has served to limit physical contact in order to reduce the risk of contracting covid- . physicians who previously disliked the use of technology and preferred face to face consultations are now forced to "see" patients remotely. the tide has started to turn and this appears to have happened also in other countries. multiple studies have shown how telemedicine has enhanced health service delivery. , , even before launching the covid- telemedicine hotline, the doh already launched multiple telehealth initiatives: a non-covid- clinical helpdesk (through hotlines), email, and chat (including a doh internet-based messaging app group that is open to lay people and another group for health care workers). physicians offer free services to decongest hospitals. one news. retrieved july , , from https://www.onene ws.ph/the-doctor-is-online-physi cians-offer-free-servi ces-to-decon gest-hospi tals at pgh. the rxbox is now being developed to have telemetry capability, which means being able to connect with a dashboard at the nurses' station where vital signs can be read. the device therefore allows for remote monitoring that minimizes risks associated with the proximity of healthcare workers to patients with communicable diseases. the installation of rxbox devices at pgh as a response to the covid- pandemic will significantly improve access by people in remote locations to health care and information. , another initiative under the up college of medicine's surgical innovation and biotechnology laboratory (sibol) in cooperation with up diliman's electrical and electronics engineering institute is a "telepresence" device, a computer programmed to automatically answer calls from authorized accounts using available teleconferencing and remote-control applications, minimizing contamination and allowing effortless access even by patients with no technological know-how. like the rxbox, a "telepresence" device allows healthcare workers and patients to communicate with each other without need for face to face contact. this paper notes the use of telehealth devices for healthcare providers to listen to stakeholders and not merely to observe them and implement programs without consultation, as we reiterate the view that caring is a two-way exercise. measures responding to the pandemic have to maintain and enhance the two-way conversation between the carer and the cared for. it has significantly improved the quality of delivery by overcoming geographic barriers, increasing accessibility and efficiency by reducing the need to travel, providing clinical support, offering access through multiple platforms that patients can easily connect with, and ultimately improving patient health outcomes. the current pandemic has hopefully provided an irreversible inertia for the doh and other healthcare authorities and stakeholders to accelerate their preparedness and capability to respond to pandemics and disasters not only in the short term but also in the foreseeable future. this approach can be possible by focusing on removing barriers to inequitable access to healthcare communication and other healthcare resources, an important strategy in support of the prioritization of the worst off. paradoxically, the use of telehealth to address one kind of need highlights a problem of another kind. this has to do with healthcare being essentially an expression of closeness, of solidarity, and of removing physical and emotional barriers to well-being. , , thus, we have seen how family members have bemoaned their inability to be close to their loved ones who are being administered critical (possibly end of life) care. , physical distancing appears to be antithetical to human beings' emotional closeness. , but this is another issue that is beyond the scope of this paper. the physical availability of health care workers is a related concern that the next section deals with. the toll that the covid- pandemic has taken on the country's to keep up with the continuing requirements for hrh, emergency hiring has been going on at a frenetic pace, sometimes to the extent of including interns who still lack the experience that would otherwise have been necessary. as part of covid- measures, the doh issued a call for volunteer doctors and nurses in three state hospitals. in response, almost filipino doctors and nurses volunteered regardless of experience and readiness to address the needs in stations for which they have not been thoroughly prepared. this has also been going on in other countries that are more economically endowed. , , here, we are made to wonder how this could be happening when, for many years, the philippines has, in effect, accepted the responsibility of providing care to patients in other countries by encouraging the migration of its own healthcare professionals. this encouragement can be seen in the country creating bureaucratic institutions and promoting legislation to facilitate labor migration since the s. , the long-standing dilemma was highlighted again recently when public officials themselves debated a proposal to allow filipino healthcare workers to leave for abroad in the midst of the pandemic. , eventually, a decision was reached to allow the departure of those who already had legally binding contractual obligations but to temporarily prevent others from entering into new contracts to work abroad. , more recently, the doh authorized the recruitment of fresh medical graduates to work as deputized physicians without having to pass medical board examinations. clearly, the measures described in this section to address the lack of hrh in the context of the covid- emergency are intended to be in place temporarily. emergency healthcare staff are being recruited to work only during the period of the pandemic under contracts lasting only for months. the ban on deployment of hrh to foreign countries will be lifted as soon as the pandemic subsides. disasters for the next epidemic. we know that we need to allocate societal resources for housing fairly to avoid this. if we do not realize how inequities have aggravated our public healthcare situation in the context of the current pandemic, we will not learn our lesson ever. in order to accommodate the rising number of persons needing isolation and quarantine facilities, the national government has coordinated with local governments and the private sector in converting hotels, sports facilities, school buildings, and churches into temporary quarantine sites. the facilities are meant to accommodate asymptomatic or mildly symptomatic patients who are either homeless or whose dwelling units do not have enough spaces to allow isolation. the temporary facilities may suffice for now, but certainly not for the near future. these facilities will be eventually returned to their original use; a more sustainable and long-term solution must be developed. it is about time we realized that the need for safe and healthy housing for all is a concern not only for the economically challenged but also for every other member of the community. in times of pandemic emergencies, anyone and everyone can be affected by the lack of safe and healthy housing suffered by disadvantaged sectors of society. when people get infected by a highly contagious virus and they have no safe isolation space to which they can withdraw, everybody else can be adversely affected as they radiate beyond their household. in a world of interconnected and interrelated human beings, anyone's virus has the potential to infect everybody else. the need for numerous safe isolation or quarantine facilities brings attention to how easily the sars-cov- virus can spread; one measure for this parameter is the basic reproduction number. the basic reproduction number or basic reproductive number (r ) of a disease indicates the number of people that an initially infected person will transmit the infection to assuming no one yet in the population is immune to the disease. on march , , the who reported a reproductive number of to . . another estimate put covid- 's r at around . based on figures from different regions in china and overseas. to make sense of r , for instance the . figure, one person who has covid- will infect around three people with covid- ; total cases are now four. each of these three newly infected will also infect three more, adding nine new cases to the previous total of four. each of the nine new cases will infect three, and so on. from these numbers, one can make sense of how covid- is said to have exponential growth, seen internationally and in the philippines . with exponential growth, as more people get infected, the faster will be the rate of new infections occurring. this growth rate is opposed to a linear growth rate where the rate of new infections occurring stays the same over time. from this picture, we can understand how quickly an entire population can be infected. as a note of comparison, on march of this year, the who announced covid- 's global mortality rate of . %, more than times higher than that reported for seasonal flu's %. we have seen how quickly seasonal influenza can be passed on from one person to another and these reproductive numbers are up to more than times higher than that for seasonal influenza's . . because if they succumbed to the virus the food chain could break. as such, farmers, fisherfolk, food delivery workers, cashiers, grocery baggers, and customer care staff have been hailed as frontliners and heroes. , , , , indeed, some people who have lived in near complete isolation have become infected even though they have been minimally exposed to such frontliners. as more people get infected, fewer and fewer safe spaces are left. this is a message that we get from the experiences in almost every community, but especially in high-density spaces such as crowded informal settlements, prisons, workplaces, public transport facilities, supermarkets, or even hospitals. hence, we are not merely talking about interconnectivity of humans in an abstract sense that is more closely associated with philosophical discourse on concepts such as human dignity or the sanctity of human life in various contexts. we are referring to the physical interconnectivity that gives rise to concrete disease and deprivation that has affected more people with various kinds of social living conditions. we can easily take this for granted in the absence of a pandemic. but recent events have caused an alarming prevalence of the virus and its effects on society. the interconnectedness of people of varying socio-economic standing as highlighted by the pandemic reinforces the view that inequality needs to be reduced and prioritization of the worst off must be observed in order to achieve the best outcomes. by giving more help to those who are more in need we move in the direction of achieving the best outcomes for more people. the impact of interconnectedness and interdependence has been felt also in relation to the increased demand for hospital facilities. in an archipelagic country composed of regions across more than , islands, healthcare facilities are unevenly distributed. in , around two thirds of hospital beds in the philippines were in one area, the national capital region. the problem of physical as public hospitals become congested, some patients have been forced to consider confinement in private hospitals. but this is a privilege that very few could afford. one patient's bill for a -day stay at a private hospital totaled php million or around usd , , which is about equivalent to a middle-class filipino worker's salary for years. an estimate for a private hospital bill for a moderate covid- case amounts to at least php million or a little under usd , . to address these financial concerns, the philippine health insurance corporation (philhealth) has come out with new policies for at least partial coverage of covid- cases. the problem with philhealth is not everyone is able to use it. in the situation in hospitals is further complicated by issues whose underlying roots are not so easy to explain. a person under investigation for having covid- escaped from a private hospital where he or she was being observed. an overseas filipino worker with covid- symptoms also escaped from a hospital to probably go back to work abroad. another patient who tested positive for the sars-cov- virus escaped by jumping from a hospital window after she was not given permission to go home. expenses or space limitations are possible explanations but the exact reasons why these quarantined patients have tried to escape need to be probed further. of course, the reasons may have to do with things that are not unique to hospitals. for instance, socio-economic conditions characterized by inequity and a lack of safety nets for the worst off may compel patients to ignore their health and avoid long hospitalizations so they can continue to try to make a living for themselves and their families. as earlier noted, the fair allocation of critical care resources is a concern that arises way before the need to prioritize patients arises about these factors helps one decide which treatment alternatives suit one's financial capability. to be able to fully understand these factors, people need to be functionally literate and to have a minimum level of health literacy. as we address these issues during the pandemic, it should be clear to us that these are also long-standing concerns that have been waiting for durable solutions. only durable solutions can help us maintain emergency readiness over the long term. in the meantime, during the covid- pandemic, guaranteeing fair access is necessary. one way for authorities to do this is to uphold fair allocation principles in the various areas taken up so far, as well as in emergency critical care. ethics and covid- distinguishes three levels of scarcity and their corresponding effects on the fair allocation of resources like ventilators: first, with little scarcity, first come, first served may be best for equality; second, with more scarcity, the prioritization of the worst off may be best; and third, "with even greater scarcity, a principle that aims to maximize benefit from the resource may be most justified." of interest in this section is the scarcest level. in extreme situations where there are simply not enough resources to accommodate everyone in need, giving protection to the vulnerable could take a backseat as medical vulnerability, in the sense of having comorbidities, could be seen to indicate futility of critical care that includes ventilatory support. an early study showed that for covid- , the case fatality rate (cfr) was elevated among those with preexisting comorbid conditions such as cardiovascular disease, diabetes, chronic respiratory disease, hypertension, and cancer. another study of laboratory-confirmed cases of covid- showed that "patients with any comorbidity yielded poorer clinical outcomes than those without" and "a greater number of comorbidities also correlated with poorer clinical outcomes." moreover, "persons with underlying chronic illnesses are more likely to contract the virus and become severely ill, . . underlying conditions compared with those without reported underlying conditions ( . % versus . %). research findings such as these resulted in elderly patients being refused ventilatory support in italy. the independent reported that a doctor gave an account of medics being forced to ration care to patients in the wake of the covid- outbreak such that elderly patients were being denied care based on their age and whether they had other conditions or not: "in bologna, we are working with -years-old as our cut off, but between and -years-old we still consider comorbidities." there are similar accounts pertaining to sweden's karolinska institute. , yet, the acceptance of advanced age in itself as an indicator of medical futility has to be conclusively established by evidence. statistical findings of high mortality rates among patients belonging to the highest age groups can merely be reiterative of the high mortality rates among patients with comorbidities --elderly patients have a higher likelihood of having more comorbidities. if we overlook this point, the elderly could be exposed to unfair allocation of resources based simply on their age rather than on their having comorbidities that leave them with poor chances of surviving with the use of critical care devices. as george kuchel asserts, "having multiple chronic diseases and frailty is in many ways as or more important than chronological age" and "an -year-old who is otherwise healthy and not frail might be more resilient in fighting off infection than a -year-old with many chronic conditions." in addition, recent studies have generated optimism about the success of measures to delay or minimize age-related immunological defects. admittedly, age serves as a useful indicator of the presence of comorbidities that the elderly are likely to have. however, the studies about chronological age and immunological developments cited above indicate that statistical correlation should not necessarily be taken to mean causal correlation. for this reason, age by itself should not be regarded as a valid basis for short-term triage decision-making. in the absence of validated empirical proof that a particular age level indicates the medical futility of applying scarce critical care resources, the vulnerability of patients that is associated with advanced age should instead signify a need for them to be given pro- everybody is hoping that solutions will soon emerge that can facilitate quick recovery and help individuals and families resume stable lives. solutions being offered are expected to give rise to a new normal. even when the government decides that the economic consequences are too much to bear for covid- quarantine arrangements to continue, we cannot go back to the state of affairs that had to be suspended because of the emergency. we should now realize that we cannot just revive the suspended state. epidemiologists tell us that the covid- pandemic will be with us far longer than we may have expected. while many studies on possible treatments or vaccines are being rushed, it has been observed that the progression of past influenza pandemics "was not substantially influenced by a vaccination campaign." bill gates has declared a plan to spend billions of dollars to build seven vaccine factories simultaneously while research is still going on in order to hasten the process of development but this extremely expensive initiative is not estimated to bring us closer than months to vaccine implementation. while we are still waiting for a vaccine, we can only count on non-pharmaceutical interventions (npis) to limit sars-cov- transmission. this makes it necessary to continue with physical distancing and isolation measures for at least years. even worse, we are reminded that "our record for developing an entirely new vaccine is at least four years -more time than the public or the economy can tolerate social-distancing orders." we appear to be playing a waiting game where the cards are stacked against us. according to studies, the pandemic is not likely to be under control until to % of the population is immune, which has been estimated to be the threshold for acquiring herd immunity in the case of the current covid- infection. , if so, this outbreak may take to months. but there are even warnings that herd immunity may not work because of uncertainty concerning the duration of individual immunity to sars-cov- and the low seroconversion rates even in huge populations known to be covid- hotspots. for instance, a study of , participants in spain showed that only % developed antibodies. seroconversion rates were all less than % for various subpopulations among , participants in china. these rates mean that a huge percentage of the population remains at risk for infection despite all the damage from the pandemic. relying too much on the emergence of natural herd immunity will possibly just increase this damage. in light of these considerations, there have been many predictions of what we are likely to see in a new normal --wearing a face mask becoming routine, an occasional cough being regarded as a threat, workplaces feeling like hot zones, and public transit being personally dangerous. we can anticipate less travel, disruptions to consumer supply chains, social anxiety, heightened agoraphobia and, overall, greater mistrust in one another. as a corollary to physical distancing, digital interconnection is going to be intensified. we have seen this already in the accelerated shift to phone and internet banking, in the move from dine-in to take-out and delivery modes of restaurant food consumption, in the spike of online shopping activities, and even in the accommodation of online religious worship. in the philippines, religious services have been broadcast through social media while physical attendance in places of worship has been limited to a handful. a similar trend is going to be part of the new normal for many aspects of healthcare. we have seen how telehealth has taken on an increased role in the country. telehealth can play a huge role in the new normal and we should make it happen. realistic estimates of how long it will take before we can have a vaccine, if possible at all, together with real concerns about the possibility that other infectious diseases (or global disasters) could come and endanger global health security, impress upon us that the radical changes in our way of life are going to persist even beyond the development of a covid- vaccine. a new normal has begun to set in. the new normal is a sum total of the things that we can do as a departure from what we could do before the pandemic, the new things that we have to learn to do and the new ways in which we have to do these things, the political and cultural structures that are developing, and in general, the ways in which we will have to live our lives because of the challenges that have confronted us and are likely to continue to confront us. the new normal also refers to the period in which citizens are expected to become accustomed to the emerging state of things. as we transition to the new normal and address the challenges that are coming our way, we have to remember that our ability to overcome the problems confronting us during the pandemic has been premised on the equitable sharing of resources. the efforts being exerted to contain the covid- pandemic in the philippines are being focused on addressing manifestations of underlying inequities -though that is perhaps happening more coincidentally than deliberately, and many efforts have been highly problematic and insufficient as pointed out in this paper. because the insufficient efforts have been triggered by the existence of an emergency, most of the response measures are meant to be temporary. people on the brink of starvation have been receiving emergency food aid, and those with no financial savings have been receiving cash assistance. however, these efforts have neither been fully successful nor sustainable. , , those who could not be isolated or quarantined have been evacuated, but these evacuation facilities are also temporary and the occupants are going to be reinstated in their cramped dwellings that cannot protect them from new transmissions or other communicable diseases in the future. if the inequities continue in the new normal, the normal is not going to be really new. the vulnerable are going to remain vulnerable and philippine society will not be more prepared for the next pandemic. clearly, the lesson is that everyone, especially the most economically disadvantaged, need to have access to the resources that relate to their healthcare, inter alia, -adequate and accurate information so they can be properly advised about their healthcare needs; clean flowing water so they can wash their hands properly; and dwelling units that will give them the capability to be isolated from neighbours or from household members who can be infected. in support of these necessities, they will require employment opportunities that can yield fair wages or other opportunities to generate adequate income, and social and health insurance coverage that they can fall back on in times of need. subject to certain logistical limitations, the philippine government has seen the indispensability of temporarily providing the required resources to disadvantaged sectors. however, a lot more needs to be done. the distribution of resources has to proceed in a way that transcends the long-standing barriers associated with structural social inequities. sustained fair allocation founded on equality, equity, and the prioritization of the worst off is indispensable. sustainability is critical because, as has been pointed out, the problems that need to be addressed are chronic pre-pandemic inequities that are being magnified by the health emergency. there is evidence that the need to improve the plight of the resource challenged has been partially acknowledged by the more economically advantaged sectors of philippine society. small and big business companies in the philippines have made huge contributions to help provide for their emergency needs. the private sector has supported the national government, local government units, and the general population by providing wages to employees who could not work, monetary assistance, relaxed working conditions, emergency transportation, food products, ventilators, test kits, personal protective equipment, and many other goods and services that can help everyone overcome the current crisis. beyond this, these privileged sectors have to realize that what they have helped provide during the emergency is something that needs to be available in the long term and institutionalized for society to survive future pandemics and for their businesses to continue to thrive. institutionalization requires arrangements that would provide realistic opportunities for disadvantaged sectors to acquire the goods and services that they need beyond the period of the current emergency. as we transition to the new normal the most economically deprived should seize the opportunity to establish how important the improvement of their situation is in order for the current widespread problems to be properly addressed. while disadvantaged sectors continue to be dependent on others because of their vulnerability, society should seek to translate the realization that the health and security of the more privileged is dependent on the health and security of everybody else in society into sustainable measures to improve the conditions of the worst off and narrow the gaps between its most endowed and least endowed sectors. in the new normal, there must be institutionalized safety nets that can be accessed when things go wrong. people should not have to beg and fight for places in dignity-sapping queues for the distribution of emergency social amelioration funds --these should be available to them as a matter of right. people should not have to be rushed to temporary isolation and quarantine places -prioritizing the concerns of the worst off is essential for the improvement of everybody's health. to provide them with home spaces that will enable them to care for the sick while still protecting themselves also advances the health interests of everybody else in the country. this reality acquires an unprecedented level of concreteness in the context of a pandemic such as the one that we are currently experiencing. in the new normal, those who require medical attention should be protected by universal healthcare; we ought to realize that "those in the greatest need often have the poorest access to care -a striking example of unfairness." very importantly, people should know all of these, what to do and where to go when they require services because, in the new normal, information will have to be dispensed efficiently and equitably regardless of the people's level of understanding. we see the entirety of the telehealth movement as a paradigm of how response measures ought to be characterized. it uses advanced technology to promote access by the underprivileged to the most important healthcare services. it listens to patients and gives them an opportunity to participate in their own care. what it is trying to do in the course of the current pandemic is something that is only a part of what it should aim to accomplish in the long term. thus, it should be part of a sustained effort that can have a good chance to narrow the gap between the economically privileged and the economically challenged. it exists in sharp contrast with measures meant to address the lack of isolation spaces in many people's dwellings. the isolation and quarantine facilities that have been set up are clearly temporary facilities that cannot be retained beyond the period of the emergency. the people currently using them will be going back to their informal settlements without any prospects of having their living conditions improved. learning from these comparisons, we see the need to observe a number of criteria for evaluating covid- response options consistent with the principles of equality, equity and the prioritization of the worst off: the short-term efforts exerted to contain the pandemic have to be aimed at addressing the inequities. having existed for a long time, these inequities deserve everyone's attention not only during the pandemic but also when we emerge from it. this glaring reality may have been overlooked as authorities focus on the short term and see the measures as a requirement to tide us over until we can go back to normal. thus, addressing the manifestations of the inequities has happened incidentally rather than deliberately, using stop-gap rather than long-term measures. yet, what we are going through now is not merely a fleeting disaster but an instantiation of chronic injustice characterized by inequities on many fronts. the totality of our experiences relating to the pandemic constitutes evidence that the inequitable access to essential goods and services needs to be overcome -not only for the sake of the underprivileged but also for the sake of everybody else regardless of economic, political, or social status. what is being asked of us is not merely to provide for people's needs during an emergency but to manifest our realization that fellow sars-cov- seroprevalence the lancet prevalence of sars-cov- in spain (ene-covid): a nationwide, population-based seroepidemiological study. the lancet seroprevalence of immunoglobulin m and g antibodies against sars-cov- in china three potential futures for covid- : recurring small outbreaks, a monster wave, or a persistent crisis life after covid- : what will change? internet banking trend to continue post-covid. the manila times key: cord- -v ncshav authors: moghadas, seyed m.; pizzi, nick j.; wu, jianhong; yan, ping title: managing public health crises: the role of models in pandemic preparedness date: - - journal: influenza other respir viruses doi: . /j. - . . .x sha: doc_id: cord_uid: v ncshav background given the enormity of challenges involved in pandemic preparedness, design and implementation of effective and cost‐effective public health policies is a major task that requires an integrated approach through engagement of scientific, administrative, and political communities across disciplines. there is ample evidence to suggest that modeling may be a viable approach to accomplish this task. methods to demonstrate the importance of synergism between modelers, public health experts, and policymakers, the university of winnipeg organized an interdisciplinary workshop on the role of models in pandemic preparedness in september . the workshop provided an excellent opportunity to present outcomes of recent scientific investigations that thoroughly evaluate the merits of preventive, therapeutic, and social distancing mechanisms, where community structures, priority groups, healthcare providers, and responders to emergency situations are given specific consideration. results this interactive workshop was clearly successful in strengthening ties between various disciplines and creating venues for modelers to effectively communicate with policymakers. the importance of modeling in pandemic planning was highlighted, and key parameters that affect policy decision‐making were identified. core assumptions and important activities in canadian pandemic plans at the provincial and national levels were also discussed. conclusions there will be little time for thoughtful and rapid reflection once an influenza pandemic strikes, and therefore preparedness is an unavoidable priority. modeling and simulations are key resources in pandemic planning to map out interdependencies and support complex decision‐making. models are most effective in formulating strategies for managing public health crises when there are synergies between modelers, planners, and policymakers. influenza pandemics have historically been devastating to humanity with significant morbidity, mortality, and socioeconomic costs. the - pandemic, the so-called ''mother of all pandemics,'' was responsible for over million deaths among countless infections worldwide. today, years after the last pandemic in , the world may be on the brink of another major global pandemic, with a toll that could exceed that of the - pandemic. while the nature of the next influenza pandemic cannot be predicted with certainty, the identification of strategies to effectively curtail the spread of disease is an unavoidable priority in responding to this global threat. in light of this, the university of winnipeg hosted a multidisciplinary workshop on the role of models in pandemic preparedness. the workshop brought together public health experts, key decision makers, and infectious disease modelers to: (i) identify the strengths and weaknesses of mathematical models, and suggest ways to improve their predictive ability that will ultimately influence policy effectiveness; and (ii) provide an opportunity for the discussion of priority components of a pandemic plan and determine key parameters that affect policy decision making. the first day of this workshop consisted of several outstanding presentations by modelers with the purpose of forging strong links between theory, policy and practice. these included evaluations and model predictions for antiviral strategies and their implications for drug stockpiling; the role of population contact networks in the emergence and spread of drug-resistance; targeting influenza vaccination at specific age groups; optimal control of pandemic outbreaks; and the usefulness of non-pharmaceutical interventions in disease mitigation. dr. chris bowman (institute for biodiagnostics, national research council canada) presented the findings of two modeling studies for the management of drug-resistance in the population, , especially when concerning the scarcity of antiviral supplies. these studies suggest that an adaptive antiviral strategy with conservative initial treatment levels, followed by a timely increase in the scale of drug-use, can minimize the final size of a pandemic while preventing the occurrence of large resistant outbreaks. dr. bowman emphasized that the strategic use of drugs may involve decisions for rationing of limited stockpiles and prioritizing high-risk individuals, and therefore ethical considerations should be taken into account for maximum protection of community health. a comparative evaluation of antiviral strategies in homogeneous and heterogeneous population interactions was presented by dr. murray alexander (institute for biodiagnostics, national research council canada). he underscored the importance of prolonging the effectiveness of antiviral drugs through an adaptive treatment strategy, in particular for heterogeneous community structure in which the wide-spread of resistance is more likely to take place. these presentations also provided a brief overview of some recent studies carried out by canadian modelers in the subject of pandemic preparedness. [ ] [ ] [ ] [ ] [ ] dr. babak pourbohloul (director, mathematical modeling, bc centre for disease control) proposed an important question regarding ''a forced marriage'' or ''necessity for integration'' between mathematical models and public health policy. in his summary of the day, dr. pourbohloul acknowledged that the talks were very encouraging and pointed towards integration and development of modeling platforms that could inform policy in canada. he also highlighted the significant progress evident since the first pandemic meeting in vancouver, , during which very little could be communicated to policymakers regarding the value of modeling perspectives. dr. pourbohloul drew attention to various models presented in the workshop, which attest to the fact that we are not lagging behind the current methodology in canada, but rather are in the forefront. [ ] [ ] [ ] [ ] [ ] [ ] [ ] however, the central issue is not this, but integration with public health, which is the approach taken by us and uk colleagues for disease modeling and management. a major drawback for canadian modelers is the lack of appropriate infrastructure, and this calls for investments from healthcare departments and government organizations that could provide modelers with the impetus to continue development of more realistic models. with regard to models used for pandemic planning, we need to critically evaluate their implications for policy implementation. there are two major reasons underlying this evaluation: first, data are limited and prior to the emergence of a novel pandemic strain, it is not possible to study the epidemiological impact of disease or interventions in a real world environment; second, public health authorities would need to be prepared for all the likely scenarios that could influence the outcome of preparedness strategies. models, by definition, are not supposed to be perfect; approximations are necessary and predictions are made on this understanding. however, a more important question is how much of the knowledge of canadian modelers has been employed to support policy decision-making? is it all based upon experience of other countries? perhaps in canada, there has not been much communication between modelers and policymakers and therefore modeling results have not been translated into the context of public health. the time has now come to build a pandemic consortium in canada to have a unified voice from modelers, and close the gaps with infectious disease experts and public health colleagues. dr. susan tamblyn (co-chair, canadian pandemic antivirals working group) also emphasized the importance of making progress on linking the modeling with decision making within canada. these enterprises are still really separate in canada, whereas the value of modeling groups working very closely with the government and health departments is clearly evident in a few countries. we seem to have this linkage in a couple of provinces in canada, but it is not elevated to the national level. as planners, they understand that modeling can help formulate pandemic policies; however, the lack of collaboration with canadian modelers obliged them to turn to outside results from published models. hopefully, the two groups can work closer together to have beneficial impact with regards to pandemic preparedness. dr. tamblyn also expressed her concern about public health questions, which often are not amenable to modeling, and about modeling studies that use unrealistic assumptions and scenarios. therefore, modelers should also be fully engaged in the process of formulating the questions that policymakers need to address in planning for a pandemic. the point was highlighted by dr. ping yan (centre for communicable disease and infection control, public health agency of canada) that models should be based on realistic assumptions to create fundamental knowledge in all aspects of pandemic research. on the second day, the workshop comprised several presentations by participants from the public health domain. these included unanswered questions concerning the emergence of novel infectious diseases; understanding the space-time dynamics of influenza spread; influenza mortal-ity in pandemics and seasonal outbreaks; the impact of global air transportation on the spread of diseases; the role of models in public health planning and decision making; the evolution of pandemic influenza viruses; and the potential for novel means to prevent these pandemics. dr julien arino (university of manitoba) outlined the objectives of an ongoing data-driven project that aims to draw out the likely patterns of disease spread through the network of all international airports in the world with direct and indirect connections. this investigation can have important implications for heading off a global pandemic, with a particular focus on the optimal allocation of containment resources in the most probable ports of disease introduction and spread in canada. this presentation was followed by an overview of the ontario government's pandemic preparedness plan (allison stuart, assistant deputy minister of the ontario ministry of health and long-term care), which provides the most comprehensive provincial plan in canada, having undergone five iterations developed over a -year period. this plan details guidance to local planners and specific strategies for health sector sub-groups (critical care, pediatrics, laboratories, long-term care, persons with chronic diseases, mental health settings), first responders, faith groups, private sector organizations, and first nations communities. this presentation also included a list of concerns which modeling should address relating to acute care services (e.g., estimated hospital surge capacity for a given jurisdiction during a pandemic); local implementation (e.g., identification of the tipping point when primary care will not be able to meet the - hour standard of care); and antivirals (e.g., identifying the optimal use of drugs and distribution methods for treatment and prophylaxis to decelerate the spread of a pandemic). dr. joanne langley (co-chair, canadian pandemic vaccine working group) presented a detailed analysis of the potential benefits and uncertainties relating to the standard pillars of pandemic influenza contingency plans, covering antiviral drugs; healthcare delivery planning; vaccines; public health measures; and infection control practices. this included the importance of personal protective equipment such as the n mask in the healthcare setting, the need for regular and frequent hand washing, and a risk analysis of potential amantadine resistance. dr. langley also stressed the need for ''real time'' modeling to provide a rapid analysis of alternative tactical decisions following the onset of a pandemic. dr. mark walderhaug (associate director, us center for biologics evaluation and research, fda) discussed a stock-and-flow model used for simulating the impact of an influenza pandemic on the us blood supply. the model assumes that susceptibility to the pandemic virus will be universal; multiple waves of infection can occur and each wave adversely impacts infected communities for - weeks; and absenteeism may reach as high as % dur-ing the peak periods. model simulations for the entire us blood supply were presented, and the need for acquiring detailed data of inter-regional flow of blood was emphasized. these data are essential for projecting various scenarios, including run-out for hospitals despite adequate national supplies and time frames for elective surgery cancellations while the blood supply recovers, which highlight the significant challenges involved in supply distribution. dr. paul gully (senior advisor, world health organization) emphasized the fact that models are essential for guiding public health, but may also raise more questions for policymakers. he expressed growing concerns about being able to fulfill the requirements for pandemic containment that come from modeling studies: ''models lead to policy but have to confront political reality''. previous work suggests that a nascent influenza pandemic can be contained at the source if antiviral therapy for a sizable proportion of affected individuals ( - %) is accompanied by a rapid implementation of non-pharmaceutical measures (such as movement restriction) over a very short period of time (days to weeks). , on serious discussions from a political standpoint, dr. gully demonstrated the significant challenges involved in building the capacity for a timely response to meet the condition for averting a global pandemic. despite these challenges, he acknowledged that models are invaluable tools for making assumptions explicit and for best using limited data, highlighting key factors determining policy needs, and providing quantitative predictions. discussions of the day were then expanded to the implementation of various strategies from a transmission dynamic standpoint. in their capacity, what models offer should be taken along with other health and economic factors to guide sound public health policies. they are not meant to make decisions on managing public health crises, but rather provide recommendations to policymakers. however, for rapid decision making, one would need to consider the interface between simple, interactive, and relatively complex models that may encapsulate population demographics pertaining to the location of a pandemic outbreak. dr. tamblyn chaired the summary and discussion session of the workshop on day , and acknowledged the true interdisciplinary nature of the meeting, enriched discussions, very interesting and relevant presentations, with kudos for planning long health-breaks that allowed for interactions and flow of emerging ideas. she distinguished the meeting as the one that has met its objectives and provided an opportunity for effective communications between modelers and public health authorities on the subject of pandemic preparedness in canada. dr. ying-hen hsieh (china medical university, taiwan) offered his perspectives on the workshop with great potential for expanding collaboration with canadian colleagues in future work. the meeting highlighted important aspects of canadian public health that will be useful for creating an effective venue to communicate with public health in taiwan. dr. hsieh, as a prominent modeler in taiwan, shared his experience with sars (severe acute respiratory syndrome) and exemplified the opportunities missed by public health to engage modelers: ''by the time they called me in, it was weeks before the end of sars outbreaks''. in , there was a cabinet agreement to promote an influenza vaccine r&d program in taiwan, partly for the economic opportunities it offers; he was brought in after the decision was made with the hope that ''modelling results will be in line with government policy''. he depicted that in public health in taiwan, a highly challenging task has been to establish collaborative efforts, but the important lesson from this workshop is to understand the process of making decisions, identify its key parameters, and determine effective ways to communicate with policymakers. dr. benjamin ridenhour (us center for disease control) acknowledged that the workshop had been successful in bringing together the communities involved in pandemic preparedness, to share their various viewpoints and expertise in modeling and public health, in a very congenial and friendly environment. the us center for disease control has made substantial efforts to co-ordinate pandemic activities through synergism between public health officials and modelers, which has led to benefits for planning strategies in the united states. as modelers, we need to strengthen our ties to public health, and exploit our potential for developing models that can inform and optimize health policy decisions. this workshop has demonstrated that strong networking is required to adequately prepare for the pressure of real time crises, and cope with surging demands in a pandemic-related emergency. in closing the workshop, dr. seyed moghadas (institute for biodiagnostics, national research council canada) valued the time and efforts of participants and appreciated their contributions to the success of this event. key points inferred from presentations and discussions include: . in canada, the pandemic goals are to (i) minimize serious illness and overall deaths; and (ii) minimize social disruption. pandemic containment has not been a priority to date and may not be feasible. development of a pandemic vaccine may take up to months following pandemic detection. however, as novel influenza strains most often emerge in asia, strong surveillance leading to early detection there can increase our lead time for pandemic vaccine production. . immunization of children can result in significant changes in contact patterns and attack rates. age is a surrogate for individual behavior that influences pathogen transmission in the population; vaccine efficacy may also vary in different age groups. . antiviral therapy is the cornerstone of the pandemic response in canada until vaccine is available; however, implementation of the strategy is determined by pandemic planners at the provincial level. the meeting provided an opportunity for modelers to engage in detailed discussions about modeling strategies that can be employed for gaining new insight into disease processes at the population level and making findings of public health significance. while models serve to synthesize data and suggest optimal scenarios in public health, they can also promote dialogue between modelers and policymakers about alternatives, uncertainties, and assumptions that underlie critical decisions. the workshop revealed that pandemic planning requires involvement of communities across disciplines with firm commitment to the notion that research must ultimately influence policy. a history of influenza influenza: the mother of all pandemics avian influenza h n : is it a cause for concern? workshop on managing public health crises population-wide emergence of antiviral resistance during pandemic influenza antiviral resistance during pandemic influenza: implications for stockpiling and drug use emergence of drug-resistance: implications for antiviral control of pandemic influenza a delay differential model for pandemic influenza with antiviral treatment simple models for containment of a pandemic the impact of prophylaxis of healthcare workers on influenza pandemic burden management of drug-resistance in the population: influenza as a case study strategies for containing an emerging influenza pandemic in southeast asia containing pandemic influenza at the source the workshop was funded by the mathematics of information technology and complex systems (mitacs), public health agency of canada (phac), international centre for infectious diseases (icid), national research council canada's institute for biodiagnostics (nrc-ibd), and the university of winnipeg. we wish to express our appreciation to all the participants for their significant contribution to the workshop. the authors, as the organizing committee, would like to thank margaret montague, sarah dietrich, and justyna swistak for assistance with meeting logistics. the authors declare that they have no competing interests. sm, np, jw, and py proposed and organized the workshop. sm summarized and drafted the preliminary version of this manuscript based on presentations and round-table discussions. all the authors have contributed to this manuscript, and approved its final version. key: cord- -rw o g authors: chen, patrick m.; hemmen, thomas m. title: evolving healthcare delivery in neurology during the coronavirus disease (covid- ) pandemic date: - - journal: front neurol doi: . /fneur. . sha: doc_id: cord_uid: rw o g nan coronavirus disease is caused by the acute respiratory syndrome coronavirus (sars-cov- ) and has led to the development of a rapidly evolving pandemic ( ) . the pandemic changed the assumptions made by most developed health care system: ample supplies and an overwhelmingly safe environment for patients and healthcare providers. hospital resources and supply are no longer secure, and the potential risk to patients and caregivers is increased. as neurologists, we face these challenges in many areas. here, we discuss the impact of the pandemic on neurology work flow in four areas: inpatient care, outpatient care, research, and ethics. one key lesson from the covid- experience internationally is the rapid depletion and scarcity of medical supplies [e.g., personal protective equipment (ppe) and mechanical ventilators], beds, and staff-an increasing occupational hazard for health care workers ( ) ( ) ( ) . we must critically evaluate our workflow and resource utilization in this crisis. acute stroke alerts present the most direct potential interface with covid- patients. existing stroke alert paradigms focus on high sensitivity for stroke detection with generally low specificity, requiring high resource utilization ( ) . several new workflows and consensus statements have been proposed for "protected" stroke alerts ( ) ( ) ( ) ( ) . overarching themes include expanded pre-screening in peri-hospital setting, widespread ppe training, designated "safety leaders" for monitoring proper precautions, limited examinations, and telemedicine. similarly, we have demonstrated the practicality of implementing tele-stroke video technology in the emergency room for initial triage during the pandemic ( ). rapidly implementing a large-scale "protected code" policy requires multidisciplinary coordination with hospital administration, other subspecialties (e.g., emergency department), and frequent feedback on the policies effectiveness from the frontline (e.g., nursing, ancillary staff, and trainees). in the future, the stroke alert could consolidate other covid- -related tests, such as chest imaging. how these protected workflow trends will affect time metrics and stroke care outcomes is yet to be determined. neurologic admissions and transfers to the hospital must be triaged and prioritized. we previously had the luxury of prolonged observation and extended outpatient workups, but we must now consider the exposure risks of prolonged hospitalization. surgical specialties have significantly reduced "elective" surgery ( ). in a similar vein, we should be judicious in determining if the benefits of admission or intervention supersede the potential dangers and resource utilization in the current crisis. we often call upon the neurological intensive care unit (icu) for co-management, though these beds and staff are also needed for covid- overflow. in a pandemic, it is reasonable to reserve resources, such as thrombectomy, to patients that would benefit the most, according to high-level (class , level a evidence) guidelines ( ) . ideally separate units should be used to isolate neurologic patients with covid- from neurology patients without the disease. beyond stroke patients, neurologists interface with the covid- population for symptoms including anosmia, encephalopathy, headache, or meningitis-encephalitis rule out. we must be cautious in pigeonholing a covid- patient and must resist substituting proxy diagnostics for a clinical exam because of infection risk. ancillary testing (e.g., eeg and ct scans) involve not only the machinery that will need to be disinfected but also personnel with risks for viral exposure. yet, standard of care, if indicated, should not be withheld due to covid- . given variability in individuals risk tolerance, a unified protocol may help remove these possible diagnostic biases in covid- patients. finally, with a need for mechanical ventilators and icu resources, our teams will need to be practical but still thorough in prognostication of catastrophic neurologic disease to assist resource allocation. many institutions share similar policies to reduce covid- transmission ( ) . at our institution, family visits are restricted, and all admitted patients receive a sars-cov pcr test. regarding ppe, aerosolized high-risk patients require n masks/powered air purifiers (papr) with eye protection, gowns, and gloves, while other inpatients require surgical masks, gloves, and eye protection ( ) . in circumstances of limited history, such as stroke codes or persons under investigation, an abundance of care should be taken. the possibility of asymptomatic covid- carriers or occult history should be considered in our patients and consults, underpinning the importance of universal precautions and rapid covid- testing when available. team members at high risk (e.g., immunosuppression and those over age ) are triaged to avoid direct contact (e.g., telemedicine role) when possible. finally, should a team member be exposed to covid- or show concerning symptoms, we follow the institutions policy regarding symptom monitoring, self-quarantine, and testing. the day-to-day routines of neurologists in the hospital have changed. for our institution, rounds have been streamlined to one senior team member, and team rounds are carried out over video conferencing. we practice six feet of distance amongst staff and patients and consider telephone-video conversation when possible except for critical physical examinations. we perform limited, but practical, neurologic examinations (at minimum: mental status, cranial nerves, and gross motor skills) focused on localization that guides changes in management. covid- positive or pui patients are seen last to reduce transmission. neurologists have the challenge of protecting the specialties tenants of diagnostic exactness and personalized patient rapport despite these limitations. finally, we have yet to see the long-term effects of covid- on trainee education and mental health. the accreditation committee of general medical education have made new exceptions to previous training requirements considering the pandemic, though there is concern this may lead to suboptimal learning conditions. currently, neurology trainees may be deployed to non-specialty services while primary teams are downsized. didactics are converted to video conferences, clinics are conducted via telemedicine, and the tradition of neurology bedside rounds and examination are curtailed. do these adaptations add to or deprive neurology training, and will these changes persist after the pandemic? similarly little is known about the impact of covid- on the psychological health of our team members who face a number of stresses: occupational risk, evolving policy changes, and unprecedented ethical decisions. the risk for trainee burnout-occupational, mental, emotional, and physical exhaustion-is high. a prophylactic solution to this by leadership should take the form of self-care initiatives, multidisciplinary mental health support groups, and frequent open forums (e.g., town halls) for trainees and all team members. a substantial portion of the neurologic population is classified by the center for disease control (cdc) as "high risk" (e.g., elderly, neuromuscular, immunosuppressed) for covid- illness ( , ). how can we best protect this vulnerable population while providing continuity of care? a review of current literature shows various subspecialtiesmultiple sclerosis ( ) the use of telemedicine platforms is critical when providing care to high-risk populations. pre-pandemic literature suggested telehealth was not inferior to face-to-face clinic visits for outcomes across neurologic subspecialties ( ) . the expansion of medicare coverage beyond rural areas and relaxing tele-hipaa requirements in response to the pandemic ( , ) has catalyzed rapid and wide implementation. the technology is versatile and could be expanded to monitoring with remote devices (e.g., accelerometers in parkinson's disease), neurorehabilitation, and providing a hotline to curb isolation in the elderly and disabled. proponents of telemedicine highlight its role in the " cs": better access to care, greater convenience, enhanced patient comfort, and better confidentiality. there is also an added new c-"contagion" ( ) . telemedicine is limited in the funduscopic, neuromuscular, and vestibular exams, and there remain concerns regarding consistent technology access and consistent privacy standards. we urge neurologist to address previous methodological flaws in the literature through collection of outcomes with neuro-telehealth. by addressing past infrastructure gaps, we may develop a feasible telehealth system for a high-quality standard of care post-pandemic. this data will help establish the marginal benefits of in-person visits over tele-visits. in many situations, this benefit may be much smaller from a risk-benefit and cost analysis standpoint than traditionally thought. a key question remains of how we will prepare for the return of neurologic patients with delayed diagnosis because of covid- . the number of stroke and myocardial disease hospital presentations decreased during the peak of the pandemic ( ) . these patients avoided and delayed health care due to isolation and quarantine, and this is likely applicable to other chronic neurologic conditions. as neurologists, we will need to explore the effects of isolation and fear on the outcomes of our neurologic patients. it is our responsibility to be proactive in educating our patients on the urgency of evaluation when appropriate, perhaps with more frequent tele-health follow-up, designated post-hospitalization follow-up coordinators, and large public organizational campaigns (e.g., stroke f.a.s.t campaign). we expect to see an upsurge in delayed neurologic complications as pandemic restrictions lighten, which may further exacerbate healthcare resource limitations. the pandemic has created a fervor within the research community, and neurology is not an exception. a number of small, observational retrospective studies have emerged with reports of guillain-barre ( ) syndrome, hemorrhagic encephalopathy ( ) , and stroke ( ) . there is speculation that anosmia may be from olfactory involvement of sars-cov ( ) . yet, it remains unclear if these reported correlations also lend to causation. editorial boards have pushed these findings to the forefront by offering pre-review releases, expedited review, and open access. while rapid information dissemination is important in uncertain times, we caution against the risk of "research exceptionalism" ( ). as the pandemic matures, the mentality of "better than nothing" should be transitioned to similar rigorous pre-pandemic publication standards if the findings are to be of clinical meaning. pandemic opportunism should not compromise the past standard of research integrity. given this, we must be cautious in how we interpret findings, especially when considering diverging from pre-pandemic standard of care. covid- has posed many challenges to ongoing large clinical trials. quarantine and travel restrictions have forced the pause of enrollment and rigid study protocols place several logistical strains on research staff. nevertheless, there remains a moral obligation to current study participants to complete these studies. how this is handled is complex and individualized by the study group. as the pandemic recedes, the impact of the pandemic directly (e.g., loss of participants or data) and indirectly (e.g., infection as a confounder) will need to be accounted for in result analysis and explored further. ultimately, we must leverage our research focus and resources wisely. the societal drive to understand covid- should not also come at the expense of our non-covid- neurologic patients. while the neurologic complications have captured the public eye, we should consider questions around quality improvement, personnel wellness, and the impact of the aforementioned workflow changes. an important task moving forward is to be methodical in our collection of data for covid- neurologic patients if we are the truly understand its role in the central nervous system. this will likely take the form of multicenter consortiums with a standardized protocol to create large prospective databases. a myriad of potential ethical situations could arise for neurologists ( ) . accounts of the lombardy region of italy detail harrowing decisions of life and death by icu physicians ( ). how do we weigh diseases such as alzheimer's or parkinson's against ventilated patients when asked about "life prognosis" or "prospective instrumental value to others" ( )? how do we factor in neurologic comorbidities when making triage decisions? while we hope to never reach this point, we must prepare for it. we must not categorically exclude those with chronic neurologic and cognitive disability. it is imperative we proactively discuss goals of care with patients outside the hospital to shield the frail from medical intervention that may provide potential harm. now, is a time to develop a robust palliative care program for patients with limitation of therapeutic effort (lte). furthermore, these difficult icu decisions should use advanced directives and living wills and be guided in a multidisciplinary fashion with ethical committees. in the first weeks of the pandemic, we noticed many subtle clinical situations that already challenge our previous framework of clinical practice. a seemingly simple example is the extent of observation and work up in a transient ischemic attack. does a patient on therapeutic anticoagulation and a low abcd score for transient numbness warrant admission? previously in our academic tertiary hospital, we would admit this patient and pursue an extensive stroke work up. currently, the risk of exposure to covid- in the hospital leads providers and patients to prefer outpatient workup, forgoing, or curtailing inpatient monitoring. how this impacts patient outcome is not certain. on the other hand, the risk of nosocomial infection previously existed, and the potential for harm was present in healthcare before covid- . how much higher this risk is now with covid- is unexplored. these questions may lead to a fundamental risk assessment going forward where the marginal benefit of improved outcome for inpatient admission is weighed against the increased risks associated with hospital stay and procedures ( ). our actions as specialists do not exist in a vacuum. we should note the impact our testing has on nurses and ancillary staff. for instance, we were consulted for abnormal neck movements in a prone-position covid- -positive patient. our initial impulse was to order a -h eeg to capture this event. but a number of questions arose. what is the benefit of a -lead eeg established by an eeg technologist over a portable and limited eeg that can be established by a bedside provider who already had used ppe and was at the bedside? how does our diagnostic plan differ from pre-pandemic? what are the effects on patient outcome if we adjust our diagnostic and treatment algorithm in the setting of the covid- pandemic? our department is developing a collaborative protocol posed from these clinical questions. finally, how do we manage outpatients with progressive neurologic disease-the ones with limited life expectancy but who not ill enough to be in the hospital? an example is a man with longstanding amyotrophic lateral sclerosis (als) who is scheduled for outpatient gastrostomy tube placement. the interventional radiology team inquires if gastrostomy tube placement can be delayed as the healthcare system reduces use of equipment and staff for elective procedures. a fully informed discussion in a controlled setting with the patient and his family regarding the goals of care is important. we are still not sure how these discussions will be framed by the current crisis or used for triage, but we as neurologists are well-equipped for these discussions and should be proactive. covid- has disrupted the neurologic healthcare ecosystem in the inpatient, outpatient, and research setting. it is paramount that we aid in preserving limited hospital resources and protect our patients and teams by critically assessing all clinical practices. what emerges are striking changes in clinical workflow and a chance to develop telemedicine and potentially difficult clinicalethical decisions. moving forward, we should be diligent in data collection and strive to understand how these workflow changes impact our patients. the silver lining in this pandemic is we have the opportunity as a specialty to revisit our practices and change for the better. pc: study concept and design, acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content. th: analysis and interpretation, critical revision of the manuscript for important intellectual content, study supervision. all authors read and approved the final manuscript. clinical characteristics of coronavirus disease in china the toughest triage -allocating ventilators in a pandemic facing covid- in italy -ethics, logistics, and therapeutics on the epidemic's front line fair allocation of scarce medical resources in the time of covid- acute stroke code accuracy in the inpatient versus emergency department (ed) setting (s . ) protected code stroke: hyperacute stroke management during the coronavirus disease (covid- ) pandemic. stroke endovascular therapy for patients with acute ischemic stroke during the covid- pandemic: a proposed algorithm acute stroke care in the coronavirus disease pandemic preparing a neurology department for sars-cov- (covid- ): early experiences at columbia university irving medical center and the new york presbyterian hospital a stroke care model at an academic, comprehensive stroke center during the covid- pandemic severe outcomes among patients with coronavirus disease (covid- ) -united states scoping review of prevalence of neurologic comorbidities in patients hospitalized for covid- treating multiple sclerosis and neuromyelitis optica spectrum disorder during the covid- pandemic covid- and neuromuscular disorders cross: keeping people with epilepsy safe during the covid- pandemic telemedicine in neurology: telemedicine work group of the american academy of neurology update medicare telemedicine health care provider fact sheet virtually perfect? telemedicine for covid- the coronavirus disease crisis as catalyst for telemedicine for chronic neurological disorders collateral effect of covid- on stroke evaluation in the united states guillain-barre syndrome associated with sars-cov- covid- -associated acute hemorrhagic necrotizing encephalopathy: ct and mri features neurologic manifestations of hospitalized patients with coronavirus disease the neuroinvasive potential of sars-cov may play a role in the respiratory failure of covid- patients ethics in the time of covid: what remains the same and what is different improving quality, minimizing error: making it happen the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.copyright © chen and hemmen. this is an open-access article distributed under the terms of the creative commons attribution license (cc by). the use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. no use, distribution or reproduction is permitted which does not comply with these terms. key: cord- -ipv awq authors: smith, richard d; keogh-brown, marcus r; barnett, tony; tait, joyce title: the economy-wide impact of pandemic influenza on the uk: a computable general equilibrium modelling experiment date: - - journal: bmj doi: . /bmj.b sha: doc_id: cord_uid: ipv awq objectives to estimate the potential economic impact of pandemic influenza, associated behavioural responses, school closures, and vaccination on the united kingdom. design a computable general equilibrium model of the uk economy was specified for various combinations of mortality and morbidity from pandemic influenza, vaccine efficacy, school closures, and prophylactic absenteeism using published data. setting the uk economy (the most up to date available with suitable economic data). main outcome measures the economic impact of various scenarios with different pandemic severity, vaccination, school closure, and prophylactic absenteeism specified in terms of gross domestic product, output from different economic sectors, and equivalent variation. results the costs related to illness alone ranged between . % and . % of gross domestic product (£ . bn to £ . bn) for low fatality scenarios, . % and . % (£ . bn to £ . bn) for high fatality scenarios, and larger still for an extreme pandemic. school closure increases the economic impact, particularly for mild pandemics. if widespread behavioural change takes place and there is large scale prophylactic absence from work, the economic impact would be notably increased with few health benefits. vaccination with a pre-pandemic vaccine could save . % to . % of gross domestic product (£ . bn to £ . bn); a single dose of a matched vaccine could save . % to . % (£ . bn to £ . bn); and two doses of a matched vaccine could limit the overall economic impact to about % of gross domestic product for all disease scenarios. conclusion balancing school closure against “business as usual” and obtaining sufficient stocks of effective vaccine are more important factors in determining the economic impact of an influenza pandemic than is the disease itself. prophylactic absence from work in response to fear of infection can add considerably to the economic impact. in the past century there were three major influenza pandemics ( , , and - ) . this century has seen an outbreak of severe acute respiratory syndrome ( ) , h n subtype of the influenza a virus ( ), and sporadic outbreaks of h n influenza subtype. in addition to the direct health impacts of a serious outbreak, we should be concerned about the economic impact; especially at a time of global recession. preparedness planning for a pandemic must therefore balance two key policy strands-maintaining "business as usual" to minimise the economic impact of a pandemic, and encouraging "social distancing" to minimise the health related impact of a pandemic -as well as using resources such as antivirals and vaccinations. this paper considers the tension inherent in these two policy strands. it provides evidence of the economy-wide impact of each approach, as well as the impact that vaccine development may have in reconciling the two objectives of minimising both the health and economic effects of a pandemic. a key consideration in this analysis is the role of public perception and confidence, expressed by "prophylactic absenteeism," where healthy people avoid social contact, including going to work. this response is likely to emerge at higher case fatality rates and to be moderated by the availability of effective vaccines (the current strain of h n influenza seems to be highly infectious but not very deadly, and this may explain its limited economic impact to date). the analysis is based on a computable general equilibrium model of the uk over one year. the economy is specified in terms of several agents, including households, producers, and government, and based on data (in the form of a social accounting matrix, which represents income and expenditure in the economy by sector) for taken from the global trade analysis database and national statistics. computable general equilibrium modelling is described in further detail by dervis et al. the economic impact of influenza in our model is assumed to occur through the labour supply, since illness and death cause both a reduction in the availability of labour and in its quality. mitigation actions can also affect the labour supply by (a) reducing labour when people are kept away from the workplace to avoid infection or (b) by increasing labour supply compared with non-mitigated pandemic scenarios by reducing the number of infections and deaths and reducing the extent to which people feel the need to engage in prophylactic absenteeism. pandemic impact pandemic planning documents anticipate clinical attack rates between % and %, with a maximum of %. we therefore use these three values in our disease scenarios. based on previous pandemics, predicted case fatality rates for the uk range from . % to . %, and the summary estimate for european pandemic preparedness plans is . %. we used . % as our base disease scenario and . % for our severe scenario, with an extreme scenario of % based on severe acute respiratory syndrome (sars). we therefore have nine possible combinations of clinical attack rate and case fatality rate. while deaths permanently remove labour from the workforce, absenteeism represents temporary removal. illness absence will result in subsequent immunity to the virus, whereas those undertaking prophylactic absenteeism will still be vulnerable to infection. the commission of the european communities suggests that the duration of pandemic influenza illness is five to eight working days, and absence for seasonal flu is approximately five days. we therefore assume five days of illness for our mild scenario, seven days for severe, and days for the extreme scenario, which is based on hospitalisation rates for sars. all absences are estimated as a percentage of time lost from a working year of days. pandemic mitigation: vaccination although the us recently announced that it expects to go from vaccine trial to mass vaccination within two months, and the uk has signed agreements (with gsk and baxter) to purchase million doses of pandemic-specific vaccine, specific vaccines are unlikely to be available for the first wave of infection. during this stage, pre-pandemic vaccines, based on existing virus strains, will be the only option for protection, giving approximately % efficacy and, when combined with other clinical countermeasures, reducing the pandemic's impact to that of seasonal influenza. once matched vaccines become available they are likely to have - % efficacy, probably requiring two doses at an interval of three weeks. vaccine shelf life is currently about one year. we assumed two vaccination strategies-a pre-pandemic vaccine with % efficacy and a matched vaccine with % efficacy (single dose) and % efficacy (double dose). for all vaccines we assumed sufficient stocks for % coverage. vaccination would have two potential impacts on a pandemic, reducing the number of infected individuals and moderating the extent of prophylactic absenteeism because people feel protected from infection. pandemic mitigation: school closure school closures are believed to reduce the impact of the pandemic, since infection rates among children are high, and this is mentioned in many pandemic planning documents. - although we witnessed closure at the early stages of the h n influenza pandemic, it has been suggested that closure later, when the epidemic is better established, will be more effective in delaying spread, but also inevitable if large sectors of the population adopt prophylactic absenteeism in the face of increasing reports of deaths. it is therefore important to distinguish between school closure as a reactive policy to a pandemic and school closure associated with prophylactic absenteeism. ferguson et al suggest that reactive school closure will result in closure for % of the weeks of the pandemic, regardless of how often they reopen (duration of school closure associated with prophylactic absenteeism cannot, of course, be known). previous studies have assumed school closure at the four week peak of the pandemic, allowing for some variation around the two or three week disease peak cited in the department of health's pandemic plan. any school closure policy will result in disruption for working parents and, based on peak pandemic duration and ferguson's estimates, we present scenarios with four weeks and . weeks of school closure. we also consider the mitigation impact of school closure, which is estimated as % for a % clinical attack rate in the ferguson paper and up to a maximum of between glossary of terms computable general equilibrium model--a mathematical model of the whole economy that includes the cost minimising and profit maximising behaviour of producers, the consumption and saving behaviour of households and government, taxation mechanisms, and the use of labour, capital, and other factors in order to produce goods for investment or consumption. the model produces a benchmark solution which is then compared with alternative solutions incorporating policy change or other events simulated by the model. counterfactual solutions can be compared with the benchmark solution to estimate the economic impact of the simulated policy or event. social accounting matrix--a matrix that represents the balanced income and expenditure flows of a regional, national, or global economy aggregated to make them a manageable size for use in a computable general equilibrium model. (the matrix rows represent income to the economy and the columns represent expenditure.) global trade model--a computable general equilibrium model of the global economy. prophylactic absenteeism--absence from work of a healthy individual in order to avoid infection. clinical attack rate--the percentage of individuals in a population who become infected. case fatality rate--the percentage of infected individuals who die. mortality rate--percentage of individuals in a total population who die (clinical attack rate × case fatality rate). reactive school closure--government closure of a school to reduce infection when a (government defined) proportion of children or staff is experiencing illness. school closure associated with prophylactic absenteeism--closure of schools caused by the amount of prophylactic absence by staff. transition point--the point at which the severity of the pandemic provokes sufficient fear to invoke a sudden increase in prophylactic absenteeism within the population. % and % in the paper by cauchemez et al, which we approximate as %. the uk labour force survey ( ) suggests that individuals aged - are in paid employment, of whom are women who have dependent children in the household. that is, . % of the workforce comprises women who are probably responsible for dependent children. a small proportion of working men is also reported to be responsible for dependent children, bringing potential absenteeism estimates through school closure to . %. however, we made some attempt to correct this estimate to account for informal care by grandparents, working from home, etc. in addition, we assumed that those % of working parents who maintain working hours during school closure because of informal care will lose working hours equivalent to one person's illness duration when their informal caregiver is ill. pandemic mitigation: prophylactic absenteeism previous studies have shown that a main driver of economic impact is behavioural change. behavioural change can include changes in consumption patterns and prophylactic absence from work to avoid infection. prophylactic absence from work is likely to be governed by personal choice related to fear and therefore is unlikely to be proportionate. there will be a transition point when the number of individuals who decide to take relatively drastic social distancing action to avoid infection increases rapidly over a short space of time. we suggest that the transition point in public behaviour related to an influenza pandemic is likely to be heavily influenced by the case fatality rate but to be reasonably independent of the clinical attack rate since illness, by itself, causes limited fear if a full recovery is anticipated. the public response to the current h n pandemic supports this. the level of the case fatality rate at which such a transition point will occur is likely to be related to the density of deaths in "effective social networks"-that is, the prospect of death becomes rapidly personalised with the death of a member of one's network of relatives, friends, colleagues, and acquaintances. to our knowledge, no study has been conducted to determine the impact of prophylactic absenteeism on modelling predictions related to disease and economic impacts. accurate estimation of this transition point for pandemic influenza would require extensive survey work, and it would be useful to undertake such research in future so as to build up a body of knowledge relevant to the kind of modelling reported here. in its absence we have selected the conservative value of about people as the effective social network, to include close contacts such as family and friends ( - people), acquaintances, and work colleagues. [ ] [ ] [ ] [ ] [ ] on this basis almost everybody in the population will know someone who has died once the mortality rate reaches one death per people, triggering prophylactic absenteeism. simple arithmetic suggests that there are discrete effective social networks in the uk ( / ). however, many of these will overlap, and so the real figure for the number of discrete social networks involved in communication of news of a death, taking into account facebook, texting, and other networking tools, is likely to be smaller. in the absence of research on this topic, a case fatality rate in the range . - % seems to be a valid assumption for the expected transition point. not all individuals will avoid work during a pandemic, but a survey conducted after the sars outbreak indicated that about % of the working population in europe would be willing to take prophylactic absence from work in the event of an infectious disease outbreak. although survey responses do not always reflect true behavioural responses, it is reasonable to assume that the % of respondents who reported themselves as willing, in theory, to avoid work for a serious pandemic, would do so at the transition point presented above. it is difficult to predict the duration of such absenteeism, as high levels of fear might cause prolonged periods of absence by some. however, it might reasonably be assumed that in most cases, absentees would be forced to take annual leave (as longer term sick leave usually requires a doctor's authorisation). on this assumption, absenteeism is likely to last up to four weeks, and, since the peak of the pandemic is likely to last two or three weeks and the transition point is unlikely to be reached before the peak, this is presumed to be a reasonable upper limit. table provides a summary of the assumed parameter estimates used in our disease scenarios together with the sources of these estimates. the accuracy of these results is subject to the scenarios we have outlined, the model specification, and the economic data from underlying the model. figure shows the impact of various disease and mitigation scenarios on gross domestic product: disease only (with no mitigation), disease with four weeks of school closure, disease with pre-pandemic vaccine, disease with matched vaccine (single dose), and disease with matched vaccine (double dose). each scenario is plotted for low, medium, and high clinical attack rate ( %, %, and %) and low, high, and extreme case fatality rates ( . %, . %, and %), although both rates are adjusted to allow for mitigation effects in the mitigation scenarios. low case fatality rate the first three histogram bars show the impact of a low case fatality rate, in which variations in clinical attack rate have little impact (loss of . - . % of gross domestic product). however, the impact of four weeks of school closure is large, doubling or even tripling the impact of the disease alone. the results also show that in a low fatality pandemic a pre-pandemic vaccine might result in savings of . - . % of gross domestic product, and a matched vaccine could result in savings of . - . % for a single dose and . - . % for a double dose. the transition point of prophylactic absenteeism is not reached in any of the scenarios with a low case fatality rate. high case fatality rate with a high case fatality rate, however, the transition point is reached (mortality rate becomes similar to that of the pandemic), so that individual change in behaviour to avoid infection yields large impacts of . %, . %, and . % of gross domestic product for the low, medium, and high infection rates, respectively-emphasising that the mortality rate can, in such circumstances, be a more important determinant of economic impact than the infection rate. the introduction of school closures in high fatality scenarios has less impact than in low fatality scenarios, with an additional impact of . - . % of gross domestic product. a pre-pandemic vaccine would be insufficient to avoid the transition point in a high fatality pandemic and so would reduce the impact on gross domestic product by only . - . %. a matched vaccine, even if only single dose, would have sufficient effect to avoid the transition point and could therefore result in savings of . - . % of gross domestic product (roughly equivalent to half of the impact of the financial crisis over the past year (www.statistics.gov.uk/instantfi gures.asp)). two doses of a matched vaccine are likely to reduce the impact further, yielding savings of - %. the extreme fatality scenarios predictably yield the largest impacts. our assumptions dictate that for such a serious pandemic the transition point would be passed, and the low, medium, and high infection scenarios yield reductions in gross domestic product of . %, . %, and . %, respectively. school closure increases this impact by . - . %, which is smaller than for the less severe scenarios as the mitigation impact of school closure reduces the severity of the disease. pre-pandemic vaccine has some effect on reducing the impact of the alternative scenarios alternatives to these scenarios have also been modelled but are not reported in detail here. in brief, schools closing for about % of the weeks of the pandemic's duration and assuming a mitigation equivalent to % if the clinical attack rate was %, as outlined by ferguson et al, produces a . % further reduction in gross domestic product compared with our four week closure scenarios; it reduces the infection rates, but the dominance of the case fatality rate in determining the transition point is such that the degree of prophylactic absenteeism remains the same. similarly, informal care by grandparents and friends, reducing the level of prophylactic absenteeism from . % to . %, reduces the loss to gross domestic product by . - . % in the four week school closure scenarios and by . - . % in the longer closure scenario. assuming the higher mitigation rate of % suggested by cauchemez et al, which would apply to longer school closure scenarios, the severity of the economic impact of school closures is reduced in proportion to the severity of the pandemic. this reduction is quite small-up to . % of gross domestic product for non-extreme scenarios and up to . % of gross domestic product in the most extreme and unmitigated scenario-so overall reductions in gross domestic product are still between % and % larger than with the four week school closure scenarios. school closure's failure to mitigate the impact of the disease despite the assumption of its efficacy is due to the large amount of absenteeism induced by school closures, which, in our model, is not affected by the clinical attack rate. additional scenarios relating to the swine flu pandemic and alternative vaccine efficacy assumptions are included in an online appendix. figure shows the impact on different sectors of the economy for the % clinical attack rate and . % case fatality rate scenario. the pattern is similar across scenarios. the lowest impacts are seen in the extraction sector (mining, quarrying, forestry and fishing) followed by crops, utilities, and health and non-health services. the largest impacts are in the meat and livestock, processed foods, textiles/paper/plastics, manufacturing, and transport and communications sectors. computable general equilibrium modelling also produces the welfare measure of equivalent variation, which represents the amount of money that, if an economic change does not happen, leaves the population just as well off as if the change had occurred. this may be thought of as the amount of money that the population might be willing to pay to avert the pandemic. for the purposes of this paper, the welfare measure is quoted as a percentage of gross domestic product, with the results presented in table . in order to avoid the economic impact of the pandemic, the cost that the population might be willing to pay ranges from . % (£ . bn) for the mildest disease-only scenario to % (£ bn) for the most extreme. school closure increases these values to . % (£ . bn) in the mildest scenario to . % (£ . bn) for the most severe scenario. our results show that, depending on the disease severity, pandemic influenza alone could reduce gross domestic product by . - . %. extending fatality rates beyond those observed in previous pandemics to a sars-like case fatality rate of % yields an impact of . - . % of gross domestic product (£ . bn to £ . bn). school closure, and its related absenteeism, causes a notable increase in economic loss, and caution might therefore be advised in pursuing this policy when the case fatality rate is low. a pre-pandemic vaccine with moderate efficacy and % coverage could result in large relative savings for any low or high fatality pandemic of £ . bn-£ . bn, or £ . bn-£ . bn for extreme scenarios. a matched vaccine, even if only available in sufficient time for a single dose to be administered to % of the population, would result in substantially higher savings, in both low and high fatality scenarios, and a double dose of a matched vaccine could keep the loss in gross domestic product to below %, even with the most extreme pandemic and long school closureswhich is little more than half the impact of the current recession, although recovery from a severe flu event would probably be much more rapid. estimates suggest that the planned h n flu vaccination will cost about £ per person (www.bloomberg.com/apps/ news?pid= &sid=auyqiqyj. i), yielding a total cost of about £ m, compared with savings that start from £ . bn for the mildest pandemic. our results suggest that, even in a mild pandemic, a vaccine costing £ . per person would be beneficial in terms of its health impact without imposing a burden on the economy. our results also consider the possibility that there is a transition point in case fatality rate, above which many individuals might change their usual behaviour and avoid work in an attempt to avoid infection. evidence suggests that % prophylactic absence, which is larger than our assumed absence rates, is likely to reduce a % clinical attack rate by only % (case fatality rate is unchanged as this is dependent on the disease). since these absence rates could cost the economy billions of pounds, prophylactic absence should be discouraged except in exceptional circumstances. limitations and strengths of study this work does not take into account consumption effects from avoidance of public places, entertainment events, and changes in shopping patterns, although further work is under way to establish an evidence base from which these effects can be modelled. impacts on trade, imports, and exports have not been examined here as it is difficult to assess these impacts accurately with a single-country model. a study with a global trade model is ongoing and will supplement the findings presented here. the strength of our findings depends on the underlying assumptions which, though based on published evidence where possible, are subject to the bias of surveys, the unpredictability of the disease and its resultant impact on policies and behavioural change. we included estimates of school closure and prophylactic absence, but their true values in the middle of a pandemic could vary widely. however, this paper extends previous work by using the best available estimates to approximate the impact of social networks on behavioural change, considering various lengths of school closure, their feedback effects on the pandemic, and the impact of informal care both in mitigating absenteeism due to school closure and in causing absenteeism by parents when informal carers are unwell, as well as considering the impact of various vaccination strategies on disease and behaviour change. pandemic influenza itself, if it occurs within the bounds of severity outlined in pandemic plans, will not yield unprecedented economic impacts: even a high fatality pandemic with high levels of infection would reduce gross domestic product by less than . %. however, two factors will compound the disease's impact. firstly, a pandemic in the near future would impose additional strain on an economy that is already stretched by recession, exaggerating the effect of recession and slowing economic recovery. secondly, although the direct economic impact of disease is relatively small, school closures and prophylactic absenteeism, whether imposed by government or the result of fear of infection in the population, could greatly increase the economic impact. in the event of a mild pandemic, long periods of school closures will not be necessary and could greatly multiply the economic impact of the disease and should therefore be minimised. in more serious pandemics, the relative economic impact of school closures decreases and the gains from school closure in mitigating the pandemic increase, so a policy of school closure should take into account the severity of the disease. however, such a policy should be limited in its duration-sufficient to maximise the lowering of peak disease levels and maintain a functioning health service, but allowing schools to open at other times. in an extreme pandemic, the relative incremental cost of school closure is small and should not influence policies that would minimise deaths. our "transition point" estimates provide an example of how fear induced behavioural change could greatly increase the economic impact of a pandemic while providing questionable health gains. we suggest that the overall mortality rate is the driver of this behavioural change, and vaccinations, whether pre-pandemic or matched vaccine, could be extremely important in preventing mortality rates from reaching the "transition point." the cost of vaccinations is likely to be less than the economic savings gained from vaccination, even in the mildest of pandemics, and in the event of a high or extreme fatality pandemic a matched vaccine fear induced behavioural changes or government sanctioned absences from work or school in response to a flu pandemic could have a substantial economic impact, and these losses may not be balanced by large health benefits vaccines play a major role in mitigating the economic impact of a pandemic regardless of the characteristics of the disease if increased fear caused by deaths within an individual's social network provokes prophylactic absence from work, large economic loss could result might be the only method to avoid the unprecedented economic effects of behavioural change. contributors: rds conceived the idea of a computable general equilibrium application for influenza, advised on the modelling and scenarios, and contributed to the drafting of the paper. mrk-b was responsible for the modelling, the underlying dataset, construction of modelling scenarios and shocks, and drafted the paper. tb and jt conceived the idea of the transition point based on social networking theory, advised on the scenarios and vaccination strategies, and contributed to the drafting of the paper. mrk-b is guarantor for the study. funding: no specific funding for this study. competing interests: none declared. ethical approval: not required for this study. data sharing: model output data are available on request from marcus. keogh-brown@lshtm.ac.uk bird flu and pandemic flu swine flu the economic impact of sars: how does the reality match the predictions? pandemic influenza: a national framework for responding to an influenza pandemic. dh a standard computable general equilibrium (cge) model in gams global trade, assistance, and production: the gtap data base balancing a social accounting matrix: theory and application parameter estimation for a computable general equilibrium model: a maximum entropy approach general equilibrium models for development policy strategies for mitigating an influenza pandemic scientific pandemic influenza advisory committee (spi): subgroup on modelling, modelling summary sars-beginning to understand a new virus scenarios on costs and savings of influenza treatment and prevention for dutch healthy working adults clinical progression and viral load in a community outbreak of coronavirus-associated sars pneumonia: a prospective study sars: a case study in emerging infections us puts flu vaccines on trial agreements secured for pre-pandemic vaccine in the uk. dh vaccine manufacturing: challenges and solutions pre-pandemic and pandemic influenza vaccines: scientific evidence base. dh european centre for disease prevention and control. technical report: expert advisory groups on human h n vaccines, scientific questions.ecdc broad clade cross-reactive immunity induced by an adjuvanted clade rh n pandemic influenza vaccine department of health. uk health departments' influenza pandemic contingency plan us department of health and human services. hhs pandemic influenza plan public health agency of canada. the canadian pandemic influenza plan for the health sector estimating the impact of school closure on influenza transmission from sentinel data the macroeconomic impact of pandemic influenza: estimates from models of the uk, france, belgium and the netherlands the possible macroeconomic impact on the uk of an influenza pandemic closure of schools during an influenza pandemic precautionary behavior in response to perceived threat of pandemic influenza estimating the costs of school closure for mitigating an influenza pandemic the economic impact of sars: how does the reality match the predictions the psychology behind the masks: psychological responses to the severe acute respiratory syndrome outbreak in different regions paris et l'agglomeration parisienne psychosocial impact among the public of the severe acute respiratory syndrome epidemic in taiwan social connectivity in america: changes in adult friendship network size from rethinking friendship: hidden solidarities today key: cord- -s kmipir authors: osier, faith; ting, jenny p. y.; fraser, john; lambrecht, bart n.; romano, marta; gazzinelli, ricardo t.; bortoluci, karina r.; zamboni, dario s.; akbar, arne n.; evans, jennie; brown, doug e.; patel, kamala d.; wu, yuzhang; perez, ana b.; pérez, oliver; kamradt, thomas; falk, christine; barda-saad, mira; ariel, amiram; santoni, angela; annunziato, francesco; cassatella, marco a.; kiyono, hiroshi; chereshnev, valeriy; dieye, alioune; mbow, moustapha; mbengue, babacar; niang, maguette d. s.; suchard, melinda title: the global response to the covid- pandemic: how have immunology societies contributed? date: - - journal: nat rev immunol doi: . /s - - - sha: doc_id: cord_uid: s kmipir the covid- pandemic is shining a spotlight on the field of immunology like never before. to appreciate the diverse ways in which immunologists have contributed, nature reviews immunology invited the president of the international union of immunological societies and the presidents of other national immunology societies to discuss how they and their members responded following the emergence of severe acute respiratory syndrome coronavirus (sars-cov- ). international union of immunological societies: faith osier. unprecedented times call for unprecedented actions. immunologists and vaccine developers across the world have committed to producing vaccines against covid- in timelines previously considered unthinkable. immunologists globally have partnered and engaged with epidemiologists, clinicians, public health officials, regulatory agencies and funding bodies to fast-track research to better understand the disease. on march , the world health organization declared covid- a pandemic: within weeks, a flurry of research activity was already under way. the scientific literature was flooded with studies describing the disease (epidemiology, transmission, onset and pathogenesis) as well as prognostic biomarkers. concurrently, innovative study designs facilitated rapid collection of data on potential immune-based therapies and drugs in multiple sites simultaneously. old and new potential therapies were do not have all the answers, together our immunology societies have been an incredible global resource, as is highlighted in the contributions herein and in fig. . (editor note: see fig. for biographies of the presidents of the immunology societies featured in this article and supplementary information for biographies of all the contributors.) american association of immunologists: jenny p. y. ting. the pandemic immediately forced the american association of immunologists (aai) to cancel our annual meeting, immunology , and to work remotely. aai members are working at the forefront of the pandemic, conducting critical immunological research that will support clinical solutions. us laboratories, however, have been challenged by pandemic restrictions, and our members need more support than ever. to provide this, the aai developed a three-pronged approach prioritizing ( ) advocacy, ( ) dissemination of information and ( ) continued funding. aai public affairs activities were critical components of the advocacy plan . since march , aai members have submitted testimonies, issued statements, written and co-signed letters, and advocated additional funding. efforts included writing to president donald trump and congressional leaders urging that they heed the advice of scientific/public health leaders, including aai member anthony fauci ; writing to national institutes of health (nih) director francis collins requesting justification for terminating an nih-funded grant focusing on understanding the risk of bat coronavirus emergence ; advocating supplemental funding for federal science agencies, including the nih, for pandemic-related research losses and additional trainee support; and issuing a statement opposing actions taken by the trump administration that will damage international scientific collaboration . aai journals accelerated the time taken for reviews of covid- papers to week and made all coronavirus-related publications free online to speed up the dissemination of crucial information . due to laboratory closures, authors and reviewers were given more flexibility . equally put to the test. and we already have some answers. education and communication between scientists across disciplines, and between scientists and the general public, has flourished. enabled by contemporary interactive online platforms, immunologists took an early lead in organizing scientific webinars for information sharing and collaborations and to spur cross-disciplinary research. the international union of immunological societies (iuis) brought together more than , immunologists from more than countries in a series of weekly covid- webinars . these not only spanned the breadth of immunology but also reflected on our responsibility to maintain the integrity of rigorous scientific peer review, especially during a pandemic. our speakers reflected our rich diversity and expertise across regional and national boundaries, and smashed stereotypes with regard to gender, race and age. we contributed to our local, national and regional response strategies. like never before, we engaged vigorously with the public in our respective constituencies and mustered the composure to face our own vulnerability. although we still the aai sustained education and funding initiatives. although the immunology meeting was cancelled, the aai published all submitted abstracts free online . furthermore, it established a 'covid- resources and information center' , transitioned aai-led immunology courses from onsite to virtual and continued funding for all aai fellowships despite laboratory closings . australian and new zealand society for immunology: john fraser. the australian and new zealand society for immunology is a very active and collegial society with more than , members spread across the seven states of australia and new zealand; and no, new zealand is not (yet) a state of australia. we have remained very active despite the pandemic putting a pin in all our regular events for . many of our members have talked whimsically over the but stringent lockdown now enjoy (almost) 'covid-free' status in the community. however, the sudden dramatic surge in cases in the australian state of victoria has brought home just how easily containment control can be lost. nevertheless, our relative success is down to two things; one, a scientifically informed and adherent public; and two, quality science-led political leadership. attention now turns to a vaccine; which ones will work and more commonly when can we expect one. with so much anticipation, it has been difficult to caution that the massively accelerated development of so many non-optimized vaccines risks making a wrong choice. it is an important time to be an immunologist! belgian immunological society: bart n. lambrecht and marta romano. belgium has been hit hard by covid- , with close to , deaths from a population of . million. almost % of deaths occurred in residential care centres. there was an early lockdown, and hospitals were well prepared to handle severe cases of covid- owing to a high density of specialized intensive care unit beds in belgium. initially, pcr testing capacity was restricted, which led to underdiagnosis of mild cases and overestimation of deaths attributable to covid- , particularly in elderly people. the belgian immunological society (bis) is a small society with only active members, but its members have been influential in this health crisis. several bis board members were part of a task force that discussed and designed all clinical interventions for covid- . the bis president, a pulmonologist by training, is the principal investigator on three national trials investigating the use of recombinant granulocyte-macrophage colony-stimulating factor (clinicaltrials. gov id nct ) anticytokine drugs targeting il- , il- and il- receptor (nct ) and the complement c inhibitor zilucoplan (nct ) . these clinical trials have incorporated highly detailed immunomonitoring, including -colour flow cytometry, single-cell rna sequencing and cellular indexing of transcriptomes and epitopes by sequencing (cite-seq) analysis of more than barcoded antibodies. several bis members are coordinating different projects, such as studies on immune correlates of protection or nationwide seroprevalence testing. much immunological knowledge was shared during discussions with clinicians on when and how to administer convalescent plasma and how to identify years about a global pandemic and now we are living it! immunology and infectious disease have been at the forefront of public awareness, and many of our members have been instrumental in communicating the science of immunology in lay terms to the public and, more importantly, in advising policymakers and politicians, who, i might add, have been very keen to learn some immunology. many of our members are also part of international research teams looking for solutions to the pandemic. the australian and new zealand society for immunology is a respected scientific society within the region and has responded to the covid- crisis with well-informed information and online resources such as ' ask an immunologist' and our 'fireside chats' . australia and new zealand responded vigorously at the first sign of community transmission, and after enduring a brief bis members also advised several ministers and health-care officials on the value and significance of antibody testing, on plans for preparedness and on deciding which immunomodulatory drugs to stockpile. bis members were frequently in the news to educate the general public on the immune response to covid- , the value of antibody testing and the impact of the cytokine storm on disease severity. we saw it as our duty to educate clinicians on the immunology of covid- through webinars, which were very well attended. our society also took care in identifying patients at particular risk of severe covid- , and all major hospitals now report their young and severely affected patients to the belgian primary immune deficiency group, which is collecting samples and will perform in-depth genetic analyses. brazilian society for immunology: ricardo t. gazzinelli, karina r. bortoluci and dario s. zamboni. today, brazil is placed in the shamed second-highest position in terms of the number of cases of severe acute respiratory syndrome coronavirus (sars-cov- ) infection and deaths due to covid- . the first official case in brazil was recorded in february . expecting a boom in transmission, brazilian scientists quickly mobilized to create strategies to fight sars-cov- . it soon became clear that the hopes to control transmission and to treat covid- would largely rely on assessment of and interventions in the immune system. the brazilian society for immunology (sociedade brasileira de imunologia) led the efforts to mobilize research laboratories into national and international networks to tackle covid- . we also intensified communications with the general media and on social networks, urging our citizens to follow scientific advice in dealing with this pandemic. this was key, as the brazilian government minimized the importance of this disease, spreading misleading information and taking decisions not supported by high scientific standards. meanwhile, our scientists have been designing new vaccine strategies and information on covid- . through our media engagement, the voices of bsi members have featured prominently in national news reports throughout the pandemic. we also produced resources for the public to demystify the science of covid- on topics including testing and vaccine development . for our members and the wider research community, we launched our highly successful 'connect on coronavirus' webinar series, which sees internationally renowned speakers discuss the latest sars-cov- research . the bsi has made a real impact in ensuring the voice of the immunology community on covid- is represented at the highest levels in the uk. we are extremely proud of what we have achieved, all made possible through our members' support. we express our deepest thanks to those who have contributed to our activities and the ongoing global covid- effort. canadian society for immunology: kamala d. patel. the canadian society for immunology (csi) represents more than biomedical researchers, clinician scientists, postdoctoral fellows and graduate students. many are directly involved in finding solutions to the problems caused by the covid- pandemic. other members actively participate in communicating with the public to dispel the myths that surround the pandemic, serving as a source for factual information across all media platforms. the csi is a rapid conduit for sharing pandemic-related information with the immunology community; for example, details of webinars and other events. the csi is also a point of contact for media outlets in canada that are searching for experts to provide facts about covid- . our society actively worked to influence the canadian institutes of health research (cihr) to reverse its cancellation of the spring project grant competition. the cancellation occurred after researchers had submitted their grants. this unprecedented response to the pandemic could have resulted in ending some research programmes as well as the loss of scientific jobs. in response to the csi and other organizations, the cihr re-established the competition. having cancelled the csi annual conference, we took our own advice and held our annual general meeting online. this meeting was held as protests against anti-black racism erupted in the usa, trying to understand how cognate innate immune receptors for sars-cov- , host cell metabolism and pro-inflammatory mediators contribute to host resistance or development of severe disease. the lack of governmental guidance makes one believe that the brazilian president's plan is to acquire herd immunity by natural transmission, even though in many cities the occupancy of intensive care units is at its limits. hence, brazilian immunologists have also been preoccupied with clinical studies. the development of reliable point-of-care immunodiagnostic tests for immuno-epidemiological surveys and clinical trials involving serotherapy, immunomodulators and anti-inflammatory drugs is under way. in addition, the high rate of sars-cov- transmission and the large governmental manufacturing plants for industrial production of vaccines have made brazil an attractive place to perform phase iii clinical trials and to eventually produce the vaccines for covid- . a silver lining of this sad scenario has been the wider spread of scientific knowledge, in particular relating to immunology, among the general public in brazil. in this sense, the brazilian society for immunology made a key contribution with daily news, live appearances, videos and debates on our social media channels, including facebook (@sbi.imuno, , followers), instagram (@sbi.imuno, , followers), twitter (@sbi_imuno, followers), youtube and our society website . in addition, many of our members have contributed to news reports in the conventional press. british society for immunology: arne n. akbar, jennie evans and doug e. brown. the covid- pandemic has seen the global immunology community come together in an unprecedented manner to drive research forwards. in the uk, the british society for immunology (bsi) has been at the centre of efforts and a vocal advocate for immunology in political circles and in wider public debate. for example, together with the academy of medical sciences, we convened an expert taskforce on immunology and covid- (ref. ), which has fed into the highest levels of the uk government information on the immunology of the pandemic . taskforce members have also given evidence to uk parliamentary select committees on topics including immunity, vaccine development and the immunopathology of covid- , as well as briefing individual members of parliament. the bsi is keen to ensure the public has access to reliable, evidence-based . the strength of a vibrant, well-established society, such as the csi, is that we are in a position of readiness to respond to pandemics and other crises with the power of numbers and an engaged, expert community. chinese society for immunology: yuzhang wu. in the very early stages of the pandemic, the chinese society for immunology launched an urgent project of popularization of immunology, with the aim of helping the public to understand immunology jargon, such as 'immune defence' , 'vaccine' , 'antisera and antibodies' , 'herd immunity' and 'cytokine storm' . these activities helped to increase public understanding of the disease, and how they could help with maintaining immunity and self-protection. at the same time, the chinese society for immunology advised the central government and local governments to rapidly start the development of immunological diagnostic, vaccine and therapeutic antibody projects. at the time of writing, more than antibody test kits using colloidal gold and chemiluminescence methods for both igm and igg detection and one nucleocapsid antigen rapid detection method have been developed for diagnosis of covid- . so far, six vaccines, including four inactivated vaccines , one adenovirus -vectored vaccine and one mrna-based vaccine, have been approved for clinical trials by the china food and drug administration, and one of the inactivated vaccines is in a phase iii clinical trial. by use of single-cell sequencing and high-throughput screening technologies, dozens of neutralizing human monoclonal antibodies were found with preventive and therapeutic potential , , and one of them has been approved for clinical trials by the china food and drug administration . during the pandemic, chinese immunologists have been involved in both basic and clinical studies of covid- . in collaboration with zoologists and virologists, they have developed a list of animal models, including rhesus monkeys, ace -transgenic mice , adenovirus -hace mice and ferrets, that can be used for immune response studies and preclinical evaluation of vaccines and therapeutics. in the clinic, chinese immunologists detailed the nature of t cell and antibody responses to sars-cov- (refs - ), identified the kidney as one of the main targets of sars-cov- infection , described the virus-associated cytokine storm and promoted clinical use of thymosin and anti-il- therapies for patients with severe disease. next, the chinese society for immunology will propose national major research projects to further our insight into the immune mechanisms involved in coronavirus infections and to develop innovative technologies to tackle these emerging infectious diseases. just as before, the chinese society for immunology is fully committed to enhancing cooperation with iuis and all regional societies to re-energize global scientific movements. immunology association: ana b. perez and oliver pérez. the cuban society for immunology has more than , associated ( titular) members, who are active in basic or clinical immunology research and work in the public health system, scientific institutions and universities and also with the latin american and caribbean immunology association (la asociación latinoamericana y caribeña de inmunología) and the iuis. as prominent members of the cuban scientific community, our immunologists were called on to respond to the challenges of the covid- pandemic. as early as february , a month before the first case was detected in cuba ( march) , the cuban government approved the creation of the cuban science group for the confrontation of covid- , which was key for decision-making in order to better control the predicted epidemic , . as a result of this coordinated work, several immunological approaches were approved and applied during the cuban covid- outbreak. first, an antibody screening test was developed and applied in cuba. second, patients with covid- were treated with immunotherapeutics developed in cuba, including human recombinant interferon alfa- b , later combined with interferon-γ, a humanized recombinant monoclonal antibody to cd (ref. ) and an immunomodulatory peptide, cigb- , which is derived from heat shock protein (hsp ) . third, preventive strategies were introduced for vulnerable populations that used cuban products to stimulate trained immunity or immunocompetence (biomodulin t) . fourth, passive immunization with convalescent serum was used to treat critically ill patients, and mesenchymal stem cell therapy was used in patients with lung complications. fifth, immunologists have identified biomarkers linked to disease severity and are trying to recognize correlates of protection. sixth, immunologists with molecular biologists were involved in the development of vaccine candidates. each of these strategies has been equally and freely available to all of the cuban population through a national integrated programme. our members have been actively communicating the evolving science of covid- through the national mass media, thereby contributing to furthering the public understanding of immunology. moreover, cuban medical and scientific experience has also contributed to the responses in many other countries during the covid- pandemic. at the time of writing, cuba has , confirmed cases of and deaths from covid- , with a recovery rate of . %. this relative success has been achieved due to cuba's high physician-to-inhabitant ratio ( : ), an effective track and trace programme, the hospitalization of all people who tested positive and application of approved experimental treatments, which have helped to reduce morbidity and mortality associated with covid- . during the pandemic, the german society for immunology (deutsche gesellschaft für immunologie (dgfi)) has been supporting our members by participating in a number of educational and outreach efforts. for example, our members have contributed to webinars organized by the european federation of immunological societies (efis) and the iuis. the dgfi has also been advising our national politicians during the pandemic. for example, we were asked to advise the national ethics council (deutscher ethikrat) on the feasibility and usability of so-called immunity passports for people who have recovered from covid- . moreover, the dgfi and the german society for virology have jointly advised the regulatory authorities on important safety issues related to the development and testing of vaccines against sars-cov- . going forwards, we think immunology societies can have an important role in public engagement. the dgfi certainly appreciates that there is a lack of understanding of basic immunological concepts in large segments of the general population. we need to increase our efforts in public outreach far beyond the current outbreak. the dgfi has a standing committee on public outreach and has produced an information booklet entitled "immunology for everyone". we encourage all immunologists to join their local immunology society if possible. the benefits of joining include first-class educational offers, networking opportunities, professional growth and the opportunity to become involved in public outreach. promoting equality and diversity is another major strategic aim of the dgfi. this is reflected, for instance, in the fact that % of the members of the dgfi's governing council are women, a large proportion of invited speakers at the annual meetings of our society are women and childcare support is offered at our annual meetings. finally, we acknowledge the good work immunology societies can do in promoting international collaboration. at the beginning of the pandemic, the dgfi received a highly encouraging letter of solidarity from the japanese society for immunology (jsi), in which it offered enormously generous practical help (for instance, in importing and maintaining critical strains of mice for facilities that had to be closed down). barda-saad and amiram ariel. when the covid- pandemic reached israel in early , a firm and swift government response elicited citizen adherence with social distancing instructions, containing the disease and preventing a more serious outbreak. as of june, , people in israel had been infected with sars-cov- , with patients still in a critical condition and deaths. the immunological community rapidly responded to assist in various ways, including through the formation of multidisciplinary discussion forums, boosting research on the virus and supplementing the ministry of health's covid- testing facilities with advanced pcr equipment and trained personnel. special funding programmes were created by the israel science foundation, the israel innovation authority and the ministry of health with an expedited review process to explore various aspects of the pandemic. these included a variety of immunological research programmes ranging from innovative vaccination strategies to immune therapy, and strategies for inhibition of the cytokine storm induced by the virus. israeli immunological society members provided support in refereeing these applications, serving on covid- -related policy-setting committees and performing research to identify therapeutic targets and immunogenic epitopes for vaccines. several advanced vaccination development programmes are under way at the israel institute for biological research, academic institutes, medical centres and biotech companies. the israeli immunological society shared its communication resources and databases to promote these efforts and to assist in rapid and responsible containment of covid- in israel. we expect that the outstanding multidisciplinary efforts and innovative approaches that arose in these challenging times will remain as a future platform for biomedical research teams even after covid- is under control. immunology and allergology: angela santoni, francesco annunziato and marco a. cassatella. italy was the first european country to face the outbreak of covid- and suffered one of the highest death tolls in the world, leading the italian government to rapidly take very restrictive measures. italian society of immunology, clinical immunology and allergology (siica) immunologists have been at the forefront of the italian response to the covid- pandemic, being interviewed by the most relevant tv programmes and journalists, and our members have worked hard to ensure rigorous dissemination of the science. this is particularly important in these 'infodemic' times. in addition, alberto mantovani and guido forni, who are both prominent siica immunologists and members of the italian science academy (accademia nazionale delle scienze), have written a document on different aspects of the covid- pandemic, including issues related to the production of a vaccine . it has been challenging for siica to maintain its usual level of activities during these times of social distancing. however, our society supported several educational events on sars-cov- and covid- between march and june , and we hosted a 'school of immunology' on the topic of viral immunology and vaccinology. this was organized by the siica junior faculty and had more than students actively participating in interactive live webinars and scientific games. to mark the occasion of the 'day of immunology' on april -which was this year dedicated to autoimmunity and autoinflammation -siica released the 'pills of immunology' on its official youtube channel, where several siica scientists discussed how the immune system is involved in fighting infections and chronic diseases, including covid- (ref. ). finally, siica and other european immunology societies strongly endorsed the gavi advanced market commitment for covid- vaccines (covax amc), which is an initiative to support the development of a covid- vaccine through multilateral, international collaborations . additional initiatives on covid- education for the italian public are already scheduled for the autumn, testifying to how siica is working hard to correctly inform public opinions surrounding the pandemic and vaccines. japanese society for immunology: hiroshi kiyono. at the time of writing (early july ), the spread of sars-cov- in japan has fortunately been controlled, although occasional increases of new cases are seen in large cities, and most japanese laboratories have been able to resume their research activities under restricted regulations. however, the pandemic continues worldwide, and the jsi wishes to extend its support and sincere appreciation to fellow physicians and medical staff across the world fighting on the front line against covid- , as well as to friends and colleagues all over the world who are suffering from the lockdown. the jsi believes that the solidarity of scientists will help and lead to the medical solutions and many of the social solutions that are necessary to deal with the covid- pandemic. to this end, we deliver a message of solidarity and support to all regional immunology societies, expressing our firm intention to help each other overcome the pandemic together . going forwards, the fundamental mission of our society is to support our scientists in their attempts to unravel the immunological mechanisms by which the host responds to sars-cov- and to understand why some patients with www.nature.com/nri covid- , but not others, develop severe disease. for this purpose, we believe that we should support both basic and clinical researchers with backgrounds in virology, immunology and infectious diseases, as well as other scientific fields, and bring these researchers together as one team. the jsi intends to play a key role in this through the creation of a scientifically interactive platform that will help us to understand the host immune response to sars-cov- . to start this mission, we are now in the process of organizing an online international symposium focusing on the immune system in covid- , which will be held in december as the th annual meeting of the jsi . furthermore, jsi members are providing their scientific resources and knowledge for the development of vaccines and immunotherapies for covid- in response to projects initiated by the japanese agency for medical research and development (amed) . the jsi believes that by showing a spirit of global solidarity and coming together as 'team immunology' , our immunology communities can help to achieve our common goal of eradicating sars-cov- . russia prepared thoroughly for the covid- pandemic. the country's leadership, in cooperation with the scientific community, quickly introduced an isolation regime, calling on the medical community and citizens to help fight the pandemic. the russian scientific society of immunologists, the russian academy of sciences, the ministry of health, and several other departments organized online conferences, at which specialists discussed various issues related to sars-cov- . in educational programmes, immunologists and virologists covered various aspects of the pandemic, ranging from the dynamics of the immune response to treatment regimens and the creation of vaccines. today, immunology has reached the very cutting edge of the fight against the pandemic and, as they say, 'we have all become immunologists and virologists' . therefore, immunologists were invited to the presidential commission to combat covid- . in june , a clinical trial of the first russian vaccine against covid- was started, and several more vaccine variants are on the way. assessing the preliminary results of the fight against sars-cov- , we come to the following conclusions. first, that quick, decisive adoption of public health measures, based on the opinion of specialists, is the main weapon in the fight against this infection. second, that new schemes for the provision of medical care and social services must be implemented, with the understanding that it is the behaviour of citizens that determines the trajectory of a pandemic. third, the best ideas of the theory and practice of immunology, virology and epidemiology should become the basis for all decision-making in order to combat the pandemic. going forwards, the russian scientific society of immunologists will be involved in supporting all of these aims. senegalese society of immunology: alioune dieye, moustapha mbow, babacar mbengue and maguette d. s. niang. through its members, the senegalese society of immunology (ssi) has joined the task force of the ministry of health and social action (ministère de la santé et de l' action sociale du sénégal) and the covid- observatory of the ministry of higher education, research and innovation (ministère de l'enseignement supérieur, de la recherche et de l'innovation) in senegal. as part of such bodies, the ssi provides advice on the diagnostic methods for sars-cov- and has made proposals to the ministry of health and social action on the roles of laboratories and the contribution of immunology research to the covid- pandemic. within this framework, an algorithm for the use of sars-cov- antibodies has been developed and presented to the ministry of health and social action, and an overview of global research efforts, including on social science aspects of the pandemic, has been presented to the ministry of higher education, research and innovation. the ssi is also conducting research projects focused on ( ) the immunological mechanisms underlying the clinical outcome of patients infected with sars-cov- , ( ) the immune correlates associated with protection from or susceptibility to covid- , with particular focus on populations from urban and rural regions and on any differences seen between africans and europeans, and ( ) determining the existence and longevity of cellular and humoral memory responses to sars-cov- . although action regarding social equality has not yet been considered in our response to the pandemic, investigation of discrimination will be taken into account. to ensure that our covid- -related activities help to further popularize immunology at the community level in senegal, we believe that the dissemination of our research findings should not only be limited to peer-review journals and scientific conferences but should also involve mainstream media outlets. we hope to hold future symposia where medical staff can stimulate interest in the importance of immunology and of joining immunology societies. south african immunology society: melinda suchard. at the time of writing, south africa is the african country most severely affected by covid- in terms of the total numbers of confirmed cases and deaths. the expertise developed in other infectious diseases facilitated a rapid and sustained public health response. members of the south african immunology society are involved in every aspect of the public health response, including molecular testing, evaluation of serology, clinical care, vaccine and treatment trials, and policy development. the society has enabled rapid sharing of information across disciplines and institutions through our well-received newsletters and a planned set of webinars. covid- has starkly highlighted the fundamental role of immunology for public health action, and we see an increasing trend of public users on our social media platforms seeking to understand the science behind the pandemic response strategies. the keen public interest in covid- vaccine development is a tool to be leveraged to strengthen vaccine acceptance more generally among the social media-savvy generation. the pandemic has brought diverse sectors together in solidarity, a noticeable trend within various medical disciplines that all seek deeper insights into the pathogenesis of covid- . a research focus for the country will undoubtedly include studies addressing the interaction of covid- with other infectious diseases, particularly tuberculosis and hiv infection, as well as with non-communicable diseases, including hypertension and diabetes, which are highly prevalent in the country. we anticipate a growing member base of south african and international society members as we work towards hosting the next meeting of the iuis congress in cape town in . international union of immunological societies. iuis-frontiers webinar series on covid- the american association of immunologists. the american association of immunologists the american association of immunologists. letter from the american association of immunologists letter to dr collins regarding grant termination the american association of immunologists. statement of aai committee on public affairs the journal of immunology. a message to our authors, reviewers, and readers the american association of immunologists the american association of immunologists. covid- resources and information center the american association of immunologists. aai courses in immunology the australian and new zealand society for immunology. asi community the australian and new zealand society for immunology. asi fireside chats sargramostim to treat patients with acute hypoxic respiratory failure due to covid- (sarpac): a structured summary of a study protocol for a randomised controlled trial treatment of severely ill covid- patients with anti-interleukin drugs (cov-aid): a structured summary of a study protocol for a randomised controlled trial sociedade brasiliera de imunologia. sbi homepage coronavirus information hub on the bsi website british society for immunology. bsi 'connect on coronavirus' webinar series csi council statement on systemic inequities a peptide-based magnetic chemiluminescence enzyme immunoassay for serological diagnosis of coronavirus disease diagnosis of acute respiratory syndrome coronavirus infection by detection of nucleocapsid protein rapid development of an inactivated vaccine candidate for sars-cov- safety, tolerability, and immunogenicity of a recombinant adenovirus type- vectored covid- vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial human monoclonal antibodies block the binding of sars-cov- spike protein to angiotensin converting enzyme receptor potent neutralizing antibodies against sars-cov- identified by high-throughput single-cell sequencing of convalescent patients' b cells a noncompeting pair of human neutralizing antibodies block covid- virus binding to its receptor ace the pathogenicity of sars-cov- in hace transgenic mice generation of a broadly useful model for covid- pathogenesis, vaccination, and treatment reduction and functional exhaustion of t cells in patients with coronavirus disease (covid- ) antibody responses to sars-cov- in patients with covid- clinical and immunological assessment of asymptomatic sars-cov- infections human kidney is a target for novel severe acute respiratory syndrome coronavirus (sars-cov- ) infection. preprint at medrxiv https:// doi pathogenic t-cells and inflammatory monocytes incite inflammatory storms in severe covid- patients thymosin alpha (tα ) reduces the mortality of severe covid- by restoration of lymphocytopenia and reversion of exhausted t cells effective treatment of severe covid- patients with tocilizumab government management and cuban science in the confrontation with covid- bringing cuban biotech research to bear on covid- : all hands and minds on deck therapeutic effectiveness of interferon-alpha b against covid- : the cuban experience an anti-cd monoclonal antibody (itolizumab) reduces circulating il- in severe covid- elderly patients cigb- immunomodulatory peptide: a novel promising treatment for critical and severe covid- patients covid : an executive report the japanese society of immunology. letter of solidarity and support from the japanese society of immunology the japanese society of immunology. homepage for the th meeting of the japanese society for immunology japanese agency for medical research and development. amed new scientific outputs related to covid- cape town) and r. glashoff (stellenbosch university). nature reviews immunology apologizes to all of the regional and national immunology societies that we were not able to feature in this article for reasons of space restrictions. we encourage all of our readers to join and support the work of their relevant immunology societies. finally, we thank all immunologists and immunology societies for their monumental contributions to tackling the covid- pandemic. j.p.y.t. is a co-founder of immvention therapeutix and goldcrest bio. all other authors declare no competing interests. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. supplementary information is available for this paper at https://doi.org/ . /s - - - . key: cord- -ks l ot authors: ward, kate a.; armstrong, paul; mcanulty, jeremy m.; iwasenko, jenna m.; dwyer, dominic e. title: outbreaks of pandemic (h n ) and seasonal influenza a (h n ) on cruise ship date: - - journal: emerg infect dis doi: . /eid . sha: doc_id: cord_uid: ks l ot to determine the extent and pattern of influenza transmission and effectiveness of containment measures, we investigated dual outbreaks of pandemic (h n ) and influenza a (h n ) that had occurred on a cruise ship in may . of , passengers and crew members, ( . %) were infected with pandemic (h n ) virus, ( . %) with influenza a (h n ) virus, and ( . %) with both. among children who visited the ship’s childcare center, infection rate for pandemic (h n ) was higher than that for influenza a (h n ) viruses. disembarked passengers reported a high level of compliance with isolation and quarantine recommendations. we found subsequent cases epidemiologically linked to passengers but no evidence of sustained transmission to the community or passengers on the next cruise. among this population of generally healthy passengers, children seemed more susceptible to pandemic (h n ) than to influenza (h n ) viruses. intensive disease control measures successfully contained these outbreaks. d uring april , pandemic (h n ) (pandemic infl uenza) virus began to circulate worldwide. in australia, public health efforts were initially focused on delaying the entry of the virus into the country. by may , , a total of cases had been identifi ed nationally, in new south wales (nsw), and all were associated with international travel. on may , the australian quarantine inspection service reported that passengers of a cruise ship had respiratory symptoms, and a point-of-care test showed positive infl uenza a virus results for all. the ship had departed from sydney on a -day cruise in the pacifi c ocean on may (cruise a) and stopped at islands, neither of which had reported circulation of pandemic infl uenza virus. none of the sick passengers had been in countries known to be affected by this infl uenza strain in the week before boarding. thus, with no reason to suspect that the pandemic strain was circulating on board, passengers were allowed to disembark in sydney on may . on may , the available respiratory samples taken from sick passengers were quickly couriered to the south eastern area laboratory service (the major public health viral laboratory serving eastern sydney) for infl uenza virus nucleic acid testing (nat) by real-time reverse transcription -pcr (rt-pcr). of these samples, were positive for pandemic infl uenza virus and were positive for infl uenza a (h n ) (seasonal infl uenza) virus. in response, nsw health requested that all passengers ( , from australia and from elsewhere) who were experiencing infl uenza-like illness (ili) isolate themselves from healthy persons and that all asymptomatic passengers quarantine themselves for days after disembarkation (or days after onset of symptoms if they developed). this advice was communicated to passengers on the day of disembarkation through media alerts, the nsw health website, and telephone information lines. subsequently, passengers were contacted by telephone to ensure that they understood containment measures (how to prevent virus spread). oseltamivir treatment ( mg ×/d for days) was recommended for passengers or crew members with ili (defi ned as > of the following: cough, fever, runny nose, or blocked nose) within hours of onset and oseltamivir prophylaxis outbreaks of pandemic (h n ) and seasonal infl uenza a (h n ) on cruise ship ( mg ×/d for days) for those in close contact with patients with laboratory-confi rmed cases. on may , all crew members were assessed for illness. symptomatic members were isolated on shore, and the rest were given oseltamivir prophylaxis and continued to serve on the ship's next voyage (cruise b), which departed later the same day. cruise b traveled along the northern coast of australia for days and made a short stop at brisbane before returning to sydney on june . to minimize the risk for infection, enhanced cleaning regimens were conducted before cruise b, and nsw health sent a public health doctor on the cruise to conduct intense surveillance for symptomatic passengers and crew. outbreaks of infl uenza have previously been reported on cruise ships ( - ), but the circumstances and extent of transmission have not been well documented. the cocirculation of pandemic and seasonal infl uenza viruses on cruise ship a provided a unique opportunity to compare symptoms, severity, and attack rates of pandemic and seasonal strains. we describe our outbreak investigation, compare the epidemiology of the infl uenza virus subtypes, and explore effectiveness of control measures. we defi ned a confi rmed infl uenza a case as illness in a cruise a passenger in whom infl uenza a virus was detected by nat during the cruise or within days after disembarkation (regardless of symptoms). a case of pandemic infl uenza was defi ned as illness in a person with positive rt-pcr results for that virus. further subtyping was conducted for of patients with positive infl uenza a but negative pandemic infl uenza virus results by nat; all had positive results for seasonal infl uenza virus. consequently, we defi ned a case of seasonal infl uenza as illness in a person with positive infl uenza a virus results by nat but negative pandemic infl uenza virus results and in whom infl uenza subtyping for seasonal infl uenza virus by rt-pcr either produced positive results or was not conducted. a primary case was defi ned as illness in the fi rst person in a cabin to report ili symptoms; a co-primary case, as illness in a person who reported symptom onset within hours after a primary case; and a secondary case, as illness in a person whose symptoms developed > hours after symptom onset in the primary case-patient. case-patients were considered infectious for hours before and days after symptom onset. for the childcare center investigation, children who remained asymptomatic throughout the cruise were considered susceptible to infl uenza infection at each childcare session attended. children in whom ili developed were considered susceptible before the infectious period began. we obtained a list of the names, sex, dates of birth, nationality, contact details, and cabin numbers of all passengers and crew members on cruise a. we reviewed the cruise ship's medical records to fi nd passengers who had sought treatment for ili during cruises a and b. isolated symptomatic passengers from cruise a were referred to nearby hospitals for testing. quarantined asymptomatic passengers were asked to report if symptoms developed; if so, laboratory testing was conducted. crew members and passengers on cruise b were asked to immediately report fever or respiratory symptoms to medical staff and were tested for infl uenza by at least point-of-care tests taken > hours apart. in all australian states and territories, public health legislation requires diagnostic laboratories to report confi rmed infl uenza cases to the jurisdictional health department ( ) . the names of infl uenza case-patients reported after completion of cruise a were checked against the ship's manifest. because the investigation was part of a public health control initiative, formal ethics committee review was not required. experienced public health staff interviewed casepatients at the time of diagnosis and used a standardized questionnaire to determine symptoms, hospitalization status, and oseltamivir use. this information was entered into a statewide database. passengers who shared a cabin with case-patients who had pandemic infl uenza were also interviewed about respiratory symptoms. laboratory testing initially focused on identifying pandemic infl uenza cases by using the specifi c rt-pcr; samples determined negative for pandemic infl uenza virus by nat were tested for infl uenza a (including seasonal infl uenza virus) several weeks after passengers had disembarked. approximately weeks after disembarking, all passengers who had had pandemic infl uenza were reinterviewed about the duration and severity of their illness. these passengers included interstate residents who had been treated in nsw (and excluded non-nsw casepatients as a convenience sample) and the nsw casepatients who had seasonal infl uenza (excluding non-nsw case-patients and nsw case-patients for whom test results were not available at the time of interview). ultimately, cases of seasonal infl uenza were identifi ed among nsw passengers; complete symptom data from passengers who were interviewed at the time of diagnosis were recorded in the statewide database. on-board childcare activities were provided in daily sessions ( : am - : pm) in areas of the ship for age groups: - , - , and > years of age. because the pandemic outbreak appeared to begin in and primarily affect children - years of age, the epidemiologic investigation focused on this group. most childcare activities for this group took place in room. we examined childcare attendance records for this group and, ≈ weeks after disembarkation, interviewed the parents of all children in this group about symptoms, vaccination history, and composition of the traveling group. all specimens collected from childcare attendees were tested for pandemic and seasonal infl uenza subtypes. to assess compliance with isolation and quarantine recommendations, we interviewed all households in which at least person with pandemic infl uenza was isolated, nsw households with at least person with seasonal infl uenza, and randomly selected quarantined nsw passengers. (nsw passengers were selected as a convenience sample.) interviews were conducted by experienced public health interviewers who used a standardized questionnaire. nat detection of pandemic infl uenza virus was performed by using real-time rt-pcr with primers targeting the hemagglutinin gene of the pandemic infl uenza virus provided by the centers for disease control and prevention and following recommended protocol or by using an in-house pandemic infl uenza virus-specifi c real-time rt-pcr. seasonal infl uenza virus was identifi ed by using a -target rt-pcr containing primers targeting pandemic and seasonal infl uenza virus strains (unité de génétique moléculaire des virus respiratoires, institut pasteur, paris, france) or a commercial infl uenza a subtyping assay (easy-plex infl uenza profi le ; ausdiagnostics, sydney, nsw, australia). we analyzed data by using epi info version . . (www.cdc.gov/epiinfo). relative risks were used to compare age (as a categorical variable split into groups), sex, and place of residence. fisher exact test results were used for cell sizes < . a mantel-haenszel value of p< . was considered signifi cant. χ tests were used to compare proportions. to compare the rates of pandemic and seasonal infl uenza infection in childcare attendees, the number of sessions a child attended while susceptible were summed, and cases per child-sessions at risk and exact poisson confi dence intervals were calculated. nonoverlapping confidence intervals were considered signifi cantly different. a total of , passengers and crew members were on cruise a. median age of passengers was years (range - years), % were female, and most were from australia ( table ) . median age of crew members was years (range - years), and most were born overseas (not in australia). ili developed in ( . %) passengers who sought medical attention during the cruise; and infl uenza a results from point-of-care testing were positive for . nat of samples from persons who were sick during the cruise or during the days after disembarkation showed positive pandemic infl uenza virus results for ( . %), positive seasonal infl uenza results for ( . %), and positive co-infection results for ( . %). ili in the days before disembarkation was reported by ( . %) crew members; nat showed positive pandemic infl uenza results for crew members and positive seasonal infl uenza results for none. these crew members were isolated on shore. the remaining crew members were given oseltamivir prophylaxis and continued to work during cruise b; among these, reported ili (all within hours of cruise b departing), and had positive nat results for pandemic infl uenza virus. therefore, ( . %) crew members from cruise a reported ili, and ( . %) of these had positive pandemic infl uenza test results; none had positive seasonal infl uenza test results. given the relatively low attack rate for the crew, we focused further investigation on the passengers, among whom the attack rate for pandemic infl uenza was highest for children - years of age, followed by children - years of age. for seasonal infl uenza, the attack rate was similar among children in all age groups ( table ) . in total, ( %) patients with pandemic infl uenza and ( %) patients with seasonal infl uenza were hospitalized (p = . ); none died. among the passengers with the pandemic strain and with the seasonal strain who were interviewed, symptoms were similar, although coryza was reported signifi cantly more often by those with pandemic infl uenza ( table ). duration of illness was similar for passengers with either strain, but a higher proportion of seasonal infl uenza patients reported that illness was severe enough to limit their activities. according to date of symptom onset, the pandemic infl uenza outbreak began in the childcare center on may , which was days after embarkation, and peaked on may , the fi nal day of cruise a. the fi rst reported seasonal infl uenza case was in an adult whose symptoms began on may ; the second, seemingly unrelated, infection developed in a childcare attendee on may . the number of seasonal infl uenza cases also peaked on may (figure) . of the passengers - years of age, ( %) attended childcare. among these were pairs of siblings. one child received seasonal infl uenza vaccine in and no child received the vaccine in . the fi rst case of pandemic infl uenza was in a child from victoria, australia, in whom symptoms developed on the third day of cruise a. the child attended childcare for sessions while infectious. after the index case was identifi ed, additional cases of pandemic infl uenza were identifi ed (including in sets of siblings: related children in whom symptoms developed at the same time and in child in whom ili developed days after symptom onset in her sibling); all but had attended the childcare while a known infectious case-patient was present. the fi rst child for whom seasonal infl uenza was diagnosed had attended childcare the afternoon and evening before symptom onset on may and for sessions while symptomatic. subsequently, an additional unrelated cases of seasonal infl uenza were identifi ed among childcare attendees. the children who did not attend childcare remained healthy. among the childcare attendees, nat results for pandemic infl uenza were positive for , for seasonal infl uenza were positive for , and for both were positive for . ili developed in an additional children, but these children had negative infl uenza results by nat; ili developed in another children who were not tested. of these children, had traveling companions with positive pandemic infl uenza virus results and had travelling companions with positive seasonal infl uenza virus results. the remain-ing children remained asymptomatic. of the children who attended childcare, attended concurrently with an infectious pandemic infl uenza case-patient and attended concurrently with an infectious seasonal infl uenza case-patient. considering the number of sessions attended by susceptible children, we determined that the risk for pandemic infl uenza infection was signifi cantly higher ( cases from sessions = . child-sessions at risk, % confi dence interval [ci] . - . ) than was the risk for seasonal infl uenza ( cases from sessions = . child-sessions at risk, % ci . - . ). a total of pandemic infl uenza case-patients in cabins were infectious while on cruise a. excluding the coprimary case-patients, passengers shared a cabin with an infectious primary case-patient. of these passengers, symptoms developed in ( %). of these case-patients, were tested and ( %) had positive pandemic infl uenza results. the secondary attack rate for those < years of age ( / ) was signifi cantly higher than for those > years of age ( / ) ( % vs. %; p = . ). of the case-patients, received oseltamivir treatment within hours of symptom onset. information about provision of oseltamivir prophylaxis was available for ( %) of asymptomatic contacts. of these, of age began receiving antiviral drug prophylaxis within days of their fi rst exposure to pandemic infl uenza virus. of these , only received prophylactic drug within days of fi rst exposure to the pandemic strain. despite being asymptomatic, ( %) of passengers underwent laboratory testing and were negative for pandemic infl uenza virus by nat. after disembarking, patients with pandemic and seasonal infl uenza were isolated in discrete (family or household-like) groups. of the ( %) interviewed, % reported that they were fi rst made aware of the need for isolation through media reports, % by their treating doctor, % by public health staff, % by the ship's staff, and % by fellow passengers. of the quarantined passengers interviewed, % were initially informed of the need for quarantine through media reports, % by work or school colleagues, % from the ship's staff, % from a friend or relative, and % from public health staff. all infl uenza case-patients reported that they had obeyed isolation requirements, and of quarantined passengers reported that they had remained in quarantine for days after disembarkation. of the passengers who did not follow quarantine requirements, reportedly attended work by private vehicle and cancelled all other outings; the other denied knowledge of the requirements. three secondary pandemic infl uenza infections among family contacts of case-patients from cruise a were identifi ed; a subsequent case-patient was identifi ed as a contact of person who had secondary infection. other than these cases, no evidence of transmission to the community or to passengers of cruise b was found. we identifi ed dual outbreaks of pandemic and seasonal infl uenza among passengers on a cruise ship. cruise ships provide ideal conditions for rapid spread of respiratory viral illnesses (e.g., many persons living closely together, frequently interacting in enclosed and partially enclosed environments, and often originating from both hemispheres). although infections spread rapidly among passengers and to some crew members during the cruise, further spread to the community and the next cruise was avoided through intensive disease control measures. after identifi cation of the outbreak, it became apparent that undetected local transmission of pandemic infl uenza virus was occurring in victoria before cruise a ( ) and that the virus was probably introduced to the ship by the index case-patient from victoria. the pandemic virus spread rapidly among other childcare attendees and their close contacts and to other passengers and crew. seasonal infl uenza virus was the predominant infl uenza virus circulating in nsw before the appearance of pandemic infl uenza virus (nsw health, unpub. data). the cocirculation of both strains in the childcare center provided a unique opportunity to compare attack rates. the pandemic strain seems to have spread among children more readily than the seasonal strain. this difference in transmissibility could have resulted from innate differences in the viruses themselves or from a level of immunity from past infection with the seasonal strain. consistent with fi ndings in other studies, the symptoms of pandemic and seasonal infl uenza were similar ( - ). after adjusting for underlying medical conditions, we found that hospitalization rates and activity-limiting effects were higher for case-patients with seasonal than with pandemic infl uenza; however, this fi nding may be explained in part by differences in the agespecifi c attack rates. the secondary attack rate for pandemic infl uenza among cabin contacts of % was higher than that reported for household contacts ( , ) , despite a small proportion of these persons having received antiviral drug prophylaxis, and may refl ect the close living arrangements in a ship's cabin. the intense passenger follow-up enabled us to assess the sensitivity of the ship's medical clinic for identifying infl uenza cases. before this outbreak, ships had active containment measures in place to minimize the spread of seasonal infl uenza, including use of point-of-care infl uenza testing for patients seeking treatment for ili and oseltamivir treatment and isolation to reduce further spread. our active case-fi nding efforts identifi ed infl uenza cases on cruise a, yet the ship's clinic identifi ed only ( %) of these. despite enhanced community awareness of the emerging pandemic, the ship's medical clinic staff underestimated the case count by -fold. the number of passengers who sought treatment at the ship's medical clinic does not accurately refl ect the extent of the infl uenza outbreak on board, possibly because the decision to seek treatment may have been infl uenced by a number of factors including cost, severity of symptoms, and unwillingness to be isolated while on holiday. our investigation had several limitations. first, the case defi nition depended on nat detection of virus in clinical samples, which may have resulted in misclassifi cation of cases. second, although the epidemiology is consistent with the fi rst cases of pandemic infl uenza appearing in the childcare center, undetected or asymptomatic infected passengers or crew could have carried the viruses onto the ship. however, this scenario is unlikely because the symptoms developed in the index case-patient days after embarkation. third, although most ill passengers were interviewed within days after onset of illness, interviews about severity, length of illness, and the experience in isolation and quarantine were conducted some weeks later, introducing possible recall bias. fourth, although cases of co-infection were detected, only the fi rst pandemic infl uenza-positive specimens from childcare attendees were subtyped for other infl uenza a subtypes; it is possible that some of the remaining pandemic infl uenza case-patients were also infected with seasonal infl uenza. fifth, some of the remaining pandemic infl uenza case-patients may have been co-infected. sixth, the secondary attack rate for cabin contacts may be an overestimate because passengers with negative nat results were not tested for other respiratory infections, and passengers with onset of symptoms > hours after symptoms developed in a cabinmate were assumed to be secondary, rather than co-primary cases. mathematical modeling suggests that containment of infl uenza is possible if appropriate resources are devoted. in some countries, isolation and quarantine measures have been used in response to severe acute respiratory syndrome ( ) ( ) ( ) ( ) , but these measures have rarely been used for infl uenza control. in the infl uenza outbreaks reported here, direct follow-up of passengers in isolation and quarantine, supported by intense media coverage, resulted in a high degree of compliance and successful outbreak containment. additionally, providing oseltamivir prophylaxis for crew members may have contributed to the successful containment of the infection during cruise b. although the robust application of containment measures can stop the spread of novel infl uenza viruses, public health resource requirements are labor-intensive and expensive and may not be sustainable except for the most virulent of pandemic viruses. emerging infectious diseases • www.cdc.gov/eid • vol. date of onset of fi rst symptoms for cruise ship passengers, by infl uenza subtype. excludes infl uenza a (h n ) case-patient for whom onset date was unavailable and pandemic (h n ) case-patient and infl uenza a (h n ) case-patients who were asymptomatic but whose laboratory test results were positive. outbreak of infl uenzalike illness in a tour group-alaska acute respiratory illness among cruise-ship passengers-asia infl uenza b virus outbreak on a cruise ship-northern europe cruise ship outbreak investigation team. a large outbreak of infl uenza a and b on a cruise ship causing widespread morbidity large summertime infl uenza a outbreak among tourists in alaska and the yukon territory bound for sydney town: health surveillance on international cruise vessels visiting the port of sydney australian government department of health and ageing. surveillance case defi nitions for the australian national notifi able disease surveillance system: communicable diseases network of australia pandemic h n infl uenza surveillance in clinical signs and symptoms predicting infl uenza infection respiratory viruses and infl uenza-like illness: a survey in the area of rome swine-origin infl uenza a (h n ) virus infections in a school comparison of adult patients hospitalised with pandemic infl uenza and seasonal infl uenza during the "protect" phase of the pandemic response household transmission of pandemic infl uenza a (h n ) virus in the united states new york city department of health and mental hygiene swine infl uenza investigation team monitoring the severe acute respiratory syndrome epidemic and assessing effectiveness of interventions in hong kong special administrative region public health measures to control the spread of the severe acute respiratory syndrome during the outbreak in toronto quarantine for sars use of quarantine in the control of sars in singapore we thank kerry chant, lisa coombs, polly wallace, and the staff of the jurisdictional public health network and nsw public health units and laboratories.dr ward is an epidemiologist and manager of surveillance in the communicable diseases branch at new south wales health. her research interests include risk factors for pandemic infl uenza and the epidemiology of hiv, blood-borne viruses, and sexually transmitted infections. key: cord- -yt k m authors: han, rachel h.; schmidt, morgan n.; waits, wendi m.; bell, alexa k. c.; miller, tashina l. title: planning for mental health needs during covid- date: - - journal: curr psychiatry rep doi: . /s - - - sha: doc_id: cord_uid: yt k m purpose of review: the ability to effectively prepare for and respond to the psychological fallout from large-scale disasters is a core competency of military mental health providers, as well as civilian emergency response teams. disaster planning should be situation specific and data driven; vague, broad-spectrum planning can contribute to unprepared mental health teams and underserved patient populations. herein, we review data on mental health sequelae from the twenty-first century pandemics, including sars-cov (covid- ), and offer explanations for observed trends, insights regarding anticipated needs, and recommendations for preliminary planning on how to best allocate limited mental health resources. recent findings: anxiety and distress, often attributed to isolation, were the most prominent mental health complaints during previous pandemics and with covid- . additionally, post-traumatic stress was surprisingly common and possibly more enduring than depression, insomnia, and alcohol misuse. predictions regarding covid- ’s economic impact suggest that depression and suicide rates may increase over time. summary: available data suggest that the mental health sequelae of covid- will mirror those of previous pandemics. clinicians and mental health leaders should focus planning efforts on the negative effects of isolation, particularly anxiety and distress, as well as post-traumatic stress symptoms. although the coronavirus (covid- ) pandemic initially resulted in roughly new covid- -related listings each week on the pubmed.gov website, very few of these publications addressed the practical matter of how mental health providers and leaders should specifically plan for the post-pandemic mental health tsunami that many predict is inevitable [ ] . the purpose of this article, written from the perspective of military medical planners, is to present available data on the prevalence of specific mental health concerns and conditions from previous recent pandemics and covid- , as well as to provide data-informed recommendations for meeting the psychological needs of affected individuals. historically, pandemics have had significant ramifications for psychological stress and mental health. the global reach and protracted course are unique to pandemics and other infectious disease outbreaks compared with other types of disasters. prolonged social distancing protocols, increased unemployment rates, and economic stress have the potential to create an unprecedented mental health crisis. from prior disasters, military researchers have learned that affected people tend to do well over time with minimal psychiatric sequelae [ ••]. however, there is still concern for residual psychopathology, including anxiety, depression, bereavement, and posttraumatic stress. among healthcare workers (hcws) in particular, decreased social support and isolation may be expected even while at work due to assignment to unfamiliar hospital areas, requirement for personal protective equipment (ppe) that obscures identities, and inability to gather in groups [ physical distancing, while important to protect against physical illness, often results in social isolation and loneliness, especially for vulnerable groups. it is well known that social isolation has a detrimental effect on mental health outcomes. both living alone and feelings of loneliness have been associated with increased suicidal ideation and suicide attempt [ ] . further, since covid- was declared a public health emergency, many employees have been either laid off or furloughed, causing economic anxiety and distress. many schools and daycares have also physically closed indefinitely, forcing families with children to take time off from work to provide childcare and take on the additional burden of assisting with virtual learning. in the past, times of economic downturn have been associated with increased rates of completed suicide in high-income countries [ ] . accordingly, we anticipate a rise in mental healthcare usage and increased susceptibility of certain groups to mental illness and its consequences as the pandemic continues. we conducted a rapid review of the twenty-first-century pandemics with the goal of establishing a preliminary projection of mental health needs related to covid- . since formal preferred reporting items for systematic reviews and meta-analyses (prisma) guidance for rapid reviews is currently pending, we referred to a published analysis of the most common rapid review elements while conducting our review [ ] [ ] [ ] . questions we hoped to answer included the following: what mental health sequelae emerged following pre-covid- twenty-first-century pandemics? and what does preliminary data on the psychological effects of covid- reveal? our rapid review included papers published from january to july on pubmed, as well as searches of various gray literature sources for guidelines, position papers, and journalistic reports. search strategies were structured around three major concepts: pandemics, mental health, and data analysis. a combination of the following keywords in the title and/or abstract was used in searches of literature on the southeast asian respiratory syndrome (sars), h n influenza (h n ), middle eastern respiratory syndrome (mers), ebola, and covid- pandemics: mental health or mental illness or psychiatry or psychology or therapist or ptsd or posttraumatic or post-traumatic stress disorder or behavioral health or anxiety [disorder] or gad or depression/depressed or complex grief and data analysis or statistic* or prevalence or percentage or increase or decrease. peer-reviewed articles addressing the mental health sequelae during or following the listed pandemics were included. other inclusion criteria were populations of all age groups, from any location, and published in english. articles that reported physical health rather than mental health were excluded. articles that reported on preventative behaviors were also excluded. additional exclusion criteria included case studies, abstracts, commentaries, and opinion pieces. titles and abstracts of the identified literature were first reviewed. literature not complying with the search criteria was excluded. the full text was obtained for articles in which inclusion/exclusion criteria were not clear, and references were independently screened. the findings presented chronologically below are based on information pertaining to recent pandemics, including severe acute respiratory syndrome (sars), h n influenza virus (h n ), middle eastern respiratory syndrome (mers), ebola, as well as the current covid- pandemic (see fig. ). findings for children pertaining to covid- are discussed separately given the unique psychological conditions considered for this population. the sars coronavirus epidemic spread through countries in , resulting in over cases, largely affecting asian countries. community-based surveys revealed that during the outbreak, almost % of community populations experienced increased stress, with % experiencing post-traumatic stress symptoms [ ] . a taiwan-based study showed . % of a nationwide sample had a psychiatric morbidity measured by the brief symptoms rating scale [ ] . hcws were also significantly affected due to risk of exposure, with higher ratings of stress and depressive and anxious symptoms persisting a year post-outbreak [ ] . six percent self-medicated with alcohol to cope with these feelings [ ] . having to quarantine also caused a significant increase in depressive symptoms [ ] . nonetheless, no rise in dsm-iv psychiatric diagnosis was found years later [ ] . elderly populations appeared to be at greater risk of suicide, with a % increase in completed suicides among adults aged and older in hong kong in at the peak of sars cases. further analysis led to identification of certain factors, including fear of contracting sars, increased isolation, disruption of social life, and increased chronic disease burden [ ] . finally, survivors had significant levels of psychiatric morbidity after the epidemic. prevalence of any psychiatric disorder at long-term follow-up was - . %, with % of survivors carrying a diagnosis of post-traumatic stress disorder (ptsd) and % having a depressive disorder [ , ] . in the usa, the h n influenza virus was first detected in april . by april , the centers for disease control and prevention (cdc) estimated about . million cases, , hospitalizations, and , deaths due to the virus in the usa alone. the published data on behavioral/ psychological responses focuses mostly on the anxiety prevalent due to uncertain conditions among hcws [ ] . in guangzhou, china, . % of university students reported feeling panicked, depressed, or emotionally disturbed as a result of h n , and % worried about them or their family catching the virus [ ] . hcws in greece experienced moderately high anxiety about the pandemic, with their predominate concern being infection of family and friends and subsequent health consequences. interestingly, perceived sufficiency of public information about h n was associated with reduced degree of worry [ ] . this finding was consistent with findings among hcws in japan, where workers who were less frequently provided information about the pandemic felt less protected than their more informed colleagues. in addition, fig. flow diagram for review of pandemic mental health outcomes japanese hospital workers in higher risk environments felt more anxious and exhausted [ ] . the middle east respiratory syndrome (mers) first emerged in saudi arabia in and spread throughout the arabian peninsula, affecting over individuals. while person-to-person transmission was limited, hcws were deemed to be at higher risk for contracting mers, with a case fatality rate of around - %. a south korean study of quarantined individuals showed . % had feelings of anxiety during quarantine, but only % had persistent anxiety at - months after release. risk factors for anxiety included inadequate supplies, somatic symptoms related to mers, financial loss, social media use, and a history of psychiatric illness [ ] . the - ebola outbreak in west africa spread rapidly due to inadequate healthcare facilities, lack of trained staff, and poor health literacy, leading to inability to receive care from hcws who were often exposed to and contracted the disease. one year after onset in sierra leone, a study on the mental health impact on the general population revealed a prevalence of almost % of any anxiety or depression symptoms via patient health questionnaire- (phq- ). prevalence of any ptsd symptom was %, as measured by six items from the impact of events scale revised. of note, only % met the clinical cut-off for anxiety and depression. for ptsd, % met levels of clinical concern, and % met probable diagnosis. factors associated with higher reporting of symptoms included region of residence, experiences with ebola such as knowing someone quarantined, and perceived threat [ ] . the outbreak reached spain, the uk, and the usa as a result of globalization and international travel, threatening global security and the world economy. in late , the us military sent troops to west africa to help curb this epidemic. a review examining the potential psychological impact of this deployment qualitatively predicted that deployed service members would return with clinically significant problems, including psychological distress, alcohol/drug use, post-traumatic stress disorder, anxiety, and most significantly depression. they also suggested that among militaryspecific sociodemographic factors (young, single, no family, less work experience, lower educational levels and income) predicted poorer outcomes [ ] . the second deadliest ebola outbreak was in and is currently ongoing. as a result, in the democratic republic of the congo, mental health professionals have joined response teams to provide psychological treatments to patients dealing with anxiety and death [ ] . a systematic review of the prevalence of mental health problems in populations affected by the outbreak revealed that approximately % of individuals exposed to the virus (survivors, families, communities, healthcare workers, safe and dignified burial teams) were diagnosed with depression [ ] . on may , , the united nations (un) policy brief on "covid- and the need for action on mental health" noted concerns over widespread psychological distress, referencing three sources [ ] . the first was a study in china claiming to be the first nationwide large-scale survey of psychological distress in the general population. in total, , responses to a self-reported questionnaire sought to identify demographic characteristics associated with higher distress levels. the authors suggested that the country's response to the covid- pandemic, including implementation of strict quarantine measures, triggered a wide variety of psychological problems, such as panic disorder, anxiety, and depression [ •] . the second was a study in iran that used the same survey as above. based on responses, the authors concluded that predictors of distress may vary across countries, citing differences in age and education that predicted distress in china but not in iran (younger age and higher education correlated with higher distress in china) [ •] . the third was a survey from april by the kaiser family foundation revealing that % of adults in the usa believed the pandemic had affected their mental health. of note, % reported increasing alcohol or drug use. sixtyfour percent of those who reported stress and worry around covid- come from front-line hcws and their families and % from americans who experienced an income loss [ ] . as recently as late june, % of us adults reported struggling with mental health issues or substance use, with % endorsing anxiety/depressive symptoms, % endorsing traumarelated symptoms, % endorsing starting or increasing substance use, and % seriously considering suicide [ ••] . in china, the immediate psychological effects of the covid- outbreak were more specifically studied in the general population. using the impact of event scale-revised (ies-r), . % reported moderate or severe psychological impact. using the depression, anxiety and stress scale (dass- ), . % had moderate to severe anxiety symptoms, . % had moderate to severe depressive symptoms, and . % had moderate to severe stress levels. notably, specific physical symptoms such as myalgia, dizziness, coryza, and poor self-rated health status were significantly associated with a greater psychological impact of the outbreak and higher levels of stress, anxiety, and depression [ •] . another similar study in the general population on generalized anxiety disorder (gad) symptoms, depressive symptoms, and sleep quality revealed similar findings. results showed that the overall prevalence of anxiety symptoms (using generalized anxiety disorder -item score > ) was . %, depressive symptoms . %, and poor sleep quality . %. of note, they also found that hcws were more likely to have poor sleep quality than the general population [ results from previous pandemics were limited and did not explore the effect of quarantine on children and families. however, initial data from the covid- pandemic has shown a detrimental effect of quarantine on children. a survey of primary school students (grades - ) in the hubei province of china during lockdown measures found that . % reported depressive symptoms and . % reported anxiety [ •] . in shanghai, parents of children with attention-deficit/hyperactivity disorder (adhd) aged - reported that their behaviors were significantly worse during lockdown [ •]. among chinese students aged - , prevalence of depressive and anxiety symptoms were . % and . %, respectively, with risk factors including female gender, higher grade level, and lower self-assessed knowledge of covid- [ • ]. published data regarding mental health sequelae from recent pre-covid- pandemics is limited. most studies have used broad-sweeping inventories of distress and psychological symptoms instead of specific diagnostic screening instruments. very few prospective clinical trials appear to have been published, and the few reasonably well-constructed retrospective trials had relatively small study populations. reported outcomes included vague, qualitative entities such as stress, anxiety, panic, worry, exhaustion, emotional disturbance, ptsd symptoms, depressive symptoms, poor sleep quality, increased alcohol use, and behavior problems. additionally, the fast-moving nature of the pandemic, combined with the challenge of getting behavioral health protocols rapidly approved by institutional review boards, has likely contributed to the scarcity of covid- -related outcome data. given these limitations, we found it difficult to predict with certainty which types of mental health problems are likely to result from covid- . however, several general trends and observations are worth noting and may provide some preliminary assistance to medical planners responsible for anticipating the psychological sequelae of covid- . the data above is consistent with what we already know about the mental health impacts after a disaster: a significant number of people will experience increased stress during the incident, but the majority will not have lasting psychological sequelae. while this is an important perspective, there are also several differences between past pandemics and the current situation. covid- appears to be more similar to influenza outbreaks than to previous coronavirus infections, with respect to high infectivity, low fatality rates, and a high percentage of asymptomatic infections [ ] . from a mental health standpoint, these conditions have the potential to lead to significant anxiety over whether one has the virus and could be unknowingly passing it on to their loved ones. compared with other recent pandemics, covid- has considerably more cases with global spread, causing significant impact on daily lives. no other outbreak in recent history has caused such devastating economic distress or the mass closure of businesses. furthermore, the sheer number of patients infected and hcws exposed could cause significant strain on the mental healthcare system, even if the majority of people affected do well in the long term. with cases continuing to surface, there is still a great degree of uncertainty regarding the final impact this pandemic will have, including when a vaccine will be developed and how long social distancing precautions will need to continue. these additional factors may lead to more severe psychosocial distress and unanticipated psychiatric disease than has been observed in previous pandemics. data on the effects of the covid- pandemic on children and families are currently limited. however, experts anticipate that all families, regardless of whether family members include patients or hcws, will be affected due to disruption of the family structure by closures of schools, financial uncertainty, and possible unemployment [ ] . while mental health professionals attempt to forecast and implement effective treatment for the most vulnerable populations, much is unknown about the long-term mental health effects of largescale disease outbreaks on children, adolescents, and families. evolving data suggests that the greatest risks among these populations will include increased anxiety regarding school and work closures, decreased social and community networks, increased pressure on parents to work from home while providing supervision and distance learning, violence when locked in with abusive family members, and unemployment potentially leading to loss of essentials, starvation, and homelessness. with numerous predictions and peer-reviewed data emerging about the mental health consequences of covid- , one may conclude that healthcare systems and providers must simply anticipate increased demand for all types of psychiatric conditions. however, the information presented above does suggest certain trends that may inform planning more specifically. first and foremost, several studies noted that individuals' levels of anxiety were indirectly correlated with the degree of communication they received about the virus. mental health providers, and particularly those trained in the military as command consultants, are uniquely suited to prepare evidence-based communication tools for patients and fellow clinicians, as well as for community leaders hoping to minimize social panic. such tools should cover what is known about transmission of the virus, for example, how individuals are likely to be infected, what mitigation strategies are most effective, how they should be employed, who is at highest risk for the worst outcomes, who is at greatest risk for psychiatric sequelae, and how mental health may be optimized among affected individuals. communication also includes providing subject matter expertise to medical and community leaders. mental health providers should not wait to be asked; they should prepare succinct talking points and intermittently remind public officials and other senior leaders of the most prominent fears fueling anxiety in the community. additionally, it is important to offer practical and viable suggestions or solutions; providers who present leaders with concerns without solutions will rapidly lose favor with the same individuals they are hoping to influence. second, the aforementioned studies found excessive worry and distress about various covid-related issues. although there are scores of evidence-based interventions likely to be useful for anxiety and depression, two widely available strategies can address both problems effectively, when used in those identified to be appropriate for treatment: cognitive behavioral therapy (cbt) and antidepressant medications [ ] [ ] [ ] . third, post-traumatic stress symptoms were surprisingly prevalent across pandemics and among numerous demographic groups, suggesting that interventions proven to be effective for ptsd may be a worthy investment of training dollars and clinical resources. traditional, - session manualized treatments using prolonged exposure, cognitive processing therapy, and eye movement desensitization and reprocessing are likely to be effective [ ] [ ] [ ] . however, recent data suggests that interpersonal therapy, written exposure therapy (wet), strategically dosed propranolol, and mantram repetition may be equally effective and easier to facilitate via telehealth [ ] [ ] [ ] [ ] . generally, individual psychotherapy has been shown to be more effective than group-based interventions or medications alone for ptsd [ ] . however, in areas where resources are limited, group-based interventions in which cohorts with similar backgrounds can process their experiences together (i.e., front-line workers, covid- survivors, unemployed individuals) may be clinically beneficial. treating ptsd may also improve insomnia, a symptom of ptsd, that was noted to be prevalent in several of the pandemic-related studies cited above. fourth, most responses seen in children during covid- and previous pandemics tend to fall into two major categories-anxiety and restless/disruptive behavior. since the latter can be a manifestation of the former, planning ways to address anxiety in children is likely to be the best investment of limited clinical resources. researchers at the yale university recently demonstrated that coaching for parents in how to manage their anxious children can be as effective as individual cbt conducted with the children themselves [ ] . children may also benefit from individual-or groupbased therapy, especially if they are focused on practical matters, such as how to be good siblings, how to prevent the spread of covid- , and ways to burn off energy that accumulates during isolation. fifth, although entrepreneurs are rapidly adapting their business models to accommodate infection control measures, sustained high unemployment rates and economic depression appear unavoidable. historically, financial crises heighten emotional despair and increase rates of suicide [ , ] . the extent to which covid- will be associated with these impacts is unknown, although some models predict that up to % of jobs lost during covid will be permanent [ ] . planning for the psychological needs of individuals facing economic devastation is challenging. not only is there stigma in acknowledging one's financial situation, but the very nature of the problem itself creates a barrier to accessing treatment. the best planning for these outcomes will likely involve nontraditional approaches, such as partnering with community leaders to educate them about the psychological impact of unemployment, getting the word out about available food and shelter, and creating per diem jobs and apprenticeship opportunities. free support groups and training seminars on topics such as unemployment rights, resume building, and civil service opportunities are likely to make a greater impact than psychotherapy in this population. finally, covid- has created many additional psychological problems not widely emphasized among available data, including domestic violence and child abuse. while physical distancing at home is necessary to prevent the spread of disease, social isolation is also a major tactic used by perpetrators of domestic abuse. strict requirements to maintain isolation may allow perpetrators to gain control by generating guilt in their victims [ ] . isolation from friends, family, and employment plays a role as fewer contacts means fewer people to recognize abuse and provide assistance. typically, % of reports to child protective services come from educators [ ] . because schools and other childcare facilities are closed, families at risk are not likely getting the resources or referrals they need. both substance misuse and domestic abuse are likely to be underreported, yet they are of critical significance. additionally, many minority populations and lowerincome front-line workers are at risk for greater exposure to covid- , greater risk of developing serious medical sequelae, lower likelihood of insurance coverage, and increased institutional bias that may negatively impact their course of treatment [ ] . providers and medical staff who regularly care for these populations should be reminded of the risks incurred by these vulnerable populations and utilized to train their medical peers on how to screen at-risk patients, as well as how to optimize patient access to treatment resources and shelters. there have also been many accounts of discriminatory behaviors against asian americans and pacific islanders (aapi) since the covid- outbreak [ , ] . it is now widely known that in general, the experience of racial discrimination is a determinant of poor mental health [ ] [ ] [ ] . thus, it is important for providers to be aware of these experiences and anticipate increases in the secondary effects of discrimination, such as psychological trauma, anxiety, and depression in these populations. lastly, bereavement will unquestionably be a significant consequence of covid- , yet available literature from covid- and past pandemics is remarkably void of data on grief and bereavement [ ] . the covid- pandemic has changed the landscape of behavioral health dramatically. expanded telehealth capabilities have increased our ability to reach those suffering and provide better patient-centered care, yet these new care delivery systems are not ubiquitously available. furthermore, testing these capabilities may be a trial by fire if predictions about a looming mental health crisis prove accurate. it is therefore important to focus planning efforts on interventions likely to have the greatest impact. evidence-based treatments for ptsd, anxiety, and depression, particularly those more easily delivered using virtual platforms, should become the standard post-covid toolkit for behavioral health clinicians. groupbased interventions will also be critical, particularly for parents, children, and cohorts of similarly impacted individuals, to decrease isolation, normalize experiences, and promote emotional validation. simply being able to direct suffering individuals to support groups and self-help/educational resources may be as impactful as traditional behavioral health interventions. such community-based support is widely used in the american military and is consistent with the doctrinal principles of military disaster response [ ] . this analysis was based on peer-reviewed and non-peer-reviewed scholarly reports, many of which were of limited quality and frequently retrospective in nature. additionally, much of the covid- data is still in pre-print form as of this writing. our rapid review of the existing literature was intended to provide military and civilian mental health planners with timely, actionable data to help guide their decisions regarding staff training and resource allocation. however, we acknowledge that our rapid method of review may have excluded some informative publications that would have been identified if we had used a full prisma systematic review. future research on planning and response to post-pandemic mental health demands should be based on prospective, randomized, controlled, peerreviewed data whenever possible. it is our hope that research will continue into the ongoing psychological impact of covid- . disclaimer the views expressed in this manuscript are those of the author and do not reflect the official policy of the department of army/navy/air force, department of defense, or us government. systematic review of suicide in economic recession a typology of reviews: an analysis of review types and associated methodologies reporting guidelines under development for systematic reviews. the equator network website and database. last updated quality of conduct and reporting in rapid reviews: an exploration of compliance with prisma and amstar guidelines psychological morbidity related to the sars outbreak in hong kong population-based post-crisis psychological distress: an example from the sars outbreak in taiwan alcohol abuse/dependence symptoms among hospital employees exposed to a sars outbreak depression after exposure to stressful events: lessons learned from the severe acute respiratory syndrome epidemic prevalence of psychiatric disorders among toronto hospital workers one to two years after the sars outbreak the impact of epidemic outbreak: the case of severe acute respiratory syndrome (sars) and suicide among older adults in hong kong community psycho-behavioural surveillance and related impact on outbreak control in hong kong and singapore during the sars epidemic long-term psychiatric morbidities among sars survivors the h n crisis: a case study of the integration of mental and behavioral health in public health crises preventive behaviors and mental distress in response to h n among university students in guangzhou, china general hospital staff worries, perceived sufficiency of information and associated psychological distress during the a/h n influenza pandemic psychological impact of the pandemic (h n ) on general hospital workers in kobe mental health status of people isolated due to middle east respiratory syndrome. epidemiol health impact of ebola experiences and risk perceptions on mental health in sierra leone psychological impact of deploying in support of the u.s. response to ebola: a systematic review and meta-analysis of past outbreaks the mental health professional at the feet of the ebola virus: individual treatment and global mental challenges prevalence of mental health problems in populations affected by the ebola virus disease: a systematic review and meta-analysis policy brief: covid- and the need for action on mental health a nationwide survey of psychological distress among chinese people in the covid- epidemic: implications and policy recommendations the distress of iranian adults during the covid- pandemic -more distressed than the chinese and with different predictors kff health tracking poll -late: coronavirus, social distancing, and contact tracing kaiser family foundation website https:// wwwkfforg/report-section/kff-health-tracking-poll-late-april- -economic-and-mental-health-impacts-of-coronavirus mental health, substance use, and suicidal ideation during the covid- pandemic -united states immediate psychological responses and associated factors during the initial stage of the coronavirus disease (covid- ) epidemic among the general population in china generalized anxiety disorder, depressive symptoms and sleep quality during covid- outbreak in china: a webbased cross-sectional survey this study identifies a major mental health burden of the public during the covid- outbreak, and healthcare workers at high risk for poor sleep factors associated with mental health outcomes among health care workers exposed to coronavirus disease this study demonstrates women, nurses, those in wuhan, and front-line healthcare workers as high risk of developing unfavorable mental health outcomes, needing psychological support or interventions covid- pandemic: stress experience of healthcare workers -a short current review occurrence, prevention, and management of the psychological effects of emerging virus outbreaks on healthcare workers: rapid review and meta-analysis this article reviews the psychological effects on clinicians of working to manage novel viral outbreaks, and successful measures to manage stress and psychological distress mental health status among children in home confinement during the coronavirus disease outbreak in hubei province, china. jama pediatr acute stress, behavioural symptoms and mood states among school-age children with attention-deficit/ hyperactive disorder during the covid- outbreak prevalence and sociodemographic correlates of psychological health problems in chinese adolescents during the outbreak of covid- . eur child adolesc psychiatry covid- : four fifths of cases are asymptomatic, china figures indicate preparing for a marathon: healthcare worker and organizational sustainment during covid- . presented virtually at the american psychiatric association spring highlights meeting using cbt effectively for treating depression and anxiety first-choice antidepressant use in adults with depression or generalised anxiety disorder. nice anxiety website a comparison of cognitiveprocessing therapy with prolonged exposure and a waiting condition for the treatment of chronic posttraumatic stress disorder in female rape victims randomized trial of prolonged exposure for posttraumatic stress disorder with and without cognitive restructuring: outcome at academic and community clinics eye movement desensitization and reprocessing (emdr): information processing in the treatment of trauma individual treatment of posttraumatic stress disorder using mantram repetition: a randomized clinical trial reduction of ptsd symptoms with pre-reactivation propranolol therapy: a randomized controlled trial is exposure necessary? a randomized clinical trial of interpersonal psychotherapy for ptsd a brief exposure-based treatment vs cognitive processing therapy for posttraumatic stress disorder: a randomized noninferiority clinical trial va/dod clinical practice guideline for the management of posttraumatic stress disorder and acute stress reaction . department of veterans affairs website parent-based treatment as efficacious as cognitive-behavioral therapy for childhood anxiety: a randomized noninferiority study of supportive parenting for anxious childhood emotions. j am acad child adolesc psychiatry suicide rates among working-age adults in south korea before and after the economic crisis suicide and the great recession of - : the role of economic factors in the u.s. states economically inactive, unemployed and employed suicides in australia by age and sex over a -year period: what was the impact of the economic recession? a new covid- crisis: domestic abuse rises worldwide. the new york times department of health & human services children's bureau website hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease -covid-net, states reports of anti-asian assaults, harassment and hate crimes rise as coronavirus spreads. anti-defamation league website incidents of coronavirus-related discrimination racism as a determinant of health: a systematic review and meta-analysis the social determinants of mental health: psychiatrists' roles in addressing discrimination and food insecurity. focus (am psychiatr publ) this article nicely describes the social determinants of mental health, including discrimination and food insecurity cumulative effect of racial discrimination on the mental health of ethnic minorities in the united kingdom supporting adults bereaved through covid- : a rapid review of the impact of previous pandemics on grief and bereavement department of the army. the u.s. army/marine corps counterinsurgency field manual: u.s. army field manual no. - : marine corps warfighting publication no. - publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -pwwgmtjr authors: lim, zheng jie; reddy, mallikarjuna ponnapa; afroz, afsana; billah, baki; shekar, kiran; subramaniam, ashwin title: incidence and outcome of out-of-hospital cardiac arrests in the covid- era: a systematic review and meta-analysis date: - - journal: resuscitation doi: . /j.resuscitation. . . sha: doc_id: cord_uid: pwwgmtjr background: the impact of covid- on pre-hospital and hospital services and hence on the prevalence and outcomes of out-of-hospital cardiac arrests (ohca) remain unclear. the review aimed to evaluate the influence of the covid- pandemic on the incidence, process, and outcomes of ohca. methods: a systematic review of pubmed, embase, and pre-print websites was performed. studies reporting comparative data on ohca within the same jurisdiction, before and during the covid- pandemic were included. study quality was assessed based on the newcastle-ottawa scale. results: ten studies reporting data from , ohca events were included. there was a % increase in ohca events since the pandemic. time from ohca to ambulance arrival was longer during the pandemic (p = . ). while mortality (or = . , %-ci . - . ) and supraglottic airway use (or = . , %-ci . - . ) was higher during the pandemic, automated external defibrillator use (or = . %-ci . - . ), return of spontaneous circulation (or = . , %-ci . - . ) and intubation (or = . , %-ci . - . ) was more common before the pandemic. more patients survived to hospital admission (or = . , %-ci . - . ) and discharge (or = . , %-ci . - . ) before the pandemic. bystander cpr (or = . , %-ci . - . ), unwitnessed ohca (or = . , %-ci . - . ), paramedic-resuscitation attempts (or = . %-ci . - . ) and mechanical cpr device use (or = . %-ci . - . ) did not defer significantly. conclusions: the incidence and mortality following ohca was higher during the covid- pandemic. there were significant variations in resuscitation practices during the pandemic. research to define optimal processes of pre-hospital care during a pandemic is urgently required. review registration: prospero (crd ). the novel coronavirus disease pandemic, caused by the severe acute respiratory syndrome coronavirus (sars-cov- ) has been associated with more than million cases and million deaths worldwide as of october th [ ] . health systems are under significant sustained stress with many parts of world experiencing second and subsequent waves of infection. the understanding of how the pandemic affects overall population health and access to health care; the nature and extent of disruptions it causes to pre-hospital and in hospital health care delivery is still evolving. for example, an increase in out-of-hospital cardiac arrest (ohca) incidence has been reported since the very early phase of the covid- epidemic [ ] . a recent population-based crosssectional study reported that out-of-hospital cardiac arrests had increased -fold during the covid- period when compared with during the comparison period in [ ] . patients with ohca during were older, more likely to have comorbidities and substantially less likely to have return and sustained return of spontaneous circulation [ ] . the chain of survival refers to a series of actions such as early access, early cardiopulmonary resuscitation (cpr), early defibrillation, early advanced life support and early post resuscitative care. these actions should be optimally executed to reduce the mortality associated with ohca. like any chain, the chain of survival is only as strong as its weakest link [ ] . a pandemic can disrupt this chain of survival in multiple ways and influence patient outcomes. the study hypothesis was that the incidence of ohca and the associated mortality was higher during the covid- pandemic period when compared to an earlier period. in this systematic review and meta-analysis, the authors aimed to determine the influence of the covid- pandemic on the incidence, processes of care and mortality among ohca patients. to evaluate the effect of the covid- pandemic, the studies with direct comparison to an earlier time frame (termed "before pandemic") were selected. this enabled a direct comparison between the two-time frames to help understand any differences in incidences. statistical analyses were performed using the review manager . (cochrane collaboration) and stata/mp . (statacorp). numerical data was summarized using mean and standard deviation and categorical data using proportion and percentage. to enable an analysis of results between studies, median values were converted to means, derived using an estimation formula [ ] . between-group differences were compared using fischer's exact test. an analysis of nonparametric values was conducted using the kruskal wallace test. a p-value < . was considered statistically significant. the mentel-haenszel random-effects model demonstrate better properties in the presence of heterogeneity accounting for both within-study and betweenstudy variances which was considered for the pooled odds ratio (or). results were presented in forest plots. heterogeneity was tested by using the χ² test on cochran's q statistic, which was calculated by means of h and i² indices. the i² index estimates the percentage of total variation across studies based on true between-study variances rather than on chance. conventionally, i values of - % indicate low heterogeneity, - % indicate moderate heterogeneity, and - % indicate substantial heterogeneity. a total of studies were obtained from the living systematic review, with full-text articles assessed for eligibility. ten studies across five countries (australia, france, italy, spain and usa) were included in the qualitative and statistical analysis [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . six studies were fair [ , , , [ ] [ ] [ ] and four studies were of good quality based on nos [ , , , ] ( supplementary table ) . six studies compared the covid- pandemic with the same period in [ , , , , , ] . one study compared ohca during the covid- pandemic against ohca earlier in the year [ ] . while one study compared data collected during covid- pandemic with data from - [ ] , the remaining studies compared covid- data against the time periods of - [ ] , - [ ] and - [ ] . the mean age reported among nine studies was . years during the covid- pandemic, and . years before the pandemic. time from call to ambulance arrival was significantly higher during the pandemic (p= . ). the incidence and outcomes of ohca of each study is outlined in table . the incidence proportion of ohca due to a medical cause was similar before and during the pandemic ( . % ( , [ , - , , ] . this is illustrated in figure a . bystander cpr (figure b ) was reported in all ten studies in a total of , / , patients ( . %) before pandemic and , / , patients ( . %) during the pandemic (p< . ) [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . bystander cpr occurred more frequently before the pandemic but was not statistically significant (or= . % ci . - . ; p= . ; i = %). unwitnessed ohca (figure c ) was reported in eight studies across , / , patients ( . %) before the pandemic and , / , patients ( . %) during the pandemic (p< . ) [ , [ ] [ ] [ ] [ ] [ ] [ ] ] . unwitnessed ohca occurred less often before the pandemic, however, was not statistically significant (or= . % ci . - . ; p= . ; i = %). resuscitation was attempted by paramedics in six studies in a total of , / , patients ( . %) before the pandemic and , / , patients ( . %) during the pandemic (p< . ) [ , , , [ ] [ ] [ ] . while there was no difference in the number of arrests who had resuscitation attempted in the two timeframes (or= . % ci . - . ; p= . ; i = %), only one study reported an increase in frequency of resuscitation attempts during the pandemic (figure d ) [ ] . the pandemic (p< . ) [ , , , , , ] . shockable rhythm or shocked events occurred more frequently before the pandemic (or= . % ci . - . ; p= . ; i = %). there were more ohca occurring at home during the pandemic (figure g ). across six studies, , / , ohca occurred at home before the pandemic ( . %) compared to , / , arrests ( . %) during the pandemic (p< . ) [ , , , , , ] . ohca more frequently occurred at home during the pandemic (or= . % ci . - . ; p< . ; i = %). airway management differed before and during the pandemic as reported in four studies [ , , , ] . more patients were intubated before the pandemic ( . % ( , / , ) versus . % survival to hospital admission, reported in six studies, occurred in , / , ( . %) patients before the pandemic and / , ( . %) during the pandemic (p< . ) [ , , , , , ] . patients were more likely to survive to hospital admission before the pandemic (or= . % ci . - . ; p=< . ; i = %) ( figure l ). similarly, survival to hospital discharge occurred in / , ( . %) of patients before the pandemic and / , patients ( . %) during the pandemic (p= . ), demonstrating that survival to hospital discharge occurred more frequently before the pandemic (or= . % ci . - . ; p< . ; i = %) ( figure m ) [ , , , , , ] . j o u r n a l p r e -p r o o f discussion across the selected studies, we observed a more than two-fold increase in ohca incidence during the covid- pandemic, with an overall significant increase in mortality. our analysis found several disruptions to the chain of survival in ohca victims during the pandemic and this may have at least in part contributed to the outcomes seen. there was reduced bystander cpr and aed use, along with increased supraglottic airway management by paramedic personnel. also, time from call to ambulance arrival was longer during the pandemic. the majority of ohca was attributed to medical causes and was more frequently the reason for arrest. public health measures may have role in reduction seen in the incidence of non-medical causes for ohca. this is potentially due to a complex interplay of heightened financial difficulties, social isolation, uncertainty about the future, redistribution of the health workforce and the disruption to clinical services due to the pandemic-related lockdown, resulting in a delay in receiving care [ , ] . there was not only a substantial reduction in the use of pre-hospital services to transport stemi patients to hospitals [ ] , but also a significant reduction in cardiology admissions [ ] and stemi activations [ ] in . conversely, trauma causes of ohca were less frequently observed, which is consistent with national lockdowns restricting mass gathering recreational and sporting events [ ] . this may have also resulted in reduced road traffic accidents [ ] . despite most ohca events occurring at home, a higher frequency of unwitnessed ohca was observed. this may be explained by strict self-quarantine measures adopted, resulting in vulnerable populations such as the elderly being isolated from family members who would otherwise visit frequently. with "stay home" measures, it is unsurprising that significantly more cardiac arrests occurred at home, where quarantine isolation may have enforced living in different areas at home or different houses from family members [ ] . it could be postulated that although ohca events occurred at home where family may be present, they may be less likely to commence cpr due to psychological and emotional effects of the sudden event [ ] . bystander cpr was more frequent before the pandemic. while there is an ongoing fear of contracting covid- during cpr administration [ ] , limited evidence exists surrounding the j o u r n a l p r e -p r o o f transmission of infection from patient to rescuer [ ] . although likely underreporting and/or identification of sars-cov- virus, the overall low prevalence of confirmed covid- cases among ohca during the pandemic suggests that any concerns regarding bystander cpr may be unwarranted especially in jurisdictions wherein risks of community transmission may be minimal. it should be noted, however, that cpr has the potential to generate aerosols [ ] and safety of bystanders and pre-hospital healthcare workers is equally important. community education, advanced healthcare planning and people wearing bands to indicate their wish not to receive cpr may go a long way in promoting dignity and comfort of the person who has suffered an ohca and who has a poor chance of survival even outside a pandemic. during a pandemic it may of even greater relevance when health services are stretched, and an element of risk exists to responders providing cpr and acls. there have been significant practice variations during the pandemic. for instance, there was an increase in use of supraglottic airway which may at least in part driven by risks of endotracheal intubation. the international liaison committee on resuscitation (ilcor) recommends the use of supraglottic airways as first line for adults with ohca (weak recommendation, very low certainty of evidence). however, the aerosol risks of supraglottic airway use when resuscitating patients with covid- remian unclear anda supraglottic airway may potentially cause a false sense of security amongst healthcare providers [ ] [ ] [ ] . similarly, although ilcor recommends the use of mechanical chest compression devices (weak recommendation, very low certainty of evidence), it is interesting to note that there was no difference in the use of mechanical cpr devices during the pandemic [ ] . interestingly, the frequency of a shockable rhythm/shocked events and rosc was higher before the pandemic. this may reflect disruptions in the chain of survival, where the probability of rosc diminishes significantly with time and it is unclear whether increased non-shockable rhythm is a consequence of delayed response or underlying pathophysiology [ ] . additionally, this may be related to the delay from call to ambulance arrival that is observed in this study. the quantitative increase in ohca calls and the need to properly apply personal protective equipment and disinfect ambulances between calls likely contributed to the delay in response and regrettably contributed to the observed increase in ohca mortality [ ] . this may also be compounded by the increased frequency of unwitnessed ohca and reduction in bystander cpr. as a result, patients may be found long after cardiac arrest where they may no longer be in a shockable rhythm. the absolute increase in ohca incidence and corresponding rise in mortality was reported in our analysis. direct covid- deaths would account for a proportion of these deaths [ , ] , while indirect factors such as lockdown and behavioral changes for fear of infection or reluctance to burden health systems may have resulted in delays in presenting to hospital [ , ] . worldwide, a decrease in acute hospital presentations have been observed, with reports of reduced st-elevation myocardial infarction presentations in spain, italy and usa [ ] . emergency department presentations have also decreased following the implementation of lockdown measures in the uk, germany and usa [ , ] . emergency medicine services may also be overwhelmed with the surge in ohca calls, resulting in a strain in pre-hospital services [ ] . there are several limitations that need to be acknowledged. firstly, most of the included studies were from the early phase of the pandemic from countries that were significantly affected and had little time to prepare. moreover, some degree of lockdown in many of the countries, due to the fear of contracting the virus, which implied that many people continued to avoid health care facilities. hence the result may still be representative during the pandemic. secondly, postmortem testing to confirm covid- was not reported, hence the direct causation of covid- infection and ohca or its indirect association due to unattended comorbid diseases during this pandemic was not readily available. thirdly, there was limited information about the previous medical history or comorbidities of these ohca patients. finally, it would been helpful to map the ohca event curve against that of the epidemiological pandemic curve (based upon hospital confirmed cases) in each of the reporting areas to observe any correlations between the incidence of covid- and ohca event rates, however this data was not provided in the studies. this information would be critical in helping systems better prepare for future resurgences in covid- cases. the incidence and mortality of ohca during the covid- pandemic was significantly higher as compared to time periods before the pandemic. multiple factors may have contributed to the increased mortality, including increased time from call to ambulance arrival and the reduced frequency of unwitnessed events, bystander cpr and aed use. there were significant practice changes during the pandemic. urgent research to improve pre-hospital care during a pandemic is required. -zheng jie lim: this author has conceived the project idea, conducted the systematic review, statistical analysis, assisted with data analysis, wrote the initial drafts of the manuscript, created tables and figures and finalized the manuscript. -mallikarjuna reddy: this author has conducted the systematic review, assisted with data analysis, wrote the initial drafts of the manuscript and finalized the manuscript. rosc: return of spontaneous circulation; aed: automatic external defibrillator. * the study did not compare the incidence of ohca between and and was thus excluded from this analysis. # out of resuscitations attempted by emergency medical services. ^ marijon et al looked at two different timeframes and compared the incidence and outcomes of ohca against data from the pandemic period in . j o u r n a l p r e -p r o o f world health organisation. coronavirus disease (covid- ) situation reports out -of-hospital cardiac arrest during the covid- outbreak in italy characteristics associated with out-of-hospital cardiac arrests and resuscitations during the novel coronavirus disease fibrillation and defibrillation of the heart preferred reporting items for systematic reviews and meta-analyses: the prisma statement living evidence on covid- prediction models for diagnosis and prognosis of covid- : systematic review and critical appraisal the newcastle -ottawa scale (nos) for assessing the quality of nonrandomised studies in meta -analyses estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range covid- kills at home: the close relationship between the epidemic and the increase of out-of-hospital cardiac arrests collateral damage: hidden impact of the covid- pandemic on the out-of-hospital cardiac arrest system-of-care indirect effects of covid- on ohca in a low prevalence region. resuscitation a population-based, observational study. the lancet public health influence of the covid- pandemic on out-of-hospital cardiac arrest. a spanish nationwide prospective cohort study out-of-hospital cardiac arrest during the covid- pandemic in the province of padua prevalence of covid- in out-of-hospital cardiac arrest: implications for bystander cpr out -ofhospital cardiac arrest during the covid- era in bologna: system response to preserve performances out -of-hospital cardiac arrest response and outcomes during the covid- pandemic effect of covid- lockdown on alcohol consumption in patients with pre-existing alcohol use disorder covid- pandemic and its impact on service provision: a cardiology prospect impact of covid- pandemic in cardiology admissions reduction in st-segment elevation cardiac catheterization laboratory activations in the united states during covid- pandemic state of emergency restrictions on presentations to two victorian emergency departments a descriptive analysis of the effect of the covid- pandemic on driving behavior and road safety: transportation research interdisciplinary perspectives disparities in bystander cardiopulmonary resuscitation performed by a family member and a non-family member the o ther side of novel coronavirus outbreak: fear of performing cardiopulmonary resuscitation covid- in cardiac arrest and infection risk to rescuers: a systematic review international liaison committee on resuscitation: covid- consensus on science, treatment recommendations and task force insights supraglottic airways in the management of covid- patients ventilation and airway management during cardiopulmonary resuscitation in covid- era time to return of spontaneous circulation (rosc) and survival in out-of-hospital cardiac arrest (ohca) patients in the netherlands covid- pandemic and the reduction in st-elevation myocardial infarction admissions where are all the patients? addressing covid- fear to encourage sick patients to seek emergency care do not stay at home: we are ready for you: nejm catal innov care deliv prof shekar acknowledges research support from metro north hospital and health service. we would like to acknowledge the work of pre-hospital health professionals in providing excellent health care during the covid- pandemic.j o u r n a l p r e -p r o o f competing interests: all authors declare no support from any organization for the submitted work, no competing interests with regards to the submitted work key: cord- - dczotbh authors: everts, jonathan title: announcing swine flu and the interpretation of pandemic anxiety date: - - journal: antipode doi: . /j. - . . .x sha: doc_id: cord_uid: dczotbh this paper discusses the ways in which novel swine‐origin influenza a (h n ) was announced and resonated with current pandemic anxieties. in particular, the us centers for disease control and prevention (cdc) are used as a lens through which recent pandemic anxieties can be analysed and understood. this entails a closer look at the securitisation of public health and the challenges and struggles this may have caused within public health agencies. in that light, cdc' formal entanglement with global health security and its announcement of the h n pandemic are interpreted, followed by an ethnographically informed focus on various people who were engaged in the h n emergency response and their practices and practical struggles in the face of pandemic anxiety. as it stands, the influenza a h n pandemic ("swine flu") is believed to have caused up to , deaths worldwide between early and august , when the world health organization (who) announced the end of the pandemic. though the pandemic of the virus has been real and caused many tragedies, observers criticised the attention it received from politicians, global health agencies and experts. critics warned especially of the potential to exploit pandemic threats for fear-mongering and profit-making (gostin ; sparke ), overshadowing at the same time other long-term global health problems, often related to social inequalities (craddock and giles-vernick ; davies ) . with hindsight, the event of swine flu appears as a small event in respect to anticipated severity and death rates. nevertheless, public health officials and experts stressed their moral obligation to abide to the "precautionary principle" to prevent as much harm as possible even if that means taking some extreme measures, spreading anxiety and playing into the hands of the pharma industry (caduff ; gallaher ; michaelis, doerr and cinatl ) . however, swine flu was a global event, not just from an epidemiological perspective. it was exceptionally widely covered by the news media, inciting a broad range of responses by state and non-state actors, occupying the attention of millions of people for a greater part of . responses included mass distribution of antiviral drugs, production and stockpiling of vaccines, mass slaughtering of pigs in egypt, quarantine for slightly feverish air passengers in china, restrictions and cancellations of flights to mexico, and asian import bans on pork products from the usa. each individual reaction contributed to swine flu as a global event of anxiety through intensifying and amplifying the sense of urgency in the face of this new infectious disease. due to the early emergence of novel h n in north america, the us centers for disease control and prevention (cdc) were at the forefront of h n emergency response. scientists working for cdc were among the first to identify the new microbe and to carry out substantial virological and epidemiological research (special issue of clinical infectious diseases january , supplement ; dawood et al ). they informed the public, politicians, who and other public health agencies worldwide. put simply, the way the world initially learned about h n was significantly shaped by cdc. from a social science perspective, its central role qualifies cdc as a powerful lens through which we can seek to understand h n 's sudden rise to prominence and the ways it was dealt with. investigating cdc's h n response may also shed light on the implications of a change in public health discourse, a change that made "emerging infectious diseases" a key concern for public health, the kernel of a new age of "pandemic anxiety" (ingram ) . for the purpose of this paper, i will employ the perspective of "anxiety as social practice" (jackson and everts ) . building upon schatzki's ( ) practice theory, the phenomenon of anxiety can be opened up to a much broader analysis since anxieties "are embodied and social, practical and practised" and like "other social practices, they are routinised, collective and conventional in character" (jackson and everts : ) . here, of particular interest is how anxieties become "institutionalised" and worked through within organisations (jackson and everts : ) . certain events engender anxieties specific to an organisation, overlapping with general concerns in respect to the event. events important to an organisation can threaten its meaning of existence, its legitimacy and its credibility. in the case of emerging diseases, pandemics pose a threat and challenge to public health agencies, creating anxieties over its reputation and expertise. although these latter anxieties are derived from pandemic anxiety, they are significant in their own right, shedding light on general anxieties pertaining to that specific organisation and its area of expertise. in the following, cdc's ways to work through the h n pandemic are first contextualised within the emerging global health security regime and second analysed from a practice-based and ethnographic perspective. research conducted within cdc in early , involving expert interviews, informal conversations and observation, provides the background for the findings presented. the aim is to use cdc as a lens through which we can, partially at least, understand the ways in which pandemic anxieties work. this entails a closer look at the securitisation of public health and the challenges and struggles this may have caused within public health agencies such as cdc. in the next section, a brief account of the securitisation of public health discourse is provided. then, cdc's formal entanglement with global health security and its announcement of the h n pandemic are presented. this is followed by shifting the perspective onto various people who were engaged in the emergency response and their practices and practical struggles in the face of pandemic anxiety. scholars from the social sciences have identified significant changes in public health discourse since the early s (collier, lakoff and rabinow ; davies ; elbe ; fidler ; king ) . the analytical kernel of this changing discourse is perhaps best captured by the term "securitisation" (fidler and gostin : ) . here, securitisation refers to the observation that much of public health discourse has become organised around concerns over security rather than, say, humanitarianism or welfare. following elbe ( : ) , we can distinguish analytically at least between four types of security relevant to the emerging "health-security nexus": national security, biosecurity, human security, and public health security. in terms of national security, king ( ; see also king b) demonstrates how the discursive production of scales allowed us american scientists, public health agencies and journalists to reframe the international problem of emerging infectious diseases as a threat to american national security. by employing scale politics, eminent scientists in the field of virology, microbiology and epidemiology were able to provide answers to uncertainties arising from globalisation. by making emerging infectious disease the key challenge, enhanced laboratory practice and disease surveillance appeared as effective and nationally manageable countermeasures against the adverse effects of globalisation. this particular discursive strategy was effectively conveyed to politicians and journalists at the conference on "emerging viruses: the evolution of viruses and viral disease", chaired by eminent virologist stephen s. morse from rockefeller university. also highly influential was the publication of the report emerging infections: microbial threats to health in the united states ( ), presenting the views of a committee convened by the national academy of science's institute of medicine in . the report became the blueprint for rapidly evolving literature and strategy plans on how to tackle the problem of emerging infectious diseases (king : - ) . public awareness was achieved through the media and journalist writers, since "the concept of emerging diseases offered journalists a powerful scalar resource for characterizing individual outbreaks as incidents of global significance" (king : ) . both scientists and journalists added bioterrorism to the problem of emerging diseases (king a (king , , emphasising once more the importance of emerging viruses to national security. from there it is only a small step to biosecurity, another security framework increasingly important to public health. for collier, lakoff and rabinow ( ) , growing concerns over bioterrorism and uncertainties in relation to new research possibilities culminating in the human genome project, provide the context of the "emerging biosecurity apparatus". the apparatus has as its main aim to "make life safe" through "attempts to monitor, regulate and/or halt the movements of various forms of life" (bingham, enticott and hinchliffe : ) . this entails a problematic justification for repressive internal politics as much as for new forms of imperial politics. as braun ( : ) argues, biosecurity is "a set of political technologies that seek to govern biological disorder in the name of a particular community, through acts that are extraterritorial" (emphasis in the original). both emphasis on national security and biosecurity are deeply entwined and brought together through the terminology of global health security. in discussing pandemic anxieties, ingram ( : - ) identifies three main facets of global health security discourse: the emergence of the global as the definitive context for infectious disease; a tendency to locate causes, origins, and responsibility elsewhere and with others; and the emergence of global health security as a guise for the consolidation of hegemonic interests. notably, global health security discourse advances at the expense of other discursive formations, in particular that of human security and humanitarianism. following lakoff ( ) , we can juxtapose global health security and humanitarian biomedicine as two competing public health regimes. "humanitarian biomedicine" refers to the ongoing effort to mitigate existing health problems prevalent especially among poorer nations. in contrast, "global health security" focuses on "emerging infectious diseases"-diseases that have not occurred yet, for which one must be prepared, and which are more relevant to richer countries. "whereas global health security develops prophylaxis against potential threats at home, humanitarian biomedicine invests resources to mitigate present suffering in other places" (lakoff : ) . similarly, davies ( ) argues: while the securitization attempt has meant that particular infectious diseases have reached the realm of high politics, a great number of communicable diseasesparticularly those that are most likely to remain in poor, low-income countries-are not receiving the same level of attention despite the fact that some of these diseases contribute to a greater number of deaths per year (davies : ). in the same vein, farmer ( : ) argued a decade earlier in respect to tuberculosis that "the degree to which this disease is seen as a threat varies with the degree to which the powerful-or, at least, the non-poor-are deemed to be 'at risk'". this particular mode of non-poor pandemic anxiety is deeply worrying in the view of critical scholars since the rich have powers to enforce various kinds of borders, through violence if necessary. as, for instance, price-smith ( : ) argues, fear and anxiety generated by infectious disease are often most visible in "vicious persecution of minorities or of other polities" and "may even lead to the oppression of the people by a governmental apparatus of coercion in order to maintain the ideology of order and the 'interests' or the state". the h n pandemic and pandemic threats such as severe acute respiratory syndrome (sars) and hpai h n (avian flu) gave evidence to the various impacts of securitisation discourse. in discussing the canadian response to sars, keil and ali claim that "racism, infection, globalized urbanization are reshuffled into a new political frame of reference" since "racism, linked specifically to infectious disease and the bodies allegedly carrying it, structures biopolitical space of the sars crisis and requires that it be understood from the point of view of affected communities: east asians and those who were identified as such" (keil and ali : ; emphasis in the original). the egyptian response to h n showed another securitisation bias towards large-scale "modern" economies. the cull affected mainly rooftop and backyard poultry but restocking was in favour of large companies . securitisation also leads to more hierarchical "chains of command" and the centralisation of decision-making, as became apparent by the uk's response to h n (chambers, barker and rouse ) . looking at public health discourse in the usa, we cannot neatly distinguish historically between a pre-securitisation phase and the current securitised one (fearnley ; french ; wald ). however, the "emerging viruses" conference and the "emerging infections" report seem to signify the beginning of an acceleration of a specific interweaving of public health and security discourse. from a cdc perspective, the tipping point was the anthrax scare that followed the / attacks. since then, cdc experienced a "culture shift", as my respondents phrased it. although us security politics were already attuned to the perceived threat of bioterrorism (king ) , anthrax gave the immediate impetus for changing the make-up of us public health organisations. and this was by no means only a discursive shift. since , cdc was gradually reformed from a scientific branch of the federal government into an intelligence service supplementing national security and defence politics. this change was achieved through a great influx of retired military personnel who began work for cdc in various divisions. some became advisor to the director, which brought further changes to the organisational and spatial structure. cdc in pre- years resembled a very large research institute or university, openly accessible to virtually everyone. however it has become more than ever a hierarchically organised agency with command structures, which resemble those of military departments; and cdc campuses are now fenced off and only accessible through security check points. within this emerging new organisational structure, two big pandemic anxieties were worked through before h n . while sars occupied cdc's attention in , it was really h n in - which had lasting effects on cdc's organisational structure and preparedness planning. from the research as much as the communications point of view, cdc looked good during h n in (see below). as an explanation for this, some of my interviewees pointed repeatedly to the response structures that were built under the impression of h n : regarding h n , the awareness was already there and somehow we could tap into it. for h n , we did a lot of pandemic influenza planning and in every [us] state we had a conference about what needs to be done. and a year later, (with h n ), we were able to turn that on. so, all the planning efforts paid off. preparedness planning also involved frequent exercises, which simulated cdc's emergency response in case of a new pandemic. when h n began, "it was just like an exercise" as one epidemiologist put it and another stated, "we all flipped into exercise mode". swine flu was treated like a possible h n pandemic. from an epidemiological and medical point of view, concerns are still in order over h n developing into an easily spreading human-to-human infection with mortality rates over %. such a devastating prospect justifies augmented surveillance of emerging viruses and provides an important context for the rapid detection of novel h n and subsequent response. however it was not only exercises that primed, cdc experts for the next pandemic. according to cdc epidemiologists, various cases of novel influenza a (h n ) were investigated in the years before the actual outbreak in . the background to this was the position statement by the council of state and territorial epidemiologists (cste) that made all novel influenza a viruses nationally reportable in (cste ) . in particular, the position statement from cste requires that "state and territorial epidemiologists in conjunction with public health laboratories will report to cdc all human infections with influenza a viruses that are different from currently circulating human influenza h and h viruses", including viruses "that are subtyped as non-human in origin and those that are unsubtypable with standard methods and reagents" (cste ) . this step was justified on two grounds. first, any novel influenza a virus could "signal the beginning of an influenza pandemic" and, in turn, "rapid detection and reporting" would "facilitate prompt detection and characterization" and "accelerate the implementation of effective public health responses". second, the usa had formally accepted the revised international health regulations (who ) in . the new regulations demand its member states to notify the who on various events detected by national surveillance systems, among them cases of "human influenza caused by a new subtype" which are deemed-among others (smallpox, polio, sars)-as "unusual or unexpected and may have serious public health impact" (who : ) . since the position statement of the cste was issued ( july ), a team of cdc epidemiologists investigated all reported cases of novel influenza a viruses in the usa. these investigations became routine. most of the time, children contracted a (h n ), suffered from flu symptoms and recovered. field investigations could confirm in most cases that children had been to a country fair or farm where they were exposed to live animals, especially pigs (cf shinde et al ) . that was also the assumption that accompanied the investigations of the very first cases, a boy and a girl aged and , respectively, of novel h n in southern california in mid april despite "rumours" within cdc about what was happening in mexico. the mexican general directorate of epidemiology (dge) reported during march to april a total of suspected influenza cases, including confirmed cases and a total of deaths. suspected and probable cases were reported from all states and from the federal district of mexico and were identified in all age groups. nevertheless, to cdc experts, the mexican events seemed to be locally isolated, possibly caused by an influenza b virus. at first sight, the cases in california had no connection to mexico and the investigating team did not fear any significant further spread. only when a case in texas was reported on april just a few days after the two cases in california did cdc epidemiologists begin to consider the likelihood of a connection to the events across the border. laboratory testing on the behalf of cdc confirmed on april the presence of the novel virus swine influenza a (h n ) (cdc a; first posted as a morbidity and mortality weekly report early release on the website on april). cdc acknowledged the "epidemiological characteristics" of novel h n and recommended monitoring of public health practices "in anticipation of a possible pandemic" (cdc a) . the connection to what was happening in mexico was officially recognised by cdc on april : "patients were infected with the same strain" (cdc b). significantly, this acknowledgement came days after director general of who, margaret chan, "declared this event a public health emergency of international concern". swine flu was by then already addressed on a global scale, following the guidelines of the recently revised international health regulations. from a cdc perspective, who did not wait for three subsequent generations of infections and thus made its announcement too early. cdc experts took another weeks of research before calling h n the "greatest pandemic threat since the emergence of influenza a (h n ) virus in " (dawood et al ). announcing swine flu met certain criteria that justified the choice of terminology. a new pathogen had been identified, its spread verified by connecting cases in different places and its origins classified as a new and as of yet unknown combination of viral genotypes that resulted from previous microbial traffic between birds, pigs and humans. however, before the actual work that led to detecting h n took place, pandemic anxiety and institutionalised heightened concerns had already worked their way through to cdc experts via global and national public health security recommendations and regulations and the announcements made by respective representatives. from this perspective, institutionalised pandemic anxiety pressed public health organisations to announce swine flu as significant global event as soon as possible. judging from the resources and work put into h n emergency response, organisations such as cdc had to play along. however, shifting the focus on the people whose work was critical in turning novel h n from an unknown viral agent into the global event of swine flu, we find a more complex and less straightforward process. in particular, the pressure on a public health agency such as cdc arises from multiple directions and dealing successfully with those pressures involves a host of creative strategies. in the following, both pressures on and strategies by cdc experts during h n will be analysed to provide a more nuanced account of the entanglement of pandemic anxieties and expert practice. the change in perspective is mirrored in a change of language. in the vein of ethnographic writing, the voices of both the author of this paper and the respondents at cdc are foregrounded, allowing for a deeper and more personal account. since recording of interviews was not possible, quotes are taken from fieldnotes and conversation protocols written down after conversations took place. accuracy was one of the terms that i heard frequently during my stay at cdc. it was specifically used in the sense of accurate data or "i need to make sure my data is accurate". as a scientific branch within the us government, to obtain, gather and provide accurate data presents a legal as much as a moral obligation for cdc. that was reflected in personal conversations i had through comments such as: "we speak with the voice of the us government. we need to make sure everything is % right"; "we are just like who or the red cross, people trust us, the cdc doesn't lie." however, frequent use of the term accuracy suggests that the term signals not only an obligation but also a key challenge. even at times with rapid data-processing technology, the process of gathering, managing and interpreting data is a time-and resource-consuming affair. hence, at first, i thought the term accuracy was being used as an indicator for the problem of lacking time and other resources. but that was only part of the explanation. the "white house theory" makes a good entrance route for clarifying the accuracy anxiety. in one group discussion, it was pointed out that "there is this theory, the white house could come in any time, asking for information, 'how bad is it'." based on this common assumption, everybody within cdc knows that information and data have to be ready at hand. this is especially the case when the emergency operations center (eoc) becomes activated as happened during h n . during emergency response, "time is compressed . . . everything is happening faster", as one of my respondents phrased it. another person i talked to, who was not a regular member of the eoc team, explained: "they don't want to be caught off guard, they want to show they take everything seriously, that they go all guns at all events." this was backed up by similar comments that stated that there was "certainly the anxiety [at the eoc] to look foolish" and that "being blamed for not doing . . . enough is probably one of the worst fears of the eoc." during the h n response, time compression became a challenge for all involved in data gathering, processing and visualization. epidemiologists were the first ones to experience exceptional pressure: "the struggle really is to stay updated. there's not any other system with this time schedule. and we get the pressure from hhs [united states department of health and human services] and washington. and especially with h n we had that." in effect, the pressure was not only to provide data as quickly as possible. it was furthermore to provide high resolution data: "it was the first time really cared in that detail, there were new demands for data on a more detailed level. you see, by and large, people are not interested in flu, it just happens, they think. and suddenly, they wanted all this detailed information." one of the most pressing needs for assessing the h n situation became acquiring data of influenza-like illnesses (ilis) throughout the united states. this, it was hoped, would yield important insights into the spread of the disease, its demographics and the localities most in need of mitigation measures. because of the federal character of the usa, ili data are gathered in aggregate numbers on the state level and shared on a weekly basis. if cdc wants more detailed information (down to the day and county level), they need to call up the states individually. thus, the emergency response team during h n had to call up all the states to get the latest data. in processing and visualising these data, a number of divisions were crucial. one of them produces maps based on those data. from my conversations with cdc cartographers it appears that during h n , requests for maps were scheduled within a -min time frame. the demand for new, timely and detailed data and the visualisation thereof thus progresses through the various branches within the organisation, making time compression an issue for hundreds of experts involved in emergency response. time compression has a bearing on people's work experience during emergency response. they need to cope with constant demands for new products, which have to be ready within minutes rather than hours. but this does not seem to be the key concern of those involved in emergency response. in the case of epidemiological maps, for instance, they were able to produce maps at very short notice within minutes thanks to thoroughly developed templates and software. the problem however lies within the time allocated for checking the data for possible flaws, "to make sure my data is accurate". working within emergency temporality, the real challenge lies in providing accurate information as fast as possible. as indicated by the above quotes about cdc's obligation, there is no allowance for communicating any faulty information. people working within cdc are well aware of the consequences that even slightly incorrect data can have. thus, within their obligation to provide information that is " percent right", cdc experts feel the need to resist all demands for timely data until they have carried out at least a few routine checks for data accuracy. this leads to elongated duration between demands for new data and their presentation. that little extra time-indicating the resistance of cdc scientists in presenting unchecked data-forms the core of a principle conflict between those who pass along the pressure for new information generated by "the white house" and the experts and scientists who provide this information. from an epidemiologist's point of view, those representing the governmental side within emergency response do not recognise the vital importance of the time lag between the demand for data and dissemination: "it feels as if they think we're withholding data or information." indeed, talking to other people at cdc, comments were made that suggested that reluctance from cdc experts in providing data as quickly as possible is frowned upon. during h n , this general suspicion was apparently augmented by a lack of reported severe cases within the usa. once the connection to h n cases in mexico became apparent, swine flu appeared as a deadly new disease. but from the epidemiologists' point of view, "as long as you don't know how many people got sick, the population denominator, you cannot say whether the mortality rate is high or not". although cdc sent an already established team to mexico that began counting cases and creating statistics, "the question from white house was, why were there virtually no reported cases in the us". according to cdc epidemiologists, hospitalisation rates in the usa were monitored closely but at no time was the threshold passed that would have led to an automated alert message. therefore, epidemiologists "felt put under microscope"; why did they not get any alerts despite all the sophisticated surveillance and report systems? did they overlook the cases? in my view, this moment represents the point when cdc scientists were at their weakest position. increasingly, their role as rightfully proclaiming scientific truths became more and more questioned. however, they were able to turn their perceived weakness into a powerful resource. since routine surveillance data appeared insufficient, money for thorough case studies research was successfully acquired. among the very first field investigations was the survey of the entire student population and faculty of the university of delaware, altogether around , people. taken together, infections were confirmed in % of the survey population, no deaths. in terms of the feared severity of the disease, the findings from this and very similar studies brought hope. if this had been a re-run of the infamous - pandemic, the delaware study would have revealed around deaths; especially since young adults were the age group hit hardest by h n . the information from this case study and others was published by the new england journal of medicine on may (dawood et al ). with hindsight, the publication of this paper at a very early stage of the pandemic was described by some of the authors as the most successful move during the unfolding pandemic, to communicate the very first findings and inform the public. as one of the authors said, they were able to "do a lot of really good work" during the beginning of h n . it seemed as if there was "no time to do it" but they "cranked the scientific work out, despite how horrible things were". only weeks after the first call informing them about the first cases in california, they had their article accepted by the new england journal of medicine. the article is mainly concerned with epidemiological core concerns (demographics, symptoms, severity, hospitalisation rates, nucleotide sequencing). though being very cautious in the interpretation of their findings, the authors state in their discussion section that to date they are not encountering a disease in the usa that would justify exaggerated concern since "most confirmed cases of s-oiv infection have been characterized by self-limited, uncomplicated febrile respiratory illness and symptoms similar to those of seasonal influenza" (dawood et al : ) . this is confirmed by comments made by others at cdc about their relief and receding worry already a few weeks after the first occurrence of swine flu, in particular after case studies showed the limited numbers of serious complications due to the novel virus. however, work for cdc epidemiologists and all other divisions involved in the response did not stop there. from then on, important decisions had to be made, including the definition of risk groups and distribution of antivirals and development of vaccine. nevertheless, the critical moment had passed; cdc experts had successfully demonstrated their ability to generate relevant knowledge and information within a very limited timeframe. nevertheless, pressure on cdc experts did not ease and arose from other directions. on may , a -year-old pregnant woman died from complications due to h n ; one of the very first deaths from swine flu in the usa. this tragic case illustrated that h n had the power to kill despite the generally mild symptoms it generated in most patients. from the news media point of view, the ability to kill young women and children made swine flu even more hideous-and more compelling. thus, another challenge to cdc arose from the way swine flu appeared in the headlines of the news media and the stance cdc was trying to convey. within cdc, risk communication has become an important area of concern since the early s. as one of the eminent cdc risk theorists stresses, we can identify certain patterns in which the "media behaves in a crisis": the media, those are only humans as everyone else. first they look at their own safety and are concerned. but once they figure out, it's not that bad for me, they begin to look for the sensation in the event. we were fortunate enough that we never had an outbreak of hemorrhagic fever (ebola) in the usa. at the same time, you notice how the media are fascinated by threats that are grotesque but distant. and it creates scares. but i know if we had an outbreak of ebola here, the whole tenor would be different. so the more distant, the more the media compounds something, the more real the threat, the more they will look for reassurance. however, the trouble with swine flu was that it was not a distant or rare and grotesque disease but it was there and widespread. thus, following the pattern identified by cdc's risk communication expert, we would expect a more responsible and reassuring media approach. but since swine flu was already pronounced to be in general mild in early may, sensationalism still became an issue for cdc scientists and communication experts. from the scientists' point of view, when in a response situation, the challenge is to strike a balance between informing the public on the one hand and to "resist the media who call all the time and ask what's new" on the other: they want quick and accurate information. but we cannot be irresponsible. we need to make sure our data is accurate, our data is valid. and then we can craft a message. and that means that even if the cnn wants to know every hour what is happening, that's too frequent, and then the information is sloppy. that would be irresponsible, especially since the health of people is at stake here. once again, the struggle seems to be over the speed of information and the accuracy of data. however, there is another aspect that becomes more prominent within cdc's engagement with the media. again from a scientist's point of view, the media appears sensationalist. although they provide the media with a lot of detailed information, what actually makes it into the news seems to be driven by sensationalism: you never really know what the press is interested in. you can give them all this information and all they would talk about is this one boy . . . who died shortly after vaccination. and of course, every single death is a tragedy but we are worried about the major changes. the media is all sensational, they have the family and the one death and that's their product and they sell it like a product. from this point of view, cdc scientists try to strike a balance between using the media as an important tool for conveying urgent information to the public but to be reassuring at the same time: "we think about it, whether something causes alarm or brings reassurance. and we try to convey reassurance. we want to bring out the scientifically most accurate data, turn it into a digestible format and reassure. the government should not be alarmist. it has to be reassurance." just as scientists are anxious to strike a balance between information and reassurance, cdc communication experts take the same approach: "we were very careful in striking the balance; we did not want people to have no concern and as well we did not want to be the cause for concern." but how can such a balance be achieved? what i deduce from my conversations with experts, the communication strategy is complex and works on many levels but one aspect came up repeatedly and is possibly the main technique harnessed for striking the balance between raising awareness and conveying reassurance: we're not just gathering data and display the data itself. we do much more than that. we put the data into context; demographics, population characteristics, infrastructure . . . c the author. antipode c antipode foundation ltd. i remember when we had this map with the deaths of children. that was not reassuring. people only see the number, and children dying. so we try and craft a language around it and to put it into context. putting data into context is an important strategy for cdc experts dealing with the media. from a communication expert's point of view, "we've done a pretty neat job [with h n ]-we had done enough in showing what it is and what it does". similarly, scientists were pleased how cdc handled the media and expressed that "the agency did a great job in controlling the media during h n ". following lakoff ( ) in his analysis of the revised international health regulations (ihr), making many different disease events reportable to who was one of the key innovations in establishing a global disease surveillance system. the new ihr was developed over concerns that nation states would try to hide outbreaks from the international public over fears they could have negative effects on trade and tourism. credibility to these concerns was lent by the way the chinese government initially handled the sars crisis. part of the new strategy epitomised by the altered ihr was to integrate the media into global public health surveillance by adding media reports as one source of relevant information over disease outbreaks to the established reporting by health authorities. but even though it seems as if global health security and news media had forged a successful alliance, my examples from cdc's struggle with the media during swine flu suggests that this alliance is contested in practice. particularly interesting is that from a cdc perspective, there is almost a race between the media and cdc of who knows first: "the media knows it at the same time as we do and we need to gear up for response as fast as we can". in order to stay ahead of the game and to have sufficient time to "gear up" before the first media calls get in, cdc experts developed other tactics of early detection that do not rely on the media: so what we do, for example, we get the data from the pharmacies about over-thecounter drugs such as tamiflu and absenteeism from school and prescriptions from doctors and the ili data. so that is real-time data and it is by place too. so say we have a huge rise in tamiflu sales and you see it on the graph, your line is going up and then you look at absenteeism, and the graph is going up as well and so on, you start to think, well, maybe something's going on here. it's not conclusive but you have some evidence that something is happening. so you go to your flu experts and tell them, there is a cluster, maybe this is a new breakout. and maybe it's not. that's what you need to find out then. . . . the aggregate tells you more than a single information. . . . you need to track the key indicators. . . . you only need four or five indicators but you'll be months ahead if something is happening. this mode of surveillance is entirely decoupled from the media and is designed to even outrun more traditional ways of detecting new diseases such as routine laboratory investigations. crucially, each data source does not tell much on its own. only "data fusion"-the aggregate information-can provide enough evidence for concern. another way of getting real-time information was installed through a -hour toll-free hotline. people can call there about anything and any topic. as one communication expert told me, "for cdc, this information is a canary in the coalmine". interestingly, concerned people who call cdc for information become themselves informants and a crucial role in cdc's early warning systems. this is also true for the cdc website and services provided through social media feeds. within cdc, a web metrics report is created daily. the report includes the most popular pages and how people did come to that site and it is understood as a part of cdc's surveillance. according to an analyst, "h n had some really interesting metrics". they had million page views in one day. the highest traffic ever seen before was half a million. from these data, growing awareness and concern could be deduced. but not only this, the analysis of traffic to the website also reveals the locations of those viewing the website: "you can show where people were concerned. [during h n ] we had this huge pipeline to our website from china and japan so we knew these are the next affected regions. same thing with h n when we got a lot of traffic from european countries to our website." to make the most out of cdc's website popularity, visitors are also asked to complete a short questionnaire: we have this section on our site "tell us what you think". we get a lot of information from that. we get actually more feedback than we can analyze but we try to read all of it. during h n , we did an eight months survey of , people . . . we have a four question survey on our website, it takes maximum five minutes. it asks about what was the reason for you recent visit, who you are, why are you coming. from that information, cdc is able, among other things, to define target groups for their communication strategy. this strategy relies on a more and more diversified approach. while the importance of "traditional" tools from leaflets to print media is still recognised, online tools and the social media become increasingly significant: right now we prepare information for twitter . . . during h n , we gained almost one million followers in the first week. since then it's grown only around %, so that was a teachable moment. other tools are popular too, widgets, or badges. the email updates were very popular during h n . once again, the information sought by others through twitter, email updates or website surfing is turned into a source of real-time information about what, where and what kind of people are concerned. cdc communication experts use this information to tailor and craft messages for specific target groups. according to cdc risk experts, the public needs advice that comes in "manageable bites". instead of asking too much (eg staying at home and taking weeks off of work etc), "you need to do it in baby steps". for h n , the most important message was vaccination: as a public health agency, our default message is, go and get vaccinated. our focus was early on to inform the risk groups well, those people who were at the highest risk in terms of death and disease rate. and that was pregnant women. early on we knew this was our main target group and we could craft our messages carefully for this group. to do that, we worked with our partner groups (physicians, nurse groups and so on) and we got the people together for discussing our communication strategy. we took mainly what the media was already saying and crafted messages that would say you shouldn't be around sick people and the obstetricians backed that up and made clear that the vaccine is safe. and if you split the vaccination rate by groups, you can see how effective we were: the vaccination rate for pregnant women was to %. this shows we got the message through. so we were quickly able to adverse events early on and to monitor in real-time what the effects were. sometimes, the cdc communication team had to be even more active then "just" disseminating what they had: with h n , we had a misinformation quest. there was this anti-vaccine blog that was recommending not to take the vaccine, mainly saying it wasn't effective. so we were able to address this and funnel specific information there. it's hard to tell whether it worked or not. maybe the supply was more of a problem than the vaccination rate and i think the rate was pretty high, especially among the targeted risk groups. and yes, the blog in question toned down their language. i mean, they didn't stop what they were doing but they were less general and more informative. once again, cdc's strategy was successful by its own standards. they provided information to the public via many different channels and vaccination rates showed that they "got the message through". regarding cdc's response to h n , former cdc director david j. sencer commented: perhaps the primary lesson learned from this pandemic will be that while decision-making is always risky, that risk can be minimized through effective communications . . . [o] n balance, the response has been a success and so far, the ultimate test of management has been met: no one has been fired (sencer :s -s ). on the grand scale of nations and supranational organisations, pandemic anxieties are met with securitisation efforts, entailing practices that install or enforce centralised chains of command, emphasise territorial borders and advocate restrictions of movement. on the scale of public health agencies such as cdc, pandemic anxieties resonate with other, "institutionalised" anxieties. in the case of h n , at least three anxieties at cdc were crucial: anxieties over the quality or "accuracy" of data; anxieties over how to deal with the media and striking a balance between raising awareness and not being alarmist; and anxieties over staying informed and being the first ones to know. these anxieties are neither new nor foreign to pre-securitised public health. nevertheless, pandemic anxiety certainly augments these "institutionalised" anxieties and makes them more pressing issues. they need to be worked through by employing various strategies and practices. the sense of urgency engendered by pandemic anxiety creates time compression for those involved in emergency response. over fears that speed threatens to compromise the validity of scientific data, resistance to constant calls for new data becomes a vital strategy. by putting the data into context, public health and communication experts try to "get the message through" without creating panic or giving the media reason for alarmist reporting. staying informed and the need to be the first ones to know is achieved through ever more sophisticated surveillance systems. at times, the new systems turn around the relationship between those who seek information and those who provide information: by registering for any cdc alert service or calling the hotline, cdc gets crucial information about emerging health-related worries and its whereabouts in real time. the latter practice of creating more sophisticated surveillance systems feeds back into general pandemic anxiety. the more early detection tools are installed, the more instances of worrying information will be gathered. this in turn contributes to calls for constant vigilance that are met with further securitisation efforts. it is difficult to say whether this is necessarily a "vicious cycle". taking the view from within cdc, securitisation has brought about changes for better and worse. being more attuned to the need for real-time data and the need to be constantly aware of emerging threats is certainly nothing that troubles public health experts and scientists as such. as one respondent phrased it: "preparing for the worst is a good thing to do and nothing that should be incriminated . . . [it]'s part of the job, always foreshadowing what could happen but without being sensational . . . [the problem is], in the ensuing discussion, hindsight seems to be more important than good decision-making." however, as we have more and better technologies at hand that help us to become aware of harmful emerging ecologies such as the changing territories of new infectious diseases, it is very likely that the chain of pandemic anxiety events proliferates and intensifies. promoting a critical understanding of how pandemic anxieties work can help in evaluating their importance. historically, slower modes of detection meant that awareness of the emerging threat was perhaps closely related to actual fatalities. nowadays, we are already aware of the potential threat before we have seen what course it will take. under these circumstances, pandemic anxieties are more and more likely to be based on anticipating the characteristics of the new pathogen rather than actual disease and deaths. thus, the new powers derived from rapid detection technologies need to be critically appraised since we have not yet developed a pragmatic culture of living with constant emergency. who.int/en/what-we-do/health-topics/diseases-and-conditions/influenza/pandemicinfluenza/about-pandemic-phases, accessed july ). biosecurity: spaces, practices, and boundaries biopolitics and the molecularization of life public prophylaxis: pandemic influenza, pharmaceutical prevention and participatory governance swine influenza a (h n ) infection in two children-southern california outbreak of swine-origin influenza a (h n ) virus infection-mexico reflections on the uk's approach to the swine flu pandemic: conflicts between national government and the local management of the public health response biosecurity: towards an anthropology of the contemporary london: earthscan cste (council of state and territorial epidemiologists) ( ) national reporting for initial detections of novel influenza a viruses. council of state and territorial epidemiologists position statement cambridge: polity dawood f, jain s, finelli l et al; novel swine-origin influenza a (h n ) virus investigation team ( ) emergence of a novel swine-origin influenza a (h n ) virus in humans toward the medicalization of insecurity. cambridge: polity farmer p ( ) infections and inequalities. the modern plagues biosecurity in the global age: biological weapons, public health, and the rule of law towards a sane and rational approach to management of influenza h n influenza a (h n ) and pandemic preparedness under the rule of international law securing life: the emerging practices of biosecurity aldershot: ashgate institute of medicine ( ) emerging infections: microbial threats to health in the united states anxiety as social practice c the author. antipode c antipode foundation ltd multiculturalism, racism and infectious disease in the global city: the experience of the sars outbreak in toronto dangerous fragments security, disease, commerce: ideologies of post-colonial global health the influence of anxiety: september , bioterrorism, and american public health the scale politics of emerging diseases two regimes of global health novel swine-origin influenza a virus in humans: another pandemic knocking at the door the site of the social: a philosophical account of the constitution of social life and change swine-origin influenza triple-reassortant swine influenza a (h ) in humans in the united states from global flu to global health swine flu c the author. antipode c antipode foundation ltd many thanks to the people at cdc who were kind enough to show me around and answer my questions; the editor rachel pain for her motivation and patience; and the four anonymous reviewers for their insightful comments. the research was made possible by generous support from dfg (german research foundation). key: cord- - kcygis authors: restauri, nicole; sheridanmd, alison d. title: burnout and ptsd in the covid- pandemic: intersection, impact and interventions date: - - journal: j am coll radiol doi: . /j.jacr. . . sha: doc_id: cord_uid: kcygis summary sentence individual physicians and hospital administration should take proactive steps to minimize the compounding effects of high baseline burnout and the acute stressors of the covid- pandemic in order to promote wellness among health-care providers. the covid - pandemic has posed unprecedented challenges to the healthcare system worldwide while revealing major deficiencies in this country's epidemic preparedness. individuals have been required to drastically modify their lifestyle in an effort to "flatten the curve" and engage in social distancing in order to allow an overwhelmed healthcare system time to respond to the novel coronavirus. in healthcare, this circumstance is so profound that the covid- pandemic has required an adoption of the language of war. there is talk of physician redeployment to the frontline and sophisticated statistics track daily causalities while military style temporary hospitals are constructed. the cable news network (cnn) has compared the epidemic's impact on our civilization to that of wwii ( ) . in their personal lives, radiologists are required to adapt to the myriad challenges imposed by the pandemic while also managing the stresses related to caring for patients with covid- and working in a healthcare system with limited resources while evaluating constantly evolving knowledge surrounding containment and management of the covid- illness. this pandemic has exacerbated stressors in a healthcare system in which physician burnout, a response to workplace stress, is already epidemic ( ) . individual physicians and hospital administration should take proactive steps to minimize the compounding effects of high baseline physician burnout with the acute stressors of the covid- pandemic. although post traumatic stress disorder (ptsd) is commonly associated with active military conflict, the context and definition of what constitutes a traumatic event is, in fact, much broader and is relevant to the covid- pandemic and it's impact on radiologists. this paper presents a conceptual paradigm for understanding the relationship between burnout, acute stress disorder and ptsd while providing an evidence based review and recommendations for systems based interventions that may reduce provider suffering and stress ensuring a stable, healthy radiology workforce. mental health providers define "trauma" as a stressful occurrence that is outside the range of the usual human experience and that would be markedly distressing to almost anyone ( ) . this type of stressor, according to the dsm iv, involves a perceived intense threat to life, physical integrity, intense fear, helplessness or horror ( ) . by this definition, the covid- pandemic and the collective and personal threats and fear that it has produced, meets the definition of a traumatic event. exposure to such traumatic events can lead to the development of acute stress disorder (asd) and finally ptsd if symptoms persist. similarly, burnout is a syndrome driven by increased exposure to workplace stressors that results in emotional exhaustion, depersonalization and a decreased sense of personal accomplishment ( ). in a , a study by shanefelt et al, a survey using the maslach burnout inventory, found the rate of radiologist burnout to be % ( ) . in this regard, the covid- pandemic presents a sort of perfect storm regarding the intersection of chronic workplace stress resulting in a epidemic physician burnout rates with the acute traumatic stress imposed by the pandemic. exploring the intersection of these two phenomena is necessary in order to inform interventions. symptoms related to ptsd fall into three categories that include: reliving the event, a sense of emotional numbness/depersonalization, and symptoms of increased arousal (difficulty sleeping, feeling irritated or easily angered, difficulty concentrating). the diagnosis of ptsd occurs when a person has experienced symptoms for at least month following a traumatic event, although symptoms may be delayed by several years. ( ) . in the initial month following exposure to a traumatic event, the diagnosis applied is acute stress disorder (asd) and includes symptoms of intrusion, dissociation, negative mood, avoidance, and arousal. the prevalence of asd is - % following a traumatic event ( ) . importantly, intervention in this early phase can reduce the progression to ptsd ( ) . increased exposure to stress and trauma in multiple life domains, including acutely increased workplace stress resulting from the pandemic, when combined with underlying baseline burnout; may result in rising rates of ptsd among physicians. additionally, as there is significant overlap in drivers of both ptsd and burnout, as well as consequences and comorbidities, the intersection of these entities may have a compounding effect (table ) . for example, lack of control over one's schedule is a known driver of burnout that may acutely worsen for individual radiologists as hospital administration responds to changes in imaging volume and economic consequences by redefining work hours, staffing and clinical responsibilities. many radiologists also face the threat of redeployment to understaffed fields of medicine taxed by the pandemic providing an example of the way in which another known driver of burnoutimbalance between skillset and work demands-may be exacerbated by the pandemic. theoretically, and in a worse case scenario, if these workplace stressors were combined with the added loss of control and sense of displacement that may arise if a radiologist were exposed to or contracted covid- and chose to quarantine away from home and family, the mental health consequences could be devastating. large-scale disasters are associated with significant increases in mental health disorders in both the immediate aftermath of the trauma and over longer periods of time with increased rates of ptsd, depression and substance abuse disorders reported ( ) . similarly, burnout is associated with higher rates of substance abuse, depression and suicide ( ) . those studies that specifically before addressing appropriate systems based responses to such stressors, it is important to also consider the role that racism may play with regard to increased ptsd susceptibility among minority healthcare providers in response to the covid- colleges (aamc) found that . % of physicians in the united states self-identified as ethnic asian ( ) . many minority groups experience higher rates of ptsd when compared with white populations and one theory for this vulnerability focuses on the traumatic nature of racism ( ) . on may , , the united nations secretary general warned against xenophobia and anti-asian sentiment, stating, "the pandemic continues to unleash a tsunami of hate and xenophobia, scapegoating and scare-mongering" and advised governments to "act now to strengthen the immunity of our societies against the virus of hate" ( ) . there is, unfortunately, an abundance of historical precedent for minority discrimination related to epidemics and pandemics. examples include violent pogroms against the jewish community during the black death ( - ) and, in recent history, discrimination in response to hiv/aids pandemic ( ) . historians cite "the newness and mysteriousness of a disease" as a predisposing factor for igniting racial violence and minority scapegoating and these elements certainly apply to the current state of the covid- pandemic underscoring the potential of this pandemic to incite racism ( ) . it is critical that radiology leadership maintain a zero tolerance policy regarding workplace discrimination while also committing to support strong diversity training programs and efforts that focus on humanism and tolerance. the impact of ptsd among healthcare workers on patient care has not been widely studied in radiologists. however, there is evidence that among those with symptoms of ptsd, burnout is also highly prevalent and a recent meta-analysis identified physician burnout as significantly and positively correlated with increased medical error ( , ) . physician burnout is costly, and not only in terms of the risk of medical error. the syndrome of burnout is associated with increased risk of physician suicide as well as substance abuse and may contribute to healthcare infrastructure instability by fostering increased turnover, early retirement and decrease in percent of professional effort; consequences certainly undesirable in the setting of a pandemic requiring increased healthcare resources and reserves ( , ) . previous conceptual models related to mitigating physician burnout focus on individual as well as systems based interventions and suggest that responsibility for maintaining a healthy physician work force lies, not only with individual physicians, but with hospital administration and department leadership ( ) . therefore both individual strategies and systems based interventions should be adopted in these challenging times ( ) . recent recommendations to improve individual radiologists well-being in the setting of the covid- pandemic have suggested "micropractices", or strategies requiring just a few seconds that are readily available to individual physicians in order to manage stress. these practices focus on managing the emotional aspects of stress and fear and leverage positive psychology, mindfulness practices and embodiment to combat the fight or flight response as well as emotional exhaustion and depersonalization ( ) . similar interventions, including mindfulness and gratitude practices, have been successful in the setting of ptsd ( , , ) . the american college of radiology (acr) radiology well-being program has compiled an on-line collection of resources to promote radiologist wellness during the covid- pandemic and site contains direct links to resources focusing on the arts, mindfulness, fitness and sleep ( ) . an additional important and potentially overlooked well-being practice involves limiting ones exposure to media coverage of the pandemic. one study found that those individuals with repeated related medial exposure following the boston marathon bombing reported experiencing higher levels of acute stress than those present during the actual event ( ) . while individual action steps are certainly required to promote resilience and well-being during this time of crisis, an appropriate and informed response from the healthcare system and radiology leadership will also be required. interestingly, the incidence of ptsd in healthcare workers following the sars pandemic positively correlated with the perceived risk of exposure and was negatively associated with provider identification with their work as altruistic ( ) . these are important factors that may be considered in informing the allocation of department resources and efforts to minimize physician burnout and ptsd. a frame work of suggested interventions to prevent burnout and treat ptsd in the radiology workforce are outlined below and in table and figure . in addition to promoting those individual based interventions discussed above, radiology leadership should direct departmental resources toward creating a physically safe work environment and support the development of an infrastructure that allows radiologists and staff to work from home. this specific strategy is in line with many public health policies promoting containment and individual well-being such as the "safer at home" policy, advocated by the government of the state of colorado ( ) . the capacity to work from home is an advantage of the digital era and may have a positive impact on radiologist mental as well as physical health. for example, a workplace centered at home mitigates several previously outlined sources of physician anxieties related to the pandemic, including concerns about bringing the virus home to family, stress regarding the impact that contracting the virus may have on family resources, while helping those who may be vulnerable, such as single parents or households where both parents work, cope with child-care requirements ( ) . additionally, maintaining a healthy radiologist workforce in the setting of a pandemic requires the type of social distancing that can only be maximized with home quarantine. therefore, developing an infrastructure whereby radiologists may care for patients directly from home is an asset that will support radiologist personal and family needs in myriad unforeseen ways in the era of covid- and should be a key component of future pandemic preparedness. creating a work environment and culture where mental illness is not stigmatized may be challenging, but it is a critical step in establishing policies and practices whereby physicians are enabled to cura te ipsum, "heal themselves" ( ) developing psycho-educational seminars on the symptoms of ptsd and burnout with direction to the appropriate resources may be an essential first-step for those who are affected but might not recognize the illness or symptoms in themselves. additional efforts that may contribute to a culture where burnout and mental illness is not stigmatized may involve coordinating expert panel discussions on stress and ptsd, allowing dedicated time away from work to attend to mental health appointments and, in unprecedented times, considering non-traditional methods of physician engagement. for example, the field of narrative medicine leverages the arts and humanities as well as reflective writing exercises that allow healthcare providers the time and space necessary to access emotions and process experiences in a structured manner ( ) . this contemplative environment facilitates cognitive reframing and self-compassion while helping to solidify professional identity and reinforce a sense of altruism at work, a factor previously shown to be protective from ptsd following a pandemic ( ) . and this should be a conversation with both value and time given to the voice of those with "boots on the ground" knowledge. in order to optimize high performing teams in the workplace, a culture of psychological safety is a pre-requisite and key components of psychological safety include trusting that one will not be punished for making a mistake or speaking one's mind ( ) . finally, responding to the covid- pandemic may be a time to recognize diverse personnel as a resource in the department. radiology leadership may ask to hear from voices of those that may have worked through prior natural disasters, such as hurricane katrina or the world trade center terrorist attacks, when creating policy and procedure. these perspectives may add elements of both wisdom and hope to those of us navigating the complex uncharted territory of this pandemic. as much as social distancing is being leveraged as a critical method of covid- disease containment, both individual and system based practices will be required to reduce workplace stress and burnout and minimize the acute stress response and risk of subsequent ptsd. the mental health consequences for physicians related to this pandemic may be significant given the common drivers of burnout and ptsd and the high rate of underlying burnout among radiologists ( ) . as the covid- pandemic has highlighted, the healthcare system in the united states is marred by imperfections. taking good care of the physical as well as mental wellbeing of physicians on the frontline of the covid- pandemic should not be among them. support an infrastructure that allows radiologists and staff to work from home decrease exposure and mitigate concerns about contracting the virus and promotes schedule flexibility increase education treatment about burnout, asd, and ptsd, via expert panel discussions and access to mental health increase awareness and early intervention, reduce stigma employ non-traditional methods of physician engagement (eg narrative medicine) facilitates cognitive reframing and self-compassion, reinforce a sense of altruism in work clear communication from leadership increase sense of safety and stability, increase team work engage radiologists in scheduling increase engagement and prevent burnout, promotes schedule flexibility virus confronts leader's with one of modern history's gravest challenges association between physician burnout and patient safety, professionalism, and patient satisfaction: a systematic review and meta-analysis post traumatic stress disorder: the management of ptsd in adults and children in primary and secondary care controlled interventions to reduce burnout in physicians: a systematic review and meta-analysis burnout among u.s. medical students, residents, and early career physicians relative to the general u.s. population uptodate: acute stress disorder in adults: epidemiology, pathogenesis, clinical manifestations, course, and diagnosis the mental health consequences of covid- and physical distancing: the need for prevention and early intervention the psychological impact of the sars epidemic on hospital employees in china: exposure, risk perception, and altruistic acceptance of risk center for disease control and prevention (cdc): severe acute respiratory syndrome(sars). sars basic fact sheet case of coronavirus (covid- ) in the u understanding and addressing sources of anxiety among health care professionals during the covid- pandemic association of american medical colleges: diversity in facts and figures assessing racial trauma within a dsm- framework: the uconn racial/ethnic stress & trauma survey national action plans needed to counter intolerance pandemics: waves of disease, waves of hate from the plague of athens to aids the prevalence and impact of post -traumatic stress disorder and burnout syndrome in nurses executive leadership and physician well-being: nine organizational strategies to promote enagement and reduce burnout coronavirus disease (covid- ) and beyond: micropractices for burnout prevention and emotional wellness fessell gratitude and ptsd symptoms among israeli youth exposed to missile attacks: examining the mediation of positive and negative affect and life satisfaction a meta-analytic investigation of the impact of mindfulness-based interventions on post traumatic stress the american college of radiology (acr) radiology well-being program: combatting the covid- pandemic: a collection of well-being resources for radiologists boston marathon bombings, media, and acute sress physician heal thyself: meaning and origin narrative medicine: a model for empathy, reflection, profession and trust high performing teams need psychological safety. here's how to create it figure : a system based model for minimizing physician workplace stress and promoting policies that simultaneously minimize burnout and acute stress disorder (asd) while decreasing the risk of subsequent post-traumatic stress disorder key: cord- - ofgekoj authors: donthu, naveen; gustafsson, anders title: effects of covid- on business and research date: - - journal: j bus res doi: . /j.jbusres. . . sha: doc_id: cord_uid: ofgekoj abstract the covid- outbreak is a sharp reminder that pandemics, like other rarely occurring catastrophes, have happened in the past and will continue to happen in the future. even if we cannot prevent dangerous viruses from emerging, we should prepare to dampen their effects on society. the current outbreak has had severe economic consequences across the globe, and it does not look like any country will be unaffected. this not only has consequences for the economy; all of society is affected, which has led to dramatic changes in how businesses act and consumers behave. this special issue is a global effort to address some of the pandemic-related issues affecting society. in total, there are papers that cover different industry sectors (e.g., tourism, retail, higher education), changes in consumer behavior and businesses, ethical issues, and aspects related to employees and leadership. there has been a long history of fear of pandemic outbreaks. the discussion has not focused on whether there will be an outbreak, but when new outbreaks will happen (stöhr & esvald, ) . the events leading to influenza pandemics are recurring biological phenomena and cannot realistically be prevented. pandemics seem to occur at - -year intervals as a result of the emergence of new virus subtypes from virus re-assortment (potter, ) . as the global population increases and we need to live closer to animals, it is likely that the transfer of new viruses to the human population will occur even more frequently. all our society can do is take preventive measures so that we are able to act quickly once we suspect an outbreak. we should also make an effort to learn from the consequences of pandemic outbreaks to prepare our societies for if-and, more likely, when-this happens again. as we are in the middle of a pandemic outbreak, it is very difficult to estimate its longterm effects. although society has been hit by several pandemics in the past, it is difficult to estimate the long-term economic, behavioral, or societal consequences as these aspects have not been studied to a great extent in the past. the limited studies that do exist indicate that the major historical pandemics of the last millennium have typically been associated with subsequent low returns on assets (jorda, singh, & taylor, ) . for a period after a pandemic, we tend to become less interested in investing and more interested in saving our capital, resulting in reduced economic growth. given the current situation, in which saving capital means negative returns, it is not at all certain that we will be as conservative as we have been in the past. behavioral changes related to pandemic outbreaks seem to be connected with personal protection (funk, gilad, watkins, & jansen, ), such as the use of face masks, rather than general behavior changes. our lives, as humans in a modern society, seem to be more centered around convenience than around worrying about what might happen in the future. on a societal level, we seem to be completely unprepared for large-scale of outbreaks. our societies are more open than ever; we rely on the importing of important products, such as food, energy, and medical equipment, rather than sourcing them from close to where they are needed; and there are limited efforts to prepare for pandemic outbreaks. the guiding principle of our society seems to be efficiency and economic gain rather than safety. this may change after the current outbreak. it is also important to point out that the principles (eg. openness and global trade) on which society is based have lifted a large number of countries around the globe out of poverty and produced well-developed economies. it is not unlikely that our societies will backoff some of them leading to more poverty in the world. the covid- pandemic outbreak has forced many businesses to close, leading to an unprecedented disruption of commerce in most industry sectors. retailers and brands face many short-term challenges, such as those related to health and safety, the supply chain, the workforce, cash flow, consumer demand, sales, and marketing. however, successfully navigating these challenges will not guarantee a promising future, or any future at all. this is because once we get through this pandemic, we will emerge in a very different world compared to the one before the outbreak. many markets, especially in the fields of tourism and hospitality, no longer exist. all organizational functions are intended to prioritize and optimize spending or postpone tasks that will not bring value in the current environment. companies, especially start-ups, have implemented an indefinite hiring freeze. at the same time, online communication, online entertainment, and online shopping are seeing unprecedented growth. as research indicates that pandemics are reoccurring events, it is very likely that we will see another outbreak in our lifetime. it is apparent to anyone that the current pandemic has had enormous-but hopefully short-term-effects on all our lives. countries have closed their borders, limited the movement of their citizens, and even confined citizens in quarantine within their homes for weeks. this is a rather unique occurrence, as we are used to freedom of movement, but in the midst of the pandemic outbreak, people have been fined just for being outside. although our societies seem to be very accepting of these limitations and condemn people that do not follow the rules, but we need to ask ourselves how this will affect the views of our society (e.g., views regarding freedom, healthcare, government intervention). we should also be aware that infrastructure and routines to monitor citizens in order to limit the spread of the virus have been rolled out, and so we should ask ourselves how accepting we will be of monitoring in the future. we must realize that once these systems are in place, it is highly unlikely that they will be rolled back. furthermore, in some countries, the ruling politicians have taken advantage of this situation and increased their control over the state, suppressing opposing opinions and thus jeopardizing democratic systems. some of the worst examples are turkmenistan, which has banned the use of the word "corona," and hungary, which is letting viktor orbán rule by decree indefinitely. as previously mentioned, people have been confined to their homes. there has also been a constant stream of news on this invisible external threat from which we cannot protect ourselves. we have been occupied trying to figure out how best to protect ourselves and our loved ones. on top of that, many feel pressure due to losing their jobs or due to working in close proximity to potentially infected people, as society depends on them fulfilling their duty. the consequences of the pandemic outbreak have hit various sectors of society in different ways. people that are working in sectors connected to healthcare must endure endless tasks and very long working days. additionally, people are losing their jobs at rates we have not seen since the great depression of the s. the sectors that have seen the largest increases in unemployment are those that are hedonic in nature and require the physical presence of the customer (e.g., hospitality, tourism, and entertainment), as demand for these services has ceased to exist. the employees in these sectors tend to be younger and female. past experience also indicates that once someone is outside the job market, it is very difficult to get back in as they will face more competition that may be more competent. all countries that can are trying to stimulate their economies to keep as much as possible of their necessary infrastructure intact and to keep citizens productive or ready to become productive once the pandemic has been overcome. in order to keep society from deteriorating, people not only need jobs or a way to support themselves but also need access to what they view as necessary products and services. if this infrastructure does not exist, people start to behave in what is considered uncivil behavior (e.g., hording or looting). countries around the globe have adopted very different approaches to handle the current stress on the job markets and infrastructure. some countries have chosen to support businesses in order to help them keep the workforce intact, but others with less financial strength cannot do the same. countries also have directly supported their citizens in various ways. there is an enormous body of rich information that researchers can collect to determine the best approaches for when when and if a major disaster happens in the future. around the globe, societies are in lockdown, and citizens are asked to respect social distance and stay at home. as we are social beings, isolation may be harmful for us (cacioppo & hawkley, ). feelings of loneliness have, among other things, been connected to poorer cognitive performance, negativity, depression, and sensitivity to social threats. there are indications that this is happening during the current pandemic, as there has been an increase in domestic violence, quarrels among neighbors, and an increase in the sales of firearms (campbell, ) . however, we have also seen an increase in other, more positive types of behavior caused by social distancing that have not been researched. people have started to nest, develop new skills, and take better care of where they live. for instance, they may learn how to bake, try to get fit, do a puzzle, or read more. there has also been an increase in purchases of cleaning products, and more trash is being recycled. at the same time, we are eating more junk food and cleaning ourselves less. people are also stockpiling essentials, panic buying, and escaping to rural areas. this is an indication that what is happening to us and our behaviors is complex, and it would be interesting to study this phenomenon further. another consequence of the lockdowns is the extreme increase in the usage of internet and social media. previous research has indicated that humans who feel lonely tend to use social media more and, in some cases, even prefer social media over physical interaction (nowland, necka, & cacioppo, ) . social media also may bring out the worst in us through trolling or sharing of fake news. this is, to some degree, not as damaging as the "real life" is lived in the physical world and the internet is an "add on" with, in most cases, limited impact on the physical world. by this, we are able to compartmentalize and distinguish what matters and what does not matter. however, the current situation has made social media the main mode of contacting or socializing with others. in many cases, the internet is at present also the main way to get essential supplies and receive essential services, like seeing a doctor. the question, then, is what happens to us when the "real life" is lived online and becomes a way to escape the physical world? as humans, we rely to a large degree on our senses; we are built to use them in all situations of life. thus, we rely on them heavily when making decisions. however, the current isolation is depriving us of our senses, as we are not exposed to as many stimuli as normal situation. thus, we are, in a sense, being deprived of stimulation. we are also being told by authorities not to use our senses; we should not touch anything, wear a mask, or get close to other humans. thus, what happens once our societies open up? how long will this fear of using our senses linger, and will we be over-cautious for a while or may we try to compensate as we have to some degree been deprived of using them? these are just some aspects of consumer behavior; many more are covered by this special issue. the covid- outbreak is likely to cause bankruptcy for many well-known brands in many industries as consumers stay at home and economies are shut down (tucker, ) . in the us, famous companies such as sears, jcpenney, neiman marcus, hertz, and j. crew are under enormous financial pressure. the travel industry is deeply affected; % of hotel rooms are empty (asmelash & cooper, ) , airlines cut their workforce by %, and tourism destinations are likely to see no profits in . furthermore, expos, conferences, sporting events, and other large gatherings as well as cultural establishments such as galleries and museums have been abruptly called off. consulting in general and personal services, like hairdressers, gyms, and taxis, have also come to a standstill due to lockdowns. finally, important industries like the car, truck, and electronics industries have abruptly closed (although they started to open up two months after their closure). there are an endless number of questions we could ask ourselves in connection to this rather abrupt close-down. for instance, how do we take care of employees in such situations? why are companies not better prepared to handle such situations (e.g., putting aside earnings or thinking of alternative sources of income)? how are the companies and even countries using the current situation to enhance their competitive situation? one of the countries that seem to be using the situation is china that is buying european based infrastructure and technology (rapoza, ) . while some businesses are struggling, some businesses are thriving. this is true for a number of internet-based businesses, such as those related to online entertainment, food delivery, online shopping, online education, and solutions for remote work. people have also changed their consumption patterns, increasing the demand for takeout, snacks, and alcohol as well as cleaning products as we spend more time in our homes. other industries that are doing well are those related to healthcare and medication as well as herbs and vitamins. typically, when studying markets, it is assumed that they are static, a natural conclusion since they tend to change slowly. however, if there is one thing the covid- outbreak has shown us, it is that markets are dynamic (jaworski, kohli, & sahay, ) and can move rapidly. furthermore, a market is not just a firm; it is a network of actors (i.e., firms, customers, public organizations) acting in accordance with a set of norms. these systems are sometimes referred to as dynamic ecosystems that exist to generate value (vargo & lusch, ) . the covid- outbreak poses a unique opportunity to study how markets are created and how they disappear within a very limited time span. it would also be interesting to explore whether the disappearance of one solution for a market may be replaced by another (e.g., combustion engines for electric or physical teaching for online teaching). based on past experiences, we have become more conservative and protective after a pandemic outbreak. we save resources in order to be prepared if the unthinkable happens again. countries are starting to stockpile things like food, equipment, and medicine or prepare to produce them locally. it is also essential for larger global firms to have reliable supply chains that do not break. consequently, it is very likely that this pandemic will make these firms rethink their supply chains and, probably, move supply chains closer to where they are needed in order to avoid stopping production in the future. furthermore, authorities have implied that other humans from other countries are dangerous as they may carry the virus. a closed border implies that the threat is from the outside. in addition, international flights are not likely to be an option for many in the coming years. together, these circumstances mean that countries may become more nationalistic and less globalized. this may be a dangerous development, as long-term protection from the consequences of a pandemic outbreak is likely to require global effort and sharing of resources. such cooperation is also key to tackle other global challenges that we may face in the future. in this special issue, we have invited scholars from different areas of business and management to write brief papers on various aspects of the effects of the covid- pandemic. in total, there are articles in the special issue, which are summarized below. the first contribution, by jagdish sheth, is titled "impact of covid- on consumer behavior: will the old habits return or die?" it explores how the current pandemic has affected several aspects of consumers' lives, ranging from personal mobility to retail shopping, attendance at major life events like marriage ceremonies, having children, and relocation. the author investigates four contexts of construed consumer behavior, namely social context, technology, coworking spaces, and natural disasters. additionally, the author foresees eight immediate effects of the pandemic on consumer behavior and consumption. hoarding-the mad scramble observed at the start of the covid- outbreak-applies not only to consumers but also to unauthorized middlemen who buy products in excess to sell at increased prices. consumers learn to adapt quickly and take an improvised approach to overcome constraints that have been imposed by governments. pent-up demand may lead to a significant rebound in sales of durable products, like automobiles, houses, and large appliances, and some of the realities of covid- will put consumers in a buying mood soon. embracement of digital technology, either through online services or information-sharing platforms like zoom, has kept people connected around the world. digital savviness will become a necessity, rather than an alternative, for schools, businesses, and healthcare providers. with the onset of lockdowns in many countries, online shopping, including grocery shopping, has become more prevalent. the desire to do everything in-home has impacted consumers' impulse buying habits. slowly but surely, work-life boundaries will be blurred when both tasks are carried out from home. there should be efforts to compartmentalize the two tasks to make this a more efficient way of life. reunions with friends and family are now restricted to digital interactions, especially for people who work and live away from their families. we can expect a dramatic change in consumers' behavior because of sophisticated technology. in addition, consumers may discover new talents as they spend less time on the road and more at home. they may experiment with cooking, learn new skills, and, soon, become producers with commercial possibilities. in the end, most consumer's habits will return to normal, while some habits may die due to adaptation to the new norm. forecasting and overcoming pandemics, global warming, corruption, civil rights violations, misogyny, income inequality, and guns," written by arch g. woodside, discusses whether there is an association between public health interventions, national and state/provincial governments interventions, and improved control of the covid- outbreak in certain countries. the paper suggests "ultimate broadening of the concept of marketing" in order to design and implement interventions in public laws and policy, national and local regulations, and the everyday lives of individuals. it also lays out effective mitigating strategies by examining designs, implementations, and outcomes of covid- interventions by examining deaths as a natural experiment. while covid- eradication intervention tests are being run for promising vaccines, these are considered true experiments, and analyzing the data from these interventions may involve examination of the success of each vaccine for different demographic subgroups in treatment and placebo groups in randomized control trials. comparing the designs and impact of the current covid- mitigation interventions across nations and states within the u.s. provides useful information for improving these interventions, even though they are not "true experiments." the third contribution, "employee adjustment and well-being in the era of covid- : hatak. they claim that covid- is becoming the accelerator for one of the most drastic workplace transformations in recent years. how we work, socialize, shop, learn, communicate, and, of course, where we work will be changed forever. person-environment (p-e) fit theories highlight that employee-environment value congruence is important because values influence outcomes through motivation. however, given the current environment, in which the fulfillment of needs and desires like greater satisfaction, higher engagement, and overall well-being is drastically altered, there is an increased likelihood of misfits working in organizations. in response to this, organizations need to use virtual forms of recruitment, training, and socialization in lieu of face-to-face interactions. increasing job autonomy will alleviate the family-related challenges that may arise within remote work environments by providing employees with the right resources to manage conflicting work and family demands. human resource leaders within the organization must enhance relationship-oriented human resources systems in order to combat the risk of unforeseen and prolonged isolation among single, independent employees and to better prepare them for situations like the current crisis. the field of entrepreneurship can offer insights that can be adapted by organizations coping with the pandemic. entrepreneurs' struggles are largely caused by the lack of work-related social support in comparison to salaried employees. nevertheless, some entrepreneurs are known to overcome these limitations by leveraging alternative, domain-specific sources of social support, such as positive feedback from customers, which ultimately enhances their well-being. recycling such approaches to identify overlooked or untapped sources of social support is likely to be beneficial for employees given the current work environment dynamic. the fourth contribution, written by hongwei he and lloyd c. harris, is titled "the impact of covid- pandemic on corporate social responsibility and marketing philosophy." the worldwide demand for hand sanitizers, gloves, and other hygiene products has risen because of the covid- pandemic. and, in some countries, there has been a surge in complaints about profiteering and opportunism. as doctors combat the virus, prosecutors are pursuing the opportunistic profiteers who prey on the fearful. many large corporations have a social purpose and set of values that indicate how much they appreciate their customers, employees, and stakeholders. this is the time for these corporations to make good on that commitment. some organizations strive to set great examples. for example, jack ma, the co-founder of alibaba, donated coronavirus test kits and other medical supplies to many countries around the world through the jack ma foundation and alibaba foundation. large corporations have often written off the costs of product failures, restructuring, or acquisitions. when writing off losses due to the coronavirus pandemic, it is understandable to pursue the bond established between the brand and consumer. this gesture can turn out to be more meaningful and lasting than when implemented during "normal" times. on the bright side, the covid- pandemic offers great opportunities for companies to supermarket will reassure them that they are being cared for. fourth, messages that retailers spread online during emergencies need to include information about products' availability on the shelves and at digital outlets; control panic buying by restricting the quantity that customers can purchase; devise and implement protection plans for consumers and employees; contribute to overall public health; and use surveillance measures to limit the spread of the virus. to these ends, retailers need to improve their customer relationship management systems and promote safe interactions with customers (e.g., through online chats with employees) to provide real-time customer assistance. smes in times of crisis," he identifies small-to medium-sized businesses with low or unstable cashflow as particularly vulnerable during crises, as they are currently struggling for profitability. studies reveal the interconnectedness between finance and strategy, particularly entrepreneurial orientation and market orientation in strategies. the paper highlights that a combination of entrepreneurial orientation and market orientation can lead to lean and flexible marketing efforts, which are particularly valuable in times of crisis. in addition, entrepreneurial orientation and market orientation can be combined into an entrepreneurial marketing postdisaster business recovery framework that highlights that seeking opportunities, organizing resources, creating customer value, and accepting risk are markedly different in a post-disaster context. sandeep krishnamurthy contributed with "the future of business education: a commentary in the shadow of the covid- pandemic." the paper highlights that social distancing is prompting educational institutions to rethink how they are connecting with their student bodies. spatial interaction is becoming the new norm, and the blurring of physical and virtual communication is likely to continue until the pandemic is overcome. globally, the higher education system will undergo a decade of radical technology-led transformation, according to the author. the author identified five trends that will revolutionize how we educate after covid- : . the algorithm as professor -rather than taking a traditional route and learning from a human professor in classrooms, students will learn remotely from an algorithm. the aienabled algorithm will provide customized personal learning experiences. students will be able to quickly master rudimentary and routinized tasks. then, the algorithm will prepare them for an in-person experience, where a "warm body" will engage them in socratic dialogue. . the university as a service -traditionally, we have followed a linear formulation of society. students go through k- education, some get an undergraduate degree, and some go on to further studies. however, the current and future environment is too volatile to sustain this educational structure. students will need to learn what they need when they need it. personalized, continuing education will become the norm. . the university as assessment powerhouse -in a world characterized by ai and automation, learning can come from many sources. students will learn from each other, algorithmic systems, and public information. however, universities will continue to have a powerful place as assessors of learning. students will come to universities to gain objective credentials based on powerful assessments of learning. . learning personalization to support diversity -students of the future will have access to multiple pathways to learn the same content. for example, a course may be available through algorithmic engagement, animation/video/augmented reality, face-to-face instruction, or any mixture thereof. using assessment data, the university of the future will be able to pinpoint the learning needs of each student and provide a personalized experience. . problem solving through ethical inquiry -as the influence of artificial intelligence and automation grow exponentially in our lives, there will be a great need for students to become problem solvers through ethical inquiry. clearly, the future will not simply be about what the answers are; it will be about which problems we wish to solve, given what we know. students will need to become more comfortable with the need to evaluate ai algorithms based on their efficacy and their ethical foundation. contribution number ten, "consumer reacting, coping and adapting behaviors in the covid- pandemic," is written by colleen p. kirk and laura s. rifkin. in it, the authors explore numerous consumer insights during a major pandemic outbreak. mainly, they examine consumer behaviors across three phases: reacting (e.g., hoarding and rejecting), coping (e.g., maintaining social connectedness, do-it-yourself behaviors, and changing views of brands), and longer-term adapting (e.g., potentially transformative changes in consumption and individual and social identity). the authors also identify a number of negative aspects of the pandemic that will likely impact consumer behavior. as they state, given the mandatory close quarters people must keep due to stay-at-home requirements, domestic abuse may be on the rise. in addition, throughout history, pandemics provide an excuse for increased racial and anti-immigrant biases. in "how firms in china innovate in covid- crisis? an exploratory study of marketing innovation strategies," written by yonggui wang, aoran hong, xia li, and jia gao, the authors explore how firms in china worked to make their marketing strategies a success. they do so by identifying the typology of firms' marketing innovations based on two dimensions: the motivation for innovations and the level of collaboration in innovations. the authors outline four innovative strategies to combat crises for businesses. the responsive strategy works predominantly for firms that involve physical contact, but it can easily be transferred from offline marketing channels to online channels. a collective strategy can be implemented by firms that are highly affected by the crisis, which need to develop new business by collaborating with other firms during the crisis. a proactive strategy is for firms that are less affected by the covid- crisis (mostly online businesses) to develop new businesses to meet the special demands of existing customers during the covid- crisis. firms that are less affected during the covid- crisis can take an alternative approach: a partnership strategy. firms should usually develop new offerings through collaboration with other firms. professors amalesh sharma, anirban adhikary, and sourav bikash borah contributed with "covid- impact on supply chain decisions: strategic insights for nasdaq firms using twitter data." during black swan events like the covid- pandemic, which may have severe long-term consequences, a deep understanding of business risks can help organizations establish the right plan. in this article, the authors identified supply chain challenges faced by companies using their twitter data. to develop insights from the findings, the authors constructed unigrams, bigrams, and trigrams that revealed the supply-chain-related aspects that gain attention on twitter. a topic analysis was performed to identify keywords used in discussions about covid- . the obtained insights show that the greatest challenge for the organizations was accessing realistic customer demands. a pandemic may increase or decrease demand for specific products, making estimation of realistic final customer demand more difficult and more urgent to address. some user accounts suggested that organizations are still lacking in terms of technological readiness and that companies are looking to gain visibility across value chains. there are growing discussions about building supply chain resilience by identifying risks. many organizations are not only focusing on social sustainability but also turning their attention toward environmental sustainability. to deal with the challenges brought on by unprecedented times, the leaders of organizations must reimagine and redesign the supply chain; rely on technology such as artificial intelligence, the internet of things, and blockchain in their supply chain designs; and focus on sustainable supply chain. finally, marianna sigala wrote "tourism and covid- : impacts and implications for advancing and resetting industry and research." tourism is experiencing a rapid and steep drop in demand during the covid- pandemic. despite the tourism industry's proven resilience in other unprecedented times, the impact of the current pandemic will likely last longer for international tourism than for other affected industries. however, the tourism industry should not only recover but also reimagine and reform the next normal economic order. currently, there is a lack of research on how crises can alter the industry, how the industry adapts to changes with innovative techniques, and how research that can establish the next norms can be conducted. to study the needs and gaps in research work, the author reviews past and emerging literature to capture its impacts and impart some ideas from different research fields that will allow tourism to grow and evolve. nearly % of hotel rooms in the us are empty, according to new data perceived social isolation and cognition an increasing risk of family violence during the covid- pandemic: strengthening community collaborations to save lives the spread of awareness and its impact on epidemic outbreaks market-driven versus driving markets longer-run economic consequences of pandemics (report no. w ) loneliness and social internet use: pathways to reconnection in a digital world a history of influenza watch out for china buying spree, nato warns will vaccines be available for the next influenza pandemic coronavirus bankruptcy tracker: these major companies are failing amid the shutdown it's all b b… and beyond: toward a systems perspective of the market key: cord- -zszeldfv authors: chang, yu-kai; hung, chiao-ling; timme, sinika; nosrat, sanaz; chu, chien-heng title: exercise behavior and mood during the covid- pandemic in taiwan: lessons for the future date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: zszeldfv the coronavirus disease (covid- ) pandemic and its associated governmental recommendations and restrictions have influenced many aspects of human life, including exercise and mental health. this study aims to explore the influence of covid- on exercise behavior and its impact on mood states, as well as predict changes in exercise behavior during a similar future pandemic in taiwan. a cross-sectional online survey was conducted between april and may (n = ). data on exercise behavior pre and during the pandemic and mood states were collected. a cumulative link model was used to predict changes in exercise frequency during a similar future pandemic by exercise frequency during the pandemic. a linear model was used to predict the influence of exercise frequency before and during the pandemic on mood states during the pandemic. a total of . %, . %, and . % of respondents maintained their exercise intensity, frequency, and duration, respectively, during the pandemic. frequent exercisers are more likely to maintain their exercise frequency during a similar pandemic (p < . ). higher exercise frequencies during the pandemic were associated with better mood states (p < . ). moreover, the effects of prepandemic exercise frequency on mood states are moderated by changes in exercise frequency during the pandemic (p < . ). additionally, maintenance of exercise frequency during a pandemic specifically for frequent exercisers are recommended to preserve mood states. these results may provide evidence for health policies on exercise promotion and mental health before and during a future pandemic. coronavirus disease , generated by severe acute respiratory syndrome coronavirus (sars-cov- ) [ ] , has spread rapidly and globally, with , , confirmed cases and , deaths reported worldwide as of july [ ] after the first case reported in wuhan, china in december [ ] . this crisis, yet, has affected each country differently. taiwan was anticipated to have the second-highest number of cases because of proximity and frequent travels to and from china [ ] . however, learning from severe acute respiratory syndrome (sars), taiwan took speedy responses, proactive deployments, as well as novel strategies to identify and contain the participants were recruited through social media, including facebook, line, instagram, twitter, as well as personal referrals. we did not use any screening questionnaire for underlying psychological conditions to exclude respondents from participating in the survey. no statistical method was used to predetermine the sample size and as many participants as possible were sampled during the time period of global lockdown. a post-hoc power analysis revealed that our sample (n = ) corresponds to the recommendation for sufficient power in linear models [ ] . all participants completed an informed consent before participating in the survey. the participants did not receive any incentive for their participation. additionally, they were able to skip any questions they did not want to answer or stop answering all questions at any point in time. we collected information on the presence of covid- symptoms or a positive diagnosis to exclude these individuals from the analysis. information on age, gender, educational level, income level, and living environment was collected. income was measured with the question "compared with the average income in your country, which one is your household income?" for statistical analysis, the answers "i don't have an income at the moment", "very low income", and "low income" were combined as "low income", "high income", and "very high income" were combined as "high income", and "medium income" stayed the same. in order to demonstrate the unique influence of covid- on human behaviors in taiwan, the presence of governmental pandemic control strategies (i.e., restrictions and recommendations) and the status of recreational facilities (e.g., gyms, clubs, and outdoor facilities) internationally were compared. additionally, participants' compliance with those regulations were presented. exercise frequency during the covid- pandemic was measured with one question on how often people exercised during the pandemic. we defined exercise for participants as any activity they chose to do as their exercise (e.g., workouts at home, running outside, etc...). participants were also informed that any physical activity as part of their occupation must not be included unless they are a professional fitness coach or have a similar profession. for statistical analysis, the answers "never", "once in a while" and " day per week" were combined as " day or less", the answers " days per week" and " days per week" were combined as " - days per week", and " - days per week", and " days per week", and "every day" answers were combined as " days per week or more". exercise frequency before the covid- pandemic was measured and processed in the same format. participants were also asked about their exercise intensity both during and prepandemic, and they could respond by choosing "low", "moderate", "high", or "very high" intensity. the options "high" and "very high" intensities were combined as "high intensity" for the analysis. participants were also asked about their exercise session length during the covid- pandemic compared to prepandemic and could choose between "shorter", "longer", or "they were of about the same duration". mood was measured with items from the profile of mood states (poms; [ ] ). the poms is a heavily used psychometric questionnaire that measures general well-being in the clinical field both with the general population and people with chronic disease, as well as in sport and exercise psychology research [ ] . in this study, participants were asked to report how they felt in the last few days during the pandemic. for this study, we used the -item poms from a german short screening version, which was psychometrically tested using data from a large national and representative sample [ ] . the german items were then matched with the english originals as thoroughly as possible, and then translated from english into traditional chinese by the research group in taiwan. these items allow subscores for "depression/anxiety", "vigor", "fatigue", and "irritability"; however, we only used the total score in our analysis. the higher values on poms indicate more positive mood states. in our study, the -item poms total score achieved an internal consistency (reliability) of cronbach's α = . . mean total scores were calculated if at least items of the scale were answered by the participants. cumulative link models (clm) were employed to analyze which variables were significant predictors of the exercise frequency during a similar pandemic condition. three levels of exercise frequency per week during the pandemic (i.e., " day or less", " - days", " or more days") were predicted by three levels of exercise frequency per week prepandemic (i.e., " day or less", " - days", " or more days") with covariates such as age, gender, and income. a linear model with a priori contrasts was used to analyze the influence of exercise behavior on mood states. this model was run with mood as the numerical response variable and "prepandemic exercise frequency" and "exercise frequency during the pandemic" as categorical predictors (with three levels of " day or less", " - days", " or more days"). we specified a priori contrasts to compare mood scores of different levels of exercise frequency pre and during the covid- pandemic, with exercising " day or less" as the intercept. the significance level was set to α = . . all analyses were performed with r software [ ] and the ordinal package [ ] for cumulative link models. a total of participants filled out the questionnaire in taiwan. we excluded participants who reported either presence of covid- symptoms or diagnosis at the time of this study (n = ). therefore, a total of participants (mean (m) age = . , standard deviation (sd) age = . , . % female) were included in the analysis. descriptive statistics of the participants, including gender distributions, age, educational level, living environment, and income, are summarized in table . participants were also asked about the presence of social restrictions and recommendations and their level of compliance. although participants reported almost no formal restrictions ( . %), . % reported that there were recommendations on social distancing, and the majority ( . %) stated that they did their best to follow these recommendations. this is in contrast to the international data of the irg on covid and exercise project, indicating that the majority of participants ( . %) reported the presence of strict formal restrictions by their governments. participants were also asked about the status of the recreational facilities (e.g., gyms, clubs, outdoor facilities, and parks) where they live. a total of . % reported that the gyms and clubs were closed and only . % reported that the outdoor facilities and parks were closed. this is in contrast with the international data indicating . % reported closures of gyms and clubs, and . % reported closures of outdoor facilities and parks. table provides more detail on this information in taiwan and a comparison with the international data. note: participants were asked: "do you live under any type of socially limiting formal restrictions that were established by your government or regional/local authorities?"; "are there recommendations from governmental, regional, or local authorities regarding 'social distancing' or 'social isolation' where you live?". the results show that . % of participants reported the same exercise frequency, . % reported a decrease in exercise frequency, and . % reported an increase in exercise frequency during the covid- pandemic compared to prepandemic. of those who exercised during the covid- pandemic, . % reported being physically active at similar, . % at lighter, and . % at higher exercise intensities. additionally, . % reported the same exercise duration, . % reported shorter, and . % reported longer exercise duration. this information is presented in figure in more detail. the results show that . % of participants reported the same exercise frequency, . % reported a decrease in exercise frequency, and . % reported an increase in exercise frequency during the covid- pandemic compared to prepandemic. of those who exercised during the covid- pandemic, . % reported being physically active at similar, . % at lighter, and . % at higher exercise intensities. additionally, . % reported the same exercise duration, . % reported shorter, and . % reported longer exercise duration. this information is presented in figure in more detail. a clm was employed to predict changes in exercise frequency during a pandemic from prepandemic exercise frequency for use in future conditions similar to the current pandemic. the results show that those who exercise - days per week before a similar pandemic have a significantly higher probability of maintaining their exercise frequency or do more during such pandemics compared to people who exercise one day or less before a similar pandemic (beta coefficient (b)pre - = . , p < . ). those who exercise four days or more per week before a similar pandemic have a significantly higher probability of maintaining their exercise frequency or do more during such pandemics compared to those who exercise - days per week before a similar pandemic (bpre - = . , p < . ). prepandemic exercise behavior could explain . % of the variance in exercise behavior during a pandemic (r nagelkerke). calculating the category probabilities from the models' prediction and location coefficients, we can see that the majority of the taiwanese will maintain their prepandemic exercise frequency during similar pandemics ( figure ). specifically, the probabilities of maintaining exercise frequency during a similar pandemic for those who exercise one day or less per week, - days per week, and four days or more per week, are . %, . %, and . %, respectively. a clm was employed to predict changes in exercise frequency during a pandemic from prepandemic exercise frequency for use in future conditions similar to the current pandemic. the results show that those who exercise - days per week before a similar pandemic have a significantly higher probability of maintaining their exercise frequency or do more during such pandemics compared to people who exercise one day or less before a similar pandemic (beta coefficient (b) pre - = . , p < . ). those who exercise four days or more per week before a similar pandemic have a significantly higher probability of maintaining their exercise frequency or do more during such pandemics compared to those who exercise - days per week before a similar pandemic (b pre - = . , p < . ). prepandemic exercise behavior could explain . % of the variance in exercise behavior during a pandemic (r nagelkerke ). calculating the category probabilities from the models' prediction and location coefficients, we can see that the majority of the taiwanese will maintain their prepandemic exercise frequency during similar pandemics ( figure ). specifically, the probabilities of maintaining exercise frequency during a similar pandemic for those who exercise one day or less per week, - days per week, and four days or more per week, are . %, . %, and . %, respectively. we also included gender, age, education, and income as covariates in separate models to predict exercise behavior during similar future pandemics. the results show that there was a main effect of age (b age = . , p < . ) for exercise frequency during a pandemic. this means that older individuals are more likely to have higher exercise frequency during similar pandemics compared to younger individuals. there were no significant main effects of gender or education. however, levels of these covariates showed significant interaction effects, meaning that the relationship between exercise behavior before a pandemic and exercise behavior during a pandemic is different for specific predictor levels. specifically, females who exercise one day or less before a pandemic are more likely to stay inactive compared to others (b pre - *female = . , p = . ). additionally, those who have "completed vocational school or college" and exercise one day or less before a pandemic are more likely to increase their exercise frequency during similar pandemics (b pre - *education = - . , p < . ) compared to other respondents. we also included gender, age, education, and income as covariates in separate models to predict exercise behavior during similar future pandemics. the results show that there was a main effect of age (bage = . , p < . ) for exercise frequency during a pandemic. this means that older individuals are more likely to have higher exercise frequency during similar pandemics compared to younger individuals. there were no significant main effects of gender or education. however, levels of these covariates showed significant interaction effects, meaning that the relationship between exercise behavior before a pandemic and exercise behavior during a pandemic is different for specific predictor levels. specifically, females who exercise one day or less before a pandemic are more likely to stay inactive compared to others (bpre - *female = . , p = . ). additionally, those who have "completed vocational school or college" and exercise one day or less before a pandemic are more likely to increase their exercise frequency during similar pandemics (bpre - *education = - . , p < . ) compared to other respondents. finally, income was a significant predictor of exercise frequency during similar pandemics with those reporting a high level of income (compared to the average income level) being more likely to have higher exercise frequency compared to those with low levels of income (bincomehigh = . , p = . ). however, when taking prepandemic exercise frequency into account, income is no longer a significant predictor of exercise frequency during a pandemic (bincomehigh = . , p = . ). importantly, prepandemic exercise frequency remained a significant predictor of exercise frequency in all models when controlling for possible covariates. complete statistical results can be seen in table . finally, income was a significant predictor of exercise frequency during similar pandemics with those reporting a high level of income (compared to the average income level) being more likely to have higher exercise frequency compared to those with low levels of income (b incomehigh = . , p = . ). however, when taking prepandemic exercise frequency into account, income is no longer a significant predictor of exercise frequency during a pandemic (b incomehigh = . , p = . ). importantly, prepandemic exercise frequency remained a significant predictor of exercise frequency in all models when controlling for possible covariates. complete statistical results can be seen in table . note: prepandemic exercise levels: = " day or less"; = " - days"; = " days or more". education levels: = "doctoral degree", = "master's degree", = "some graduate school", = "completed vocational school or college", = "some vocational school or college", = "high school graduate or ged", = "less than high school. in this analysis, the mood state was predicted by both prepandemic exercise frequency and exercise frequency during the covid- pandemic. the results show that there was a significant main effect of exercise frequency during the pandemic on mood states. those who exercised four days or more had significantly higher mood states compared to those who exercised for - days (b during - = . , p = . ), and those exercised for - days had significantly higher mood states compared to those who exercised one day or less per week during the pandemic (b during - = . , p < . ). there was also a significant main effect of prepandemic exercise frequency on mood states. specifically, those who exercised four days or more per week prepandemic had a significantly lower mood state during the pandemic, compared to those who exercised for - days per week prepandemic (b pre - = − . , p = . ). however, there was a significant interaction effect on exercise frequency levels during the pandemic × prepandemic exercise frequency levels on mood (b pre*during = − . - . , p = . - . ). meaning, the effects of prepandemic exercise frequency on mood were dependent on exercise frequency during the pandemic (figure ). table summarizes the complete statistical results. exercisepre - × income high − . ( . ) . note: prepandemic exercise levels: = " day or less"; = " - days"; = " days or more". education levels: = "doctoral degree", = "master's degree", = "some graduate school", = "completed vocational school or college", = "some vocational school or college", = "high school graduate or ged", = "less than high school. in this analysis, the mood state was predicted by both prepandemic exercise frequency and exercise frequency during the covid- pandemic. the results show that there was a significant main effect of exercise frequency during the pandemic on mood states. those who exercised four days or more had significantly higher mood states compared to those who exercised for - days (bduring - = . , p = . ), and those exercised for - days had significantly higher mood states compared to those who exercised one day or less per week during the pandemic (bduring - = . , p < . ). there was also a significant main effect of prepandemic exercise frequency on mood states. specifically, those who exercised four days or more per week prepandemic had a significantly lower mood state during the pandemic, compared to those who exercised for - days per week prepandemic (bpre - = − . , p = . ). however, there was a significant interaction effect on exercise frequency levels during the pandemic × prepandemic exercise frequency levels on mood (bpre*during = − . - . , p = . - . ). meaning, the effects of prepandemic exercise frequency on mood were dependent on exercise frequency during the pandemic (figure ). table summarizes the complete statistical results. . each column indicates exercise frequency before the pandemic, and exercise frequency levels within each column are exercise frequency levels during the pandemic. error bars indicate % confidence intervals. there was a significant difference in mood for those who exercised days or more before the pandemic (right columns) and decreased their exercise frequency during the pandemic. for those, who exercised for - days before the pandemic (middle column), only those who exercised day or less reported significantly lower mood than those who maintained their exercise frequency. note: exercise levels pre and during the pandemic: = " day or less"; = " - days"; = " days or more". along with post-hoc contrasts (see table ), figure shows that those who exercised four days or more before the covid- pandemic and decreased their exercise frequency during the pandemic experienced a decline in their mood states. specifically, individuals who decreased their exercise frequency to - days per week, had significantly lower mood states than those who maintained their exercise frequency (b pre : during - = − . , p = . ), and if they decreased their exercise frequency to one day or less per week, they experienced even a more significant decline in mood states (b pre : during - = − . , p < . ). those who exercised for - days per week prepandemic and were able to maintain their exercise frequency, had higher mood states compared to those who decreased their exercise frequency to one day or less during the covid- pandemic (b pre :during - = − . , p < . ). exercise frequency during the covid- pandemic had no significant effect on mood states for those who exercised one day or less prepandemic (p > . ). overall, exercise behavior could explain . % of the variability in mood states. the study presents the data from a larger study, "irg on covid and exercise", to examine changes in exercise behavior and its relation to mood in taiwan during the covid- pandemic. our results showed that the majority of respondents were able to maintain their exercise behavior during this pandemic. prediction analysis further revealed that taiwanese are likely to maintain their prepandemic exercise frequency during future similar pandemics. additionally, those who exercise more frequently before a similar pandemic have higher probabilities of maintaining their exercise frequency during such pandemics. notably, individuals who "completed vocational school or college", and are rarely active (i.e., exercise one day or less) before a pandemic are more likely to increase their exercise frequency during a future pandemic, while females who are rarely active (i.e., exercise one day or less) before a pandemic tend to maintain their exercise frequency during a future pandemic. additionally, it seems that older individuals and those with higher levels of income are more likely to engage in higher exercise frequencies. the relationship between exercise frequency and mood during the covid- pandemic was dependent on the change in exercise behavior (before vs. during). in general, higher frequencies of exercise during the covid- pandemic resulted in better mood states. additionally, exercising " - days" or "four days or more" before a pandemic was associated with worse mood states if these individuals reduced their exercise frequency during the pandemic. generally, a decline in exercise levels is expected during the covid- pandemic and our study indicated that nearly % of individuals decreased their exercise frequency. however, our results are inconsistent with previous studies showing a dramatic decrease in physical activity during the covid- pandemic in other parts of the world [ , , ] ; that is, the majority of taiwanese maintained their exercise frequency, duration, or intensity during the covid- pandemic. these differences may be partially the result of a relatively safe living environment and taiwanese self-discipline in epidemic prevention. given the geographical proximity to and the number of visits from mainland china, taiwan central epidemic control center (cecc) of taiwan centers for disease control has been on constant alert about the epidemic in china. after the initial suspicious unknown acute respiratory syndrome case reported in december in china [ ] , taiwan cecc has quickly mobilized and established comprehensive and proactive deployments to counteract and reduce the transmission of covid- . these included air and sea border control (e.g., assessing passengers for fever and pneumonia symptoms and restrictions at entries of international and cross-strait ports), case identification and containment (e.g., rapid screening tests for covid- , digital contact tracing, and quarantining suspicious cases), increase production rates and control of the domestic market price of medical face masks, and measuring body temperature at all entrances [ ] [ ] [ ] [ ] ] . furthermore, a high percentage of taiwanese ( . %) reported that they were willing to comply with taiwan cecc derived public propaganda and school education for covid- (e.g., maintaining social distance, regular disinfected living areas, and wearing medical face masks in public places) during the early days of the outbreak, which further decreased the spread of covid- . therefore, taiwan remained free from lockdown restrictions and kept the majority of health and fitness gyms and outdoor recreation facilities (e.g., parks, and playgrounds) open, and was able to maintain social activities per usual which reflect the successful containment of covid- . the prediction analysis demonstrates that exercise frequency during the pandemic is dependent on prepandemic exercise frequency. specifically, those who are more frequent exercisers prepandemic are more likely to stay active during a similar future pandemic. this finding reflects the importance of "prevention is better than cure" for exercise behavior during a future pandemic (e.g., second wave of the covid- pandemic). notably, some demographic variables might moderate exercise behavior. specifically, older individuals are more likely to have higher exercise frequency during similar pandemics. the result is similar to other studies showing that older adults in taiwan and mainland china exercise more regularly compared to younger individuals [ , ] . additionally, our data show that inactive individuals who have "completed vocational school or college" are more likely to increase their activity levels compared to the rest of our sample. this is not surprising as generally, individuals with higher educational levels might have better financial resources [ ] and more access to health information [ , ] . finally, we observed that females who are rarely active are more likely to maintain their low levels of exercise frequency. a lower prevalence of physical activity among females compared to males has been previously reported [ , ] . it is plausible that females, in general, perceive more barriers to exercise, such as lack of time due to multitasking (e.g., requiring to take care of others while working) and therefore, they are less likely to change their exercise behavior during such pandemics [ , ] . collectively, given that age, education, and gender can influence exercise behavior, specific strategies are required to consider and implement for these populations. interestingly, approximately % of participants reported an increase in exercise frequency and the prediction analysis showed that . % of the individuals who exercise one day or less per week, and % of individuals who exercise - days per week, might increase their exercise frequencies during a future similar pandemic. this shows that inactive or rarely active individuals might increase their exercise frequency or adopt exercise behavior during a pandemic. our finding is similar to data that showed increased health-seeking behavior (e.g., spending more time exercising) after the sars epidemic in hong kong [ ] . additionally, the perceived severity and susceptibility to disease is associated with both increased likelihoods of conducting health-seeking behavior according to the health belief model [ ] , and moving to the higher stages of the transtheoretical model of behavior change (e.g., stages of action and maintenance) [ ] . that is, covid- or a similar pandemic would increase awareness of health-seeking behavior such as exercise, and further facilitate the motivation to initiate and maintain the behavior. therefore, public health policy-makers should not only consider strategies to encourage exercise before a pandemic, but also take this pandemic as an opportunity to promote exercise for future similar pandemics. we observed that exercise frequency both pre and during the covid- pandemic impacts mood states. generally, higher exercise frequency during covid- was associated with better mood states, while the effect of prepandemic exercise frequency on mood states was moderated by the change in exercise frequency (before vs. during). specifically, those who frequently exercised before the pandemic (i.e., exercised for - days or four days or more) experienced a significant decline in their mood states when they decreased their exercise frequency during the pandemic. these results are in line with other research on the positive psychological benefits of exercise. for example, a meta-analytic study indicated an association between exercise and improved mood states, with an overall effect size of . and a mean change effect size of . for the treatment versus the control group and pretest-posttest studies, respectively [ ] . frequent exercise or physical activity might lead to adaptation of biological systems, including changes in neural hormones and endorphins [ ] , increasing density and efficiency of mineralocorticoid receptors and diminishing the cortisol synthesis [ ] , as well as improving cardiorespiratory fitness and strength [ ] . furthermore, exercise also elevates self-efficacy, self-esteem, feelings of mastery [ ] [ ] [ ] , and cognitive function [ ] [ ] [ ] . these positive physiological and psychological changes might be the mechanisms for improvements in mood states associated with both exercise before and during the pandemic. notably, higher total poms scores reflect either higher positive mood states (e.g., vigor) or less negative mood states (e.g., depression/anxiety, fatigue, or irritability). research has shown that the ratings of the arousing emotional pictures were significantly decreased after an exercise session [ ] , suggesting exercise reduces anxiety and increases resilience toward emotional stressors. additionally, alleviation of negative mood states [ ] , a decrease in trait anxiety [ , ] , and a decrease in the emergence of depression [ ] have also been observed with exercise. based on the cross-stressor adaptation hypothesis [ ] , exercise might result in the adaptation of the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis [ , , ] , which in turn lead to anxiolytic effects. this suggests that frequent exercisers might benefit from anxiolytic effects of exercise, especially during the covid- pandemic [ ] [ ] [ ] . it should be noted that prepandemic frequent exercisers (e.g., frequency of four days or more) experienced worse mood states if they decreased their exercise frequency during the pandemic. decrease in exercise levels, known as detraining [ ] , can have adverse effects both on exercise-induced physiological adaptation [ , ] , as well as psychological adaptations [ ] . other studies have shown that the cessation of regular exercise is linked to negative mood states [ , ] , as well as increases in somatic depressive symptoms (e.g., fatigue, berlin, kop, and deuster [ ] ). it is possible that a decrease in cardiorespiratory fitness [ ] , self-efficacy [ , ] , or changes in obligatory exercise beliefs [ ] contributed to declines in mood states when frequent exercisers decreased their exercise frequency during the covid- pandemic. in sum, maintenance of exercise behavior patterns, particularly in the active population, is essential to preserve mood states during the covid- pandemic or any similar future pandemics. some drawbacks of the study should be acknowledged. the translated questionnaires used in this study were not validated due to time limitations. in order to conduct this study during the brief window of governmental recommendations and restrictions related to covid- , the questionnaires were translated from english into different languages including traditional chinese for use in taiwan, resulting in the lack of time to proceed with the validation of the questionnaires as well as cultural adaptations. an additional limitation is the cross-sectional design of the study and the use of self-report data. however, the "irg on covid and exercise study" is planning to conduct a second wave after the cessation of the covid- pandemic to investigate the trends of exercise behavior and mood states of the respondents over time. finally, collecting data through the internet might potentially limit the participation of certain groups (e.g., individuals who do not have internet access). however, the internet penetration rate in taiwan reached . % in , and the internet access rate for individuals aged and above is as high as . % [ ] , suggesting the high accessibility and usage of the internet by taiwanese. our findings indicate that exercise behavior before a pandemic outbreak is likely to affect exercise behavior and mood states during a pandemic. specifically, the results show that age, gender, and educational level played a role in exercise behavior change during the pandemic. therefore, exercise professionals and policy-makers should work together to provide comprehensive and practical strategies specifically for the populations who are at risk of decreasing their exercise frequency before a similar pandemic in the future. for example, exercise training sessions can shift from in-person to online settings [ ] . this shift might require exercise practitioners acquiring several new skills such as online communication strategies, online exercise program design, and online evaluation of the clients' progress. additionally, sending motivational messages through the internet, such as edtech [ ] and social media (e.g., facebook, wojcicki et al. [ ] ), could be incorporated to promote exercise participation. our study is the first study conducted to investigate the changes in exercise behavior and mood states during the covid- pandemic in taiwan. the majority of taiwanese were able to maintain their exercise behavior with respect to frequency, intensity, and duration during the covid- pandemic, and predictive data shows that they are also likely to maintain their exercise frequency during a future similar pandemic. additionally, the mood state was affected by exercise frequency both during and before the pandemic, and it was negatively impacted if active individuals decreased their exercise frequency during the pandemic. this study thus provides evidence of the importance of promoting exercise both before and during a pandemic. covid- -new insights on a rapidly changing epidemic world health organization. coronavirus disease (covid- ) pandemic a novel coronavirus from patients with pneumonia in china response to covid- in taiwan: big data analytics, new technology, and proactive testing contact tracing, testing, and control of covid- -kearning from taiwan initial rapid and proactive response for the covid- outbreak-taiwan's experience legal preparedness as part of covid- response: the first days in taiwan impact of covid- pandemic on children and adolescents' lifestyle behavior larger than expected determinants of taiwan's early containment of covid- incidence can exercise affect immune function to increase susceptibility to infection? the compelling link between physical activity and the body's defense system pathological findings of covid- associated with acute respiratory distress syndrome coronavirus disease- : a tocsin to our aging, unfit, corpulent, and immunodeficient society cardiovascular implications of fatal outcomes of patients with coronavirus disease (covid- ) lifestyle risk factors, inflammatory mechanisms, and covid- hospitalization: a community-based cohort study of , adults in uk exercise arrangement is associated with physical and mental health in older adults association between physical exercise and mental health in · million individuals in the usa between and : a cross-sectional study mental health consequences of exercise withdrawal: a systematic review the lancet psychiatry. mental health and covid- : change the conversation a longitudinal study on the mental health of general population during the covid- epidemic in china covid- related depression and anxiety among quarantined respondents physical activity, health-related quality of life, and stress among the chinese adult population during the covid- pandemic immediate psychological responses and associated factors during the initial stage of the coronavirus disease (covid- ) epidemic among the general population in china mental health problems faced by healthcare workers due to the covid- pandemic-a review mental health care for international chinese students affected by the covid- outbreak mental health and the covid- pandemic when pandemic hits: exercise frequency and subjective well-being during covid- pandemic statistical power analyses using g*power . : tests for correlation and regression analyses manual for the profile of mood states; educational and industrial testing services profile of mood states research in sport and exercise psychology: past, present, and future revised short screening version of the profile of mood states (poms) from the german general population r: a language and environment for statistical computing; r foundation for statistical computing cumulative link models for ordinal regression with the r package ordinal prevalence of insufficient physical activity, sedentary screen time and emotional well-being during the early days of the novel coronavirus (covid- ) outbreak in china: a national cross-sectional study measures of covid- ; ministry of health and welfare the perceived neighborhood environment is associated with health-enhancing physical activity among adults: a cross-sectional survey of townships in taiwan does education improve cognitive performance four decades after school completion? demography education, income inequality, and mortality: a multiple regression analysis the causal effect of education on health: what is the role of health behaviors? health econ the international prevalence study on physical activity: results from countries worldwide trends in insufficient physical activity from to : a pooled analysis of population-based surveys with . million participants correlates of physical activity: why are some people physically active and others not? physical activity and sedentary behavior: a population-based study of barriers, enjoyment, and preference impacts of sars on health-seeking behaviors in general population in hong kong the health belief model the relationships among constructs in the health belief model and the transtheoretical model among african-american college women for physical activity the effects of exercise on mood in older adults: a meta-analytic review neuromodulation of aerobic exercise-a review links between physical fitness and cardiovascular reactivity and recovery to psychological stressors: a meta-analysis physical activity and psychological well-being in advanced age: a meta-analysis of intervention studies self-efficacy: toward a unifying theory of behavioral change depressive symptoms among older adults: long-term reduction after a physical activity intervention associations between cardiorespiratory fitness, physical activity, intraindividual variability in behavior, and cingulate cortex in younger adults exercise, cognitive function, and the brain: advancing our understanding of complex relationships the exercise-cognition relationship: a virtuous circle effects of emotional exposure on state anxiety after acute exercise the effect of regular aerobic exercise on positive-activated affect: a meta-analysis regular exercise participation mediates the affective response to acute bouts of vigorous exercise differential effects of acute and regular physical exercise on cognition and affect physical activity and incident depression: a meta-analysis of prospective cohort studies the cross-stressor adaptation hypothesis and exercise training limbic regulation of hypothalamo-pituitary-adrenocortical function during acute and chronic stress limbic system mechanisms of stress regulation: hypothalamo-pituitary-adrenocortical axis covid- and anxiety: a review of psychological impacts of infectious disease outbreaks depression, anxiety, stress levels of physicians and associated factors in covid- pandemics epidemiology of mental health problems in covid- : a review loss of training-induced physiological and performance adaptations. part ii: long term insufficient training stimulus effects of resistance training and detraining on muscle strength and blood lipid profiles in postmenopausal women training load does not affect detraining's effect on muscle volume, muscle strength and functional capacity among older adults effects of months of detraining on functional fitness and quality of life in older adults who regularly exercise depressive mood symptoms and fatigue after exercise withdrawal: the potential role of decreased fitness inflammatory markers and negative mood symptoms following exercise withdrawal self-efficacy relationships with affective and exertion responses to exercise the effect of exercise absence on affect and body dissatisfaction as moderated by obligatory exercise beliefs and eating disordered beliefs and behaviors taiwan network information center. taiwan restrictercise! preferences regarding digital home training programs during confinements associated with the covid- pandemic internet-based exercise intervention systems: are more interactive designs better? promoting physical activity in low-active adolescents via facebook: a pilot randomized controlled trial to test feasibility this article is an open access article distributed under the terms and conditions of the creative commons attribution (cc by) license we thank ralf brand to initiate the international research group (irg) on covid and exercise. the authors report no conflicts of interest.data availability statement: data are available upon request. key: cord- - vtgd s authors: Çetİn, ceren; kara, ateş title: global surveillance, travel, and trade during a pandemic date: - - journal: turk j med sci doi: . /sag- - sha: doc_id: cord_uid: vtgd s pandemics have had very important consequences in human history. lots of people lost their lives and countries have been intensively affected in terms of socioeconomic problems. unfortunately, avoidance of pandemics and limiting the spread are still currently not always possible. maybe the most important factor for this is the increasing frequency of traveling. increasing airline traveling rate also increases the rate of spread. global organizations like the world health organization and united nations are trying to play a supreme role over the countries. pandemics do not have borders; therefore, efforts should be given globally, definition of pandemic should be established as soon as possible, and protective measures should be shared with countries. if these are not done, severe health consequences and serious economic problems are inevitable. spanish flu led to the death of - million people worldwide (world population was approximately . billion during that time) and estimated case-fatality rate was determined as - % [ ] . the - pandemic, known as the asian flu, resulted in the death of - million people worldwide, and the - pandemic, referred to as the hong kong flu, caused the death of - million people worldwide. estimated case-fatality rate of the - influenza a (h n ) pandemic was established as . %. the age group the pandemic affected the most was children and young adults. it resulted in the death of - thousand people worldwide [ ] . last year around the end of , a novel coronavirus pneumonia case group was identified in the wuhan city of the province of hubei in china. rapidly spreading around the country, an epidemic arose and increasing number of cases started to be seen in other countries. in february , the world health organization defined covid- , which meant coronavirus disease. the virus causing covid- was referred to as severe acute respiratory syndrome coronavirus (sars-cov- ). an interim guideline was published by the world health organization and the centers for disease control and prevention (cdc) [ , ] . covid- was announced as a pandemic by the world health organization in march , and the pandemic is still continuing. during a pandemic, steps include controlling and surveilling the outbreak, finding the center, bringing the source under control, preventing human-to-human transmission, ensuring social distancing, and determining vaccination and treatment agents [ ] . in a model based on the flu pandemic analysis, it is assumed that one-third of the transmissions occurred in houses, one-third occurred in schools and workplaces, and the other one-third among the general public in the united states of america. thus, an important control strategy would target the closing of schools and workplaces [ ] . it should be seriously questioned whether hospitals would have the extreme capacity to treat a large number of patients or not. if not at sufficient capacity, necessary planning should be made by local supporters and public health officials in order to meet the deficit. other measures include planning healthcare services in alternative settings other than hospitals, taking necessary infection control measures, and drawing up clear guidelines in favor of public health for patient consent [ ] . it is necessary to form appropriate infrastructure and credible communication systems to coordinate public health intervention and plan and appoint leaders at national and local levels [ ] . the world health organization (who) recommends countries to make their own pandemic risk evaluations since incidence of human and animal cases in different countries in the world and the procedures to be done thereafter would differ. who updated its pandemic influenza risk management guideline in . this guideline can be used to inform and conform national and international pandemic preparations and interventions. countries should review and/or update their national flu preparation and intervention plans in order to reflect the approach taken in this guideline. moreover, roles and responsibilities of who regarding pandemic preparations were also stated in terms of supporting member countries in line with the crisis and risk management policies. this guideline does not intend to replace national plans that should be developed by each country. national pandemic influenza risk evaluation aims at determining the probability and outcomes of events affecting public health at a global, national, and local level. it constitutes the basis to act against and decrease the negative consequences of public health risks [ ] . it is attempted to make predictions with statistical models on when the agent would penetrate into the country or cities in the event of a pandemic [ ] . pandemic influenza phases reflect risk assessment of the global status concerning each and every influenza virus with a potential to be pandemic and to infect people. initially, these assessments are carried out when these types of viruses are defined and afterwards updated according to virologic, epidemiologic, and clinical data obtained. global phase represents the spread of the novel flu subtype to the world taking the disease it causes into consideration and separating it into interpandemic, alarm, pandemic, and transition phases. global phases are used by who to convey global status. pandemic phase is the period of global spreading. transitions between interpandemic, alarm, and pandemic phases can be rapid and gradual [ ] . as pandemic viruses emerge, countries and regions face different risks at different times. therefore, it is strongly recommended for countries to develop their own national risk assessments by considering information provided by who. hence, decisions for national risk management of any country are expected to be based on local risk assessments but also to be informed by global risk assessments [ ] . who should be able to follow the development process of the pandemic and guide countries with appropriate methods like strengthened surveillance and active monitorization. who should make suggestions in medical and nonmedical issues for this purpose. who should announce data independently and in a transparent manner; thus, who requires accurate and rapid data flow from every government in order to fulfill its obligation [ ] . united nations (un), on the other hand, is a much larger system. un aids in countries to adapt themselves to necessary arrangements strengthening technical capacities of the countries during pandemics through the peacekeeping commission, united nations development program, and united nations children's fund [ ] . risk assessment regarding pandemic influenza includes defining influenza viruses, reviewing significant virologic and clinical information on each and every influenza virus and classifying these as regards pandemic potency and probable outcomes. evaluation of exposure aims at identifying exposure to an upsetting flu virus, individual groups with a probability to become ill, and defining the sensitivity of these groups in terms of immunity and disease severity. this process contains epidemiologic and sensitivity factors such as travel history, incubation period, and estimated transmission potential. following risk and exposure assessments, these two assessments are finalized with a content evaluation. content evaluation is the assessment of the setting the event has taken or is taking place. content evaluation includes social, technological, scientific, economic, ethical, and political factors. exposure and content evaluations are made, and risk is characterized. risk characterization seeks to regulate the probability and impact of every risk. risk characterization uses these evaluations in order to assess if a specific flu virus has the potential to become pandemic and to what extent the society will be affected by such event and thus to judge the urgency and scope of risk management activities. risk assessment is a constant process during risk management continuity. for the evaluation of pandemic severity to be beneficial, it should be performed when public health decisions are required [ ]. to that end, surplus information should be provided in order to answer all critical questions regarding the pandemic that has emerged. questions on new cases and their progression and those regarding the type of diseases and complications encountered, which group of patients would be severely ill and die (i.e. age groups and groups at risk for severe outcomes), whether or not the virus is susceptible to antiviral agents, the number of people that would become ill, and the impact of the cases on the use of healthcare services and workforce should be answered. these questions will be of help in directing decisions on vaccination production and utilization strategy, antiviral use, mobilization of healthcare sources, school closings, and social distancing strategies. data responding to each critical question will be addressed in the context of three indicators. each of these indicators will contain information obtained from various data types including virologic, epidemiologic, and clinical data. data will be grouped so that they would be more accessible and comprehensible by the public and policymakers. national action plans have been charted according to six categories of principal components of emergency risk management for health. these include policy and resource management; planning and coordination; information and information management; health infrastructure and logistics, healthcare and related services; and community emergency situation risk management capacities [ ] . research projects, their budget and the number of researchers to work on these projects should also be carefully constructed. cooperation with the government for these plans is crucial [ ] . pandemics require globally compatible actions. pandemics are extremely destructive events that can cause serious social, economic, and political stress. preparation demands the approach of all communities in order to enable the world to respond quickly and effectively to decrease morbidity and mortality in the next pandemic. not only the healthcare sector, but also all other sectors, individuals, families, and communities play a role in lightening the effects of a pandemic. nonpharmaceutical interventions can be the only effective measure in many countries. during the onset of a pandemic, there would probably be no pandemic vaccination that would be effective against the novel virus. non-pharmaceutical interventions in the early stage of the pandemic should be implemented in order to slow down transmission and decrease its effect. these interventions include social distancing (staying home when ill), coughing etiquette (covering the mouth with a handkerchief while coughing or sneezing), and hygiene rules such as washing the hands and cleaning the surfaces and objects touched. extreme measures can be taken and implemented during severe pandemics including patients wearing masks (surgical masks), school closings, and diminishing contact between people. nonpharmaceutical interventions will help decrease the number of people exposed to and afterwards infected by the virus [ ] . since pandemics necessitate an approach for the whole community, individuals and communities should be cared about, listened to, and relieved of anxieties. people should be informed on how to protect themselves and stop the spreading of the virus [ ] . at the present time, airports, harbors and ports, road transportation and entry points to the country may have a critical role in the international transmission the diseases via persons, goods, and vehicles. therefore, countries should be ready to detect and respond to any healthcare event that would cause international concern by bringing healthcare-based restrictions in international travel and trade. thus, developing necessary public health capacities in entry points of the country will limit the spread of public health hazards ( ) . particularly frequent travelers may have a part in accelerating the international spread of the virus during the early period of the pandemic. hence, in the event of the onset of the pandemic being at a countryside where international travel is scarce, the transmission of the agent to frequent travelers will be much late and the spread of the pandemic will be much slower [ ] . international health regulations ( ) try to "limit public health measures preventing unnecessary intervention to international travel and trade". in order to reach this goal, who regularly makes recommendations on trade and travel measures regarding public health events. along with not interfering with measures related to specific trade and travel, international health regulations ( ) mandate countries to inform who on the justifications of the time of interventions and important measures taken by the administration of the countries. this is defined as the cause of a more than -h delay in the movement of international passengers, luggage, cargos, containers, vehicles, and items by the international health regulations ( ). apart from providing information to countries on these measures, who may demand from the implementing country to reevaluate these applications [ ] . world health organization continues to make recommendations against travel and trade restrictions for countries fighting with the covid- pandemic. travel measures interfering significantly with international traffic can only be justified at the onset of a pandemic since countries may be allowed to rapidly implement preliminary measures even for a few days. these kinds of restrictions should be based on meticulous risk assessment, be proportional to public health risk, not last long, and be reevaluated regularly as the event advances. travel ban to affected regions or rejection of entry of passengers traveling from affected regions is not effective in preventing case imports but may have important economic and social impact. temperature scan at entry and exit points is not an efficient way to stop international spread since infected people may be within the incubation period and not show early symptoms during the disease. for an adequate risk assessment and a follow of a probable case, the patients should be provided with disease-preventing messages, health statements should be collected upon entry, and contact information of the passengers should be obtained, which would be much more efficient [ ] . it is necessary to delay or prevent travel to affected regions for elderly patients and for those with underlying chronic diseases. personal hygiene, coughing etiquette, and putting an at least one-meter distance between yourself and those showing symptoms are important for all passengers. frequent hand hygiene after contact with particularly respiratory fluids is mandatory. hand hygiene includes washing the hand with soap and water or cleaning the hand with alcohol-based liquids. the mouth and nose of the person coughing or sneezing should be closed with a handkerchief or using the inner part of the elbow. touching the mouth and nose should be avoided [ ] . unless a person shows symptoms, s/he does not need to wear a medical mask since there is no evidence on any kind of masks protecting the noninfected person from the virus. besides, masks can be commonly worn in some cultures. it is important to follow the best practice on how to wear, remove, and dispose of the mask, and ensure hand hygiene if medical masks are to be worn [ ] . passengers returning from the affected regions should monitor the symptoms for days on their own and also follow the national protocols of the receiving countries. some countries may demand the returning passengers to be put in quarantine. should symptoms such as fever, cough, and difficulty in breathing manifest, it is recommended to the passengers to contact local healthcare providers preferably over the phone and inform them of their symptoms and travel history [ ] . it is suggested to follow the recommendations of who for designated passengers in entry points. the management of ill passengers in the context of present covid- disease pandemic in international airports, harbors, and motorway/road gates should include measures to be implemented according to the priorities and capacities of each country. in order to detect ill passengers and determine the symptoms of covid- disease and the possibility of virus exposure, interviewing with ill passengers, reporting cases with suspected covid- infection, isolation of those with suspected covid- infection and initial case management and referral are necessary [ ] . airport operators, aircraft/airplane operators, airline and airport crew, and ground personnel should be informed on how to recognize covid- signs and symptoms. crew and ground personnel should be informed on and frequently reminded of measures preventing the spread of covid- including social distancing, hand hygiene, respiratory etiquette, environmental cleaning, waste disposal, when and how to wear masks, and avoiding contact with people showing respiratory symptoms. medical face mask should be reserved for individuals with respiratory symptoms to prevent contamination with others. the personnel should be trained for hand hygiene and how to wear and remove protective equipment. personnel in close contact with symptomatic individuals should wear medical mask, eye protection (face shield or goggles), gloves, and gown [ ] . a number of factors should be taken into account to prevent the spread of covid- for countries that have decided to bring back citizens from affected regions. these include scanning right before flight, risk communication with the passengers and crew, infection control resources for the flight/journey, preparation of the crew for a possible infected passenger, entry scan upon arrival, and closemonitoring for days after arrival [ ] . countries should intensify surveillance for severe pneumonia and uncommon flu-like disease pandemics and attentively monitor the development of covid- pandemics by strengthening epidemiologic surveillance. countries should continue raising awareness in the public opinion, healthcare specialists and policy-makers through effective risk communication regarding covid- and should refrain from actions of stigmatization and discrimination. countries should share all related information on covid- for its timely evaluation and management as necessitated by the international health regulations ( ) [ ] . countries implementing additional health measures that significantly interfere with international traffic need to share related scientific data for the implementation of these measures and public health justification with who within the first h after the implementation. who will share this information with other countries. significant intervention generally means a more than -h delay in or rejection of international passengers, luggage, cargos, containers, vehicles, goods, and similar items [ ] . airline travel has the most important role in spreading pandemics. in a study considering airline network in the prediction of the spread of pandemics, rate and density of transmission have been detected with high accuracy [ ] . therefore, making predictions in early periods of pandemics using these modellings can be effective in rapidly taking necessary measures [ ] . if a country decides to quarantine arriving passengers who do not show symptoms, some factors should be taken into consideration. there is no universal guideline regarding the infrastructure of the quarantine facility; however, an area that will not increase the potential contamination and those put in quarantine should be recorded to be followed in the event of potential disease. accommodation and supplies, sufficient food and water to passengers, sleep arrangements and clothing, protection of luggage and other items, appropriate medical treatment, necessary communication devices should be adequately provided for in a language they can understand. medical mask is not required for those put in quarantine. if masks are used, the best practice should be followed. quarantine period, which lasts days (according to the currently known incubation period of the virus), can be extended due to delayed exposure [ ] . social and economic life continues during pandemics. a pandemic has the potential to affect all sectors. in the event of declaration of disaster as regards the severity of the pandemic, there is legislation oriented at covering fiscal charges. however, regulation should be made for pandemics that do not necessitate declaration of disaster in order to meet unexpected/unanticipated needs, and additional financial needs should be met. during a rapidly spreading pandemic, vital setbacks can be seen in the transfer of goods and services. the need for social support programs due to economic problems arising from the shutdown of businesses and interim unemployment [ ] . it is predicted that covid- pandemic will cost the world economy as much as an approximate trillion dollars, which is a much deeper and worse global crisis compared to that of - . institutions like the un are run with the aid of developed countries in particular. it is feared that a serious crisis will be felt in un resources as part of the effect of this pandemic and lead to weakness in the function of the un [ ] ). pandemic diseases may result in acute, short-term fiscal shocks and long-term damage in economic growth. early period public health efforts (such as monitoring contact, implementing quarantine, isolating contagious cases) in order to cover or limit pandemics require significant human resources and personnel cost. as a pandemic expands, new facilities may be needed to be constructed to manage additional contagious cases, and health system expenses will tremendously increase as a result of demand in medical supplies, personal protective equipment, and medicine. decreasing tax revenue may deepen the fiscal stress caused by increasing expenses in low-and middle-income countries that have weak tax systems and severe fiscal restrictions. this dynamic was seen in the western africa ebola pandemic in liberia in . as costs increased, economic activity slowed down, and quarantines and curfews decreased the government's capacity to collect revenues. during a mild-to-moderate pandemic, high income countries that are not affected can balance fiscal crises in low income countries by providing official recovery support including direct budget support. meanwhile, high income countries may be faced with the same fiscal stresses and be unwilling to provide help. during a severe pandemic, low-and middle-income countries may cut back in government expenses. negative economic crises are derived from workforce reduction due to disease and deaths and behavior change out of fear. fear manifests itself with many behavioral changes. the analysis of the economic effects of the western africa ebola pandemic has shown decrease in workforce, shutdown in businesses, delay in transportation, closing of land borders by some governments, restrictions implemented on citizens arriving from affected regions in entry to the country, cancellation of commercial flights, decrease in shipment and prevention in travel and trade. these effects decrease the participation of the pandemic to workforce and constrict local and regional trade. preventive behavior (such as prevention of travel, restaurant and public spaces and workplace discontinuity as prophylactics) also has economic outcomes. during a severe pandemic, all sectors of the economy (agriculture, manufacture, services) encounter shortages, rapid price elevation is basic necessities, deterioration that causes economic stress for the household, private firms, and governments. a severe pandemic may result in a significant and permanent economic damage [ ] . in order to take a pandemic under control, coordination should be established, flow of information should be regulated, necessary health interventions (case management algorithms, vector control) should be determined, health systems (hospitals, healthcare personnel, medicine) should be strengthened, the society should be informed, and the community should be included in pandemic surveillance and control. dictionary of epidemiology the classical definition of a pandemic is not elusive paleomicrobiology: past human infections health impacts of globalization: towards global governance world health organization. managing epidemic key facts about major deadly diseases novel coronavirus ( -ncov) technical guidance [online the risk of seasonal and pandemic influenza: prospects for control strategies for mitigating an influenza pandemic the health care response to pandemic influenza seasonal and pandemic influenza: recommendations for preparedness in the united states world health organization. pandemic influenza risk management. a who guide to inform & harmonize national & international pandemic preparedness and response global disease spread: statistics and estimation of arrival times to-concerns-in-serbia-over-its-actions-duringthe-influenza-a-h n - -pandemic/role-of-who-inpandemic-preparedness-and-response the covid- pandemic and research shutdown: staying safe and productive updated who recommendations for international traffic in relation to covid- outbreak frequent travelers and rate of spread of epidemics world health organization. management of ill travellers at points of entry -international airports, ports and ground crossings -in the context of the covid- outbreak management-of-ill-travellers-at-points-of-entryinternational-airports-seaports-and-ground-crossings-in-thecontext-of-covid-- -outbreak world health organization .operational considerations for managing covid- cases or outbreak in aviation interim guidance forecast and control of epidemics in a globalized world modelling the global spread of diseases: a review of current practice and capability key considerations for repatriation and quarantine of travellers in relation to the outbreak of novel coronavirus -ncov covid- pandemic and economic cost; impact on forcibly displaced people the international bank for reconstruction and development / the world bank key: cord- -ykxvaqcz authors: abbas, myriam; dhane, malek; beniey, michèle; meloche-dumas, léamarie; eissa, mohamed; guérard-poirier, natasha; el-raheb, myriam; lebel-guay, florence; dubrowski, adam; patocskai, erica title: repercussions of the covid- pandemic on the well-being and training of medical clerks: a pan-canadian survey date: - - journal: bmc med educ doi: . /s - - - sha: doc_id: cord_uid: ykxvaqcz background: the covid- pandemic has been an unprecedented and potentially stressful event that inserted itself into the – canadian medical curriculum. however, its impact on stress and subsequent professional pathways is not well understood. this study aims to assess the impact of the covid- pandemic on the mental well-being, training, and career choices of canadian medical clerks within the first three months of the pandemic. it also aims to assess their use of university support systems and their appreciation of potential solutions to common academic stressors. methods: an electronic survey composed of four sections: demographics, stressors experienced during the pandemic, world health organization (who) well-being index, and stress management and resources was distributed to canadian clerks. results: clerks from of the canadian medical faculties participated in this study (n = ). forty-five percent of clerks reported higher levels of stress than usual; % reconsidered their residency choice; and % reconsidered medicine as a career. the factors that were most stressful among clerks were: the means of return to rotations; decreased opportunities to be productive in view of residency match; and taking the national licensing exam after the beginning of residency. the mean who well-being index was . / ± . , indicating a poor level of well-being among a considerable proportion of students. clerks who reconsidered their residency choice or medicine as a career had lower mean who well-being indices. most clerks agreed with the following suggested solutions: training sessions on the clinical management of covid- cases; being allowed to submit fewer reference letters when applying to residency; and having protected time to study for their licensing exam during residency. overall, clerks were less concerned with being infected during their rotations than with the impact of the pandemic on their future career and residency match. conclusion: the covid- pandemic had a considerable impact on the medical curriculum and well-being of clerks. a number of student-identified solutions were proposed to reduce stress. the implementation of these solutions throughout the canadian medical training system should be considered. the well-being of university students has been a subject of particular concern in recent times. a national study conducted in canada found that % of undergraduate university students reported elevated psychological distress, which was significantly higher than the general population [ ] . medical trainees are no exception to these statistics as they report a high prevalence of anxiety and stress [ , ] . evidence suggests that these trends among medical students tend to worsen during their medical curriculum, with a significant increase of perceived stress among third-year medical students when compared to their first-year of medical school [ ] . high levels of stress and anxiety were correlated with depression and burnout [ , ] . one study found that % of third year and % of fourth year medical students experienced moderate or high degree of burnout [ ] . the deleterious impact of this psychological distress on clerks' lives has been well documented, such as a detrimental effect on cognitive functioning and academic performance, as well as intention of dropping out [ ] [ ] [ ] . an unprecedented and potentially stressful event that inserted itself into the - medical curriculum is the covid- pandemic. the impact of this pandemic on the wellbeing of health-care workers has already been well documented [ ] [ ] [ ] . yet, its impact on stress and subsequent professional pathways for medical trainees is still not well understood. during the pandemic, although the academic curriculum of preclinical students continued online, the situation was different for most medical clerks. in many countries, senior clerks had to graduate prematurely, [ ] while, in other parts of the world, clerks were pulled from their respective rotations. in canada, most junior and senior clerks saw their medical rotations be suspended. the canadian medical curriculum follows a traditional format where students in third-year transition to clerkship in a teaching hospital. the impact of this pandemic may be particularly pronounced for students during clerkship who are preparing for their future careers. in fact, in canada, it is during clerkship that third-year medical students, also known as junior clerks, choose electives and obtain reference letters from attendings in order to apply to residency. on the other hand, fourthyear medical students, known as senior clerks, are tasked with completing the national licensing exam. however, due to the pandemic, the specific requirements and dates of the canadian resident matching service (carms) and the medical council of canada qualifying examination (mccqe) are being reconsidered. given their known predisposition to decreased mental well-being, [ , , ] this study aims to assess the impact of the covid- pandemic on the mental well-being, training, and career choices of canadian medical clerks within the first three months of the pandemic. it also aims to assess the use of mental well-being support systems, as well as their appreciation of potential solutions to common academic stressors. an electronic survey composed of four sections: demographics, stressors and their impact on residency and career choice, world health organization (who) wellbeing index and stress management and resources was distributed to clerks (third-and fourth-year medical students) in all canadian medical schools, with of the faculties participating and forwarding the survey to their clerks. the survey was developed and delivered in french and english. the study protocol, consent form and recruitment documents were approved by the institutional review board of the université de montréal (cerses- - -d). eligible participants were clerks attending one of the canadian medical faculties, and whose rotations were suspended due to the covid- pandemic. clerks whose clerkship had been suspended for any other reason were excluded. the survey (additional file ) contained four sections: ( ) demographics, ( ) stressors ( ) who well-being index, and ( ) stress management and resources. these four sections of the survey were developed by either adapting existing sources [ ] or by conducting short focus group sessions with a small sample of junior and senior clerks from a single canadian medical school. the first section of the survey consisted of questions on demographics; age, gender, level of education, university, implications and occupations, covid- infection status and preferred residency. senior clerks were asked about the specialty to which they had already matched. stressors included in the survey were developed with a focus group of canadian medical clerks. this focus group was composed of four third year medical students and two fourth year medical students whose clinical rotations were suspended due to the covid- pandemic. a meeting was held in order to select the main stressors by reflecting on their own experience as clerks and the experience of their classmates. this section included an initial question allowing an assessment of the respondent's stress level in the context of the covid- pandemic. the three subsequent questions assessed the impact of the pandemic on their choice of residency and their decision to pursue a medical career. if the respondent reconsidered his residency choice, an additional question was asked to see the type of residency change they considered. this section also contained a question allowing the respondent to rate, on a likert scale, the level of stress associated with potential stressors they may have experienced. most of these stressors were directly linked to future educational and professional pathways. the third section of the survey assessed the respondent's state of well-being by using the who well-being index [ ] . this measurement tool consists of five statements that respondents apply to their own lives. it has high clinical validity and is among the most widely used questionnaires assessing subjective psychological well-being [ ] . it has been translated into over languages, including french [ ] . the maximum score of this index is and a score of or lower indicates a poor state of well-being [ ] . the fourth section of the survey contained five questions evaluating whether the respondent used university psychosocial resources during the covid- pandemic, as well as the perceived usefulness of the resource. this section also included a question exploring the level of agreement regarding certain academic solutions. the level of agreement with each solution was assessed using a -point likert scale ranging from "strongly agree" to "strongly disagree". a final open-ended question allowed respondents to offer other potential solutions. in order to ensure validity of the survey, its contents were reviewed by a group of experts composed of members of the medical stimulation and education research group at the université of montréal and the ontario tech university, consisting of physicians, researchers in medical education, residents, and medical students. the survey was developed and distributed using the qualtrics xm platform [ ] . the request to participate was sent to the deans and curriculum directors of all canadian medical faculties. they were asked to review the summary of the study and the survey and decide if the faculty would participate. because the aim of this study was to capture the well-being, stressors, and management within the acute stage of the covid- pandemic, we requested a response within a month. for the faculties that agreed to participate, the clerkship directors were asked to send the survey to all eligible clerks by distributing an email containing a digital link. for faculties that chose not to participate, the clerkship directors were asked for a short explanation and reasoning for not participating in the study. participation in this study was voluntary and consent was obtained with a consent form at the beginning of the survey. the survey was anonymous and took to min to complete. the study was conducted between april th, and june rd, . data collected for each of the four sections of the survey were analyzed separately. the data was first cleaned and analyzed in microsoft excel. except for participants' characteristics, missing data from participants who elected not to answer certain questions were excluded from all calculations. categorical variables (age, level of study, home university, preferred residency match, covid status, and family covid status) were described as proportions of the study population. descriptive statistics were performed. proportions were used to assess the number of clerks who reconsidered medicine as a career and their residency choice, and to assess levels of stress during the pandemic. first, we assessed the frequency distribution of the index and performed descriptive statistics for all participants with the mean and standard deviation. second, we compared the mean who well-being index between two groups of participants: participants who reconsidered medicine as a career and participants who did not. this data was obtained from part of the survey (stressors). we used unpaired t-tests to compare these two means. for each analysis, confidence intervals were computed for a %-degree confidence. p-values less than . were interpreted as indicating a statistical difference. all inferential statistics were performed in graphpad prism [ ] . descriptive statistics were performed using proportions. for the final open-ended question, responses were grouped by theme. the themes that came up more than ten times by different students were considered valid solutions. of the canadian medical faculties, accepted to participate and were able to send the survey to their students within an acceptable timeframe. of the seven faculties that chose not to participate, one did not reply, two chose not to distribute the survey without providing a reason, and four chose not participate because their institutional research ethics board reviewing process could not meet the deadline of the study. there were responses, of which ( . %) were excluded because their clerkship rotations had not been suspended due to covid- , and two did not provide informed consent. therefore, a total of participants were included in the final survey. table shows the major characteristics of the participants. the majority of the included participants were female (n = , . %). during the confinement period, most clerks resided at home with their parents (n = , . %) or with a partner (n = , . %). a minority of respondents were taking care of a dependent, including a child and/or an elderly person (n = , . %). the vast majority of students reported partaking in hobbies and/or self-care activities during the pandemic (n = , . %) and most were involved in volunteering (n = , . %). only a minority of students participated in remunerated work outside of clerkship (n = , . %). many students had already had online medical classes at some point during clerkship suspension (n = , . %). figure reports that clerks ( %) reconsidered medicine as a career, and clerks ( %) reconsidered their residency choice. figure shows the clerks' level of stress during the pandemic with clerks ( %) reporting higher levels of stress than usual. figure describes participants' self-reported level of stress for various stress factors. the factor that was the most stressful for all clerks was the means of return to rotations (e.g., lack of supervision, lack of learning opportunities). the most stressful factors for junior clerks were feeling the need to stay productive in view of carms, and stress regarding all aspects of carms application. for senior clerks, having to take the mccqe after the beginning of residency was the most stressful factor. the overall mean who well-being index of the included participants was . ± . , indicating a poor level of well-being among a considerable proportion of students. figure shows the proportion of participants who reconsidered their medical career (n = ) and those who reconsidered their choice of residency (n = ) during the pandemic. participants who reconsidered medicine as a career had a mean who well-being index of . ± . . this value was significantly different when compared to participants who did not reconsider medicine ( . ± . ; t ( ) = . , p = . ). the mean who well-being index of participants who reconsidered of the included participants, ( . %) reported using various university mental health support resources to assist them during the pandemic. of these students, ( . %) did not find the resource they used helpful. with the recent covid- pandemic sweeping across canada, medical clerks were removed from clinical rotations and had their clerkship suspended, missing-out on valuable clinical experience [ ] . our study aimed to assess the impact of the covid- pandemic on the mental well-being, training, and career choices of canadian medical clerks. it also aims to assess the use of mental well-being support systems, as well as their appreciation of potential solutions to common academic stressors. the need to adapt to new environments is one of the challenging elements of medical students' educational journey [ , ] . the relative lack of tolerance for uncertainty and ambiguity has been found to be an important predictor of psychological distress among medical students [ ] . our study showed that approximately % of surveyed students had higher stress levels than usual during the pandemic (fig. ) . this may be due to the challenge of facing such a unique event. historically, there has been very few dropouts from canadian medical schools. according to the association of faculties of medicine of canada, only . % of students had dropped out of a medical school in [ ] . as shown in fig. , our study found that % of surveyors reconsidered medicine as a career during this pandemic, with % reconsidering their choice of residency. this could be due to limited clinical exposure, or perhaps the fear of not being competitive for selective residencies [ ] . however, this change in perspective may also be due to their mental state during the pandemic. in fact, the results of the third part of our survey showed that a considerable amount of respondents had a who wellbeing index below , which suggests poor well-being and would require psychological support [ ] . furthermore, clerks who reconsidered medicine as a career or reconsidered their residency choice had significantly lower mean who well-being indices. yet, our results showed that only a minority of students used a university support system, and of those who used a resource, half regarded it as unhelpful. this begs the question on whether the resources currently available to medical clerks are both accessible and well-tailored to their needs. our study also identified several factors that could explain this increase in stress levels during the pandemic (fig. ) . both junior and senior clerks were found to have increased stress with respect to means of clerkship resumption. as shown in fig. , the majority of clerks were not in favour of the resumption of rotations only at the end of the pandemic. instead, returning when cases cease to increase was deemed more favorable to them. interestingly, clerks were less anxious about contracting covid- during their rotations despite the inherent risk, which challenges the pertinence of suspending clerkship altogether. indeed, as evidenced by fig. , clerks were more concerned with their eventual return to rotations and the impact of the pandemic on their education and future careers than with contracting the disease or contaminating others. according to the demographics part of our survey, clerks were also more willing to stay active during clerkship suspension as more than half decided to volunteer during the crisis. it could therefore be argued that suspending rotations may not have been in the clerk's best interest. that being said, faculties made such a decision with more than just the interest of their students' in mind, as reducing the amount of vectors in clinical settings was pivotal to flattening the curve [ ] . among junior clerks, the need to stay productive during the pandemic in view of carms was a major source of anxiety (fig. ) . literature has shown that medical students utilize clerkship to make career decisions [ ] . it also provides students with a chance to undertake projects and obtain reference letters from senior staff members to help support their residency applications. with clerkship suspension, clerks were impeded from participating in patient care and working with attendings or residents [ ] . junior clerks were also in favour of flexibility so as not to be penalized for a lack of electives in their specialty of choice (fig. ) . this is particularly important as many faculties have decided to prioritize core rotations, and the possibility of doing electives outside one's home university has been suspended for an undetermined amount of time across the country [ ] . regarding senior clerks, a major stress factor was writing the mccqe part i during residency (fig. ) . traditionally, senior clerks were able to write the exam prior to starting their residency. however, due to social distancing rules, many test centers were shut down causing postponement of the exam [ ] . at the time of the survey, the majority of clerks were in favour of having multiple time periods to take the mccqe part i examination and having protected time during residency to study for it (fig. ) . surprisingly, as shown in fig. , graduating prematurely to actively help during the crisis was not a major source of stress. this is in keeping with the notion that most students were not afraid of contracting the disease or contaminating others. as part of the solutions that were explored in our study, the majority of clerks were highly in favor of novel learning methods (fig. ) . for many years, medical faculties have been aiming to incorporate technology into their teaching methods, and with the pandemic many were able to quickly transition their teaching sessions into online formats [ ] . this can provide a solid foundation to permanently incorporate remote learning in medicine. a limitation in our study is that medical schools in alberta, british colombia and saskatchewan are not represented. also, participating in the survey was optional and may have introduced a selection bias. furthermore, some elements of the survey were designed to be as specific as possible to the reality of canadian medical clerks. as such, not all means of measuring outcomes utilized validated questionnaires and may have introduced response bias. overall, the results of this survey should be viewed as a qualitative and descriptive assessment of the general impact of the pandemic on canadian clerks rather than an analytical assessment. the covid- pandemic has forced medical students to adapt to a unique situation in order to achieve their educational goals. the pandemic resulted in considerable stress among clerks which medical faculties should address. various solutions regarding the medical curriculum were viewed more favourably than others. this study can serve as a reference for faculty leaders when taking important decisions on behalf of their students. centre for addiction and mental health., canadian electronic library (firm) systematic review of depression, anxiety, and other indicators of psychological distress among u.s. and canadian medical students levels and sources of stress in medical students depression and stress amongst undergraduate medical students stress, coping, and well-being among third-year medical students burnout in medical students: examining the prevalence and associated factors perceived stress during undergraduate medical training: a qualitative study sources of stress for residents and recommendations for programs to assist them burnout and suicidal ideation among u.s. medical students mental health problems faced by healthcare workers due to the covid- pandemic-a review factors associated with mental health outcomes among health care workers exposed to coronavirus disease when health professionals look death in the eye: the mental health of professionals who deal daily with the coronavirus outbreak covid- and early medical school graduation: a primer for m s accessed supporting the well-being of medical students provision of mental health support for medical students the world health organisation-five well-being index (who- ) the who- well-being index: a systematic review of the literature who (five) well-being index (who- ) graphpad prism. . . for mac ed the association of faculties of medicine in canada emotional challenges of medical students generate feelings of uncertainty uncertainty and ambiguity and their association with psychological distress in medical students why do students quit medical school far less often in canada than in other countries? a systematic review of the factors affecting choice of surgery as a career medical students are not essential workers: examining institutional responsibility during the covid- pandemic free choice and career choice: clerkship electives in medical education medical student education in the time of covid- notice of suspension of application to the mccqe part i due to covid- springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations the authors wish to acknowledge every member of clerkship direction who helped with the distribution of the survey. received: july accepted: october the online version contains supplementary material available at https://doi. org/ . /s - - - . this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sector. the datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. the study protocol, consent form and recruitment documents of this study were approved by the institutional review board of the université de montréal (cerses- - -d). participation in this study was voluntary and consent to participate was obtained with a consent form at the beginning of the survey. participation in this study was voluntary and consent to participate was obtained with a consent form at the beginning of the survey. the consent form explained that the data obtained from the survey would be used for the purpose of publication. there is no conflict of interest to declare. key: cord- -tguhrqvz authors: zavattaro, staci m.; hall, jeremy l.; battaglio, r. paul; hail, michael w. title: introduction: covid‐ viewpoint symposium, part ii date: - - journal: public adm rev doi: . /puar. sha: doc_id: cord_uid: tguhrqvz nan communication, political astuteness, and collaborative capacity. he offers practical suggestions, such as maintain network control and building social media skills, which are best practices in administrative structures and even more valuable in a crisis. taking a european view, bouckaert et al ( ) introduce the term -coronationalism‖ to explain the differences in response between belgium, france, germany, and italy. a nationalistic approach pushed european union ideals to the side as countries struggled with virus containment. they highlight the importance of institutional and cultural variance, points we argue are crucial for future studies about the virus response. christensen and laegrid ( ) focus also on europe, using norway as an in-depth case study. similarly to bouckaert et al ( ) , these authors point out cultural and political wills that made strong response possible. they draw attention specifically to the relationship between democratic legitimacy and government capacity, noting perception is key when it comes to crisis response. this point meshes with van der wal's ( ) recommendations for engaging stakeholders to build trust prior to cataclysmic events. charbonneau and doberstein ( ) consider work surveillance practices and their relationship to performance management with so many public servants being forced to shift to remote working from home in response to the covid- pandemic, such oversight is increasing in importance. their article presents the results of three surveys conducted during the onset of the covid- pandemic in canada that compare public servant and citizen attitudes to various cutting-edge digital surveillance tools that can be used to monitor employee work patterns. the resulting data can help governments navigate difficult questions of reasonable privacy intrusions in an increasing digitally-connected workforce. schuster et al ( ) introduce a survey instrument to study covid- via the world bank's bureaucracy lab. the survey is already deployed in several countries, and the authors are open to collaboration with others as they argue survey data are important to gather during the ongoing situation that is testing administrative capacity. in their study, dai et al ( ) take the china case and examine the crucial need for reliable, timely, and persuasive public information to gain compliance with prevention measures. using survey data of citizens throughout china, the authors find detailed pandemic information, positive risk communication, rumor refutation, and adequate supplies combined to help people engage in protective behaviors. future research could study this model in other contexts taking culture into account as bouckaert et al ( ) suggest. one of the most widely used and scientifically backed measures to slow virus spread remains social distancing, and in their essay, pedersen and favero ( ) survey americans to find what factors might influence compliance with social distancing. their results highlight again the critical role of crisis communication and reliable public information, coupled with prosocial motivation. the study provides insights into behavioral adaptations similar to dai et al ( ) , and both studies provide rich avenues for future research especially when it comes to the nudging behaviors crucial for crisis communication. this article is protected by copyright. all rights reserved. taking a bit of a turn, fay and ghadimi ( ) examine labor relations and what changed during and because of covid- . labor relations is a critical management strategy, and they outline evidence-based strategies for engaging in meaningful labor negotiations during crisis, focusing on emphasizing needs of the most vulnerable first, negotiating early and regularly with leaders, and securing protections for all members. their essay brings to light additional streams of research regarding labor negotiations during times of social and economic crisis. without question, the pandemic has exacerbated social inequalities and brought about what some are calling the dual pandemic of covid- and systemic racism (mccandless & zavattaro, ) . wright and merritt ( ) explicitly link systemic racism and the covid- response. health inequities, segregation, food insecurity, underrepresentation in the medical profession, and exclusion from full participation in democratic ideas and ideals contribute to the inequitable response to covid- . in the end, the authors outline a path forward for practice and research, the latter of which outlines an agenda for better incorporating social equity meaningfully into administrative studies. similarly to wright and merritt ( ) , gaynor and wilson ( ) use the social vulnerability index to examine the effects of racism on covid- deaths. they argue black people are historically segregated into vulnerable communities, and the pandemic is visibly highlighting these systemic inequities. as a path forward, they offer targeted universalism to develop inclusive policiesoffering a lot of potential for future research. deslatte, hatch and stokan ( ) explain the critical role local governments can play in addressing some of the inequalities. for instance, the community development block grant and energy efficiency and conservation block grant programs can be ways to equitably rebuild marginalized communities. also highlight the health inequities, martin-howard and farmbry ( ) use the social determinants of health theory to discuss strategies for mitigating these inherent inequities. using the bronx, new york as a case study, the authors examine the ways in which unequal access to adequate medical care increased community vulnerability and death among marginalized communities. like gaynor and wilson ( ) , they offer questions for future research aimed at mitigating these ingrained problems. using refugee migration as the object of performance, schomaker & bauer ( ) seek to understand patterns of administrative performance by examining networks and knowledge management within and between crises. drawing from two german public administration surveys their results demonstrate that those administrations that were structurally prepared, those which learned during preceding crises, and those that displayed high quality network cooperation with other administrations and with society more broadly performed significantly better in the respective crises. this article is protected by copyright. all rights reserved. rounding out the viewpoint symposium are contributions centering on coproduction and partnership. complex and wicked problems such as covid- require collaboration and coordination, and these essays offer insights and paths for future research. steen and brandsen ( ) note how the pandemic necessitated this kind of coordinated response, and they pose an important question that should guide research for years to come: will it last? they argue commitment to the partnerships, supportive regulatory frameworks, sustained funding, legal flexibility, and incentives should keep the collaborations moving forward, but that remains to be seen as the crisis still unfolds globally. the essay provides a clear path for examining their propositions in future research. using lessons learned from the haiti earthquake, entress, tyler and sadiq ( ) provide practical steps for building community resilience related to mass fatality management (mfm). the covid- pandemic showed the crippling holes in existing mfm plans, and the authors, using lessons learned from the earthquake, recommend increased collaboration, psychological support, and network leads when it comes to developing viable mfm plans going forward. similar to deslatte et al ( ) , wilson et al ( ) look at the local government collective action and engaging in economically focused partnerships to mitigate damaging effects from the pandemic. they offer economic development approaches requiring coordination, and like the other essays in this viewpoint symposium offer a path for future research to see if these strategies work, such as active versus passive partnerships. cheng et al ( ) explain the role that community-based organizations in zhejiang province in china played in responding to the pandemic. looking at what worked in that province, the authors offer four points for future research and practice when it comes to community-based organizations: strategically leverage strengths of community-based organizations; incentive volunteers to participate in prevention and control; provide technology that can facilitate effective response; build trust and long-term capacity for response. cultural contexts also can underlie these findings as well, so future research can examine that aspect of community-based organizations. shi et al ( ) detail the role of nonprofit organizations in providing critical response, focusing specifically on the homeless population. using interviews from four dallas, texas-area nonprofit leaders, they find each organization experienced disruptions to mission and service delivery. they also faced serious ambiguity that limited how staff could respond, forcing innovation and creativity. the authors introduce the disruptions, ambiguity, innovation, and challenges framework based on these interviews, giving practitioners immediate ideas and scholars a path forward for additional research. in their article, van den oord et al ( ) use the case of the antwerp port authority to showcase network governance's strengths and limitations. when the pandemic hit, port authority leadership needed to change network structures to succeed. the dynamism of the network allowed for brokering to take place, bringing in experts who could round out the response. network flexibility and dynamism seems to be an emerging theme ripe for future research. this article is protected by copyright. all rights reserved. finally, hu et al ( ) look at paired assistance programs in china to show differences in hierarchical versus network approaches to emergency management response and coordination. the intricacies involved in their study highlight again the need for network flexibility to foster positive response to crises. as you review these contributions, the next chapter in this pandemic will have already been written. lives will have been lost. elected officials will have been deeply criticized for their efforts. public managers will have worked seemingly endless hours, with many wearing thin and others growing disenchanted as the end seems further and further from sight. strategies will have been proven; others will have been disproven. the price of liberty and the value of security will have been weighed out more accurately in different ends of the earth. decisions will have been made with dire consequences to health or to the economy. the tradeoffs inherent in the rapid-fire nature of executive-driven policy decisions are real, and they are perceived more clearly by individuals than at any time in recent history. elected officials' choice of frames to describe and respond to the problems generate strategies and actions that will be more strongly influenced by their framing than by prevailing evidence. as the research articles appearing earlier in this issue demonstrate, elections have consequences, and the impact of this pandemic on the outcome of the u.s. general election may be its most significant enduring effect. each party seems to have a dominant frame that will guide the policy responses to be advanced as they prepare to take office in . our sincere hope is that the evidence presented here will be used to influence many of those decisions. we hope that it will stimulate research that will reshape the way we understand many of the core concepts of our discipline. as the response continues, we will continue to seek out work that makes ever increasing conceptual advancements. while we saw many patterns across the articles in our two covid- symposium issues, we also noticed some elements missing or needing stronger attention. for instance, while our contributors were intentionally global, voices from the global south need amplification regarding pandemic response. also, while some of the authors noted the cultural differences between countries and pandemic response, more could be done regarding administrative functions within those varied systems. some of the pieces necessarily took a broad view, and future research can drill further down into the relationship between culture and administrative response. finally, a collection of articles in this issue focus on social justiceand rightly sobut broadening that lens to be more intersectional and inclusive would help spur additional research. administrative burdens need to be better understood across subsets of the population as equality in the pandemic response is pursued. european coronationalism? a hot spot governing a pandemic crisis an empirical assessment of the intrusiveness and reasonableness of emerging work surveillance technologies in the public sector coproducing responses to covid - with community-based organizations: lessons from zhejiang province, china balancing governance capacity and legitimacy: how the norwegian government handled the covid - crisis as a high performer the effects of governmental and individual predictors on covid - protective behaviors in china: a path analysis model how can local governments address pandemic inequities? managing mass fatalities during covid - : lessons for promoting community resilience during global pandemics collective bargaining during times of crisis: recommendations from the covid - pandemic social vulnerability and equity: the disproportionate impact of covid - global reflection, conceptual exploration, and evidentiary assimilation: covid - viewpoint symposium introduction hybrid coordination for coping with the medical surge from the covid - pandemic: paired-assistance programs in china framing a needed discourse on health disparities and social inequities: drawing lessons from a pandemic editors' introduction: since we last spoke network of networks: preliminary lessons from the antwerp port authority on crisis management and network governance to deal with the covid- pandemic social distancing during the covid - pandemic: who are the present and future noncompliers? what drives successful administrative performance during crises? lessons from refugee migration and the covid- pandemic responding to covid - through surveys of public servants nonprofit service continuity and responses in the pandemic: disruptions, ambiguity, innovation and challenges co-production during and after the covid- pandemic: will it last? being a public manager in times of crisis the art of managing stakeholders, political masters, and collaborative networks institutional collective action during covid- : lessons in local economic development social equity and covid - : the case of african americans this article is protected by copyright. all rights reserved. this article is protected by copyright. all rights reserved. key: cord- -gi zj m authors: gersons, berthold p. r.; smid, geert e.; smit, annika s.; kazlauskas, evaldas; mcfarlane, alexander title: can a ‘second disaster’ during and after the covid- pandemic be mitigated? date: - - journal: european journal of psychotraumatology doi: . / . . sha: doc_id: cord_uid: gi zj m in most disasters that have been studied, the underlying dangerous cause does not persist for very long. however, during the covid- pandemic a progressively emerging life threat remains, exposing everyone to varying levels of risk of contracting the illness, dying, or infecting others. distancing and avoiding company have a great impact on social life. moreover, the covid- pandemic has an enormous economic impact for many losing work and income, which is even affecting basic needs such as access to food and housing. in addition, loss of loved ones may compound the effects of fear and loss of resources. the aim of this paper is to distil, from a range of published literature, lessons from past disasters to assist in mitigating adverse psychosocial reactions to the covid- pandemic. european, american, and asian studies of disasters show that long-term social and psychological consequences of disasters may compromise initial solidarity. psychosocial disruptions, practical and financial problems, and complex community and political issues may then result in a ‘second disaster’. lessons from past disasters suggest that communities and their leaders, as well as mental healthcare providers, need to pay attention to fear regarding the ongoing threat, as well as sadness and grief, and to provide hope to mitigate social disruption. en la mayoría de los desastres que han sido estudiados, la causa subyacente que genera el peligro no persiste por mucho tiempo. sin embargo, durante la pandemia covid- una amenaza a la vida progresivamente emergente es mantenida, exponiendo a todos a variados niveles de riesgo de contraer la enfermedad, morir o infectar a otros. distanciarse y evitar la compañía tiene un gran impacto en la vida social. además, la pandemia covid- tiene un impacto económico enorme para muchos por la pérdida de trabajos e ingreso, lo que está incluso afectando las necesidades básicas como la comida o la vivienda. en adición a esto, la pérdida de seres queridos puede agravar los efectos del miedo y la pérdida de recursos. el objetivo de este artículo es sintetizar a partir de una variedad de literatura publicada, lecciones de desastres pasados para ayudar a mitigar las reacciones psicosociales adversas a la pandemia covid- . trabajos europeos, americanos y asiáticos sobre desastres muestran que las consecuencias a largo plazo tanto sociales como económicas de los desastres pueden poner en peligro la solidaridad inicial. las disrupciones psicosociales, los problemas prácticos y financieros, y los complejos problemas comunitarios y políticos pueden resultar en un 'segundo desastre'. las lecciones de desastres pasados sugieren que las comunidades, sus líderes y también los proveedores de atención en salud mental necesitan prestar atención al miedo en relación a la amenaza en curso, así como a la tristeza y al duelo, y proveer esperanza para mitigar la disrupción social. extensive research on previous disasters has yielded a usable definition of disaster as the result of exposure to a hazard that threatens personal safety, disrupts community and family structures, and results in personal and societal loss, creating demands that exceed existing resources (ursano, fullerton, weisaeth, & raphael, ) . it seems that the current pandemic shares certain characteristics with previous disasters (jacobs et al., ; mcfarlane & van hooff, ; puente, marín, Álvarez, flores, & grassau, ; sundram et al., ; van der velden, bosmans, bogaerts, & van veldhoven, ; watson, brymer, & bonanno, ) . one of the critical challenges is how to use available information and knowledge to inform those who are in charge of the response (fogli & guida, ; krumkamp et al., ) . important sources are the responses to the spanish influenza pandemic (martini, gazzaniga, bragazzi, & barberis, ) and the severe acute respiratory syndrome (sars) epidemic (mak, chu, pan, yiu, & chan, ). specific to the coronavirus disease (covid- ) pandemic is the progressively emerging life threat. this leads, as in other disasters, to a loss of safety; people becoming dependent on each other's behaviour (help and compliance with measures to limit the spread of the virus); the breakdown of infrastructure, with hospitals and healthcare institutions being critically hit and social networks disrupted by lockdowns; and chaos, as illustrated by people hoarding and searching for reliable information, aggravated by the different restrictive measures taken across countries worldwide. finding accurate and reliable sources of information in this pandemic is critical in these circumstances. this has been complicated by the rise of social media as the preferred source of information by some groups in the community, rather than their depending on more carefully edited conventional media outlets (depoux et al., ) . the covid- pandemic and social restrictions have already been shown to impact mental health (fiorillo & gorwood, ; vindegaard & eriksen benros, ) . a sizeable proportion of people recovering from treatment at an intensive care unit (icu) develop posttraumatic stress disorder (ptsd) (davydow, gifford, desai, needham, & bienvenu, ; paparrigopoulos et al., ) . healthcare workers are affected, for whom stressors include confrontation with suffering and death, risk of contracting disease, and moral dilemmas (williamson, murphy, & greenberg, ) . they are at risk of psychological and post-traumatic distress (kisely et al., ) and grief reactions (wallace, wladkowski, gibson, & white, ) . relatives of covid- patients are affected, as they may experience caregiver stress and be confronted with the death of their loved one (hawryluck et al., ) . the initially successful measures taken for containing the virus may be followed by far more socially disruptive consequences related to the psychosocial isolation and the economic consequences (galea & abdalla, ; vigo, thornicroft, & gureje, ; zhang et al., ) . what can we learn from previous disasters? people's response to disasters has previously been described as a phased process (neal, ; raphael, ) . this phased approach enables the identification of the most common reactions to disasters (sundnes, ) . various analyses of these longitudinal models have been conducted and can assist in planning and anticipating the emerging issues in the covid- pandemic response (birnbaum, daily, & o'rourke, ; mcfarlane & williams, ) . in the threat phase, there is an appraisal of the emerging risk, which has been reflected differently between individuals and nations, from the polarity of denial to planning and adaptive action. perhaps, more than in most other disasters, we can see the differential and cascading consequences of the variable willingness to accurately assess an emerging threat. during the initial impact phase, the disaster unfolds, measures to contain its impact are taken, and an emotional outcry is manifested. however, covid- is a continuous disaster and responses to this disaster may vary among different populations as the disaster unfolds (dara, ashton, farmer, & carlton, ) . indeed, communities and countries may differ significantly in the extent to which the spread of the disease is brought to a halt. this, in turn, may lead to great variations in the sense of threat. the covid- pandemic shows a protracted impact phase: expressions of sadness and anger are muted, while powerlessness and alertness remain. the subsequent, in this case less prominent, honeymoon phase is characterized by feelings of relief and connection that are marked by spontaneous acts of solidarity and connectedness, such as clapping for healthcare providers. without a vaccine or established evidence-based treatment, the threat is still ongoing. the disillusion phase reactions may also vary between populations, in part driven by the extent of fractious social media debates and the politicization of the response options, such as whether to wear or not to wear face masks. people have become increasingly tired of chaos and fear, and those affected by the pandemic, such as slowly recovering covid- patients and the families of the deceased, will increasingly feel forgotten. the spotlight progressively will fade out on healthcare workers and caregivers in nursing homes who worked so hard without the necessary equipment. people suffering from diseases such as cancer and cardiovascular disease, and their caregivers, in families who have experienced restricted access to the required health services during lockdown, will have major concerns about their health. others are hit by the economic impact and many will long for the return of normal affective social relations. this phase therefore carries the risk of splintering society between groups that are affected differently, thereby creating a breeding ground for a 'second disaster' to take place (erikson, ; yzermans & gersons, ) . the final phase, the reintegration phase, still seems far away. a further important dynamic of this disaster and its phases is that the source of the threat has not lessened, and a constant reappraisal and adaptation to the risks is required as the impact phase will not come to an end until a vaccine has been developed or the virus has been eliminated from the community. what do previous disasters teach us about containing psychosocial impacts? in response to the / attacks in the usa, five essential elements of interventions were identified to be promoted as part of the disaster response, ranging from provision of community support and public health messaging to clinical assessment and intensive intervention (hobfoll et al., ) . the five elements are summarized in table and applied to the covid- pandemic. first, to promote a sense of safety; for example, by taking measures to limit the spread of the virus and disseminating knowledge about the virus. in the covid- situation, eliminating the disease threat may not be possible, as herd immunity and a vaccine are yet to come. secondly, for authorities and experts to promote calming. during the pandemic this can be achieved by clearly explaining measures, considering the implications involved, and showing genuine compassion. thirdly, to promote a sense of self-and collective efficacy. self-efficacy is the individual's belief that his or her actions generally lead to positive outcomes, and this can be extended to collective efficacy, which is the sense that one belongs to a group that is likely to experience positive outcomes. efficacy beliefs result from accurate information appraisal, considered decision making, behavioural skills, and practised repertoires, as well as access to resources (patterson, weil, & patel, ) . thus, during the covid- pandemic, leadership may enhance collective efficacy by communicating the effects of the measures, showing genuine empathy, sharing the economic burdens, promoting solidarity, and promoting activities that are conceptualized and implemented by the community, such as religious activities and mourning rituals. fourthly, to promote connectedness by preventing disadvantage or exclusion of specific groups, and adjustment of social services to the needs of the most vulnerable groups. fifthly, to instil realistic hope by providing perspective and mitigating feelings of powerlessness and discouragement. sources of hope include effective threat appraisal, self-reliance, demonstrated benefits of scientific appraisal and rational action, religious beliefs, belief in a responsive government, and superstitious beliefs. indeed, the covid- pandemic has seen a rise in religious coping (bentzen, ) . do these elements translate differently to the different affected groups in the process of setting policy and designing intervention strategies? for patients and healthcare workers, the disaster experience involves intense fear of one's own death or the death of someone close, and promoting safety and calming are the first priorities. this requires the active and effective resourcing of the health system, which includes the provision of high-quality personal protective equipment and ensuring the welfare and protection of families of healthcare workers. proper financial support for healthcare workers who become sick and adequate compensation for the families of those who die from the infection are critical. for people experiencing the loss of loved ones or economic needs of the population amid the pandemic actions required by authorities and experts to mitigate the impact of covid- sense of safety immediate actions of public health measures to limit the spread of the infection delivery of reliable information for the general population and various groups about the disease effective resourcing of required medical equipment calming active communication and constant explanation of the actions needed to contain the spread of the infection to the population compassion of authorities towards victims and various groups affected by the pandemic sense of self-and collective efficacy communication of plans on coping with the economic and social effects of the pandemic stimulating in everyone the sense that one belongs to a group promotion of solidarity and community activities, such as mourning or religious rituals connectedness active implementation of digital services in education, public institutions, and other services to ensure social functioning of different groups ensuring the functioning of social services, and adjustment of services to the new models of care for vulnerable groups acknowledgement of loss and sadness in the community hope providing perspective and mitigating feelings of powerlessness and discouragement communication about progress of treatment and vaccine developments symbolic rituals and events to promote resilience facilitation of various community, charity, and business initiatives targeted towards a better future losses, the disaster causes isolation and despair, and promoting connectedness and instilling hope are paramount. promoting a sense of self-and collective efficacy is a key priority for all affected groups. collective failure may create or deepen societal splits along historical and intergenerational fault lines, resulting in a second disaster. this variety in affected groups creates a challenge in dealing with the pandemic's consequences. decision makers may be tempted to focus more on certain affected groups, to the detriment of others, thus creating a hierarchy of suffering. with growing tension, there is a risk that affected groups will come to stand directly opposite each other while losing confidence in the government. a split along intergenerational lines carries particular risks. counterbalancing disillusionment is possible when loss and grief are given a place and when government and businesses explicitly create prospects for those affected economically. efforts are crucial to prevent and treat the mental health impact of the pandemic in all sectors of society, including healthcare workers . care providers in hospitals and residential care organizations for elderly people need peer support, spiritual care, and access to mental healthcare for treatment of burnout, ptsd, moral injury, and other conditions. aftercare for recovered covid- patients needs to include access to specialized treatment of icu-treatment-related ptsd. there is also the risk of post-infection syndromes including chronic pain, depression, and fatigue (moldofsky & patcai, ) . specific attention needs to be paid to the management and treatment of bereaved individuals. grief interventions taking into account the complex circumstances of the loss, such as ritual omissions and other cultural and intergenerational determinants of meaning attribution (smid, ) , may support meaning reconstruction following loss and thereby contribute towards increasing connectedness and inspiring hope. the pandemic affects the traditional means of delivery of psychosocial services, including psychological treatments for mental disorders. this causes challenges in the delivery of the available evidence-based practice models, as novel digital models of care need to be developed and implemented to ensure access to mental health services in various phases of the pandemic (javakhishvili et al., ) . while a number of studies on the effects of the covid- pandemic are emerging, this disaster is still unfolding, with a lot of uncertainty about its course. based on the studies of previous disasters, we identified possible psychological responses to the covid- pandemic. we also foresee that psychosocial disruptions, practical and financial problems, and complex community and political issues associated with the pandemic could result in a second disaster. lessons from past disasters suggest that communities and their leaders, as well as mental healthcare providers, need to address the different needs of various populations in society. in particular, there is a need to pay attention to fear regarding the ongoing threat, as well as sadness and grief; and to provide a sense of safety, connectedness, and hope to mitigate social disruption. we have no commercial interest to disclose. we have not asked for or received any funding for this study. in crisis, we pray: religiosity and the covid- pandemic. london: centre for economic policy research and evaluations of the health aspects of disasters, part iii: framework for the temporal phases of disasters worldwide disaster medical response: an historical perspective posttraumatic stress disorder in general intensive care unit survivors: a systematic review the pandemic of social media panic travels faster than the covid- outbreak the wake of the flood the consequences of the covid- pandemic on mental health and implications for clinical practice covid- pandemic, unemployment, and civil unrest: underlying deep racial and socioeconomic divides sars control and psychological effects of quarantine five essential elements of immediate and mid□term mass trauma intervention: empirical evidence the organization of post-disaster psychosocial support in the netherlands: a meta-synthesis trauma-informed responses in addressing public mental health consequences of the covid- pandemic: position paper of the european society for traumatic stress studies (estss) occurrence, prevention, and management of the psychological effects of emerging virus outbreaks on healthcare workers: rapid review and meta-analysis evaluation of national pandemic management policies-a hazard analysis of critical control points approach long-term psychiatric morbidities among sars survivors the spanish influenza pandemic: a lesson from history years after learning for the future: the challenge of disaster mental health services required after disasters: learning from the lasting effects of disasters chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-sars syndrome; a case-controlled study reconsidering the phases of disasters increased co-morbidity of depression and post-traumatic stress disorder symptoms and common risk factors in intensive care unit survivors: a two-year follow-up study the role of community in disaster response: conceptual models mental health and media links based on five essential elements to promote psychosocial support for victims: the case of the earthquake in chile in when disaster strikes: how individuals and communities cope with catastrophe a framework of meaning attribution following loss chapter : framework for the longitudinal phases of disasters psychosocial responses to disaster: an asian perspective social organizational stressors and post-disaster mental health disturbances: a longitudinal study the differential outcomes of coronavirus disease in low-and middle-income countries vs high-income countries covid- pandemic and mental health consequences: systematic review of the current evidence grief during the covid- pandemic: considerations for palliative care providers postdisaster psychological intervention since / covid- and experiences of moral injury in front-line key workers toxic turmoil: psychological and societal consequences of ecological disasters mental health and psychosocial problems of medical health workers during the covid- epidemic in china key: cord- -yw rzrb authors: prateepko, tapanan; chongsuvivatwong, virasakdi title: patterns of perception toward influenza pandemic among the front-line responsible health personnel in southern thailand: a q methodology approach date: - - journal: bmc public health doi: . / - - - sha: doc_id: cord_uid: yw rzrb background: thailand has joined the world health organization effort to prepare against a threat of an influenza pandemic. regular monitoring on preparedness of health facilities and assessment on perception of the front-line responsible health personnel has never been done. this study aimed to document the patterns of perception of health personnel toward the threat of an influenza pandemic. methods: q methodology was applied to a set of health personnel in charge of influenza pandemic preparedness in the three southernmost provinces of thailand. subjects were asked to rank statements about various issues of influenza pandemic according to a pre-designed score sheet having a quasi-normal distribution on a continuous -point bipolar scale ranging from - for strongly disagree to + for strongly agree. the q factor analysis method was employed to identify patterns based on the similarity and dissimilarity among health personnel. results: there were three main patterns of perception toward influenza pandemic with moderate correlation coefficients between patterns ranging from . to . . pattern i, health personnel, which we labeled pessimistic, perceived themselves as having a low self-efficacy. pattern ii, which we labeled optimistic, perceived the threat to be low severity and low vulnerability. pattern iii, which we labeled mixed, perceived low self-efficacy but low vulnerability. across the three patterns, almost all the subjects had a high expectancy that execution of recommended measures can mitigate impacts of the threat of an influenza pandemic, particularly on multi-measures with high factor scores of in all patterns. the most conflicting area was vulnerability on the possible impacts of an influenza pandemic, having factor scores of high ( ), low (- ), and neutral ( ) for patterns i, ii, and iii, respectively. conclusion: strong consistent perceptions of response efficacy against an influenza pandemic may suggest a low priority to convince health personnel on the efficacy of the recommended measures. lack of self-efficacy in certain sub-groups indicates the need for program managers to improve self-confidence of health personnel to participate in an emergency response. an influenza pandemic is a significant natural health threat that has periodically occurred over the past years [ ] . its severe impacts to global human health, healthcare service, society, and economy were evidently documented during the previous pandemics [ , ] . for a coming one, influenza experts have agreed that this threat is inevitable and possibly imminent [ ] . if the next pandemic occurs, it is expected that % of the global population will become ill, nearly million will be hospitalized and a quarter of these would die within a few months of its attack [ ] . to mitigate the impacts of this threat, the world health organization (who) has recommended that all countries should consider this threat as very important and urged them to make preparations a high national priority. thailand occasionally has had serious outbreaks of avian influenza a (h n ) since early , in both poultry and humans. in response to these outbreaks and a possible future influenza pandemic, the national committee on avian influenza control and influenza pandemic preparedness has issued a national strategic plan for influenza pandemic preparedness. beyond preparedness, the perception of each individual is also a fundamental factor that contributes to the spread, prevention, and control of infectious diseases. for example, during the severe acute respiratory syndrome (sars) epidemics, the perceptions toward this disease had an effect on the preventive health behaviors (e.g., hand hygiene, mask wearing) and that consequently contributed to containing the outbreaks [ ] [ ] [ ] . for a current threat of an influenza pandemic, sporadic perception surveys among health workers have been done in developed countries [ ] [ ] [ ] [ ] . yet this issue has not been explored in developing countries, particularly in the southeast asian region where it is more likely to be a source of the next pandemic [ ] . southern thailand experienced a probable sars case in , but there has been no reported case of avian influenza a (h n ) in both poultry and human. however, the region faces a serious problem of ethnic violence. this unrest has led to the loss of over , lives and more than , injuries in the past years. it is possible that the local health systems may have deteriorated due to the unrest leading to loosening of preparedness against the threat of an influenza pandemic. we have therefore conducted a study to investigate the preparedness. the current report is confined to perceptions related to the threat of an influenza pandemic with the objective to document the patterns of perception of health personnel toward this threat in southern thailand. as health personnel are key persons for influenza pandemic preparedness and con-trol, it is hoped that understanding their patterns of perception will allow control programs to properly improve the training. it may also be useful for other developing countries where an influenza pandemic is a serious threat, but the personnel are not fully prepared. q methodology, which basically originated from the theory of factor analysis [ ] was applied. while conventional factor analysis is used in scale development and tries to group items or variables, q method tries to group subjects. therefore, people of the same group or having the same factor will have a similar pattern of chosen statements. the implication would be that it would be easy to put people of the same factor into the same intervention program. this method was taken into our study because this is a scientific and systematic study of human subjectivity, involving perceptions, attitudes, and opinions [ , ] . furthermore, it is also unique since it mixes the strong points of both qualitative and quantitative research techniques, compared to traditional surveys [ , ] . in doing q, the flow of communication surrounding the study topic (concourse) is firstly formed to get a wide range of ideas toward that topic. this is generally collected from various sources (e.g., scientific papers, books, news, interviews, focus group discussions, etc.). it is commonly presented in the form of statements. afterward, a q sample (a representative set of statements) is selected from the concourse and developed to be more meaningful, which represents various issues of the study topic and eventually is compiled into the instrument. the study subjects are then asked to rank the representative statements and place them into a score sheet, which is designed in a continuous scale ranging from strongly disagree to strongly agree, following a standardized instruction based on the judgment of each subject. this is known as the q sorting procedure. the sheets that are completely ranked by each subject (qsort) are finally correlated and analyzed by q (subjectwise) factor analysis, and the factors are then interpreted. in our study, statements on various issues of an influenza pandemic were initially gathered from scientific articles, newsletters, and books to form a concourse. the protection motivation theory (pmt) was used as a basis for grouping and developing the statements into four domains: perceived severity, perceived vulnerability, perceived response efficacy, and perceived self-efficacy, by refining, clarifying, and combining the raw statements to be more meaningful and more understandable. to catch various aspects of an influenza pandemic and keeping the total number of the statements suitably manageable by our subjects, we included eight refined statements in each of such four domains with one additional item added to make the total number of the statements equal (qsample). these statements were then placed into the score sheet (figure ), and forced to follow a quasi-normal distribution, that is, - - - - - - - - . the reliability of this instrument was tested with cronbach's alpha. each statement was randomly assigned a number from to for the subjects to arrange and place into the score sheet. to get more understandability, the statements were pilottested with health personnel and were then revised as appropriate before the study. the study was conducted in the three southernmost provinces of thailand: yala, pattani, and narathiwat, during april to october . apart from the problems of ethnic violence, the area is in a remote part of the country where the logistic problems will be easily visible. the area is also close to malaysia, so cross-border diseases have a high chance of spread due to the movement of populations. the research protocol was approved by the ethics committee of the faculty of medicine, prince of songkla university, prior to conducting the study. a list of all health facilities in the study area was obtained from the local health offices. health personnel designated by each facility to be responsible for influenza pandemic preparedness were identified. these included a numbers of doctors, nurses, pharmacists, laboratory personnel, public health specialists, public health administrators, and junior health workers. all were invited to participate in the study. the selected personnel were sent a set of documents, which included a cover letter, an overview describing the study importance and objective, a set of statements (q sample), a standardized step-by-step set of instructions for responding to the study, and a score sheet. following the initial mailing, two phases of follow up were performed: a sequence of telephone calls at one month, with nonresponders contacted by the first author after three months. each consenting subject was asked to rank the statements about different issues concerned with an influenza pandemic into the levels of agreement and disagreement based on their own judgments. each participant was requested to place two statements in the columns of strongly disagree (- ) and strongly agree (+ ), three in disagree (- ) and agree (+ ), four in - and + , five in - and + , and five statements in the neutral response column ( ). however, if they thought that our distribution did not represent their real perceptions, they were encouraged to sort such statements accordingly. each q-sort was considered as complete if all statements were placed into the score sheet without repetition of the statements. the data from each completed score sheet were entered and analyzed in pqmethod . (free software). betweensubjects correlation matrix was computed and a q (subject-wise) factor analysis by principle components analysis (pca) method was performed using a varimax rotation technique. factors that could explain more than % of the variance were adopted and retained into the final solution. a participant who had absolute factor loadings of larger than ± . , which suggests high significance (p < . ) with the group, was included into that particular factor. in each factor, the ascending sorted normalized scores (z-scores) of assigned number of each statement were returned into the score sheet from right to left order (figures , , and ) . each final score sheet thus displays the pattern of the defined factor. comparisons among patterns were based on the factor scores and the mean values of the domain of the statements. for visualization of the patterns, the domains of each statement were linked to different colors or grey shadings in the final q-sort models that are shown in figures , , and . since the cells in the extreme score regions reflect strong perceptions in the domains, they are the primary target for comparing similarity and dissimilarity of each group of health participant score sheet figure participant score sheet. strongly agree [ ] [ ] [ ] [ ] [ ] pattern i. pessimistic with perceived low self-efficacy figure pattern i. pessimistic with perceived low self-efficacy. personnel's perceptions on the threat of an influenza pandemic. after consultation with an expert in instrument development, statements listed in table of a total health personnel, ( %) persons completed the score sheet. there were no statistically significant differences between responders and non-responders in terms of gender, age, religion, educational level, total period of working, job classification, experience of getting training on influenza pandemic preparedness and perceived levels of knowledge about an influenza pandemic, public health measures against an influenza pandemic and impacts of an influenza pandemic. however, the nonresponders had a lower educational level than those of the responders ( % vs. %, respectively). the basic characteristics of the respondents are presented in table . q factor analysis gave three factors that met our criteria with the percentages of explained variance being . %, . %, and . %, respectively. after varimax rotation, subjects were classified into factor i (in other words, the first pattern composites of health personnel), into factor ii, and into factor iii. the other subjects were not classified into any factor because all their loading values were less than . or had high loading on more than one factor. the composite reliability of each factor was . , with the corresponding standard errors of factor scores being . , . , and . . the correlation coefficients between the three factors were . (factor i vs. ii), . (factor i vs. iii), and . (factor ii vs. iii), indicating a moderate similarity among the patterns. the three patterns had scores for each specific statement distributed into the q-sort model or composite factor array and are displayed in figures , , and . the same information is displayed in table . factor scores of statement were , - , and - as shown in the first row of table . in the q-sort model, statement is in column + of figure , and column - of figure , and column - of figure . from table , statement number has a common factor score of for all three patterns. this indicates that all three patterns of health personnel strongly perceived that multimeasures must be performed during an influenza pandemic. statement number was also in columns + of figures and , and + of figure , which is related to response efficacy on multilevels of responsibility for preparedness against the threat. in contrast, statement was the most dissenting issue with factor scores of , - , and . health personnel classified as pattern i quite strongly perceived that thailand will have possibly high impacts from an influenza pandemic if and when one occurs, but those classified in pattern ii strongly disagreed, and those in the remaining group were neutral. the right extremes of all three q-sort models are consistently filled with three black cells (statements , , and ) out of cells of that region. this indicates that all three pattern ii. optimistic with perceived low severity and low vul-nerability figure pattern ii. optimistic with perceived low severity and low vulnerability. pattern iii. mixed with perceived low self-efficacy but low vulnerability figure pattern iii. mixed with perceived low self-efficacy but low vulnerability. means of factor scores for each component of the pmt are displayed in table . all groups had positive perceived response efficacy of the measures. patterns i and iii, however, perceived low self-efficacy, in contrast to high perceived self-efficacy of pattern ii. optimistic personality of pattern ii was also expressed as perception of low severity and low vulnerability where the pattern i has isolated neutral perception of severity with a moderate level of perceived vulnerability. finally, more mixed appraisal is found in pattern iii, the group who perceived a low level of vulnerability but a very high level of severity. we identified three main patterns of health personnel in southern thailand based on the perception toward a threat of an influenza pandemic. pattern i was pessimistic (strongly perceived response efficacy, but perceived low self-efficacy). pattern ii was optimistic (strongly perceived response efficacy, but perceived low severity and low vulnerability). pattern iii was mixed (strongly perceived response efficacy, but perceived low vulnerability and low self-efficacy). a high perception on response efficacy was predominantly found in all health personnel groups. perceptions on vulnerability were more varied. the majority of our health personnel perceived low selfefficacy toward an influenza pandemic. self-efficacy is one important component of coping appraisal of the pmt [ ] . it has powerful influence on human's feeling, thinking, motivation, and behavior [ ] [ ] [ ] . previous metaanalyses provided evidence for self-efficacy having the largest effect size and was the strongest predictions of protection motivation [ , ] . people with low self-efficacy usually believe that tasks are harder than they can handle. this can lead to limit task planning, increase stress, reduce the low level of attempt, and having a tendency to avoid duties and activities [ ] [ ] [ ] . balicer et al. reported that nearly a half of local health workers may be unwilling to report to duty during a pandemic event [ ] . however, that study did not identify different patterns of health workers as our study has done. another conventional survey conducted among a general population (rather than health workers) in developed countries of europe and asia on avian influenza risk perception showed a similar result. the level of self-efficacy among the respondents was also low and the authors concluded that a low level of self efficacy may obstruct any interventions [ ] . the most dissenting issue among our health personnel toward this threat was on vulnerability of possible impacts in the country (statement number ). naturally, the occurrence and severity of an influenza pandemic cannot be predicted [ ] . fifteen per cent of our health per- showed that more than half did not consider that the risk of an imminent influenza pandemic was more than a possibility [ ] . both perceived severity and perceived vulnerability are components of threat appraisal of the pmt [ ] . perception of low level of severity and vulnerability or low levels of appraised threat of an influenza pandemic may inhibit motivation of health personnel to engage in protective behavior [ , ] . however, the effect sizes of such two components in previous meta-analyses were small to medium and barely predicted of protection motivation and behavior compared to the components of coping appraisal (response efficacy and self-efficacy) [ , ] . perception of response efficacy was stronger than other domains. this may be influenced by past experiences of the country, which after employing on multi-sectors and multi-measures could successfully suppress avian influenza a(h n ) [ ] . this study used a wide range of front-line health personnel responsible for influenza pandemic preparedness. thus, it may reflect the problems specific to this area with acceptable accuracy. the study was confined to the three southernmost provinces of thailand where avian influenza a (h n ) has never occurred. our study subjects might be different from those in other regions of the country where the infected cases of that avian influenza in both humans and poultry have been reported, and intensive avian influenza controls have been fully activated. the study subjects were also predominated by personnel from health centers and community hospitals in rural areas. the threat of a pandemic may be less compared to in urban areas. the study was based on q methodology which had never been employed among local health workers; thus, the data have to be interpreted with caution. approximately % of the respondents were not able to be classified into any of the three groups determined by our factor analysis. the patterns are therefore far from ideal. the statements about influenza pandemic that were used in our study should be improved to be more specific for health workers in future work. despite the above limitations, this study highlights important findings. strong consistent perceptions of implementing recommended measures against an influenza pandemic can remove or mitigate impacts of this threat, and may suggest a low priority to convince health personnel on the efficacy of the measures. perception of low self-efficacy in certain subgroups who gave low scores on the statements related to self-efficacy on an influenza pandemic indicates the need to improve self-confidence of health personnel to participate in an emergency response by the control program. potter cw: a history of influenza seasonal and pandemic influenza preparedness: a global threat influenza pandemics of the th century are we ready for pandemic influenza? will vaccines be available for the next influenza pandemic? sars transmission, risk factors, and prevention in hong kong sars-related perceptions in hong kong. emerg infect dis monitoring community responses to the sars epidemic in hong kong: from day to day local public health workers' perceptions toward responding to an influenza pandemic physicians' perception of pandemic influenza perception in relation to a potential influenza pandemic among healthcare workers in japan: implications for preparedness koh d: concerns, perceived impact and preparedness in an avian influenza pandemic -a comparative study between healthcare workers in primary and tertiary care capacity of thailand to contain an emerging influenza pandemic doing q methodology: theory, method and interpretation a primer on q methodology q methodology-a journey into the subjectivity of human mind q methodology: definition and application in health care informatics cognitive and physiological processes in fear appeals and attitude change: a revised theory of protection motivation self-efficacy: toward a unifying theory of behavioral change human agency in social cognitive theory self-efficacy: the exercise of control a meta-analysis of research on protection motivation theory prediction and intervention in health-related behavior: a meta-analytic review of protection motivation theory avian influenza risk perception blaser mj: pandemics and preparations protection motivation theory effects of components of protection motivation theory on adaptive and maladaptive coping with a health threat grotto i: a systematic analytic approach to pandemic influenza preparedness planning this study was part of the first author's thesis to fulfill the requirement for phd in epidemiology at prince of songkla university (psu). we sincerely acknowledge all health personnel who participated in the study. appreciative thanks to the graduate school, psu, and the disease control department, ministry of public health, thailand for supporting the study. we also wish to thank dr. alan geater, dr. vorasit sornsrivichai, mr. edward mcneil, the epidemiology unit, faculty of medicine, psu, and mr. darrell beng, adelaide, south australia. the authors declare that they have no competing interests. tp designed this study, was the principal investigator of the project, performed data analysis, and drafted the manuscript. vc provided supervision, suggestion, and development on manuscript writing. all authors have contributed to revision of the draft version and have read and accepted the final version of this manuscript. the pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/ - / / /pre pub key: cord- - m k t authors: kuzemko, caroline; bradshaw, michael; bridge, gavin; goldthau, andreas; jewell, jessica; overland, indra; scholten, daniel; van de graaf, thijs; westphal, kirsten title: covid- and the politics of sustainable energy transitions date: - - journal: energy res soc sci doi: . /j.erss. . sha: doc_id: cord_uid: m k t in this perspectives piece, an interdisciplinary team of social science researchers considers the implications of covid- for the politics of sustainable energy transitions. the emergency measures adopted by states, firms, and individuals in response to this global health crisis have driven a series of political, economic and social changes with potential to influence sustainable energy transitions. we identify some of the initial impacts of the ‘great lockdown’ on sustainable and fossil sources of energy, and consider how economic stimulus packages and social practices in the wake of the pandemic are likely to shape energy demand, the carbon-intensity of the energy system, and the speed of transitions. adopting a broad multi-scalar and multi-actor approach to the analysis of energy system change, we highlight continuities and discontinuities with pre-pandemic trends. discussion focuses on four key themes that shape the politics of sustainable energy transitions: (i) the short, medium and long-term temporalities of energy system change; (ii) practices of investment around clean-tech and divestment from fossil fuels; (iii) structures and scales of energy governance; and (iv) social practices around mobility, work and public health. while the effects of the pandemic continue to unfold, some of its sectoral and geographically differentiated impacts are already emerging. we conclude that the politics of sustainable energy transitions are now at a critical juncture, in which the form and direction of state support for post-pandemic economic recovery will be key. covid- is, above all, a global health crisis with devastating implications for a great many as people lose their lives and as we live through an array of direct and indirect effects of lockdown and social distancing measures. this perspectives piece is written at a time when the pandemic is still unfolding, but some of its dramatic and varied impacts on the global economy, energy and financial markets, governance, and our ways of living are already evident. our purpose here is to explore how the changes wrought by the pandemic might influence the complex and dynamic politics of sustainable energy transitions. this question is particularly pertinent now, as governments, companies, and wider publics consider what the pandemic means, how to respond and, importantly, the extent to which responses should be 'green'. there had been some positive trends in the politics of sustainable energy transitions, as broadly defined below, in the years running up to the outbreak of the pandemic. for example, the paris agreement instituted nationally determined climate goals; sustainability transitions were placed on the agendas of many local, national and global governing bodies; the cost of renewable energy continued to fall rapidly, making it an increasingly politically and economically viable option; divestment campaigns were taking off; and there was a surge in public buy-into the argument that urgent action was required to address climate change. the hope was that cop- , due to take place in glasgow in november , would see increased ambition to meet the goals of the paris agreement. meanwhile, however, global greenhouse gas (ghg) emissions continued to rise rather than fall, albeit not in [ ] , and there remains a considerable emissions gap between the paths we are on and where we need to be [ ] . early reports of the economic impact of the pandemic, and the 'great lockdown', are bleak: the global economy is predicted to shrink by % in , with the possibility that million people lose their jobs [ ] . there will, however, be significant variance in impacts with some sectors and countries harder hit, and some recovering more quickly than others. predictions are that the open, service-oriented economies that dominate the oecd are likely to suffer more for longer [ ] , whilst china's economy is already showing strong signs of recovery. equally, those economies already carrying significant debt and/or a reliance on fossil fuel exports are also likely to be harder hit. in april , almost % of the global population were subject to complete or partial lockdowns and, as such, the share of energy use that was exposed to containment measures reached % [ ] . unsurprisingly, therefore, the early implications of covid- were also significant but varied for emissions, fossil fuel and sustainable energy. daily global co emissions fell by % in april , compared to april , with just under half this reduction coming from surface transport as social practices changed [ ] [ ] , and expectations are of an overall % drop in taking emissions to levels of years ago [ ] . lower emissions are connected, in turn, to energy use: demand for, and prices of, fossil fuels and electricity fell quite dramatically. the biggest drop was for oil, which saw a % fall in april , with us oil prices falling negative for a period of time [ ] . renewable demand was, however, less affected and is expected to rise overall, by %, in . as a result, the share of renewables within the overall energy mix may jump several years ahead of pre-pandemic expectations [ ] . the debate has, however, already started to turn to what kind of recovery, in sustainability terms, we can expect. there is considerable concern that, as with the post- recovery, there will be a rapid return to high levels of emissions and urban air pollution, and severe inequalities in terms of social outcomes. by may air pollutant levels in china had already over-shot their pre-crisis levels [ ] , whilst it is evident that a green recovery is not a luxury that all can afford and short-term survival strategies, that support business-as-usual, are underway in many parts of the world. at the same time, however, many are arguing forcefully that sizeable global stimulus packages provide an historic opportunity to drive sustainable energy transitions whilst, at the same time, delivering positive societal outcomes such as jobs, green growth and equity [ ] . as such, the economic and social impacts of covid- will do much to shape the politics of sustainable energy transitions over the next few years. we structure our discussions below around how important trends emerging in four thematic areas: energy system change; finance and investment; multi-scalar governance; and social practices, might be affected by covid- . whist we recognise limitations in reaching conclusions at a time of rapid change and uncertainty, indications so far are that the pandemic overall is likely to be continuous with, and to accelerate, many of these trends. our emphasis on the politics of transitions tends to foreground the notion that policy decisions taken as we emerge out of lockdown and into prolonged periods of social distancing will be vital to the success of sustainable energy transitions. it is important, before we proceed, to provide some key definitions. sustainable energy transitions are conceived here as complex socio-technical processes of decarbonisation within energy systems, and involve both bringing in low, or zero, carbon energy and phasing out old, high carbon energy [ ] . our understanding of sustainable also includes due consideration for social issues of energy poverty, equity and justice. in turn, energy systems, old and new, are understood as being made up not just of supply, but also demand and social infrastructures [ ] . energy systems and practices are, of course, already undergoing sustainable changes, in particular in electricity, whilst there is significant variety between countries, in terms of pace, scale and technologies [ ] , partly related to political approaches to sustainability. politics is broadly understood here as consisting of power relations, formal and informal political processes, and their outcomes. energy politics is increasingly multi-scalar in that it involves a growing multiplicity of actors at global, national and sub-national scales [ ] [ ] , a theme to which we return below. sustainable energy transitions and politics are deeply intertwined: politics can shape the nature of energy systems, i.e. the degree to which they become sustainable, but politics is also, in turn, affected by energy systems [ ] [ ] . this observation informs our choice of energy system change as one of our themes. sustainable energy policy is, in turn, shaped by embedded power relations and institutions, but exists today because of the successful articulation of new ideas, particularly about climate change [ ] [ ] . within our definition, energy power relations also include institutionalised financial practices, and investment choices, that have long facilitated fossil fuel lock-in in energy systems [ ] , to which we return in section . below. lastly, as part of our multi-actor view of the politics of sustainable energy transitions we consider social practices, and the role of the public, to be of paramount importance: as voters, particularly within democracies; as participants in political movements; and as consumers and, increasingly, generators of energy [ ] [ ] . indeed, habits, norms and culture, can be considered both a constituent element of existing energy systems [ ] , as well as a key aspect of how systems can change given the right political conditions [ ] . this aspect of the politics of sustainable energy becomes particularly relevant given that lockdown led to, more or less temporary, new social practices. partly for these reasons, but also because of wider socio-technical lock-ins [ ] , sustainable energy transitions have frequently required conscious efforts by public actors to steer towards a more sustainable path. the nature of policy responses to the covid- pandemic emerge as key given that these have the potential to speed up or slow down sustainable energy transitions [ ] [ ] [ ] . or, put more dramatically, to determine whether or not political pandemic responses prevent the world from leaping from the covid- frying pan into the climate fire [ ] . equally it is important to consider whether covid- has the potential to change the politics of energy and, if so, in what ways. we approach these questions by identifying continuities and discontinuities with sustainable energy politics trends, outlined above and below, and by thinking in terms of whether these trends are accelerating or decelerating. this is what we turn to next. the below is clearly not intended as an exhaustive discussion of all possible implications of covid- for the politics of sustainable energy. the thematic areas that shape the discussion tie in with our understanding of the politics of sustainable energy transitions outlined above, and are further informed by emerging analyses of the effects of the pandemic and related debates. what this represents is an early attempt at analysing complex politics at a time of ongoing change and uncertainty, with some emphasis on the oecd countries. questions of acceleration and deceleration highlight the importance of time frames, and the analysis below is sensitive to the temporalities of covid- : i.e. in some parts of the world, the short-term, defined as the period of lockdown, is over; whilst the medium-term can be defined as the period over which social distancing and recovery take place; and the longer term, mid s to , where the consequences of decisions made now will be most apparent [ ] . what's key in this thematic area is the impact of the pandemic on the pace and nature of whole energy system change, an issue that was already the subject of considerable debate [ ] , on the growth of the low carbon energy system, and the looming demise of the incumbent fossil-fuel based system [ ] . historical price crashes and demand shocks left indelible marks on the evolution of the global energy system, and the current crisis is no different. the counterfactual when considering implications for whole energy systems is to consider what the structure of the global energy system might have been in had there not been a pandemic. the short-term impact is clear: an unprecedented fall in energy demand, especially for oil, along with a more modest, but still significant, decline in electricity demand and prices. after the march oil price war, opec+ reached an agreement, that was subsequently supported by the g , to reduce global oil production, but, as is always the case with such deals, the final outcome will only be perceptible later on. the initial impact on natural gas demand was more muted, but global production of liquefied natural gas was constrained by a lack of demand and the future is increasingly uncertain [ ] . coal demand in china was hit early by falls in industrial output and electricity demand, both have swiftly rebounded in china, but remained constrained elsewhere [ ] . natural gas and coal demand are both linked to power generation, the relative impact there was related to the extent and duration of the 'lockdown', and its varied impact on industrial activity, and this complicates matters in relation to coal, domestic gas and electricity demand [ ] . renewable power generation has fared relatively well, particularly in those markets where capacity is already significant, and it tops the merit order. at the same time, the pandemic has impacted on the operation of energy installations, such as offshore wind platforms, and also slowed the construction of new production facilities and infrastructure. first, because construction activity was hindered by new safety measures and second because the breakdown in international trade disrupted supply chains [ ] . indeed, the iea, forecasts approximately % less growth in than in , with growth rebounding in which is a discontinuity with pre-pandemic trends, albeit the growth of renewables as a percent of the overall mix is continuous with longer-term trends [ ] . the pandemic has also exposed the vulnerabilities of relying on international supply chains for vital healthcare products and appliances, and the energy industry has been affected here too. for renewables and batteries, government-ordained work stoppages and border and port closures have also led to a disruption of trade in materials, components and assembled goods [ ] . as the reliability of global supply chains can no longer be taken for granted, governments and corporations are considering 're-shoring' essential and strategic industries, which typically includes the energy sector. as such, the pandemic might accelerate an ongoing trend of 'de-globalization' and the re-shoring of critical energy industries, especially those in which china has obtained a pivotal position in the supply chain and production line. covid- has also underscored the need to closely monitor security of supply for certain minerals that are essential for the energy transition, including cobalt, nickel and copper [ ] . in the medium term we will need to closely watch recovery programmes and the degree to which struggling fossil fuel companies are supported, and whether there are any decarbonisation conditions. and the struggle is apparent: already, many energy companies have slashed their investment plans, final investment decisions (fids) have been delayed and the longer-term prospects for new production are threatened, though not everywhere. the iea estimates that total energy investment will fall by % in [ ] . the lng industry is instructive with fids delayed in north america and mozambique, whilst prospects in the eastern mediterranean now seem bleak, although qatar is going ahead with its expansion. as such, whether or not fossil fuel producing states decide to support their ailing producers is a critical factor in determining the medium-term oil, gas and coal outcome. the plight of the shale industry in the us is also instructive: the rig count has plummeted, production is falling, and bankruptcies are rising. just as in - , the us shale industry will survive, but production will probably never return to its - peak [ ] . this will take the shine off us 'energy dominance' with potentially wide-ranging geopolitical consequences. although it is still early days, companies invested in renewable energy are more optimistic about their future, but it remains to be seen whether international oil companies (iocs), such as bp, shell and total, will accelerate their diversification into 'new energy' as they grapple with the loss of fossil fuel revenue. much also depends on the pace and scale of demand recovery, but there are those who argue that might turn out to be the date of global peak fossil fuel demand [ ] , and, as such, in hindsight covid- may be viewed as having accelerated the demise of fossil fuels. the long-term outlook will be shaped by the pace of economic recovery and the degree to which the trillions of dollars of government stimulus support fossil-fuel incumbents and to which they accelerate clean energy production and demand side management. equally, reduced electricity demand growth may weaken the appetite for new coal power in emerging economies. the sentiment of the financial sector is also a critical factor here, and, see below, accelerated fossil fuels divestment seems one likely outcome [ ] . the medium-term cuts in investment in production, discussed above, may result in high oil and gas prices and volatility in the second half of the decade, although bp have revised their long-term oil price outlook, and announced a usd bn to . bn write-off [ ] . however, it is worth remembering that over % of states are not net fossil fuel exporters. the very prospect of future high oil and gas prices may accelerate the transition away from such fuels; and fossil-fuel demand destruction would gather pace, which would constrain prices. thus, we can conclude that, for most states, investing in the low-carbon transition is a win-win strategy that both stimulates economic recovery and reduces the cost of future fossil-fuel imports. an historically intransigent aspect of sustainable energy transitions has been the financial practices that have heretofore supported fossil fuel industries, as well as the financial power of many incumbent actors. transnational, and national, oil and gas companies have kept up investments in long-term projects; coal investments, often by japan and china, have continued in developing countries thereby underpinning the expansion of coal fired electricity; whilst state subsidies for fossil fuels continue to far outstrip support for sustainable energy [ ] . prior to this crisis, and the implications for fossil fuel companies listed above, these investment practices were partly responsible for locking-in difficulties associated with phasing out fossil fuels [ ] . over the past few years, however, there have been growing moves to divest away from fossil fuels by increasingly high profile private and quasi-state actors in many oecd countries. there is also growing recognition of financial risks associated with continued fossil fuel investment, as well as re-evaluations of fossil fuel reserves associated with concerns about stranded assets. lastly, energy policy has played a strong role in, directly or indirectly, supporting investment in renewables, energy efficiency, grid improvements, and storagealbeit investment levels remain too low [ ] . evidence thus far suggests that the implications of covid- may accelerate some of these more recent trends. the stronger demand and price performance of green energy compared to fossil fuels through the crisis is a core aspect of expected longer-term sustainable energy transitions [ ] . this potential for relatively improved financial returns for green versus brown energy is further underpinned by recent analysis showing superior investment returns from renewable versus fossil fuel shares since the pandemic, and indeed over the past years [ ] . we have already seen, above, that low oil and gas demand and prices have resulted in falling investment in, especially, us shale but also a range of other petroleum provinces. there is also, however, and this is more of a discontinuity with existing trends, potential for a fall in investment flows into coal plants as economic growth in emerging economies weakens [ ] . it is also important to also think about who is investing at the moment given that so many national governments, and some international actors, are currently implementing, and devising, significant rescue and stimulus packages which might offer an historic chance for sustainable investment [ ] . indeed, the iea has already pointed out that % of funds invested in energy come, directly or indirectly, from the state [ ] , and that governments, globally, are planning to spend usd tn in the next months on recovery packages [ ] . thurs far, short-term government spend has been focused on reacting to the health challenge and protecting livelihoods, jobs and businesses and, as such, tends to support 'business-as-usual' [ ] . indeed, a point of comparison regularly made is with the recovery process post which, given limited green stimulus, returned the world quite quickly to an upward trajectory of emissions [ ] , [ ] , [ ] . there is more hope, however, this time around, of medium and longer-term stimulus packages leading to green outcomes. significant cleantech market progress [ ] , mainly in efficiency and electricity sectors, means that 'business-as-usual' in energy is now greener than in for a lot of countries. what can be inferred from this is that, for those countries that have strong and/or growing cleantech sectors, focusing investments on green energy may well mean effective short-and medium-term stimulus. hepburn et al [ ] , argue that green investments, for example in energy efficiency building retrofits, renewables, and clean energy infrastructure, can be delivered quickly and have high economic and jobs multipliers, see also [ ] , [ ] . indeed, relative fossil fuel and sustainable energy share performances and the longer-term demand outlook for oil and coal provides more evidence to support the argument that sustainable initiatives offer superior economic returns for government spending [ ] , as well as contributing towards longer term resilience and national emissions targets. although the evidence base for green stimulus is much stronger this time around, it is not yet clear whether, or to which extent, policymakers in oecd countries will choose that path. what is clear is the emergence of high-profile, and widely disseminated, arguments that state actions in this time period are crucial to a recovery that supports, and perhaps even accelerates, sustainable energy transitions [ ] [ ] [ ] . it is also worth noting that there will be significant variety in whether countries pursue green stimulus, partly in relation their existing commitments to sustainable energy, and how financially embedded clean and fossil fuel energy sectors are. sustainable energy transitions have played out against an historical backdrop of globalisation -in the sense of increasing interdependence of energy systems, global supply chains, and energy-associated externalities -albeit more recent trends, exacerbated by the pandemic, have been towards 're-shoring'. yet, there has been a general lack of coordinated and inclusive global energy governance that spans across all actors and sectors. the historically dominant global governance institutions typically consist of either producer or consumer clubs, and they tend to be preoccupied with energy security (of supply or demand) rather than with decarbonization per se [ ] . the last decade, however, has seen major innovations in intergovernmental governance, notably the creation of the international renewable energy agency (irena) in , the adoption of un sustainable development goals, and the paris agreement. the latter, in particular, now requires most national governments to devise and regularly update their climate pledges, the so-called nationally determined contributions (ndcs). while this has prompted countries like the uk and regions like the eu to adopt or propose net zero emission targets by the middle of the century, other major players, most significantly the united states, have backtracked at the national level. even within the eu there are divisions: most western eu member states have embraced the energy transition as a means to green and diversify their energy supply, and as an industrial opportunity, whilst many eastern eu members are more reluctant, for example poland is opting to secure jobs in coal [ ] . in this sense, the world in general and the eu in particular face a multi-speed energy transition. the paris agreement has, importantly, both underpinned the notion of sub-national and non-state action and galvanized new actors, including cities, civil society groups, investors, transnational movements and corporations. overall, one could say that the site of sustainable energy governance has been gravitating away from multilateral diplomacy and across national, transnational and local scales [ ] . this dynamic was explicitly supported by the paris agreement which, in starting from nationally determined pledges, took an explicitly more bottom-up approach. as things stand, however, policies and regulatory frameworks in almost every country are insufficient in terms of reaching the new emissions targets [ ] . such was the state of affairs when covid- struck. the pandemic will have multiple implications for multi-scalar energy governance. one immediate consequence is that the cop climate summit, which was planned to take place in november in glasgow, has been postponed by a year. this raises the possibility that the us is represented at the cop by a new administration with a more positive climate stance, depending on the outcome of the upcoming us elections. more broadly, the response of governments to the covid- crisis thus far seems to bode ill for the system of multilateral cooperation. regional and international organizations from the eu to the un have struggled to muster a coordinated response to the pandemic, the us has announced its withdrawal from the world health organization (who), and geopolitical tensions between china and the united states have escalated. the frailty of the current system of global cooperation might reinforce the decentralization of energy governance from the multilateral to national, transnational and local scales marking some continuity with direction of travel in governance. it will also be interesting to see in this regard whether, for example, covid- exacerbates or diminishes the aforementioned differences in speed and enthusiasm with which the eu member states pursue the energy transition and how the european commission will cope with that. another impact of covid- on the multi-scalar nature of sustainable energy governance is that the role of national governments has been stepped up, markedly in many places, in order to respond to the pandemic [ ] , [ ] . indeed, the pandemic has led to levels of government intervention in markets and private life not seen in many decades and, as such, marks some discontinuity with longer term trends. the effectiveness of government intervention, however, will partly depend on their economic and institutional capacities [ ] , which may be stretched thin as a result of the unprecedented responses required so far to covid- . at the same time, there is also evidence of cities around the world responding quite rapidly, often by changing transport modes and enabling distancing while travelling [ ] , [ ] , [ ] , sometimes even as national governments take a different course. again, this appears to be an acceleration of the pre-covid- trend of greater multi-scalarity in how energy is governed, as the pandemic so far shows signs of re-localizing and re-calibrating places and spaces of energy governance. clearly, how different social groups are affected by sustainable transitions differs markedly between and within countries. those employed within fossil fuel industries may feel very differently from those living within regions at high risk from rising sea levels -hence recent calls to adjust for such inequalities when governing for sustainable energy transitions [ ] . within many oecd countries, however, in the years immediately preceding covid- , public support for action on climate change was at an all-time high [ ] , [ ] . for example, mass transnational movements, like extinction rebellion and the youth climate movement, took a considerable step up in the late s, whilst opinion polls showed increasing levels of concern about climate change as well as support for solutions, like renewables. reports, in particular ipcc . degrees [ ] , provided a far clearer picture of the human and social implications of not mitigating, whilst more publicly visible, physical evidence of climate change had also been mounting. all of which led to a consensus in many oecd countries that the s are vital for action to mitigate. at the time of writing, june , much of society is understandably focused on human security, improved health, protection of jobs and incomes, and economic recovery. those working in high carbon and clean energy industries will seek support as part of recovery packages. arguably, however, pre-covid- surges in support for climate action as well as how attitudes evolve during the pandemic will be important considerations for policymakers as they make decisions about what priority they give to green stimulus, and to developing much needed new sustainable policies over the medium term. this, in turn, raises the relevance of debates in the public sphere, across newspapers, social media and civil society, on what a post-covid- world will look like -i.e. the 'new normal'. one of the key outcomes of lock-down and ongoing social distancing has been considerable, albeit partly non-voluntary, changes in social practices -including in mobility and work practices [ ] . transport has been one of the hardest hit sectors, especially air, rail, car and bus travel, as people have stayed home. by contrast, in many countries walking and cycling has proven the obvious travel replacement for shorter journeys [ ] , [ ] . as we have seen, these practice changes have had clear implications for oil demand, whilst reduced high carbon travel has been a major contributor to covid- related emissions reductions. the key question here is whether social practice changes persist firstly beyond lock-down, and then through social distancing phases -i.e. staying with the example of transport, will demand for transport overall be lower longer term, and how will transport choices differ? there are various clues that we can consider in relation to this question. firstly, in terms of preferred modes of transport, some national and many local governments, as mentioned above, have announced new policies aimed at structurally reinforcing moves towards cycling and walking within cities. conversely, with relevance for longer journeys, social distancing lowers demand for public transport, which may mean a switch to more car journeys for those that have that choice. at the same time, however, although car sales have fallen dramatically, and car companies are amongst those clamouring for government support, electric vehicle sales are still up globally [ ] . secondly, lockdown has provided new evidence about the effectiveness of working from home, not least due to the time saved from not having to commute [ ] , [ ] . because social distancing also affects people's willingness to return to work, and some workplaces may not have sufficient space, the duration of social distancing is a key variable in determining longer term travel demand. this is also because, as some sociologists have noted [ ] , the longer the time period over which people are compelled to change practices the more likely some behavioural changes become new norms or habits. in sum, in terms of the carbon content of travel, covid- appears so far to be continuous with and accelerated existing trends, like cycling and working from home, but may present some difficulties in the medium-term for policies encouraging public transport as an alternative to cars. lastly, when thinking about public responses to the pandemic, there is evidence emerging that covid- has demonstrated, in more vivid terms, links between human activity, biodiversity loss, environmental degradation and health [ ] . air pollution was already climbing up political agendas in many parts of the world and the who estimates that annually . million deaths result from exposure to outdoor air pollution [ ] . now it has also become a key focus within the pandemic. various studies linking covid- deaths with air pollution have been widely circulated, including comments from the who that if you are exposed to air pollution your chances of being severely affected are much higher [ ] , [ ] . at the same time, it has not gone unnoticed that air pollution has dropped significantly and, in the case of china, started to rise again as lockdown eases. indeed, a recent ipsos mori poll, undertaken in europe, shows not only that people have noticed the clean air, but that they are now asking policymakers to refocus on wellbeing over other indicators such as gdp [ ] . indeed, covid- , like climate change, was no 'black swan' event -there have been several warnings of a pandemic of this nature [ ] , [ ] . what covid- has more widely demonstrated, therefore, is the devastating consequences of ignoring such warnings, thereby offering some potential to argue for an accelerated shift in political focus onto long-term measures of broad resilience, and away from short-term gains. it is clear that the pandemic occurred at a critical juncture in terms of the relationship between politics and sustainable energy transitions. state support and policy intervention has been key to promoting efficiency and accelerating decarbonisation of the energy system, particularly in a just manner; now the need for the state to invest to support post-pandemic economic recovery presents an opportunity to energise green growth. many of the main drivers of what happens next represent a continuation of processes that pre-date the pandemic. a key question that has emerged here is whether or not there will be an acceleration of trends towards a more sustainable future, or whether the desire to protect existing jobs and incumbent industry will retard the momentum that was emerging in some countries under the banner of a 'green new deal' or 'green growth'. one lesson from the crisis was that, when it comes to emissions, a rebound to the ways of old is as likely as not. however, this perspectives piece has found good reasons to think that this time might be somewhat different. given relative economic performances between fossil fuels and sustainable energy during the pandemic, there appears to be a greater chance of green stimulus this time around. much also depends on whether changes imposed in the lockdown result in longer term behavioural and structural change in relation to issues like fossil fuel demand, air quality, and support for climate change mitigation. new global accords now exist, in the form of the paris agreement and the un's agenda and associated sdgs, that provide targets and direction for politicians and policy makers to strive towards and, importantly, against which increasingly active publics can hold them to account. furthermore, the covid- crisis has explicitly exposed a lack of political response to warnings of human disaster and of resilience in public health and welfare, which provides further support for arguments that a post-pandemic world should not be politics, or indeed business, as usual. rising diversity and inequality, both within and between countries, were also a hallmark of recovery from the global financial crisis, but these issues may well become even more significant as some parts of the world, europe, some us states and cities, focus more on sustainable change, whilst others cannot afford, or will not be politically incentivised, to do so. clearly, it will be critical to see what happens in the major economies, china, the us and the eu, but as over % of future demand growth between now and lies outside the oecd, the road to recovery in the emerging economies of asia, latin america and sub-saharan africa is just as significant. the oil price crash that accompanied the pandemic has made clear the need for so the so-called 'producer economies' to finally put themselves on a more sustainable path, particularly if a green recovery results in an earlier peak in fossil fuel demand and an acceleration of permanent demand destruction. failure of fossil fuel-dominated economies to adapt to such a trajectory will likely result in instability and conflict, both within and between states. in this context, there is an urgent need to explore further what these geographical diversities mean for the future politics of sustainable energy transitions, whilst not forgetting the growing significance of scale and diversity in political responses within countries. last, but far from least, there is the matter of publics and political participation. some argue that publics will now be focused on jobs/recovery only, but there are some early indications that this is an over-simplification. thus, it will be important that those policymakers tasked with ensuring sustainable transitions appeal to new behaviours, values, and evidence as they design recovery packages, alongside reviving some aspects of business-as-usual in the economy. it is in this wider societal context that academics can play a critical role in helping to understand possible futures, making clear that what is done today can shape those futures in a positive way. rather like the archivist in the film, 'the age of stupid', who in reflects back on why society failed to take the actions necessary to avoid catastrophic climate change, we do not want to look back on - as a time when we were unable to turn a global health crisis into an opportunity to finally put the world on a more sustainable path, both in terms of human security and environmental sustainability. supplementary data to: le quere et al ( ) temporary reduction in daily global co emissions during the covid- forced confinement' global progress report on climate change sustainable recovery imf ( ) world economic outlook temporary reduction in daily global co emissions during the covid- forced confinement covid- , changing social practices and the transition to sustainable production and consumption. version . china's air pollution overshoots pre-crisis levels for the first time global energy politics a climate for change? the impacts of climate change on energy politics re-scaling ipe: local government, sustainable energy, and change how the energy transition will reshape energy geopolitics' caution! transitions ahead: politics, practice and sustainable transition management toward a cultural politics of climate change: devices desires, and dissent understanding carbon lock-in will covid- fiscal recovery packages accelerate or retard progress on climate change? navigating the clean energy transition in the covid- crisis the history and politics of energy transitions: comparing contested views and finding common ground the speed of the energy transition: gradual or rapid quarterly gas review: the impact of covid- on global gas markets anouke honoré ( ) natural gas demand in europe: the impacts of covod- and other influences in . oxford: oxford institute for energy studies covid- weakens both sides in the battle between coal and renewables. behavioural and social sciences in nature research susceptibilities of solar energy supply chains. global policy opinion (blog). a clean energy progress after the covid- crisis will need reliable supplies of critical minerals accessed the oil crash's unlikely winner: saudi arabia. foreign policy was the peak of the fossil fuel era? carbon tracker progressing strategy development, bp revises long-term price assumptions energy investing: exploring risk and return in the capital markets ministerial roundtable on economic recovery through investments in clean energy $ tn us coronavirus relief comes without climate stipulations', the guardian pandemic, price wars, petrostates and the new energy order the political economy of decarbonisation: from green energy 'race' to green 'division of labour fiscal impacts of energy efficiency programmes -the example of solid wall insulation investment in the uk green versus brown: comparing the employment impactsof energy efficiency, renewable energy, and fossil fuels using an input-output model global mayors launch covid- economic recovery task force a place in the sun? irena's position in the global energy governance landscape new directions in the international political economy of energy prospects for powering past coal city leaders aim to shape green recovery from coronavirus crisis biking provides a critical lifeline during the coronavirus crisis covid- crisis hammers auto industry could climate change and biodiversity loss raise the risk of pandemics? ambient air pollution: health impacts is air pollution making the coronavirus even more deadly?', guardian th assessing nitrogen dioxide (no ) levels as a contributing factor to coronavirus fatality addressing climate change in post-pandemic world covid- stimulus measures must save lives, protect livelihoods, and safeguard nature to reduce the risk of future pandemics', ipbes website th the multi-speed energy transition in europe: opportunities and challenges for eu energy security key: cord- -ulsz d authors: grabia, monika; markiewicz-Żukowska, renata; puścion-jakubik, anna; bielecka, joanna; nowakowski, patryk; gromkowska-kępka, krystyna; mielcarek, konrad; socha, katarzyna title: the nutritional and health effects of the covid- pandemic on patients with diabetes mellitus date: - - journal: nutrients doi: . /nu sha: doc_id: cord_uid: ulsz d covid- related restrictions aimed at curbing the spread of the coronavirus result in changes in daily routines and physical activity which can have a negative effect on eating and health habits. the aim of the study was to assess the impact of the covid- pandemic on patients with diabetes and their nutrition and health behaviours. a survey conducted in july included individuals with type (n = ) and (n = ) diabetes mellitus from poland. to assess nutritional and health behaviours, an online questionnaire covering basic information, anthropometric data, and details regarding physical activity, eating, and hygiene habits was used. almost % of all respondents with type and diabetes mellitus (dm) stated that their disease self-management had significantly improved. over % of all participants declared that they had started eating more nutritious and regular meals during the covid- pandemic. enhanced hygiene, in particular, during the period, a statistically significant increase in hand sanitiser use was reported by respondents ( % vs. %, p < . ). the study demonstrated that the pandemic had a significant impact on the behaviour of patients with dm. improved disease self-management and making healthy, informed food and hygiene choices were observed. since the emergence of sars cov- , a new coronavirus known as severe acute respiratory syndrome coronavirus- , at the end of , the related disease called covid- has spread rapidly around the world [ ]. from march , a "cordon sanitaire" was formed around poland and on march the state of epidemic including home confinement was introduced in the country. at the time of writing, the peak number ( ) of daily cases in poland occurred on june . at the time of commencing the study, there had already been , infections and deaths in poland [ ] . from july to july , the period when the survey was conducted, the following regulations were in force in the country: nose-and-mouth coverings in confined public areas; closure of primary and secondary schools, and institutions of higher education; food and drink establishments were operational with enhanced sanitary measures in place (nose-and-mouth coverings required when not at the table, disinfecting tables, keeping a minimum distance of . m between patrons); gyms and swimming pools were reopened on june ; individuals were allowed to socialise indoors in small groups; in most places, access to specialist medical care was provided at outpatient clinics [ ] . diabetes mellitus (dm), a metabolic disorder of various etiologies, is characterised by chronic hyperglycaemia and disturbances in insulin secretion or its activity, or both. type diabetes mellitus (t dm) is an insulin-dependent, multifactorial autoimmune disease which results in degradation of the beta cells of islets of langerhans, which causes impaired insulin production and secretion [ ] . patients with t dm require intensive treatment involving administration of exogenous insulin in the form of multiple daily injections or as continuous subcutaneous infusion of insulin using personal insulin pumps [ ] . type diabetes mellitus (t dm) is described as a condition of insulin resistance with relative insulin deficiency, commonly caused by qualitative and quantitative secretory defects [ ] . initial treatment of this type of diabetes involves administration of medication to achieve glycaemic stability. ultimately, many patients require insulin therapy because of progressive failure of the beta cells and development of complications [ ] . regulations imposed to curb the transmission of covid- are likely to have an impact on daily routines, including exercise and eating habits. for people with diabetes mellitus, exercise is an integral part of their disease management [ , ] . patients may also experience increased mental stress caused by the unpredictability of the situation and as a result of social isolation [ ] . this may lead to excessive consumption of products rich in simple carbohydrates which can alleviate stress, since their ingestion stimulates the production of serotonin and enhances the mood. consuming such products is associated with an increased risk of obesity and complications of covid- [ ] . a lack of physical activity, poor food choices, and heightened psychological stress may have a detrimental effect on the immune system, which may not produce a proper response when exposed to the new virus [ ] . according to a report by the centers for disease control and prevention, individuals with t dm and t dm may be at an increased risk for severe illness from covid- due to susceptibility to lung infection, which is a consequence of dm-related metabolic disturbances and immunosuppression [ , ] . an in vitro study demonstrated that chronic hyperglycaemia changed the innate immune system, thereby acting on chemotaxis, phagocytosis, but also on bactericidal activity of neutrophils and macrophages [ ] . according to the american diabetes association (ada), currently available data regarding covid- is not comprehensive enough to show whether individuals with dm, particularly well-controlled dm, are more prone to developing the disease as compared with the general population. however, if patients are not metabolically balanced, they may experience more considerable blood glucose fluctuations which can cause a number of diabetes-related complications. these complications may make patients with dm more susceptible to contracting covid- and other viral infections due to the body's limited ability to fight them [ ] . the aim of the present study was to assess the impact of the covid- pandemic on the nutritional and health behaviours of patients with dm. the study, which collected data via an online survey, was conducted among polish patients with dm, with a median age of years (lower to upper quartile, - years old) between july and july via private facebook groups of polish diabetes societies. the main study inclusion criterion was completion of the survey section regarding diabetes, which was a prerequisite for completing the remaining sections. responses from individuals residing abroad, women with gestational diabetes, and individuals in quarantine were rejected. each participant was informed of the anonymity and confidentiality of the survey and its purpose. each respondent was allowed to complete the survey only once and exit it at any time, which would result in unsaved responses. participants confirmed their voluntary consent for study participation by completing the survey. they could not provide names and personal data. parents of young children completed the questionnaire on their behalf. the study was conducted in full compliance with national regulations (consent of bioethical commission of the medical university of bialystok no. r-i- / / ) and the declaration of helsinki. the questionnaire (see appendix a) consisted of three sections. the first section contained questions regarding type of diabetes mellitus the participant suffered from, their gender, age, body height and weight, level of education and place of residence. anthropometric measurements were self-reported. the body mass index (bmi) is a measure used to determine nutritional status. it was calculated using the following formula: body weight in kg divided by height in meters squared. in paediatric patients (under years of age), bmi was interpreted in relation to norms contained in clinical growth charts. the th, th, and th centiles correspond to the limits of underweight, overweight, and obesity, respectively [ ] . for adults, the following who approved standards were applied: underweight (below . kg/m ), normal ( . - . kg/m ), overweight ( . - . kg/m ) and obese (above . kg/m ) [ ] . the second section contained questions relating to disease duration, type of treatment received, and result of the hba c test performed within three months of questionnaire completion. the last section contained questions regarding physical activity, eating behaviours, and hygiene habits such as stress level, daily screen time, and sleep routine. as for physical activity, respondents could indicate whether and how the type of activity they participated in had changed. the activities included dancing, fitness, swimming, running, gym, cycling, gymnastics, and walking. the frequency of exercise sessions could be described by respondents as "i don't exercise", " - times per week", " - times per week", " and more times per week". assessment of changes in eating habits was based on the consumption of the following products: coffee, convenience food, dairy products, delivery meals, eggs, energy drinks, fresh bread, fresh fish, fresh vegetables, frozen fish, grain products, homemade bread, nuts, red meat, salty snacks, sweet beverages, sweet snacks, water, and white meat. as for hand washing and sanitiser use, the respondents could indicate the following situations: "after coming home", "after using the toilet", "before cooking", "after contact with animals", "after leaving public transport", and "after leaving shops". the number of hours the respondents spent sleeping fell into the following categories: "under - h", " - h", or "over h". as for time spent in front of the computer or tv, the respondents could select from the following: "less than h a day", " - h a day", " - h a day", or " or more hours a day". stress levels could be classified as follows: "low", "medium", "high", and "very high". the questionnaire was based on previously published work of other authors with modifications reflecting the situation under investigation and study cohort [ , ] . furthermore, questionnaires originally published in foreign languages were translated into polish and assessed by a polish native speaker to exclude bias in interpretation. the questionnaire was pretested on a small sample of respondents from the target population to allow for subsequent eradication of formal and substantive errors. statistical analysis was performed using statistica software (version ; statsoft inc., krakow, poland). normal distribution of the studied variables was checked using the shapiro-wilk test. the mann-whitney u test was used when data was not symmetrically distributed. relationships between qualitative features (e.g., periods before and during the covid- pandemic) were evaluated using the chi-square independence test. in justified cases, yates' correction was used. prior to conducting the survey, a minimum sample size was calculated, which was used for estimating of the number of people who should be tested in order for intended results to be obtained with a specified confidence level (α = . ) and a maximum error ( %). the p-value < . was considered to be statistically significant. due to the possibility of confounding between variables, additional characteristics of the results for all items in which it occurred were included in the supplementary material. the results section contains outcomes relating to all study participants (adults and children together). due to the fact that / of respondents with t dm were children, we presented the results obtained in this group of patients in a separate subsection. the outcomes obtained, after the exclusion of children under years of age from the study group, were consistent with the results for the entire study cohort. characteristics of the study cohort are presented in table . the majority of respondents were individuals with type diabetes mellitus ( %) and women ( %). among survey participants, % of patients with t dm used personal insulin pumps, while % used insulin pens. as for patients with t dm, % used insulin pens and % oral drugs. none of the participants reported simultaneous use of insulin injections and oral medication. among the completed questionnaires, % were filled in by parents of children with t dm. a normal bmi was observed in % of the study cohort, overweight in %, obesity in %, and underweight in %. the majority of study participants ( %) had a university degree, % of respondents were unemployed, % worked in the office, % worked from home, and the remainder were students ( %). there were no participants who were quarantined prior to questionnaire completion. over half ( %) of the respondents lived with their parents, % lived with a partner, and the remaining % resided alone. the study participants were asked if their disease self-management had improved during the covid- pandemic. among the participants, % individuals with t dm declared that their disease control had deteriorated, % stated that it had improved, while % did not report any changes. as for body weight, % of study participants reported an increase in body weight during the pandemic, % reported an increase of ≤ kg, and % reported > kg. only % of patients with dm stated that their body weight did not change. the remaining % of patients reduced their body weight, % by ≤ kg and % by > kg. prior to the covid- pandemic, % of study participants did not engage in any physical activity, % participated in physical activity - times a week, % - times a week, and % over times a week as compared with the period during the pandemic ( %, %, %, and %, respectively). there were statistically (p < . ) significant differences among the above variables (see table ). figure shows the type of physical activity chosen before and during the covid- pandemic. a statistically significant increase in walking was demonstrated ( % vs. %, p < . ) while a statistically significant decrease in participation in gymnastics, swimming, and dancing (p < . each), gym and fitness classes (p < . each) was observed. additional characteristics between type of disease and gender are presented in supplementary table s ). nutrients , , x for peer review of abbreviations: type diabetes mellitus (t dm), type diabetes mellitus (t dm). differences between "before" and "during" the covid- period were evaluated by the chi-square test (* p < . ). differences between the type of physical activity "before" and "during" the covid- pandemic. differences between "before" and "during" the covid- pandemic were evaluated by the chi-square test (* p < . and ** p < . ). when asked if they started eating more healthily during the pandemic, % of respondents declared improvements in their dietary habits. survey results demonstrated that % of respondents had started eating more regular meals, in particular main meals. the same total percentage of the study cohort declared that they had started preparing their own meals (see supplementary table s ). differences between the type of physical activity "before" and "during" the covid- pandemic. differences between "before" and "during" the covid- pandemic were evaluated by the chi-square test (* p < . and ** p < . ). ( ) % ( ) % ( ) % ( ) city (≥ k inhabitants) % ( ) % ( ) % ( ) % ( ) % ( ) % ( ) up to years % ( ) % ( ) % ( ) % ( ) % ( ) % ( ) hba c (%) d . ( . - . ) . ( . - . ) . ( . - . ) values are expressed as median, lower, and upper quartile (me (q -q )) or percentage and number of respondents (% (n)). abbreviations: type diabetes mellitus (t dm), type diabetes mellitus (t dm). differences between "before" and "during" the covid- period were evaluated by the chi-square test (* p < . ). when asked if they started eating more healthily during the pandemic, % of respondents declared improvements in their dietary habits. survey results demonstrated that % of respondents had started eating more regular meals, in particular main meals. the same total percentage of the study cohort declared that they had started preparing their own meals (see supplementary table s ). the results revealed that % of respondents consumed one to two meals per day before the pandemic as compared with % during the pandemic, % vs. % consumed three to four meals a day, and % vs. % had more than five meals a day. no statistical significance was demonstrated between the pre-covid- period and the period during the pandemic for any of the above variables, in any of the study participants. more than % of respondents admitted that frequency of snacking between meals increased during the pandemic. consumption of selected food products during the covid- pandemic is presented in figure and the breakdown by the type of diabetes and gender is included in supplementary table s . the most marked increase in intake was revealed for the following products: water ( %), fresh fruit ( %), vegetables ( %), and grain products ( %). the most substantial decrease in consumption was recorded for the following products: fast food ( %), convenience food ( %), salty snacks ( %), delivery meals ( %), red meat ( %), and sweet snacks ( %). nutrients , , x for peer review of ( %), vegetables ( %), and grain products ( %). the most substantial decrease in consumption was recorded for the following products: fast food ( %), convenience food ( %), salty snacks ( %), delivery meals ( %), red meat ( %), and sweet snacks ( %). the study revealed a statistically significant increase in hand sanitiser use during the covid- pandemic (p < . ). prior to the pandemic, % of study participants never used hand sanitisers, % used them sometimes, while % used them very often. use of sanitising solutions increased during the study revealed a statistically significant increase in hand sanitiser use during the covid- pandemic (p < . ). prior to the pandemic, % of study participants never used hand sanitisers, % used them sometimes, while % used them very often. use of sanitising solutions increased during the pandemic, i.e., % of respondents declared that they used them very often, while % reported using them sometimes. a statistically significant relationship between frequent hand washing/antibacterial agent use before and during the covid- pandemic was found (figure ). the biggest, statistically significant differences were observed in hand washing after leaving shops ( % vs. %, p < . ), public transport ( % vs. %, p < . ), and after returning home ( % vs. %, p < . ). additional characteristics regarding the type of disease and gender are presented in supplementary table s ). nutrients , , x for peer review of figure . frequency of hand washing/antibacterial agent use before and during the covid- pandemic. differences between "before" and "during" the covid- period were evaluated by the chi-square test (* p < . ). a statistically (p < . ) significant dependence between the period before the start of the covid- pandemic and the time during the pandemic was demonstrated in the number of hours spent in front of the tv or computer. prior to home confinement caused by covid- , only % of study participants spent more than h per day in front of the tv or computer, while % spent - h, % spent - h, and the remainder ( %) had less than h of screen time (during the pandemic it was %, %, %, and %, respectively). the dependence between the period before the covid- pandemic and that during the pandemic, and the number of hours of sleep was also statistically significant (p < . ), i.e., % of respondents declared sleeping more than h per day prior to the pandemic, with the figure reaching % during the pandemic. the percentage of study participants sleeping less than the recommended number of hours decreased, i.e., % vs. % of respondents slept between and h per day, and % vs. % slept less than h per day. statistically significant (p < . ) differences were observed in stress levels before, at the beginning of the covid- pandemic, and at the time of completing the questionnaire. average stress levels increased at the start of the pandemic and returned to nearly pre-pandemic levels at the time of survey completion, as shown in figure . detailed characteristics of the above variables (screen time, sleep routine, and stress levels) in relation to the type of diabetes and gender are presented in supplementary tables s -s . differences between "before" and "during" the covid- period were evaluated by the chi-square test (* p < . ). a statistically (p < . ) significant dependence between the period before the start of the covid- pandemic and the time during the pandemic was demonstrated in the number of hours spent in front of the tv or computer. prior to home confinement caused by covid- , only % of study participants spent more than h per day in front of the tv or computer, while % spent - h, % spent - h, and the remainder ( %) had less than h of screen time (during the pandemic it was %, %, %, and %, respectively). the dependence between the period before the covid- pandemic and that during the pandemic, and the number of hours of sleep was also statistically significant (p < . ), i.e., % of respondents declared sleeping more than h per day prior to the pandemic, with the figure reaching % during the pandemic. the percentage of study participants sleeping less than the recommended number of hours decreased, i.e., % vs. % of respondents slept between and h per day, and % vs. % slept less than h per day. statistically significant (p < . ) differences were observed in stress levels before, at the beginning of the covid- pandemic, and at the time of completing the questionnaire. average stress levels increased at the start of the pandemic and returned to nearly pre-pandemic levels at the time of survey completion, as shown in figure . detailed characteristics of the above variables (screen time, sleep routine, and stress levels) in relation to the type of diabetes and gender are presented in supplementary tables s -s . in children under years of age (n = ), statistically significant (p < . ) differences were found between the frequency of physical activity before and during the pandemic (see supplementary table s ). the percentage of young respondents who practiced gymnastics ( % vs. %, p < . ), swimming ( % vs. %, p < . ), and running ( % vs. %, p > . ) decreased. however, participation in walking ( % vs. %, p < . ) and cycling ( % vs. %, p > . ) increased. prior to the pandemic, over % of surveyed children consumed one to two meals per day while the remainder had five or more meals. during the covid- pandemic, more than % of respondents consumed three to four meals, % had five or more meals while fewer than % reported having one to two meals per day. survey results demonstrated a statistically significant relationship between the number of meals consumed per day before the pandemic and the number of meals eaten during the pandemic (p < . ) (see supplementary table s ) . study results revealed several improvements in dietary habits of the youngest respondents during the pandemic (see supplementary table s ). over % of children reported drinking increased amounts of water during the pandemic, whereas % declared that their intake of grain products, fresh bread, fruit, and vegetables had increased. additionally, % of all respondents reported a higher intake of dairy products, while % declared increased consumption of eggs. it is worth noting that the intake of fresh fish also grew, i.e., % of children reported increased consumption. additionally, decreased consumption of red meat, fast food, and snacks (both salty and sweet) was observed. a statistically significant increase in hand sanitiser use by the youngest respondents during the covid- pandemic (p < . ) was observed. prior to the pandemic, % of all study participants never used hand sanitisers, % used them sometimes, while % used them very often. use of sanitising solutions increased during the pandemic, i.e., % of all respondents declared that they used them very often while % reported using them sometimes. a statistically significant relationship between frequent hand washing/antibacterial agent use before and during the covid- pandemic was found (see supplementary table s ). the biggest statistically significant differences were observed in hand washing after leaving shops ( % vs. %, p < . ) and public transport ( % vs. %, p < . ). statistically significant differences were found when screen time of the youngest respondents was analysed (p < . . survey results demonstrated that prior to the pandemic, the majority of in children under years of age (n = ), statistically significant (p < . ) differences were found between the frequency of physical activity before and during the pandemic (see supplementary table s ). the percentage of young respondents who practiced gymnastics ( % vs. %, p < . ), swimming ( % vs. %, p < . ), and running ( % vs. %, p > . ) decreased. however, participation in walking ( % vs. %, p < . ) and cycling ( % vs. %, p > . ) increased. prior to the pandemic, over % of surveyed children consumed one to two meals per day while the remainder had five or more meals. during the covid- pandemic, more than % of respondents consumed three to four meals, % had five or more meals while fewer than % reported having one to two meals per day. survey results demonstrated a statistically significant relationship between the number of meals consumed per day before the pandemic and the number of meals eaten during the pandemic (p < . ) (see supplementary table s ) . study results revealed several improvements in dietary habits of the youngest respondents during the pandemic (see supplementary table s ). over % of children reported drinking increased amounts of water during the pandemic, whereas % declared that their intake of grain products, fresh bread, fruit, and vegetables had increased. additionally, % of all respondents reported a higher intake of dairy products, while % declared increased consumption of eggs. it is worth noting that the intake of fresh fish also grew, i.e., % of children reported increased consumption. additionally, decreased consumption of red meat, fast food, and snacks (both salty and sweet) was observed. a statistically significant increase in hand sanitiser use by the youngest respondents during the covid- pandemic (p < . ) was observed. prior to the pandemic, % of all study participants never used hand sanitisers, % used them sometimes, while % used them very often. use of sanitising solutions increased during the pandemic, i.e., % of all respondents declared that they used them very often while % reported using them sometimes. a statistically significant relationship between frequent hand washing/antibacterial agent use before and during the covid- pandemic was found (see supplementary table s ). the biggest statistically significant differences were observed in hand washing after leaving shops ( % vs. %, p < . ) and public transport ( % vs. %, p < . ). statistically significant differences were found when screen time of the youngest respondents was analysed (p < . . survey results demonstrated that prior to the pandemic, the majority of young respondents ( %) spent - h a day in front of the tv or computer, almost one fifth had less than h of screen time a day, whereas only % spent or more hours watching tv or using electronic devices. during the covid- pandemic, all respondents declared spending more than h a day in front of the tv or computer, % - h, % - h, and % more than h. there was a statistically significant (p < . ) increase in the number of hours devoted to sleep, i.e., % of children slept for up to h and % for more than h per day before the covid- pandemic as opposed to % and %, respectively, during the pandemic. survey results revealed that prior to the pandemic, more than one third of the youngest respondents suffered moderate or high levels of stress. at the start of the pandemic, the majority of participants experienced moderate levels of stress, while over % suffered high stress levels. at the time of questionnaire completion, fewer than % of all respondents declared suffering very high levels of stress and over % of all children evaluated their stress levels as low. comparison of periods before, at the beginning of the covid- pandemic, and the time of completing the questionnaire revealed statistically significant (p < . ) relationships (see supplementary table s ). the present study demonstrated that the pandemic had a significant impact on the nutritional and health behaviour of patients with dm. frequency of the consumption of both recommended and non-recommended products changed. the covid- pandemic also contributed to more frequent hand washing and increased use of antibacterial agents. due to limited access to medical care, some patients with dm may have experienced difficulty managing their disease. however, the study showed that the majority of respondents were metabolically balanced (median of hba c . % to . %). only % felt that they were less able to control their disease. it is worth noting that % of all surveyed patients started to monitor their disease more rigorously and over % improved their diet by eating more regular, nutrient-dense meals. a negative effect of the covid- pandemic and related government-imposed restrictions on movement was limited outdoor activity. as compared with the pre-covid- period, the study demonstrated an increase in the percentage of individuals not practicing any physical activity ( % vs. %) and those exercising one to two times per week ( % vs. %). the number of people who took up walking increased one and a half times ( % vs. %). this can probably be explained by the fact that from april , residents of poland were allowed to leave home only in the following circumstances: commuting to and from work, voluntary involvement in the fight against the covid- pandemic, and to address matters necessary for everyday living. outdoor activity was to be kept to a minimum with only walks allowed, as public parks, boulevards and playgrounds were closed. at the time the survey was conducted, the gradual process of relaxing restrictions started. swimming pools and gyms re-opened a month before the commencement of the study but were not extensively patronised [ ] . when the results of our investigation were compared with those of an italian study by renzo et al., a similar decrease in the frequency (three to four times per week) of physical activity before and during the lockdown in italy was noted ( . % vs. . %, our study % vs. %). the authors also observed a decline in interest in sports such as fitness classes, running, and gym workout [ ] . nachimuthu et al. published a brief survey conducted among indian patients with dm which revealed that % of respondents monitored their diet regularly and engaged in physical activity at home [ ] . the present study revealed that the percentage of individuals consuming five or more meals increased during the covid- pandemic ( % vs. %). an increase in the number of meals consumed ( % vs. %) was also observed by ammar et al. who investigated eating habits of healthy people in different countries [ ] . the results obtained by scarmozzino also confirmed that home confinement caused by covid- resulted in increased food consumption for around % of respondents [ ] . the problem with body weight management experienced by almost % of participants of our study may have been caused by a higher number of meals consumed per day, and thus increased calorie intake. a polish study, conducted during the lockdown, found that individuals with a higher bmi, particularly obese people, were at a heightened risk of adverse dietary changes (increased food consumption and snacking) [ ] . a study by renzo et al. investigated whether there were differences in the consumption of selected products among italians. as in our study, they observed an increase in the consumption of certain foods such as grain products, hot beverages, eggs, dairy products, fresh bread, white meat, and fresh vegetables [ ] . scarmozzino also observed an increase in consumption of fresh vegetables [ ] . several eating patterns emerged among the youngest participants of our study. on the one hand, over % of the surveyed children declared drinking increased amounts of water and nearly half reported that their consumption of grain products, dairy products, fruit, and vegetables had increased. almost a third of the surveyed children declared a higher consumption of fresh fish. on the other hand, decreased consumption of red meat, fast food, as well as snacks (both salty and sweet) was also reported. white meat and dairy products are beneficial foods which contribute to the prevention of t dm [ , ] . increased consumption of fruits and vegetables is associated with a reduced risk of t dm not only because they contain dietary fibre, essential vitamins and minerals, but also due to the antioxidant and anti-inflammatory effects of their components which include vitamins b and c, carotenoids, and polyphenols [ , ] . similar to the results of our study, a decrease in the consumption of salty snacks, sweet beverages, and delivery food was observed in an italian survey [ ] . a high intake of such products may contribute to unstable diabetes. in patients with dm, a high salt intake may carry a risk of microalbuminuria, particularly in overweight individuals. sodium retention and blood volume in dm can cause the progression of diabetic microangiopathy [ , ] . excessive sugar consumption may accelerate the development of t dm and sugar-sweetened drinks (ssbs) can be particularly harmful to children genetically predisposed to t dm [ ] . high consumption of fructose, ssbs, and high-fructose corn syrup contributes to an epidemic of insulin resistance, visceral obesity, and t dm [ , ] . bleich and wang studied consumption patterns of sugar-sweetened beverages among adult americans with t dm. they observed high consumption of these products in young adults and in low-income individuals [ ] . the glycated haemoglobin (hba c) reflects mean glycaemia over the period of approximately three months and is a useful retrospective marker of blood glucose levels as there is an association between blood glucose levels and mean glycaemia, and the risk of developing chronic diabetic complications [ ] . a healthy lifestyle involving consumption of regular, nutrient-dense meals prepared at home with quality ingredients brings many beneficial effects, in particular a reduction in hba c level. poor metabolic control is associated with frequent dining out, particularly in fast food establishments, and consumption of high-fat products and snacks between meals [ , ] . our study demonstrated a statistically significant increase in the use of sanitising agents and frequency of hand washing, particularly after coming home and leaving shops or public transport. however, a surprising finding of the study was that the percentage of people sanitising their hands before preparing food decreased. this can be explained by the fact that sanitising solutions are provided at shop entrances and their use is monitored, whereas being home gave individuals a sense of security, and therefore the need for using an antibacterial agent was removed. mental stress activates neuroendocrine processes that affect blood glucose levels by releasing cortisol, endorphins, and growth hormone [ ] . this is of adaptive importance for a healthy body but in patients with dm, post-stress hyperglycaemia can exacerbate the disease. moreover, negative emotions can reduce motivation to adhere to the prescribed treatment and to follow dietary recommendations, which can contribute to poor glycaemic control and increase susceptibility to infections [ ] [ ] [ ] . the results of our study revealed that at the beginning of the covid- pandemic, stress levels in patients with dm increased sharply (high % vs. %, very high % vs. %). at the time the survey was conducted, stress levels were starting to return to pre-pandemic levels. this may have been related to an increase in respondents' awareness that taking care of their health helps to strengthen the immune system through proper nutrition and compliance with hygiene rules. our study has several limitations. the study was retrospective and allowed us to only estimate the impact of the covid- pandemic, some respondents could not fully or accurately recall information they were required to provide. body weight and height were not measured by a qualified individual, they were self-reported and may not have been accurate. the male subgroup was not sufficiently representative, although it is a common problem in voluntary research. this study was conducted among the inhabitants of one country (poland). performing such a study on populations of other countries would allow for a more comprehensive understanding of eating habits and hygiene behaviours of patients with dm. another limitation was the fact that changes in eating habits were estimated and not correlated with data regarding the sale of particular product groups. the study could only collect data via an online questionnaire since no unauthorised persons were allowed to enter healthcare facilities due to pandemic-related restrictions. the aim of the investigation was to describe eating and health habits that occurred during the covid- pandemic, and therefore these results should not be interpreted in the context of long-term effects. despite the fact that the sample size was small (n = ), the power of the test reached %, with a confidence level (α = . ). to our knowledge, this is the first nutritional behaviour study conducted among patients with dm during the covid- pandemic. a significant effect of the pandemic on the behaviour of patients with dm was observed. the surveyed patients reported improved disease self-management and making healthy, informed food choices and hygiene habits. the success of nutritional therapy in patients with dm depends on the selection of appropriate food products by individuals, and therefore short reports in the form of questionnaires regarding patients' nutritional behaviours and their adherence to the recommended dietary regimen should be part of routine nutritional assessment performed by healthcare providers. the results reported in the present study should be used to promote public health during the covid- pandemic. supplementary materials: the following are available online at http://www.mdpi.com/ - / / / /s , table s : characteristics of the subgroups, type of physical activity before and during the covid- pandemic, table s : characteristics of the subgroups, healthy/regularity of meal consumption during the covid- pandemic, table s : characteristics of the subgroups, variation in food intake during the covid- pandemic, table s : characteristics of the subgroups, frequency of hand washing/antibacterial agent use before and during the covid- pandemic, table s : characteristics of the subgroups, duration of screen time before and during the covid- pandemic, table s : table s . characteristics of the subgroups, sleep length before and during the covid- pandemic, table s : characteristics of the subgroups, stress level distribution before, at the beginning of the pandemic and at the time of survey completion, table s : frequency of physical activity before and during the covid- pandemic in children population, table s : number of meals per day in children before and during the covid- pandemic, table s : variation in food intake during the covid- pandemic in children population, table s : frequency of hand washing/antibacterial agent use before and during the covid- pandemic in children population, table s : stress level distribution before, at the beginning of the pandemic and at the time of survey completion in children population. main meals/yes, most meals q have you started cooking more meals yourself? no/yes q has the frequency of eating certain foods changed during the pandemic? i eat more often/ i eat less often/ no change/ i don'tever eatthese products • salty snacks (crisps, crackers, bread sticks, etc.) • sweet snacks (cakes, cookies, chocolate bars) meat (beef, pork) • white meat (chicken, turkey) • fresh fish • frozen fish • eggs • dairy products (milk, yoghurt, cottage cheese) products (rice, pasta etc epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study coronavirus outbreak map (sars-cov- ) polish ministry of health. current rules and restrictions definition, diagnosis and classification of diabetes mellitus and its complications. part : diagnosis and classification of diabetes mellitus. provisional report of a who consultation natural history, and prognosis diabetes in covid- : prevalence, pathophysiology, prognosis and practical considerations physical activity/exercise and diabetes: a position statement of the american diabetes association eating habits and lifestyle changes during covid- lockdown: an italian survey relationship between diabetes and respiratory diseases-clinical and therapeutic aspects neutrophil and lymphocyte function in patients with diabetes mellitus how covid- impacts people with diabetes the height-, weight-, and bmi-for-age of polish school-aged children and adolescents relative to international and local growth references obesity: preventing and managing the global epidemic effects of covid- home confinement on eating behaviour and physical activity: results of the eclb-covid international online survey coping with diabetes during the covid - lockdown in india: results of an online pilot survey covid- and the subsequent lockdown modified dietary habits of almost half the population in an italian sample dietary choices and habits during covid- lockdown: experience from poland dietary protein consumption and the risk of type diabetes: a dose-response meta-analysis of prospective studies meat consumption, diabetes, and its complications effect of increasing fruit and vegetable intake by dietary intervention on nutritional biomarkers and attitudes to dietary change: a randomised trial fruit and vegetable intake and type diabetes: epic-interact prospective study and meta-analysis the twin white herrings: salt and sugar +sugar intake is associated with progression from islet autoimmunity to type diabetes: the diabetes autoimmunity study in the young consumption of sugar-sweetened beverages is associated with components of the metabolic syndrome in adolescents consumption of sugar-sweetened beverages among adults with type diabetes use of glycated haemoglobin (hba c) in the diagnosis of diabetes mellitus: abbreviated report of a who consultation eating behavior among type diabetic patients: a poorly recognized aspect in a poorly controlled disease food habits are related to glycemic control among people with type diabetes mellitus the relationship between stress and diabetes mellitus empirically derived patterns of perceived stress among youth with type diabetes and relationships to metabolic control disease-related distress, self-care and clinical outcomes among low-income patients with diabetes this article is an open access article distributed under the terms and conditions of the creative commons attribution (cc by) license the authors thank the participants of the study. the authors declare no conflict of interest. key: cord- -buj u b authors: corbet, shaen; (greg) hou, yang; hu, yang; larkin, charles; oxley, les title: any port in a storm: cryptocurrency safe-havens during the covid- pandemic date: - - journal: econ lett doi: . /j.econlet. . sha: doc_id: cord_uid: buj u b controlling for the polarity and subjectivity of social media data based on the development of the covid- outbreak, we analyse the relationships between the largest cryptocurrencies and such time-varying realisation as to the scale of the economic shock centralised within the rapidly-escalating pandemic. we find evidence of significant growth in both returns and volumes traded, indicating that large cryptocurrencies acted as a store of value during this period of exceptional financial market stress. further, cryptocurrency returns are found to be significantly influenced by negative sentiment relating to covid- . while not only providing diversification benefits for investors, results suggest that these digital assets acted as a safe-haven similar to that of precious metals during historic crises. the onset of the covid- pandemic has resulted in many variants of international response across social, epidemiological and economic frontiers. the same variation was similarly observed in the response of both financial markets and investors when attempting to evaluate the scale of the issue to which they were confronted. chinese financial markets acted as the initial epicentre of the shock ), however, international contagion effects quickly escalated. in the midst of this confusion, traditional flight-to-safety channels within energy markets dissipated with the escalation of geopolitical tensions largely instigated by the us, russia and saudi arabia, with investors struggling to identify credible safe-havens (goodell [ ] , ). within this environment, we test the hypotheses as to whether cryptocurrencies acted in this capacity. one mechanism through which we can proceed is through the use of sentiment data obtained through social media, based on a lexicon of terms developed to quantify the polarity and subjectivity of time-stamped data. such techniques allow for analysis not only of sentiment based on the severity of the covid- pandemic, but also as to interlinkages between such sentiment and cryptocurrencies as a safe-haven asset in such time of extreme financial market panic. such research builds on the growing literature that has identified a sharp elevation of cross-asset correlations during the early stages of the pandemic, prior to who identification ). cryptocurrencies as a hedging mechanism during periods of financial market chaos, while further validating the product's place as a credible financial market asset, would cause particular concern for regulators and policy-makers due to the wide-ranging issues present with regards to illicit usage (foley et al. [ ] ), manipulation and instability (gandal et al. [ ] ). despite these concerns, china has continued to educate and support the use of cryptocurrencies through official channels, providing government-produced literature on cryptocurrencies, which has been used to educate the population of china about the nature and future of digital currencies ). such government reassurance could act as both a catalyst and supporting structure to perceived investment safety during market panic. we collect data for cryptocurrencies from the binance exchange, which is the most liquid international exchange throughout and . data on the other included assets are collected from bloomberg. we focus on larger cryptocurrency assets, those with a market value over $ million as of end january . in figure and , we observe the volatility these assets' prices and volumes traded for the period january through march respectively, as separated by the average return and volumes of bitcoin, altcoins, exchange tokens and privacy coins, with extensive summary statistics between the periods analysed provided in table . as per corbet et al. [ ] , we define returns as the daily log changes and volatility as the five-day standard deviation. in particular, during the onset of the covid- pandemic in the aftermath of the official who pandemic declaration on january and the first case of international transmission on january , there is a pronounced and sustained increase in cryptocurrency volumes traded across each category. the next stage of data collection surrounded the identification of investor sentiment. to complete this task, twitter data was collected for a period between january and march for each of the identified companies. all tweets mentioning the terms ' , and at the same time the terms 'cryptocurrency' or 'crypto' or 'bitcoin' or 'blockchain' with inclusive search using the terms 'financial' or 'markets' were computationally collected through the search twitter function on https://twitter.com/explore using the python 'twitterscraper' package, observing platform rate limiting policies. a total number of , unique tweets were collected . the data was then aggregated by company and by day as to specifically analyse the effects of covid- sentiment on cryptocurrency returns, we employ a standard garch ( , ) methodology of bollerslev [ ] of the following form: ( ) r t−j represents the lagged value of the selected cryptocurrency returns, j number of periods before r t is observed. b v t represents the natural logarithm of cryptocurrency volumes traded, while b u sd t represents the value of the gbp/usd on the same day on which the cryptocurrency returns were generated. finally b λ t measures the influence of both the polarity and subjectivity of covid- sentiment respectively. we repeat the analysis for both the harvard general inquirer iv- and loughran and mcdonald financial sentiment dictionaries. bollerslev [ ] argued for restrictions on the parameters for positivity, ω > , α ≥ and β ≥ , and the wide-sense stationarity condition, α + β < . while the garch ( , ) process is uniquely stationary if e[log(β + αǫ t )] < , bollerslev [ ] also proved that if the fourth order moment exists, then the model can handle leptokurtosis. bonferroni adjusted results are presented in this analysis. to cater the multiple hypothesis problem, we adjust the significance level using the bonferroni correction, which leads to a significance level of . %. the generalised bonferroni method adjusts the significance level such that hypothesis h ,(i) , i = , . . . , s, is deemed rejected if and only if: this procedure has the advantage of being robust to the dependence structure of the hypothesis tests. the selection of this methodological structure enables robust analysis with regards the influence of negative sentiment relating to the outbreak of covid- on cryptocurrency prices, where significant positive interactions would reflect direct pricing effects as controlled for volumes traded as reflected, and international effects as controlled for through the addition of the gbp/usd exchange rate. the results of the garch( , ) analysis are presented in tables and when considering the role of negative sentiment relating to the outbreak and development of the covid- pandemic, our results suggest that there developed significant and pronounced timevarying price-volatility effects as investors identified both the severity and nature of the pandemic's growth trajectory and potential economic repercussions. such results are supported by the continued chinese-guidance and support of cryptocurrencies as a viable and stable asset class. such government reassurance could act as both a catalyst and supporting structure to perceived investment safety during a market panic. the use of cryptocurrencies as a safe-haven during episodes of severe market volatility will cause alarm within regulatory and policy-making authorities. the widespread lack of continuity, regulation and international legislation, along with the substantially pronounced risks associated with relatively unsophisticated fraud pose serious challenges for policymakers to resolve. j o u r n a l p r e -p r o o f generalized autoregressive conditional heteroskedasticity aye corona! the contagion effects of being named corona during the covid- pandemic the influence of the covid- pandemic on asset-price discovery: testing the case of chinese informational asymmetry pandemic-related financial market volatility spillovers: evidence from the chinese covid- epicentre the contagion effects of the covid- pandemic: evidence from gold and cryptocurrencies exploring the dynamic relationships between cryptocurrencies and other financial assets sex, drugs, and bitcoin: how much illegal activity is financed through cryptocurrencies? price manipulation in the bitcoin ecosystem covid- and finance: agendas for future research key: cord- -nzgnpi f authors: karligkiotis, apostolos; arosio, alberto d.; battaglia, paolo; sileo, giorgio; czaczkes, camilla; volpi, luca; turri‐zanoni, mario; castelnuovo, paolo title: changing paradigms in sinus and skull base surgery as the covid‐ pandemic evolves: preliminary experience from a single italian tertiary care center date: - - journal: head neck doi: . /hed. sha: doc_id: cord_uid: nzgnpi f background: italy was the first european country suffering from covid‐ . health care resources were redirected to manage the pandemic. we present our initial experience with the management of urgent and nondeferrable surgeries for sinus and skull base diseases during the covid‐ pandemic. methods: a retrospective review of patients treated in a single referral center during the first months of the pandemic was performed. a comparison between the last ‐month period and the same period of the previous year was carried out. results: twenty‐four patients fulfilled the inclusion criteria. a reduction of surgical activity was observed (− . %). a statistically significant difference in pathologies treated was found (p = . ), with malignancies being the most frequent indication for surgery ( . %). conclusions: although we feel optimistic for the future, we do not feel it is already time to restart elective surgeries. our experience may serve for other centers who are facing the same challenges. since december , the covid- outbreak has spread from wuhan to almost individuals globally infected across countries, resulting in more than deaths. the first italian patient affected by sars-cov- was from codogno, lombardy, on february , . since then, more than covid- cases have been confirmed in italy, which is now one of the most affected countries in the world, with more than deaths. the majority of italian cases occurred in lombardy ( ), home to a sixth of the italian population ( . million inhabitants), accounting as of th of may, of . % of cases and . % of deaths in the country. the regional government and local health authorities adopted strategies to contain the infection while trying to protect patients and health care workers as much as possible. health care resources were redirected to support the management of the pandemic, to the detriment of regular elective clinical and surgical activities. therefore, since monday, february , , all elective surgeries have been suspended in our hospital, too. only emergency cases and those that could not be postponed were eligible for hospital admission, in order to cope with the increased needs for beds and intensive care unit (icu) availability for patients affected by covid- . moreover, many otolaryngology departments throughout lombardy ceased their activity, becoming areas exclusively intended for covid- patients care, thus increasing the burden of patients affected by various head and neck diseases referring to our division. besides, considering that our tertiary care center is a national referral center for sinus and skull base surgery, the hospital general manager decided to allocate resources for providing care to as many urgent and nondeferrable cases affected by sinus and skull base diseases as possible. the critical issue was providing logistics that were compatible with the ongoing epidemiological emergency, which still represents today's challenge. therefore, a task force of experts was created to produce an institutional protocol for hospital admission, preoperative work-up, intraoperative precautions, and postoperative care to be followed. the aim of the present paper is to report our preliminary experience with the management of urgent and nondeferrable endoscopic surgeries for sinus and skull base diseases, during the covid- period, describing the evolving recommendations which have been implemented day by day, as new evidences emerged, until reaching the actual protocol of precautions. clinical and surgical data, as well as the outcomes of patients and information about health care workers' exposures, are provided. a comparison between the last -month period and the same period of the previous year was carried out in order to investigate the impact of covid- outbreak. a retrospective review of all patients affected by urgent or nondeferrable sinonasal or skull base diseases who were treated at the division of otorhinolaryngology of the university hospital of varese (italy) between february , and april , (pandemic-group), was carried out. all other nonsinus and skull base urgent cases treated at our hospital have been excluded from the present analysis. epidemiological and clinical data, surgical reports, complications, and follow-up information were reviewed, as well as covid- detection tests (eg, nasopharyngeal swab results). a retrospective analysis of all patients affected by sinonasal or skull base diseases, surgically treated at our institution in the same -month period of (control-group) was carried out. epidemiological, clinical, surgical, and follow-up data of such patients were retrieved as well. the pandemic-group was compared with the controlgroup in order to evaluate the changes of our surgical activity in terms of volume cases, diseases treated, patient's geographical origin, and hospitalization time. indications for nasopharyngeal and/or oropharyngeal swab collection evolved during the covid- -month period. in the early period, swab testing was performed before hospitalization in case of body temperature more than . c and/or in presence of at least one of the following factors: fever, cough, dyspnoea, gastrointestinal signs/symptoms, myalgias, fatigue, headache, pharyngodynia, rhinorrhea, active pneumonia, and close contact with a sars-cov- positive patient. otherwise, patients were admitted without getting tested. given the worsening of the pandemic and the growing body of data available, indications changed on march , , when all inpatients were systematically submitted to swab specimen collection, so that only emergencies have been performed notwithstanding their covid- status. more specifically, the execution of two swabs, with an interval between the two tests of at least days and the latest performed within hours prior to surgery, has become mandatory, in order to minimize the possibility of false negatives. indications for the use of personal protective equipment (ppe) have also evolved during this period. at the beginning, no specific protection was recommended during surgery and all health care workers in the operating room (or) continued to wear standard surgical masks and gowns, leaving viral-filtering-ppe available to be used only in case of confirmed covid- patients. however, after march , , indications for ppe use changed and, since then, surgical procedures in covid- negative patients required the use of the highest individual protection standards (at least ffp masks), in consideration of the significant number of false negatives resulting from the swab tests currently used. for positive patients, procedures were postponed until after swab test negativization, when feasible. if the procedure was strictly necessary for the patient's survival, surgery was performed in a dedicated negative-pressure-or with a preestablished allocated run, without interfering with the covid- -free areas. all medical and nursing staff in the or were recommended to wear ffp and/or powered air-purifying respirators, goggles, full-face visor, double gloves, water-resistant gowns and protective caps, not only for the entire duration of surgery but also for the whole of the patient's stay in the or. if testing for covid- was not available (emergency procedures such as trauma, major bleeding, abscesses), patients were considered covid- positive unless otherwise demonstrated. postoperative management and follow-up for patients undergoing sinus and skull base procedures followed standardized protocols already established at our department. [ ] [ ] [ ] nasal packing are removed on the second postoperative day and following endonasal medications are performed as needed, until hospital discharge. then, patients are prescribed daily nasal rinses and postoperative control in the outpatient clinic, where further medications are performed. even though the sars-cov- outbreak influenced long-term follow-up of outpatients in our clinic, postoperative medications were guaranteed in all cases, even during the covid- era, thanks to an accurate reorganization of several aspects of the outpatient service. in order to investigate the health of the patients belonging to the pandemic-group after their last postoperative medication, a telephone interview was carried out retrospectively, examining the following factors: fever, cough, dyspnoea, anosmia, dysgeusia, gastrointestinal signs/symptoms, myalgias, fatigue, headache, pharyngodynia, rhinorrhea, active pneumonia, need for hospitalization for any reason, potential swab or serological tests performed, and if they had been in contact with covid- positive individuals. health care workers have been monitored during the study period and followed up for at least days after the last patient enrolled in this study was operated, in order to rule out hospital-acquired viral infection, since incubation time it is currently estimated to range between and days, up to a maximum of days. the monitoring policies of health care staff evolved during the pandemic, based on new evidence gradually emerging. between th of february and nd of march, no indications were given to perform swab and/or serological tests for covid- on the medical staff involved in patients' care, even if they had been in contact with a subsequently ascertained covid- positive patient. in this case, the worker, if asymptomatic, was asked to constantly wear a surgical mask during service and notify the occupational medicine department if suspected symptoms (eg, fever) were to develop. if symptomatic, the worker was recommended to self-confinement and further investigation was performed according to regional dispositions. starting on rd of march, as for hospital guidelines, checkpoints were set up where all workers underwent body temperature measurement every day, at the beginning of their shift, and if above . c, the worker was restricted from taking service and submitted to sars-cov- testing and subsequent home isolation until the test's result was available. in case of negative swab testing, self-confinement was prolonged to week after symptoms resolutions. in case of positivity of the swab, home confinement was prolonged until collection of two consecutive negative swabs, repeated days apart from each other. nonetheless, some people among medical staff developed symptoms compatible with the viral infection other than temperature increase, hence they have not been tested according to hospital provisions. therefore, all the medical staff who served during the covid- -month period were asked to fill out a survey, which investigated the following items: temperature increase, development of any symptoms compatible with sars-cov- infection, results of covid- swab, rapid qualitative test ( -ncoc igg/igm rapid test, screenitalia, perugia, italy) or quantitative serological elisa test. nurses, scrub staff, and anesthesiologists were excluded from the present analysis since they have been allocated to multiple wards and operative rooms during this -month period and therefore they have been potentially exposed to viral infection in other settings different from otorhinolaryngology procedures. conversely, all medical doctors of our department, both residents and seniors, were not assigned to other tasks and were therefore suitable for assessing the impact of otorhinolaryngology procedures on viral cross contamination. mean and sd for age, length of stay, and postoperative days were calculated for each group of patients. t test was performed to investigate whether the period of treatment could influence these three parameters. patients' gender, provenance, and pathology were compared between the different groups using chi-square test. ( . %) occurred. a female patient affected by recurrent skull base chondrosarcoma after multiple endoscopic resections and irradiations, ended years earlier, underwent endoscopic endonasal debulking of the recurrence of disease and developed a temporal lobe abscess, diagnosed on th postoperative day after hospital discharge. the patient was readmitted to the hospital for neurosurgical intervention of stereotactic aspiration and drainage of brain abscesses and her sars-cov- swab collection performed upon readmission on seventh of april was negative. the culture tests were compatible with serratia marcescens infection and the patient was discharged after days of intravenous targeted antibiotic therapy, with mri confirmation of resolution of the abscess. at last follow-up, the patient was asymptomatic, she has not developed symptoms compatible with covid- and she is going to start adjuvant treatments as soon as possible. the follow-up period for the patients ranges from to days (mean days). during the postoperative follow-up, updated to fifth of may, patients ( . %) did not refer any symptom. two patients ( . %) referred headache and two patients ( . %) complained diarrhea, in all cases with onset of symptoms occurring after th of april. the two patients complaining diarrhea performed nasopharyngeal swab, which tested negative in both of the cases. no patients were hospitalized nor developed covid- respiratory manifestations. in the same period in , operated patients met the inclusion criteria. there were men and women, with a male to female ratio of . : . the ages ranged from to years. the distribution of the cases according to the pathology treated is provided in table . table provides a description of the comparison between pandemic-group and control-group as regards age, gender, patients' geographic origin, mean hospitalization time, and postoperative stay. no statistically significant differences were observed when comparing the two groups according to these parameters. the proportion of surgeries performed according to the pathology treated changed during the two considered periods and a summary is provided in table . a statistically significant difference in the proportion of pathologies treated was found between pandemic-group and control-group (p = . ). when pairwise comparison was performed, the proportion of patients treated for malignancies was statistically significantly higher than the ones treated for inflammatory diseases (p = . ). other pairwise comparisons between patients treated for other than tumor pathologies with inflammatory diseases, were not statistically significant (p > . ). table provides a summary of the survey conducted, highlighting data regarding exposition to covid- positive patients, the use of ppe and the diagnostic tests performed. italy has been the first european country suffering from covid- . the unexpected spread of a scarcely known virus was accompanied by initial confusion and disorganization. by recalling our memories and reading the emails and text messages of the past months, we identified two different periods from different factors, setting march , as the turning point. during the first month (from th of february to nd of march), no protection was recommended during examinations of apparently healthy people, thus asymptomatic carriers were not taken into consideration as possible transmission vehicles. however, since sars-cov- is transmitted through droplets, progressive evidence that otolaryngologists are at particularly high risk even when performing routine clinical procedures has suggested to use surgical masks as individual protection. at that time, surgical procedures continued to be performed wearing standard medical masks, leaving viral-filtering-ppe available for use only in case of confirmed covid- patients. however, around the globe the shortage of ppe, along with the lack of clear recommendations about their correct use, have contributed to increased infections among otorhinolaryngologists. in fact, it is noticeable that the first physician who died of covid- in wuhan, china, on january , was an ent surgeon, but the fact was only reported globally on march , . more or less at the same time, patel et al published a letter, which was diffused through emails and websites, about the first case of covid- transmission during an endoscopic transsphenoidal pituitary surgery in wuhan, that resulted in cross contamination of health care workers, emphasizing the high potential for hospital-acquired viral infections. , this has generated reluctance to perform endonasal endoscopic procedures worldwide. preliminary data emerging from international laboratory and clinical experiences show that surgical procedures involving the airways, or using them as a surgical corridor, such as transnasal skull base surgery, must be prudentially considered high-risk procedures, at least until further evidence becomes available. , [ ] [ ] [ ] the concurrent publication of recommendations by the italian society of otorhinolaryngology, the european rhinologic society, and ent uk as well as the italian skull base society led us from rd of march, to elevate the standard of protection for health care providers during sinus and skull base procedures. to the best of our knowledge, this is the first paper reporting the largest case series of patients operated for urgent and emergent sinus and skull base pathologies during the covid- pandemic in a tertiary care referral center. a considerable reduction was observed during the covid- outbreak, as high as − . %. this is due to the compliance with the regional and hospital provisions, establishing elective and nonurgent surgical procedures to be suspended. one of the aims of this paper was therefore to assess how these provisions, together with the logistical changes imposed by the ongoing outbreak, impacted the surgical activity of our division. a significant difference was found between the two groups analyzed (p = . ). pairwise analysis was significant (p = . ) when comparing malignancies with inflammatory diseases in the two groups, due to the high number of cancers treated during the covid- period. we believe that this is attributable to both a reduction of the inflammatory cases treated due to suspension of elective surgery, as well as to a reduction of the surgical activity in other italian sinus and skull base referral centers, which led to a centralization of skull base malignancies cases toward our division. the percentage of extra-regional patients was comparable between pandemic and control groups ( . % vs . %, respectively) without statistically significant differences (p = . ) (figure ). our otorhinolaryngology division is a well-known referral center for skull base disease, receiving many extra-regional patients every year. notwithstanding this unprecedented scenario, there were several high-priority sinonasal and skull base diseases whose treatment could not be delayed, because of the risk for significant worsening of the patient's quality of life and negative impact on overall survival rates. our preliminary results emphasize the need for sinus and skull base referral centers able to continue providing care even in such emergencies like the covid- outbreak, in order to manage selected critical patients at risk for a fatal course if not treated promptly. this can be done only if the reorganization of the referral centers, realized to face covid- emergency, is able to reserve appropriate resources for sinus and skull base surgery, namely preserving the activity of some departments which are essential for this specific procedures (neurosurgery, interventional radiology, pathology, plastic surgery), as well as setting up a covid- free icu for proper postoperative monitoring. the mean follow-up time after surgery for the pandemic-group in our study was days, with a minimum of at least days, which corresponds to the estimated time of incubation for sars-cov- . all patients have been followed in the outpatient clinic by means of endoscopic medications accordingly. at the retrospective telephonic survey conducted on fifth of may, a total four patients ( . %) referred symptoms (headache and diarrhea, two cases each) after hospital discharge and only two of them underwent nasopharyngeal swab collection, which tested negative in both of the cases. we acknowledge that performing a single telephone interview retrospectively to investigate the patients' state of health cannot provide certainty about their health status, but it allowed us to easily retrieve information while avoiding unnecessary or unauthorized movements during the lockdown period. protection and health of medical staff are a highly debated topic during the covid- outbreak. , in this regard, the initial confusion progressively faded away and the supply of ppe became more adequate over time, so that, month after the beginning of the outbreak in italy, more stringent measures for protecting health care workers were adopted with widespread ppe usage and restrictions from duty in case of suspected symptoms. interestingly, according to the survey performed, all symptoms referred by the physicians serving in our division began before the time when clear indications were disposed by the hospital. at present, no indication is given to test asymptomatic medical staff for covid- infection, even in presence of epidemiologic criteria. this explains why only half of the ent medical staff was tested, either with a nasopharyngeal or a rapid serological test. the latter was performed based on personal decision in all cases. in such a critical time of resources constraints, with stringent indications for execution of diagnostic tests, it seems reasonable to concentrate efforts on prevention, with appropriate ppe use and logistic rearrangements focused on protecting the health of both patients and health care workers. in this regard, our experience may serve for the other centers who are facing sudden emergency conditions. to date, all medical and nursing staff wear appropriate ppe, as prescribed in several guidelines. , however, even establishing the aerosolization risk of endoscopic procedures, as hypothesized by a preliminary study performed on cadaver with detection of particles measuring less than μm, we still do not know exactly which procedures generate aerosolization of mucus and possible viral particles measuring less than . μm. therefore, although the risk for health care providers has been decreased by wearing proper ppe, we still do not know the actual risk for nonsuspect patients undergoing endoscopic transnasal surgery, considering that covid- remains viable in aerosol particles up to hours. moreover, the use newer tests like the one from abbott (abbott laboratories, chicago, illinois), administered shortly before entering the patient's or and results ready within minutes, could impact the logistics of elective surgeries planning, especially in the next phase of the pandemic. these considerations move us to future directions regarding the or environment and air turnover, how long one surgery should be distanced from the other, and if it is necessary to change or, always use negative pressure ors, use specific high efficiency particulate air (hepa) filters for suction or uv lights. [ ] [ ] [ ] finally, neurotropism of sars-cov- is under investigation and the consequences of surgically creating a direct cerebral access route through skull base surgeries are still unknown to date. as happens in all preliminary studies, there are some limitations to our paper that deserve to be mentioned. first of all, it is a retrospective study with confounding factors which were not considered in the analysis (eg, change of staff between and , pandemic vs normal conditions, sensitivity and specificity of diagnostic tests, etc). second, it was not possible to establish with certainty the covid- status of all patients and physicians due to stringent indications to perform nasopharyngeal swabs and/or serological tests based on current regulations. their widespread use would certainly strengthen the value of this study. third, the present paper analyzed only the first months of the covid- outbreak in italy, which represents a reasonable time to report an initial experience but not to draw definitive conclusions. in this regard, it is too early to infer how the covid- pandemic might influence other aspects of patients' care, such as long-term follow-up. taking into account the similar situation happened in wuhan, we can anticipate that this will be a crucial aspect to put efforts into during the following months. although we feel optimistic for the future, we do not feel it is already time to restart elective surgeries, since the pandemic, according to who on may , , is not over yet. we believe that only urgent and nondeferrable cases should be treated until further evidence shows adequate safety measures for both patients and health care providers. here we share our institution's preliminary surgical experience aiming to facilitate the adoption of similar measures by other referral centers. more studies and research are necessary in order to collect data and provide more accurate recommendations, considering that the evolution of the pandemic is unpredictable. covid- -situazione in italia critical care utilization for the covid- outbreak in lombardy, italy: early experience and forecast during an emergency response ulteriori determinazioni in ordine all'emergenza epidemiologica da covid- skull base surgery during the covid- pandemic: the italian skull base society recommendations. int forum allergy rhinol letter: precautions for endoscopic transnasal skull base surgery during the covid- pandemic sinonasal malignancies of anterior skull base the role of a post therapeutic surveillance program for sinonasal malignancies: analysis of patients european position paper on rhinosinusitis and nasal polyps how to reorganize an ear, nose, and throat outpatient service during the covid- outbreak: report from northern italy covid- , questions and answers how fragile we are modes of transmission of virus causing covid- : implications for ipc precaution recommendations practical aspects of otolaryngologic clinical services during the novel coronavirus epidemic: an experience in hong kong in reply: precautions for endoscopic transnasal skull base surgery during the covid- pandemic in reply: precautions for endoscopic transnasal skull base surgery during the covid- pandemic endonasal instrumentation and aerosolization risk in the era of covid- : simulation, literature review, and proposed mitigation strategies. int forum allergy rhinol personal protection and delivery of rhinologic and endoscopic skull base procedures during the covid- outbreak information for rhinologists on covid- guidance for ent during the covid- pandemic managing care for patients with sinonasal and anterior skull base cancers during the covid- pandemic aerosol and surface stability of sars-cov- as compared with sars-cov reflections and new developments within the covid- pandemic perioperative covid- defense: an evidence-based approach for optimization of infection control and operating room management clinical evidence based review and recommendations of aerosol generating medical procedures in otolaryngology-head and neck surgery during the covid- pandemic endoscopic skull base and transoral surgery during the covid- pandemic: minimizing droplet spread with a negative-pressure otolaryngology viral isolation drape (novid) neurotropism of sars-cov : mechanisms and manifestations rapid implementation of an evidence-based remote triaging system for assessment of suspected head and neck cancer referrals and patients on follow up after treatment during the covid- pandemic: a model for international collaboration acknowledgment m. t.-z. is a phd student on the "biotechnologies and life sciences" course at università degli studi of insubria, varese, italy. the authors declare no conflict of interests.orcid apostolos karligkiotis https://orcid.org/ - - - alberto d. arosio https://orcid.org/ - - - mario turri-zanoni https://orcid.org/ - - - key: cord- - q ujnjq authors: sanderson, william c.; arunagiri, vinushini; funk, allison p.; ginsburg, karen l.; krychiw, jacqueline k.; limowski, anne r.; olesnycky, olenka s.; stout, zoe title: the nature and treatment of pandemic-related psychological distress date: - - journal: j contemp psychother doi: . /s - - - sha: doc_id: cord_uid: q ujnjq the covid- crisis has created a “mental health pandemic” throughout the world. scientific data are not available to fully understand the nature of the resulting mental health impact given the very recent onset of the pandemic, nevertheless, there is a need to act immediately to develop psychotherapeutic strategies that may alleviate pandemic-related distress. the psychological distress, in particular fear and sadness, is a function of the pandemic’s negative impact upon people’s ability to meet their most basic needs (e.g., physical safety, financial security, social connection, participation in meaningful activities). this paper presents evidence-based cognitive behavioral strategies that should prove useful in reducing the emotional suffering associated with the covid crisis. mental health issues such as anxiety, depression, substance abuse, and suicide were increasing in the u.s. well before the pandemic (substance abuse and mental health services administration ). thus, it is no surprise that the very recent "mental health pandemic" as a result of covid- (covid) will further accelerate the increasing prevalence of these disorders (marques et al. ; strakowski et al. ) as a result of its impact upon people's day-to-day functioning (brooks et al. ) . indeed, a recent survey by the kaiser family foundation found that percent of people reported that the worry or stress tied to covid had a negative effect on their emotional well-being (panchal et al. ) . moreover, many individuals may attempt to cope with these negative psychological effects in unhelpful ways (e.g., alcohol/ substance use) that can actually result in an increased susceptibility to covid- (da et al. ; volkow ) . clearly, the covid crisis is likely to have an enormous negative impact upon mental health if left ignored. the pandemic has disrupted the ability to satisfy core human needs in almost all areas to an alarming extent (e.g., brooks et al. ) . much of the population is worried about meeting their most basic needs (e.g., paying rent, buying food) as a result of economic hardship (e.g., unemployment) as well as an increasing scarcity of resources (e.g., food, cleaning products, personal protective equipment such as masks). people are living in a chronic state of fear of contracting the virus. socially distancing and disconnecting rather than affiliating has increased loneliness and decreased social support, particularly in elderly and disabled populations and those with underlying health conditions. the artificial substitutes for social connection such as online video events often exacerbate, rather than relieve, the feeling of disconnection. people have been removed from the sources of activity that allow them to feel esteem, status, and pleasure (e.g., work, graduation ceremonies, weddings, engaging in sporting activities). the impact upon dating and finding a mate is profound in an era of remaining six feet from others and fearing any close contact may lead to transmission of the virus. finally, for those who are parents, the stress of this role is enormous (e.g., home schooling, explaining the pandemic to young children), and certainly the idea that children will flourish in the present environment seems implausible. given the sudden onset and impact of the pandemic, scientific data are not available to fully understand the nature of the resulting psychological distress, but existing research suggests anxiety, depression, and worsening stress are common reactions (rajkumar ) . people are suffering and reaching out for assistance-there was a need to act immediately in order to develop strategies that may alleviate psychological distress. typically, when we produce a paper or treatment manual we spend months planning, writing, and reviewing it before making it available to others. given the rapidly evolving mental health crisis that occurred, we produced an initial product after only weeks of the first coronavirus cases in new york, which we continued to revise as we learned more about covid-related problems (cf. sanderson et al. ) . to develop this guide, we brainstormed using our clinical observation skills to identify pandemic-related triggers and resultant psychological problems we were seeing in our patients, family, friends-and our own lives. thus, we are confident that the areas identified in the original document ) represent the spectrum of covid related psychological distress. once we created this list we developed strategies that would allow people to manage these negative emotional states using a self-help format (this guide can be accessed at www.psych rescu e-covid .com or at the permanent doi address provided in the reference section). this self-help guide can be used in conjunction with the current paper, which more concisely outlines therapeutic strategies, to maximize the effectiveness of one's intervention. nearly all of the strategies that we included were taken from evidence-based psychological treatments for individuals with anxiety disorders, depression, and related emotional distress (table ). the approach we used is identical to that which led to the development of a variety of evidence-based treatment manuals for psychological disorders (e.g., panic disorder, depression) where basic cognitive behavioral strategies were tailored to address the specific psychopathology of the disorder. we expected that these strategies would prove useful for those suffering from similar emotional states secondary to the challenges associated with the covid crisis. in fact, since so many individuals are struggling as a direct result of the covid crisis, we have started to conceptualize these symptom clusters as a pandemic-related stress disorder (prsd) . while there has been progress, as outlined above, in understanding the nature and interventions for covid related psychological distress, an additional problem has emerged as a result: the already overburdened mental health system must now provide treatment for a substantial wave of persons in need. similar to the concern of flattening the curve for medical disorders to avoid overburdening the healthcare system, mental healthcare may find itself in the position of having more patients than can be reasonably accommodated (marques et al. ) . in fact, it is probable that this substantial increase in patients will last well beyond the pandemic itself (fiorillo and gorwood ) . many individuals, particularly younger generations, are table summary of commonly encountered distress provoking triggers and recommended evidence based therapeutic strategies stimulus control experiencing significant consequences of the economic crisis (e.g., financial uncertainty) that will take considerable time to resolve. a national survey conducted by the national center for health statistics indicated that approximately % of americans reported experiencing symptoms of an anxiety or depressive disorder during the end of may into june , when several states had already started to reopen (cdc ). furthermore, the process of reopening in itself may result in increased feelings of anxiety. as individuals have become accustomed to staying at home for safety, beginning to reintegrate into society is nerve-wracking for many; psychologists have started to refer to these fears as "re-entry anxiety" (dusharme ) . moreover, the centers for disease control and prevention alerted that the second wave of covid- is likely to be far more devastating than the first (sun ). as a result, in line with the suggestions of marques et al. ( ) , we have been examining scalable psychotherapeutic intervention models to increase our proactivity, reach out to those with distress, and attempt to decrease the likelihood of more severe responses later on. schleider ( ) has developed and tested brief, accessible interventions delivered in non-traditional settings (i.e., telepsychology). she found that a single session of a solution-focused consultation was associated with a reduction in psychological distress in adults seeking psychotherapy ). thus, we adopted her approach and have developed and are in the process of field-testing a consultation-oriented intervention (rather than a more traditional "psychotherapy" model) consisting of two -min telepsychology online video sessions (cf. limowski et al. ) . the focus of the first session is to identify factors that appear to be causing the most distress and providing evidence-based strategies for the client to utilize. the focus of the second session, held approximately one week later, is to assess the success of the initial recommendations and to provide additional strategies if necessary. based upon the results of our field-testing we may ultimately increase the number of sessions in this intervention. fear is an emotion provoked by the perception of danger or threat that evolved to protect us and enhance our ability to survive. given that the core concerns of this pandemic are about illness and death, fear is an expected emotion. the first step in working with pandemic-related fear is to validate the person's emotional experience, within reason. it is also important to help the person understand that fear can become one's ally rather than something to get rid of. when channelled appropriately, fear protects the individual as well as others by leading to protective behaviors such as hand washing, mask wearing, social distancing, and minimizing non-essential activities. individuals with obsessive-compulsive disorder (ocd), many of whom hold contamination fears independent from covid, may be particularly impacted by widespread concern over the coronavirus and may require specific adjustments to treatments (fontenelle and miguel ) . however, that being said, what can be modified is one's level of fear. many are at a panic level of fear, meanwhile, the overwhelming majority of people are in fact not overly vulnerable to covid. for those individuals, the following should become their guiding principle: covid- will pass, humankind will survive, almost everyone will still be alive in its aftermath. the scientific evidence clearly supports this statement. to varying degrees media (television, newspapers, social media, websites) coverage of events such as the covid crisis increases one's perception of risk (ropiek ) . there is an old saying in the media: if it bleeds, it leads. the idea is the more horrific the story (e.g., the more frightening), the more likely it will be the headline and receive a lot of time or space in the way the media source covers it. thus, media outlets are biased towards presenting the most threatening scenarios (people dying on ventilators, overfilled morgues, stories of the sickest patients, etc.) and not focused on alternative information which may present a more balanced or nuanced view (e.g., interviewing tens of thousands of people who had no or mild symptoms-overwhelmingly the typical course of covid-or even people that were fairly sick who recovered). consequently, these messages shape the general public's reality of the covid crisis as overall more threatening than it is because of the biased information. it is also worth noting that it is not uncommon for false information to be spread by social media. the news media can be viewed as a stimulus that triggers a certain response (immediate fear, skewed beliefs). since this stimulus is something that everyone does in fact have control over the recommended strategy is stimulus control (borkovec et al. ; mcgowan and behar ) : reduce or eliminate exposure to the stimulus to prevent the undesirable response. while one needs to be informed, watching or reading the news for approximately - min per day should be sufficient to keep up with the necessary information. accurate, non sensationally-oriented, print media is recommended. the johns hopkins coronavirus resource center (https ://coron aviru s.jhu.edu/) meets these criteria and thus, is a highly recommended source to avoid unrealistic risk perception. news from local and state health departments which present factual and locally-oriented information are other reputable sources through which individuals can stay informed. the topic of media information provides an excellent segue to perception of risk (danger). as discussed above, the media impacts beliefs about coronavirus in that it increases the perception of danger by presenting somewhat skewed information. with regard to the experience of fear, for the most part, the more dangerous one perceives something, the greater the amount of fear that is experienced. thus, the therapeutic goal is to help an individual develop accurate risk perception so that his or her fear is in proportion to the threat. the primary strategy to use is cognitive reappraisal (lazarus and alfert ; gross and john ) to identify, examine, and when appropriate reappraise the situation. clearly, coronavirus is a threat. but like most threats, it is not the same for everyone. it is essential to keep in mind that fortunately most everyone will survive coronavirus. the following are several examples of how media consumption distorts a person's risk perception because of the way information is presented: you see covid in extremes: either you do not get it, or you end up on a ventilator. there is no middle ground or shades of grey. you only focus on the worst cases. if a celebrity announces they are covid positive but only have mild or no symptoms, you forget about him or her. but if a celebrity is very ill, that is the example that sticks in your brain. you only focus on the worst outcome and personalize it: you are going to end up hospitalized with covid just because that is a possibility. you lose the distinction between possibility (anything is possible) and probability (what is likely to happen based upon knowledge of base rates). because you feel anxious about this highly contagious virus that everyone else is anxious about, you assume it is dangerous-just because you feel it is. watching media that displays cases and deaths like a scoreboard continues to exaggerate your anxiety further even though proportionally these are relatively low numbers compared to the entire population. central to human behavior is the motivation to stay aliveeven before the covid crisis. if evolution designed the mind for anything it is to guide human survival. as mentioned above, fear is the invariable reaction that occurs when a threat is perceived and it guides our behavior towards maximizing survival (e.g., avoiding and escaping from danger, reducing the threat). some individuals seem to want certainty about their risk and likelihood that nothing bad will happen. unfortunately, the fact is, there is no certainty that one will live beyond this moment. the probability for most everyone is that they will be here tomorrow-that is almost % certain. but since it is possible that something can happen at any moment, it is not a full %. that is a point that must be accepted. otherwise, attempting to gain certainty when it does not exist will exacerbate fear. the following three points are important to keep in mind as we try to help individuals to accept the existential reality of our existence and consequently decrease fear driven by the attempt of obtaining certainty: ( ) one can never be % certain that nothing will happen at any point in the future starting with now, ( ) we take risks every day living our lives, and there is no alternative; very few of us would want to live in a bubble to maximize our safety and give up our lifestyle, ( ) the best one can do is manage risks, not eliminate them fully. in the covid environment, one must ultimately confront death to move forward with some level of comfort. it is important to work towards accepting that we risk our survival every day so that we can live the life we want to live. the best one can do to manage their fear in the coronavirus landscape is to: ( ) acknowledge this reality, ( ) control whatever is reasonably possible (e.g., wear a mask while shopping, wash hands regularly, socially distance), and ( ) move forward and live life. we attempt to get people not to deny the possibility of death, but to do their best to attend to managing risk and focus on realistic probabilities. sadness (depression) is an emotional response that is primarily triggered by the occurrence of personal losses that are important to an individual and cannot easily be restored (e.g., loss of a job, failing a test) or in some instances are not able to be restored (irrevocable losses). these can be tangible losses, such as the death of a loved one or the breakup of a relationship, and they can be more abstract losses, such as failing to live up to one's expectations, or failing to have the marriage that one expected. the most severe form of sadness occurs when a person experiences, or perceives an experience, where the loss cannot be undone. the classic example is the death of a loved one (i.e., bereavement) where the loss is clearly irrevocable. however, it can also apply to a situation where a person believes (perceives) the loss is irrevocable; for example, a person who has a breakup of a relationship and truly believes he/she will never find anyone else. with regard to the pandemic, what most are feeling are the effects of transient losses. for example, if someone misses seeing their friends during this period of social distancing and quarantine, the fact that the sadness is experienced is in fact because what was lost is important. the degree of sadness mirrors the importance of the loss. when irrevocable loss occurs, or is perceived or believed to have occurred, the individual may go into a state of "resignation"-an evolved response to preserve energy when using effort would be futile (the loss is irrevocable so the person needs to adjust rather than continue to attempt to restore it). however, when the resignation is triggered by perceptions of irrevocable losses (e.g., the world is never going to survive this pandemic, there is no way to fix the economy-it will be bad forever, i'll never see my friends again), it can lead to a state of resignation characterized by hopelessness and helplessness. these two states, as well as several other triggers of sadness, end up contributing to and maintaining the intense sadness, and people end up in a downward spiral from which it is difficult to escape. when helping people manage their sadness, the goal is to build their resilience, their ability to increase behavior to access what is important to them. individuals may begin to experience an overwhelming lack of hope for the future as a result of the negative impact of the pandemic and the constant flooding of bleak news reports. while there are many unknowns, it is relatively certain that the transition back to our accustomed lives will not happen in the immediate future. this realization understandably adds to an individual's experience of hopelessness and depressive resigning behavior. as mentioned previously, stimulus control is recommended in order to combat feelings of hopelessness. although it is unhelpful, attending to negative news is in our nature. checking the news frequently may be contributing to hopelessness, even in hopes of more positive announcements. we are often reinforced to check more often due to intermittent segments of uplifting news, or anticipation of positive news, even if the overall message conveyed is overly negative. as aforementioned, individuals are recommended to limit covid- related news consumption to a specified amount (i.e., once a day for min) and are urged to use accurate, non-sensationalized sources (borkovec et al. ; mcgowan and behar ) . reappraisal of hopeless attitudes towards our current situation is also recommended as it is important to keep the reality in mind that for the most part these pandemic-related stressors are not permanent, although they may feel this way when one is in the midst of them. focusing on the notion that humans are resilient and have previously overcome countless tragic crises (e.g., recessions, war, epidemics) is also imperative to provide a context of hope and survival-rather than resignation. (note. for those in crisis, the national suicide prevention lifelife ( - - - or https ://suici depre venti onlif eline .org/chat/) is available / .) relatedly, helplessness is both the belief that a situation will not change and the belief that one is unable to enact change on a situation. in other words, individuals who feel helpless believe that there is nothing they can do to change their undesirable circumstances; they have been convinced that their hopeless feelings are true. unfortunately, helplessness may inadvertently create a self-fulfilling prophecy, that is one may behave in accordance with the predicted or expected outcome, thus creating a reality that confirms the faulty belief (e.g., if you do not study for an exam because you believe you will fail, you will in fact fail because you did not study, not because you were destined to fail). additionally, feeling helpless may result in all-or-nothing thinking (e.g., "if i cannot fix the economy, i shouldn't bother ordering takeout from a local restaurant to support them"). taken together, individuals are encouraged to reappraise allor-nothing thoughts (e.g., "the economy is doing poorly but i can do something to make a difference") and expand one's thinking to the "bigger picture" (e.g., "the economy is doing poorly but if everyone did something small, the scale of the impact would be enormous"). the pandemic might also be viewed as an opportunity to develop a new skill (e.g., sewing) that could be used to prompt supportive actions (e.g., distributing masks to others). with these changes in perspective, coupled with engaging in behaviors that are cognitively consistent, individuals can increase their sense of empowerment (i.e., the opposite of helplessness) and move out of the helpless frame. while many will experience grief related to a loss of a loved one due to covid- , this crisis has also introduced an array of non-bereavement related loss (e.g., loss of social connection, jobs, normalcy, economic stability). these losses have been found to instill a similar grief reaction, especially when the loss is directly associated with one's identity (papa et al. ) . the level and intensity of grief varies per individual, as do the order of the stages of grief (i.e., denial or avoidance, anger, bargaining, sadness, and acceptance). while grief reactions are expected as a result of pandemic-related loss, research on grief has indicated several strategies to cope with and process these losses. expressive writing in the form of identifying and naming the experienced loss can help individuals increase awareness of the associated emotions and recognize previous strategies that were effective in coping with that emotion in the past. after naming the losses, outlining ways to move forward in or amend those loss areas can help individuals accept their loss and work towards reproducing what has been lost (e.g., after job loss, reading or attending webinars on new innovations of your field; briggs and pehrsson ) . additionally, social support is largely indicated in grief interventions. while social distancing limits physical social contact, grieving individuals can still access social support. phone and online platforms can increase the social support experience through voice or video methods, in comparison to texting which can be less personal. global quarantine and social distancing regulations have resulted in significantly limited social contact. as a result, many individuals have started to socially and physically resign and are overwhelmed by upsetting thoughts related to loneliness. although these reactions are understandable, they typically exacerbate feelings of social disconnection. instead, individuals are encouraged to validate their feelings, challenge unhelpful thoughts, and problem solve in order to increase connection in novel ways . helpful strategies that can be used to think about the current regulations in a more balanced manner include: relabeling the current guidelines from "social distancing" to "physical distancing;" remembering that individuals are apart now so they can be together later; and reframing the situation as a time to focus on, build, and/or create meaningful relationships. several practical ways to increase connection include but are not limited to: zoom video chats, facetime, netflix movie parties, handwritten letters, video games, virtual exercise classes, online forums, online support groups, virtual game nights, virtual paint nights, virtual book clubs, hugging a stuffed animal, and purchasing long distance friendship lamps. loss of income and loss of social reinforcement are two ways the pandemic has decreased reinforcement among individuals (pfefferbaum and north ) . such losses can decrease effective behaviors leading to psychological distress and increase ineffective behaviors which pose health risks (e.g., socially isolating, avoidance, washing hands irregularly; brooks et al. ) . engaging in a range of activities that balance pleasure, mastery, and social connection is often most helpful for boosting reinforcement and promoting positive moods. for example, cooking different meals at home can be inherently enjoyable (i.e., flavorful food), result in a sense of achievement (i.e., learning a new recipe), and promote social connection (i.e., sharing the recipe or meals with others). with regards to health behaviors that individuals may struggle to implement (e.g., wearing a mask, handwashing), basic principles of contingency management can be used to increase the desired behavior. individuals can set goals for themselves, track their progress, and reward themselves when goals are met. this can be helpful to increase behaviors that are not immediately pleasurable, but are important to do in the current context. as the pandemic continues, many perceive a sense of meaninglessness due to uncontrollable circumstances (e.g., unemployment, decreased social interaction, and various other role losses). the disruptions in daily life lead many individuals to feel a loss of purpose which they normally derive from involvement in careers, caregiving, or other activities. therapeutic approaches that prioritize meaning have been shown to be effective in improving quality of life (breitbart et al. ) . relatedly, as aforementioned, cbt emphasizes increasing engagement in pleasant and masteryoriented activities as a general mood management strategy. a helpful strategy is for individuals to mourn the unavoidable role-related losses while simultaneously shifting focus to aspects in their control. individuals can connect purposefully with the world by engaging in hobbies, learning new skills, keeping a pandemic journal, or helping others. small contributions like phoning someone who lives alone, shopping for others, or donating to causes more directly (e.g., blood drives, buying supplies, fundraising) hold tremendous potential for cultivating a sense of meaning and are activities that can be safely conducted during social distancing efforts. individuals are being exposed to a deluge of negative information about a problem that-at least in the short term-has no clear solution. additionally, given that this negative information is relevant to the current public health crisis, it is unsurprising that individuals are more likely than ever to attend to it. initially, increased attention to negative information may appear to be solution-focused or goal-directed thinking and, due to the current crisis, individuals may be more likely to continue engaging in such behavior. however, individuals can easily become stuck in a cycle of ruminative (i.e., brooding and dwelling) thoughts about the current situation which results in exacerbated emotional distress, agitation, and/or sadness. while this reaction is unsurprising, self-monitoring is recommended to help individuals identify specific external cues (e.g., media consumption, speaking with a friend or relative who catastrophizes), emotional states (e.g., loneliness, sadness, boredom), and locations or times of day (e.g., isolated in home office, late at night) when ruminative thinking is more likely to occur again. increased awareness of cognitive, behavioral, and environmental triggers then creates a personalized guide for what cues the individual should remove or avoid from their environment (e.g., limiting news intake, schedule "socializing" breaks throughout the workday). however, it is important to note that if the "socializing break" is a virtual one; changing one's physical location during the call is crucial to differentiating this break from the workday (i.e., the work environment in one's home). thoughts of hopelessness and helplessness, rumination and worry, and overall negative thinking are expected when individuals are exposed to an overwhelming amount of negative information regarding the pandemic (i.e., death statistics, case increases, economic collapse). in combination with a predisposition to negativity bias, (ito et al. ) a pandemic undoubtedly exacerbates depressive thinking (i.e., negatively oriented news focused on dangers and losses). practicing gratitude is a recommended strategy that may help lessen our negativity bias by transferring a portion of our attention to positive stimuli. individuals can begin to assess what they are thankful for, and deliberately attend to simple moments of pleasure each day to transfer focus to contentment rather than loss. being mindful during pleasurable activities (i.e., recognizing emotions) and when engaging one's senses (i.e., taste of a meal) can help increase awareness of moments for which one can be grateful. similarly, increasing awareness of negative thoughts and of their frequency can help individuals notice the onset of the thought, and engage in a positively salient activity in order to halt the depressive thinking cycle. thought monitoring and cognitive reappraisal are particularly powerful ways to combat depressive thinking as outlined above. finally, engaging in physical exercise (see below for section on sedentary behavior) can be an excellent way to change thoughts through behaviors. guilt has been a frequent consequence of the pandemic. some may discover they tested positive for covid after they were in contact with others, some may be struggling with not being able to actively help during this crisis, healthcare workers may not be able to save patients, and some may be feeling more privileged than others. as a result, individuals are blaming themselves, questioning their behaviors, punishing themselves (whether intentionally or not), and resigning. to manage feelings of guilt, individuals are often encouraged to identify the source of their guilt, evaluate how much responsibility they have for it, take the appropriate amount of responsibility, make reparations for any harm they might have caused, and ultimately forgive themselves. additionally, engaging in prosocial behaviors is recommended (e.g., sending a care package to someone struggling, ordering takeout from local restaurants, reaching out to someone who might be lonely, making a donation) to help with thoughts about not doing enough and increasing one's sense of empowerment. shame occurs when individuals engage in reputation-damaging behaviors or those that have a heavy cost to society (cibich et al. ). in the current context, a positive covid status can be shame-inducing due to the stigma associated with being contagious, as well as the costs it has to society (i.e., potential of infecting others). shame can be problematic if the feeling is so intense that it negatively affects self-esteem and mental health (e.g., feeling worthless despite taking adequate quarantine precautions). shame can also lead to avoidance or ineffective behaviors (e.g., not telling housemates about positive test results). the first step to manage shame is to determine if it is justified or not. shame experienced from disease status per se is not justified, but other behaviors (e.g., not wearing a face covering when symptomatic) can be. shame can be functional if it guides one to rectify a negative behavior (i.e., informing others, taking precautions). for unjustified or excessive shame, identifying and acknowledging the emotion is the first step to reduce the intensity. next, individuals can identify behaviors driven by the emotion and engage in the opposite behavior (the 'opposite action' skill in dialectical behavior therapy; rizvi and linehan ) . to reduce the effects that shame has on self-esteem, it is important to first differentiate qualities of oneself that do not change from having the virus, and to identify and reframe "shame thoughts." for example, instead of not disclosing testing positive for the virus because of thoughts that they are "bad" or "dirty", individuals can be encouraged to disclose it to appropriate people in their lives and see themselves as "brave" and "proud" for socially isolating and taking steps to protect others, which is valuable to society. as aforementioned, the media frequently highlights biased information and often focuses on those who appear to be maximizing productivity and accumulating accolades during this pandemic. the tendency to make comparisons between these featured individuals and ourselves can lead to personal feelings of inadequacy, as well as attempts at radical behavioral changes with goals that may be difficult to attain, resulting in increased feelings of failure and reduced selfesteem (vogel et al. ). while it is common to engage in these comparisons, it may be more helpful to practice reappraisal, recognizing that those featured likely represent only a small percentage of the population, and that what is shown is highly selected for, thus leading to a biased perception (i.e., sitting on the couch and watching television is an activity many individuals participate in, but is not broadcasted as it is not especially attention-grabbing). additionally, rather than setting broad, ambitious goals that may be exceedingly difficult to achieve, focus should be on setting goals that are smaller, observable, specific, and measurable. research has shown that two key factors in maintaining commitment in working towards a goal include ( ) the belief that one can realistically attain the goal, and ( ) importance given to the outcome expected as a result of attaining the goal (locke and latham ) . thus, it is critical to set goals that are challenging enough to feel a sense of accomplishment when achieved, while not being overly onerous. lastly, specificity aids in accountability, and detailing what the goal is and how to measure it, as well as scheduling the time and day during the week to engage in goal-focused activity, can help facilitate action towards reaching a goal. collectively, the population is encountering an increase in daily and repeated frustration (i.e., achieving one's goals is either more difficult or currently impossible). frustrations may be the result of external (e.g., experiencing interrupted internet connection), internal (e.g., low self-confidence after failing to meet work deadlines), or particularly salient (e.g., specific cleaning supplies consistently being out of stock) daily experiences. experiencing frustration may lead to an increase in negative mood and result in maladaptive thinking such as, catastrophizing (e.g., "i am the worst employee ever"), overgeneralizing (e.g., "my internet never works"), and fortune telling (e.g., "if the cleaning product was out of stock at the first store, none of them will have what i need"). additionally, an individual's interpretation of any given event is influenced by a number of factors (e.g., current emotions, life circumstances, relationships, the weather, etc.) and tends to change over time. given the heightened level of emotional distress an individual may be experiencing, interpretation of neutral or even somewhat negative events as catastrophic is expected. cognitive reappraisal is recommended to shift the individual's perception of the increased meaning and significance of these negative events and ultimately decrease negative emotion. furthermore, encouraging individuals to reframe the situation which led to frustration in a more positive way or as an opportunity to increase effortful action and goal-directed behavior (e.g., problem solving) will be helpful. we propose the existence of a condition that can best be described as pandemic-induced claustrophobia; not claustrophobia in the traditional sense of the psychological disorder, but a unique feeling of discomfort related to being "trapped" at home. this "condition" may be particularly prevalent for those living in apartments, in cities where ample space is rare, and/or with several other people. such individuals may feel stir-crazy yet exhausted, exhibit negative affect, and be tempted to break social distancing policies. an effective mental strategy to combat pandemic-specific claustrophobia is cognitive reappraisal. in the current situation, this tactic can take the form of changing one's attributions for the quarantine: viewing staying inside as an intrinsically motivated behavior as opposed to a punitive decree from an external source. an example strategy is thinking of a specific person one knows who is a member of a high-risk population, and telling oneself that one's decision to stay inside is in the service of protecting this person. alternatively, some individuals may interpret stay-at-home orders as prohibitive of going outside even for fresh air or exercise. this type of appraisal may contribute to a feeling of being "trapped." by consciously reframing the situation (e.g., "i should limit my contact with others, but going for walks outside is acceptable"), individuals can feel a greater sense of agency and control over their current circumstances and reduce claustrophobic feelings that may be exaggerated from these misinterpretations. feeling stressed or overwhelmed is one of the most commonly reported emotional experiences of the pandemic; a cumulative effect of being faced with a variety of new challenging circumstances. this response is unsurprising, but also problematic, given that the body responds to stressful external circumstances with increased production of the hormone cortisol. elevated levels of cortisol are associated with numerous negative health consequences-including, ironically, diminished immune response. stress management is therefore crucial for both mental and physical well-being during the pandemic, and one major tool for combating the negative effects of stress is meditation (see section below on lifestyle factors for additional tools to help manage stress, most notably the section on exercise). in fact, numerous studies over recent decades have demonstrated the benefits of meditation for many facets of physical, emotional, and mental health (lynch et al. ). this practice may be particularly relevant at this time given that many individuals do not have access to their regular stress relief outlets (going to the gym, gathering with friends, etc.). an abundance of meditation-related offerings exist online, from formal training programs to guided mindfulness exercises. thus, the first step in establishing a meditation practice is taking the time to explore different meditation resources and determine what type of meditation one finds to be the best personal "fit." by cultivating an enjoyable and sustainable practice, individuals are more likely to remain consistent in their meditation, which is key for reaping maximum health benefits. more than ever, individuals are working from home and spending more time at home, leading to increased contact with families and roommates. stress-induced negative emotions, boredom, and irritability naturally contribute to more conflict in households. of note, incidents of domestic violence have substantially increased worldwide since the onset of stay-athome orders (boserup et al. ) . self-care methods and relaxation strategies can reduce irritability in the long-term, potentially making conflicts less likely to occur. conflict may arise from reductions in privacy or from disagreements about safety precautions due to variability in risk tolerance. individuals are encouraged to recognize that others differ in the extent to which they desire solitude as well as their comfort level in taking health precautions. while there are certain public health guidelines for navigating health behaviors, ideally households can be respectful in conversations and seek a compromise. specific communication strategies are also useful for anticipating, reducing, and navigating interpersonal conflicts. for example, it can be helpful to first become aware of emotions in the moment and take a "time out" as necessary (e.g., counting to , leaving the room) before responding. if tensions are still high, deciding on a future time to have discussions can be effective. communicating using "i" statements and making requests instead of demands are other helpful tactics for more effectively resolving disputes. (note. for anyone affected by abuse and needing support, call - - - , go to thehotline.org, or text loveis to - - - ). research suggests a strong positive relationship between sunlight and serotonin levels (lambert et al. ) , a neurotransmitter central to biological explanations of depression. the pandemic cancelled many outdoor events and shuttered businesses, workplaces, and other establishments. as a result, many are spending more time indoors, away from sunlight. sunlight can promote positive moods, so individuals should aim to get at least min of sunlight each day. this practice could take the form of walking around neighborhoods, sitting outside, or engaging with nature (e.g., hiking, walking near water). several of these suggestions can be combined with other pleasurable activities (e.g., reading, listening to podcasts, making telephone calls). if outdoor activity is still not possible, light therapy lamps can also have antidepressant benefits (kripke ). social distancing efforts are disrupting routines, leading to less daily structure and negatively impacting sleep. many individuals also report increased screen time and anxious thoughts at bedtime, making insomnia a problematic consequence of the pandemic. decades of research show that adequate sleep is necessary for physical health, immune functioning, and mental well-being. cbt for insomnia involves working with dysfunctional beliefs about sleep, utilizing stimulus control, and practicing good sleep hygiene. in addition to getting sunlight and physical exercise throughout the day, keeping a regular sleep schedule, engaging in a relaxing wind down routine, and limiting electronic use before bed are all helpful strategies. if individuals cannot sleep at night, they should go to another part of their home and do a calming activity until they feel sleepy, ensuring that bedrooms are used for sleep only. finally, anxious thoughts should be dealt with prior to bed time (e.g., worry time) and dysfunctional beliefs about sleep (e.g., catastrophic outcomes resulting from not achieving a "perfect" night's sleep) can be addressed with cognitive reappraisal and psychoeducation. telework and home entertainment-common during the pandemic-lead to prolonged sitting and a normalization of sedentary lifestyles. social distancing may greatly reduce individuals' activity levels, since gyms are closed and organized team sports are cancelled. even before the pandemic, many people failed to get the min/week of aerobic exercise recommended by the american heart association. however, physical activity promotes positive moods and can be protective against depression (schuch et al. ) so becoming more active is very important. activities such as walking, running, hiking, or indoor activities (e.g., fitnesscentered video games, zoom yoga classes) are all helpful. individuals who are beginning new exercise routines should consider physical activity as they would any new habit, emphasizing starting small and being consistent. for many, the pandemic has caused a prolonged increase in stress, which often leads to an increase in the consumption of highly palatable high-fat and high-sugar foods (adam and epel ) . the intake of calorically-dense foods has been found to stimulate the reward center of the brain, thus reinforcing this behavior by temporarily reducing negativeaffect. however, consequences of eating such foods include inflammation in the body, which has been linked to various health conditions such as depression (kiecolt-glaser ) . therefore, the strategy of eating such foods to manage stress and increase feelings of well-being is counterproductive. instead, more prudent strategies involve cognitive appraisal, deliberate behavioral changes, and awareness around stimulus control. for example, avoid purchasing these highly caloric foods, since reduced access will likely equate to decreased consumption. additionally, taking advantage of time at home by planning and preparing meals in advance can help override the tendency to reach for highly caloric foods when hungry or stressed. while social connection is of utmost importance during a period of social distancing, a distinct set of challenges related to boundary infringement emerged within the social lives of those asked to stay at home, work at home, and socialize from home. this change is in part a result of a prevalent aspect of the "new normal" which includes the utilization of videoconferencing platforms (e.g., zoom) for work meetings, academic classes, and social calls. individuals working from home were asked to do so within the context of unclear expectations (e.g., increased availability) and increased demands (e.g., homeschooling children). unsurprisingly, individuals struggling with the effects of boundary infringement may react by either withdrawing and avoiding particularly aversive work-related tasks or by being overly accommodating and working increased hours. however, neither of these responses is sustainable; avoidance often leads to increased anxiety and overworking often leads to burnout. a helpful strategy is to develop and implement a behavior management plan in order to set a metaphorical boundary between work and home, given that the physical boundary is no longer in place. in addition, despite the usefulness of video conferencing software, a newly-recognized phenomenon is "zoom fatigue," described in the media as a feeling of being disengaged during video conferences and/or mentally drained after signing off. virtual meetings lack many of the nuances that make in-person interactions feel connected and organic, while also presenting challenges such as internet connectivity issues, background noises, and awkward pauses or moments of cross-talk. as a result, those with many zoom obligations may emotionally withdraw, becoming less participative in work meetings and choosing not to join video calls with friends despite already feeling socially isolated. this unique brand of burnout can be combated with specific behavioral strategies aimed to help individuals re-engage with their zoom activities by treating virtual get-togethers the same way they would treat those events in real life. for example, to get into a "work" mindset, individuals should keep the same pre-work morning routine as they held before the pandemic, create one designated workspace in their home, and practice staying engaged in meetings by asking questions. to help maintain enthusiasm about virtual social activities, individuals should seek to create a clear delineation between work-related video calls and social video calls. this distinction can be accomplished by using different video apps for each kind of call, changing out of one's work clothes at the end of the day and into clothes one would normally wear for social events, and not taking social calls in one's designated workspace area. finally, individuals may benefit from reaching out to family and friends to process feelings of burnout, and recruiting loved ones to help hold them accountable. on the other hand, in the service of "staying connected," individuals may feel pressured to respond quickly to alerts on mobile devices or participate in virtual get togethers even when their time might be better spent in solitude. others may participate in virtual social events only to find themselves begrudgingly talking about news, politics, or the pandemic. for those who feel sufficiently connected, communicating clearly about feelings and intentions using assertive statements is important. setting appropriate boundaries with electronic communications can also be very helpful, either by silencing mobile notifications, lengthening delays before responding to others, or skipping virtual meetups all together if feeling socially "worn out." whatever approach is taken, increasing agency within communications may decrease feelings of resentment and, as a result, make socialization more fulfilling. to address these various concerns, our clinic has created a two-session consultation service for psychological distress related to covid (for materials, see limowski et al. ). the consultation service was advertised on the university clinic's website so that the link could be easily shared by students and faculty. the description is as follows: "in order to offer our expertise in helping individuals cope with psychological distress and emotional difficulties related to covid- , the staff of the anxiety and depression clinic (director: william c. sanderson, phd-a ny state licensed psychologist) is offering a consultation series consisting of two -min online sessions with an adc staff member." clients are asked to provide responses to questions that assess their current and pre-pandemic levels of fear, sadness, and emotional distress on a -point scale, identify and provide information about their most challenging pandemicrelated circumstance, and provide some information about their mental health functioning (e.g., past/current medication use, therapy, diagnosis). sessions are scheduled by email and take place over hipaa compliant zoom. our first session is based on the single-session model used by schleider ( ) and involves targeting one or two main problem areas with cognitive behavioral strategies. our clinic additionally offers a follow-up session one week later to further assist clients in utilizing strategies previously discussed. at time of writing, four clients have completed our brief consultation service. issues addressed most commonly involved managing job-related stress, setting healthy boundaries, practicing sleep hygiene, managing excessive worry related to uncertainties, and reducing alcohol consumption. while of course, these data are very preliminary given the small sample size, it is worth noting that self-report assessment conducted following the second session indicates that the consultation service was of value clients. specifically, clients reported experiencing approximately % reductions in fear, sadness, and general distress over the course of one week following the implementation of the recommended strategies. all clients rated the intervention as "very helpful" in addressing their concerns and developing an action plan (both rated as on a point scale). similarly, therapists conducting these sessions believed they were effective in administering a very focused, useful intervention. these data are promising with regard to delivering a remote, scalable, and effective intervention for those suffering from pandemicrelated psychological distress. as is evident, many individuals are struggling with a plethora of covid-related triggers; however, a variety of therapeutic strategies (indicated above) can be helpful in managing the resulting distress. in fact, highly stressful life events that are often associated with periods of grief and loss are also typically associated with hopeful periods of readjustment and healing (tedeschi and calhoun ) . thus, during the covid crisis, it is possible that many individuals will convey healthy response patterns-some may exhibit resilience (i.e., maintaining baseline functioning in the context of disruption) and others may even experience posttraumatic growth (i.e., improving baseline functioning in the context of disruption) as a result of dealing with a new reality. generally, individuals report experiencing at least one positive change after a potentially traumatic event (e.g., an increased appreciation for life, stronger and closer relationships; tedeschi and calhoun ) . therefore, dealing with the abrupt and ongoing changes of the pandemic can actually have positive psychological effects over time. during the covid crisis, it is understandable that individuals feel down and distressed at times; however, expecting to only feel this way won't allow for the possibility of even momentary health and wellness. instead, a curious, open, and appreciative mindset can promote self-maintenance and growth. commuting time can be repurposed in new and valuable ways, individuals can focus on meaningful activities they may not have had time for previously, and new hobbies can be embraced and potentially result in longterm lifestyle changes. as regulations are slowly lifted, individuals can also begin to practice appreciating life's day to day activities that may have been previously interpreted as mundane or even aversive (e.g., grocery shopping, sitting in traffic, running errands). additionally, being proactive and deliberate with one's actions towards growth (e.g., setting goals) and embracing resilience resources (e.g., individual characteristics and skills, social support within communities, finding a sense of meaning/purpose) are also particularly helpful in cultivating progress (rosenberg ) . importantly, while some may experience resilience and growth, expecting this outcome at all times is unreasonable and unhelpful. there is no "right" way to cope with the pandemic, and growth isn't essential to survive. instead, individuals need to simply do what works best for them during these challenging times. in sum, although the covid crisis has resulted in numerous problems, resilience and growth are not only possible, but probable. however, resilience requires a "growth mindset"-one which acknowledges the negative but also looks for opportunities for improvement. the covid- crisis is expected to have an enormous negative impact upon the mental health of the world's population (marques et al. ; strakowski et al. ) . unfortunately, the mental health system in the u.s.-and perhaps other places in the world-is not well poised to deal with the psychological distress associated with the pandemic. given the novelty of this situation, specific treatments have not yet been developed to target the pandemic-related triggers that are resulting in a significant amount of stress. in addition, the present system may not be able to meet the current and future increased need for mental health services and thus, scalable interventions will be necessary to better distribute the resources available to a greater number of individuals. it is important to note that based upon responses to similar stressors, most individuals, even if acutely distressed, are likely to recover on their own once the pandemic passes (rauch et al. ) . indeed, humans are resilient! nevertheless, providing evidence-based cognitive behavioral emotion regulation skills to those experiencing significant distress in the moment has obvious value in that it can facilitate increased comfort as well as decrease the likelihood of more severe problems emerging down the road. if mental health professionals view all psychological distress as a "normal" response to the pandemic, and thus not requiring intervention, this may ultimately lead to significantly worse mental health outcomes for many individuals down the road. as a result, identification and an appropriate level of treatment for those with pandemic-related mental health issues now-ranging from providing self-help information to brief specific interventions to longer term psychotherapeutic treatment-is critical to prevent the development of a mental health pandemic that lasts beyond the covid- crisis. the data were not collected. conflict of interest the authors declared that they have no conflict of interest. informed consent there was no need for informed consent. stress, eating and the reward system stimulus control applications to the treatment of worry alarming trends in us domestic violence during the covid- pandemic individual meaning-centered psychotherapy for the treatment of psychological and existential distress: a randomized controlled trial in patients with advanced cancer use of bibliotherapy in the treatment of grief and loss: a guide to current counseling practices the psychological impact of quarantine and how to reduce it: rapid review of the evidence mental health household pulse survey moving beyond "shame is bad": how a functional emotion can become problematic. social and personality psychology compass covid- hangover: a rising tide of alcohol use disorder and alcohol-related liver disease how to soothe your 're-entry anxiety' as covid- lockdowns lift the consequences of the covid- pandemic on mental health and implications for clinical practice the impact of coronavirus (covid- ) in the diagnosis and treatment of obsessive-compulsive disorder individual differences in two emotion regulation processes: implications for affect, relationships, and well-being negative information weighs more heavily on the brain: the negativity bias in evaluative categorizations stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge light treatment for nonseasonal depression: speed, efficacy, and combined treatment effect of sunlight and season on serotonin turnover in the brain short-circuiting of threat by experimentally altering cognitive appraisal covid- mental health consultation service: intervention protocol building a practically useful theory of goal setting and task motivation: a -year odyssey impact of mantra meditation on health and wellbeing: a systematic review protocol three steps to flatten the mental health need curve amid the covid- pandemic a preliminary investigation of stimulus control training for worry: effects on anxiety and insomnia the implications of covid- for mental health and substance use commonalities in grief responding across bereavement and non-bereavement losses mental health and the covid- pandemic covid- and mental health: a review of the existing literature rising tide: responding to the mental health impact of the covid- pandemic the treatment of maladaptive shame in borderline personality disorder: a pilot study of "opposite action how risky is it, really?: why our fears don't always match the facts cultivating deliberate resilience during the coronavirus disease pandemic coping with fear and sadness during a pandemic physical activity and incident depression: a meta-analysis of prospective cohort studies single-session consultation for emotional and behavioral health open pilot trial of a singlesession consultation service for clients on psychotherapy waitlists new projections on suicide, substance abuse, and covd- [video key substance use and mental health indicators in the united states: results from the national survey on drug use and health center for behavioral health statistics and quality, substance abuse and mental health services administration cdc director warns second wave of coronavirus is likely to be even more devastating posttraumatic growth: conceptual foundations and empirical evidence social comparison, social media, and self-esteem collision of the covid- and addiction epidemics publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -it ygo authors: lotzin, annett; acquarini, elena; ajdukovic, dean; ardino, vittoria; böttche, maria; bondjers, kristina; bragesjö, maria; dragan, małgorzata; grajewski, piotr; figueiredo-braga, margarida; gelezelyte, odeta; javakhishvili, jana darejan; kazlauskas, evaldas; knefel, matthias; lueger-schuster, brigitte; makhashvili, nino; mooren, trudy; sales, luisa; stevanovic, aleksandra; schäfer, ingo title: stressors, coping and symptoms of adjustment disorder in the course of the covid- pandemic – study protocol of the european society for traumatic stress studies (estss) pan-european study date: - - journal: european journal of psychotraumatology doi: . / . . sha: doc_id: cord_uid: it ygo background: during the current covid- pandemic, the people in europe are exposed to self-isolation, quarantine, job loss, risk of contracting covid- , or grief of loved ones. such a complex array of stressors may lead to symptoms of adjustment disorder or posttraumatic stress disorder. this research protocol describes a study launched by the european society of traumatic stress studies (estss) to investigate the impact of the covid- pandemic on symptoms of adjustment disorder across european countries. objective: the longitudinal online cohort study aims ( ) to explore psychosocial reactions to the covid- pandemic across ten european countries; ( ) to examine the relationships between risk and resilience factors, stressors and symptoms of adjustment disorder during the pandemic; and ( ) to investigate whether these relationships are moderated by coping behaviours. method: in ten countries (austria, croatia, georgia, germany, italy, lithuania, netherlands, poland, portugal, and sweden), between , and , participants will be recruited, depending on the size of the country. participants will be assessed at two timepoints with a six-month interval. following a conceptual framework based on the who’s social framework of health, an assessment of risk and resilience factors, covid- related stressors and pandemic-specific coping behaviours will be measured to estimate their contribution to symptoms of adjustment disorder. the adjustment disorder new module (adnm- ) will be used to assess symptoms of adjustment disorder. as a secondary measure, symptoms of posttraumatic stress disorder will be measure using the primary care ptsd screen for dsm- (pc-ptsd- ). data analysis: the relative contribution of risk factors, resilience factors, and stressors on symptoms of adjustment disorder or symptoms of posttraumatic stress disorder will be estimated using multilevel analysis. to determine the moderating effects of different types of coping behaviours on these relationships, a multilevel mediation analysis will be carried out. estresores, afrontamiento y síntomas de trastorno de adaptación en el curso de la pandemia de covid- -protocolo de estudio de la sociedad europea de estudios de estres traumático (estss) estudio pan-europeo antecedentes: durante la actual pandemia de covid- , las personas en europa están expuestas a autoaislamiento, cuarentena, pérdida de empleo, riesgo de contraer covid- o duelo de sus seres queridos. un conjunto tan complejo de factores estresantes puede provocar síntomas de trastorno de adaptación o trastorno de estrés postraumático. este protocolo de investigación describe un estudio lanzado por la sociedad europea de estudios de estrés traumático (estss) para investigar el impacto de la pandemia covid- en los síntomas del trastorno de adaptación en países europeos. objetivo: el estudio longitudinal de cohorte en línea tiene como objetivo ( ) explorar las reacciones psicosociales a la pandemia de covid- en diez países europeos; ( ) examinar las relaciones entre los factores de riesgo y resiliencia, estresores y síntomas de trastorno de adaptación durante la pandemia; e ( ) investigar si estas relaciones son moderadas por comportamientos de afrontamiento. método: en diez países (austria, croacia, georgia, alemania, italia, lituania, países bajos, polonia, portugal y suecia) serán reclutados entre , y , participantes, dependiendo del tamaño del país. los participantes serán evaluados en dos momentos con un intervalo de seis meses. siguiendo un marco conceptual basado en el marco social de salud de la oms, una evaluación de los factores de riesgo y resiliencia, factores estresantes relacionados con covid- y el comportamiento de afrontamiento específico de la pandemia serán medidos para estimar su contribución a los síntomas de trastorno de adaptación. el nuevo módulo de trastorno de adaptación (adnm- ) se utilizará para medir los síntomas del trastorno de adaptación. como medida secundaria, se evaluarán síntomas de trastorno de estrés postraumático usando el cribaje de tept en atención primaria para dsm- (pc-ptsd- ). análisis de datos: la contribución relativa de los factores de riesgo, factores de resiliencia y los estresores sobre los síntomas de trastorno de adaptación o síntomas de trastorno de estrés postraumático se estimará mediante análisis multinivel. para determinar los efectos moderadores de diferentes tipos de conductas de afrontamiento en estas relaciones, se llevará a cabo un análisis de mediación multinivel. with the global covid- pandemic, europe faces one of the most significant challenges in many years. population-wide public health measures to reduce the spread of covid- have disrupted social and economic systems. as in other regions of the world, the european populations are exposed to a variety of persistent stressors that can lead to mental health problems. these include social isolation, lack of childcare, loss of employment, having covid- , and loss of loved ones (brooks et al., ; fiorillo & gorwood, ; galea, merchant, & lurie, ) . given the psychological, social and economic burden placed on entire populations, the impact of the pandemic on mental health is a critical issue to be addressed (holmes et al., ) . subgroups of the general populations might be particularly vulnerable to develop mental health problems. people with a low socio-economic position may experience greater social and economic burden due to unemployment, low financial reserves and precarious working conditions (van dorn, cooney, & sabin, ). frequent consumption of news about covid- in social media seems to increase the perceived distress (gao et al., ) . elderly persons might be more distressed by measures of self-isolation than younger person due to fewer social contacts (armitage & nellums, ) . previous or current mental or physical health conditions (liu, chen, lin, & han, ) and previous trauma exposure (frewen, zhu, & lanius, ) may be additional factors that may place people at greater risk. people who have covid- , or who have personal contact with people who may have covid- , are prone to mental health problems. frontline health care workers may experience distress related to moral injury if they are unable to provide appropriate treatment due to a lack of needed resources (greenberg, docherty, gnanapragasam, & wessely, ; kang et al., ; lai et al., ) . when facing stressful situations, most individuals may cope in a resilient manner and react with strength to personal and social adversity (kitson, ) . however, during the current uncertain and acute crisis of the covid- pandemic, the accumulated stressors may disrupt mental health (rajkumar, ) . based on findings from earlier pandemics, one out of four individuals suffered from clinical symptoms (mihashi et al., ) . a study conducted in italy at the beginning of the current covid- pandemic showed that many individuals experienced psychological distress, particularly women (rossi et al., ) . symptoms of adjustment disorder or posttraumatic stress disorder (ptsd) were most often reported (rossi et al., ) . given the psychological burden during the covid- pandemic (lima et al., ) , the relationships between the cumulative risk and resilience factors, stressors, and stress-related symptoms should be investigated. the covid- pandemic characteristics and its development are not well understood. the course of the pandemic is unpredictable, although the most likely scenario is that covid- will continue to spread (cyranoski, ) . previous research has shed light on risks and mitigating factors of trauma and stress-related disorders; such knowledge could be helpful to design timely prevention strategies. at present, knowledge of the risk factors and stressors that contribute most to the psychological burden in the general population across different countries in europe is still sparse. according to the who's multilevel social framework of health (solar & irwin, ) , both social determinants of health inequalities and social determinants of health impact on mental health and disorders. such determinants include risk factors and stressors on the individual, community and country level nation. the covid- pandemic may have an impact on many, if not all, of these risk factors and stressors (see figure ). determinants of adverse mental health may include biological factors (e.g. having covid- or chronic illness), psychosocial factors (e.g. fear of contracting covid- , feeling isolated, perceived lack of social support, having intensive care unit treatment, death of loved ones, severe covid- infection of loved ones, working in health care), and material circumstances (e.g. financial and job loss, restricted housing conditions). behavioural factors, i.e. behaviours to cope with the stressors of the pandemic (e.g. physical exercise or substance use) may buffer or heighten the impact of pandemic-related stressors on mental health (allen, balfour, bell, & marmot, ) . determinants of mental health inequalities during the covid- pandemic comprise socioeconomic characteristics (e.g. loss of job, access to financial support), culture and societal values (e.g. stigmatization of vulnerable groups, limitation of individual rights), social and health policies (e.g. short-term work, access to health services), and public policies (e.g. physical distancing, restriction of free movement, quarantine, enforcing surveillance of individuals). tackling the covid- pandemic has placed immense pressure on healthcare systems around the world, health care workers are at increased risk of extreme stress and trauma exposure williamson, murphy, & greenberg, ) . different european countries enforce different public policies to respond to and manage the covid- crisis. some apply more restrictive and less participatory public policies (e.g. georgia, italy), while others decided upon less restrictive and more participatory approaches (e.g. sweden). european countries also differ in terms of socioeconomic factors, onset of the outbreak, social security, healthcare system, and in the extent to which supportive social policies are planned and implemented. moreover, european countries have different cultural values which not only shape the perception of the stressors, but have an impact on individual, family and collective coping strategies to deal with them. this study protocol describes a study launched by the european society for traumatic stress studies (estss). the study was planned with a specific focus on stress-and trauma-related disorders. an estss task force on psychosocial responses to covid- identified the need for such studies to fill the gap of knowledge about stress-and traumarelated mental health problems during the covid- pandemic (javakhishvili et al., ) . the study will examine the relationships between these complex risk and resilience factors, stressors, coping behaviour and stress-related symptoms during the covid- pandemic across ten european countries. the cohort study aims ( ) to explore psychosocial reactions to the covid- pandemic across ten european countries; ( ) to examine the relationships between risk and resilience factors, stressors and symptoms of adjustment disorder during the covid- pandemic; and ( ) to investigate whether the relationships between risk factors, resilience factors, stressors and symptoms of adjustment disorder are moderated by different types of coping behaviours. it is assumed that the selected risk factors, resilience factors and stressors are significantly associated with severity of adjustment disorder symptoms at t and t . the study was planned to be an online cohort survey involving the general population. the study will be conducted in ten european countries: austria, croatia, georgia, germany, italy, lithuania, netherlands, poland, portugal, and sweden. participants will be assessed at baseline (t ) and will be reassessed months later (t ) (figure ). the study will recruit participants from the general population who have access to internet. the inclusion criteria require all participants to be at least years old and to be willing to take part in the survey. in accordance to ethics standards, all participants are requested to provide an informed consent before taking part in the study. the countries involved in this study differ by population size. in light of this, the sample sizes will be n = , for countries with less than mio. inhabitants (austria, croatia, georgia, lithuania, portugal, sweden), and n = , participants for countries with more than mio. inhabitants (italy, germany, netherlands, poland). recruitment strategy complies with the need of having a fast data collection; therefore, most of the participants will be recruited via social platforms (e.g. facebook, twitter, instagram, whatsapp, linkedin). additional strategies will include recruitment through universities, stakeholders and professional organizations, and advertisements in television, newspapers and magazines. a range of different methods will be used to increase variability of the sample in terms of gender, age, education, and regions of the countries (e.g. posting on interest groups and websites that address different age, gender, and education groups). participants may or may not receive incentives, depending on the financial resources of the participating countries. the core set of instruments includes sociodemographic characteristics (e.g. age, gender, nationality, relationship status, education, income and work situation), risk and resilience factors and stressors related to the covid- pandemic, coping behaviours during the pandemic, symptoms of adjustment disorder, and symptoms of posttraumatic stress disorder. for the selection of risk and resilience factors and stressors, a conceptual framework on the determinants of mental health during the covid- pandemic has been developed (figure ), based on the who framework for social determinants of health (solar & irwin, ) . individual risk factors include age, gender, single-parent status, migration status, health worker (e.g. nurse, care assistant, front-line health worker), being at work with frequent personal contact, education, previous or current mental illness, and childhood trauma exposure, among others. childhood trauma exposure will be assessed using the first five items of the adverse childhood experiences (ace) questionnaire (felitti et al., ) . respondents are asked ('yes' vs. 'no') whether they experienced five different types of aces before age of (emotional, physical, and sexual abuse; emotional and physical neglect). the ace questionnaire has been validated in nonclinical and clinical samples and demonstrated satisfactory internal consistency and evidence for its convergent validity with the childhood trauma questionnaire (schmidt, narayan, atzl, rivera, & lieberman, ) . the remaining risk factors will be assessed by self-constructed items. perceived cognitive, behavioural, and emotional burden of covid-related stressors will be assessed with -point scales ( = not at all burdened, = somewhat burdened, = moderately burdened, = strongly burdened) during the last month. more specifically, we will assess stressors related to health (e.g. fear of contracting covid- , having covid- ; severity of covid- ; loved ones having covid- ; severity of covid- of loved ones, death of loved ones); public-life restrictions (e.g. restricted leisure activity, being at home most of the time); social relations (e.g. perceived lack of social support; restricted personal contact to loved ones; stigmatization); home (e.g. difficulties with combining work with childcare, conflicts at home; restricted housing conditions); work (e.g. financial and job loss, reduced working hours); and social media (e.g. consumption of social media coverage of the pandemic). risk and resilience factors and stressors on the country level, e.g. population demographics (density, age structure), public policies to respond to the covid- pandemic, the time of the outbreak, social security, healthcare system characteristics, and social policies will be collected from publicly available data sources (e.g. john hopkins coronavirus resource centre, centre for health security). to address all covid-related coping behaviours, a brief questionnaire on coping behaviour was specifically developed (pandemic coping scale, pcs; lotzin, ). the first set of items was developed by the university of hamburg, based on the recently published recommendations on how to cope with the covid- pandemic (ama, ; cdc, ; csts, ; who, ) , and on a review of studies about coping during previous pandemics. the resulting questionnaire includes items representing coping behaviour in six areas: preventive action (e.g. 'i have been following the recommendations to limit the spread of the coronavirus'); health lifestyle (e.g. 'i have been paying attention to a healthy diet.'); rest (e.g. 'i have been paying attention to take enough breaks.'); meaningful activities (e.g. 'i have been doing something that i enjoy.'); daily structure (e.g. 'i have been paying attention to maintain my daily routine.'); and social support (e.g. 'i have been spending a good time with loved ones, friends, or my pet.'). respondents rate on a -point-scale ranging from to ( = i have not been doing this at all; = i've been doing this a little bit; = i've been doing this a medium amount; = i've been doing this a lot) what best applies to them. items were constructed by a clinical psychologist with expertise in traumatic stress research and psychological treatment of posttraumatic stress disorders (first author of this protocol). items were then reviewed, refined and selected by consensus of an expert group of professionals in the field of traumatic stress (authors of this protocol). use of supportive services (telephone consultation, online coaching, psychotherapy or self-help group; personal coaching, psychotherapy or self-help group) during the pandemic will be also assessed. symptoms of adjustment disorder will be assessed with the adjustment disorder -new module (adnm- ; kazlauskas, gegieckaite, eimontas, zelviene, & maercker, ) . the adnm- measures adjustment disorder symptoms with eight items ranging from to ( = never, = rarely, = sometimes, = often). a total score (ranging from to ) can be calculated by summing up the item scores. the measure has been psychometrically evaluated in helpseeking individuals with symptoms of adjustment disorder, where it has indicated factorial validity (kazlauskas et al., ) . symptoms of posttraumatic stress disorder will be assessed using the primary care ptsd screen for dsm- (pc-ptsd- ; prins et al., ) . the pc-ptsd- is a brief -item screening measure for ptsd according to dsm- . respondents rate on dichotomous items whether the respective ptsd symptom was experienced within the last month ( = no, = yes). the total pc-ptsd- score is obtained by summing the scores of the five items. the pc-ptsd- has been developed from the ptsd- , a widely used screening measure for ptsd that showed reasonable performance characteristics in community settings (spoont et al., ) . the pc-ptsd- has demonstrated strong preliminary results for its diagnostic accuracy (prins et al., ) . in addition to the core set of measures described above, each participating country may include optional instruments to assess the following constructs: resilience, coping behaviours, symptoms of depression, and positive consequences of the covid- pandemic. resilience will be assessed using the resilience evaluation scale (res; van der meer et al., ) . the scale comprises nine items tapping self-confidence and self-efficacy. the participants indicate how they think about themselves and the way in which someone usually responds to difficult situations on a -point scale (from = completely disagree to = completely agree). in addition to the pandemic coping scale that measures the pandemic-specific coping behaviour, coping behaviours can be assessed using the brief cope (carver, ) . the brief cope is a multidimensional inventory to assess coping with distress. fourteen types of behaviours (self-distraction, active coping, denial, substance use, use of emotional support, use of instrumental support, behavioural disengagement, venting, positive reframing, planning, humour, acceptance, religion, self-blame) are measured by items on -point rating scales ( = i have not been doing this at all to = i've been doing this a lot). in addition to symptoms of adjustment disorder and posttraumatic stress disorder, symptoms of depression can be measured using the patient health questionnaire (phq- ; kroenke, spitzer, & williams, ) . respondents rate on nine items ( = not at all to = nearly every day) whether they experienced symptoms of fatigue, loss of appetite or negative thoughts related to depression within the last weeks. positive consequences due to the coronavirus pandemic can be assessed by a set of items developed for the purpose of this study. they ask the participants to indicate whether they see that the covid- pandemic may have had any positive aspects. the items are designed in a -point response format, ranging from 'not at all positive' to 'strongly positive'. these items cover the potentially positive consequences in the following areas: social, health, job, learning, joyful time, reflection, and recovery. the study was registered in a study registry prior to its start (osf registry, https://doi.org/ . /osf. io/ xhyg). participants are expected to be recruited from end of may to november . potential participants will receive an invitation to participate in the survey by providing a website link to the study. all eligible participants will be included in the study. participants will be asked to complete an online survey consisting of several questionnaires (see measurement section). participants will be contacted again after months and asked to participate in the survey for the second assessment point. to explore psychosocial reactions to the covid- pandemic across the ten european countries, descriptive statistics of the covid-related stressors, symptoms of adjustment disorder and posttraumatic stress disorder will be computed, stratified by country and relevant risk groups (e.g. health workers, elderly, low income). mean and standard deviation or median and interquartile range will be computed, as appropriate, for the continuous variables; absolute and relative frequencies will be computed for categorical variables. the prevalence of adjustment disorder (adnm- > ) and posttraumatic stress disorder (pc-ptsd > ) will be estimated for each timepoint with mixed logistic regression for the sample and for risk-groups (p-level %, two-sided). for examining the impact of risk and resilience factors and stressors on symptoms of adjustment disorder, we will apply a longitudinal multilevel model with the adjustment disorder symptom score (adnm- ) as dependent variable, all defined risk and resilience factors and stressors (see measures section) and time point (repeated measurement using a firstorder autoregressive covariance matrix) as independent variable. if the data will not follow a normal distribution, the data will be transformed with appropriate data transformation methods (e.g. linear square, cube root or logarithmic transformation, depending on the distribution of the skewed data) prior to data analysis (Šimkovic & träuble, ) . after a backward selection using a likelihood ratio test in each step, a final model with the most important determinants will be obtained. this model will be extended to a moderation model to examine the moderating effect of coping behaviour. to test the robustness of the results, missing values will be imputed using the full information maximum likelihood approach in a sensitivity analysis. the same procedure will be followed for examining the impact of risk and resilience factors and stressors on symptoms of posttraumatic stress disorder. in addition to the analysis described above using continuous scores, the presence (vs. absence) of adjustment disorder (adnm- > ) or posttraumatic stress disorder (pc-ptsd> ) will be used as a dependent variable for a secondary data analysis to examine the impact of risk and resilience factors and stressors on adjustment disorder. the study will meet all ethical regulations as required by the regulations of the ethics committees which are responsible for the respective study sites. each country will obtain ethical approval of the study on a national level. informed consent to participate in the study will be obtained from all participants. participants will be informed that they are under no obligation to participate and that they can withdraw at any time from the study without consequences. data will be stored on a server of the coordinating centre (centre for interdisciplinary addiction research, ciar, at university of hamburg), or on a secure server of the study site, depending on the country. data handling will follow the eu general data protection regulation (dsgvo); data will be stored for at least years. we will follow the strobe statement on good reporting practice. the results will be published in open access journals, following the guidelines on open access to scientific publications and research data in h . participant countries will retain the property and administration of their national data, and all countries will share the core dataset in order to enable analyses from the whole sample of the ten countries. after study completion and publication of the results of the primary study aims, data will be made available to the public. al designed the study in cooperation with the project steering committee formed by the representatives of the estss countries (all authors of this protocol). al, da, mb, mf-b, jdj, va, ek, bls, and is drafted the manuscript of the study protocol; all authors revised sections of the manuscript and approved the final version of the manuscript. margarida figueiredo-braga http://orcid.org/ - - - evaldas kazlauskas http://orcid.org/ - - - matthias knefel http://orcid.org/ - - - social determinants of mental health managing mental health during covid- covid- and the consequences of isolating the elderly. the lancet public health the psychological impact of quarantine and how to reduce it: rapid review of the evidence sustaining the well-being of healthcare personnel during coronavirus and other infectious disease outbreaks profile of a killer: the complex biology powering the coronavirus pandemic relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. the adverse childhood experiences (ace) study the consequences of the covid- pandemic on mental health and implications for clinical practice lifetime traumatic stressors and adverse childhood experiences uniquely predict concurrent ptsd, complex ptsd, and dissociative subtype of ptsd symptoms whereas recent adult non-traumatic stressors do not: results from an online survey study the mental health consequences of covid- and physical distancing: the need for prevention and early intervention mental health problems and social media exposure during covid- outbreak managing mental health challenges faced by healthcare workers during covid- pandemic multidisciplinary research priorities for the covid- pandemic: a call for action for mental health science trauma-informed responses in addressing public mental health consequences of the covid- pandemic: position paper of the european society for traumatic stress studies (estss) impact on mental health and perceptions of psychological care among medical and nursing staff in wuhan during the novel coronavirus disease outbreak: a cross-sectional study a brief measure of the international classification of diseases- adjustment disorder: investigation of psychometric properties in an adult help-seeking sample rising from the ashes: affirming the spirit of courage, community resilience, compassion and caring the phq- : validity of a brief depression severity measure factors associated with mental health outcomes among health care workers exposed to coronavirus disease the emotional impact of coronavirus -ncov clinical features of covid- in elderly patients: a comparison with young and middle-aged patients pandemic coping scale. unpublished manuscript predictive factors of psychological disorder development during recovery following sars outbreak the primary care ptsd screen for dsm- (pc-ptsd- ) national center for ptsd covid- and mental health: a review of the existing literature covid- pandemic and lockdown measures impact on mental health among the general population in italy. an n = web-based survey childhood maltreatment on the adverse childhood experiences (aces) scale versus the childhood trauma questionnaire (ctq) in a perinatal sample robustness of statistical methods when measure is affected by ceiling and/or floor effect a conceptual framework for action on the social determinants of health assessing psychological resilience: development and psychometric properties of the english and dutch version of the resilience evaluation scale (res) world health organization (who). ( ). mental health and psychosocial considerations during the covid- outbreak risk factors of icd- adjustment disorder in the lithuanian general population exposed to life stressors the authors thank the study personnel and collaborators for their support: irina zrnic (team austria); prof. tanja franciskovic and helena bakic (team croatia); ilaria cinieri, alessandra gallo and chiara marangio (team italia); monika kvedaraite (team lithuania); lonneke lenferink (team netherlands); monika folkierska-Żukowska and magdalena skrodzka (team poland); aida dias (team portugal); dr filip arnberg, dr josefin sveen, dr kerstin bergh johannesson and ida hensler (team sweden).we greatly thank the study team of the coordinating site at university of hamburg (team germany) that prepared the questionnaires, in particular laura kenntemich, who was supported by lennart schwierzke and laura gutewort. we also would like to thank dr sven buth and eike neumann-runde for their technical support in the setup of the survey. special thanks are due to zoran sukovic for his continuous organizational support as secretary of estss. the authors declare that the research was conducted in the absence of any commercial or financial interests that could be perceived as a potential conflict of interest. the authors did not receive specific funding for the planning of this research or for the preparation of this study protocol. key: cord- -ucd ooob authors: bartoszek, adrian; walkowiak, dariusz; bartoszek, agnieszka; kardas, grzegorz title: mental well-being (depression, loneliness, insomnia, daily life fatigue) during covid- related home-confinement—a study from poland date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: ucd ooob the covid- pandemic is a great threat to both physical and mental health as it may lead to psychological stress connected with an economic crisis, threat of unemployment, or fear of losing family members. emerging data shows that the general public may be vulnerable to the pandemic-related stress and experience frequently prevalent anxiety. a study involving subjects ( . % female) was conducted online during the covid- pandemic. we used the following scales: insomnia severity index (isi), beck depression inventory (bdi), revised university of california, los angeles (r-ucla) loneliness scale, and daily life fatigue scale (dlf). women had higher mean scores of depression, loneliness, and daily life fatigue and more often than males started exercising. among people professionally active before the pandemic, there were more cases of increased alcohol consumption than among students. no differences in alcohol consumption patterns were found between genders. people living alone had higher scores of loneliness and daily life fatigue compared to those living with someone. respondents who started taking any new drugs during covid- home confinement had higher outcomes in all questionnaires. during home confinement, high scores of depression, insomnia, loneliness, and everyday fatigue were observed. the outbreak of the global covid- pandemic revealed that the world had been completely unprepared for it. as of may , the global number of reported cases has reached . million and is still rising [ ] . so far, there is no specific anti-covid- treatment, nor targeted prevention. fortunately, currently over vaccine candidates are in pre-clinical studies with some in phase i [ ] . hopefully, an effective vaccine is expected to be available in early . the first confirmed covid- case in poland was announced on march . on march, the polish government announced strict restrictions, which forced the vast majority of polish citizens to obey home confinement. this meant that people were obliged to spend most of their day at home-schools, universities, public institutions operated remotely (online), most of the workers were asked to work from home. the restrictions included: mandatory covering of mouth and nose in public spaces, keeping a minimum two-meter distance between pedestrians, the cancellation of public events, limited number of customers in shops, closed shopping centers, international travel ban, and closed airports. on april the polish government started to gradually abolish the restrictions. the global health crisis of the covid- pandemic is a great threat not only in terms of physical health. as multiple countries worldwide have decided to apply the technique of social distancing, this creates a huge challenge in terms of mental health, greatly reinforced by other factors that may lead to psychological and psychiatric disturbances, such as economic crisis, the threat of unemployment, or fear of losing family members. emerging data show that the general public may be vulnerable to pandemic-related stress and frequently experience prevalent anxiety [ ] . psychological and psychiatric disorders are complex in terms of pathogenesis with multiple causative factors including genetics, physical state, socioeconomic status, etc. however, in general, psychological and social factors may play a role in triggering some of these disorders (e.g., anxiety or depression). in light of that, social distancing and home confinement regulations are important factors that shall be considered in managing social and psychological well-being [ ] [ ] [ ] [ ] [ ] . since the beginning of the covid- pandemic at the end of , some research on mental health has been published. the issues covered include mostly depression and anxiety, with some preliminary reports also on insomnia. however, these reports are mostly from china and other asian countries, where the pandemic first started and lessons on the issue were learned first [ ] [ ] [ ] . some reports from other regions confirm a declining tendency in peoples well-being and mental condition during the covid- pandemic [ ] [ ] [ ] . moreover, many of these studies are focused on the mental health of healthcare workers [ ] , who are on the frontline of the pandemic, yet fewer studies are focused on those not involved in healthcare [ ] . to date, very limited data is available on the issue of the impact of the covid- pandemic on mental health in european countries [ ] . only one study covered some aspects of this topic in poland, whose authors studied the effects of mandatory face mask restrictions on anxiety, depression, insomnia, and social dysfunction questionnaire scores [ ] . as described above, certain areas of research on mental health during home confinement were not covered, particularly, especially regarding the geographic distribution of the studies. moreover, in june a position paper was published in the lancet with a call-for-action for studies on mental health effects of the covid- pandemic across population and vulnerable groups [ ] . this is particularly important as not only is the pandemic still active, but the world may also face its second wave. in fact, some countries already re-implemented social distancing requirements and home confinement regulations. to extend the scope of the research on the topic, we decided to include some further factors that may be associated with varying mental health outcomes during covid- home confinement. these factors included: alcohol consumption, taking psychiatric drugs (antidepressants, anxiolytics, sedatives or others), and living alone or with others during home confinement. the aim of the study was to measure indicators of mental well-being in a polish sample with regard to selected sociodemographic and health behavior data during home confinement related to covid- pandemic. we suspected that selected sociodemographic and health behavior data could differentiate mental well-being during home confinement related to covid- pandemic. this was an online study involving polish adult citizens, conducted during the covid- pandemic. current/recovered covid- patients were excluded from participation in the study. study participants were invited to complete a self-administered online questionnaire (google forms) . weeks after home confinement restrictions were introduced in poland ( april ) and the questionnaire was available for the following two weeks. participation in the study was generally requested through the researchers' university emails and their official websites. a request for participation was also sent via the researchers' institution social media profile (facebook). the survey was created on the basis of a literature review on mental well-being and with the use of standardized research tools examining symptoms of depression, loneliness, insomnia, and fatigue. sociodemographic questions concerning age, gender, professional status, number of household members, and the questions related to alcohol consumption, physical activity, and administration of new drugs at the time of questionnaire filling (that is during current covid- -related home confinement) were collected. we also asked about the date at which an individual began his/her home confinement. the insomnia severity index (isi) was used to measure the potential severity of insomnia. each item of that tool is rated on a - scale, and its total score ranges from to . a higher score suggests more severe insomnia symptoms [ ] . the scale is widely used in polish population [ ] . internal consistency of isi, assessed with cronbach's α and mcdonald's ω, was found to be sufficient for the study (α = . , ω = . ). the beck depression inventory (bdi), developed by aaron t. beck, is a self-administered questionnaire consisting of multiple-choice questions. it is one of the most commonly used instruments for measuring the severity of depression. the global score of bdi is an arithmetic summation of the ratings of all symptoms scored on a final scale ranging from to . the higher the global score, the greater the depression level [ ] . the scale has been validated in poland [ ] . internal consistency of bdi was found to be sufficient for the study (α = . , ω = . ). revised university of california, los angeles (r-ucla) loneliness scale is a -item scale designed to measure one's subjective feelings of loneliness as well as feelings of social isolation. participants rate each item on a scale from (never) to (often) [ ] . the scale has been validated to polish conditions [ ] . internal consistency of r-ucla was found to be sufficient for the study (α = . , ω = . ). the daily life fatigue scale (dlf) is a polish questionnaire which consists of three subscales: physical fatigue (pf), associated with daily physical activity; mental fatigue (mf), associated with the mental activity (e.g., calculations in memory or remembering a phone number); and social fatigue (sf), regarding social activities, e.g., planning time with loved ones. the result of the scale is a measure of general everyday fatigue, which is the sum of points obtained in all positions of the three subscales in the range from to . the higher the score, the higher the level of general everyday fatigue felt [ ] . internal consistency of dlf was found to be sufficient for the study (α = . , ω = . ). participation in the study was fully voluntary. all participants were familiarized with the study conditions and gave informed consent to participate. confidentiality and anonymity were maintained as no data that potentially identified a responder was collected. bioethics committee confirmed that according to polish law and good clinical practice regulations this research does not require an approval of a bioethics committee (kb nr / ). the data collected in the questionnaires were verified and checked for completeness, quality, and consistency. then it was coded and exported into statistical packages: jasp (version . . ; university of amsterdam, amsterdam, the netherlands) and statistica . (tibco, palo alto, santa clara, ca, usa). for all scales, the mean, median, and standard deviation (sd) values were calculated. welch's unequal variances t-test was used to compare differences between sub-groups (gender, age, activities, and others). effect size is given by cohen's d. we used kendall's tau b to measure the strength of the relationships between variables. a % level of significance was used for all hypothesis tests. sociodemographic characteristics and other personal data are presented in table . generally, most of the respondents were women, students. standard deviation (sd) the average dlf result was . , with results ranging from to ( table ). the results of bdi ranged from to , with a mean score of . . the average r-ucla result was . , ranging from to . the mean isi result was . , with results in a range of - . in our group, % participants scored above the cut-off point of isi questionnaire for acute/chronic insomnia (> points). the average isolation period of our respondents was days (range . - ). we did not observe the impact of isolation time on bdi, r-ucla, and isi results. for dlf, an effect of isolation time on results was observed (kendall's tau b = . , p = . ). the results of all scales were analyzed in terms of age, activities, solitude, employee vs. student status, traditional work vs. telework, and gender. statistically significant differences in the reaction to the new social experience of isolation and social distancing were only observed between genders (table ). women had significantly higher mean scores in dlf, bdi, and r-ucla, but not in isi, where the difference was borderline, but higher than the assumed level of statistical significance. among the other factors examined in connection with the social isolation period were also issues related to physical activity. while individual groups (female /male, working/not working) did not differ in the declared frequency of leaving the house, it turned out that there were some differences regarding lifestyle choices. no statically significant differences in physical activity among genders was shown (see table a ). in the group of people professionally active before the pandemic, there were more cases of drinking alcohol more or more often than in the case of students (table b ). no differences in alcohol consumption patterns, however, were found between genders. we also studied the impact of living alone on the well-being of people during pandemic-enforced isolation. table a presents the results of the scales broken down into two groups, one where the respondents were in home confinement with a partner or family and the second group in which people were living alone. differences for individual scales between people who started taking new drugs during a pandemic and those who did not were also investigated (table b) . as for depression, measured with bdi, the mean score in the group that declared increased alcohol consumption was . compared to . in the group that declared not consuming more alcohol (bdi cut-off for mild depression is > ). research on mental health during the covid- pandemic is an important study area that possibly concerns many individuals, considering that the government announced strict restrictions, which forced the vast majority of polish citizens to obey home confinement, to study and work remotely, and to adjust to the new situation. for this reason, our study aimed to measure mental well-being (levels of depression, insomnia, daily life fatigue, and loneliness) in a sample of the polish population during covid- related home confinement. we focused on differences between genders, physical activity, alcohol consumption, drugs, and living alone. in a review of studies on depression among healthcare workers (over , cases) the depression prevalence was estimated to be %. moreover, another review on depression, which was focused on the general population, showed a . % depression prevalence. this clearly shows the scale of psychological and psychiatric problems related to the pandemic, both among healthcare workers-who in their previous work have already dealt with numerous stressful situations related to other peoples' health-and the general public, for whom this situation may be a kind of a reminder of value and fragility of humans' health [ , ] . a very recent study from china, where the authors used similar methodology as we did in studying insomnia (online isi questionnaire, pre-and during the pandemic) found a significant increase of insomnia (isi > ) from . % to . %. the authors of that study conclude that their findings suggest that insomnia is associated with the covid- outbreak-related psychological reactions and poor sleep hygiene [ ] . another recent report from greece found that % of respondents scored above the cut-off score for insomnia. in our study, this percentage was %. both of these values are above the generally reported worldwide insomnia (acute and chronic) prevalence, estimated before the pandemic to be between . % and % [ ] . these findings may be an indication that some exacerbations of sleep disturbances happen during the covid- pandemic. moreover, differences in insomnia scores between genders were confirmed in the cited study from greece, contrary to our results [ ] . some explanation of these findings may be that during home confinement, people experience less physical fatigue and sun exposure, as well as possibly tend to more prominently use electronic devices that altogether may influence sleep homeostasis [ ] [ ] [ ] . also, without a doubt, the psychological stress caused by this unprecedented situation greatly contributes to this phenomenon. a study similar to ours was carried out in italy online on respondents during march and april . the results have clearly shown that the pandemic and associated psychological stress are risk factors for sleep disorders and psychological diseases, e.g., the authors have shown that all of the elements of the psychological well-being (pgwb) questionnaire (anxiety, depressed mood, positive well-being, self-control, general health, vitality) were significantly worse among study respondents than in previous general population data [ ] . in a very recent meta-analysis of studies on depression, anxiety, and insomnia among healthcare workers during the covid- pandemic the authors analyzed the results of articles on these subjects, all of which were reports from asia (china predominantly). insomnia was found in five out of these studies. the conclusion of this meta-analysis was that insomnia prevalence during the covid- pandemic was . %. the authors did not perform gender sub-group analysis due to limited data available [ ] . although the issue of insomnia is complicated and little is known on the impact of covid- -related stress on it, we may find some practical recommendations addressing this issue. in april the european cognitive behavioral therapy for insomnia (cbt-i) task force published their recommendations on dealing with sleep problems during this pandemic [ ] . existing reports show positive correlations between home confinement during covid- pandemic and perceived loneliness. tull et al. have shown this using the ucla questionnaire in u.s. adults. surprisingly, in the same study, the perceived impact of covid- itself was negatively associated with loneliness and additionally positively associated with social support [ ] . studies suggest that loneliness during covid- home confinement is more strongly felt by younger people [ ] . however, interventions addressing loneliness during covid- home confinement, which are discussed in literature, are proposed to be particularly important among the elderly [ , ] . these include, for example, telehealth and online group interventions targeting these psychological needs [ ] . although societies have-in a way-become used to the fact that loneliness concerns the elderly, in these difficult times it has affected almost every age group. in fact, regardless of the age group, the possibility of psychological support and maintaining social life, e.g., online, should provide an opportunity to improve individual's well-being. a specific type of psychological fatigue is the daily life fatigue (dlf). the author of the questionnaire (urbańska) defines dlf as subjective overall fatigue, which is expressed by the reluctance to undertake daily physical, mental, and social activities [ ] . similar to the other scales used in the study, women had significantly higher mean scores in dlf, comparing to men. living alone and taking new drugs during covid- home confinement, were both variables associated with higher scores of dlf. of importance in the perceived dlf is the self-interpretation of an individual's situation; one may subjectively feel considerably tired while having objectively few everyday activities and vice versa. to the best of the authors' knowledge, there has not yet been a study that addressed the issue of dlf during covid- home confinement. this may be caused by the fact that the dlf scale is a relatively novel tool, developed in polish and has no english translation and validation yet. however, a study that covers the topic of 'psychological fatigue' in turkey has recently been published by morgul et al. the authors concluded that although knowledge, attitudes, and behavior concerning covid- preventive measures are important to prevent transmission of the disease, they are also associated with participants' fatigue. this, in turn, might lead to a psychological outcome e.g., pandemic-related fear and anxiety [ ] . we found that, compared to pre-pandemic times, higher declared alcohol consumption is associated with higher beck depression inventory scores. this outcome implies that some specific caution regarding addiction and mental health should be addressed to those people-both by healthcare professionals and, most importantly, by family members that are together during home confinement. this is particularly important as alcohol misuse during the covid- pandemic may be considered one of the potential public health crises [ ] , since rising alcohol sales and consumption have been reported in european countries [ ] . with social isolation and home confinement, there are also a number of social consequences related to mental health. among them, it is worth mentioning the risk of intensification or exacerbation of domestic violence, which has been highlighted in the literature [ ] . this and other themes, combined with the observations on mental health, should particularly lead to interventions aimed at improving people's well-being. this is one of the very first studies on the impact of covid- pandemic on mental health in europe. in particular, it is only the second covering this topic in poland. to date of article submission, one report from poland has shown that face mask restrictions, apart from preventing the spread of covid- , may in a way increase the level of perceived self-protection and social solidarity, which may improve the general mental health well-being [ ] . certain limitations apply to the results of our study. first of all, it is important to acknowledge this was an online only study which was performed via sharing the link to the survey. this implies that the results are limited to those with access to the internet only. moreover, we acknowledge that our study group is predominantly female, yet we believe that the statistical analysis we provided still allows an objective analysis of the results obtained. moreover, gender differences in r-ucla, bdi, and dlf have strong statistical significance. due to the study design (social media) we are unable to provide the response rate to the survey. with time and downturn of the epidemic in poland, the home confinement regulations were (and at the time of article submission constantly are) being loosened, thus further data collection would possibly result in biased results. the final limitation of our research is that it is a survey from which a nation-wide scale should not be directly extrapolated. this would have been possible only with nationally representative study. however, we believe that our results may still provide useful information on the impact of covid- pandemic on the peoples' mental health. we have shown some general tendencies across genders that imply that further studies in the area may be needed. the other issue is the - age predominance in our study group. however, we found that studies with a similar approach to ours (web-based questionnaire studies during covid- in europe) faced similar problems of female and - sample predominance [ ] . self-selection bias for interest in psychological themes next to bias due to the online administration system is possible. what we report are results on depression, insomnia, loneliness, and fatigue across covid- free individuals. however, it should be remembered that the above-mentioned problems also apply to patients diagnosed with covid- , as reported in the literature [ ] . the outbreak of any infectious disease is associated with panic among people. people's response to a pandemic determines not only the rate of the spread of the disease but also psychosocial disorders both during and after the pandemic. despite this, there are not enough tools that could help maintain the social well-being of the population. this is understandable at the beginning of the spread of the disease where all funds are directed directly to fighting the disease. as the pandemic progressed, severe restrictions were imposed in many countries to keep people at home. this can lead to further disorders related to social isolation. during homestay, people have higher scores of depression, insomnia, loneliness, and everyday fatigue. an important role in the development or deepening of mental disorders can be caused by new drugs that inadequately administrated can cause an increase in the number of hospitalizations, which is not desirable during a pandemic. most mental health studies focus on healthcare workers, while the society at large is usually overlooked. we intended to pay special attention to these disorders that may appear in society during isolation because it is as important as fighting the disease itself, and the consequences can be serious in the long run. world health organization coronavirus disease (covid- ) situation report- milken institute covid- treatment and vaccine tracker the psychological and mental impact of coronavirus disease (covid- ) on medical staff and general public-a systematic review and meta-analysis social integration and mental health -a decomposition approach to mental health inequalities between the foreign-born and native-born in sweden self-rated mental health and socio-economic background: a study of adolescents in sweden associations between subjective social status and dsm-iv mental disorders results from theworld mental health surveys increased -month prevalence rates of mental disorders in patients with chronic somatic diseases gene-environment interaction and psychiatric disorders: review and future directions generalized anxiety disorder, depressive symptoms and sleep quality during covid- outbreak in china: a web-based cross-sectional survey prevalence of depression, anxiety, and insomnia among healthcare workers during the covid- pandemic: a systematic review and meta-analysis survey of insomnia and related social psychological factors among medical staff involved in the novel coronavirus disease outbreak mental health consequences during the initial stage of the coronavirus pandemic (covid- ) in spain the effect of covid- on mental health and wellbeing in a representative sample of australian adults mental health before and during the covid- pandemic: a longitudinal probability sample survey of the uk population mental health and psychosocial problems of medical health workers during the covid- epidemic in china covid- pandemic and mental health consequences: systematic review of the current evidence diakogiannis, i. insomnia during the covid- pandemic in a greek population psychopathological responses and face mask restrictions during the covid- outbreak: results from a nationwide survey multidisciplinary research priorities for the covid- pandemic: a call for action for mental health science validation of the insomnia severity index as an outcome measure for insomnia research occurrence of sleep disorders among nursing staff an inventory for measuring depression psychometric properties of the polish version of the aaron t. beck's depression inventory bdi-ii nonlinear dynamical models in psychology are widespread and testable analysis of the psychometric properties of the revised ucla loneliness scale in a polish adolescent sample prevalence of stress, anxiety, depression among the general population during the covid- pandemic: a systematic review and meta-analysis insomnia and psychological reactions during the covid- outbreak in china advances in the management of chronic insomnia the impact of glucocorticoids and statins on sleep quality covid- anxiety symptoms associated with problematic smartphone use severity in chinese adults covid- fatalities, latitude, sunlight, and vitamin d the enemy who sealed the world: effects quarantine due to the covid- on sleep quality, anxiety, and psychological distress in the italian population dealing with sleep problems during home confinement due to the covid- outbreak: practical recommendations from a task force of the european cbt-i academy psychological outcomes associated with stay-at-home orders and the perceived impact of covid- on daily life we're staying at home". association of self-perceptions of aging, personal and family resources and loneliness with psychological distress during the lock-down incorporating issues of elderly loneliness into the covid- public health response loneliness and social isolation in older adults during the covid- pandemic: implications for gerontological social work using telehealth groups to combat loneliness in older adults through covid- covid- pandemic and psychological fatigue in turkey alcohol use and misuse during the covid- pandemic: a potential public health crisis? lancet public health , , e covid- and alcohol-a dangerous cocktail danger in danger: interpersonal violence during covid- quarantine anxiety and suicidality in a hospitalized patient with covid- infection this article is an open access article distributed under the terms and conditions of the creative commons attribution (cc by) license funding: this research received no external funding. the authors declare no conflict of interest. key: cord- -vhuw gwn authors: demertzis, nicolas; eyerman, ron title: covid- as cultural trauma date: - - journal: am j cult sociol doi: . /s - - -z sha: doc_id: cord_uid: vhuw gwn this paper has two aims. the first is to introduce the concept of compressed cultural trauma, and the second is to apply the theory of cultural trauma in two case studies of the current covid- pandemic, greece and sweden. our central question is whether the pandemic will evolve into a cultural trauma in these two countries. we believe the pandemic presents a challenge to cultural trauma theory, which the idea of compressed trauma is meant to address. we conclude that, while the ongoing covid- pandemic has had traumatic consequences in sweden and greece, it has not evolved into cultural trauma in either country. this paper has two aims. the first is to introduce the concept of compressed cultural trauma and the second is apply the theory of cultural trauma in two case studies of the current covid- pandemic, greece and sweden. our central question is whether the pandemic will evolve into a cultural trauma in these two countries. we believe the pandemic presents a challenge to cultural trauma theory, which the idea of compressed trauma is meant to address. we begin with a short presentation of cultural trauma theory, and then discuss the idea of a compressed cultural trauma before moving into our two cases. there can be little doubt that the ongoing covid- pandemic poses a global threat that has created crisis on many levels, from local communities to states and nations. as eric woods et al. ( ) puts it, 'it has significant potential to trigger multiple, cascading crises in nearly every aspect of our lives. in addition to the presence of a threat, crises typically involve systemic disruption, uncertainty and stress'. a cultural trauma is a form of crisis, a crisis of identity that affects individuals and collectives. both greece and sweden experienced severe crisis during the first stages of the pandemic yet neither, to this point, have developed into cultural traumas. no matter how severe, not all crises become cultural traumas and the point of our comparison is to explain why. a cultural trauma occurs as the taken-for-granted foundations of individual and collective identity are shattered, setting in motion a discursive process to understand what happened, assign blame, and find pathways to repair an interpreted situation. in this ensuing meaning struggle various actors propose answers to these questions, articulating trauma narratives that compete for attention and acceptance. cultural traumas are not the aggregate of individual traumas, nor are they determined by gradations of suffering. cultural trauma is a specific form of collective trauma, affecting collective identity, where groups of individuals feel similarly affected by a fracturing of the existential security that a firm sense of identity affords. a step towards regaining that security, a human requirement, is to understand what happened and who or what was responsible, and then to act accordingly. cultural traumas imply anxiety and suffering, but also opportunity. the latter stems from the human capacity to learn and adjust to new conditions, to remake the world as well as to live in it. cultural traumas are usually studied in retrospect from a distant point in time, allowing one to isolate a point of origin, often a cataclysmic incident, and then trace the ensuing meaning struggle through a range of forums and media, toward memorialization and the impact with regard to collective memory. it is also possible, though more speculative, to study cultural trauma as it is occurring. an example is neil smelser's essay on / that appeared as an epilogue in cultural trauma and collective identity (alexander et al. ) . written just months after the event, smelser ( , p. ) suggests that the distinctive culture of the united states shaped the cultural trauma process in a way that was 'fused, telescoped and undifferentiated'. explaining this, smelser writes: 'with respect to the dimension of time alone, the traumatic process was truncated… the moment of the attacks to the recognition that they constituted a national trauma was a matter of short days, if not hours…the scope of the trauma and the identity of the victims were established immediately… there was an instant consensus that it was a trauma for everybody, for the nation… there was no significant divergence in the reactions of government and community leaders, the media, and the public in assigning meaning to the events as a national tragedy and outrage…there was little evidence of social division around the trauma' (smelser , p. ) . in this article, we look at the ongoing covid- pandemic through the lens of cultural trauma theory, asking what kind of trauma is this, for whom, and what are the possible outcomes? we will illustrate this further through the examples of greece and sweden, addressing the issue raised by smelser about how national cultures and a compressed time/space postmodern condition shape the trauma process. heuristically speaking, the pandemic covid- erupted as a total social fact manifested as an unexpected chain of ruptures (kasuga ) in all socioeconomic, political and cultural institutions and every aspect of everyday life at local, national and international levels. millions are experiencing the greatest disruption of their lifetimes. even during wwii businesses and schools remained open, restaurants served customers, major cultural and sporting events took place and life went on. there has never been anything affecting modern daily life as the current pandemic. it is imposing itself physically and virtually, as an image, with unprecedented and expanding force, condensing time and space worldwide in the most critical way, a phenomenon known as 'time-space compression' (harvey ) . some historians assure us that the coronavirus is a juncture where the river of history changes direction that could lead to the best of times or to the worst of times (macmillan ; garton ash ). as total social fact, the pandemic forces itself into existence in at least four interrelated ways: (a) it is global: it encompasses almost half of the world's population since trillion people are under lockdown as we write. due to international transportation and trading this virus has been transmitted with unusual speed in all continents causing very serious damage to most national economies and world finance markets. also, it deepened the antagonism between the usa and china with regards to g technology, the discovery of the vaccine, and the blame game over the cause of the pandemic. (b) it is risky and uncertain: the pandemic instantiates the quintessence of risk society; a hazardous situation systematically spread through global interconnectivity. it is individually experienced as an anticipated threat to be realized or not, eliciting negative and positive emotionality: anxiety, fear, sadness, and grief, for one's own vulnerability. at the same time, it evokes a sense of loss and anger; feelings of resentment, hope, confidence and trust in a government's efficiency or its opposite. for the time being, insofar as the genomic attributes of the virus are not fully discovered, we claim that the pandemic generates an emotional climate of uncertainty, not as in 'we know that we don't know', but as in 'we don't know what we don't know'. (c) it is highly mediatized: in variable proportions, individuals form a synthetic experience of the pandemic; either as infected or as locked down at home. they live the pandemic through firsthand experience and through the information disseminated by the communications media. the aesthetics of media coverage (dramatization, personalization, fragmentation) are likely to affect the way viewers perceive the health crisis and the concomitant risks. with a lack of effective medical care and the much sought-after vaccine, an individual's need for orientation increases all the more. this need for orientation is contingent upon the relevance of an issue for that individuals' life interests, and the degree of certainty they have concerning their knowledge about it. whenever an issue is highly relevant to one's personal agenda and one's information and knowledge about it is limited, the need for orientation increases. therefore, a person's media dependency increases and the media agenda setting effect rises with conspiracy theories being a possible side effect. with both the radical diversity in media access and representation, the conflict over what happened and who is responsible intensifies, adding more uncertainty with regard to orientation. who is one to believe? (d) it is traumatic: several hundreds of thousands of people around the world are grieving due to the unexpected and sudden loss of loved ones. those deaths often occurred under dire circumstances, in poorly equipped and crowded hospitals, or isolated and abandoned in caretaking facilities. in many countries, normal grieving rituals are prohibited for fear of further contagion. millions of middle aged or elderly people infected by the coronavirus are at home, vulnerable, insecure and isolated, while many others, tired of 'social distancing', harbor anxiety about the upcoming months and an uncertain future. photographs of empty and unpopulated metropolitan areas, in new york, london or paris, may be comprehensible, yet also inconceivable. this is certainly a situation full of traumatic potential. who could imagine the long lines of trucks carrying coffins in italy or the innumerable makeshift caskets stored in refrigerated vehicles outside new york hospitals, or the unclaimed victims buried in mass graves? one can rightly ask, is this europe? is this america? as we noted at the outset, studies of cultural trauma are carried out in retrospect, at the end of a process where discursive themes and central actors can be identified and studied over time. the covid- pandemic is ongoing, but as a total event, it already has many of the characteristics that circumscribe cultural trauma. these include a fundamental disruption of the taken for granted in daily life, a potential loss of trust in leaders and social institutions, negative attribution in the media, a contentious meaning struggle to determine what happened and who is responsible, with many competing accounts aired in various forums. there is constant reference to collective memory, the search for comparable historical incidents, as grounds for understanding, and various carrier groups have formed to articulate and defend their interpretation. this is certainly a collectively aggregated trauma: innumerable people are experiencing the pandemic as traumatic, characterized by a loss of existential security, a biopolitical condition that can potentially create new modalities of subjection and subjectivation, shaping both collective and individual subjectivities. the global dimensions of a public health crisis, its rapid expansion, and the instant circulation of images depicting deep human tragedy have already initiated a trauma drama process. the public discourse about the coronavirus and its effects is multifaceted, antagonistic, and replete with emotionality; it revolves around the meaning of normality, discipline, and self-discipline, trust, confidence and distrust toward institutions and political authority. in many countries, the covid- trauma drama has triggered new forms of artistic expression, such as online concerts, musical and theatrical performances, humorous offline and online creations, the production of books about pandemics throughout the centuries, novels and poetry. blame attribution and the politics of fear through the designation of the virus as 'invisible enemy' and bellicose metaphors of the efforts to cope with it as 'war', permeate public discourse in the same way warfare language was used to tame tb and cancer in the nineteenth and twentieth century. globalization and the accompanying ubiquitous presence of the internet and digital social media have contributed to an intensified time-space compression, whereby the trauma drama that is the core of cultural trauma phenomenon is deepened. in previous theorizing and comparative analysis, cultural trauma studies have noted a belated reaction to a triggering incident or series of incidents that leave indelible marks on collective memory and group identity. as with / and hurricane katrina, this seems no longer the case with regard to covid- , should this be generalized it would expand the trauma potential of related incidents. in many places, a sense of crisis, with a trauma potential, began immediately. under what is identified as time-space compression, some-if not all-elements of the tenets of cultural trauma are visibly present at once: (a) emotionality (mostly negative); (b) blame attribution (carrier groups, media claims etc.); (c) identity formation processes; (d) defense mechanisms (artistic creation). if the indelible marks on social body (i.e. change in personal and group identity, alteration in value priorities) are always noted at a later time, then the coronavirus crisis is not a cultural trauma proper. the 'period effect ' inglehart , pp. - ; norris and inglehart , p. ) of the health crisis has to be traced retroactively, not in anticipation. another issue to cope with is the distribution of the disease and its trauma potential. at first glance, the pandemic seems to be inherently universal because it threatens everyone, irrespective of class, ethnicity and religion. it might also be possible to be perceived differently from the way individuals perceive existential threats, war and terrorism for example, which are unambiguously anthropogenic and particularistic. however, the extant differences in death rates and different patterns of the disease dispersal inevitably poses once more the question 'trauma for whom?' and at what level. as already mentioned, the pandemic reveals the dynamics of risk society. yet, we should take heed of the fact that despite the genomic indeterminacy of the sarscov- there is a background assumption and a reasonable expectation about the upcoming cure and protection after a vaccine becomes readily available. the current pandemic is encountered by disease-experienced lay people and a knowledgeable community of experts. as a species, we are more or less confident that this is not a repetition of the black death. the covid- is not entirely surrounded with horrible and unsolvable mystery and it is not regarded as a totally intractable and capricious disease like tb or cancer before finding their cure (sontag , pp. - ) . this might mitigate the prospect of the pandemic to become a future point of reference for collective and/or global memory. not infrequently, harsh pandemics leave no trace in social memory. although the pandemic influenza virus identified in hong kong in caused one million casualties, it passed almost unnoticed, since people in many countries had other priorities (keck ; keck and lachenal ) . on the other hand, it might be plausible to argue that even if the number of deaths will not be comparable at all, for example, that of the great influenza or aids, it will mark collective memory and identities because it forcefully damaged the illusion of invulnerability modern science can confer. by turning a spotlight on the dark sides of the present-day technocracy and technopoly (postman ) , this pandemic may point to a threshold in the 'imaginary institution of society' creating an anticipation of human extinction. building up a 'pandemic imaginary' drawn from the 'apocalyptic catastrophism' of risk society, people are seen as unable to selfcreate as before (lynteris , pp. , ) ; as a total social fact, this pandemic like other pandemics and epidemics in the past, instills a feeling of being 'lost in the world' and as such is deeply traumatic. a pertinent question is whether we should think of the pandemic not only as a total social fact, but also in terms of a trauma-ridden 'historical event'; namely, as a ramified sequence of rupturing occurrences that is recognized as notable by contemporaries, and that results in a durable transformation of structures (sewell ) . currently, at least as far as most of the eu countries and the usa are concerned, it seems that the pandemic meets most of the criteria sewell ( , p. ff) identified as relevant in the conceptualization of historical events: dislocation and re-articulation of socioeconomic structures; cultural-aesthetic transformation; heightened emotionality; institution of rituals; conducive 'structure of the conjunction'. these are traits to be found in the accelerated trauma drama already unfolding in terms of time-space compression and ensuing presentism. the case in point, however, is not only the pace but also the depth and the possible duration of these traits, as we will discuss in our case studies. how then does this compression affect an unfolding trauma drama? eyerman ( , p. ) identified several factors that influence the development of a cultural trauma: timing, political context, performance of authority, mass-mediated representations, carrier groups, and collective memory. the relative weight of these factors is determinant in the appearance of cultural trauma. refers to the relative proximity of triggering incidents, the closer in time the more chance of a cumulative collective emotional response. under the conditions of compressed trauma, the triggering responses are continuous, with local, national and international reports of cases and deaths flowing together, intensifying anxiety and fear. everything seems to be happening at once and threats everywhere, undermining the existential security of individuals. the very air breathed cannot be trusted, turning family members and neighbors, as well as strangers, into potential carriers. basic notions of humanity, morality, and empathy are undermined; all that's solid melts into air. one of the first casualties of the pandemic was the cooperative relations between nations. if by globalization, one refers to the systematic interconnectedness and indepth interdependency of nations, the pandemic revived the nation-state as the natural site of collective reference. similar to the way the outbreak of the first world war fragmented the international socialist movement in a wave of emotional nationalism, the first response to the pandemic was to withdraw behind national boarders, to turn inward for protection. this was especially prominent in the european union, where borders were shuttered and international travelers looked upon with suspicion. like city walls built to keep out the plague, airports and train stations were manned with border guards. as the enemy was invisible, national identification became the main means of determining purity from danger. nevertheless, the cunning of history herein consists in the extant global cooperation between bio-laboratories and pharmaceutic big companies for the production of a vaccine, on the one side, and, on the other, the instant global transmission of news items about the disease which leaves room for empathetic feeling and acting towards distant others. in polarized political contexts, such as the u.s. the possibility of radically different accounts is more likely to appear. this is aided by the presence of alternative means of communication to distribute such accounts. as a rule, whenever there is dispute among elites over a public issue the media are prone to disseminate divergent accounts of it. central to the pandemic are public health authorities, usually medical professionals and epidemiologists who, more often than not, are represented as professional heroes. how well they argued for various control measures and how they interact with political authorities is crucial; as is the quality and availability of health care systems. in antagonistic political cultural contexts and discordant public spheres, the performance of national authorities and the relative strength of traditions of confidence in the institutions they represent call for more attention as drivers of cultural trauma. there is frequent use of war metaphors, bombast and fear mongering on the one side and cold, factual, scientific representations on the other. the general public is dependent on media for information and on authorities for dealing with an invisible and unknown enemy. it is through such means that what is happening and who is responsible is articulated and transmitted. the mass media create story lines, highlight victims and heroes and generally construct meaningful accounts of what is happening. articulate the alternative narratives, to interpret what is happening, who is responsible and what is to be done. besides the authorities mentioned above and those working in the mass media, important actors here are professional organizations, trade unions and other interest organizations that speak in the name of their members. in polarized contexts, the relative strength of these carrier groups, their access to mass media, and their support from political and religious authorities is crucial. those nations that have experienced trauma appear to be better prepared, provided with a memory and a means to deal with crisis (keck and lachenal , pp. , ) . 'this' is like 'that', we survived that and can survive this. in the process, various historical instances are recalled through previous trauma, from earlier pandemics to aids. such associations are meant to offer hope as well understanding. we can illustrate the interplay of these factors under the intense conditions of ongoing compressed cultural trauma through two short case studies. we chose these countries for practical reasons, from firsthand knowledge and because they represent varied responses to the pandemic. both countries had the advantage of some advance knowledge of the virus and the means of its spread. sweden has been held up as a unique approach, for some exemplary, for others dangerous. however, despite initial high levels of anxiety the pandemic did not evolve into cultural trauma in either, even with an exceptionally high death rate in sweden and the great difference in trust in authority that distinguishes the two countries. we hope to explain why. like many south and east european countries, greece was much less exposed to global transactions during the - winter and that might be a reason why the disease spread and the death toll remained at quite low levels compared to other eu countries. the first covid- case was diagnosed in greece on february th. the virus came through those returning from travel to holy sites in jerusalem and from a group of fur trade businessmen who visited milan a few days before. contact tracing was initiated on the first and all subsequent confirmed cases, with all contacts being tested and isolated. on february th, the annual carnival in patra (an event which draws large crowds from all over the country) was cancelled. on march th, with officially cases and deaths, all schools and universities across the country were closed. on march th, libraries, movie theaters, gyms and courtrooms were closed. on march th, with confirmed cases and death, malls, cafés, restaurants, bars, beauty parlors, museums and archaeological sites were closed. on march th, supervised beaches and ski resorts were also closed. all stores but big food markets were closed four days later and on march rd, a nation-wide lockdown was enforced, whereby citizens could leave their house only for specific reasons and with a special permit and under strict time limits. as we write confirmed cases amount to since the start of the outbreak with the death toll at . as a country that was pulling out of a decade-long financial crisis, greece is considered surprisingly successful in containing the pandemic. with its national health care system weakened by the crisis and with one of the oldest populations in the eu the outbreak of the disease alarmed the authorities and the majority of the people to the extent that greece would be the next italy or spain. at the outset, a gloomy atmosphere of fear and anxiety was documented in numerous opinion polls. soon after the curve began to flatten, hope, pride and confidence improved in the emotional agenda of the public sphere. since may th the lockdown measures are gradually loosening in view of approaching the greek summer. to avoid overcrowded hospitals with a limited number of intense care units, public authorities acted in a very cautious and unusually efficient way. mobilization had to be very fast because the health care system could not have otherwise handled the outbreak. the government has been strictly following the strategic directions given by a committee of experts in public health, composed of prestigious professors of epidemiology and other disciplines. the pandemic has been handled by a rather strong center-right government that took office in july , with a good number of technocratic members. in a polity traditionally permeated by fierce antagonism, apart from minor reservations opposition parties raised no substantive objections to the lockdown measures. there were however disputes and skirmishes on resource allocation policies, especially in view of the expected economic fallout caused by the pandemic. however, there has been consensus over the need to keep tourism alive during the summer in order to shield the per cent drop in gdp, a dire prospect that would make the greek economy the hardest hit across the entire eurozone. the necessity of the lockdown measures was also reinforced by the extremely poor reserves of test kits for the general population. until substantive amounts of kits were imported, less than one percent of the population had been tested for the virus. testing was focused on people admitted to hospitals with symptoms and those closely connected to confirmed cases, as well on all those returning from abroad. this raised concerns about the accuracy of the case numbers announced during briefings held by sotiris tsiodras, the president of the experts committee, a soft-spoken, infectious disease specialist at the university of athens, and nicholas hardalias, the deputy minister for civil protection. since the death toll was small, concerns were alleviated and these two became the most trusted authorities and their briefing became a sort of news event, thus crediting television with a trace of its old rhapsodic fun action (fiske and hartley ) . consecutive opinion polls during the spring of indicated an impressive increase in public confidence towards most social and political institutions of the country, as well as the raising popularity of political figures. for a good many years-if not decades-political institutions and the political authorities in greece were much discredited and this change in public mood might be taken as a signal of the remaking public trust in the face of a collective trauma. yet, that upswing was brought about more because of an ensuing 'rally round the flag' reaction, and was not a sign of a regained and restored institutional credibility. if anything, as documented by a social attitude research directed by nicolas demertzis in may , the covariance between institutional credibility and social trust was limited (r = . ), which means that amidst the trauma drama there was a paradox of trustworthy institutions and a misanthropic-like attitude. this paradox is contingent upon the duration of the rally round the flag effect. in this respect, if a deep recession is imminent, much of the confidence in political and social institutions will evaporate and the trauma drama will deepen, especially because any new economic crisis will overlap with the previous one, occurring no more than a year ago. after the crash test of the gradual removal of restrictions in may , the 'stay home' message of authorities was replaced by a 'stay safe' logo. yet, in many instances social distancing and other safety measures were not observed. in some cases where young people from extremist social networks initiated festive gatherings in public spaces violating any precaution, police had to intervene. in greece's over-politicized public culture, these incidents were enough to trigger grievances and controversy. more or less, however, they sprung more from spontaneous reactions to stringency and not as organized massive protest like the mobilizations in the usa, australia, poland, and germany, where lockdown is viewed as an unjustified tyrannical policy. it is striking that due to the customarily weak civil society in greece (demertzis ) , organizations representing the elderly and pensioners haven't been given (or taken) the opportunity to get involved in the debate concerning the repercussions of social distancing. after all, the chief objective of the entire strategy was to avoid a massive loss of older people who, nevertheless, in greece are not placed in care homes due to strong family ties. national and international ngos are at pains to warn authorities about the risk of the disease spreading among the overcrowded clusters of asylum seekers in identification and reception centers. although the living conditions in these camps are unacceptable, according to official sources only a few tested positive. yet, right-wing voices often decry them as 'health-bombs'. apart from the community of doctors and experts whose voice are respectfully heard, other carrier groups include think tanks organizing webinars on the socioeconomic impact of the pandemic, major cultural organizations like the national theater, the national opera, the onassis foundation and the stavros niarchos cultural center delivering a vast number of artistic creations and performances online. another influential carrier group has been the greek orthodox church. drawing from the byzantine tradition of lesser caesaropapism and its legendary role as the only religious and juridical-political institutional mediation of the orthodox populations under the ottoman rule, the orthodox church accommodated itself to the greek nation-state as a claimant of the national identity. we cannot delve into its impact and to greek religiosity except to stress its perpetual stronghold on public life to roughly understand the fierce dispute between political parties, secularized civil society groups, health experts groups, and religious cycles when the greek orthodox church announced on march that coronavirus could not be transmitted by communion wine or water. as the greek easter approached, a dispute grew with the government hesitant to ban public rituals due to its political cost, especially when orthodox hardliners and rogue bishops made public declarations and followed practices undercutting government efforts to come to grip with the pandemic through social distancing in the first crucial weeks in march. eventually, the government regulated the issue and easter church services were held without the participation of parishioners. after the gradual loosening of restrictions on may, church attendance was permitted as long as social distancing was observed. however, despite its marginal and grotesque character, it is striking that on may a media-based former bishop excommunicated the prime minister, the minister of education, and the deputy minister for civil protection. although this would have been much more serious if that gesture was undertaken by an ordinary bishop or the archbishop himself, it is indicative of the spiritual and political power the church entertains during the pandemic trauma drama. sweden's current statistics as of july , were , tested positive, deaths, of a population of . million. sweden's death toll, with . deaths per , , remains among the worlds highest. most of these deaths, %, were persons over years of age, many living in state run care facilitates. by comparison, greece's population is . million, cases and deaths, or . deaths per , . sweden has experienced few traumas of national proportion. it remained neutral during the two world wars and, as opposed to scandinavian neighbors, avoided the trauma of occupation and as opposed to greece its handling of recent financial crises has been exemplary. the two political assassinations that rocked the nation in and did not shake the foundations of collective identity as similar events did in the us and the netherlands (eyerman ) . the virus came to sweden through those returning from travel (over million returned to sweden during these early weeks), many from ski vacations in italy and other parts of europe, as this was winter sport vocation for students, and from china. the news of the treat however preceded the arrival. once the source was identified, identification, tracking of contacts and isolation was put in place. sweden's landbased access to the european continent closed when denmark shut its borders on march , setting up roadblocks on the bridge made famous by a television show. international rail and air traffic shut down for all travel deemed 'unnecessary'. the many swedes who commuted to work in denmark were forced to show proof of the necessity of their daily commute. the same was true for truckers carting food and other goods into sweden. effectively cut off from the rest of the world, swedish authorities designed their own path of response to the internal spread of the virus, though communication with other members of the european union continued. close contact with other scandinavian countries was also maintained. at the center of this strategic planning was the national public health authority (folkhalsomyndighten) working in close contact with elected political authorities. as distinctive from other countries, even its nordic neighbors, these exists a very tight institutional connection between heath and political authorities in sweden. however, there also exists distinctive regional autonomy. through its daily press conferences, anders tegnell, the 'state epidemiologist', became the public face of this strategy. at these televised press conferences, tegnell and other authorities offered statistics over the 'state of the cov- virus' in sweden and the rest of the world. interviewed for the journal nature, tegnell described the daily planning sessions and meetings with regional authorities that lay the foundation for the swedish response to the pandemic. at this point (april ) he noted that the death rates amongst older swedes was not yet 'traumatic', indicating that there was some critical threshold, presumably connected to public sensitivity, where a response by the authorities would become necessary. sweden is unique in the sense that officials held fast with this strategy of containment, with a minimum of enforced restrictions. the idea of managing the spread of the virus and 'flattening the curve' so that hospitals never became overwhelmed was generally discussed, including in the united states. however, most countries changed to much stricter restrictions after death rates in italy and spain climbed seemingly out of control. along with strict restriction of movement, germany and other countries began general testing in order to identify new cases and then trace contact networks in order to isolate those infected. such measures were accompanied by strict hygiene measures, such as wearing masks in public places. what was (perhaps wrongly) called the 'south korea solution' was followed by many european countries. sweden did not waiver however; it followed the original strategy of minimal restriction to manage the spread without overwhelming the health care system to reach 'herd immunity'. at the same time, after considering who was dying in other countries recommendations were made to protect those over the age of . defined as a risk group, those over were cautioned to stay at home, with food shopping and other essential activities suggested for special hours of the day. these were recommendations however, with no enforced restrictions or penalties, as in other parts of europe. this stems in part from the stipulations of the swedish constitution, which prohibit restrictions on mobility, but primarily on the belief that citizens would follow the stipulations, especially social distancing, on their own. as the very young appeared the least at risk, day care centers and grade schools remained open. an additional rationale was that those who worked in the vital health care system, doctors, nurses and others, were likely to have young children and in need of child care. high schools, colleges and universities shut down and their activities shifted to the internet. stores and restaurants stayed open, with social distancing requirements put in place. several restaurants were temporarily closed for not following social distancing recommendations. crowds of over persons were banned, thus cancelling sporting events, though teams were permitted to practice and, later, to play to empty stadiums. people were encouraged to exercise, especially outdoors, gyms, voluntarily closed at first, soon re-opened. as death rates climbed to alarming proportions compared to neighboring countries, it became clear those working in care facilities as well as those they cared for were especially vulnerable and visitors were forbidden. the specificity of the death rates, especially in care facilities, remains unclear and a matter of concern. a formal inquiry is now ongoing. as for testing, sweden began by opening public booths to administer tests, but soon abandoned this policy in favor of testing only those displaying specific symptoms, as well as professionals working in the care sector. there is no general testing policy or program, in part because general testing was deemed unreliable, as well as costly. anyone showing symptoms was advised to call a hot line and to stay at in an op-ed in the major national newspaper dagens nyheter in april signed by researchers with the headline 'the national board of public health has failed, now it time for politicians to step in' (https ://www.dn.se/debat t/folkh alsom yndig heten -har-missl yckat s-nu-maste -polit ikern a-gripa -in/), it was argued that the strategy being followed was not working and that elected officials ought to step in to change it. the authors pointed to italy as evidence, arguing that sweden should follow other european countries in imposing stronger restrictions. the public health authorities met this criticism by denying that reaching 'herd immunity' through such callous means was their strategy, rather the aim was to flatten the curve, to slow the spread of the virus but not eliminate it. the issue of herd immunity was the subject of another article in dagens nyheter on may . the paper's science editor defined herd immunity as a state where a sufficient number of a community is immune to an illness to prevent further spread. this can be reached, she pointed out, by vaccination or immunity from having the illness and carrying antibodies. the issue with covid- is twofold, one that it remains uncertain if one can become immune through having the virus and ) even if the body does produce antibodies, it is still uncertain how long they last. the article points out that the price of achieving this state too quickly is the death of many elderly. home until symptoms became acute. the population was told that the vast majority of those who fall ill with the virus will have only mild symptoms, and that the real danger is infecting others. sweden's death rate is significantly higher than its scandinavian neighbors and they have been some of its most vocal critics. the alleged 'herd immunity' policies were called immoral and utilitarian. while opening its boarder to germany, denmark has refused to do the same with sweden; greece announced an opening to european tourists, but excluded sweden as well. in defense, swedish authorities have publicly acknowledged failures with regard to elderly care facilities and new policies and finances are promised. the swedish prime minister explained the high death rate as 'communications problem' within the care sector, rather than a problem stemming from the overall strategy (interview in sydsvenska dagbladet july : a ). public debate has begun addressing this issue, though at this point relative political unity prevails even with a weak coalition government in place. all parties remain united behind the leadership, even the anti-immigrant party (though its leader has called the death rates among the elderly a 'massacre'). trust remains high and the daily press conferences of the public authorities are exemplary in their fact-based seriousness. these civil servants and the science-based expertise they represent continue to be held in high regard (though polls noted a % drop in approval between april and june), and the approval ratings given the social democratic prime minister have been rising, with an . % increase since the last survey in november . if the death rates continue to rise however, how long this trust in leadership and collective solidarity will last is an open question. at this point the feared 'second wave' has not occurred. even at this date, one can identify stages in an ongoing trauma drama. concerning the question of who is to blame: there was first denial, the hope that the virus could be contained in asia or other parts of the world. with the sudden rise in italy, there was the recognition that it could come to sweden. the presumptive early carriers were swedes returning from vacations and business travel; thus, they could not be outwardly blamed or stigmatized as outside carriers, however there were a few reported incidents of harassed asian travelers and immigrants as outside carriers. the right-wing internet has focused on immigrants as carriers and what they consider their 'over representation' in the number of cases. another form of denial, with the fact of rising death rates in sweden, is the claim that other countries are less accurate in their reporting, or that they are 'at a different place in the curve' and will soon catch up. both such claims have been made by swedish health authorities. following denial came acceptance. swedish authorities turned to modeling science and to managing the spread of the virus from that standpoint. it is a form of bargaining with natural forces and predicting that most of the cases will be mild, that primarily only the elderly are seriously at risk. this freed most of the population from some anxiety, but could induce guilt or worry about older relatives, who were being 'sacrificed for the herd', which is to say, the nation. the greater good for the greatest number. given these assumptions, daily life proceeded almost normally for a good portion of the population. there are several features of the swedish national culture that have influenced this strategy and its general acceptance. the first is a tradition of identification and trust in government and representative authorities in general. sweden lacks the strong opposition between the people and the state that exists in some other countries. there is also an underlying faith in science and technology and a good health care system available to all. all of which have contributed to a general following of the suggested regulations. the regulations are viewed as rational responses to an exceptional incident, not as restrictions imposed by an alien authority over the natural rights of individuals. swedish political life builds around consent and consensus and the general populace has been willing to give up some of the most basic human interactions, including the possibility to grieve their dead. survey results concerning trust in the authorities (https ://www.msb.se/conte ntass ets/ f a c fa c b e d / -msb_resul tat-coron aunde rsokn ng_ .pdf) with the highest ranked being the health care system ( % positive), the national public health authority ( %) the police %) lower down the government at %. one exception that became apparent during the pandemic can be found in some immigrant communities, where there remain traces of different social traditions of communication and interaction. an example is that of the tightly knit somali community in stockholm that was overrepresented among those infected, that either did not receive or ignored the imposed regulations. there is also evidence that trust in political authority is lower in immigrant communities. all this has been fodder for the extreme right and their anti-immigrant rhetoric, at least behind the scenes, on the internet, and on social media. the problem of social segregation has been further illuminated through the pandemic; one recent study revealed that death rates among middle-aged and older immigrants from syria, iraq and somalia were % higher for the months during the pandemic than for the same period last year. the differences for ethnic swedes for the same period was very much less (cited in sydsvenska dagbladet july a: ). in answering the question 'trauma for whom?', one would look to immigrant communities and minority groups, both for their being stigmatized as well as being disproportionally impacted by the virus itself. as in many parts of europe, immigrant groups and minorities work in some of the most vulnerable and exposed occupations, under the most precarious conditions. like the elderly, they are a group at risk, but unlike the elderly (an abstract category), they, as a stigmatized and stereotyped group, are not as respected. there are also specific demographic factors that have affected the levels of contagion in sweden, including the countries low population density, high share of single person households (not the cross generation extended family of italy or greece for example), generally high life expectancy, low level of chronic illness, low levels of obesity ( % as compared to % in the us, and low rates of diabetes ( . % as compared to . in the us). the high death rate however remains to be explained and public debate has begun. faith in the system and its representatives remains high, for covid- to lead to cultural trauma the sense of existential security in the general populace would have to be fractured. for the moment, the pandemic is viewed as a public health crisis, not a threat to basic values or collective identity(/ies). for that to happen trust in leadership and institutions and faith in science-based medicine would have to be broken. foundational issues, such as what it means to be a swedish citizen and the relationship between individual freedom and responsibility to the collective have been opened by the pandemic. an example being the need to follow directives that restrict individual mobility for the collective good. also being debated is the question of who should bear for the extra (financial, political, and moral) burden in a health care in a system where there are wide differences between regions affected by the virus; are localities where there are few cases of the virus responsible for those where there are many; should those living in southern sweden where there have been relatively few deaths be held accountable (by other countries) for those in other regions where there have been many? sweden is a nation very much aware of how it is viewed by the rest of the world. with its handling of the pandemic now the subject of global discussion and the resulting stigmatizing of swedish citizens as dangerous, potential carriers, strikes at the heart of the basic trust in political and expert authority and the relationship between state and citizen. if trusting authority leads to others distrusting swedish citizens, what then? with the proviso that the pandemic crisis and responses to it continue to change from day to day, we argue that the covid- pandemic can be usefully studied as a cultural trauma, but with modifications. previous studies have been retrospective accounts of the cultural trauma process, while here we offer a means to use the framework for a trauma that is ongoing. in this final section, we summarize these modifications, ending with comments on the outcome. in retrospective studies, timing has to do with the sequence of incidents that initiate and propel the trauma process. the flow of information is constant and confusing but the distance of time (and theory) one knows what to look for. in studying the trauma process as it occurs one does not have a clear notion of an underlying logic or an end in sight. in the current pandemic, nations face the future with uncertainly. there is no surety concerning the immunity of those who have been ill and no sure knowledge with regard to the availability of a vaccine. strategies of containment have had relative and varied success, but deciding when to end restrictions, to open borders and permit international travel is a guessing game, with frightening consequences. the fear of new waves of infection and rising death rates is real and most be included in all proposals. as in war, one needs exit strategies. all this increases uncertainly and anxiety amongst leaders and within the general population bringing to the fore a painful interplay between normality and exceptional. added to this is the prospect of future pandemics of similar consequence though with different cause, raising the possibility of cumulative affect with regard to collective trauma. retrospective studies can isolate relatively distinct incidents; compressed trauma faces the simultaneity of incidents without clear order or value. it is not only the fear of infection and death; there is also the collapsing economies and rising rates of unemployment that create another level of fear and anxiety within a population. these fears must be balanced in the strategies formulated by elites and is conditioned not only by levels of trust and faith in leadership but also by the type of rule. authoritarian or competitive authoritarian systems have a different relation to those they represent than democracies, where election cycles are an important rhythm and consideration in the choices made by those holding power. sitting leaders do not have the luxury of trial and error to the dimensions available in authoritarian systems, adding to the pressure imposed by time. in the midst of the pandemic, many countries have experienced collective solidarity and political unity, a real question is how long this will prevail? as a global historical event, the covid- pandemic appears as facilitator and accelerator of structural calibrations and cultural shifts. in all likelihood, it condenses social time and identity formation processes within the terms of late modern time-space compression. as with / and hurricane katrina, it triggered a trauma process from the very beginning giving us the opportunity to comparatively study it in vivo with the aid of cultural trauma theory. yet, a caveat to keep in mind is necessary at this point; time-space compression is both a result of technological and informational globalization and a globalizing driver of shifting our sense of time towards presentism. it brings about a 'nowist culture' (bertman ) , the 'tyranny of the moment' (eriksen ) , and an experience of a 'continuous present' in the sense that, severing the present from history. one lives in a 'flat collection and arbitrary sequence of present moments' (bauman , p. ) . therefore, it is not only a pandemic induced trauma that is deeply inscribed in the time-space compression, but also those commentators (like ourselves) who are hermeneutically dealing with it. this might express itself in hasty postures like those of giorgio agamben who, on february , , denounced the measures taken by the italian government as 'absolutely unwarranted', as a pretext to the imposition of a state of exception. to avoid the error of theorizing too quickly under the pressure of presentism, it is better to consider the pandemic as cultural trauma in the making. the lure of presentism can cause one to jump to conclusions, even if all the components of cultural trauma-with the possible exception of collective memoryappear at hand. a possible conceptual means to avoid hasty theorizing is to look at the pandemic not only as compressed, but also as virtual cultural trauma. as long as it 'is not the result of an event but the effect of a sociocultural process … the result of an exercise of human agency' (alexander , p. ), cultural trauma is not meant to be historically realized, but rather socially constructed. ontologically it is understood as a status nascendi, the specificity of which is conditioned by the interplay between virtuality and actuality (lévy ) . contrary to the predetermined correspondence of potentiality to reality, where all possible attributes of the real are already inherent in the potential, virtuality is replete with openness and contingency so that the actual outcome of an historical event emerges from unpredictable agentic action. as historical constructs cultural traumas may or may not emerge out of the discursive mediation of abrupt fractures of the societal fabric, and in this respect, as a compressed shocking experience, the pandemic trauma process signals a virtual cultural trauma. relatedly, as customarily held, traumas break and remake societal bonds regarding in-group and out-group relations. among others, the social marketing campaign for diminishing the pandemic in greece was a first-class opportunity for the restitution of the damaged national pride driven by the debt crisis. for nearly ten years greece was depicted in the international media as the black sheep of europe but now, with the successful handling of the first wave of the pandemic and employing an 'we and them' schema, a repetitive message campaign claims that 'this time others can learn from us'. in a retroactive way, the present trauma drama presents an opportunity to symbolically heal the past trauma of economic collapse. the greek government and the party in power are doing their best to regain trust through this success, however as mentioned above, this is a precarious and ephemeral enterprise due to the long-standing distrust of the greek public with regard to political institutions. if anything, according to certain estimations, implemented policies against the pandemic were more successful in low-trust societies than in high-trust nations. although efficient coping with the pandemic is a multi-variable task, the cases of greece and sweden seem to support this estimation. in the main, greeks complied with the stringency rules because they were afraid that a discredited political and administrative system would be unable to protect them. ultimately, greeks began feeling confident in the system as soon as it worked efficiently. this resulted from elites addressing the public in a convincing manner and keeping the death toll at a relatively low level. to the contrary, the allegiance of the swedish populace to the loose restrictions was premised on their prior well-established confidence in political institutions and scientific discourse. should the death toll continue to rise dramatically, the likelihood is that distrust will increase in sweden, as well as instigate a contentious political debate; yet this short-term entropic tendency will likely be counterbalanced by the long-term culture of trust in national institutions. as explained above, quite the opposite could be expected in greece. comparatively speaking the countries are almost entirely different: high trust versus low trust tradition; economic success and security versus the opposite; rational and secular value orientations versus traditional and religious. there is also a sharp contrast in their death and infection rates, with greece incredibly low and sweden the reverse. unless major upheavals in public trust, economic performance, and the number of deaths occur, the likelihood of a cultural trauma unfolding in either country is small for however different reasons. the compressed condition stemming from covid- is unlikely to end up doing serious harm to habitual value patterns and collective identification in either these two countries. how do we explain this? with regard to sweden, one can point once again to long-standing traditions of trust in national authorities and institutions. the performance of these authorities in articulating and managing the crisis potential was swift and transparent. with the pandemic framed and understood as a public health emergency, not a political crisis, the management of the threat was turned over to non-partisan health authorities. their televised press conferences, organized around factual presentations and preventive recommendations, were models of authoritative representation in their non-dramatic tone and format. these daily performances had a large and receptive audience. those entrusted the public good spoke with one voice. that the policy recommendations were minimally invasive and appeared to work was essential to their being followed. as the unusually high death rates became apparent, these were acknowledged as policy failures, with accompanying explanation and the promise of reparation. that these deaths could be explained as largely restricted to identifiable groups, the elderly and ethnic minorities, also freed the majority of the population from a degree of anxiety. that all political parties and mass media outlets accepted this definition of the situation is also an important factor in explaining the absence of collective trauma. had there been political contestation and mass-mediated rhetorical challenges to the prevailing framing, the trust in leadership and the management of the threat would have been more difficult. this is to speak of cultural trauma at the national level. there is greater potential for such trauma at the group level, most particularly amongst the elderly, immigrant groups and minorities, those, that is, that bear the statistical brunt of the virus. the isolation felt by the elderly, especially those in care facilities, has not been remedied and a sense of uncertainly remains as restrictions have not been lifted, nor has any time frame been noted. this, however, is largely a group without voice and representation, a statistical rather than social or political group. it is also a fleeting group, with little possibility for narrative collective identification or collective memory formation. this is not the case for ethnic minority groups, where the impact of the virus is great and where marginalization and stigmatization are prevalent. here there is more potential for individual trauma to find collective voice and representation. finally, with regard to collective memory, one can ask if the pandemic will leave an indelible mark on collective memory. the spanish flu left little or none. the theory of cultural trauma is a heuristic framework that offers little grounds for prediction. that said, given the secular nature of swedish society and the absence of strong commemorative traditions, there mostly likely will not be any collective memorialization for those who died of the coronavirus. a recent national recognition of the dead occurred after the tsunami, where over swedish tourists died. in , the swedish church and embassy organized a th anniversary ceremony and a memorial has been erected in stockholm. at a ceremony marking the th anniversary of the estonia ferry disaster of , the swedish prime minister called it 'a trauma for the entire nation' and representatives of the swedish royal family offered flowers during the memorial ceremony. the individualized deaths resulting from the covid- pandemic, visible primarily through statistics, do not appear to lend themselves to collective commemoration in the same way. against this however, one should point out that in both the other cases initiative for the memorial celebrations and national recognition of the victims came from the bottom up, from survivors and family members. the emergence of such carrier groups cannot be excluded in the covid- case. as for greece, the low death toll is unlikely to make a traumatic impact on public memory since it is represented as a mark of elite success, to further boost the rebound of the economy predicted for . most probably, any traumatic memory will be set aside in public discourse and mourning made a private matter, as is the case with the people who suffered to death amidst a wild fire in attica on july after a blatant failure of civil protection. albeit in that incident, there was clearly someone to blame for the hecatomb of burn victims, yet no indelible mark was left on social identity or public memory; this time there is virtually nowhere to place blame. insofar as losses remain low, individual family tragedies will not turn into a collectively shared suffering that could initiate a cultural trauma. a collective trauma might virtually arise if families were to lose the grandparents living at home. as family ties remain very strong in greece, living in care facilities or on their own is the exception, not the rule as it is in sweden and other countries. in a country with a shame-oriented culture, the mass loss of generational predecessors would inflict painful shame and guilt, strong emotions that when shared shatter individuals and collectives alike. such might be sufficient cause for the unfolding of a cultural trauma, especially if a reform in the protection measures was not forthcoming. for the time being however, in greece as in sweden, there has been a basic consensus among the elites regarding the handling of covid- ; therefore, the mainstream media were unable to amplify strategic differences and polarize public opinion. in greece however, this served to regain national pride, while it sweden it preserved it. we are not claiming an absence of trauma in these countries. as we indicated, despite great differences in the number of cases and the death tolls, both countries have their victims and large segments of the population that face the future with great anxiety. these are troubles confined and maintained in the private sphere. by and large, albeit references to 'trauma' are made in both countries, on a societal level the covid- is perceived and framed in terms of crisis and crisis management, rather than a traumatic catastrophe that fractures value priorities and collective representations. compressed cultural trauma means that the trauma drama begins immediately, but makes not prediction that it will result in indelible marks on the social body. if anything, the core idea of compressed cultural trauma idea is its virtuality, implying that the constellation of meaning making processes will shift when and if societal variables change. trauma. a social theory cultural trauma and collective identity berkeley from pilgrim to tourist-or a short history of identity hyperculture: the human cost of speed the political sociology of emotions. essays on trauma and ressentiment greece german cinema-terror and trauma: cultural memory since tyranny of the moment: fast and slow time in the information age the cultural sociology of political assassination a better world can emerge after coronavirus. or a much worse one the condition of postmodernity hegel's logic (trans: wallace, w.) total social fact: structuring, partially connecting, and reassembling the new emerging viruses are unpredictable. kathmerini simulations of epidemics: techniques of global health and neo-liberal government qu' est-e que le virtuel human extinction and the pandemic imaginary the world after covid- social capital. summing up the debate on a conceptual tool of comparative politics and public policy technolopy. the surrender of culture to technology logics of history. social theory and social transformation cultural trauma and collective identity illness as metaphor covid- as cultural trauma covid- , nationalism, and the politics of crisis: a scholarly exchange publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations nicolas demertzis is professor at the department of communications and media studies at the university of athens. since , he has been director and president of the board of administrators of the national centre for social research (ekke) we thank the editors for the opportunity to approach this subject and especially jeffrey alexander for the constructive criticism he offered. key: cord- -xjrrw wr authors: megahed, naglaa a.; ghoneim, ehab m. title: antivirus-built environment: lessons learned from covid- pandemic date: - - journal: sustain cities soc doi: . /j.scs. . sha: doc_id: cord_uid: xjrrw wr before developing medications for an epidemic, one solution is to go back to the physical and built environment to reduce its impact. epidemics have transformed our built environment because of the fear of infection. consequently, architecture and urbanism after the covid- epidemic will never be the same. although the current global epidemic poses a challenge at all levels in the built environment, it will take time to develop an antivirus-enabled paradigm to reduce the potential risks or stop the virus from spreading. this study imagines what the antivirus-built environment looks like based on the lessons learned and the importance of designing a healthy and sustainable built environment. many unanswered questions require further multidisciplinary studies. we aim to search for answers and learn from this forced experiment to add additional security layers to overcome future virus-like attacks. covid- affects physical health most directly and has alarming implications for emotional and social functioning, the coronavirus has proven that a disaster doesn't fight with a known opponent. the enemy can simply be invisible with devastating consequences (goniewicz et al., ; pfefferbaum and north, ) . the real world is fragile, and this virus is frighteningly causing massive disruptions across the globe (budds, ; saadat et al., ) . moreover, the digital world is fragile regarding cyberattacks. this could be a teachable moment to apply lessons from the cybersecurity world to protect our built environment during the covid- pandemic. the coronavirus is quickly spreading and causes significant damage, mimicking the spread of computer viruses within a network (kindervag, ) . in the digital world, it is common practice to design and incorporate solutions that can help overcome virus attacks; for every new generation, a new security layer is added to ensure the ever-mutating computer viruses do not harm the digital structure (ahlefeldt, ) . could policymakers, planners, and architects inspired by the digital world learn from its cybersecurity to make our built environment more resistant to the virus? could we design and build our cities to stop the virus from spreading? if so, could we install an antivirus-built environment ready to help in the protection from coronavirus or other pandemics? infectious disease has already transformed our places through architecture, design, and urban planning. previously, many trends in architecture and urbanism that we see today were derived from similar measures taken before to ensure the health, hygiene, and comfort of urban residents. our built environment has always exhibited the capacity to evolve after the crisis (chang, ; dejtiar, ; muggah and ermacora, ). this study encourages the search for suitable design ideas, trends, and planning theories to provide the required protection from virus attacks and continue to add more layers in the defense system of our built environment. to cope with this pandemic, professionals in architecture, urban planning sectors, and design agencies have already switched their focus to visualize j o u r n a l p r e -p r o o f the post-pandemic era. however, there is inadequate research conducted to imagine how the antivirusbuilt environment would look. to address this gap, this study reviews architecture and urban story developments from the past centuries. we then review research areas affected by the covid- pandemic and highlight their related questions. we then analyze the social distancing and quarantine as a design problem in the post-pandemic era. subsequently, some lessons learned from the pandemic are presented to visualize and introduce the study's vision about the antivirus-built environment. during pandemics, the form has always followed the fear of infection, just as much as the function (ellin, ) . from interiors to city planning, our built environment is shaped by diseases. previously, to minimize the risk of infectious diseases, people redesigned interior design, architecture, cities, and infrastructure. considering historical events of the last two centuries, the architecture and urban story includes several developments. in the th century, the bubonic plague motivated the fundamental urban improvements of the renaissance. cities cleared overcrowded living quarters, expanded their margins, developed early quarantine facilities, and opened large public spaces. in the th century, infectious disease was one of the drivers of urban renewal. modernist architects saw design as a cure to the sickness of overcrowded cities, where tuberculosis, typhoid, polio, and spanish flu breakouts encouraged urban planning, slum clearance, tenement reform, and waste management (chang, ; lubell, ). during the industrial era, cholera and typhoid influenced the sanitary reform movement. these epidemics contributed to developing water and sewage systems to fight the pathogens, eventually leading to a sanitary innovation and required the streets to be straighter, smoother, and wider to install underground pipe systems. furthermore, the third plague pandemic in changed the design of everything from drainpipes to door thresholds and building foundations (budds, ; klaus, ; wainwright, ). the wipe-clean esthetic of modernism can be partially attributed to tuberculosis. the modern architectural designs were inspired by an era of purity of form, strict geometries, modern materials, and a rejection of ornamentation. modernist architects designed these curative environments as cleansed (physically and symbolically) from disease and pollution. beyond their esthetic appeal, these features embodied modernist preoccupations with the healing effects of light, air, and nature. these buildings included large windows, balconies, flat surfaces that would not collect dust, and white paint, emphasizing the appearance of cleanliness (budds, ; chang, ). against this background, the current health crisis should develop our built environment to increase the security layers that help to j o u r n a l p r e -p r o o f prevent the spread of infections and diseases. in this context, there are multiple areas of research needed regarding covid- . when the world health organization (who) declared the fast-spreading covid- as a pandemic, citizens around the globe hastened to go home. this global pandemic significantly influenced our personal and professional lives and has a direct bearing upon the very foundations of urban planning and architecture theory and practice (allam and jones, ; haleem et al., ; saadat et al., ) . consequently, the pandemic has led to questions of how architects and planners could present and install antivirus-related ideas or update the existing spaces, as well as at what stage can the pandemic affect our physical and built environment. to extend the scope of research needed from the academic community, table reviews certain required research areas affected by covid- and highlights their related questions. professional and extensive research is required on all levels and scales in these areas to prevent the virus from spreading. the answers to these questions could help in predicting the postpandemic style and visualizing the required antivirus system. in the absence of a specific vaccine to of the coronavirus, physical distancing and the lockdown of the since most humans spend most of their daily lives inside the built environment, it is essential to based on the potential transmission dynamics of covid- and the required measures, several competitions, conferences, and leagues have been cancelled or postponed. the coronavirus has motivated authorities to restrict access to most public spaces and large shopping areas. this pandemic could fundamentally change the way they operate in the future and requires further analysis (honey-roses et al., ). architects, planners, and built environment professionals are keen to examine many social and spatial implications to generate new patterns and configurations of use (paital, ; salama, problems and challenges in all building types and urban spaces as illustrated in figure . the pandemic of covid- has caused serious consequences that can be an opportunity to review individual and collective choices and priorities. most architecture today shows evidence of how humans have responded to infectious diseases by redesigning our physical spaces. thus, social distancing could change the design and planning process (budds, ; chang, ), specifically with the increased acceptance of distance learning, online shopping, and the cultural connection of online entertainment. the use of media for information sharing, and webinars for sharing knowledge and expertise have seen according to the affected lifestyles, the increased reliance on digital channels in the built environment may endure long after the pandemic and affect in every design and urban aspects. humanity is facing a global crisis, perhaps the greatest of our generation. many measures adopted during the emergency will become part of daily life, changing habits, and behaviors, they may be a positive or negative intervention in architecture and urban planning approaches. household size. a big household, large, or extended families will have a higher chance to bring the virus home (saadat et al., ). this will need special consideration in design solutions to prevent infection. social distancing level. working from home might reduce social contact but is only available to some people focused on jobs linked to a higher socioeconomic status. moreover, stay-at-home regulations would be more than a challenge for those who live in smaller and crowded houses or without outside spaces (saadat et al., ) . forced to stay and work from home, post-pandemic house and office spaces will witness a great transformation because we will be more aware of the functionality of our homes and workspaces in an interestingly new approach. some of these transformations are reviewed in following sections. the pandemic has brought a greater sense of appreciation for our homes. people need houses that can effectively provide social isolation and offer protection from viruses and infections. the expectation is that even after the quarantine period, more people will work from home. consequently, the future of while it is uncertain how much change will follow covid- , mechanisms increasing its spread will not be forgotten or ignored (priday, ) . the pandemic has highlighted the lack of how we manage our built environment and presented certain lessons from this forced experiment. in this context, how should architects, planners, and policymakers react and learn? beyond helping to design medical spaces limiting the spread of infections (acuto, ; betsky, ), the pandemic will allow them to reset and reshape our built environment. however, the time to reset and reshape our built environment is now, and not after the next pandemic. this study analyzes the lessons learned based on two approaches, namely, look step back to nature and look step forward to advanced technology. a key lesson that we are going to learn is the requirement to return to nature with its healing effects. although the situation is still unfolding, the covid- pandemic has already highlighted the importance of certain design concepts and reassessed fundamental assumptions in urban and architecture approaches. to accommodate work from home situations, we could even reexamine old urban typologies. many urban approaches might increase the protection and defense system of our cities and avoid high density and overcrowding. policymakers and planners should use the current crisis to review planning theories and, based on the results, they should take a step back in searching about how past cities are structured. previously, many architecture approaches were related and increased the healthy spaces of our buildings and enhanced sustainability. self-sufficient strategies. in future, a high priority will be placed on self-sufficient buildings and lifestyles (ali et al., ; greer, ; priday, ) . in addition to all the energy-efficient strategies with heating and cooling systems, architects might inspire additional methods of thinking concerning water supply and food production. refocusing on green spaces. we require physical interaction with living plants for our mental health, and to grow what we eat to reduce risk, specifically during self-isolation (constable, ; makhno, ) . consequently, planting our gardens, terraces, and implementing green roof systems have multiple advantages for sustainability (hui, to receive the maximum benefits from the previous approaches, the antivirus-enabled paradigm requires advanced technology in the construction sector and a tool to quicken the pace of digital transformation. this approach requires using techniques outside the mainstream to secure our built environment by j o u r n a l p r e -p r o o f running alternatives, exploring, and inspiring new ways of constructing more sustainable and safe buildings. the post-pandemic emphasizes the importance of look step forward of the innovations in construction techniques that speed the creation of emergency architecture. the covid- pandemic represents an unprecedented challenge for healthcare systems internationally. medical facilities and their human resources are usually overwhelmed (scarfone et al., ; robbins et al., ) . the sheer scale of the pandemic puts enormous stress, most countries built field and temporary hospitals in a matter of a few weeks or reused other building types and spaces to add thousands of beds. table reviews the most construction strategies used in constructed additional healthcare systems to prevent further covid- infection. the hospital designed to be the quickest response to an immediate care center. a , -square-meter structure prepared to see up to covid- patients daily. ucsf medical center, san francisco bay, usa the hospital sets up two outdoor tents to prep for possible influx of covid- patients which employed as triage and emergency room extensions, waiting and treatment areas. adaptive reuse. this strategy is a sensitive and sustainable approach to create emergency facilities. during a pandemic, sports facilities, parking lots, and other buildings are converting into medical facilities and temporary hospitals. there will be a requirement for more efficient, effective, and flexible reuse plans for future crises (lubell, ) . this strategy is beneficial when integrated with other advanced technologies in the construction sector. lightweight and adaptable structures. when responding to the pandemic, lightweight and adaptable structures are often preferable for their speed and portability. designers are developing and assembling these temporary structures to create field hospitals that can be easily transported and erected for covid- patients (constable, ; lubell, ) . the global pandemic has forced us into an entirely new world and has increased digital transformation in all our activities. after the crisis, we will have entered a new digital normal. in a few months, the pandemic has offered virtual and augmented reality alternatives, which are expected to continuously increase (gracy, ; muggah and ermacora, ). ability to work from home. as a lesson learned, this pandemic brought to light the possible reduction of air pollutant emissions by increasing expand remote working. during the quarantine, most people have been forced to work from home (nakada and urban, ). more consideration will be given to the arrangement of the workplace at home. the spatial organization will change. it will be a separate room with large windows, blackout curtains, and comfortable furniture. it will be technically equipped, and sound insulated (allam and jones, ; capolongo et al., ). while working from home is a benefit many employees value and reduces pollution, the long-term impact is unclear and requires further investigation. artificial intelligence and touchless technologies. automation, voice technology, and facial recognition-based in artificial intelligence could influence post-pandemic architecture. with % of infectious diseases transmitted by touching polluted surfaces, touchless technology could become a new interface and remove the requirement for physically pushing or touching a surface. post-pandemic principles search for more contactless pathways, such as lifts being called from a smartphone, avoiding the need to press any buttons, and doors to open automatically (molla, ; wainwright, ) . these technologies could include other programs to both control space temperature and automatically clean it j o u r n a l p r e -p r o o f to kill harmful organisms, viruses, and bacteria. although there is an added cost, it might be an amenity that will gain popularity to be integrated into future buildings (kashdan, ; makhno, ). one positive impact of the current pandemic is the time it offers to the built environment professionals to reflect on past events and learn what can be improved for future responses (goniewicz et al., ) . although pandemics have long been catastrophic, they have forced architecture and city planning to cope with it. covid- might have similar effects on architecture and urban planning developments (budds, ; chang, ; saadat et al., ) . life after the pandemic will never be the same; values, lives, and habits will change, and our architecture will change under that influence. in all these circumstances, we might enter a completely post-pandemic style in which form follows fear of infection. cities are currently being tested to the extreme with the pandemic and multiple questions are arising in terms of how cities are planned and managed. its impact is showing the extent to which each city can function, or not, especially during times of crisis (lubell, ; wahba and vapaavuori, ) . our built environment is not designed or built to effectively help limit the effects of pandemics, such as the covid- pandemic. however, we are learning fast and there are already lessons worth learning and remembering. the pandemic will not last forever, but our response to it will shape our future built environment (ahlefeldt, ; novakovic, ) . the significance of adding human health as one of the sustainability development goals can be seen through the current pandemic. from a conceptual perspective, adding human health as the fourth pillar to the overall definition of sustainability is a logical step (hakovirta and denuwara, ). many architecture and urban approaches might increase the protection of our cities and avoid overcrowding. in normal times, there might be many attributes attempted by the built environment to achieve sustainability. the pandemic's influence in the densest areas raises questions about sustainable development and fundamental assumptions of past theories. however, the future is still unclear; perhaps we hope to see a shift towards a greener, smarter, and a more sustainable built environment. alternatively, distance communication and digital transformation could change our long-term habits and dramatically cut traffic and pollution. what if we harnessed telecommuting and digital city strategy as a way of social distancing and to help employees and citizens achieve work-life balance? based on the feasibility of working continuing remotely after the pandemic passes, our cities might require fewer spaces for highways and parking lots. in this case, we could recover these spaces for use as safe cycling and walking networks. it sounds utopic but this vision might encourage people to take their bikes to work and give more space to pedestrians (gonzalez, ; muggah and ermacora, ). postpandemic design and planning strategies must reflect this change. the right design and planning strategies now could help to position our built environment in the post-pandemic era. however, there are many other social effects beyond the pandemic; however, the long-term impact is unclear, requiring j o u r n a l p r e -p r o o f further studies. let us hope we do not encounter this scenario; however, if it comes again, at least we can understand the risks and be better prepared in the prevention and quickly react in mitigation. as shown from the lessons and the complexity of the pandemic, it is no longer safe to solely rely on a strategy to protect our architecture and urbanism. instead, we must install an antivirus-built environment that incorporates a multi-layered approach of protection into its defense system. architects and planners should design our built environment such as to stop the virus from spreading by creating an antivirusenabled paradigm. this paradigm must improve new tools, options, and strategies that are more flexible, holistic, and responsive to better address the pandemic response at all levels and scales from interior design to city planning. based on the lessons learned from this crisis, figure shows the proposed vision about how nature and advanced technology approaches help in visualizing antivirus-built environments to stop the virus from spreading. however, selecting the best antivirus strategy depends on many factors, posing new challenges to choose that could be used or planned as long-term reforms. we must be proactive, not reactive, and continue to update this antivirus-enabled paradigm and install new approaches within its framework. many questions still require further multidisciplinary studies. this study does not present answers; it originates insights for areas where future research will be critically required to update the proposed vision. the proposed vision in this study does not have an expiration date, when the covid- pandemic ended, most of healthy architecture and urban approaches could be applicable to the pandemics to come. we could imagine all housing buildings as self-sufficient, independent and healthy neighborhoods and making smart use of the available technologies. it is crucial to make urban areas more resilient to emergencies response, to face epidemics and other possible future emergencies of every kind. j o u r n a l p r e -p r o o f there is no end in sight to the covid- pandemic, but it has helped us predict what post-pandemic architecture and urbanism might look like. although we are not going to overhaul how we have been building architecture and cities before, based on the current circumstances and emergency measures, we should review our design strategies and planning theories. we could more effectively use healthy design and planning strategies to face pandemics and create a less pullulated, more sustainable architecture, and urbanism in general. moreover, if we harnessed the security layers not only to prevent ever-mutating virus attacks but a healing approach that could be implemented in the post-pandemic era, it could help build a sustainable environment. therefore, is this transformation in our physical and built environment a temporary reaction or the new normal? with spread of the covid- pandemic, additional questions will undoubtedly arise, and additional security layers should be added to update an antivirus-enabled paradigm. this study does not present answers; it only provides insights for areas where future research will be critically required to extend the scope of research required. based on the lessons learned from this crisis, this study introduces a vision about the required antivirus-built environment that can be updated to stop the virus spreading or mitigate its impacts. however, selecting the best antivirus strategy depends on many factors such as the abilities and capabilities of each community and environment. the global pandemic has highlighted the limitations of how we manage our built environment regarding how we should design, build, and run our built environment; however, it has given us a chance to learn. nevertheless, certain questions remain such as will we regard these unique lessons? if so, we should think more specifically about the benefits of this forced experimentation and implement further developments to select which could be used or planned as long-term reforms from a transformative viewpoint. in this context, the pandemic increased the requirement for policymakers, planners, and architects to think more out of the box, trying to reshape our physical spaces, and reset the existing build environment or develop more ideas to face future virus attacks. these changes give us a glimpse at how our cities could change for the better, and the worse, in the long-term. however, it is too early to judge how responses to covid- will affect design and urbanism theories. these results call for urgent efforts to further explore our built environment and not wait for another pandemic to serve as a reminder. this approach must be parallel to other sustainable approaches embracing not impinging natural resources and not harming our environment. if we can manage that, our present architecture and cities will continue to serve us well. however, the post-pandemic era will see multiple challenges that require a better understanding of covid- and its socioeconomic effects on society. the future remains uncertain and thus future multidisciplinary studies are required. methodology for the design and evaluation of green roofs in egypt covid- : lessons for an urban(izing) world, one earth antivirus architecture as urban design pandemic stricken cities on lockdown. where are our planning and designprofessionals [now, then and into the future self-sufficient community through the concepts of collective living and universal housing architecture after the coronavirus an engineering approach to the control of mycobacterium tuberculosis and other airborne pathogens: a uk hospital based pilot study teleworking in the context of the covid- the coronavirus, meatspace, and architecture, architect magazine turbulent gas clouds and respiratory pathogen emissions: potential implications for reducing transmission of covid- covid- guidance for shared or congregate housing grow your own: urban farming flourishes in coronavirus lockdowns the post-pandemic style using technology to maintain the education of residents during the covid-pandemic covid- pandemic: prevention and protection measures to be adopted at the workplace uk opens new hospital erected in conference centre to fight covid- how do you build a city for a pandemic? bbc is coronavirus pandemic accelerating the digitalization and automation of cities? novel coronavirus (covid- ) pandemic: built environment considerations to reduce transmission urbanization: challenge and opportunity for soil functions and ecosystem services how covid- will change the design of our cities effect of green roofs on the efficiency of thermal performance of residential buildings in egypt postmodern urbanism coronavirus is crowding limited outdoor spaces, says fiu architecture professor current response and management decisions of the european union to the covid- outbreak: a digital transformation: ways to plan for the post-pandemic normal, enterprisers project the ecotechnic future: envisioning a post-peak world reinterpreting sustainable architecture: the place of technology areas of academic research with the impact of covid- how covid- redefines the concept of sustainability modular buildings in the time of covid- pandemic thoughts, civil infrastructure and sustainable development: five insights from covid- across travel lenses the impact of covid- on public space: a review of the emerging questions building upon current knowledge and techniques of indoor microbiology to construct the next era of theory into microorganisms, health, and the built environment green roof urban farming for buildings in high-density urban cities six ways urban spaces may change because of coronavirus cybersecurity lessons from the covid- pandemic the post-pandemic urban future is already here evaluation of an ultraviolet room disinfection protocol to decrease nursing home microbial burden, infection and hospitalization rates emerging study on the transmission of the novel coronavirus (covid- ) from urban perspective: evidence from china commentary: past pandemics changed the design of cities. six ways covid- could do the same how relevant is 'planning by neighbourhoods' today? life after coronavirus: how will the pandemic affect our homes? dezeen local food systems: concepts, impacts, and issues, err how the covid- pandemic is fast-tracking digital transformation in companies vic hospital gets covid- unit installed photocatalytic technology in architectural context: from science to societal debates this is the end of the office as we know it housing layout, perceived density and social interactions in gated communities: mediational role of territoriality. sustainable cities and society opinion: redesigning the covid- city editorial jth -the coronavirus disease covid- and implications for transport and health covid- pandemic: impacts on the air quality during the partial lockdown in são paulo state, brazil, science of the total environment the socio-economic implications of the coronavirus and covid- pandemic: a review will covid- spell the end of urban density? don't bet on it osu researchers examine social distancing models, encourage caution nurture to nature via covid- , a self-regenerating environmental strategy of environment in global context braced for impact: architectural praxis in a post-pandemic society (version ) mental health and the covid- pandemic architecture after coronavirus creating urban agricultural systems: an integrated approach to design the failure of modern buildings. adapting buildings and cities for climate change covid- : a new digital dawn? digital health environmental perspective of covid- coronavirus questions that will not go away: interrogating urban and sociospatial implications of covid- measures hospitalbased pandemic influenza preparedness and response: strategies to increase surge capacity housing characteristics and staying at home during the covid- pandemic airborne transmission route of covid- : why meters/ feet of inter-personal distance could not be enough offsite architecture: constructing the future, routledge urban agriculture of the future: an overview of sustainability aspects of food production in and on buildings urban villages as self-sufficient, integrated communities: a case study in london's docklands. urban design international sustainable communities: the potential for eco-neighbourhoods farming in and on urban buildings: present practice and specific novelties of zero-acreage farming (zfarming). renewable agriculture and food systems health effects of viewing landscapes -landscape types in environmental psychology a functional city's response to the covid- pandemic smart lifts, lonely workers regional office for europe & ranson, ray p. guidelines for healthy housing. who regional office for europe social inequalities in neighborhood visual walkability: using street view imagery and deep learning technologies to facilitate healthy city planning. sustainable cities and society the authors declare that there is no conflict of interest. key: cord- - mu rrql authors: fakhruddin, bapon; blanchard, kevin; ragupathy, durga title: are we there yet? the transition from response to recovery for the covid- pandemic date: - - journal: nan doi: . /j.pdisas. . sha: doc_id: cord_uid: mu rrql abstract there is no corner of the planet that has not been impacted by the rapid spread of the novel coronavirus, covid- . while the covid- pandemic has already had far-reaching socioeconomic consequences commonly associated with natural hazards (such as disruption to society, economic damage, and loss of lives), the response of governments around the world has been unparalleled and unlike anything seen before. governments are faced with a myriad of multi-dimensional effects of the pandemic, including direct impacts on public health systems and population health and indirect socioeconomic effects including disruption to every single sector of the economy and mass unemployment. there is, additionally, the growing realisation that the timescale associated with this crisis may permanently change the very foundations of societies ‘normal’ day-to-day life. as the world transitions to recovering from covid- , those developing that recovery need support in adjusting and improving their policies and measures. the situation seems dire, the stakes are high. literature about the transition between the response and recovery phase in relation to pandemics is scarce. further complication is that the pandemic will not allow countries to simply transition to the full-scale recovery, instead, a rebound from recovery to response phase is expected for a certain period until the immunization is in place. pandemics indeed force us to think beyond typical emergency management structures; the cycles of the disaster risk management in the case of biological and other natural hazards are not exactly the same and no one-size-fits-all approach may be used. still, some parallels may be drawn with the efforts to combat natural hazards and some lessons may be used from previous and the current pandemic. based on these experiences and reflections, this paper provides a set of policy directions to be considered during the transition towards, as well as throughout, this transition phase. it is suggested that meeting this global, multi-dimensional, and complex challenge will require considerable international collaboration (even convention) and macro-scale changes to global and national policies. the recovery issues are mainly going to be dominated by politics, economics and social science. necessary for an effective recovery, the pandemic response needs to be a holistic response, combined with an improved data ecosystem between the public health system and the community. we should also view this outbreak and our response to it as an opportunity to learn lessons and reaffirm our universal commitment to sustainable development and enhancing wellbeing around the world. governments are faced with a myriad of multi-dimensional effects of the pandemic, including direct impacts on public health systems and population health and indirect socioeconomic effects including disruption to every single sector of the economy and mass unemployment. there is, additionally, the growing realisation that the timescale associated with this crisis may permanently change the very foundations of societies 'normal' day-to-day life. as the world transitions to recovering from covid- , those developing that recovery need support in adjusting and improving their policies and measures. the situation seems dire, the stakes are high. literature about the transition between the response and recovery phase in relation to pandemics is scarce. further complication is that the pandemic will not allow countries to simply transition to the full-scale recovery, instead, a rebound from recovery to response phase is expected for a certain period until the immunization is in place. pandemics indeed force us to think beyond typical emergency management structures; the cycles of the disaster risk management in the case of biological and other natural hazards are not exactly the same and no one-size-fits-all approach may be used. still, some parallels may be drawn with the efforts to combat natural hazards and some lessons may be used from previous and the current pandemic. based on these experiences and reflections, this paper provides a set of policy directions to be considered during the transition towards, as well as throughout, this transition phase. it is suggested that meeting this global, multi-dimensional, and complex challenge will require considerable international collaboration (even convention) and macro-scale changes to global and national policies. the recovery issues are mainly going to be dominated by politics, economics and social science. necessary for an effective recovery, the pandemic response needs to be a holistic response, combined with an improved data ecosystem between the public health system and the community. j o u r n a l p r e -p r o o f the consequences of any new virus are always unforeseen and become more and more multisectoral as time compounds them, at all levels, from an individual to the macro level . these consequences, although uncertain, can be reduced with sound policy. however, the policy for pandemic crisis is unlike that applied to natural hazards. pandemics force us to think outside of the box, or in this case, outside the typical emergency management cycle (figure ) . in other words, while four phases to reduce the impact of a natural hazard (preparedness, response, recovery, and mitigation) are principally linear, the response and recovery phases for a pandemic are essentially non-linear. to illustrate, unlike earthquakes, cyclones or other natural hazards, which are usually one-off events occurring within a limited period, covid- or any other pandemic, tend to come in several waves over a protracted period -until the effective vaccine or herd immunity is in place such as influenza pandemic and ebola virus disease occurred in multiple waves (saunders-hastings & krewski, ) . also, natural hazards tend to impact relatively confined areas. the covid- outbreak was declared a global pandemic by the world health organization (who) on march and already in april , the virus has affected out of countries (johns hopkins university, ). a response to biological and natural hazards follows the same disaster risk management cycle -but in the case of pandemics, alert and pandemic phases (reporting the increase of the global average of cases, with the highest number in the pandemic phase) correspond to the response phase of disaster risk management, while a transition phase (reporting the significant decrease of the global average of cases) correlates with the recovery from a disaster. biological disasters present challenges for both the response and recovery stages due to their sheer complexity (jeremias & martin, n.d.) . due to the very nature of pandemics, there will be a constant change in the way we approach and implement organisation structure, tools and technologies, as well as emergency management, recovery, and business continuity plans. each new wave of a at an individual level, a person's income, access to food, other health care (outside of that related to the pandemic) are all impacted. at the macro end of the consequences, financial structures (of both public and private institutions), political stability (or instability and tensions) are impacted. j o u r n a l p r e -p r o o f pandemic is distinct, where the same approach in policy may not be applicable, and revisions after each wave may be required to minimise the new consequences (figure ). transitioning from pandemic response to recovery in a spiral fashion: there is a high probability of the second and even the third wave of a pandemic if there is no vaccine or immunization, each new wave pushing the disaster risk reduction cycle from the recovery back to response phase. in the midst of the covid- emergency, on march , zagreb, croatia was hit by a . magnitude earthquake, as the country dealt with covid- patients (walker, ) . in canada, manitoba province and ottawa city fought against flooding caused by snow melting. a month later, cyclone harold wreaked havoc on the solomon islands, fiji, vanuatu and tonga, placing extra stress on their already stretched governments, as the need for additional funds, medical supplies and food rose (lyons, ) . in vanuatu, this was further strained by the measures put in place for the covid- response (sbs, ) . while local governments in japan suspended receiving volunteers engaged in rehabilitation works in areas devastated by typhoon hagibis in , the bangladesh government prepared for both cyclones and a covid- outbreak in the cox's bazar camps which shelter some , rohingya refugees (ishiwatari et al., ) . the world is facing the same type of difficulties to manage natural hazards as pre-pandemic whilst also investing in considerable efforts to flatten the covid- curve. and yet, with rapidly changing climate and ecology, hastily marching urbanisation, and increased travel, pandemics will become j o u r n a l p r e -p r o o f more frequent and more complex. perhaps the single common thread of pandemics, cyclones, floods and earthquakes is that they become ever more intense, magnified and complex in nature. fundamentally the issues to respond to these events are political at a number of levels including within the scientific community, with competing interests between the various sciences (social, biological and health-based) particularly noticeable. this will be no different in the recovery phase. ensuring consideration at all levels on government response, policies, plans and logistics regarding the process in which they respond to other emergencies during the pandemic, whilst ensuring scientific harmony, is crucial in ensuring effective response, recovery times, and financial and political stability. the existing framework of disaster risk management policies (national, regional and global) has largely been designed to ensure a swift and effective recovery along the traditional disaster risk management cycle. the sendai framework for disaster risk reduction, agreed in , focused the attention of signatory member states on preparing for a range of hazards including those of a geophysical, hydrological, climatological and meteorological nature. importantly, it also included a strong public health focus and consideration of the risks from biological hazards (maini, et al, ) . however, the sendai framework did not distinguish the cascading impact of biological and other hazards in a systematic risk management approach. the emerging thinking is that the concept of pandemic must evolve from crisis response during discrete outbreaks to an integrated cycle of preparation, response and recovery (bedford et al., ) . the recent global risk assessment framework (graf) promises to inform and focus action within and across sectors and geographies by decision makers at local, national, regional and global levels to improve the understanding and management of current and future risks, at all spatial and temporal scales (gordon, ). despite the two-decade experience of public health crises caused by novel virus infections (such as hiv, influenza a virus subtype h n and h n , sars-cov , mers-cov and ebola), the epidemiological novelty of covid- and its rapid spread caught many governments unprepared . the response of all governments, organisations and individuals at all levels, national or internationals, has been put to the test. a number of governments around the world failed to act on their warnings about a pandemic due to not understanding the magnitude of the problem, so-called 'strong man' politicians, lack of updated or public risk registers and other various reasons (tyler and gluckman, ). as the world continues to combat the covid- pandemic impacts, rapid evaluations of the strategies of various countries provide insights for all stakeholders to adjust and improve policy options. not all strategies have yielded positive results; in fact, while some were commended as effective (such as the response from singapore, germany and new zealand), others were criticised as devastating (for example, high infection and death rates in iran, italy, south korea, and the united states) . as an illustration, singapore's approach to the covid- outbreak has been rated as effective as it managed to keep both the infection rates low and the economy strong (lai & tan, ) . one of the key success factors of singapore's efforts has been assigned to the fact that singapore has learned from their recent pandemics experience. in , singapore experienced an outbreak of hand-foot-mouth disease, which affected more than , young children, causing three deaths. later in , sars hit singapore, infecting people, of whom died of this disease. in , avian influenza h n struck singapore, affecting , people with deaths (lai, a. y., & tan, s. l., ) . one of the most important lessons that the singapore government learned from the sars epidemic was the detrimental role of j o u r n a l p r e -p r o o f the bureaucratic structure in handling fluid and unprecedented situations. recognising that the effective response and recovery for covid- depends on a large number of stakeholders ("the health of all depends on each of us", https://www.gov.sg/), the singapore government has led a well-coordinated, multi-stakeholder response and recovery, which has been praised by other countries. however, singapore paid far too little attention to their hundreds of thousands of migrants living in crowded dorms, excluded from government initiatives, among whom sars-cov is now spreading quickly (ratcliffe, ) . sadly, this was also reported in germany where there was a rise in cases where refugees were not accommodated properly (oltermann, ) . new zealand's success factors were determined leadership and bold action early in the pandemic outbreak. because of early and strong action, only a small number of new zealanders got infected, were tested, contact was traced, and they were isolated. this prevented widespread transmission overwhelming the medical system along with the inherent effects such as widespread shortages of tests and personal protective equipment. experiences from the previous pandemic crisis offer more insights, and the responses of different governments may broadly be categorised as effective or ineffective (table ) . briceño, ; lai and tan, ; and spiekermann et al., ) . lack of knowledge on how to disseminate information correctly weak community vigilance and lack of public education measures lack of collaboration between major parties with the lack of risk management integration into major sectors (e.g., health, infrastructure, tourism, environment) evidence-based decision making, with the effective use of big data lack of support to community in lockdown j o u r n a l p r e -p r o o f parallels may also be made between the effectiveness of the country's response to pandemics and to natural hazards. for instance, the response to the devastation caused by the hurricane maria in dominica and the surrounding caribbean nations was characterised by most of the ineffective responses from table . the combination of poor technology and data collection systems, inadequate reporting, lack of public awareness and inclusiveness led to poor information being disseminated to people during the hurricane; this in turn inhibited people from preparing and therefore led to inaction and placed people at greater risk to the hurricane (tonkin & taylor international limited, ). these very factors seem to also arise when reviewing the responses to covid- in countries such as iran and italy . the primary mission during the response phase is saving lives and livelihoods (jeremias & martin, n.d.) . this, as seen from the response of many governments to the covid- outbreak, relies on the communications policy. the limited capacity for vaccinating against a novel coronavirus in the early stages results in a more concerted policy direction around communication of public health guidance and instructions (including lockdown and social distancing) (dickmann et al, ) . this policy is often targeted at the most vulnerable community members or is aimed at informing the wider public audience about the risks to the most vulnerable (dickmann et al, ) . indeed, much of the work in the response phase of a biological disaster revolves around the dissemination of information at national or regional levels (figure ) . one of the tried-and-tested approaches to responding to pandemic disasters is the epidemiological process of understanding disease transmission, including by contact tracing (o'sullivan et al, ) . this type of response differs to that of a geophysical hazard in that it is concerned with individuals, rather than the wider picture (lee & riley, ) . while this strategy requires a considerable amount of resources, it has been effective in reducing the impacts of an outbreak (for example, in south korea), implemented along with wide-scale testing and containment (mccurry, ). while many countries are only just managing the multiple aspects of the response phase, the covid- outbreak will very likely subside eventually (through herd immunity or vaccination) and there will be a period of recovery. policy for the recovery from pandemics will differ from traditional recovery in a number of ways, largely due to the global scale and sheer complexity of covid- pandemics (furnival, ) . one of the initial policy manoeuvres many governments will want to make will be returning economic activity to normal (or as close to normal as possible). this effort to restart trade, manufacturing, and services will differ from those during natural hazards in both scale and complexity (table ) . table : some elements of the response and recovery phases during natural hazards (hydrometeorological and geohazards) and biological disasters (from pandemics) are the same -but each needs to be carefully considered and specified unless or until we acquire full natural or vaccine-induced immunity to covid- , or if an eventual vaccine is only partially protective, we face the threat of a new endemic disease that will fundamentally change human society. it sounds alarmist -we admit -but it is becoming distinctly possible, based on what we have learned so far. like the human immune system, whose reaction may sometimes be part of the cause of death from the viral disease -reactions of all stakeholders and the public to the pandemic can have positive as well as negative consequences. therein lies the greatest risk and, with it, the strongest need to remain calm and in control. we are now in a global, high-risk situation and the direct threat of covid- may not turn out to be our biggest problem. as the world is transitioning to recovery, the following policy considerations are important and need to be considered: picture the governments playing whack-a-mole , hammering the new waves of virus reemerging in hotspots with the yet again forced stay-at-home measures, reactivated temporary hospitals, sourcing extra healthcare personnel and personal protective equipment. this is indeed an unwanted but warranted scenario. as with fire, it is not a question of "if?" but "when?". wildland fire suppression personnel and equipment serve as an excellent model for preparedness levels and mobility of resources throughout the fire season. countries shall be in this mindset for pandemics too. covid- hotspot outbreaks may be managed in the same way, with the inclusion of testing, monitoring, and contact tracing. data-based modelling may provide a framework within which the details are hammered out among key stakeholders (government, private, and non-governmental organisations). our concept of pandemics shall move to an interdisciplinary science, with an integrated approach of medical science and public health with medical research and development, social sciences, diplomacy, biomedical science, big data, information technology, artificial intelligence, statistics, meteorology, biotechnology, ecology and so on -combined to provide an integrated cycle of prevention, preparation, response and recovery. the international community should recognise the opportunity afforded them through already agreed policy frameworks such as the sendai framework for disaster risk reduction, united nations' sustainable development goals, and climate change conventions and agreements. these policy tools have been largely agreed and ratified in each of the countries impacted and as such, many of the processes to respond, monitor and recover are already established within domestic legislations. building recovery around these frameworks can also provide a greater level of cohesion among member states who may be at different stages of the pandemic. we have seen a number of countries reducing the level of public funding for their healthcare systems or internationally focused biological observation and scanning initiatives. these funding reductions have been cited as one reason the covid- pandemic has been so destructive. governments and international organisations should use the opportunity of j o u r n a l p r e -p r o o f recovery and demand from their public to invest in measures to ensure future novel viruses or biological threats are identified early. beyond health risks, depending on the characteristics of the pathogen, pandemics cause risks and related disasters in multiple sectors such as agriculture, public transport, logistics, finance and security. a very lethal pathogen could cause a total global shutdown, resulting in famine or another unforeseeable secondary disaster. because each new pathogen usually has unknown characteristics, the response decision making is highly flawed and error-prone. the pandemic response needs to be a holistic response. multi-sector pandemic planning and active drills with representatives from different sectors can help countries and cities to prepare for such complex chains of decisions and consequences. international communication, cooperation, collaboration, and even established convention should be considered, reconsidered and strengthened for prevention of pandemics. leadership (in terms of financial support and policy development) will need to come from established international organisations such as the world bank, asian development bank and united nations, and groupings like the g and g . while advanced organisations and groups will need to lead these efforts (they have the financial capacity and resources to do so), the inclusion of developing countries and non-traditional agents (including nongovernmental organisations) is necessary and ultimately, inevitable. while a number of countries in recent years have taken domestic policies that have gone against international cooperation and some responses to the covid- pandemic have seen bilateral spats between countries, the scale and complexity of this crisis calls for an international recovery that will only be achieved through global cooperation at all levels. also, strengthening epidemiology, public health and laboratory capacity in low-and middle-income countries is essential though collaboration. j o u r n a l p r e -p r o o f cascading problems. in fact, the director-general of the who mentioned an infodemic, referring to unprecedented misinformation that spread faster and more easily than the virus, hampering a public health response. improved information flow between the public health system and the community is necessary for an effective recovery. the use of data from people is becoming strictly controlled, whereas contact tracing is needed to better understand how infections spread. a data ecosystem is critical to ensure a stable transition from the response to the recovery phase (fakhruddin, ) . a system shall be used, where communities feed information into the public health system and the feedback loop offers a fast and direct way to provide people with details of potential actions they can take. some have called the covid- outbreak a dress rehearsal for climate change. large-scale, global impacts on the economy and our day-to-day lives, those living in poverty being among the worst impacted, have been evidenced during the covid- outbreak but are also predicted (and in some cases, already happening) in relation to our changing climate. the international community, as well as individual countries, should use the lessons we are learning through the outbreak, to ensure we are better prepared for the changes happening already and to limit or stop the increasing levels of risk caused by climate change. the sendai framework for disaster risk reduction: renewing the global commitment to people's resilience, health, and wellbeing a new twenty-first century science for effective epidemic response what to expect after sendai: looking forward to more effective disaster risk reduction building resilience against biological hazards and pandemics: covid- and its implications for the sendai framework review and analysis of current responses to covid- in indonesia: period of biological risks to public health: lessons from an international conference to inform the development of national risk communication strategies: report of an international conference on risk communication strategies before, during, and after public health emergencies a data ecosystem to defeat covid- how can society recover from covid- ? alliance manchester business school is the response over? the transition from response to recovery in the health sector post-haiyan shifting the paradigm: introducing the global risk assessment framework (graf) managing disasters amid covid- pandemic: approaches of response to flood disasters & martin (n.d.), h. bio-hazard disaster risk governance through multi-agency cooperation dashboard data retrieved on bridging the gap between evidence and policy for infectious diseases: how models can aid public health decisionmaking disease modeling for public health: added value, challenges, and institutional constraints impact of disasters and disaster risk management in singapore: a case study of singapore's experience in fighting the sars epidemic public health and disasters cyclone harold batters fiji on path of destruction through pacific. the guardian the sendai framework for disaster risk reduction and its indicators-where does health fit in? test, trace, contain: how south korea flattened its coronavirus curve. the guardian refugees in german centre fear lack of protection as covid- cases soar. the guardian from sars to pandemic influenza: the framing of high-risk populations uncertainties in biological responses that influence hazard and risk approaches to the regulation of endocrine active substances. integrated environmental assessment and management we're in a prison': singapore's migrant workers suffer as covid- surges back. the guardian reviewing the history of pandemic influenza: understanding patterns of emergence and transmission vanuatu needs aid after cyclone harold, but there are fears it could cause a coronavirus emergency the disasterknowledge matrix -reframing and evaluating the knowledge challenges in disaster risk reduction governance, technology and citizen behavior in pandemic: lessons from covid- in east asia coronavirus: governments knew a pandemic was a threathere's why they weren how korea responded to flattening the curve on covid- provision of coordination and standardization services of early warning systems in dominica zagreb hit by earthquake while in coronavirus lockdown. the guardian key: cord- -mwgccbfo authors: casado-aranda, luis-alberto; sánchez-fernández, juan; viedma-del-jesús, maría i. title: analysis of the scientific production of the effect of covid- on the environment: a bibliometric study date: - - journal: environ res doi: . /j.envres. . sha: doc_id: cord_uid: mwgccbfo the fight against covid- since january has become the top priority of more than countries. in order to offer solutions to eradicate this global pandemic, the scientific community has published hundreds of articles covering a wide range of areas of knowledge. with the aim of synthesizing these publications, academics are resorting to bibliometric analyses from the perspectives of the disciplines such as biology, medicine, socioeconomics and tourism. yet no bibliometric analysis has explored the diffuse and little-known growth of covid- scientific publications in the field of environmental studies. the current study is the first of this type to fill this research gap. it has resorted to scimat software to evaluate the main topics, authors and journals of publications on the subject of covid- combined with environmental studies spanning the period between december and september . the search yielded a collection of articles published in scientific journals indexed on by web of science and scopus databases. these publications can be broken down into six main themes: (i) a sharp reduction in air pollution and an improvement of the level of water pollution; (ii) the relationship of wind speed (positive), ultraviolet radiation (positive) and humidity (negative) with the rate of infections; (iii) the effect of the pandemic on the food supply chain and waste habits; (iv) wastewater monitoring offers a great potential as an early warning sign of covid- transmission; (v) artificial intelligence and smart devices can be of great use in monitoring citizen mobilization; and (vi) the lessons gleaned from the pandemic that help define actions to mitigate climate change. the results of the current study therefore offer an agenda for future research and constitute a starting point for academics in the field of environmental studies to evaluate the effects of covid- . the struggle initiated in january to combat the severe acute respiratory syndrome coronavirus (sars-cov- or covid- ) has become the top priority for more than countries. the pandemic is putting a massive strain on, among others, health care personnel, law enforcement agencies, public administrations and information and communication professionals. in order to offer solutions to this global health problem, the scientific community is also facing one of the most important challenges in recent times. it is responding by publishing hundreds of articles every day in a variety of fields, from medicine and epidemiology to psychology and the environment. many also appear in the field of economics due to the severe financial consequences of the virus. the ongoing scientific contributions confirm that the academic response to covid- is both massive and multifaceted (bonilla-aldana et al., ; felice and polimeni, ; nowakowska et al., ) . a revealing fact in this regard is that since the pandemic's outset, the number of scientific papers on covid- have doubled every days (torres-salinas, ) . this sheer volume of the scientific output in response to the pandemic renders it difficult even when resorting to accurate keywords to pinpoint information from the databases such as pubmed, web of science and scopus. in order to facilitate the search for scientific information related to covid- , academics are following two different alternative paths. the first, applied by academics from various branches, consists of carrying out comprehensive reviews and bibliometric analyses so as to synthesize and simplify the results. papers between december and april . bonilla-aldana et al. ( ) and radanliev, de roure and walton ( ) proceeded further by evaluating the scientific literature on coronavirus types and potential vaccine treatments. verma and gustafsson ( ) in the sphere of socioeconomics conducted a bibliometric study of covid- literature in the domains of business and management so as to identify current areas of research and propose future lines of research. sigala ( ) , in the field of tourism, likewise undertook a critical review on the impacts and implications of covid- so as to offer solutions to reset the industry. at the same time, efforts are being conducted to build covid- -oriented databases of scientific papers to continually update the scientific contributions to the subject. examples are the databases of the world health organization ( ) and the center for disease control and prevention ( ). in this period of pandemic, the audiovisual and written media bear the responsibility (now more than ever) to disseminate true and quality information, and prevent the proliferation of hoaxes and fake news in the face of an uncertain future. nevertheless, the spread of fake news and misunderstandings is occurring, more than ever, and at a very rapid pace. this is due to the growth of accessibility to internet, the popularity of social media and the nature of how it works (i.e., post sharing) combined with the appetite of the media to increase their visibility via click-baiting techniques and sensational headlines. in their effort to avoid misconceptions, information and communication professionals have turned to scientific texts on virology, epidemiology, law, economics or psychology to attempt to transfer the scientific results through their newsletters in a simple, informative and accessible manner. journalists from the newspaper el país (de benito, ) , for example, reported on the findings of crucial scientific research with the aim to explain the drugs available to treat covid- . the new york times (debgupta, ) , likewise based on scientific data, offered a guide on how to attend to supermarket food purchases. the world health j o u r n a l p r e -p r o o f organization ( ) also reported on how to cope with the stress related to covid- . this reporting on the effect of covid- at pharmacological, nutritional and psychological levels contrasts with the little data advanced by the international media as to the consequences of covid- on the environment. exceptions are reports by the bbc (henriques, ) that offered scientific details from other pandemics to answer the query "will covid- have a lasting impact on the environment?" the online newspaper eldiario.es (garcía-charton, ) likewise delved into the environmental consequences of new methods of consumption, migration and mobility subsequent to the crisis. it is also noteworthy that different media reported opposite data as to covid- 's biomedical-environmental origin and ecological consequences (anon., ; o'callaghan, ) . due to the low quality of the current information regarding the main environmental consequences of covid- and the diffuse and little-known growth of reports on the subject, a descriptive and visual quantification of scientific research on the virus and its effect on the environment would be of assistance to information professionals and environmental academics to gain an objective perspective of the evolution, current scope and main results to include in their reporting and research. this task would lend a hand to information professionals to disseminate the effects of covid- on the environment consistently and clearly and depict the encroaching phenomenon of the coming months. although certain bibliometric analyses on covid- exist in a general level (e.g., bonilla-aldana et al., ; chahrour, ; felice and polimeni, ; hossain, ; nowakowska et al., ; torres-salinas, ) , no study has explored the evolution of publications related to covid- or identified its main thematic axes and environmental consequences in the specific area of the environment. prior environmental research resorting to bibliometric analyses have examined the characteristics and implications of the patterns in shale gas literature between and j o u r n a l p r e -p r o o f (wang and li, ) or have attempted to identify a research profile on the natural gas acquired from these types of deposits (wang and lin, ) . closer to the current covid- topic are studies delving into the effects of temperature and relative humidity on the viability of previous types of coronavirus (casanova et al., ; chan et al., ) . other studies have focused on the survivability of earlier strains of coronavirus in water and wastewater (gundy et al., ; ye et al., ) . recent environmental literature is placing great weight on the antecedents and consequences of covid- on the environment and its interaction with human activities (e.g., sims and kasprzyk-hordern, ; wang and su, ; xie and zhu, ) . the intention of the current study is to offer a first straightforward report on the evolution of publications combining the effect of covid- on the environment since the outset of the pandemic, as well as to identify the main lines of research that are surging as a result of the crisis and establish a research agenda for environmental scholars. the study specifically pursues five objectives: (i) quantification of the volume of production of covid- -related scientific articles in the field of environment studies including peer-reviewed publications indexed in the main databases (i.e. web of science and scopus) spanning december to september . environmental studies is a multidisciplinary field which systematically delves into human interaction with the environment. it specifically draws together principles from the physical sciences, commerce/economics, and humanities and social sciences to address complex contemporary environmental issues (soulé and press, ) . (ii) identification of the main authors and scientific journals publishing research on covid- and the environment. this study is not only a first in the evolution of covid- research from the specific perspective of environmental studies, but will be of extreme utility for information professionals to disseminate objective and quality coverage on the effects of the virus on the environment. furthermore, the results will offer insight into the authors, research journals and themes worth considering in future environmental research. the databases web of science core collection and scopus served for this study. the information gleaned from them was from a consultation carried out on september . the query equation for scopus was the following: all (( " -ncov" or "covid- " or "covid- " or "sars-cov- " or the initial search yielded over , papers in english, of which were duplicates (i.e., indexed in both databases) and thus excluded from further analysis. the corpus was then narrowed down to articles within the scope of environmental studies so as to eliminate contributions linked to covid- treatments, or others related to the implications of the virus on public health. this manual screening process led to a collection of documents published between december and september . the data analysis was carried out with scimat software (cobo et al., ) , a technique serving to examine the social, intellectual and conceptual framework of a specific field. based on the two files extracted from consulting the scopus and web of science databases, the scimat software: (i) sorted and ranked all the documents by year of publication, number of citations, and titles of journals; and (ii) carried out a co-word analysis aiming to identify emerging themes related to covid- stemming from the realm of environmental research (cobo et al., ) . thus the co-word analysis applied text-mining techniques to the titles, abstracts, and keywords leading to the design, based on fundamental bibliometric indicators such as the number of publications, of a strategic diagram illustrating the main themes of interest related to the issue of environment in covid- research. to accurately detect the main topics garnered from the co-word analysis, the authors specifically followed the steps outlined in the study by cobo et al. ( ) consisting of isolating the author and journal keywords after an initial manual elimination of the documents not directly linked to the environment. the second step was to collect the relevant information from the raw data of these documents. as noted by cobo et al. ( ) , this information is gathered by analyzing the co-occurrence of keyword frequency. individually, this frequency j o u r n a l p r e -p r o o f of two keywords is extracted from the corpus by computing the number of documents in which the two keywords appear together. the third step is to calculate the similarities between the items collected in the second step. the similarities are calculated from keywords co-occurrence frequency. following the recommendation of cobo et al. ( ) , an equivalence index is the most appropriate means to normalize the frequency of co-occurrence. the fourth step was to determine the clusters that serve to identify subgroups of linked keywords that signal topics of interest. likewise, following the method suggested by cobo et al. ( ) , the simple center algorithm (with the values and representing the minimum and maximum size of the network) was applied to detect the themes of relevance. finally, the values of the "number of citations" and "number of documents" served to measure the quality of the strategic diagram. the results of the bibliometric analysis applying the web of science and scopus databases yielded a corpus of articles published in peer-reviewed scientific journals since the outset of the pandemic (december ) combining the subject of covid- and the environment. % were identified through scopus. the remaining % were through both scopus and web of science. of note is that % indexed through the web of science finds are of open access, while . % of this type were identified through scopus. the recent interest of the effects triggered by the international covid- health crisis (table ). the authors with the greatest number of publications the effects of covid- on the environment are primarily chinese and american universities and research institutes (table ) . the two-dimensional graph generated by scimat software (figure and ( ) lessons learnt from covid- applicable to climate action. one of the motor themes of environmental study literature linked to the covid- pandemic is the role of the virus in air and water quality. a number of studies have explored the reduction of air pollutants (e.g., nitrogen dioxide, no ; carbon dioxide, co ; particulate matters, pm) and the decrease in fossil fuel emissions stemming from the daily lockdown. another thematic area that stands out among the main analyses of covid- and the environment is the effect of meteorological factors (i.e., temperature, humidity, wind speed and ultraviolet radiation) on the rate of covid- infection. xie and zhu ( ) other research has focused on the relationship between wind, ultraviolet radiation and covid- rates. rendana ( ) specifically concluded that low wind speed correlates with a rise in covid- cases (r = - . ). the study also reveals that low temperatures and the number of sunshine hours match with a higher number of covid- cases. Şahin ( ) environmental studies are now paying particular attention to the effects of covid- on wildlife and ecosystem conservation. certain initial enquiries, such as that by yuan et al. environmental specialists have more recently attempted to evaluate the effects of covid- on food supply chain efficiency and security, i.e., the availability and delivery of food and its accessibility. this is an important issue in environmental research as after the covid- crisis rose to the top of policy agendas, several decision makers warned of the problem of food supply and spikes of food prices (keulertz et al., ) . deaton and deaton ( ), for instance, in their appraisal of canada's food security and agricultural systems during the pandemic, noted that despite surges in demand and supply chain disruptions, there was no broad, rapid hike in food prices suggesting an adequate short-term supply of food. kerr ( ) environmental study academics also have explored how the monitoring of environmental settings can serve to prevent and predict such outbreaks and, consequently, improve public health. sims and kasprzyk-hordern ( ) their results suggest the great potential of wastewater monitoring to offer early warning signs on the extension of covid- circulation in a community, especially among those marked by mild or no symptoms. similar findings were reported by la rosa et al. ( ) in italy, kumar et al. ( ) in india, and mlejnkova et al. ( ) in the czech republic. in order to implement strategies to prevent the spread of covid- , environmental researchers have also evaluated aerosol transmission. morawska and cao ( ) , for example, recommend that the authorities take into account the airborne spread of covid- in their regulations to prevent transmission in indoor spaces. tang et al. ( ) review the evidence of aerosol transmission and concluded its plausibility and scored, based on the weight of the combined evidence, at out of . j o u r n a l p r e -p r o o f applying the concept of smart cities to tourism is known as smart tourism, that is, the creation of innovative spaces and improve services founded on a state-of-the-art technological infrastructure taking advantage of the surge of information and communication technologies. its objective is to guarantee a sustainable development of a territory, accessible to all, and facilitate the interaction and integration of the visitor with the environment. in the framework of the current pandemic, tourism companies and institutions are increasingly boosting these intelligent environments as a way to monitor and guarantee tourist security. jamal and budke ( ), for example, explain the importance of smart destinations and offer directions for tourism research and practice subsequent to the pandemic. specifically, the authors state that there is a need of a greater responsibility among residents and tourists to seek correct scientific facts about the virus and take sensible precautions, as well as exercise care to those suffering its adverse impact. they also advise of the need of a greater global coordination and attention to vulnerable destinations and an increase in the use of smart devices. chang et al. ( ) likewise advance the need of development of a more sustainable tourism as a way to balance tourism, travel, and the hospitality industry. among other measures, the authors highlight the urgency of personal protection equipment during travel, the need to implement comprehensive and frequent monitoring to control diseases and pandemics, as well as the necessity to impose updated rules to monitor medical facilities and highly trained on-board healthcare workers. gallego and font ( ) also advanced a method of the early detection of the reactivation of tourist markets to help mitigate the effects of the covid- crisis resorting to analyzing skyscanner data as to flight searches between november and december . their results reveal how big data can offer timely information crucial to identify highly volatile situations and that destination firms must improve their big data analytical competence. environmental studies are also evaluating the effects of artificial intelligence (a field of science and technology investigating the combination of algorithms designed to create machines emulating human capabilities) on how to control covid- . ghazaly et al. ( ) , for example, conclude that artificial intelligence can be applied to deploy intelligent diagnostic and treatment devices. in addition, they surmise that it can serve for teleworking, distance education and intelligent production to ensure a minimal disruption of daily life. along a same vein, nadikattuan et al. ( ) propose an innovative localization method to track through sensors the position of individuals in an outdoor environment. specifically, the authors suggest a novel smart device resorting to artificial intelligence to maintain social distancing as well as to detect covid- symptoms. similarly, simsek and kantarci ( ) recommend an artificial intelligence-driven strategy for mobile assessment agents during epidemics/pandemics. by means of simulations of real street map mobile crowd-sensing simulator, the authors signal "… that on the th day following the first confirmed case in the j o u r n a l p r e -p r o o f city under the risk of community spread, ai-enabled mobilization of assessment centers can reduce the unassessed population size down to one fourth of the unassessed population under the case when assessment agents are randomly deployed over the entire city" (simsek and kantarci, , p. ). main thematic networks serving to evaluate the interaction between covid- and smart cities a last research theme among the documents identified by the searches of the databases focuses on the future tasks that we, as a society, and environmental researchers, must develop to mitigate climate change. howarth et al. ( ) , for example, posit that covid- has raised our awareness of how vulnerable we are in the face of climate change. according to these authors, mitigating climate change requires a more carefully planned, inclusive, less disruptive and greater sustained response through deliberative engagement mechanisms aiming to build a social mandate for post-covid climate action. in an effort to clarify the measures of sustainability that we must assume in the future help mitigate climate change, meles et al. ( ) examined the impact of the covid- pandemic on the eu co emissions target. the authors claim that although existing climate policy measures in the wake of the pandemic will reduce emissions more than % by , this will not be enough to meet the guidelines of the paris agreement. hence a need for more strict and sustainable measures. klenert et al. ( ) summarized the main lessons of covid- applicable to reduce climate change: (i) delayed action increases mitigation costs; therefore, institutions and long-term incentives should be drawn up; (ii) there is a need to involve citizens in the reasons of climate change, thereby policies should be more appealing; (iii) actions in the future should address distributive concerns as well as measures of mitigation; (iv) individuals, governments and organizations must work together to encourage multilevel collaboration, tying in large emitters; and (iv) citizens must be inoculated against misinformation. environmental researchers have likewise highlighted that covid- should serve as a starting point to promote social sustainable habits. kleinschroth and kowarik ( ) resorted to google trends to estimate changes in online searches for basic activities typically carried out in urban green areas (e.g., walking) before and after the onset of the pandemic. their results indicate that searches for outdoor walks and parks during the pandemic increased exponentially. the authors therefore suggest that the crisis underscores the value of preserving and further developing urban green infrastructure. along the same line, mukanjari and sterner ( ) propose that efforts to revitalize the economy after covid- should resort to green and renewable resources as more polluting means and materials (e.g., airports, fossil fuel, carbon) experienced the largest decreases in stock value during the crisis. furthermore, goffman ( ) states that the best way to simultaneously alleviate the rapidly moving pandemic crisis and the slower moving environmental crisis is through glocalization, that is, a world in which people live far more local lives than in recent decades but foster a greater global awareness through a connective world. the author adds that these measures j o u r n a l p r e -p r o o f should be accompanied by a reduction of air and automobile travel and an increase in local production and smart growth. the global spread of the severe acute respiratory coronavirus syndrome and the response to the pandemic by national authorities is unprecedented in its speed and scope. the current crisis has likewise placed information professionals in the centre of an information pandemic (torres-salinas, ) as they are required to turn to scientific texts as sources to offer the public simple, instructive and accessible information. moreover, academics are turning to bibliometric surveys to facilitate navigating through the scientific databases to synthesize and simplify access to the findings of research on covid- . despite the fact that covid- bibliometric studies have been carried out in the fields of biology and medicine (bonilla-aldana et al. ), socioeconomics (verma and gustafsson, ) and tourism (sigala, ) , no study of this ilk has explored the growing number of covid- - this also suggests that populations suffering from poorer air quality suffer more covid- infections, hospital admissions and deaths. water pollution improved during the covid- lockdown as evidenced by decreases in spm and metal concentrations in lakes and rivers. (ii) covid- and meteorological factors. environmental studies indicate significant correlations between wind speed, air pressure, humidity, ultraviolet radiation and covid- rates. despite certain findings suggesting an opposite effect between temperature and virus cases, little research corroborates such a link. (iii) effects of covid- on wildlife and agricultural conservation. environmental study specialists exploring the changes provoked of covid- on food supply chains and changes in waste habits during the pandemic offer arguments as to its impact on the conservation of biodiversity. (iv) covid- and epidemiology. environmental researchers claim that monitoring wastewater has a great potential to offer early warning signs on the degree of distribution of covid- in a community, especially among individuals bearing mild symptoms or no symptoms at all. (v) covid- and smart cities. environmental and urban researchers coincide that the use of artificial intelligence, sig and smart devices can serve in monitoring the mobilization of citizens in urban and tourism destinations, and thus play a vital role in preventing an advance of the pandemic. propagation. hence prospective studies are now in a good position to evaluate this relationship in different tropical zones. thirdly, future studies exploring social changes in energy consumption, real environmental purchases, waste behavior and leisure activities is required to advance in the understanding of the effects of pandemics on social daily routines. fourthly, although studies have identified airborne transmission of covid- , no analysis to date has specifically enquired into what extent meteorological factors or urban contexts affect this type of transmission. lastly, more environmental studies are required to assess the manner in which smart devices and monitoring platforms can assist prevention and avoidance of covid- propagation. finally, the current study only isolated documents indexed in the web of science and scopus and has not identified all published materials. this study likewise did not take into account preprints, early versions of scientific articles, which also represent a rapid means of dissemination of information (torres-salinas, ). however, despite the fact that preprints enable a rapid dissemination of findings, commentaries and critical reviews through open access platforms, we contend that they increase the risk of spreading false information as they are posted devoid of independent quality control. considering the daily coverage that covid- receives from the international media, erroneous conclusions could be quickly replicated beyond the scientific sources leading to misinformation. finally, the current study did not account for the different methods applied by environmental researchers. future research should discuss these diverse methods applied to each of the above-mentioned thematic networks. hence the findings of this article offer information professionals with a true and objective framework of the main current scientific research combining covid- and the environment. journalists as well as information and documentation professionals, by incorporating these findings into their news stories and narratives, would bolster and guarantee their credibility in a time marked by an unprecedented information explosion. a bibliometric analysis. travel medicine and infectious disease a spatio-temporal analysis for exploring the effect of temperature on covid- early evolution in spain impact of covid- event on the air quality in iran effects of air temperature and relative humidity on coronavirus survival on surfaces covid- research articles downloadable database a bibliometric analysis of covid- research activity: a call for increased output exposure to nitrogen dioxide (no ) from vehicular emission could increase the covid- pandemic fatality in india: a perspective the effects of temperature and relative humidity on the viability of the sars coronavirus a charter for sustainable tourism after covid- smart korea: governance for smart justice during a global pandemic an approach for detecting, quantifying, and visualizing the evolution of a research field: a practical application to the fuzzy sets theory field scimat: a new science mapping analysis software tool air pollution exposure and covid- in dutch municipalities. environmental & resource economics, - lockdown for covid- in milan: what are the effects on air quality? the science of the total environment air pollution and covid- : the role of particulate matter in the spread and increase of covid- 's morbidity and mortality can atmospheric pollution be considered a co-factor in extremely high level of sars-cov- lethality in northern italy? environmental pollution la agencia del medicamento ha aprobado en un mes ensayos de fármacos para el covid- . el país, de abril will the coronavirus threaten our food? cleaning the river ganga: impact of lockdown on water quality and future implications on river rejuvenation strategies coronavirus disease (covid- ): a machine learning bibliometric analysis changes in air passenger demand as a result of the covid- crisis: using big data to inform tourism policy el escenario post-covid- , una ventana de oportunidades. eldiario.es, de abril novel coronavirus forecasting model using nonlinear autoregressive artificial neural network the wake of covid- , is glocalization our sustainability future? sustainability: science, practice and policy agriculture, transportation, and the covid- crisis survival of coronaviruses in water and wastewater air pollution aggravating covid- lethality? exploration in asian cities using statistical models will covid- have a lasting impact on the environment? bbc current status of global research on novel coronavirus disease (covid- ): a bibliometric analysis and knowledge mapping. ssrn, april nd building a social mandate for climate action the nexus between covid- , temperature and exchange rate in wuhan city: new findings from partial and multiple wavelet coherence smart tourism destinations: ecosystems for tourism destination competitiveness covid- virus outbreak lockdown: what impacts on household food wastage? environment covid : lets act now: the urgent need for upscaling agroecology in uganda ( ) air pollution improvement and mortality rate during covid- pandemic in india: global intersectional study the impact of covid- on water and food systems: flattening the much bigger curve ahead covid- crisis demonstrates the urgent need for urban greenspaces five lessons from covid- for advancing climate change mitigation first proof of the capability of wastewater surveillance for covid- in india through detection of genetic material of sars-cov- first detection of sars-cov- in untreated wastewaters in italy potential impacts of covid- on canadian farmland markets bat origin of a new human coronavirus: there and back again containing the spread of coronavirus disease (covid- ): meteorological factors and control strategies conserving africa's wildlife and wildlands through the covid- crisis and beyond effects of temperature variation and humidity on the death of covid- in wuhan, china. science of the total environment air quality variation in wuhan, daegu, and tokyo during the explosive outbreak of covid- and its health effects can a paper-based device trace environmental science & technology covid- and eu climate targets: can we now go further? environmental & resource economics preliminary study of sars-cov- occurrence in wastewater in the czech republic airborne transmission of sars-cov- : the world should face the reality charting a "green path" for recovery from covid- novel economical social distancing smart device for covid- (ssrn scholarly paper id ) preventing bat-born viral outbreaks in future using ecological interventions when science goes viral: the research response during three months of the covid- outbreak salud planetaria y covid- : la degradación ambiental como el origen de la pandemia actual. instituto de salud global, de abril assessing nitrogen dioxide (no ) levels as a contributing factor to coronavirus (covid- ) fatality. science of the total environment mental health and covid- impact of covid- lockdown on pm , so and no concentrations in salé city (morocco) investigating a serious challenge in the sustainable development process: analysis of confirmed cases of covid- (new type of coronavirus) through a binary classification using artificial intelligence and regression analysis temperature significantly changes covid- transmission in (sub)tropical cities of brazil data mining and analysis of scientific research data records on covid- mortality, immunity, and vaccine development-in the first wave of the covid- pandemic (ssrn scholarly paper id ) smart sanitation-biosensors as a public health tool in sanitation infrastructure covid- impact on fruit and vegetable markets covid- and the canadian cattle/beef sector: some preliminary analysis impact of weather on covid- pandemic in turkey covid- challenges to pakistan: is gis analysis useful to draw solutions? science of the total environment imprints of pandemic lockdown on subsurface water quality in the coastal industrial city of tuticorin, south india: a revival perspective increased ozone levels during the covid- lockdown: analysis for the city of rio de janeiro, brazil. the science of the total environment tourism and covid- : impacts and implications for advancing and resetting industry and research future perspectives of wastewater-based epidemiology: monitoring infectious disease spread and resistance to the community level artificial intelligence-empowered mobilization of assessments in covid- -like pandemics: a case study for early flattening of the curve converting home spaces into food gardens at the time of covid- quarantine: all the benefits of plants in this difficult and unprecedented period what is environmental studies? -day lockdown in india dramatically reduced air pollution indices in lucknow air quality development during the covid- pandemic over a medium-sized urban area in thailand sunlight ultraviolet radiation dose is negatively correlated with the percent positive of sars-cov- and four other common human coronaviruses in the u.s. science of the total environment aerosol transmission of sars-cov- ? evidence, prevention and control changes in air quality during the lockdown in barcelona (spain) one month into the sars-cov- epidemic ritmo de crecimiento diario de la producción científica sobre covid- análisis en bases de datos y repositorios en acceso abierto investigating the emerging covid- research trends in the field of business and management: a bibliometric analysis approach a preliminary assessment of the impact of covid- on environment -a case study of china natural gas from shale formation: a research profile research status of shale gas: a review covid- . global literature on coronavirus disease effects of temperature and humidity on the daily new cases and new deaths of covid- in countries association between ambient temperature and covid- infection in cities from china the -ncov epidemic control strategies and future challenges of building healthy smart cities survivability, partitioning, and recovery of enveloped viruses in untreated municipal wastewater regulating wildlife conservation and food safety to prevent human exposure to novel virus. ecosystem health and sustainability covid- and surface water quality: improved lake water quality during the lockdown. the science of the total environment drastic improvements in air quality in ecuador during the covid- outbreak air quality changes in new york city during the covid- pandemic nox emission reduction and recovery during covid- in east china this study was supported by an excellence project awarded by the junta de andalusia [ref:b-sej- -ugr ] and by a grant from the fundación ramón areces [rareces - ]. adams, m. d. ( ). air pollution in ontario, canada during the covid- state of emergency. total environment, , . anónimo ( ). trump reaviva la teoría de que el virus surgió en un laboratorio chino. la razón, key: cord- -nx m authors: trisolino, giovanni; origo, carlo enrico; de sanctis, nando; dibello, daniela; farsetti, pasquale; gigante, cosimo; guida, pasquale; marengo, lorenza; panuccio, elena; toniolo, renato maria; verdoni, fabio; memeo, antonio title: recommendations from the italian society of pediatric orthopaedics and traumatology for the management of pediatric orthopaedic patients during the covid pandemic and post-pandemic period in italy date: - - journal: ital j pediatr doi: . /s - - - sha: doc_id: cord_uid: nx m the rapid spread of the covid- outbreak in italy has dramatically impacted the national healthcare system, causing the sudden congestion of hospitals, especially in northern italy, thus imposing drastic restriction of almost all routine medical care. this exceptional adaptation of the italian national healthcare system has also been felt by non-frontline settings such as pediatric orthopaedic units, where the limitation or temporary suspension of most routine care activities met with a need to maintain continuity of care and avoid secondary issues due to the delay or suspension of the routine clinical practice. the italian society of pediatric orthopaedics and traumatology formulated general and specific recommendations to face the covid- outbreak, aiming to provide essential care for children needing orthopaedic treatments during the pandemic and early post-peak period, ensure safety of children, caregivers and healthcare providers and limit the spread of contagion. the coronavirus disease (covid- ) caused by severe acute respiratory syndrome coronavirus (sars-cov- ) was first identified in wuhan (hubei province, china) in late , rapidly spread worldwide, and, on march th, , the world health organization (who) officially declared covid- as a pandemic [ ] . in the same days, the government of italy imposed a national quarantine that locked down for about months all commercial and industrial activities (with some exceptions), school and universities, sports, cultural and leisure activities [ ] . as the contagion rate and death toll covid- related continued to decrease, on april th, the prime minister announced the so-called "phase " for the reopening and resumption of the activities scheduled for may th, . on may th, , the who reported , , confirmed cases of covid- ( , cases in italy), including , deaths ( , in italy) [ ] . so far, along with the hubei province, italy (and in particular northern italy) has had the longest period of lockdown during the covid- pandemic (almost months in northern italy). the rapid spread of the covid- outbreak has immediately caused the congestion of many hospitals, thus imposing the temporary interruption of all non-essential medical cares. this exceptional adaptation of the italian national health service was significantly evident also within non-frontline healthcare settings such as pediatric orthopaedic units, where limitation and temporary suspension of most routine care activities was necessary to reduce the risk of infection in patients, families, and healthcare providers and to reallocate healthcare personnel from routine tasks to emergency. on the other side, the limitation of healthcare services to the essential ones, along with the general reluctance among people to access care for fear of covid- exposure, led to a in increased risk and worsening of covid -unrelated diseases. in italy, an increase of death and worsening pediatric diseases due to delayed access or provision of care has been reported [ ] . therefore, a need for preventing the risk of delays in access to care is essential especially in children, in order to avoid complications due to the alteration or suspension of the typical patient care. given the profound uncertainty about the actions to be taken, on march , the advisory board of the italian society of pediatric orthopaedics and traumatology (sitop) launched an initiative to gather local experiences and epidemic risk management protocols from nine tertiary referral centers for pediatric orthopaedics and traumatology in italy concerning the covid- outbreak (fig. ) . this produced an initial emergency document that was approved on april th, , concerning the measures to be adopted during the pandemic period and a second document that was approved on may th, the present document provides general and specific recommendations for pediatric orthopaedic surgeons, who face the so-called "pandemic period" and "post-peak period". additional protocols and guidelines concerning the management of pre-pandemic and inter-pandemic periods are included into the who guidance document [ ] . the recommendations listed in this document have the following aims: . provide essential care to pediatric patients needing orthopaedic treatments during the covid- pandemic and early post-peak period; . ensure safety of children and caregivers in case of hospital admission; . ensure safety of medical staffs; . limit the spread of outbreak. these recommendations should be considered not as mandatory guidelines but rather as a support to reassure families and pediatric orthopaedic surgeons regarding the possibility to treat children safely during the pandemic and post-peak period. therefore, they can be adapted and modified depending on locally available resources and personal experience of the pediatric orthopaedic staff. we believe that they could be useful for future management of upcoming pandemics or during an eventual second wave of covid- , after that safety and effectiveness of these approaches will be analysed, using the data collected during this period. we are also confident that the experience gained across some of the main italian pediatric orthopaedic hospitals could be helpful also in other countries which are facing the pandemic at an earlier phase. separate access to triage areas, emergency, wards, outpatient clinics, operating theatres must be defined, based on suspected or confirmed infection (path a: sars-cov negative patients. path b: sars-cov positive or suspected patients). the paths must be physically separated, limiting asmuch as possible the possibility of communication between path a and path b [ ] . staff within path b must take level iii precautions and protective measures (see table ). the personnel within the path a and b should take precautions and protection measures, according to the current who guidelines [ ] (table ) . filter areas and covid- testing using nasopharyngeal swabs must be implemented for patients/caregivers scheduled for urgent/elective surgery before admission to hospital. cancel all deferrable outpatient appointments with clear notice to the patient through their phone numbers, in order to reduce the circulation of users and staff within hospital structures. regular follow-up visits should be temporarily suspended. appointments should be preserved for children requiring non postponable post-operative care (for example percutaneous k-wires removal, cast removal or renewal, medication of complicated wounds). children with recent onset and progressive exacerbation of pain or functional impairment, even in absence of trauma, should be also visited in person, in order to rule out severe diseases such as bone tumors, infections and acute rheumatic diseases (septic arthritis, osteomyelitis, juvenile arthritis) or severe developmental orthopaedic diseases (scfe, perthes disease, etc..), which may necessitate non deferrable treatments. newborns should be visited in person in agreement with neonatologist or pediatric recommendation. the interval between appointments must be prolonged, in order to avoid crowding the waiting rooms and allow disinfection of the outpatient facilities. in any case, telemedicine must be encouraged whenever possible. follow up imaging should be taken near the locality of the patient and e-mailed to the institute, only if likely to make a significant change to care [ , ] . carefully define and organize the management and priority of urgent and emergent interventions. children should be visited and treated by surgeons experienced in pediatric orthopaedics and nonoperative treatments should be encouraged and performed directly by the experienced senior surgeons. whenever feasible, use and teach parents to remove self-removable casts or splints, to reduce the follow-up requirement. when considering surgical management, the following priority protocol should be adopted: fractures or acute injuries with severe neurovascular involvement and potential risk for life, limb loss, or permanent damage. screen the patient using rapid response sars-cov tests (nasopharyngeal swab). if absent, or if surgery is required in less than - h, treat the patient as covid- -positive, until proven otherwise, in order to minimize infection spread. provide patient with ffp during transit from emergency to operation theatre. clean her/his in case of elective surgery, a strict priority must be maintained in the waiting list, especially if the duration of the pandemic period cannot be precisely estimated [ , ] . the advisory board of the sitop has provided a panel of priority levels in order to safely schedule deferrable surgical treatments, reducing the risk of missing children who require non postponable operations, during the pandemic and post peak period (see table ). this priority panel has considered several factors such as: . duration of the pandemic period and the local epidemic density; . availability and accessibility of hospitals and surgical rooms; . characteristics and severity of the pediatric orthopaedic disease; . range of age of patients, since the favourable outcomes and even the feasibility of some pediatric orthopaedic procedures (for example, closed or open reduction of severe cdh, ponseti method for severe ctev, growth modulation procedures,) are significantly impacted by age at treatment; . type of operation and surgical technique, since some procedures are at higher risk for dissemination of the infection. based on this priority panel elective surgical procedures should be categorized in four classes: table sars-cov- related personal protection management. adapted from the who guidance for rational use of personal protective equipment for covid- [ ] . ffp / = filtering facepiece particles. a the screening procedure refers to prompt identification of patients with signs and symptoms of covid- . b agp: tracheal intubation, non-invasive ventilation, tracheotomy, cardiopulmonary resuscitation, manual ventilation before intubation, bronchoscopy. c : this category includes the use of no-touch thermometers, thermal imaging cameras, and limited observation and questioning, all while maintaining a spatial distance of at least m. d : the number of visitors should be restricted. if visitors must enter a covid- patient's room, they should be provided with clear instructions about how to put on and remove ppe and about performing hand hygiene before putting on and after removing ppe; this should be supervised by a health care worker (continued) . priority a: intervention that should be performed within days from the start of the pandemic phase; . priority b intervention that could be performed within months from the start of the pandemic phase. cases belonging to this priority should carefully monitored both for age of the child and local epidemic density, in order to start treatments as much as possible close to the start of the postpeak phase . priority c: intervention that could be performed within the first months from the start of the postpeak period . priority d: intervention that can be safely performed at the end of the pandemic. healthcare providers must inform the family that only one parent/caregiver can assist the child during hospitalization. at hospital admission, both child and parent/caregiver must be mandatory screened for sars-cov . in patient care must be organized so that only one child and only one parent/caregiver per room are allowed. if the patient or parents are known or suspected to be covid -positive, the operation should be postponed until the covid tests are negative. as tests can occasionally become negative after more than month, if such delay can seriously threaten the health of the child due to the orthopaedic pathology, the surgeon must evaluate if the treatment must be anticipated and the patient can be safely managed through the path b. surgical treatments belonging to the priority class a or b should not be suspended during the pandemic period especially if the duration of this period lasts for more than two to months. the possibility to continue with high priority interventions in children should be preserved. wherever possible, depending on the local setting of healthcare services, the management of such pediatric orthopaedic conditions should be centralized in non-covid hospitals. strict surveillance of the infection should be maintained and all measures taken to ensure patient safety in the hospital (filter areas, separated paths, screening measures, protections, distancing measures) should be continued in anticipation of a possible second wave of infection. outpatient care can be progressively resumed, maintaining the distancing measures. wherever feasible, local health facilities should coordinate in order to redistribute outpatient visits, avoiding overcrowding of hospital facilities. patients should be contacted by phone and/or e-mail to confirm re-appointment. emergency and surgical care should maintain the same organization, recommendations and priority classes of the pandemic period. elective surgery can be gradually resumed, respecting the order of priority established during the pandemic phase. priority b-c surgical treatments could be prioritized close to the end of the pandemic period, depending on the local stage of outbreak, the accessibility and availability of operating rooms. when elective surgery must be scheduled in the immediate post-peak period consider to prioritize those operations, which: . require minimally invasive, arthroscopic or percutaneous techniques; . do not require post-operative intensive care unit recovery; . can be safely managed within day-surgery or with minimal in-patient care (possibly < days); . when possible, postponing at late stage of post-peak patients with comorbidities (especially cardiovascular or respiratory); . must be performed within a definite range of age (for example guided growth procedures). wherever possible we recommend using surgical techniques that significantly reduce the risk of aerosolgenerating procedures (see table ). local/regional anesthesia should be preferred to invasive airway management whenever possible for elective orthopaedic procedures of the upper and lower extremity [ ] . the covid- pandemic has dramatically impacted the health systems at a global level. the need for a rapid adaptation and response of the health providers to the pandemic has imposed the suspension of most routine healthcare services, potentially harming children who require covid unrelated care. the sitop working group has drawn up these recommendations with the aim of supporting the decisions of the pediatric orthopaedic surgeons for ensuring continuity of care in children requiring orthopaedic treatments during a pandemic. we are confident that the experience gained across the main italian pediatric orthopaedic hospitals could be helpful for other professionals involved in children's care, as well as for pediatric orthopaedic surgeons from other countries, which are facing the pandemic at an earlier phase. the sitop will also monitor, through multicenter data collection and analysis, the adherence to these recommendations and their safety and effectiveness, to estimate the impact of this coordinated initiative on the health of children with orthopaedic diseases. world health organization: rolling updates on coronavirus disease (covid ) covid- pandemic in italy delayed access or provision of care in italy resulting from fear of covid- world health organization. pandemic influenza preparedness and response. a who guidance document. geneva: world health organization surgery in covid- patients: operational directives rational use of personal protective equipment for coronavirus disease ( covid- ) and considerations during severe shortages: interim guidance recommendations for control and prevention of infections for pediatric orthopaedics during the epidemic period of covid- recommendations for the care of pediatric orthopaedic patients during the covid pandemic covid- -esska guidelines and recommendations for resuming elective surgery the sitop advisory board wishes to thank riccardo contessi for his work and support in organizing the web meetings which allowed the formulation of the recommendations contained in this article. authors' contributions gt, ceo and am conceived and wrote the manuscript. gt, ceo, nds, dd, pf, cg, pg, lm, ep, rmt, fv, am critically formulated the guidelines and recommendation included in the manuscript, edited drafts, read and approved the final manuscript. the authors did not receive funding for the present study.availability of data and materials not applicable.ethics approval and consent to participate not applicable. not applicable. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- - e kt c authors: pitt, michael b; li, su-ting terry; klein, melissa title: novel educational responses to covid- : what is here to stay? date: - - journal: acad pediatr doi: . /j.acap. . . sha: doc_id: cord_uid: e kt c nan in this issue of academic pediatrics, we feature ten innovations that highlight novel educational responses to the covid- pandemic. our recent call for educational innovations resulted in submitted manuscripts from institutions, in four countries ( % from the united states). submissions were reviewed for innovation, outcome, and sustainability after the covid- pandemic by three educational researchers blinded to author name and institution. the innovations encompassed the pediatric medical education continuum, with the majority (n= ; %) targeting residents, followed by medical students (n= ; %), fellows (n= ; %), and faculty (n= ; %). several papers (n= ; %) described approaches targeting multiple levels of learners. as expected, given the urgency to respond, many outcomes related to feasibility, participation and completion rates, and perceptions of learning. four themes emerged from submissions: ) virtual learning (n= ; %); ) telehealth/telerounding (n= ; %); ) administrative responses (n= ; %); and ) wellness (n= ; %). papers describing virtual learning included modifications to existing conferences (e.g., morning report, grand rounds, boot camp) (n= ; %), conversion of electives (n= ; %) or clerkships (n= ; %), virtual simulation (n= ; %), and approaches to equip learners to advocate for patients and populations during the covid- pandemic (n= ; %). submissions describing remote patient care via telehealth included the rapid implementation of outpatient telehealth (n= ; %), inpatient tele-rounding (n= ; %), and inpatient tele-consultation by specialists (n= ; %). administrative responses included staffing modifications or clinic management (n= ; %), development of clinical practice guidelines (n= ; %), and leveraging economies of scale via cross-institutional sharing of resources (n= ; %). submissions describing approaches to learner wellness described initiatives aimed at coming together virtually for support, with storytelling events (n= ; %) being the most common approach. while all submissions originated in response to the unique circumstance of covid- , papers selected for publication highlight modifications to pediatric education which we believe may change future educational practice. here, we highlight innovations that we think will be longlasting impact. the covid- pandemic has made the corporate world realize that not all meetings need to be in person to return to business as usual. similarly, covid- affords us an opportunity to decide which elements of medical education should continue in virtual or hybrid formats. virtual learning can overcome the barrier of travel and increase attendance. while next steps must evaluate educational outcomes associated with virtual learning, we suspect that some conferences (e.g. grand rounds) may continue to offer an easily accessible, virtual option. as medical students were barred from direct patient care, educators developed meaningful strategies to engage students. from outside medical centers, students were empowered to tackle disinformation. quadri and colleagues shared a curriculum to equip students as advocates for science at the virtual frontlines via their social media presence. reardon et al. described how students created a virtual covid- classroom to teach school-aged children age-appropriate and accurate information about the pandemic. both showcase the impact of tapping into students' experience and skill with social media to develop future pediatric advocates, more critical now, post-covid- , than ever. our ability to connect with patients virtually will undoubtedly be an enduring element of the covid- pandemic. as educators, we will need to determine the competencies necessary to provide effective care via telehealth. huffman et al. described one approach of how to teach and observe fellows providing outpatient telehealth encounters. patients, institutions, accrediting bodies, and insurance providers have rapidly adopted telehealth, providing future opportunities to evaluate care provision, supervision, and outcome comparison. while inpatient tele-rounding was developed to minimize personal protective equipment usage, a critical, but short-term necessity, this innovation has accelerated incorporation of teleconsultation, which may be useful for smaller programs to provide subspecialty advice when a specialist is not locally available. in addition, as roger and colleagues describe, the ability to conference in family members who are not available during inpatient rounds may serve as a key strategy to keep families at the center of family-centered rounds. covid- presented unprecedented challenges, requiring educational innovations to ensure trainees continue to learn to provide high-quality, evidence-based care, advocate for patients and populations, and maintain wellness. we believe the papers featured in this issue highlight innovative educational responses to the covid- pandemic and serve as a foundation for shaping future medical education. next steps will need to include expanded evaluation to determine which innovations have greatest effectiveness necessitating their continuation. work from home is here to stay: the future of jobs after the pandemic is a blurry mix of work, life, pajamas, and zoom virtual cafes: an innovative way for rapidly disseminating educational best practices and building community during covid- popcorn one-pagers: educational materials for pediatric providers caring for adults megaflip primary care mock codes during a pandemic: interprofessional team-based emergency education while maintaining social distance remote assessment of clinical skills during covid- :a virtual, high-stakes, summative pediatric osce do no harm: lessons learned from a storytelling event for pediatric residents during the covid- pandemic deploying medical students to combat misinformation during the covid- pandemic medical student development of k- educational resources during the covid- pandemic tele-training and telehealth. acad pediatr patient and family centered (tele)rounds: the use of video conferencing to maintain family and resident involvement in rounds we want to thank the panel of reviewers (maneesh batra, rebecca blankenburg, caroline paul, pattie quigley, michael ryan, daniel schumacher, and teri turner) who generously gave their time to review the blinded submissions. we appreciate the extent of educational innovations occurring in so many settings and all of the authors that took the time to submit their work. key: cord- -ezp mery authors: china, anne; simona, gregory l.; anthamattena, peter; kelseya, katharine c.; crawforda, benjamin r.; weavera, amanda j. title: pandemics and the future of human-landscape interactions date: - - journal: nan doi: . /j.ancene. . sha: doc_id: cord_uid: ezp mery pandemics have accelerated in frequency in recent decades, with covid- the latest to join the list. emerging in late in wuhan, china, the virus has spread quickly through the world, affecting billions of people through quarantine, and at the same time claiming more than , lives worldwide. while early reflections from the academic community have tended to target the microbiology, medicine, and animal science communities, this article articulates a viewpoint from a perspective of human interactions with earth systems. we highlight the link between rising pandemics and accelerating global human impacts on earth, thereby suggesting that pandemics may be an emerging element of the “anthropocene.” examples from denver, colorado, usa, show how policy responses to the covid- pandemic changed human-environment interactions and created anomalous landscapes at the local scale in relation to the quality of air and patterns of acquiring and consuming food. in recognizing the significance of novel infectious diseases as part of understanding human-landscape interactions in the anthropocene, as well as the multi-scale interconnectedness between environment and health, this viewpoint converges toward an urgent need for new paradigms for research and teaching. the program required extends well beyond the already broad interdisciplinary scholarship essential for addressing human-landscape interactions, by integrating the work of health scientists, disease specialists, immunologists, virologists, veterinarians, behavioral scientists, and health policy experts. the covid- pandemic originated in wuhan, china, in late and spread quickly through the rest of the world. by late august , the virus is responsible for nearly million known cases and has claimed over , lives globally (johns hopkins university, ) . the pandemic has affected billions more people through shuttered economic activity and widespread quarantine. the all-encompassing nature of the covid- pandemic has prompted much reflection (e.g., chin et al., ) , as scholars gather their thoughts to decipher lessons for the future. many such articles focus on the microbiology, medicine, and animal science communities (e.g., bonilla-aldana et al., ; frutos et al., ) . this contribution articulates a viewpoint from a perspective of human interactions with earth systems, targeting an interdisciplinary community of human-environment scholars. as humanity is at a crossroads, with a pandemic raging amidst unprecedented environmental change, the current situation offers opportunity to gain clarity about human-landscape interactions at the origin of pandemics, as well as their effects and possible human responses and adaptations. below, we first examine the trend of rising pandemics against the backdrop of the global-scale emergence of the "anthropocene," an era of ever intensifying human interactions with earth systems, which poses risks for increasingly frequent global-scale pandemics. next, we present two examples from the city of denver, colorado (usa), showing how policy responses to the spread of the virus triggered exchanges that altered human-environment interactions and created emergent new landscapes-in relation to the quality of air and ways of obtaining and eating foods-with implications for managing the effects of pandemics at a local scale. lastly, we highlight the significance of an anthropocene lens in going forward from the covid- pandemic, linking the origin and effects of pandemics across scales. such a perspective leads toward an urgent need for broader collaborations than ever before in a new paradigm for research and teaching. parasitic organisms have afflicted human beings throughout history. the establishment of networks of villages and towns, in particular, provided conditions to sustain a variety of pathogenic lifeforms (dobson and carper, ) . the earliest communicable diseases included measles, smallpox, rubella, typhoid, dysentery, and influenza. we are familiar with these diseases because, over time, with continual exposure to their outbreaks, human societies develop resistance and achieve herd immunity, controlling outbreaks well enough to prevent transition into pandemics. when people have no immunological resistance to new pathogens, however, novel emerging infectious diseases (eid) can devastate human health on a global scale. the exponential trend in increasing frequency of pandemics since the mid- th century is eerily similar to other trends that signify accelerating human impacts on earth (fig. ) . what is now known as the "great acceleration" documents a sharply rising intensity of human activity since about (steffen et al., ) . the many socio-economic indicators documenting the accelerating human imprint include urban and ex-urban populations, economic development, transportation, energy use, and international tourism. at the same time, the growing human impacts on the structure and functioning of the earth system during the same period are apparent in many key metrics. they include the loss of tropical forests, terrestrial biosphere degradation, increases in domesticated lands, ocean acidification, and increased emissions of greenhouse gases. the scale and pace of these human-induced changes on earth are so vast and comprehensive that they are among the basis for a proposed new epoch in earth's history, the anthropocene (waters et al., ) , with the great acceleration period a possible beginning (zalasiewicz et al., ) . a careful look at pandemics during the time of the great acceleration indicates that pandemics are also apparently an element of the "anthropocene." the concurrent trend of accelerating pandemics and anthropogenic change on earth is perhaps not surprising, given what is known about the origin of such diseases and their subsequent spread (supplemental table ). nearly all novel eids originate in animal populations. a "spillover event" occurs when a zoonotic infection passes to human populations. hiv/aids in the s had simian origins, for example, and transferred to humans through the bushmeat trade in africa (sharp and hahn, ) . covid- likely originated in bats (zhou et al., ) , with pangolins as a possible intermediate host and reservoir . the risks that a spillover event transforms into a pandemic increases with accelerated contact between human and animals. deforestation and agricultural intensification are key activities through which people encroach into wildlife habitats and increase risks of disease transmission (chaves et al., ) . agricultural development and urbanization also simplify ecosystems by changing habitats, often leading to a loss in predator species and enabling disease-carrying reservoirs and vector species to thrive (keesing et al., ) . processes such as rapid urban growth create new habitats j o u r n a l p r e -p r o o f for attracting a range of species (e.g., bats, mice) that are common origins and hosts of infectious diseases (afelt et al., ) . further, the processes of globalization through trade and travel can quickly turn outbreaks into pandemics (saunders-hastings and krewski, ) , though pathogens disproportionately impact underprivileged communities less connected to these global transactions (dorn et al., ) . the relation between the origin of eids and anthropogenic environmental change is quantifiable at a global scale. allen et al. ( ) empirically linked the occurrences of zoonotic diseases and many indicators representing human activity interacting with environment, including human population, proportional cover and change of pasture and cropland area, and change in urban cover extent. these quantitative results are particularly important because the anthropocene is characterized by the acceleration of many of these same human interactions with the earth system ( fig. ). the results also provide compelling evidence that the association between the accelerating rate of pandemics and the key metrics of the anthropocene is not by chance. current data indicate that these interactions are still intensifying. some of the greatest rates of loss of tropical forests, for example, have occurred within the last few decades, driven by agricultural expansion (curtis et al., ) . these trends suggest that the human-environmental processes responsible for the anthropocene will continue to be significant for the health of humans and animals globally into the future. bramanti et al., ; kempińska-mirosławska and woźniak-kosek, ; kilbourne, ; snowden, ; (b) percent loss of tropical rainforest relative to (after steffen et al., ) ; (c) urban population (data for and from klein-goldewijk et al., ; data for from united nations, ; (d) atmospheric carbon dioxide (co ) (historical data from co -earth, ; data since data since from noaa, . though the origins of pandemics are rooted in global-scale human impacts on environment, i.e., the anthropocene, the covid- case shows how their riveting effects can also alter humanlandscape interactions locally, with consequent cross-scale feedbacks. historically, one can look to the bubonic plague in europe in the sixth century and the smallpox epidemic/pandemic (particularly in the americas) between and ad for examples of such human-landscape interactions. according to ruddiman ( ) , the dramatic declines in human population following the pandemics may have caused a drop in atmospheric co concentrationsthrough abandonment of farms and decrease in deforestation. this reduction in co may have been large enough to cool global temperature by up to . o c. so far, the current covid- pandemic has not resulted in changes of this magnitude, but it nevertheless offers examples of how pandemics can contribute to the increasingly complex and altered human-landscape systems that characterize the anthropocene (harden et al., ) . from denver, colorado, we outline two examples of ways in which the response to the covid- pandemic has already produced, even if temporarily, anomalous humanenvironmental outcomes. as a representative growing city (with a population nearly million) in the usa, located in the eastern foothills of the rocky mountains, the human-environmental responses documented in denver enable broader generalizations that coincide with growing observations reported elsewhere. although these closures disrupted society and economy, with consequences that included loss of j o u r n a l p r e -p r o o f employment, these policy responses also triggered interacting effects and feedbacks between people and environment, giving unique circumstances for observing changing human-environmental interactions. we focus on two examples that arose from the same circumstances: policy responses to the impacts of the covid- virus that significantly limited movement and altered human behavior in the region. in early march, data show that people began to alter their daily routines to travel less (streetlight data, ) . the stay-at-home order, however, daily lives changed drastically-including work patterns, employment habits, modes of teaching and learning, and social and recreational activities. the end result was an abrupt and dramatic drop in mobility in denver county (fig. a) . whereas denver has historically struggled with poor air quality (e.g., flocke et al., ) , the widespread reduction in human activity during the "stay at home" period led to noticeable improvements. during this period, concentrations of the pollutants sulfur dioxide (so ), carbon monoxide (co), nitrogen dioxide (no ) and airborne particulate matter (pm) were to % lower than values for the same dates during and (not controlling for variable year-to-year weather conditions) (fig. b) . the only measured component of air quality that did not improve was ozone (o ) concentration. consistent with other cities (e.g. sharma et al., ; nakada et al., ) , this lack of change is likely attributable to sources un-related to human activity, such as interannual variability in local weather conditions, reduction of nocturnal ozone chemical decomposition (jhun et al., ) , or natural gas extraction outside denver. improvements in denver's air quality during april brought pollution below the national ambient air quality standards of the u.s. environmental protection agency (fig. c) . the data from denver are representative of trends documented in cities worldwide after installation of pandemic-related social controls. examples of dramatic improvements in air quality and visibility have come from urban areas in india (- % pm . , sharma et al, ) , china (- % no , adams and johnson, ), brazil (- % no , nakada et al., ) , and europe (- % no , baldasano, ) . in the usa, urban counties experienced a % reduction in no on average, as well as declines in pm . (pm with diameter < . µm; berman and ebisu, ). worldwide decreased mobility had also reduced daily co emissions by - % globally in early april (le quéré et al., ) . in this way, denver's improvement in air quality represents a broader anomalous landscape of clean air, generated as a byproduct of the pandemic response, conceivably akin to novel ecosystems in the anthropocene (morse et al., ) . while it was the declining health of individuals that prompted the policy measures of quarantine, the resulting improvements in air quality nevertheless may return health benefits. although this analysis did not quantify human health, the benefits of good air quality are well documented. both short-and long-term exposure to pm . , o , and especially no are known to contribute to asthma (anenberg et al., ) . in china, a % decrease in pm (pm with diameter < µm) concentrations during the beijing olympic games correlated with an % reduction in mortality (he et al., ) . fine pm is the leading risk factor for disease worldwide and contributes to . million premature deaths annually (brauer et al. ) . the rippling effects of the pandemic, therefore, had unintended consequences of creating an anomalous landscape of clean air, while providing a glimpse of a positive human-environmental trajectory. denver's "stay-at-home" period ( march - may ) . (a) data representing vehicular travel relative to a reference period of january (streetlight data, ) quality standards (epa, ). the policy response of the stay-at-home order in denver also changed peoples' activities abruptly with respect to acquiring, cooking, and eating foods. the closure of restaurants required people to prepare and eat meals at home, leading denver residents to purchase large quantities of j o u r n a l p r e -p r o o f groceries. this behavior, in turn, led to a shortage in grocery supplies in supermarkets, particularly meats, eggs, and vegetables. consequently, demand for locally produced foods skyrocketed around the greater denver area (fig. a) . what drove denver's increased demand for local foods differs from typical factors influencing demand. changing demographics (zepeda and li, ) and cultural norms (kumar and smith, ) , greater affluence (holt-gimeenez and wang, ) , and changing supplies and marketing (blake et al., ) commonly drive demand for local food. the agricultural response during the "special period" in cuba, however, gives a close analogy to the pandemic context in denver (díaz-briquets and pérez-lópez, ) . when the dissolution of the soviet union stopped both food imports and chemical inputs required for cuba's industrialized sugar exports, the country moved suddenly to local and more sustainable production. similar to the case with air quality (section . ), the societal changes exhibited in the shifting local food scene altered human-environment interactions and created unintended and anomalous conditions in denver. with a heightened need to cook at home, along with a shortage of groceries in stores, growing food in backyards has become popular, turning them into "edible landscapes" (fig. b ). people also bought more baby chicks to raise for egg production, so that chicks in backyards and home garages have also become a common landscape feature in denver during the covid- pandemic. though sample sizes are small, the sharp increase in sales and demand for agricultural products within nurseries and home improvement stores illustrates the surge in local domestic farming activities (fig. a) . changes in the supply and demand in food during the covid- pandemic are not isolated to denver (hobbs, ) . a recent study in wales, for example, revealed a significant growth in demand for fruits and vegetables immediately following the onset of the pandemic (pitt et al., ) . to ensure future resilience in the urban food system around the world, experts from diverse regions have suggested greater allocation of resources for urban agriculture (pulighe and lupia, ) , home gardening (lal, ) , and local food networks (kolodinsky et al., ) . this recent engagement in eating locally, making food at home, or engaging in "personal" agriculture (e.g., gardening, raising backyard chickens) has implications for long-term humanenvironmental sustainability. generally speaking, producing and eating local foods promotes a shorter and more resilient supply chain (reisch et al., ) and more environmentally sustainable practices and community-based distribution methods (e.g., farmer's markets, local restaurant sales) (fig. b; halweil, ) , and increases the likelihood of eating fresh healthy foods (kortwright and j o u r n a l p r e -p r o o f wakefield, ) . local food production also avoids many risks that industrialized agriculture poses for the emergence of novel infectious disease, including "rendering" animal waste products into livestock feed (walters, ) and use of antibiotics (khachatourians, ). yet, local food production also bring additional ripple effects at both broad and fine scales that are not well understood. these potential effects include increases in prices for certain food staples (de paulo farias and araujo, ) , soil and water contamination due to home gardening (lal, ) , the spread of pathogens (davis and kendall, ) , and inadequate access to those without available resources (bublitz et al., ) . the fact that pandemics-in part through our policy responses-also alter the relationship between people and environment, with ripple effects still poorly understood and even unknown. the complex and changing interactions are creating emergent landscapes that may be analogous to novel ecosystems of the anthropocene. as such, pandemics may be a currently under-recognized and emergent facet of the "anthropocene." such realization suggests that the work of human-environment scholars is as consequential and urgent as ever. addressing the roots of pandemics requires clarifying the complexities of humanlandscape interactions and making their global-scale management a high priority. controlling the effects of novel infectious diseases also requires revealing their rippling impacts and feedbacks, and understanding human-environment interactions at local scales. additionally, covid- has illuminated the tight, rapid, and far-reaching pathways connecting the broad-scale origin and local-scale responses that affect social wellbeing. this connectedness contrasts with other global-scale human-environmental crises, such as climate change, that operate across decades or even centuries. the onehealth perspective promoted by the world health organization, in fact, advocates such a view of interconnectedness of health, people, animals, and environment with respect to pandemics (bonilla-aldana et al., ). as difficult as some of the impacts are, we suggest that the covid- pandemic offers a "teachable moment" to broadly communicate just how closely the drivers and impacts of environmental health relate to human health. finally, the lessons derived from a perspective of human-landscape interactions point toward an urgent need to develop new paradigms for research and teaching. building upon the recognition of the importance of environment in addressing zoonotic diseases, an outstanding need remains to explicitly integrate a predictive understanding of human-landscape dynamics with the emergence and spread of diseases. we suggest that new scientific questions, theories and frameworks are needed to merge these critical strands within an anthropocene context, as well as to address the complex rippling effects. new "anthropocenic" methods and approaches, too, will be necessary to bridge the cross-scale responses and feedbacks involved. the program required extends well beyond the already broadly interdisciplinary science essential for addressing human-landscape interactions in the anthropocene (harden et al., ) , because it must integrate the work of health scientists, disease specialists, immunologists, virologists, veterinarians, behavioral scientists, and health policy experts. though challenging, such collaborations could stimulate powerful support for policies driving more sustainable human-environmental interactions in the future, with the aim of j o u r n a l p r e -p r o o f flattening the upward trajectory of both pandemics and underlying processes that have led to an anthropocene. the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. satellite observed tropospheric no concentration decreased over east asia in early bats, coronaviruses, and deforestation: toward the emergence of infectious diseases? frontiers microbiology global hotspots and correlates of emerging zoonotic diseases estimates of the global burden of ambient pm . , ozone, and no on asthma incidence and emergency room visits covid- lockdown effects on air quality by no in the cities of barcelona and madrid (spain) changes in us air pollution during the covid- pandemic buying local food: shopping practices, place, and consumption networks in defining food as "local revisiting the one health approach in the context of covid- : a look into the ecology of this emerging disease. advances in animal and veterinary sciences the third plague pandemic in europe ambient air pollution exposure estimation for the global burden of disease pandemic reveals vulnerabilities in food access: confronting hunger amidst a crisis global consumption and international trade in deforestation-associated commodities could influence malaria risk anthropocene in an age of pandemics co -earth, . historical co datasets cases of covid- in colorado by date reported to the state classifying drivers of global forest loss preventing e. coli from garden to plate will covid- affect food supply in distribution centers of brazilian regions affected by the pandemic? annual proceedings of the association for the study of the cuban economy infectious diseases and human population history -throughout history the establishment of disease has been a side effect of the growth of civilization covid- exacerbating inequalities in the us national ambient air quality standards air quality in the northern colorado front range metro area: the front range air pollution and photochemistry Éxperiment (frappÉ) covid- : the conjunction of events leading to the pandemic and lessons to learn for future threats home grown: the case for local food in a global market understanding humanlandscape interactions in the "anthropocene the effect of air pollution on mortality in china: evidence from the beijing olympic games food supply chains during the covid- pandemic reform or transformation? the pivotal role of food justice in the us food movement. race/ethnicity: multidisciplinary global contexts the impact of nitrogen oxides concentration decreases on ozone trends in the usa global trends in emerging infectious diseases impacts of biodiversity on the emergence and transmission of infectious diseases the influenza epidemic of - in selected european cities--a picture based on the reports of two poznań daily newspapers from the second half of the nineteenth century agricultural use of antibiotics and the evolution and transfer of antibiotic resistant bacteria influenza pandemics of the th century long-term dynamic modeling of global population and built-up area in a spatially explicit way: hyde . . holocene food systems disruptions: turning a threat into an opportunity for local food systems edible backyards: a qualitative study of household food growing and its contributions to food security understanding local food consumers: theory of planned behavior and segmentation approach home gardening and urban agriculture for advancing food and nutritional security in response to the covid- pandemic. food security. temporary reduction in daily global co emissions during the covid- forced confinement novel ecosystems in the anthropocene: a revision of the novel ecosystem concept for practical applications covid- pandemic: impacts on the air quality during the partial lockdown in são paulo state, brazil. science of the total environment national oceanic and atmospheric administration (noaa), . global monitoring laboratory trends in atmospheric carbon dioxide report from the "c horticulture summit: results from edible producers in wales food first: covid- outbreak and cities lockdown a booster for a wider vision on urban agriculture sustainable food consumption: an overview of contemporary issues and policies. sustainability: science, practice and policy plows, plagues, and petroleum: how humans took control of climate reviewing the history of pandemic influenza: understanding patterns of emergence and transmission effect of restricted emissions during covid- on air quality in india origins of hiv and the aids pandemic. cold spring harbor perspectives in medicine emerging and reemerging diseases: a historical perspective the trajectory of the anthropocene: the great acceleration covid- vmt monitor seven modern plagues: and how we are causing them the anthropocene is functionally and stratigraphically distinct from the holocene the working group on the anthropocene: summary of evidence and interim recommendations who buys local food probable pangolin origin of sars-cov- associated with the covid- outbreak a pneumonia outbreak associated with a new coronavirus of probable bat origin key: cord- - gqn z authors: watkins, rochelle e; cooke, feonagh c; donovan, robert j; macintyre, c raina; itzwerth, ralf; plant, aileen j title: influenza pandemic preparedness: motivation for protection among small and medium businesses in australia date: - - journal: bmc public health doi: . / - - - sha: doc_id: cord_uid: gqn z background: community-wide preparedness for pandemic influenza is an issue that has featured prominently in the recent news media, and is currently a priority for health authorities in many countries. the small and medium business sector is a major provider of private sector employment in australia, yet we have little information about the preparedness of this sector for pandemic influenza. this study aimed to investigate the association between individual perceptions and preparedness for pandemic influenza among small and medium business owners and managers. methods: semi-structured face-to-face interviews were conducted with small and medium business owners or managers in new south wales and western australia. eligible small or medium businesses were defined as those that had less than employees. binomial logistic regression analysis was used to identify the predictors of having considered the impact of, having a plan for, and needing help to prepare for pandemic influenza. results: approximately per cent of participants reported that their business had a plan for pandemic influenza, per cent reported that they had not thought at all about the impact of pandemic influenza on their business, and over per cent stated that they required help to prepare for a pandemic. beliefs about the severity of pandemic influenza and the ability to respond were significant independent predictors of having a plan for pandemic influenza, and the perception of the risk of pandemic influenza was the most important predictor of both having considered the impact of, and needing help to prepare for a pandemic. conclusion: our findings suggest that small and medium businesses in australia are not currently well prepared for pandemic influenza. we found that beliefs about the risk, severity, and the ability to respond effectively to the threat of pandemic influenza are important predictors of preparedness. campaigns targeting small and medium businesses should emphasise the severity of the consequences to their businesses if a pandemic were to occur, and, at the same time, reassure them that there are effective strategies capable of being implemented by small and medium businesses to deal with a pandemic. since late the risk of pandemic influenza and the need for preparedness have featured reasonably frequently in the news media in australia, often associated with overseas reports of large outbreaks of infection among birds or small clusters of infection among humans. strategic plans have been prepared for an outbreak of pandemic influenza associated with human avian influenza infection at national and global levels [ , ] . many of these plans include mechanisms to facilitate and manage community-wide responses in recognition of the likelihood that pandemic response requirements will exceed the response capacity of health authorities and governments. preparation by the business community for an influenza pandemic is encouraged by governments, but much of the onus is on businesses to inform themselves about the threat posed by pandemic influenza and develop their own plans. as such, large corporations often have detailed plans, but less is known about pandemic preparedness in small and medium sized businesses. small and medium businesses are a major employer in australia, accounting for approximately half of all private sector employees [ ] . small businesses, which include businesses with less than employees, were alone estimated to employ almost . million people in australia in [ ] . pandemic influenza is likely to have a major impact on businesses, yet little is known about the needs and preparedness of small and medium sized businesses. government and health authorities in australia and overseas have recommended that businesses, community organisations and individuals implement a range of strategies to prepare for pandemic influenza, and an increasing number of resources are being produced to provide guidance on pandemic preparedness and business continuity planning [ ] [ ] [ ] [ ] . a resource specific to pandemic preparedness planning among small businesses in australia is also available [ ] . pandemic planning resources generally describe the nature of the anticipated threat, highlight the role of government and health authorities, outline essential business continuity planning and response requirements, and describe specific measures that may be implemented to limit or prevent disease spread. specific strategies recommended to limit disease spread within the workplace include promoting improved hygiene and infection control practices, using social distancing measures and flexible work arrangements to minimise contact between individuals within the workplace and the community, using personal protective equipment, restricting workplace entry and isolating individuals who may be infectious [ ] . a greater understanding of the factors associated with planning for pandemic influenza among small and medium businesses is required to inform communication strategies that promote improved preparedness for a pandemic. protection motivation theory [ ] is a commonly used framework for fear-appeal research [ ] . protection motivation theory conceptualises an individual's acceptance of advice on how to protect themselves from a health threat as primarily a function of four specific beliefs: the perceived severity or seriousness of the threat and the likelihood of the threat occurring (which together constitute 'threat appraisal'); and the perceived effectiveness of actions to avoid the threat and the individual's perceived self-capacity to implement those actions (which together constitute 'coping appraisal'). if a sufficient level of threat is perceived to exist, and coping appraisal is high, then the individual will take appropriate action. however, where a threat appraisal is high but coping appraisal is low, the individual is unlikely to take appropriate action. protection motivation theory suggests that campaigns using threats must include information about how to avert the threat, and ensure that members of the target audience have the skills and resources necessary to adopt the recommended actions. investigations of the effectiveness of health threat communications are supportive of the protection motivation theory framework [ ] , finding that communication effectiveness is associated with the extent to which the communications present real but controllable threats [ ] . the health belief model [ , ] also conceptualises behaviour as dependent upon individual perceptions including the perceived likelihood and severity of the potential health threat, and the perceived effectiveness of responses to the threat. similarly, research has supported the importance of health belief model constructs in behaviour change [ ] , particularly where illness avoidance and perceived threat are of central importance [ , ] . among health behaviour theories that identify similar constructs as important determinants of health behaviour, current research provides no clear indication of the superiority of any single approach [ ] . guided by the concepts considered to be of importance in these health behaviour theories, and the protection motivation theory framework in particular, we aimed to investigate the association between selected beliefs and preparedness for pandemic influenza among small and medium business owners and managers. between may and july , structured face-to-face interviews were conducted with either the owners or managers of small or medium businesses in australia. eligible businesses were defined as businesses which have less than employees [ ] . participating businesses were recruited from new south wales ( ) and western australia ( ), with approximately per cent of the sample in each state being selected from businesses located in the capital cities (n = ), per cent being recruited from large satellite cities (n = ), and the remaining per cent from rural centres (n = ). participating businesses in western australia were randomly sampled from a membership database of businesses obtained from the local chambers of commerce and industry. in new south wales businesses were randomly sampled from a purchased list of businesses stratified by industry type. in both instances the lists of businesses were checked to ensure that the sampling frames included only businesses which operated in the eligible study areas prior to recruitment. a flow chart was used to guide the recruitment of interviewees in both states to ensure recruitment processes were standardised, including gaining confirmation that the business had less than employees, ensuring that a minimum of three attempts were made to establish contact with each business to be recruited, and ensuring that an appropriate person was interviewed. face to face interviews with business owners or senior managers were administered by trained interviewers from a market research firm in new south wales, and by trained interviewers contracted by the local chambers of commerce and industry in western australia. prior to the study interview verbal consent to participate was obtained following the provision of, and discussion of, a study information sheet. study procedures were approved by the human research ethics committee of curtin university of technology. focus group discussions with business owners and managers in perth and sydney were used to inform and develop the structured interview schedule. the interview schedule was pre-tested among a small sample of business owners to ensure the questions were acceptable, understandable, unambiguous, and that open ended questions elicited the expected type of response. basic characteristics of the participating businesses assessed included the job classification of the interviewee (owner, chief executive officer/managing director, senior manager), main business location (capital city, satellite city, rural centre), industry type, business size (number of employees), average number of customers per day, and the educational level of employees (proportion of employees who attended university). the response categories for industry type were pre-coded based on the divisions in the australian and new zealand standard industrial classification [ ] . for analysis purposes, businesses operating in the primary and secondary industry sectors (i.e., businesses engaged in production and manufacturing) were aggregated; and classifications for tertiary industry businesses (i.e., businesses operating within the service sector) were aggregated according to the following three industry type categories: property and business services; retail trade; and other tertiary. the following beliefs about pandemic influenza were each assessed by a single question: the perceived severity of the threat; the risk of the threat; and the ability to respond effectively to the threat. the general belief about the severity of the threat was operationalised as the perceived proportion of people that could become sick if pandemic influenza were to affect the local community. the perceived risk of the threat was operationalised as the likelihood that pandemic influenza would become a significant health issue in australia in the near future, and assessed on a four point scale (very unlikely, unlikely, likely, very likely). an additional business-specific indicator of risk, the perceived level of risk that pandemic influenza poses to the interviewee's business, was also rated on a four-point scale (no risk, some risk, moderate risk, high risk). a dichotomous indicator of coping appraisal was derived from the open-ended question: "can you think of any steps you can take to protect your business from pandemic influenza?" responses were independently reviewed by two coders, and participants who were unable to identify any potentially useful steps that could be taken to protect their business or limit disease spread were classified as having low coping appraisal. a small proportion of participants nominated the responses 'don't know' and 'no idea' to represent their beliefs about the risk and severity of pandemic influenza (table ) . when dichotomous indicators of risk and severity were used in the analysis, these responses were aggregated with the other low risk or low severity responses for analysis purposes on the basis that these responses indicated an absence of perceptions of high risk or high severity. this coding did not significantly affect the findings of the analysis. three dependent variables in the analysis provide different indicators of engagement in adaptive processes associated with the threat of pandemic influenza. participants were asked "before being contacted about this study, how much have you thought about the impact of pandemic influenza on your business?" (not at all, a little, a lot). the need for help with planning for pandemic influenza, which can be considered an indicator of an adaptive response to the threat of pandemic influenza, was assessed using the following open-ended question: "is there anything you need to help you prepare for pandemic influenza?" responses were dichotomised into a variable which indicated whether help was or was not required. lastly, the presence of a plan for pandemic influenza was assessed by the single question "has your business made any specific plans should pandemic influenza arise?" (yes, no, unsure). the chi-square test of independence was used to test for associations between categorical study variables, and the independent samples t-test was used to test for differences between groups on continuous variables. phi, which is a measure based on the chi-square test of association, is used to assess the strength of association between two dichotomous variables, and indicates the amount of total variance explained by the association between the variables. binomial logistic regression analysis was used to identify the significant independent predictors of the health behaviour theory-based belief variables and the three main dependent variables: having considered the impact of, hav- ing a plan for, and needing help to prepare for pandemic influenza. dependent variables were dichotomised for analysis due to skewed distributions and the small sample size. initial model development included entry of variables into a forward stepwise model, with the probability criterion for entry set at . and exit at . . the final models were developed manually to allow exploration of alternative model forms. a main effects model was initially determined. effect modification was also explored, and the inclusion of interactions was determined by the significance of the change in log likelihood of the model. crude odds ratios (cor), adjusted odds ratios (aor) adjusted for the other variables in each model, and % confidence intervals ( %ci) are used to summarise the magnitude of association found between variables. all analyses were performed using spss version . (spss inc., ) and the significance level was set at p ≤ . . in total, eligible businesses were contacted and interviews were completed, producing an overall response rate of per cent. the response rate of per cent ( / ) for new south wales (nsw) was considerably lower than the per cent ( / ) achieved for western australia (wa), but consistent with the different sampling methods used. there was no significant difference between participating and non-participating businesses in wa according to business size (p = . ) or industry type (p = . ). similar data on the characteristics of non-participating businesses in nsw were not available for analysis. nonparticipation was most frequently associated with the business owner or manager being either too busy or unavailable during the interview period, explaining per cent and per cent of refusals in the wa and nsw samples respectively. the characteristics of participating businesses are summarized in tables and by state. most participating busi-nesses had less than employees and more than half of the individuals interviewed were business owners. business owners were significantly more likely to be interviewed in wa than nsw ( table ) . most of the participating businesses operated within the tertiary or service sector. the representation of businesses from different industry types was significantly different by state, with the wa sample having a higher proportion of retailers (table ) and reporting a significantly lower proportion of university educated staff compared with the nsw sample (table ) . approximately per cent of participants believed that pandemic influenza was likely or very likely to become a significant health issue in australia in the near future (table ) , and, on average, participants believed per cent of people in affected communities would become sick ( table ). around per cent of participants reported that they had not spent any time thinking about the impact of pandemic influenza on their business, and over per cent could not identify any steps that they could take to protect their business (table ). only per cent of participants reported having a pandemic influenza plan for their business ( per cent were unsure), and over per cent of participants reported needing help to prepare for pandemic influenza (table ) . beliefs about the risk and severity of pandemic influenza and the amount of time spent considering the impact of pandemic influenza on the business did not differ significantly between states. beliefs about being able to respond to the threat and perceptions about the need for help did differ between states, with businesses in wa having a significantly lower level of response efficacy and being less likely to need help to prepare than businesses in nsw (table ) . businesses in nsw were also significantly more likely to have a plan for pandemic influenza than businesses in wa (table ) ; however, the difference in response rate for the two states renders the generalisability of such differences as tenuous. beliefs about the perceived severity of pandemic influenza and the perceived risk of pandemic influenza to the business were not significantly associated with any business characteristics. business characteristics which were significant predictors of beliefs about the perceived risk of pandemic influenza and coping appraisal are summarized in table . the perceived risk of apandemic in australia was significantly associated with the role of the person interviewed, with non-owners being about twice as likely to consider pandemic influenza as a likely or very likely risk than business owners. both state and the role of the individual interviewed were significantly associated with response efficacy, with businesses in nsw and non-owners being about twice as likely to be able to identify actions which could protect their business in the event of a pandemic than businesses in wa and owners. each of the significant predictors of beliefs identified only explained a small proportion (less than per cent) of the overall variance associated with the belief variables. bivariate associations between beliefs and the dependent variables (table ) indicate that almost all beliefs and dependent variables assessed were significantly associated. the high correlation between the general belief about the risk of pandemic influenza and the specific belief about the risk of pandemic influenza to the business, which explained over per cent of the total variance in responses (equivalent to a pearson correlation coefficient of approximately . ), was among the strongest associations found. there was no significant association between having a plan and the need for help, and coping appraisal was independent of perceptions of severity. logistic regression models were used to determine the significant independent predictors of having considered the impact of, having a plan for, and needing help to prepare for a pandemic. all models were tested for interaction terms and no significant effect modification was found. the significant independent predictors of dependent variables, based on the inclusion of both belief variables and business characteristics, are summarised in table . thinking a lot (versus a little or not at all) about the impact of pandemic influenza on the business was most strongly associated with the perceived risk of pandemic influenza, with participants who perceived a pandemic as likely or very likely to be a health issue in australia in the near future being approximately times more likely to have reported thinking a lot about the impact of a pandemic on their business. businesses that were located in the capital city were about three times more likely to have spent a lot of time thinking about the impact of a pandemic compared with businesses in satellite city or rural locations. these same factors were also significant predictors of having considered the impact of a pandemic on the business when this variable was dichotomised as thought at all (a little or a lot) versus not at all. the perceived need for help was most strongly associated with the perceived risk of pandemic influenza to the business, with participants who perceived the risk of a pandemic to the business as moderate or high being approximately times more likely to report needing help to prepare. state was a significant independent predictor of the perceived need for help, with businesses in nsw more likely to report needing help than those in wa. the perceived need for help was also significantly associated with industry type, with businesses in the property and business services and retail trade sectors being significantly less likely to need help than other service sector businesses. industry type was not significantly associated with perceptions about the risk or severity of a pandemic, but was significantly associated with coping appraisal (χ = . , p = . ), with per cent of retailers unable to think of steps to protect their business as opposed to per cent of other service sector businesses and per cent of production and manufacturing businesses. the presence of a specific plan for pandemic influenza was significantly and independently associated with both perceived severity of a pandemic and coping appraisal. participants who believed that per cent or more of the local community would become sick were over times more likely to have a plan, and participants who were able to identify steps that could be taken to protect their business were over times more likely to have a plan for pandemic influenza. there is a lack of empirical data to inform public health response strategies for pandemic influenza. to our knowledge this study provides the first systematically collected information on preparedness among small and medium businesses in australia, and is among only a few studies in the field worldwide. we found that only a small proportion of businesses studied had thought a lot about how pandemic influenza may impact on their business, that few had made any specific plans to protect their staff or their business in the event of pandemic influenza, and that over per cent state they need help to prepare for pandemic influenza. these findings suggest that additional strategies are required to promote increased awareness of the threat of pandemic influenza in the community, to promote the resources available to assist with preparedness, and to facilitate engagement in preparedness planning. behaviour change is a process, and time is required to initiate and establish new behaviours. according to the protection motivation theory, coping appraisal responses which lead to the establishment of protection motivation occur after the threat-appraisal process, as a threat needs to be identified before coping options can be evaluated [ ] . as such, and as has already been highlighted by others, occasional media reports are insufficient to adequately inform individuals about pandemic influenza, and interventions are required before a pandemic occurs to improve public awareness, build mutual trust, promote effective coping responses and assist in the successful implementation of plans when they are required [ ] . national influenza plans require collective communitywide efforts for an effective response to pandemic influenza. however, they lack information relating to strategies to enable the effective dissemination of this information beyond the availability of these plans on websites [ ] . given that the strategy for response to pandemic influenza in australia is based on containment and reducing transmission of the virus [ ] , and that key response strategies such as isolation, social distancing, and improved personal hygiene which have been supported by mathematical modelling studies [ ] depend on community-wide behaviour modification, additional strategies are required to enable an effective shared response. our findings suggest that the beliefs of small and medium business owners and managers are likely to have important consequences for preparedness. beliefs about the risk of and severity of pandemic influenza were the most important independent predictors of having thought about, and having a plan for pandemic influenza respectively. the perceived risk of pandemic influenza to the business was also the most important predictor of needing help to prepare. these findings are consistent with the relationships proposed by prominent theories of health behaviour, including the protection motivation theory [ , ] , and suggest that these theories provide a useful model for understanding preparedness behaviours among small and medium businesses in australia and elsewhere. protection motivation theory and health belief model concepts have been found to be valuable for understanding and promoting a variety of health-related behaviours [ , , , ] , including the performance of protective behaviours during the outbreak of the severe acute respiratory syndrome in hong kong [ ] . the importance of perceptions about risk and severity in understanding preparedness behaviour suggests that health behaviour theories provide a useful framework for the design of communication strategies that aim to promote preparedness for pandemic influenza among the business community. based on the temporal relations identified in these theoretical frameworks, our results suggest that communications containing information about risk and severity are likely to promote both threat appraisal and coping appraisal processes, and can motivate protective behaviours given a perceived ability to implement recommended actions. promotion of the ability to respond effectively to the threat of pandemic influenza appears to be an important factor associated with protective responses to the threat of pandemic influenza. this finding is consistent with research findings based on other health threats which indicates that low levels of self efficacy and response efficacy provide a barrier to action [ , ] . the high proportion of participants reporting needing help with preparation indicates that self efficacy may be an important factor limiting planning for pandemic influenza, which is consistent with the findings of recent research in europe and asia [ ] . individual business characteristics were relatively unimportant among the predictors of having thought about or planned for pandemic influenza. apart from beliefs about risk, the only other significant predictor of having considered the impact of pandemic influenza on the business was whether the business operated within or outside a capital city. it is possible that this association reflects a factor which can modify the perceived threat of pandemic influenza based on understandings about population density and the probability of exposure to infection. in contrast, individual business characteristics were more important predictors of needing help to prepare, with industry type and state being significant predictors in addition to beliefs about risk. retail traders and businesses that provide property and business services were less likely to report the need for help. differences in the need for help by industry type, given the significant association between industry type and coping appraisal, suggests that some businesses may have difficulty identifying effective protection strategies that are appropriate for specific high-risk business environments, such as retail outlets. this finding highlights the importance of providing support to identify effective response strategies and overcome response difficulties within all business environments. furthermore, our finding that the need for help was not significantly related to whether a plan for pandemic influenza exists appears to highlight the difficulties associated with planning for pandemic influenza, even among those businesses that have already made specific plans for pandemic influenza. our finding of a difference in the need for help by state is likely to be associated with the different sampling and recruitment processes used in the two study locations. in wa the local chambers of commerce was directly contracted to supply the business contact details and conduct the interviews. thus, the existing relationship with the businesses sampled is likely to explain the higher response rate in wa, why a higher proportion of owners were interviewed, and provide a sample which may be less biased in terms of either having a specific interest in pandemic influenza or time or resource pressures than the nsw sample. selection bias associated with the different recruitment strategies may explain why participants from nsw were more likely to have a plan, were more likely to need help and reported lower response efficacy. alternatively, these findings may be due to real differences in beliefs and behaviour between states, which may for example be associated with differences in media exposure or other local influences. regardless of the cause, these differences did not significantly influence the associations found between beliefs and preparedness. due to the cross-sectional study design we are limited in the type of conclusions that we can draw about causality based on the associations observed. for example, having prepared a pandemic influenza plan is likely to result in improved levels of coping appraisal. however, experimental research [ ] has provided support for the impact of beliefs on protection motivation and current behaviour. the associations found in this study explained a low proportion of variance in preparedness behaviour, although the magnitude of the associations found is similar to those reported for protection motivation theory concepts and other health-related behaviours [ , ] . several factors could have contributed to the low explanatory power in the present study, including the assessment of a limited number of theory-based belief constructs, the use of single-item and thus limited operationalisations of the key belief and outcome variables which have unknown reliability, and the use of dichotomous indicators due to the small sample size. also we did not assess behavioural intentions. further work is required to extend the scope of this study and considered other relevant constructs including social norms and response costs. the non-random nature of the sampling frames used to recruit study participants and the small scale of the study limits the generalisability of the study findings. it is also likely that response bias associated with the low response rate may have resulted in an overestimation of the proportion of businesses that have a plan for pandemic influenza, particularly in nsw. the use of financial or other incentives for participation is recommended in future studies to facilitate improved response rates, particularly where industry partners are not used. the findings of this study may also be limited in that self-report methods were used to assess whether the business had a pandemic influenza plan. responses may have been biased in favour of reporting the presence of a plan or having considered the impact of pandemic influenza on the business associated with social desirability bias. there is a shortage of data available to guide public health policy and practice in pandemic influenza planning and response [ ] . current guidance for pandemic influenza preparedness appears to have had little impact on preparedness among the small and medium business sectors in australia. our findings suggest that further investment by governments is required to improve both the specification of and utilisation of available planning resources, as has been highlighted previously [ ] . further work is required to underpin both the design of communication strategies to promote behavioural change, as well as the feasibility and effectiveness of strategies for disease control, which also support beliefs about being able to respond effectively to the threat of pandemic influenza. the findings of this study should be interpreted alongside more in-depth knowledge about the beliefs of business owners and managers that underlie the protection motivation theory constructs, as has been illustrated elsewhere [ ] . in this way, a greater understanding about beliefs to be reinforced or changed, and responses to specific strategies can be gained, helping to promote improved effectiveness of the communication strategies developed. also, particularly in the small and medium business sectors that may have significant resource constraints, the presence of alternative adaptive responses to the threat of pandemic influenza require further investigation. we found that only a small proportion of small and medium sized businesses in australia have made formal plans to guide their response in the event of pandemic influenza. effective communication strategies and support structures to promote preparedness for pandemic influenza are essential to facilitate large-scale community involvement in response efforts. findings from this study provide knowledge which can be used in the preparation of strategies to enable the effective delivery of information on preparedness for businesses. our results indicate that to motivate improved planning among the small and medium business sector, campaigns targeting small and medium businesses should emphasise the severity of the consequences to their businesses if a pandemic were to occur, and, at the same time, reassure them that there are effective strategies capable of being implemented by small and medium businesses to deal with a pandemic. world health organization: epidemic and pandemic alert and response: avian influenza the australian response: pandemic influenza preparedness australian government department of industry tourism and resources: business continuity guide for australian businesses australian government department of health and ageing: australian health management plan for pandemic influenza interim pre-pandemic planning guidance: community strategy for pandemic influenza mitigation in the united states -early targeted layered use of nonpharmaceutical interventions new zealand government ministry of economic development: influenza pandemic planning: business continuity planning guide australian government department of industry tourism and resources: being prepared for an influenza pandemic: a kit for small businesses a protection motivation theory of fear appeals and attitude change protection motivation theory and skin cancer risk: the role of individual differences in responses to persuasive appeals a meta-analysis of research on protection motivation theory a meta-analysis of fear appeals: implications for effective public health campaigns the health belief model and personal health behaviour the health belief model: a decade later a meta-analysis of studies with the health belief model with adults psychosocial factors influencing the practice of preventive behaviours against the severe acute respiratory syndrome among older chinese in hong kong health behaviour theory and cumulative knowledge regarding health behaviors: are we moving in the right direction? australian bureau of statistics: australian and new zealand standard industrial classification (anzsic) preparing for an influenza pandemic: ethical issues using mathematical models to assess responses to an outbreak of an emerged viral disease. final report to the department of health and ageing. canberra, national centre for epidemiology and population health effects of a psychosocial intervention on breast self-examination attitudes and behaviours adolescents' cognitive appraisals of cigarette smoking: an application of the protection motivation theory avian influenza risk perception prediction and intervention in health-related behaviour: a meta-analytic review of protection motivation theory people at risk of flooding: why some residents take precautionary action while others do not world health organization writing group: nonpharmaceutical interventions for pandemic influenza, national and community measures managing fear in public health campaigns: a theory-based formative evaluation process the research was funded by the national health and medical research council of australia (project grant number ) and the australian biosecurity cooperative research centre for emerging infectious disease. the authors would also like to thank the local chambers of commerce and industry in east victoria park for their assistance with and support of the research. the author(s) declare that they have no competing interests. ajp, rew and crm conceived, designed and supervised the study; fcc and ri entered the data; rew and fcc analyzed the data; rew drafted the manuscript; and rjd, ajp, crm and fcc provided feedback on the interpretation of results and editorial comments on the manuscript. we wish to dedicate this paper to the memory of our colleague and much loved friend professor aileen joy plant who died suddenly on the th of march while on an avian influenza mission for the world health organization. this work would not have been possible without her leadership. her outstanding vision for and contribution to the advancement of global public health will be greatly missed. the pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/ - / / /pre pub key: cord- -k wrory authors: prieto, diana m; das, tapas k; savachkin, alex a; uribe, andres; izurieta, ricardo; malavade, sharad title: a systematic review to identify areas of enhancements of pandemic simulation models for operational use at provincial and local levels date: - - journal: bmc public health doi: . / - - - sha: doc_id: cord_uid: k wrory background: in recent years, computer simulation models have supported development of pandemic influenza preparedness policies. however, u.s. policymakers have raised several concerns about the practical use of these models. in this review paper, we examine the extent to which the current literature already addresses these concerns and identify means of enhancing the current models for higher operational use. methods: we surveyed pubmed and other sources for published research literature on simulation models for influenza pandemic preparedness. we identified models published between and that consider single-region (e.g., country, province, city) outbreaks and multi-pronged mitigation strategies. we developed a plan for examination of the literature based on the concerns raised by the policymakers. results: while examining the concerns about the adequacy and validity of data, we found that though the epidemiological data supporting the models appears to be adequate, it should be validated through as many updates as possible during an outbreak. demographical data must improve its interfaces for access, retrieval, and translation into model parameters. regarding the concern about credibility and validity of modeling assumptions, we found that the models often simplify reality to reduce computational burden. such simplifications may be permissible if they do not interfere with the performance assessment of the mitigation strategies. we also agreed with the concern that social behavior is inadequately represented in pandemic influenza models. our review showed that the models consider only a few social-behavioral aspects including contact rates, withdrawal from work or school due to symptoms appearance or to care for sick relatives, and compliance to social distancing, vaccination, and antiviral prophylaxis. the concern about the degree of accessibility of the models is palpable, since we found three models that are currently accessible by the public while other models are seeking public accessibility. policymakers would prefer models scalable to any population size that can be downloadable and operable in personal computers. but scaling models to larger populations would often require computational needs that cannot be handled with personal computers and laptops. as a limitation, we state that some existing models could not be included in our review due to their limited available documentation discussing the choice of relevant parameter values. conclusions: to adequately address the concerns of the policymakers, we need continuing model enhancements in critical areas including: updating of epidemiological data during a pandemic, smooth handling of large demographical databases, incorporation of a broader spectrum of social-behavioral aspects, updating information for contact patterns, adaptation of recent methodologies for collecting human mobility data, and improvement of computational efficiency and accessibility. results: while examining the concerns about the adequacy and validity of data, we found that though the epidemiological data supporting the models appears to be adequate, it should be validated through as many updates as possible during an outbreak. demographical data must improve its interfaces for access, retrieval, and translation into model parameters. regarding the concern about credibility and validity of modeling assumptions, we found that the models often simplify reality to reduce computational burden. such simplifications may be permissible if they do not interfere with the performance assessment of the mitigation strategies. we also agreed with the concern that social behavior is inadequately represented in pandemic influenza models. our review showed that the models consider only a few social-behavioral aspects including contact rates, withdrawal from work or school due to symptoms appearance or to care for sick relatives, and compliance to social distancing, vaccination, and antiviral prophylaxis. the concern about the degree of accessibility of the models is palpable, since we found three models that are currently accessible by the public while other models are seeking public accessibility. policymakers would prefer models scalable to any population size that can be downloadable and operable in personal computers. but scaling models to larger populations would often require computational needs that cannot be handled with personal computers and laptops. as a limitation, we state that some existing models could not be included in our review due to their limited available documentation discussing the choice of relevant parameter values. conclusions: to adequately address the concerns of the policymakers, we need continuing model enhancements in critical areas including: updating of epidemiological data during a pandemic, smooth handling of large demographical databases, incorporation of a broader spectrum of social-behavioral aspects, updating information for contact patterns, adaptation of recent methodologies for collecting human mobility data, and improvement of computational efficiency and accessibility. the ability of computer simulation models to "better frame problems and opportunities, integrate data sources, quantify the impact of specific events or outcomes, and improve multi-stakeholder decision making," has motivated their use in public health preparedness (php) [ ] . in , one such initiative was the creation of the preparedness modeling unit by the centers for disease control and prevention (cdc) in the u.s. the purpose of this unit is to coordinate, develop, and promote "problem-appropriate and data-centric" computer models that substantiate php decision making [ ] . of the existing computer simulation models addressing php, those focused on disease spread and mitigation of pandemic influenza (pi) have been recognized by the public health officials as useful decision support tools for preparedness planning [ ] . in recent years, computer simulation models were used by the centers for disease control and prevention (cdc), department of health and human services (hhs), and other federal agencies to formulate the "u.s. community containment guidance for pandemic influenza" [ ] . although the potential of the exiting pi models is well acknowledged, it is perceived that the models are not yet usable by the state and local public health practitioners for operational decision making [ , [ ] [ ] [ ] . to identify the challenges associated with the practical implementation of the pi models, the national network of public health institutes, at the request of cdc, conducted a national survey of the practitioners [ ] . the challenges identified by the survey are summarized in table . we divided the challenges (labeled a through a in table ) into two categories: those (a through a ) that are related to model design and implementation and can potentially be addressed by adaptation of the existing models and their supporting databases, and those (a through a ) that are related to resource and policy issues, and can only be addressed by changing public health resource management approaches and enforcing new policies. although it is important to address the challenges a through a , we consider this a prerogative of the public health administrators. hence, the challenges a to a will not be discussed in this paper. the challenges a through a reflect the perspectives of the public health officials, the end users of the pi models, on the practical usability of the existing pi models and databases in supporting decision making. addressing these challenges would require a broad set of enhancements to the existing pi models and associated databases, which have not been fully attempted in the literature. in this paper, we conduct a review of the pi mitigation models available in the published research literature with an objective of answering the question: "how to enhance the pandemic simulation models and the associated databases for operational use at provincial and local levels?" we believe that our review accomplishes its objective in two steps. first, it exposes the differences between the perspectives of the public health practitioners and the developers of models and databases on the required model capabilities. second, it derives recommendations for enhancing practical usability of the pi models and the associated databases. in this section, we describe each of the design and implementation challenges of the existing pi models (a -a ) and present our methods to examine the challenges in the research literature. in addition, we present our paper screening and parameter selection criteria. design and implementation challenges of pandemic models and databases validity of data support (a ) public health policy makers advocate that the model parameters be derived from up to date demographical and epidemiological data during an outbreak [ ] . in this paper we examine some of the key aspects of data support, such as data availability, data access, data retrieval, and data translation. to ensure data availability, a process must be in place for collection and archival of both demographical and epidemiological data during an outbreak. the data must be temporally consistent, i.e., it must represent the actual state of the outbreak. in the united states and other few countries, availability of temporally consistent demographical data is currently supported by governmental databases including the decennial census and the national household travel survey [ ] [ ] [ ] [ ] . to ensure temporal consistency of epidemiological data, the institute of medicine (iom) has recommended enhancing the data collection protocols to support real-time decision making [ ] . the frequency of data updating may vary based on the decision objective of the model (e.g., outbreak detection, outbreak surveillance, and initiation and scope of interventions). as noted by fay-wolfe, the timeliness of a decision is as important as its correctness [ ] , and there should be a balance between the cost of data updating and the marginal benefits of the model driven decisions. archival of data must allow expedited access for model developers and users. in addition, mechanisms should be available for manual or automatic retrieval of data and its translation into model parameter values in a timely manner. in our review of the existing pi models at provincial and local levels, we examined the validity of data that was used in supporting major model parameters. the major model parameters include: the reproduction number, defined as the number of secondary infections that arise from a typical primary case [ ] ; the proportion of the population who become infected, also called infection attack rate [ ] ; the disease natural history within an individual; and fractions of symptomatic and asymptomatic individuals. the first row of table summarizes our approach to examine data validity. for each reviewed pi model, and, for each of the major model parameters, we examined the source and the age of data used (a a, a b), the type of interface used for data access and retrieval (a c), and the technique used for translating data into the parameter values (a d). public health practitioners have emphasized the need for models with credible and valid assumptions [ ] . credibility and validity of model assumptions generally refer to how closely the assumptions represent reality. however, for modeling purposes, assumptions are often made to balance data needs, analytical tractability, and computational feasibility of the models with their ability to support timely and correct decisions [ ] . making strong assumptions may produce results that are timely but with limited or no decision support value. on the other hand, relaxing the simplifying assumptions to the point of analytical intractability or computational infeasibility may seriously compromise the fundamental purpose of the models. every model is comprised of multitudes of assumptions pertaining to contact dynamics, transmission and infection processes, spatial and temporal considerations, demographics, mobility mode(s), and stochasticity of parameters. credibility and validity of these assumptions largely depend on how well they support the decision objectives of the models. for example, if a model objective is to test a household isolation strategy (allowing sick individuals to be isolated at home, in a separate room), the model assumptions must allow tracking of all the individuals within the household (primary caregivers and others) so that the contact among the household members can be assigned and possible spread of infection within the household can be assessed. this idea is further discussed in the results section through an analysis of some of the model assumptions regarding contact probability and frequency of new infection updates that were made in two of the commonly referenced pi models in the pandemic literature [ , ] . it has been observed in [ ] that the existing pi models fall short of capturing relevant aspects of human behavior. this observation naturally evokes the following questions. what are the relevant behavioral aspects that must be considered in pi models? are there scientific evidences that establish the relative importance of these aspects? what temporal consistency is required for data support of the aspects of human behavior? the third row of table summarizes our plan to examine how the existing models capture human behavior. for each reviewed pi model, we first identify the behavioral aspects that were considered, and then for each aspect we examine the source and the age of data used, the type of interface used for data access and retrieval, and the technique used for translating data into model parameter values (a a-d). we also attempt to answer the questions raised above, with a particular focus on determining what enhancements can be done to better represent human behavior in pi models. public health practitioners have indicated the need for openly available models and population specific data that can be downloaded and synthesized using personal computers [ ] . while the ability to access the models is essential for end users, executing the pi models on personal computers, in most cases, may not be feasible due to the computational complexities of the models. some of the existing models feature highly granular description of disease spread dynamics and mitigation via consideration of scenarios involving millions of individuals and refined time scales. while such details might increase credibility and validity of the models, this can also result in a substantial computational burden, sometimes, beyond the capabilities of personal computers. there are several factors which contribute to the computational burden of the pi models, the primary of which is the population size. higher population size of the affected region requires larger datasets to be accessed, retrieved, and downloaded to populate the models. other critical issues that add to the computational burden are: data interface with a limited bandwidth, the frequency of updating of data during a pandemic progress, pre-processing (filtering and quality assurance) requirement for raw data, and the need for data translation into parameter values using methods, like maximum likelihood estimation and other arithmetic conversions. the choice of the pi model itself can also have a significant influence on the computational burden. for example, differential equation (de) models divide population members into compartments, where in each compartment every member makes the same number of contacts (homogeneous mixing) and a contact can be any member in the compartment (perfect mixing). in contrast, agentbased (ab) models track each individual of the population where an individual contacts only the members in his/her relationship network (e.g., neighbors, co-workers, household members, etc.) [ ] . the refined traceability of individual members offered by ab models increases the usage of computational resources. further increases in the computational needs are brought on by the need for running multiple replicates of the models and generating reliable output summaries. as summarized in the last row of table , we examine which models have been made available to general public and whether they are offered as an open or closed source code. we also check for the documentation of model implementation as well as for existence of user support, if any. in addition, we look for the ways that researchers have attempted to address the computational feasibility of their models, including data access, retrieval and translation, model execution, and generation of model outputs. the initial set of articles for our review was selected following the prisma reporting methodology, as applicable. we used the pubmed search engine with the keyword string "influenza" and "pandemic" and "model" in english language. a total of papers were found which were published between and . we filtered those using the following selection criteria (also depicted in figure ). -articles that evaluate one or more strategies in each of the mitigation categories: social distancing, vaccination, and antiviral application. we limited the paper (by excluding models that do not consider all three categories) to contain the scope of this review, as we examined a large table plan for examination of the design and implementation challenges of the existing pi models design and implementation challenges validity of data support (a ) for model parameters for each pi model and for each of the major model parameters (e.g., reproduction number, illness attack rate) examine: a a. data source for parameter values (actual, simulated, assumed) a b. age of data a c. type of interface for data access and retrieval (manual, automatic) a d. technique to translate raw data into model parameter values (e.g., arithmetic conversion, bayesian estimation) credibility and validity of model assumptions ( body of related papers from which our selected articles drew their parameters (see additional tables). -articles with single-region simulation models. we defined single-region for the purpose of this review as either a country or any part thereof. models presenting disease spread approaches without mention of any regional boundary were included, as these approaches can directly support decision makers at provincial and local levels. there exists a significant and important body of literature that is dedicated to global pandemic influenza modeling that aims at quantifying global disease spread [ ] [ ] [ ] [ ] , assessing the impact of global vaccine distribution and immunization strategies [ ] [ ] [ ] and assessing the impact of recommended or self-initiated mobility behaviors in the global disease spread [ , ] . as these overarching aims of the global models do not directly impact operational decisions of provincial and local policy makers during an evolving pandemic, we have not included them in our final selection of articles. -articles that include data sources for most model parameter values and, when possible, specify the methods for parameter estimation. we included this criterion in order to evaluate models with respect to the challenge of "validity of data support." see table where we outline our evaluation plan. clearly, models not satisfying this criterion would not support our review objectives. using the above filtering criteria, an additional snowball search was implemented outside pubmed, which yielded additional eligible papers [ , [ ] [ ] [ ] [ ] and bringing the total number of papers reviewed to twentythree. we grouped the twenty-three selected articles in eleven different clusters based on their model (see table ). the clusters are named either by the name used in the literature or by the first author name(s). for example, all three papers in the imperial-pitt cluster use the model introduced initially by ferguson et al. [ ] . in each cluster, to review the criteria for the design and implementation challenge (a ), we selected the article with the largest and most detailed testbed (marked in bold in table ). as stated earlier, credibility and validity of model assumptions (a ), were examined via two most commonly cited models in the pandemic literature [ , ] . the challenges a -a were examined separately for each of the selected articles. out of the ten model clusters presented in table , eight are agent-based simulation models, while the rest are differential equation models. also, while most of the models use purely epidemiological measures (e.g., infection attack rates and reproduction numbers) to assess the effectiveness of mitigation strategies, only a few use economic measures [ , , ] . in our review, we examined epidemiological, demographical, and social-behavioral parameters of the pandemic models. we did not examine the parameters of the mitigation strategies as a separate category since those are functions of the epidemiological, demographical, and social-behavioral parameters. for example, the risk groups for vaccine and antiviral (which are mitigation parameters) are functions of epidemiological parameters such as susceptibility to infection and susceptibility to death, respectively. another example is the compliance to non-pharmaceutical interventions, a mitigation strategy parameter, which can be achieved by altering the social behavioral parameters of the model. in this section, we present the results of our review of the models that evaluate at least one strategy from each mitigation category (social distancing, vaccination and antiviral application). we also identify areas of enhancements of the simulation based pi models for operational use. our discussion on validity of data support includes both epidemiological and demographic data. additional file : table s summarizes the most common epidemiological parameters used in the selected models along with their data sources, interface for data access and retrieval, and techniques used in translating raw data into parameter values. additional file : table s presents information similar to above for demographic parameters. the most commonly used epidemiological parameters are reproduction number (r), illness attack rate (iar), initial set of articles filtered from pubmed using keyword search (n = ) remaining articles (n = ) exclusion of articles that do not examine pandemic influenza spread under a comprehensive set of mitigation strategies (n = ) exclusion of articles that examine global pandemic spread (n = ) remaining articles (n = ) remaining articles (n = ) inclusion of articles that meet the above criteria but are obtained using snowball search outside pubmed (n = ) exclusion of articles that do not provide a comprehensive support for data collection and parameterization methods (n = ) articles reviewed (n = ) figure selection criteria for pi models for systematic review. disease natural history parameters, and fraction of asymptomatic infected cases. in the models that we have examined, estimates of reproduction numbers have been obtained by fitting case/mortality time series data from the past pandemics into models using differential equations [ ] , cumulative exponential growth equations [ ] , and bayesian likelihood expressions [ ] . iars have been estimated primarily using household sampling studies [ ] , epidemic surveys [ , ] , and case time series reported for h n [ , ] . the parameters of the disease natural history, which are modeled using either a continuous or phase-partitioned time scale (see additional file : table s ), have been estimated from household random sampling data [ , , ] , viral shedding profiles from experimental control studies [ , , , ] , and case time series reported for h n [ , ] . bayesian likelihood estimation methods were used in translating case time series data [ , ] . fraction of asymptomatic infected cases has been estimated using data sources and translation techniques similar to the ones used for natural history. recent phylogenetic studies on the h n virus help to identify which of the above epidemiological parameters need real-time re-assessment. these studies suggest that the migratory patterns of the virus, rather than the intrinsic genomic features, are responsible for the second pandemic wave in [ , ] . since r and iar are affected not only by the genomic features but also by the migratory patterns of the virus, a close monitoring of these parameters throughout the pandemic spread is essential. real-time monitoring of parameters describing disease natural history and fraction of asymptomatic cases is generally not necessary since they are mostly dependent on the intrinsic genomic features of the virus. these parameters can be estimated when a viral evolution is confirmed through laboratory surveillance. estimation methods may include surveys (e.g., household surveys of members of index cases [ , ] ) and laboratory experiments that inoculate pandemic strains into human volunteers [ ] . current pandemic research literature shows the existence of estimation methodologies for iar and r that can be readily used provided that raw data is available [ ] . there exist several estimators for r (wallinga et al. [ , ] , fraser [ ] , white and pagano [ ] , bettencourt et al. [ ] , and cauchemez et al. [ ] ). these estimates have been derived from different underlying infection transmission models (e.g., differential equations, time since infection and directed network). with different underlying transmission models, the estimators consider data from different perspectives, thereby yield different values for r at a certain time t. for example, fraser [ ] proposes an instantaneous r that observes how past case incidence data (e.g., in time points t- , t- , t- ) contribute to the present incidence at time t. in contrast, wallinga et al. [ , ] and cauchemez et al. [ ] propose estimators that observe how the future incidences (e.g., t + , t + , t + ) are contributed by a case at time t. white and pagano [ ] considers an estimator that can be called a running estimate of the instantaneous reproduction number. further extensions of the above methods have been developed to accommodate more realistic assumptions. bettencourt extended its r estimator to account for multiple introductions from a reservoir [ ] . the wallinga estimator was extended by cowling [ ] to allow for reporting delays and repeated importations, and by glass [ ] to allow for heterogeneities among age groups (e.g., adults and children). the fraser estimator was extended by nishiura [ ] to allow the estimation of the reproduction number for a specific age class given infection by another age class. the above methods for real-time estimation of r are difficult to implement in the initial and evolving stages of a pandemic given the present status of the surveillance systems. at provincial and local levels, surveillance systems are passive as they mostly collect data from infected cases who are seeking healthcare [ ] . with passive surveillance, only a fraction of symptomatic cases are detected with a probable time delay from the onset of symptoms. once the symptomatic cases seek healthcare and are reported to the surveillance system, the healthcare providers selectively submit specimens to the public health laboratories (phl) for confirmatory testing. during the h n pandemic in , in regions with high incidence rates, the daily testing capacities of the phl were far exceeded by the number of specimens received. in these phl, the existing first-come-first-serve testing policy and the manual methods for receiving and processing the specimens further delayed the pace of publication of confirmed cases. the time series of the laboratory confirmed cases likely have been higher due to the increased specimen submission resulting from the behavioral response (fear) of both the susceptible population and the healthcare providers after the pandemic declaration [ ] . similarly, time series of the confirmed cases likely have been lower at the later stages of the pandemic as federal agencies advocated to refrain from specimen submission [ ] . the present status of the surveillance systems calls for the models to account for: the underreporting rates, the delay between onset of symptoms and infection reporting, and the fear factor. in addition, we believe that it is necessary to develop and analyze the cost of strategies to implement active surveillance and reduce the delays in the confirmatory testing of the specimens. in our opinion, the above enhancement can be achieved by developing methods for statistical sampling and testing of specimens in the phl. in addition, new scheduling protocols will have to be developed for testing the specimens, given the limited laboratory testing resources, in order to better assess the epidemiological parameters of an outbreak. with better sampling and scheduling schemes at the phl, alterations in the specimen submission policies during a pandemic (as experienced in the u.s. during the outbreak) may not be necessary. the above enhancements would also support a better real-time assessment of the iar, which is also derived from case incidence data. our review of the selected pi models indicates that currently all of the tasks relating to access and retrieval of epidemiological data are being done manually. techniques for translation of data into model parameter values range from relatively simple arithmetic conversions to more time-consuming methods of fitting mathematical and statistical models (see additional file : table s ). there exist recent mechanisms to estimate incidence curves in real-time by using web-based questionnaires from symptomatic volunteers [ ] , google and yahoo search queries [ , ] and tweeter messages [ ] and have supported influenza preparedness in several european countries and the u.s. [ , ] . if real-time incidence estimates are to be translated into pi models parameters, complex translation techniques might delay execution of the model. we believe that model developers should consider building (semi)automatic interfaces for epidemiological data access and retrieval and develop translation algorithms that can balance the run time and accuracy. additional file : table s shows the most common demographic parameters that are used in the selected models. the parameters are population size/density, distribution of household size, peer-group size, age, commuting travel, long-distance travel, and importation of infected cases to the modeled region. estimation of these parameters has traditionally relied on comprehensive public databases, including the u.s. census, landscan, italian institute of statistics, census of canada, hong kong survey data, uk national statistics, national household travel survey, uk department of transport, u.s. national centre for educational statistics, the italian ministry of university and research and the uk department for education and skills. readers are referred to additional file : table s for a complete list of databases and their web addresses. our literature review shows that access and retrieval of these data are currently handled through manual procedures. hence, there is an opportunity for developing tools to accomplish (semi)automatic data access, retrieval, and translation into model parameters whenever a new outbreak begins. it is worth noting that access to demographic information is currently limited in many countries, and therefore obtaining demographic parameters in real-time would only be possible for where information holders (censing agencies and governmental institutions) openly share the data. the data sources supporting parameters for importation of infected cases reach beyond the modeled region requiring the regional models to couple with global importation models. this coupling is essential since the possibility of new infection arrivals may accelerate the occurrence of the pandemic peak [ ] . this information on peak occurrence could significantly influence time of interventions. some of the single region models consider a closed community with infusion of a small set of infected cases at the beginning [ , , ] . single region models also consider a pseudo global coupling through a constant introduction of cases per unit time [ , ] . other single region models adopt a more detailed approach, where, for each time unit, the number of imported infections is estimated by the product of the new arrivals to the region and the probability of an import being infected. this infection probability is estimated through a global disease spread compartmental model [ , ] . the latter approach is similar to the one used by merler [ ] for seeding infections worldwide and is operationally viable due to its computational simplicity. for a more comprehensive approach to case importation and global modeling of disease spread, see [ ] . recall that our objective here is to discuss how the credibility and validity of assumptions should be viewed in light of their impact on the usability of models for public health decision making. we examine the assumptions regarding contact probability and the frequency of new infection updates (e.g., daily, quarterly, hourly) in two models: the imperial-pitt [ ] and the uw-lanl models [ ] . choice of these models was driven by their similarities (in region, mixing groups, and the infection transmission processes), and the facts that these models were cross validated by halloran [ ] and were used for developing the cdc and hhs "community containment guidance for pandemic influenza" [ ] . we first examine the assumptions that influence contact probabilities within different mixing groups (see table ). for household, the imperial-pitt model assumes constant contact probability while the uw-lanl model assumes that the probability varies with age (e.g., kid to kid, kid to adult). the assumption of contact probability varying with age matches reality better than assuming it to be constant [ ] . however, for households with smaller living areas the variations may not be significant. also, neither of the papers aimed at examining strategies (e.g., isolation of sick children within a house) that depended on age-based contact probability. hence, we believe that the assumptions can be considered credible and valid. for workplaces and schools, the assumption of % of contacts within the group and % contacts outside the group, as made in the imperial-pitt model, appears closer to reality than the assumption of constant probability in the uw-lanl model [ ] . for community places, the imperial-pitt model considered proximity as a factor influencing the contact probability, which was required for implementing the strategy of providing antiviral prophylaxis to individuals within a ring of certain radius around each detected case. we also examined the assumptions regarding the frequency of infection updates. the frequency of update dictates how often the infection status of the contacted individuals is evaluated. in reality, infection transmission may occur (or does not occur) whenever there is a contact event between a susceptible and an infected subject. the imperial-pitt and the uw-lanl models do not evaluate infection status after each contact event, since this would require consideration of refined daily schedules to determine the times of the contact events. instead, the models evaluate infection status every six hours [ ] or at the end of the day [ ] by aggregating the contact events. while such simplified assumptions do not allow the determination of the exact time of infection for each susceptible, they offer a significant computational reduction. moreover, in a real-life situation, it will be nearly impossible to determine the exact time of each infection, and hence practical mitigation (or surveillance) strategies should not rely on it. the above analysis reveals how the nature of mitigation strategies drives the modeling assumptions and the computational burden. we therefore believe that the policymakers and the modelers should work collaboratively in developing modeling assumptions that adequately support the mitigation strategy needs. furthermore, the issue of credibility and validity of the model assumptions should be viewed from the perspectives of the decision needs and the balance between analytical tractability and computational complexity. for example, it is unlikely that any mitigation strategy would have an element that depends of the minute by minute changes in the disease status. hence, it might be unnecessary to consider a time scale of the order of a minute for a model and thus increase both computational and data needs. contact rate is the most common social-behavioral aspect considered by the models that we have examined. in these models, except for eichner et al. [ ] , the values of the contact rates were assumed due to the unavailability of reliable data required to describe the mobility and connectivity of modern human networks [ , , ] . however, it is now possible to find "fresh" estimates of the types, frequency, and duration of human contacts either from a recent survey at the continental level [ ] or from a model that derives synthetic contact information at the country level [ ] . in addition, recent advances in data collection through bluetooth enabled mobile telephones [ ] and radio frequency identification (rfid) devices [ ] allow better extraction of proximity patterns and social relationships. availability of these data creates further opportunity to explore methods of access, retrieval, and translation into model parameters. issues of data confidentiality, cost of the sensing devices, and low compliance to the activation of sensing applications might prevent the bluetooth and rfid technologies from being effectively used in evolving pandemic outbreaks. another possibility is the use of aggregated and anonymous network bandwidth consumption data (from network service providers) to extrapolate population distribution in different areas at different points in time [ , ] . other social-behavioral parameters that are considered by the reviewed models include reactive withdrawal from work or school due to appearance of symptoms [ ] , work absenteeism to care for sick relatives or children at home due to school closure [ , , , ] , and compliance to social distancing, vaccination, and antiviral prophylaxis [ , ] . once again, due to the lack of data support, the values of most of these parameters were assumed and their sensitivities were studied to assess the best and worst case scenarios. existing surveys collected during the h n outbreak can be useful in quantifying the above parameters [ , ] . recent literature has explored many additional socialbehavioral aspects that were not considered in the models we reviewed. there are surveys that quantify the levels of support for school closure, follow up on sick students by the teachers [ ] , healthcare seeking behavior [ ] , perceived severity, perceived susceptibility, fear, general compliance intentions, compliance to wearing face masks, role of information, wishful thinking, fatalistic thinking, intentions to fly away, stocking, staying indoors, avoiding social contact, avoiding health care professionals, keeping children at home and staying at home, and going to work despite being advised to stay at home [ ] . there are also models that assess the effect of selfinitiated avoidance to a place with disease prevalence [ ] , voluntary vaccination and free-ride (not to vaccinate but rely on the rest of the population to keep coverage high [ ] . other recognized behaviors include refusal to vaccinate due to religious beliefs and not vaccinating due to lack of awareness [ ] . we believe that there is a need for further studies to establish the relative influence of all of the above mentioned social-behavioral factors on operational models for pandemic spread and mitigation. subsequently, the influential factors need to be analyzed to determine how relevant information about those factors should be collected (e.g., in real-time or through surveys before an outbreak), accessed, retrieved, and translated into the final model parameter values. it is important to mention very recent efforts in improving models for assessment of relevant social behavioral components including commuting, long distance travel behavior [ , , ] , and authority recommended decline of travel to/from affected regions [ ] . for operational modeling, it would be helpful to adapt the approaches used by these models in translating massive data sets (e.g., bank notes, mobile phone user trajectories, air and commuting travel networks) into model parameter values. in addition, available new methodologies to model social-behavior that adapts to evolving disease dynamics [ ] should be incorporated into the operational models. with regards to accessibility and scalability of the selected models, we first attempted to determine which of the simulation models were made available to general public, either as an open or closed source code. we also checked for available documentation for model implementation and user support, if any. most importantly, we looked into how the researchers attempted to achieve the computational feasibility of their models (see additional file : table s ). three of the models that make their source codes accessible to general public are influsim [ ] , ciofi [ ] and flute [ ] . influsim is a closed source differential equation-based model with a graphical user interface (gui) which allows the evaluation of a variety of mitigation strategies, including school closure, place closure, antiviral application to infected cases, and isolation. ciofi is an open source model that is coupled with a differential equation model to allow for a more realistic importation of cases to a region. flute is an open source model, which is an updated version of the uw-lanl [ ] agent-based model. the source code for flute is also available as a parallelized version that supports simulation of large populations on multiple processors. among these three softwares, influsim has a gui, whereas ciofi and uw-lanl are provided as a c/c++ code. influsim's gui seems to be more user friendly for healthcare policymakers. flute and ciofi, on the other hand, offer more options for mitigation strategies, but requires the knowledge of c/c++ programming language and the communication protocols for parallelization. other c++ models are planning to become, or are already, publicly accessible, according to the models of infectious disease agent study (midas) survey [ ] . we note that the policy makers would greatly benefit if softwares like flute or ciofi can be made available through a cyber-enabled computing infrastructure, such as teragrid [ ] . this will provide the policy makers access to the program through a web based gui without having to cope with the issues of software parallelization and equipment availability. moreover, the policy makers will not require the skills of programming, modeling, and data integration. the need for replicates for accurate assessment of the model output measures and the run time per replicate are major scalability issues for pandemic simulation models. large-scale simulations of the u.s. population reported running times of up to h per replicate, depending on the number of parallel threads used [ ] (see additional file : table s for further details). it would then take a run time of one week to execute replicates of only one pandemic scenario. note that, most of the modeling approaches have reported between to replicates per scenario [ , [ ] [ ] [ ] [ ] [ ] [ ] , with the exception of [ , , , ] which implemented between to replicates. clearly, it would take about one month to run replicates for a single scenario involving the entire u.s. population. while it may not be necessary to simulate the entire population of a country to address mitigation related questions, the issue of the computational burden is daunting nonetheless. we therefore believe that the modeling community should actively seek to develop innovative methodologies to reduce the computational requirements associated with obtaining reliable outputs. minimization of running time has been recently addressed through high performance computing techniques and parallelization by some of the midas models (e.g., epifast) and other research groups (e.g., dicon, gsam), as reported in [ ] . minimization of replicates can be achieved by running the replicates, one more at a time, until the confidence intervals for the output variables become acceptable [ , ] . in addition to the need of minimizing running time and number of replicates, it is also necessary to develop innovative methodologies to minimize the setting up time of operational models. these methodologies should enable the user to automatically select the level of modeling detail, according to the population to mimic (see a discussion of this framework in the context of human mobility [ ] ), and allow the automatic calibration of the model parameters. there exist several simulation models of pandemic influenza that can be used at the provincial and local levels and were not treated as part of the evaluated models in this article. their exclusion is due to their limited available documentation discussing the choice of demographic, social-behavioral or epidemiological parameter values. we mention and discuss their relevant features in this manuscript, whenever applicable. for information about the additional models, the reader is referred to [ , , ] . there also exist a body of literature evaluating less than three types of mitigation strategies that were not considered as part of the review, as we discussed in the methods section. this literature is valuable is providing insights about reproduction patterns [ , ] , effect of cross-immunity [ ] , antiviral resistance [ ] , vaccine dosage [ , ] , social-distancing [ ] and public health interventions in previous pandemics [ , ] . though the literature on pandemic models is rich and contains analysis and results that are valuable for public health preparedness, policy makers have raised several questions regarding practical use of these models. the questions are as follows. is the data support adequate and valid? how credible and valid are the model assumptions? is human behavior represented appropriately in these models? how accessible and scalable are these models? this review paper attempts to determine to what extent the current literature addresses the above questions at provincial and local levels, and what the areas of possible enhancements are. the findings with regards to the areas of enhancements are summarized below. enhance the following: availability of real-time epidemiological data; access and retrieval of demographical and epidemiological data; translation of data into model parameter values. we analyzed the most common epidemiological and demographical parameters that are used in pandemic models, and discussed the need for adequate updating of these parameters during an outbreak. as regards the epidemiological parameters, we have noted the need to obtain prompt and reliable estimates for the iar and r, which we believe can be obtained by enhancing protocols for expedited and representative specimen collection and testing. during a pandemic, the estimates for iar and r should also be obtained as often as possible to update simulation models. for the disease natural history and the fraction of asymptomatic cases, estimation should occur every time viral evolution is confirmed by the public health laboratories. for periodic updating of the simulation models, there is a need to develop interfaces for (semi)automatic data access and retrieval. algorithms for translating data into model parameters should not delay model execution and decision making. demographic data are generally available. but most of the models that we examined are not capable of performing (semi)automatic access, retrieval, and translation of demographic data into model parameter values. examine validity of modeling assumptions from the point of view of the decisions that are supported by the model. by referring to two of the most commonly cited pandemic preparedness models [ , ] , we discussed how simplifying model assumptions are made to reduce computational burden, as long as the assumptions do not interfere with the performance evaluation of the mitigation strategies. some mitigation strategies require more realistic model assumptions (e.g., location based antiviral prophylaxis would require models that track geographic coordinates of individuals so that those within a radius of an infected individual can be identified). whereas other mitigation strategies might be well supported by coarser models (e.g.,"antiviral prophylaxis for household members") would require models that track household membership). therefore, whenever validity of the modeling assumptions is examined, the criteria chosen for the examination should depend on the decisions supported by the model. incorporate the following: a broader spectrum of social behavioral aspects; updated information for contact patterns; new methodologies for collection of human mobility data. some of the social behavioral factors that have been considered in the examined models are social distancing and vaccination compliance, natural withdraw from work when symptoms appear, and work absenteeism to care for sick family members. although some of the examined models attempt to capture social-behavioral issues, it appears that they lack adequate consideration of many other factors (e.g., voluntary vaccination, voluntary avoidance to travel to affected regions). hence, there is a need for research studies or expert opinion analysis to identify which social-behavioral factors are significant for disease spread. it is also essential to determine how the social behavioral data should be collected (in real-time or through surveys), archived for easy access, retrieved, and translated into model parameters. in addition, operational models for pandemic spread and mitigation should reflect the state of the art in data for the contact parameters and integrate recent methodologies for collection of human mobility data. enhance computational efficiency of the solution algorithms. our review indicates that some of the models have reached a reasonable running time of up to h per replicate for a large region, such as the entire usa [ , ] . however, operational models need also to be set up and replicated in real-time, and methodologies addressing these two issues are needed. we have also discussed the question whether the public health decision makers should be burdened with the task of downloading and running models using local computers (laptops). this task can be far more complex than how it is perceived by the public health decision makers. we believe that models should be housed in a cyber computing environment with an easy user interface for the decision makers. additional file : additional file : table s epidemiological parameters in models for pandemic influenza preparedness. the excel sheet "additional file : table s " shows the epidemiological parameters most commonly used in the models for pandemic influenza, the parameter data sources, and the means for access, retrieval and translation. additional file : table s demographic parameters in models for pandemic influenza preparedness. the excel sheet "additional file : table s " shows the demographic parameters most commonly used in the models for pandemic influenza, the parameter data sources, and the means for access, retrieval and translation. additional file : table s accessibility and scalability features investigated in the models. the excel sheet "additional file " shows the different models examined, together with their type of public access, number and running time per replicate, and techniques to manage computational burden. use of computer modeling for emergency preparedness functions by local and state health official: a needs assessment cdc's new preparedness modeling initiative: beyond (and before) crisis response interim pre-pandemic planning guidance: community strategy for pandemic influenza mitigation in the united states modeling community containment for pandemic influenza: a letter report m bd: recommendations for modeling disaster responses in public health and medicine: a position paper of the society for medical decision making. med decision making yale new haven center for emergency preparedness and disaster responsem, and us northern command: study to determine the requirements for an operational epidemiological modeling process in support of decision making during disaster medical and public health response operations national household travel survey (nths) viii censimento generale della popolazione e delle abitazioni real-time database and information systems: research advance how generation intervals shape the relationship between growth rates and reproduction numbers concepts of transmission and dynamics strategies for mitigating an influenza pandemic mitigation strategies for pandemic influenza in the united states heterogeneity and network structure in the dynamics of diffusion: comparing agent-based and differential equation models the role of population heterogeneity and human mobility in the spread of pandemic influenza potential for a global dynamic of influenza a (h n ) the global transmission and control of influenza multiscale mobility networks and the spatial spreading of infectious diseases modeling human mobility responses to the large-scale spreading of infectious diseases human mobility networks, travel restrictions, and the global spread of h n pandemic flute, a publicly available stochastic influenza epidemic simulation model targeted social distancing design for pandemic influenza a large scale simulation model for assessment of societal risk and development of dynamic mitigation strategies a predictive decision aid methodology for dynamic mitigation of influenza pandemics: special issue on optimization in disaster relief strategies for containing an emerging influenza pandemic in southeast asia modeling targeted layered containment of an influenza pandemic in the united states reducing the impact of the next influenza pandemic using household-based public health interventions scalia tomba img: mitigation measures for pandemic influenza in italy: an individual based model considering different scenarios simple models for containment of a pandemic a model for influenza with vaccination and antiviral treatment containing pandemic influenza with antiviral agents containing pandemic influenza at the source economic evaluation of influenza pandemic mitigation strategies in the united states using a stochastic microsimulation transmission model modelling mitigation strategies for pandemic (h n ) effective, robust design of community mitigation for pandemic influenza: a systematic examination of proposed us guidance rescinding community mitigation strategies in an influenza pandemic health outcomes and costs of community mitigation strategies for an influenza pandemic in the united states assessing the role of basic control measures, antivirals and vaccine in curtailing pandemic influenza: scenarios for the us, uk and the netherlands mathematical assessment of canadas pandemic influenza preparedness plan a model for the spread and control of pandemic influenza in an isolated geographical region the influenza pandemic preparedness planning tool influsim transmissibility of pandemic influenza epidemic influenza; a survey chicago: american medical association pandemic potential of a strain of influenza a (h n ): early findings an influenza simulation model for immunization studies non-pharmaceutical interventions for pandemic influenza, national and community measures local and systemic cytokine responses during experimental human influenza a virus infection the early diversification of influenza a/ h n pdm phylogeography of the spring and fall waves of the h n / pandemic influenza virus in the united states estimates from a national prospective survey of household contacts in france household transmission of pandemic influenza a (h n ) virus in the united states timelines of infection and disease in human influenza: a review of volunteer challenge studies different epidemic curves for severe acute respiratory syndrome reveal similar impacts of control measures real-time estimates in early detection of sars estimating individual and household reproduction numbers in an emerging epidemic a likelihood-based method for real-time estimation of the serial interval and reproductive number of an epidemic real time bayesian estimation of the epidemic potential of emerging infectious diseases estimating in real time the efficacy of measures to control emerging communicable diseases the effective reproduction number of pandemic influenza. prospective estimation estimating reproduction numbers for adults and children from case data pros and cons of estimating the reproduction number from early epidemic growth rate of influenza a (h n ) global infectious disease surveillance and health intelligence monitoring influenza activity, including using internet searches for influenza surveillance detecting influenza epidemics using search engine query data the use of twitter to track levels of disease activity and public concern in the u.s. during the influenza a h n pandemic the role of the airline transportation network in the prediction and predictability of global epidemics social contacts and mixing patterns relevant to the spread of infectious diseases little italy: an agent-based approach to the estimation of contact patterns -fitting predicted matrices to serological data reality mining: sensing complex social systems dynamics of person-to-person interactions from distributed rfid sensor networks cellular census: explorations in urban data collection. pervasive computing mobile landscapes: using location data from cell-phones for urban analysis. environ and planning b: plann and des social and economic impact of school closure resulting from pandemic influenza a/h n compliance and side effects of prophylactic oseltamivir treatment in a school in south west england using an online survey of healthcare-seeking behaviour to estimate the magnitude and severity of the h n v influenza epidemic in england behavioural intentions in response to an influenza pandemic modelling the influence of human behaviour on the spread of infectious diseases: a review the scaling laws of human travel understanding individual human mobility patterns adaptive human behavior in epidemiological models stochastic modelling of the spatial spread of influenza in germany simple models of influenza progression within a heterogeneous population planning for the next influenza h n season: a modelling study a populationdynamic model for evaluating the potential spread of drug-resistant influenza virus infections during community-based use of antivirals optimizing the dose of pre-pandemic influenza vaccines to reduce the infection attack rate finding optimal vaccination strategies for pandemic influenza using genetic algorithms living with influenza: impacts of government imposed and voluntarily selected interventions public health interventions and epidemic intensity during the influenza pandemic the effect of public health measures on the influenza pandemic in the us cities the authors wish to thank doctor lillian stark, virology administrator of the bureau of laboratories in tampa, florida, for providing valuable information on the problems faced by the laboratory during the h n pandemics. the authors also wish to thank the reviewers of this manuscript for providing valuable suggestions and reference material. we appreciate the support of dayna martinez, a doctoral student at usf, in providing some literature information on social-behavioral aspects of pandemic influenza. authors' contributions dp conducted the systematic review and analysis of the models. td and as guided dp and au in designing the conceptual framework for the review. all three jointly wrote the manuscript. ri and sm provided public health expert opinion on the conceptual framework and also reviewed the manuscript. all authors read and approved the final manuscript. the authors declare that they have no competing interests. key: cord- -zz walri authors: chellamuthu, girinivasan; muthu, sathish title: pandemic response protocol of a non-frontline specialty in a multispecialty tertiary health care centre—a pilot model in orthopaedics date: - - journal: int orthop doi: . /s - - -w sha: doc_id: cord_uid: zz walri background: , , cases and , deaths in regions of the world—this is the status of covid- (coronavirus disease ) pandemic as of may , . this pandemic has managed to overwhelm the health care system of the most advanced countries in the world. as the whole of the medical fraternity stands robed as health care professionals to fight against covid- , specialty emergencies like trauma continue to pester the already overburdened health care community. this situation calls for the need for a pandemic response protocol (prep) in each specialty that helps the doctors to manage specialty emergencies without chaos and at the same time allowing them to play their part in pandemic management. conclusion: prep as an integrated pragmatic approach is essential in containing pandemics as they need international cooperation at various levels starting from knowledge sharing to monetary support. prep which is in line with the who action plan, will be an essential minimum response of a non-frontline pandemic response specialty like orthopedics to combat and curtail the effects of a pandemic in a multispecialty tertiary health care centre. background , , cases and , deaths in regions of the world-this is the status of covid- (coronavirus disease ) pandemic as of may , [ ] . this pandemic has managed to overwhelm the health care system of the most advanced countries in the world. as the whole of the medical fraternity stands robed as health care professionals to fight against covid- , specialty emergencies like trauma continue to pester the already overburdened health care community [ ] . this situation calls for the need for a pandemic response protocol (prep) in each specialty that helps the doctors to manage specialty emer-gencies without chaos and at the same time allowing them to play their part in pandemic management. the prep should allow a non-frontline pandemic specialist like an orthopaedician to be alert and trained to evolve as a frontline health care provider, as and when the situation demands, on the lines of development of a pandemic. we intend to formulate a response protocol based on the current guidelines from various national orthopaedic associations [ ] [ ] [ ] and international orthopaedic organizations [ , ] along with available relevant covid literature that will help us to be well prepared for the upcoming pandemics or the second wave of covid- if at all one comes. before any protocol that has to be designed for a pandemic situation, there are certain factors to be considered in their design. they include: the aim of prep is to tide over the pandemic crisis as an efficient health care workforce in the most effective way. . attend to orthopaedic emergencies. . patient and healthcare worker protection. . conserve and educate the orthopedic workforce on pandemic control. . rise to the occasion as a frontline pandemic control team when needed. the world health organization (who) divided the development of pandemic into six phases in . this was further revised in and after the h n flu pandemic [ ] ( table ). the phases were devised in such a way that they apply to the whole world providing a global framework to help countries in pandemic preparedness and response planning [ ] . a specialty prep should closely evolve in stages with who phases of development of pandemic to achieve its aim as shown in table . the prep activation should begin ideally when a country enters phase of pandemic and continue until the beginning of the post-pandemic phase. the various stages of orthopaedic prep are summarized in fig. . this stage begins with phase of the pandemic. awareness about the pandemic is important and the national orthopedic forum should take up this responsibility and be in close lines with the who action plan. it should impart the information including signs and symptoms of possible pandemic and personal protective measures needed to combat the pandemic through scientific media to its fellow members. this prepares an orthopaedic surgeon to be socially more responsible and pick up the initial cases that he may come across. this also alerts him to be more responsive to the next stage of pandemic. institutes should take adequate steps to ensure a continuous and adequate supply of personal protective equipment (ppe) for pandemic response. they should ensure the availability of adequate isolation beds and wards. this stage begins with phase of the pandemic. at this stage, essentially, the orthopaedic surgeons would have to become a part of the pandemic response task force which includes the entire health care workforce. our primary aim must be the prevention of human-tohuman transmission thereby averting impending pandemic [ ] while we balance orthopaedic care to the general public. at this stage, the orthopaedic workload is not expected to decrease yet. however, as a containment measure, it is essential to split up the orthopaedic workforce into two dedicated teams including one inpatient and one outpatient team which alternate every week without a reduction in workforce. these teams do not come in contact with each other. the doctors in the outpatient department are those that are about to pick up initial positive or suspect cases of the ongoing pandemic. so, they must hold a high vigil and at the same time be armed with adequate ppe. it is essential to have an institute specific history form to be filled in by all outpatients that warn the hospital of those with relevant travel history or symptoms. symptomatic cases should be categorized as either suspect or non-suspect cases according to national or international guidelines [ , ] and should be treated accordingly. the use of removable casts and splints should be maximized to reduce follow-up requirements. patients requiring emergency/early orthopaedic intervention must be attended to immediately as in normal scenarios. these include patients with orthopaedic oncology, trauma, and non-traumatic paediatric and spine conditions requiring immediate attention [ ] . day care procedures can still be carried out as they do not affect the inpatient beds available for pandemic preparedness. day care procedures include arthroscopy surgery and simple procedures like implant removals which require < h of hospital care [ ] . elective procedures in high-risk patients such as joint replacement procedures and spinal decompression procedures in the elderly should be avoided completely. adequate analgesics including intra-articular analgesic injections or nerve root blocks can be provided to prevent their frequent hospital visits. documented evidence shows elderly patients with comorbid conditions and low physiologic reserves succumb to pandemic diseases [ ] [ ] [ ] ; hence, they should be advised of the potential threat and their surgery should be deferred. orthopaedic trauma and oncological patients taken up for inpatient surgical care must be provided with prompt consultant driven surgical and anaesthetic care whenever possible which might aid in reducing the period of hospital stay. principles of early total care in trauma patients whenever possible are to be followed. rehabilitative services may be provided on a home-based approach through various online tools to aid in expedited discharges in reasonably quick time to have the manpower and beds available for the ongoing pandemic. we should avoid advising non-essential follow-ups. local or telemedicine follow-up of post-operative patients, home visits, and local refilling of essential medications should be implemented where ever possible. inpatient visitor's records should be maintained. only one visitor for a patient should be allowed. visitors should also be asked to fill the history form and must be screened for symptoms. the institutes and departments must strictly follow the directives of the health ministry of the country and the who while handling the international patients. the department must set standard protocols to handle interdepartmental referrals. each referral must be categorized into a suspect and non-suspect referral and handled accordingly by a dedicated team. the orthopaedic training for registrars and post-graduates in the department during this phase must essentially include daily updated knowledge on the nature of pandemic, the rationale behind ppe, and method of robing and disrobing ppe among others. this can be through video lectures or interdepartmental lectures if manpower is available. this stage begins with phase of the pandemic. phase of the pandemic with documented human-to-human transmission needs extreme containment measures [ ] . the department must be split into four groups. specialty specific workload is expected to be reduced due to national/ regional lockdown. . management of outpatient department . management of theaters and inpatients . training in intensive care/pandemic preparedness . shifts in screening pandemics the institute must cancel all the outpatient appointments with clear notice to the patient through their phone numbers. only non-postponable paediatric outpatient procedures like casting for congenital deformity like clubfoot, vertical talus, and hip dysplasia can be addressed to avoid complex surgery with unsuccessful outcomes in the future. other inevitable services like routine chemotherapy regimens can be administered at the nearest possible primary health centres under supervision. if such measures are not feasible, they can be given as a day care service in the hospital. telemedicine must be encouraged whenever possible. follow-up x-rays if needed can be advised to be taken near the locality of the patient and emailed to the institute. the institute must have a standard set of physiotherapy videos that can be advised to the patient through telemedicine. only emergency trauma surgeries and non-postponable spine and paediatric surgery like slipped capital femoral epiphyses (scfe) fixation, growth rod lengthening, and growth modulation procedures should be taken up with as minimal hospital stay as possible. history forms should be maintained. each patient should be categorized as suspect/non-suspect before being admitted. operating rooms with a negative-pressure environment, frequent air exchange, and separate access are needed. when the airborne spread of the pandemic is a concern during aerosolgenerating procedures such as drilling, intubation, or extubation, it is important to have proper ppe and protocols in place to limit the spread of infection in this setting [ ] . ante-rooms in which to put on and remove protective equipment should be available or even constructed adjacent to the operating room [ ] . the operating room must work with minimal staff pattern. adequate time between procedures is needed for decontamination. a senior-most surgeon on call should be advised to perform all the procedures. surgical time and blood loss must be kept to minimal as far as possible. regional and local anaesthesia is preferred to general anaesthesia when the pandemic is suspected to be airborne [ ] . with the decrease in need of residents and fellows in operation theaters as the senior consultants perform most of the procedures, we should wisely engage the seemingly excess workforce. more number of them should be deployed in emergency rooms and casualties to relieve emergency physicians for a more responsible role in handling pandemic emergencies. routine anaesthesia and intensive care postings of the residents should be preponed in the initial phase of the pandemic so that they get trained when the need arises and at the same complete their curriculum. the psychological trauma to the doctors during the time of pandemic is multifactorial including the inability to fulfill their standards of patient care, separation from family, inability to fulfill the family needs, isolated working pattern, the spread of infection to colleagues, fear of the spread of infection, and long working hours [ ] . the institute must put in place adequate measures to avert psychological trauma due to all of these issues. this is the single most important part of prep. a group of surgeons must take part in formal training in non-surgical skills like handling icu equipment. they should have first-hand knowledge of screening and treatment of patients of the pandemic. they should be prepared to step up as the frontline pandemic response team when the situation demands [ ] . this stage begins with phase of the pandemic. the surgical group should be split into two teams: one to handle the orthopaedic workload and the other for pandemic response. the fluency of specialty people to get transformed into the frontline pandemic workforce will have positive psychological and health impacts in pandemic mitigation [ ] . this will satisfy the ultimate aim of our response protocol. pandemic orthopaedic case handling protocol [ - , , ] emergencies . polytrauma, pelvi-acetabular fractures with major haemorrhage, compartment syndrome, and exsanguinating injuries should be prioritized for early surgical management. . dislocations should be attended immediately. . septic arthritis and prosthetic joint infections should be attended immediately. . localized abscesses without signs of sepsis should be drained in the emergency department. should be managed by suppressive antibiotic therapy orally where ever possible. . complex fractures fixations are planned in such a way to minimize the hospital stay and if a staged approach is used, the aim is to discharge and re-admit the patient whenever possible. pre-pandemic and post-pandemic stages of prep stage : pre-pandemic stage the twentienth century saw influenza pandemics. thus, the pre-pandemic stage typically lasts for years together. this phase should be used for research, development, and testing of pandemic response protocols which should also follow the lines of research and development of who pandemic response. annual pandemic response mock drills should be a routine in every country. this stage corresponds to the post-peak phase and possible new wave phase of a pandemic by the who [ ] . in case of favourable regional scenario, stepping down of pandemic response to stage and then to stage should be carried out. resting a part of the exhausted workforce is essential. quasi emergency procedures that have been postponed because of pandemic response like a highly painful disc herniation on analgesics should be timed during this period. every patient posted for surgery must be screened for the pandemic infection and necessary consent must be obtained for change in treatment options depending upon the results of the screening. once the elective surgeries are resumed, the hospital must follow a priority list of waitlisted patients made based on the severity of the condition and age of the patient. we should, however, be prepared to step up the pandemic response if the second wave of pandemic occurs. unfolding its deadliness in more than regions of the world, this covid- pandemic has made it clear the importance of pandemic preparedness. one good example is the disease outbreak response system condition (dorscon) of singapore [ , ] . this was developed after the severe acute respiratory syndrome (sars) infection in singapore. this system is a nation-wide color-coded guidance protocol to alert the health care system depending on the level of threat by the epidemic. effective implementation of dorson resulted in effective covid- containment in singapore [ ] . though who and most of the national health care agencies have their pandemic control strategies, they will not invoke the desired effects at the grass-root level unless they are supported coherently by departmental pandemic response systems. national associations and international organizations drawing new guidelines every fortnight in the middle of a pandemic will only create confusion among their members. hence, a pre-defined prep model prevents chaos, instills order, and provides moral support in the to-be stressed up health care system. we hope such a prep model will evoke a better coherent response against the pandemic. this pandemic response protocol is just a pilot model in this direction. the inclusion of pandemic response knowledge in the academic training of all specialties is a must. additive knowledge of centuries is essential to deal with these oncein-lifetime catastrophes. so, literature must be analyzed, review articles must be published, and evidence-based changes should be made to the protocol in line with international pandemic preparedness protocols. a basic infrastructure that every institute or department should include must be standardized and improved. this model applies to a full-fledged orthopaedic department in a multispecialty corporate or tertiary care teaching hospital. this does not apply to a dedicated orthopaedic specialty hospital or small-town multispecialty center where the scenario and resources are quite different. the efficiency of disaster management in any region is dependent on the availability of resources. it falls on the shoulders of the administration and national governing bodies to make sure adequate resources are available to meet the demands. protocols like prep makes difference in their ability to help us utilize the available limited resources to the maximum to mitigate the pandemic. some customization of the protocol for every pandemic is going to be essential and unavoidable. integrated pragmatic approach under the who is essential in containing pandemics as they need international cooperation at various levels starting from knowledge sharing to monetary support [ ] . prep as the one described above in line with the who action plan will be an essential minimum response in a non-frontline pandemic response specialty like orthopaedics to combat and curtail the effects of a pandemic. compliance with ethical standards coronavirus disease (covid- ) situation dashboard maintaining trauma center access & care during the covid- pandemic: guidance document for trauma medical directors indian orthopedic association guidelines covid guidelines management of patients with urgent orthopaedic conditions and trauma during the coronavirus pandemic statement from the ota health policy committee world health organisation ( ) pandemic influenza preparedness and response community mitigation guidelines to prevent pandemic influenza -united states ) investigation and initial clinical management of possible cases specialty guides for patient management during the coronavirus pandemic: clinical guide for the perioperative care of people with fragility fractures during the coronavirus pandemic novel coronavirus and orthopaedic surgery: early experiences from singapore epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study severe outcomes among patients with coronavirus disease (covid- ) -united states similarity in case fatality rates (cfr) of covid- /sars-cov- in italy and china personal protection equipment (ppe) novel coronavirus covid- : current evidence and evolving strategies managing mental health during covid critical care crisis and some recommendations during the covid- epidemic in china specialty guides for patient management during the coronavirus pandemic: clinical guide for the management of trauma and orthopaedic patients during the coronavirus pandemic the surgical royal colleges of the united kingdom and ireland ( ) guidance for surgeons working during the covid- pandemic singapore ministry of health ( ) what do the different dorscon levels mean evaluation of the effectiveness of surveillance and containment measures for the first patients with covid- in singapore publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations the authors declare that they have no conflict of interest. key: cord- -c jq j authors: tagliabue, fabio; galassi, luca; mariani, pierpaolo title: the “pandemic” of disinformation in covid- date: - - journal: sn compr clin med doi: . /s - - - sha: doc_id: cord_uid: c jq j in recent years, mass media and social networks have played an important role in disseminating information regarding public health. during the covid- epidemic, misinformation and fake news have represented an important issue generating confusion and insecurity among the population. in our analysis, we investigate the role of mass media as a critical element during the sars-cov- outbreak that has influenced the public perception of risk. the role of the mass media and social networks has always been fundamental in the management of health-related information. during this current pandemic, people have been continually searching for information regarding the coronavirus infection. in many cases, people have unfortunately found themselves overwhelmed with news containing fake reports and misinformation, which, for those without the right skills, can be complicated to digest. this situation has generated confusion within the population and has also influenced some statements by public figures and politicians, which have in turn have led to further repercussions on public opinion. the general population has, in good faith, taken the information, including fake news, most relevant to their own personal situation and has used it to formulate their own interpretation of the pandemic. at the beginning of the pandemic, the medical community also played a role in making the situation even more confusing by giving, in some cases, inaccurate and sometimes contradictory indications on covid- . there have been numerous media debates about who advocated distinct conflicting positions. two opposite positions could be recognized from the numerous interviews between members of the medical community: on the one hand those who were inclined to spread alarming news and on the other who had optimistic ideas that supported a non-hazardous nature of covid- . a few weeks after the start of the pandemic, comments from non-specialists in infectious-respiratory problems could be seen in the mainstream media. it seemed as though the entire scientific community (gastroenterologists, nephrologists, surgeons, neurologists…) were releasing statements and writing articles as if they were the main experts of covid- . people were so overwhelmed by this flood of information that they did not have time to understand it correctly. the massive presence in the mass media of doctors who expressed their opinions, sometimes not supported by scientific evidence, could be interpreted as a desire to appear rather than the need to provide the correct indications. the alarming tone of some experts has caused in some cases a rush to purchase personal protective equipment (ppe) and alcoholic detergents; this fact partially contributed to the lack of ppe in the clinical sector and to a disproportionate increase in the prices of these products. in psychologically fragile subjects, an exacerbation of psychiatric pathologies [ ] and determined headline stress disorder [ ] has been manifested. initial, and overly optimistic medical statements that judged the epidemic as a simple influenza lowered social attention on the covid- pandemic and instilled in some people conspiracy or denial ideas supported by statements by some doctors and non-medical professionals who said, "it's just a flu." [ ] the poor perception of the risks related to covid- infection also manifested itself despite the exponential growth of infections and deaths. in italy, on march , , while [ ] . in the usa, the lockdown, imposed to reduce contagion, has been strongly opposed and its purpose diminished by comments in the media from public figures who have a greater following than the scientific community in influencing public opinion. similarly, the mass media, in an attempt to gain visibility, have perhaps unwittingly misinformed the public whenever a new experimental treatment started. the beginning of an experimental treatment was reported by newspapers who reported it as the decisive discovery to combat sars-cov- , thus accentuating people's sense of security [ ] . moreover, the search for journalistic scoops has triggered a race to find responsibility for the covid- pandemic, and has thus reduced the trust of people in the national and international institutions responsible for preserving public health. social media platforms are well known for the spread of misinformation and denial of scientific literature [ ] . fake news has reduced the relevance to evidence-based precautions promoted by national health services [ ] , and perhaps, little has been done to stop this virus on social networks. the who has offered a whatsapp service to refute fake news, but unfortunately the rapid, viral spread of disinformation on social networks has been so widespread that we have in fact witnessed the appearance of attitudes harmful to health. in some cases, patients refused to take ibuprofen or other anti-inflammatory drugs because of the erroneous idea that they could increase the chances of getting infected with the coronavirus [ ] . misleading information about treatment for covid- has resulted in an increasing number of vitamin d abuse and even mass poisoning from methanol intake [ ] . after the lockdown, in countries where social distancing and the use of face masks were mandated, news of correlation between cancer and mask coverings appeared on social networks [ ] . the lockdown and consequent social distancing has resulted, especially in those residing in highly infected areas, in a posttraumatic stress syndrome (ptsd) characterized by anxiety, sleep disturbances, distress, and a drop in the tone of the mood with a decrease of positive mood such as happiness and serenity and an increase of sadness or boredom [ , ] . misinformation and fake news contributed to the onset of ptsd and headline stress disorder cases [ ] . the consequences of these disorders have not only had effect in the peak infection phase but will also have future repercussions. the historical importance of the covid- pandemic is such that, also in the future, covid- -related news will be published cyclically in the mass media and on social networks. poor quality information may in the future amplify anxiety to the state of panic especially in the event of a new wave of infections; people will relive the moments of the first phase of the peak of covid- and will return to look for information to safeguard their health and that of their loved ones. fake news also stimulated indignation with the consequent reaction of people for an alleged injustice. the incomplete or incorrect news reported by the mass media and then reworked on social networks have also focused attention on possible errors of some hospital structures. in some cases, this will mean that patients will be reluctant to go to hospitals or medical centers in the fear of becoming victims of medical errors or to be at a greater risk of contagion. healthcare workers, subject to ptsd risk, may have an additional psychological burden as they may suffer lawsuits brought by relatives of victims of covid- who will accuse them of not having undertaken for their loved one's therapies that the mass media described as effective, but which were actually experimental. even an effective vaccine against covid- could run the risk of falling victim of fake news by reducing the number of people who will join the vaccination campaigns. the rapid evolution of the covid- pandemic has not permitted immediate and certain scientific data. considering this, the need therefore arises that, especially in the event of pandemics, doctors must provide the public only with evidence-based information in a simple and shared way in order to avoid misinterpretation and misunderstanding. better coordination between the medical community, governments, and the mass media is therefore needed to avoid the spread of disinformation through different channels, limiting the dissemination of fake news and thereby better engaging the general public to adhere to correct guidelines. author contributions all authors conceived and planned this paper, devised the project and the main conceptual ideas. moreover, all authors provided critical feedback and helped shape the research, analysis, and writing the manuscript. conflict of interest the authors declare that they have no conflicts of interest. covid- effect on mental health: patients and workforce letter to the editor: headline stress disorder caused by netnews during the outbreak of covid- il coronavirus è poco più di una normale influenza italian ministry of the interior. monitoraggio dei servizi di controllo inerente le misure urgenti per il contenimento della diffusione del sn compr antimalarial drug has curative effect on coronavirus, chinese experts say the twitter pandemic: the critical role of twitter in the dissemination of medical information and misinformation during the covid- pandemic going viral: doctors must tackle fake news in the covid- pandemic headache medication and the covid- pandemic methanol mass poisoning outbreak: a consequence of covid- pandemic and misleading messages on social media le mascherine fanno venire il cancro? la teoria di montanari fa infuriare burioni covid- pandemic in the italian population: validation of a post-traumatic stress disorder questionnaire and prevalence of ptsd symptomatology the enemy which sealed the world: effects of covid- diffusion on the psychological state of the italian population publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -ezxvgku authors: henneberg, maciej; rühli, frank title: covid- and evolutionary medicine date: - - journal: evol med public health doi: . /emph/eoaa sha: doc_id: cord_uid: ezxvgku nan microorganisms evolve quickly due to their short generation times and because point mutations are expressed easily. when new microorganisms evolve or are introduced to the human population, they may be highly virulent or transmissible, with further evolution shifting these parameters over time. a lot of infections are spread by human contacts. in the past, human interactions were usually limited to local communities and their immediate neighbours. many pathogens that become pandemic are similar to gene flow, i.e., they require close physical contact for their spread. it has been estimated that to pass a gene (or an endemic pathogen) from china to south africa would require more than , years in hunter-gatherer populations of our evolutionary past (henneberg ) . thus, rapid pandemics are a modern phenomenon. this novel global transmission dynamic amplifies the consequences of infectious disease introductions. a pathogen entering a local community elicits adaptive reactions. these are immune responses of individuals, and gene pool adaptations through fast acting natural selection. before the advent of effective preventive methods and therapies, opportunities for the operation of natural selection were very large -due to premature mortality, only about one third of individuals born had an opportunity to pass their genes to the next generation (rühli and henneberg ) . thus, adaptations of local gene pools to new pathogens were fast. because pathogen transmission via human contact was slow, worldwide pandemics were rare. the historically recorded pandemics were related to invasions at the end of classical antiquity and in the middle ages. they caused enormous numbers of deaths that destroyed economies and altered the biological characteristics of human populations (e.g., historical selective pressures for the ccr -delta hiv-resistance allele) . public health measures in many of past pandemics were very similar to those i ntroduced in the current pandemic, such as isolating sick individuals which was already described e.g.in the london privy council rules and orders ( ). yet they were not effective because the only way to eradicate a pandemic -instead of allowing it to run its course and, through acquired immunity and natural selection to leave behind a decimated population not susceptible to the pathogen -is to find effective means of killing the pathogen or providing immunity to the population. to what extent the current pandemic can be compared to previous pandemics -such as the influenza pandemic -will continue to be debated as this pandemic's course takes shape. its dynamics is somewhat different for example due to the level of public and scientific awareness in the present situation. although the death toll of past pandemics was enormous, they did not kill everyone. one factor that has enabled humanity to persist involves a basic characteristic of populations: variation. biological variability produced by mutation/selection balance, genetic polymorphisms, adaptive responses during ontogeny, life histories, and particular ways of infections and immune responses results in different phenotypic characteristics that enable some individuals to survive pandemics. in the covid- pandemic, the course of disease varies in different patients, from completely asymptomatic to fatal. although initial clinical observations indicate characteristics of specific susceptibility such as age, sex and some co-morbidities, it is far from known to what extent these phenotypes reflect genetic variation, ontogenetic adaptability, and particular characteristics of infection, such as timing of infection and viral load. understanding the evolutionary drivers of these characteristics is of particular importance to public health, including because some of these traits may be enhancing existing health disparities. fast viral evolution makes it difficult for hosts to acquire lasting immunity to repeated infection, and not all organisms produce lasting immunity. vaccines may therefore be only partly effective (innis et al. ) . the only way to effectively eradicate covid- is to remove its cause from bodies of individual patients and reduce contact with the (as yet unknown) natural reservoir. we need to develop an efficient medication that will stop reproduction of the virus in humans, and then use that medication in a way that will avoid evolution of resistance by the virus. such "evolution proof" solutions are another way that evolutionary medicine can contribute to stopping the current pandemic. innovations appear randomly. one can foster a potentially innovative climate but not force an innovation. thus, it is important to have free discussions and true collegiality in the research community, including across disciplines. at the moment many groups of medical scientists are working diligently and selflessly to control covid- , but their communications are limited and occur in the organisational structure of research institutions hampered by a multitude of complex regulations and informed by competition for commercial gain, grants, and publication scores. individual researchers in the process of doing research consider their incomes, professional careers and reputation. governments who support medical research are concerned about appropriateness of their methods and quantities of support. furthermore, humans did not evolve to cope with logical, mathematical problems. to understand exponential epidemiological data is beyond primary abilities of human individuals, especially non-scientists making decisions in the current situation. all this slows response of medical science to quickly arising global health threats. at present (june ) no effective vaccines, nor cures are available. in an emergency, the complex machinery of medical science finds it difficult to become efficient and follow the principle of parsimony -cut out all the "fluff" and go straight to the main aim. only by taking evolutionary perspectives into account will we effectively solve the issue of the current and future pandemics. this must involve communication and collaboration across disciplines, and an open mindset. the gradual eurytopic evolution of humans: not from africa alone meeting report: convening on the influenza human viral challenge model for universal influenza vaccines, part : value; challenge virus selection; regulatory, industry and ethical considerations; increasing standardization, access and capacity privy council rules and orders reprinted in bell wg the great plague in london biological future of humankind: ongoing evolution and the impact of recognition of human biological variation both authors contributed equally. not applicable key: cord- -pprxwij authors: elshami, wiam; akudjedu, theophilus n.; abuzaid, mohamed; david, leena r.; tekin, huseyin ozan; cavli, b.; issa, bashar title: the radiology workforce’s response to the covid- pandemic in the middle east, north africa and india date: - - journal: radiography (lond) doi: . /j.radi. . . sha: doc_id: cord_uid: pprxwij introduction this study aimed to investigate the response of the radiology workforce to the impact of the coronavirus disease (covid- ) pandemic on professional practice in india and eight other middle eastern and north african countries. it further investigated the levels of fear and anxiety among this workforce during the pandemic. methods a quantitative cross-sectional study was conducted using an online survey from may- june among radiology workers employed during the covid- pandemic. the survey collected information related to the following themes: ( ) demographic characteristics, ( ) the impact of covid- on radiology practice, and ( ) fear and ( ) anxiety emanating from the global pandemic. results we received responses. fifty-eight percent had completed training on infection control required for handling covid- patients. a large proportion ( . %) of the respondents strongly agreed or agreed that personal protective equipment (ppe) was adequately available at work during the pandemic. the respondents reported experiences of work-related stress ( . %), high covid- fear score ( . %) and anxiety ( %) during the study period. conclusion there was a perceived workload increase in general x-ray and computed tomography imaging procedures because they were the key modalities for the initial and follow-up investigations of covid- . however, there was adequate availability of ppe during the study period. most radiology workers were afraid of being infected with the virus. fear was predominant among workers younger than years of age and also in temporary staff. anxiety occurred completely independent of gender, age, experience, country, place of work, and work status. implications for practice it is important to provide training and regular mental health support and evaluations for healthcare professionals, including radiology workers, during similar future pandemics. the radiology workforce's response to the covid the radiology workforce's response to the covid the radiology workforce's response to the covid the radiology workforce's response to the covid---- we received responses. fifty-eight percent had completed training on infection control required for handling covid- patients. a large proportion ( . %) of the respondents strongly agreed or agreed that personal protective equipment (ppe) was adequately available at work during the pandemic. the respondents reported experiences of work-related stress ( . %), high covid- fear score ( . % ) and anxiety ( %) during the study period. there was a perceived workload increase in general x-ray and computed tomography imaging procedures because they were the key modalities for the initial and follow-up investigations of covid- . however, there was adequate availability of ppe during the study period. most radiology workers were afraid of being infected with the virus. fear was predominant among workers younger than years of age and also in temporary staff. anxiety occurred completely independent of gender, age, experience, country, place of work, and work status. implications for practice: implications for practice: implications for practice: implications for practice: the r the r the r the radiology adiology adiology adiology workforce's workforce's workforce's workforce's response to response to response to response to the the the the covid covid covid covid---- pandemic in pandemic in pandemic in pandemic in the the middle east, the the middle east, the the middle east, introduction introduction introduction introduction the world health organisation officially announced the coronavirus disease (covid- ) outbreak as a pandemic in march ( ) after the virus was initially detected in the chinese city of wuhan in december ( , ) . radiological investigations, such as chest radiography and computed tomography (ct), play a major support role in the diagnosis of respiratory manifestations in covid- ( - ) along with the patient's clinical history and blood biomarkers ( , ) . thus, radiology departments are essential in the management of highly infectious patients, and the radiology workforce (rwf) is a part of the multidisciplinary healthcare team on the front lines of combating the covid- . most of the rwf comes into physical contact with patients while positioning them for radiological examinations. therefore, it is essential for the imaging team to strictly adhere to appropriate rules of conduct to protect themselves from the risk of exposure and contracting coronavirus, especially as a nosocomial infection ( ) ( ) ( ) . however, the pandemic has brought a risk of infection and a high mortality rate as well as psychological and mental trauma to the public and medical personnel ( , ) . in response to the pandemic, health care professionals (hcps) have dedicated themselves to the service of others despite the impact on their emotional and physical wellbeing due to uncertainties, varying work requirements and extended work schedules ( ) ( ) ( ) . moreover, significant amounts of variance in work may indirectly impose a considerable amount of anxiety and stress among hcps ( , ) , as has been revealed in other outbreaks, such as severe acute respiratory syndrome and ebola ( , , ) . anxiety can be either stimulus-related or general in nature ( ) , and these experiences can lead to negative impacts and long term adverse mental health consequences among hcps ( , ) . thus, hcps face incredible challenges while having to deliver radiological services to patients during this unprecedented time ( ) . stress is an emotional experience that increases when events are uncontrollable and unpredictable ( ) . stress can produce biophysical reactions, such as headache, abdominal pain, chest pain, eating and sleep disturbances and heart palpitation, as well as; psychological-j o u r n a l p r e -p r o o f emotional reactions, such as anxiety, depression, tension, anger, nervousness and frustration ( ) . stress and anxiety are linked to fear ( ) . fear is a present response when facing a real or supposed threat, while anxiety is a future response that indicates an impending danger ( ) . anxiety and fear are likely distinct emotional states but often overlap due to underlying behavioural mechanisms ( ) . furthermore, in an attempt to maintain adequate healthcare workers to cope with covid- cases, it is likely that work-related anxiety may affect all members of the healthcare team. this impact can lead to variation in the team's psychosocial variables along with burnout and emotional exhaustion ( , ) . additionally, these experiences may weaken the team's morale and confidence and can affect the healthcare delivery system and its associated reassurance to the public ( ) . prevention and intervention are requirements that focus on the individual along with the working conditions to reduce high levels of emotional tension and to positively impact workrelated behaviour ( ) . to improve the current situation and plan for future similar incidents, this was an exploratory, quantitative, cross-sectional study that investigated the impact of covid- and related anxiety and fear among the rwf across the menain region. the study was needed to capture the impact of the current urgent situation of the covid- outbreak. the current study design was generally quick, easy, and cheap to perform and was particularly suitable for estimating the impact of covid- on the population ( , ) . participants included the rwf working at hospitals during the pandemic, such as radiologists, radiographers, advanced practitioners, and radiology nurses. the population size was unidentified, as there have been no previous studies in this region to the best of our knowledge. therefore, we used the formula of cross-sectional studies to calculate the sample size with a % confidence level, the margin of error was set at %, and the population size was infinite. the calculation proposed a minimum of participants. the study used convenience sampling as it is an easy method to access participants in different geographical proximity. the survey consisted of four sections: ( ) demographic characteristics, ( ) psychological symptoms of fear or anxiety that respondents experienced when exposed to covid- related thoughts or information. the total score was calculated by adding up each item's score (ranging from - ). based on a cas cut-off score of ≥ , current users of the cas may consider lowering the cut-off score to ≥ when assessing the general population but retaining a cut-off score of ≥ when screening at risk or anxious groups ( ) . the fc- s was used to assess fears caused by covid- ( ) . the participants indicated their level of agreement with the statements using a five-item likert-type scale ranging from ( = 'strongly disagree', = 'disagree', = 'neither agree nor disagree', = 'agree', and = 'strongly agree'. the total score was calculated by adding up each item's score (ranging from - ). the higher the score, the greater the fear of covid- ( ) . the professional practice questionnaire was adopted from a previous study carried out in the uk ( ) . a pilot study was conducted, and minimal language edits were performed based on the feedback received from participants. participants of the pilot study were not included in the current study. the cas is a highly reliable (α = . ) and factorially valid measure that meets conventional standards for model fit ( , ) . the fc- s is also a highly reliable measure with acceptable internal consistency (α = . ) ( ) . moreover, the cas and fc- s have been validated and used in previous studies for hcps and the general public ( ) ( ) ( ) ( ) ( ) ( ) . the link to the online survey was shared amongst the radiology health board leads across multiple countries via email and was advertised on social media platforms. participants were given an electronic informed consent form to indicate their willingness to participate in the study, and a completed form was mandatory before filling in the survey. ethical approval for the study was obtained from the research ethics committees of three institutions (id: , id: - - - and id: / ). the data were collected, categorized and processed using the statistical package for social sciences (spss), version ®. the quantitative variables were expressed as percentages, and comparisons were made using independent sample t-tests and pearson chi-square tests. p-value of < . were considered statistically significant. all graphs were created using microsoft office excel ®. cut-off point ≥ was used to assess the level of anxiety among participants,and the score of ≥ was considered dysfunctionally anxious. the mean cas score was calculated based on the total score of all items scores. there was no defined cut-off point for the fc- s; therefore, the authors suggested a score of > as a high fear score, while scores from - as medium fear, and < were regarded as low fear. nine hundred and three responses were received from radiology workers. of these, % percent (table ) . of participants, . % had received training on infection control and handling infected patients. figure ( ) shows that . % strongly agreed and agreed that they understood the methods of covid- transmission, and . % strongly agreed and agreed that their current understanding of infection prevention principles and control was adequate to protect themselves and their patients during the covid- pandemic. finally, . % of the respondents strongly agreed and agreed that ppe was adequately available at the workplace ( figure ). the main diagnostic tools used for both the initial and follow-up investigations of covid- patients were general x-ray and ct; these modalities were used by and of the respondents, respectively. therefore, . % (n = ) and . % (n = ) of respondents reported an increased workload for general x-ray and ct, respectively, during the study period. the overall workload in the radiology department increased during the study period for . % of the participants, while . % reported an irregular pattern ( figure ). the results indicated that . % of the respondents began to experience work-related stress during the covid- pandemic, and . % experienced stress sometimes. the analysis revealed that . % strongly agreed and agreed that their family, partners and friends were significantly affected by their recent work-related stress. while . % strongly agreed and agreed that they had adequate social and psychological support structures at work for dealing with stress, . % of the participants felt that they might need professional help to cope with their stress during the covid- outbreak (figure ). fear of becoming infected with covid- was a major ( . % n = ) stressor at work since the covid- pandemic (figure ). the mean of the total score of the cas was . ± . out of points. the analysis of the cas revealed that only % (n = ) of respondents were anxious, and % (n = ) were not anxious. the percentage of anxiety was %, . % and . % for nurses, radiology residents and radiographers, respectively ( figure ). almost seventy percent of respondents did not feel nauseous or had no gastrointestinal problems at all when they thought about or were exposed to information about the covid- . similarly, . % did not have trouble falling or staying asleep because they were thinking about the covid- (table ) . the mean of the total score of fear for covid- among participants was . ± . out of possible points. the fc- s analysis revealed that . % (n = ) had a high fear score, . % (n = ) had a medium fear score, and only . % (n = ) had a low score of fear for covid- . the group of workers that experienced the greatest fear about covid- were advanced practitioners ( %) and radiologists ( . %) ( figure ). we found that . % of the participants strongly agreed and agreed that they felt uncomfortable when thinking about covid- . similarly, . % reported being afraid of covid- (table ). the pearson chi-square correlation showed no significant association between anxiety level and gender, age, length of experience, country, working place, or work status. similarly, pearson chi-square correlation results revealed no significant association between fear of covid- and either gender, length of experience, or country. nevertheless, there were statistically significant correlations with age (Χ ( ) ( ) . radiographers are usually in close proximity to the patient during image acquisition ( , ) . therefore, it is important for rwf to demonstrate a comprehensive understanding and application of infection control knowledge during practice ( , ) . however, the current study found that only % of and ct services were perceived as expected because these modalities were the key recommended initial and follow-up investigation tools in use during the current pandemic ( - ). baseline chest x-ray showed a sensitivity of % in covid- infection and imaging follow-up ( ) ; chest ct has a limited but important role in the clinical management of covid- patients ( ) . the perceived reduction of patient numbers may also have been potentially due to adherence to national and international guidance to minimize non-urgent work in the radiology department ( , ), as well as due to infection control issues related to transporting covid- patients to ct scanners and availability of ct modality in the departments ( ) . while the study did not investigate the occupational radiation dose, it is worth emphasising the importance of radiation safety for all rwf members ( ); corrective actions are needed to comply with radiation safety and protection during radiology examinations ( ) . moreover, proper radiation protection for patients should be implemented ( ) to ensure radiation safety practice in both routine and crisis situations. it was apparent that the number of patients needing care in the imaging modalities was increased; as a result, hospitals recruited temporary staff to work during the covid- pandemic ( ) . the result of the current study showed that the temporary staff recruited during the pandemic constituted % of the total workers to augment service delivery. previous studies have shown that epidemics can lead to the development of new or worsening psychiatric symptoms or ailments, such as fear, depression, anxiety, panic attacks, somatic symptoms, psychosis and even suicide ( ) ( ) ( ) . another recent study reported similar findings during the covid- pandemic, with a heightened risk for mental health problems among hcp who in direct contact with confirmed or suspected covid- cases ( ) . even though . % reported adequate availability of ppe, . % were afraid that they would be infected with covid- . a higher percentage of fear was reported in china; % of hcps were afraid of becoming infected at work ( ). although some hcps might need psychosocial support, they rarely seek help ( ) . similarly, the current results showed that % of the participants suggested a need for professional support to deal with stress during the covid- pandemic. hcps involved in the care of covid- patients should undergo regular evaluations of stress, depression, and anxiety levels to support their wellbeing ( , ) . our findings also acknowledge the requirement of creating awareness of the need for professional support amongst the rwf in dealing with stress, anxiety and other psychological disorders that might arise during the covid- pandemic and similar crises. stress can produce biophysical reactions, such as headache, abdominal pain, chest pain, eating and sleep disturbances and heart palpitation, as well as; psychological-emotional reactions, such as anxiety, depression, tension, anger, nervousness and frustration ( ) . the current study showed that % of respondents had eating problems, such as nausea and stomach problems, and % reported trouble falling or staying asleep after the pandemic began. eating problems are often associated with anxiety ( ) and anxious people find it difficult to fall asleep and may wake up frequently during the night ( ) . the covid- pandemic has become a significant stressor and studies in china found that medical professionals reported elevated levels of depression, stress, anxiety and insomnia ( , ) . stress and anxiety are linked to fear ( ) . fear is a present response when facing a real or supposed threat, while anxiety is a future response that indicates an impending danger ( ) . anxiety and fear are likely distinct emotional states but often overlap due to underlying behavioural mechanisms ( ) . the result of the current study found no significant association between anxiety level and gender, age, experience, country, workplace, or work status was demonstrated in the present j o u r n a l p r e -p r o o f study, even though the countries varied in their readiness and strategies for tackling the new pressures. the lack of association with age or gender may indicate that the interaction and support level between different workers was so high and effective during stressful times that it helped to lift people and homogenize their responses. likewise, no significant association was found between the fear of covid- and gender, experience, or country. nevertheless, in the current study, fear of covid- was strongly associated with participants from - years of age and also with respondents'work status. a recent study documented that the safety of medical staff during the pandemic and lack of treatment for covid- were the main factors that induced stress in all medical staff, with no significant differences between the study groups ( ) . furthermore, a different review study found that increasing evidence suggests that covid- can be an independent risk factor for stress among hcps ( ) . in the current study, temporary staff showed a higher level of fear, which might be due to the relatively lower practical experience of students or the experience of retired workers of being away from work. therefore, it is suggested that temporary staff be engaged in expeditious training to update their skills and knowledge. our findings accordingly suggest that training in infection control does influence fear, and workers who attended this type of training had a lower fear score than those who did not. moreover, training in stress management helped to prevent and reduce covid- fear, stress and anxiety ( , ) . the main strengths of this study were the robust actions taken to document the radiology response in multiple countries and providing insight into the rwf's health and wellbeing. moreover, our ability to assess the impact of the covid- pandemic on radiology practices and associated factors, such as fear and anxiety, among the rwf provided more insight into the psychological needs of medical workers to continue providing quality service. the study was limited by our inability to capture the underlying reasons for participants' responses as well as their expectations and ideas for service improvement during future pandemics. we also acknowledge the existence of differences in social and cultural stress factors across the countries studied, which likely influenced our findings. j o u r n a l p r e -p r o o f fear was associated with workers younger than years of age and also with temporary staff. nevertheless, anxiety occurred completely independently of gender, age, experience, country, working environment and work status. therefore, professional support is needed to reduce or prevent fear, stress, and anxiety among hcps. it is imperative to establish clear directives, initiate precautionary measures, provide informed health interventions, obtain support from family and increase the productivity of the rwf in preparation for both current and future outbreaks. radiographers are a part of the major frontline healthcare management team in response to covid- . my personal radiation exposure has changed as imaging protocols have changed after covid- outbreak. i have a great understanding of how the covid- virus is transmitted. my understanding of the principles of infection prevention and control as a radiographer is adequate to deal with the covid- outbreak. my facility has made available adequate personal protective equipment (ppe) for work during the covid- outbreak. j o u r n a l p r e -p r o o f world health organization. who director-general's opening remarks at the media briefing on covid- - a novel coronavirus from patients with pneumonia in china radiology management and covid- in resource limited setting clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan imaging and clinical features of patients with novel coronavirus sars-cov- infection control against covid- in departments of radiology covid- screening on chest x-ray images using deep learning based anomaly detection clinical and high-resolution ct features of the covid- infection: comparison of the initial and follow-up changes c-reactive protein correlates with computed tomographic findings and predicts severe covid- early imaging and clinical features of patients with novel coronavirus sars-cov- : a systematic review and meta-analysis knowledge and understanding among medical imaging professionals in india during the rapid rise of the covid- pandemic management of patients with covid- in radiology departments, and indications regarding imaging studies -recommendations of the polish medical society of radiology a novel approach of consultation on novel coronavirus (covid- )-related psychological and mental problems: structured letter therapy mental health of medical workers in pakistan during the pandemic covid- outbreak. asian journal of psychiatry burnout, job satisfaction, and medical malpractice among physicians supporting the health care workforce during the covid- global epidemic factors associated with the psychological impact of severe acute respiratory syndrome on nurses and other hospital workers in toronto immediate psychological responses and associated factors during the initial stage of the epidemic among the general population in china narrative synthesis of psychological and coping responses towards emerging infectious disease outbreaks in the general population: practical considerations for the covid - pandemic immediate and sustained psychological impact of an emerging infectious disease outbreak on health care workers ebola and psychological stress of health care professionals emotion and adaptation depression after exposure to stressful events: lessons learned from the severe acute respiratory syndrome epidemic the psychological impact of the sars epidemic on hospital employees in china: exposure, risk perception, and altruistic acceptance of risk fear of covid- and positivity: mediating role of intolerance of uncertainty, depression, anxiety, and stress job satisfaction and prevalence of stress signs stress, definitions, mechanisms, and effects outlined: lessons from anxiety. instress: concepts, cognition, emotion, and behavior the biology of fear-and anxiety-related behaviors. dialogues in clinical neuroscience the relevance of psychosocial variables and working conditions in predicting nurses' coping strategies during the sars crisis: an online questionnaire survey understanding and addressing sources of anxiety among health care professionals during the covid- pandemic work-related behaviour and experience pattern in nurses: impact on physical and mental health long-term psychological and occupational effects of providing hospital healthcare during sars outbreak. (research) general hospital staff worries, j o u r n a l p r e -p r o o f perceived sufficiency of information and associated psychological distress during the a/h n influenza pandemic analysis of the impact of renewable energy consumption and economic growth on carbon dioxide emissions in mena countries. clean technologies and environmental policy the population of india interpersonal communication: everyday encounters: nelson education atlas of global development: a visual guide to the world's greatest challenges cross sectional studies: advantages and disadvantages the production of knowledge: enhancing progress in social science impact of the covid- pandemic on radiography practice: findings from a uk radiography workforce survey. bjr| open coronavirus anxiety scale: a brief mental health screener for covid- related anxiety replication analysis of the coronavirus anxiety scale the fear of covid- scale: development and initial validation covid- anxiety among frontline nurses: predictive role of organisational support, personal resilience and social support measuring anxiety related to covid- : a turkish validation study of the coronavirus anxiety scale. death studies study on the public psychological states and its related factors during the outbreak of coronavirus disease (covid- ) in some regions of china fear of covid- , psychological distress, work satisfaction and turnover intention among front line nurses adaptation of the fear of covid- scale: its association with psychological distress and life satisfaction in turkey covid- fear in eastern europe: validation of the fear of covid- scale. international journal of mental health and addiction coronavirus disease in the radiology department: what radiographers need to know knowledge, practice and associated factors of infection prevention among healthcare workers in debre markos referral hospital, northwest ethiopia. bmc health services research a survey of doctors' and nurses' knowledge, attitudes and compliance with infection control guidelines in birmingham teaching hospitals social media for rapid knowledge dissemination: early experience from the covid- pandemic frequency and distribution of chest radiographic findings in covid- positive patients technicalguidance/infection-prevention-and-control . department of health. temporary pause of routine screening programmes portable chest x-ray in coronavirus disease- (covid- ): a pictorial review occupational dose and radiation protection practice in uae: a retrospective cross-sectional cohort study ( - ). radiation protection dosimetry assessment of the professional practice knowledge of computed tomography preceptors effectiveness of breast and eye shielding during cervical spine radiography: an experimental study challenges and issues about organizing a hospital to respond to the covid- outbreak: experience from a french reference centre. clinical microbiology and infection wen soon s. psychosocial and coping responses within the community health care setting towards a national outbreak of an infectious disease the kikwit ebola outbreak: lessons hospitals and physicians can apply to future viral epidemics the emotional impact of covid- : from medical staff to common people knowledge, attitude and practice regarding covid- among health care workers in henan timely mental health care for the novel coronavirus outbreak is urgently needed. the lancet psychiatry; the comorbidity between eating disorders and anxiety disorders: prevalence in an eating disorder sample and anxiety disorder sample the effects of social support on sleep quality of medical staff treating patients with coronavirus disease (covid- vicarious traumatization in the general public, members, and non-members of medical teams aiding in covid- control. brain, behavior, and immunity zhuang q psychological impact and coping strategies of frontline medical staff in hunan between mental health problems faced by healthcare workers due to the covid- pandemic-a review pandemic fear" and covid- : mental health burden and strategies the authors would like to thank all participants in the study for taking time off their busy schedules in such unprecedented times to complete the survey. we also appreciate the support received from the society of radiographers & radiological technologists and colleagues and alumni of the department of medical imaging technology, manipal university, india. also, would like to thank dr saravanan coumaravelou for his advice. j o u r n a l p r e -p r o o f j o u r n a l p r e -p r o o f key: cord- -x xe n authors: ertl-wagner, birgit b.; lee, wayne; manson, david e.; amaral, joao g.; bojic, zoran; cote, michelle s.; fernandes, joanne m.; murray, darlene; shammas, amer; therrien-miller, natalie; shroff, manohar m. title: preparedness for the covid- pandemic in a tertiary pediatric radiology department date: - - journal: pediatr radiol doi: . /s - - - sha: doc_id: cord_uid: x xe n nan the outbreak of the novel coronavirus disease of (covid- ) has led to unprecedented challenges in health care systems worldwide. it was first described in wuhan, china, in december and rapidly spread across the world. the center for systems science and engineering at johns hopkins university publishes international case numbers daily [ ] . at the time of writing, many countries were in an exponential phase of spread, so numbers were expected to steeply rise further in the next weeks to months [ ] [ ] [ ] . there is evidence that substantial undocumented infection and community transmission facilitate the rapid dissemination of the novel coronavirus [ ] . in the following, we use the term covid- regardless of the presence of clinical symptoms, even though this terminology is somewhat imprecise. radiology departments are at the crossroads of patient care. with high patient volumes, rapid patient throughput, a range from elective to high-urgency examinations, and often a mix of in-and outpatients, they face particular challenges in these unprecedented times. the radiological society of north america (rsna) and its journal radiology recently assembled a scientific expert panel on radiology department preparedness for covid- and published their perspective [ ] . the situation continues to evolve rapidly. local, national and international rules and regulations vary widely and pediatric radiology departments are in a unique situation. pediatric patients generally tend to be less commonly affected and tend to have a less severe clinical course [ ] . on the other hand, with children there is typically more patient interaction, a notable number of examinations require sedation, and children are usually accompanied by caregiversall factors that need to be taken into account for patient, caregiver and staff protection during this pandemic. we therefore summarized our current experience in departmental preparedness for covid- at a canadian tertiary pediatric radiology department. we are aware that the situation is fluid and rapidly evolving on a daily basis. recommendations valid today might become obsolete tomorrow, and new insights are bound to evolve in a short timeframe. nevertheless, we consider it important to have a description and analysis of current processes as a basis for discussion for pediatric radiology departments at this point in time. the department of diagnostic imaging of the hospital for sick children (sickkids), located in toronto, canada, is an academic tertiary pediatric radiology department that embraces the entire spectrum of pediatric imaging, including general pediatric radiology (with specialized cardiac and musculoskeletal imaging), neuroradiology, interventional radiology, nuclear medicine and imaging-based research. the department consists of staff radiologists. it has a large education program that includes approximately fellows and - rotating residents. front-line operational staff includes approximately radiologic technologists and registered nurses. sickkids is a standalone children's hospital affiliated with the university of toronto. it has approximately inpatient beds and a very wide referral base, expanding across large parts of the province of ontario and even the country in some situations. the department of diagnostic imaging performs more than , examinations per year. prior to the covid- pandemic, the department of diagnostic imaging had developed a high-level departmental emergency preparedness plan to ensure effective and timely response in the event of a disaster and to minimize risks to the health and safety of patients, families, staff and visitors. the plan includes up-to-date fan-out lists, provides clear instructions on what to do during an emergency and is easily accessible to staff even when computer systems are down. the departmental preparedness plan was used and adapted during the severe acute respiratory syndrome (sars) outbreak in - . although sars necessitated departmental preparedness, as well, there are notable differences to the covid- pandemic, making the current situation novel and necessitating new preparedness strategies. compared to covid- , sars was characterized by an overall lower case number, more contained geographic distribution, and lower community transmission. the departmental emergency preparedness plan is fully aligned with the hospital incident management system and serves as a standardized framework for dealing with a wide range of emergencies and disasters. we adapted this plan for the covid- pandemic in terms of key operating principles that include but are not limited to having defined command structure; proactive risk management; streamlined, centralized and integrated communication pathways; clear roles and responsibilities; use of common terminology; defined action planning; and coordinated management of resources. compared to preparedness for other disasters, such as natural disasters or infrastructure collapse, planning for a pandemic situation such as covid- requires a much longer-term adaptation of processes. in the current preparedness planning for the covid- pandemic, change management and people management are of paramount importance. in the pre-pandemic phase, as information on covid- emerged initially from china and subsequently from other countries, preparations for a potential canadian epidemic or global pandemic began in our department ( table ). the current literature emphasizes social distancing to be an important factor in disease containment [ , ] . as information on covid- containment in china [ ] and disease evolution in italy [ ] and other countries was becoming available, we continuously updated and adapted our processes for pandemic preparedness. departmental preparedness in the pre-pandemic phase was planned in coordination with the general hospital preparedness while taking into account the radiology-specific contexts. during the pre-pandemic phase, services in all areas and modalities continued as per regular schedule. all employees were encouraged to meet with occupational health to update their n- mask-fitting requirements and immunization records. hand hygiene stations were properly placed and maintained. a skill-set inventory was created for all non-physician staff to allow for potential re-deployment to areas in need within (and potentially also outside) radiology. the infrastructure for virtual on-line conferencing was updated. opportunities for table checklist of preparations in the pre-pandemic and pandemic alert phase measures of preparedness in the pre-pandemic and pandemic alert phase a ✓ ensure ongoing compliance with mask fit testing requirements ✓ ensure compliance with all mandatory staff training requirements ✓ re-educate staff on proper infection control protocols and donning and doffing of personal protective equipment (ppe) ✓ maintain appropriate stock of ppe and centralize distribution of departmental ppe supplies to prevent shortages ✓ ensure proper placement and maintain hand hygiene stations ✓ ensure that all fan-out lists are up-to-date and accessible to radiology leadership team ✓ schedule and complete regular updates of the radiology emergency preparedness plan ✓ ensure that downtime procedures are up-to-date and available to staff, and re-educate staff ✓ build infrastructure for video-conferencing and remote interpretation of images ✓ identify essential resources required to maintain delivery of services ✓ establish a radiology incident management team (imt) with clear roles and responsibilities ✓ coordinate all pandemic planning activities with the hospital imt ✓ increase situational awareness and involve staff in the pandemic planning process ✓ prepare for fully segregated isolation in collaboration with other programs ✓ determine and prepare for radiology role in the screening and diagnosis of pandemic patients ✓ create appropriate warning and room access control signage ✓ define activities that will be maintained during the pandemic and activities that will have to be discontinued ✓ establish a plan to manage staff absenteeism and to address service gaps ✓ complete an accurate skill set inventory for all non-physician staff ✓ identify opportunities for staff redeployment and designate back-ups for key roles ✓ designate rooms for rapid isolation of suspected cases and specify process steps ✓ determine standardized protocol for decontamination of equipment and imaging rooms ✓ develop pandemic communication plan and build redundancy into communications ✓ identify staff members that are particularly vulnerable to the pandemic a note that this is an abbreviated list as an excerpt from our pandemic preparedness plan. also note that parts were adapted as the situation evolved remote reporting were enhanced, and an increasing number of workstations for remote reporting were deployed. signage was created for the different patient areas. initially, this mostly pertained to patients and families with a recent travel history, but this was subsequently broadened as the situation evolved. screening tools and alerts were implemented within the hospital electronic medical record (emr) to provide centralized communication and information-sharing across distributed registration areas. specific alerts were created to recommend the use of ppe for aerosol-generating procedures for patients who may have been exposed to covid- or had had recent travels outside canada. the world health organisation (who) declared the covid- outbreak a pandemic on march , [ , ] . as the global situation evolved into the pandemic period, our department followed a pandemic preparedness plan ( table ). an inter-professional radiology incident management team (imt) was established, consisting of physician leaders, operational leaders, senior managers including quality and technology leaders, and nursing leaders. roles and responsibilities were assigned. virtual huddles of the imt via a videoconferencing system were established, twice daily on weekdays and once a day on the weekends. these imt huddles aimed to augment situational awareness, to allow for a centralized decisionmaking and to establish a consistent communication to the entire team. the responsibilities of the radiology imt were aligned with the hospital imt. in the following sections we discuss the processes we initialized in the current early pandemic phase. at the time of writing, the situation continued to evolve rapidly and we were still in the early phase. many of the concepts outlined might become obsolete. a critical post hoc analysis will be necessary after the pandemic phase subsides. as the covid- pandemic continues to progress rapidly, shortages of personal protective equipment (ppe) are becoming a reality in many countries and geographic areas. in addition, our knowledge about the novel coronavirus continues to grow. therefore, rules and regulations regarding ppe are bound to evolve further. they depend on local infection prevention and control guidelines and vary across institutions, regions and countries. at the time of writing the ppe recommendations in our institution were as follows ( fig. ) : & during routine patient care for children without precautions only a surgical mask should be worn. goggles or face shields and gowns and gloves are generally not necessary, unless required by a specific procedure. measures of preparedness in the pandemic phase a ✓ implement and monitor standardized screening of patients prior to examinations ✓ implement and monitor standardized triaging and workflow process ✓ use standardized protocol for decontamination of imaging rooms ✓ ensure that all staff complete employee attestation document and retain a copy ✓ operationalize team rotations and separate patient streams to reduce exposure ✓ establish a team rotation system, where possible ✓ organize daily radiology incident management team (imt) meetings to manage resources and respond to the pandemic ✓ implement pandemic communication plan and keep staff, patients and families informed ✓ anticipate and address fear and anxiety, rumors and misinformation ✓ limit all non-essential activities and personnel in the department including research and teaching of pre-licensure students ✓ defer elective outpatient examinations; make decisions for deferral on a case-by-case basis in consultation with radiologist and referring physicians ✓ ensure that patients requiring urgent imaging will not be impacted ✓ aim to perform imaging at sites with less foot traffic and with fewer patients ✓ eliminate or reduce the possibility for staff to work using the same work stations ✓ wipe workstations, dictaphones and telephones before use ✓ ensure the most judicious use of personal protective equipment (ppe) and infection control supplies ✓ monitor inventory levels and order ppe and infection control supplies as required ✓ store ppe in areas not available to public or in areas that can be monitored ✓ apply a wide range of strategies to increase social distancing ✓ perform an ongoing assessment of risks from the interaction of all potential hazards ✓ take proactive steps to protect staff that are particularly vulnerable to pandemic ✓ assess the need to enact downtime procedures ✓ provide the ability for staff to work from home while balancing needs in the hospital ✓ use video-conferencing for necessary meetings whenever feasible ✓ show compassion and provide support to staff experiencing fatigue, burnout and distress ✓ sharpen and maintain focus on patient, family and staff safety during pandemic ✓ monitor evolving situation and rapidly respond to changing needs a note that this is an abbreviated list as an excerpt from our pandemic preparedness plan. also note that parts were adapted as the situation evolved & a surgical mask should also be worn for interacting with other staff or caregivers, when an appropriate social distance ( ft) cannot be maintained. these regulations are likely to evolve and are likely to differ across institutions, and therefore we strongly advise consultation of the respective current institutional guidelines. the donning and doffing of ppe was re-trained at the beginning of the pandemic phase, and the hospital released an elearning module on this, which became mandatory across the organization. staff was encouraged to handle the masks with care and to minimize the amount of times masks are taken on and off. they were reminded that masks need to cover the nose fully and should not be hung around the neck and ears when taken off. we established an inventory of ppe and started monitoring supply and usage. staff was encouraged to bundle tasks where possible to preserve ppe. the number of staff requiring ppe was limited as far as possible (e.g., limiting the number of technologists to position patients). in addition, solutions to potential shortages needed to be considered, including the use of one mask for several procedures, sterilization and reuse of ppe, and -d printing methods. dedicated rooms are used for all imaging examinations or image-guided interventions in patients with confirmed covid- and those with respiratory symptoms and suspected covid- infection. additional rooms were identified and designated to serve for rapid isolation for when cases were identified. these rapid isolation rooms allowed for a secondary screening to determine the next steps. concepts regarding room disinfection and turnover as well as equipment decontamination continue to evolve and depend on local infection prevention and control (ipac) guidelines, which are likely to vary across institutions. standardized protocols were developed, implemented and adapted according to the current evidence for decontaminating imaging rooms. our room preparation processes are continuously adapted to our institutional ipac guidelines. when feasible, portable imaging of patients with suspected covid- is performed. the choice of modality used (e.g., ct vs. ultrasonography) depends on the specific situation, symptomatology and available resources. diagram shows current guidelines on use of personal protective equipment (ppe) at our institution. please note that concepts are likely to evolve and vary depending on local and institutional regulations and availabilities. column recommends n- mask, goggles or face shield, and gown and gloves for aerosol-generating medical procedures. column demonstrates surgical face mask plus goggles or face shield, or a combination of mask and face shield, as well as gown and gloves as recommended for droplet/contact isolation. column shows surgical masks only as recommended for routine cases, unless specifically required otherwise. column recommends n- mask, goggles or face shield, and gown and gloves for all code blue situations in interventional radiology, the minimum number of people required for the procedure is allowed in the room. if possible, technologists control the angiography equipment from the control room. access to the room is limited to one entrance only. all interventional team members have to adhere to donning and doffing at the entrance of the room. personal radiation protection lead aprons have to be wiped with virucidal wipes containing . % hydrogen peroxide after each procedure. because endotracheal intubation is an aerosol-generating medical procedure, special care needs to be taken. we made every effort to defer all elective, non-emergent and non-urgent examinations and interventions under general anesthesia. for people with pending covid- testing results and urgent imaging or image-guided interventions under general anesthesia, test results are expedited. induction for general anesthesia is to be performed in a designated contaminate area. crying and coughing should be reduced with sedative premedication. all unnecessary room equipment should be removed; drawers and shelves should be closed and surfaces covered with a clean sheet. traffic should be minimized. appropriate signage should be displayed. only necessary disposables should be taken out. a special tray should be used for placement of contaminated equipment, and a highefficiency particulate air (hepa) filter between the patient and the circuit should be used during mechanical ventilation. a pre-intubation/pre-procedure time-out should be done to ascertain that the required equipment is present, that personnel is limited to only those who are clinically required, that inand-out movement is minimized and that the correct ppe is donned. examinations or image-guided interventions should be completed expeditiously. a safety coach should be present before beginning the examination or imageguided intervention under general anesthesia or sedation to oversee actions and processes. this safety coach should remain outside the interventional/examination room. safety coaches are individuals with special training in infection control and the correct use of ppe. in our department, two senior registered nurses are trained as safety coaches. after the procedure, a post-intubation/post-procedure timeout should be done to verify that all soiled equipment and soiled medical supplies are properly disposed of. nondisposable personal equipment such as lead aprons should be cleaned, e.g., with appropriate virucidal wipes containing hydrogen peroxide . %, after each use. there has been restricted access to the hospital since the beginning of the covid- pandemic. screeners at the hospital entrance triage whether access to the hospital is granted. employees have had to fill in an electronic attestation form prior to coming into the hospital since march , ; this includes an attestation not to have respiratory symptoms including but not limited to cough, runny nose or fever, not to come to work with respiratory symptoms, to adhere to return-from-travel regulations ( -day self-quarantine) and to access information regarding covid- on the website on a regular basis, among others. the list of symptoms was later adapted and broadened. the e-mailed confirmation of this attestation form has to be presented at the hospital entrance and employees are subsequently provided with special stickers to their hospital badges clearing them for access. pre-licensure trainees (e.g., medical students) and volunteers were no longer allowed on-site at the time of this writing. all patients, families and visitors have to present to special screening stations with glass windows. the number of caregivers accompanying patients is restricted to one (two in exceptional circumstances). specialized medical equipment representatives are only allowed in clinical areas if required to deliver supplies for urgent medical care. care was taken to allow for enough distance in the waiting areas of the radiology department. this was facilitated by the deferral of elective outpatient examinations outlined above and would have otherwise been very challenging. all communal toys and books were removed and, where feasible, seating areas (benches, chairs) were separated by ft ( m) in waiting areas. if outpatient examination numbers rise again in a continuing pandemic situation, different strategies might need to be discussed. among these is the potential solution to have patients and their caregivers wait either in their cars in the parking garage (where feasible) or in a larger but more remote waiting area and to call them into the examination area only shortly before the examination is to commence to avoid waiting and reduce traffic in imaging areas. on march , , the radiology leadership in consultation with hospital leadership decided that all outpatient elective, nonurgent and non-emergent examinations should be deferred. the overarching aim for this measure was to primarily reduce potential exposure for patients, their families and staff, and to create additional capacity for potential surges in patients with covid- . this created a considerable logistic challenge because the radiology department has a very large elective outpatient population and is one of the sole providers of sub-specialized pediatric imaging in a large and very populated area. even though it was considered preferable by the radiology imt to have the referring provider (being the most responsible provider, usually a physician and occasionally a nurse practitioner) prioritize the examinations for potential deferral, this was considered not feasible because examination deferral was expected to start the very next day. therefore, data from the electronic scheduling system were extracted and spreadsheets were created that included all elective outpatient examinations scheduled for the weeks starting march , , for each imaging modality. the spreadsheets were kept on a secure in-house server and contained the ordering information and medical record number for each examination. the excel spreadsheets were assigned to the radiology division head (body radiology, neuroradiology, interventional radiology, nuclear medicine). radiologists reviewed the ordering information, available imaging and electronic patient charts to decide whether an elective outpatient examination could be deferred. a standardized approach was chosen for the decisions on examination deferral. a small group of radiologists decided on the deferrals in their area of subspecialty based on urgency. electronic medical records and prior imaging studies were reviewed. categories for non-deferral of diagnostic examinations and interventional procedures included cancer care, acute infection/sepsis risk, risk of obstruction, severe pain management, acute risk of progression from delay, immediate diagnostic necessity, prevention of major surgery, time-sensitive treatment sequence, promotion of immediate hospital discharge, and urgent vascular access. deferred examinations to be reassessed in weeks were specifically flagged. four columns were created for the division heads (or radiologists designated by them) to fill in: who reviewed the order, comments, whether the examination should be deferred (yes/no), and whether the examination should be re-assessed in weeks (yes/no). the last of these columns was designed to indicate elective outpatient examinations that should be re-booked with priority as soon as the situation allowed for this. another four columns were created for the radiology administrator contacting the family to indicate: who contacted, when the contact was made, who was spoken to, and comments. four additional columns were made for the radiology administrator contacting the referring provider to show: who contacted, when the contact was made, who was spoken to, and whether a prioritized rebooking was requested. in addition, it was checked whether the radiologic examination was coordinated with any other in-house patient visits at sickkids. if so, the coordinating clinic was contacted, it was discussed whether to keep the booking, and the results were documented in the spreadsheet. in addition, referring providers were asked to provide lists of their most urgent patients and these lists were amalgamated with our spreadsheet to ensure timely examinations for more urgent indications. table gives an example of the column headers with fictional data for illustration. a sample of standardized communication with parents/caregivers is provided under supplementary material. for the weeks starting march , , the elective outpatient examination requests were screened, labeled to be deferred and marked to be reassessed in weeks for prioritized rebooking as follows: & for mri, requests were screened, ( %, / ) were labeled to be deferred and of these ( %, / ) were marked to be reassessed in weeks. & for ct, requests were screened, ( %, / ) were labeled to be deferred and of these ( %, / ) were marked to be reassessed in weeks. & for ultrasonography, , requests were screened, ( %, / , ) were labeled to be deferred and of these ( %, / ) were marked to be reassessed in weeks. & for interventional radiology, requests were screened, ( %, / ) were labeled to be please note that these numbers only reflect elective outpatient imaging requests with low urgency for the weeks starting march , . inpatient examinations, examinations referred by the emergency department and all urgent outpatient examinations were performed as before, so the actual number of examinations was markedly higher. for radiographic examinations, the schedule did not explicitly change. these are usually performed on a short-term notice without long-term advance scheduling. as the covid- pandemic evolved, the stream of walk-in patients with external orders for outpatient imaging and the requests for non-urgent radiographic examinations largely subsided as outpatient clinics were canceled and parents and caregivers were reluctant to come to the hospital. starting at the beginning of the second week (march , ), we created a process to have the referring providers decide on whether to defer an elective outpatient examination for all examinations scheduled for the weeks starting on april , . figure outlines the process. almost , examination requests have been screened with over referring providers. it will be important to monitor this process closely in the weeks to come. as the situation continues to evolve very dynamically, the time horizon of the deferrals and rebookings needs to be continuously monitored and adapted in a rolling plan. the rapid deployment of manual-entry dependent processes outside the hospital's emr is susceptible to human error and communication gaps. to mitigate the risk of an appointment being overlooked, a custom program was built in python to merge spreadsheets containing ( ) radiologist prioritization, ( ) provider phone calls and emails, and ( ) patient/family confirmations, with emr extracts containing ( ) previously scheduled appointments, ( ) newly deferred appointments and ( ) unexpected patient/family no shows because of covid- travel concerns. this daily reconciliation program further integrated ambulatory clinic cancellations to provide a master list, ensuring that all appointments scheduled during covid- were accounted for, and rescheduled in a timely manner. as the number of covid- cases continued to escalate both locally and worldwide, we decided that further measures were needed to brace for the impact of potential further surges in infections [ ] , so we initiated a multi-team rostering approach. the overarching aims of this multi-team approach were to: ( ) prevent contamination and spread of the virus, ( ) allow for social distancing and ( ) have a backup team in case of sick leaves or quarantines. the teams were formed within each subspecialty area (e.g., neuroradiology, body radiology, interventional radiology and nuclear medicine) and there were no overlaps between the two teams. each team was rostered to work for week and be away from the hospital practicing social distancing and self-quarantine at home during the other week, with alternating schedules. radiology teams consist of staff radiologists and radiology fellows and cover day-service and on-call services for the given week. teams not in-house were asked to stay at home, practice social distancing, provide remote image reading, administrative help and academic work, and be available to be called into the hospital within min, if the situation required it. it was also decided to protect especially vulnerable staff members while maintaining a high level of confidentiality. staff with preexisting conditions or immunosuppression and those who are more vulnerable because of their age were enabled for home reporting. they were removed from direct patient/caregiver contact. the roster was created for weeks at a time; the multi-team approach will be continued if the situation continues to evolve. radiology residents usually rotate through various sites in toronto to gain a wide spectrum of experience. in the current pandemic situation, rotations were halted. each site now has a fixed team of residents covering weekday nights and weekends. daytime resident coverage was paused because it was not considered an essential service. other frontline staff was distributed into multi-team models where possible. the following guiding principles were considered to review and adapt staffing models based on personnel, equipment and patient streams. personnel considerations included shift length, frequency, team size and other personnel considerations (age, co-morbidities, dependants requiring care, recent travel, and illness/symptoms/rate of absenteeism). because the majority of frontline staff is compensated on an hourly pay model, care was taken to balance work hours. implementation varied by department. in some areas, teams moved to -or -h shifts, reducing their onsite presence to or days a week, respectively. where appropriate, staff members were redeployed into support or administrative work rotations that could be completed in a non-patient-facing or work-from-home capacity. staff members are expected to be available to be called into clinical duty within min if the situation requires it (sick leaves or quarantines). equipment and modality room considerations were intended to minimize exposure among patients and were based on cleaning protocols (process and turnaround times), volumes of cases, potential downtime and location (i.e. portable vs. fixed rooms). where possible, patient streams are considered to rotate staff and protect vulnerable staff performing imaging on patients. as the pandemic situation started to evolve around the time of march school break in ontario, numerous employees were returning from travel. provincial regulations regarding selfisolation initially exempted health care workers, but eventually all employees with an international travel history within the last days had to be in home self-isolation for days following the date of their return to canada. this rule was also retrospectively applied. a notable portion of employees therefore had to be sent home to self-quarantine and the schedules and rosters had to be accommodated accordingly. the reading situation needed to be adapted to allow for social distancing. everyone was encouraged to use the same workstation throughout a shift and, where feasible, for the rest of the week. wherever possible, fellows are deployed to separate reading rooms. if more than one fellow needs to read in one large reading room, care is taken that adequate distancing is possible (at least ft/ m). as outlined, residents are only providing weekday night and weekend coverage and have separate reading rooms. staff radiologists are mostly using individual work stations in offices. options for home reporting have been expanded. depending on the subspecialty and service, home reporting for on-call situations had already been in place. this was further expanded in the pre-pandemic planning phase. for home reporting, full workstations with medical-grade imaging monitors are used in a three-monitor configuration, identical to the inhospital workstations. the workstations are connected to the hospital's picture archiving and communications system (pacs), radiology information system (ris) and emr system via a virtual private network (vpn). departmental networking resources had already been managed separately from the hospital-wide resources before the covid- pandemic and could be rapidly expanded. hand disinfectant and disinfecting virucidal wipes containing . % hydrogen peroxide were distributed to all reading rooms. everyone was instructed to thoroughly wipe the workstation (keyboard and mouse), dictaphone and phone with a virucidal wipe prior to use and to use only one given workstation and phone throughout the shift and if possible throughout the week. staff and fellows are encouraged to read out over the phone, with both sitting in separate rooms at workstations and going over the cases on the phone. the fellow then creates the initial report in the radiology information system, and the report is reviewed and signed electronically by the radiology staff. access to the reading rooms is limited. within the firewalls of our hospital, consultations and clinical conferences are performed using microsoft teams, which allows for the sharing of pacs screens. the hospital also quickly moved to virtual clinics via the province-wide ontario telemedicine network. the current pandemic situation creates a high degree of uncertainty among employees, trainees, patients and their families. communication needs to find a fine balance between informing, supporting and encouraging on the one hand, and not overwhelming with information on the other. ideally, the information should be timely and clear, top-down and consistently from the same source. however, in this unprecedented and highly dynamic situation, information changes rapidly. what holds true one day might not be relevant the next. this needs to be acknowledged and openly dealt with. provincial return to travel policies, for example, rapidly changed in ontario, and communication to employees necessarily had to be updated in rapid succession. it will be important to regularly communicate and update the information and policies for the weeks to come. fear and anxiety, rumors and misinformation need to be anticipated and addressed. care must be taken to ensure that communication is as consistent as possible. communication for clinical rounds has also rapidly changed with the need for social distancing and tight limits of people in one room. clinical rounds are now held electronically. it is important to follow data protection guidelines for protected health information, which may vary among provinces, states and countries. at sickkids, an institution-wide license allows us to use secure microsoft teams for discussing patient information at clinical case conferences and multidisciplinary rounds (e.g., neonatal intensive care unit rounds, oncology rounds); these have been successfully conducted from within the hospital or via vpn connection from home. teaching rounds have been continued using a wider variety of web conferencing solutions with videoconferencing options and shared screens. it is important to remember that these teaching rounds should not contain any protected health information. last but not least, communicating a sincere thank you to the teams regularly is important as we all struggle together to get through this unprecedented situation. daily leadership walkarounds were instituted in the department to support and boost morale. these leadership walk-arounds are also conducted on the weekends and care is taken to maintain social distance. during this pandemic situation, staff and trainees may experience stress, fatigue and challenges regarding self-isolation, provision of additional clinical services, exam postponements, or child care in the face of the school closings. several resources are available to provide support for staff, physicians and trainees through the hospital, university and medical association such as the wellness office and physician health program. while we are all desperately waiting for the post-pandemic time, this period will bring specific challenges, and preparing for these challenges is of utmost importance ( table ) . one of the major challenges will be to catch up with the large number of elective outpatient examinations that were deferred. waiting lists are already long, especially for examinations under general anesthesia, and extra shifts will become necessary to make up for the deferred examinations. plans need to be developed and implemented to prioritize and address this backlog of examinations. currently, we are operating on a rolling plan, in which deferred elective examinations are continuously reassessed for prioritized re-booking. deferred elective examinations that need to be reassessed after weeks are specially flagged. it will be crucially important to develop a process to rebook the deferred appointments without any patient being lost to follow-up. this process will need to be continuously monitored. teams should be recognized and rewarded for their exemplary performance and dedication during challenging times. in addition, a post hoc analysis of our response and processes during the pandemic should be performed and lessons learned should be documented. the pandemic preparedness plan should be updated and adapted as required because it is uncertain when another pandemic may arise. we are in a highly dynamic situation that is bound to evolve further. our processes outlined here are expected to develop table checklist for the post-pandemic phase measures of preparedness in the post-pandemic phase a ✓ ramp up activities and services in all modalities to appropriate levels ✓ assess and address radiology inventory needs related to equipment and supplies ✓ rebook canceled or deferred appointments due to pandemic ✓ initiate communication and consultations with referring physicians as required ✓ develop and implement plans to prioritize and address the backlog ✓ conduct post hoc analysis of the pandemic response and document lessons learned ✓ improve processes and update pandemic plans as required ✓ initiate strategic planning for innovative models of diagnostic imaging operations ✓ recognize and reward teams a note that this is an abbreviated list as an excerpt from out pandemic preparedness plan and change. new processes are likely to become necessary. we provided a snapshot and analysis of our status quo situation at the time of writing and of the changes we implemented thus far. the literature suggests that swift measures are vital in containing the pandemic spread [ , , [ ] [ ] [ ] [ ] and radiology departments play a major role in this. we need to monitor the situation continuously and to react and adapt to the changes around us rapidly. in all the uncertainty, we need to stay focused, alert and informed and need to stand together and united to master this unprecedented challenge. coronavirus covid- global cases by johns hopkins csse covid- : towards controlling of a pandemic rapidly increasing cumulative incidence of coronavirus disease (covid- ) in the european union/european economic area and the united kingdom substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (sars-cov ) radiology department preparedness for covid- : radiology scientific expert panel epidemiological characteristics of , pediatric patients with coronavirus disease in china covid- and community mitigation strategies in a pandemic isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus ( -ncov) outbreak successful containment of covid- : the who-report on the covid- outbreak in china covid- and italy: what next? who declares covid- a pandemic covid- : who declares pandemic because of "alarming levels" of spread, severity, and inaction publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations acknowledgments we would like to acknowledge dr. marie-louise greer, dr. elaine ng and logi vidarsson, phd, from the hospital for sick children, and dr. marc ossip from william osler hospital in brampton, ontario. we would also like to sincerely thank the hospital leadership, the entire team of the department of diagnostic imaging, all employees of the hospital for sick children as well as all our patients and their families for their courage, caring, patience and stamina in these challenging and unprecedented times. conflicts of interest none key: cord- -jp hvcg authors: freer, phoebe e. title: the impact of the covid- pandemic on breast imaging date: - - journal: radiol clin north am doi: . /j.rcl. . . sha: doc_id: cord_uid: jp hvcg starting in wuhan, china, followed quickly in the united states in january , an outbreak of a novel coronavirus, or covid- escalated to a global pandemic by march( , ). by september , , there were almost million cases worldwide and nearly . million u.s. cases, with almost million and , deaths, respectively( ). the outbreak dramatically disrupted global public health as well as precipitated upheaval to the economy and society. with no vaccine or adequate treatment, the most significant weapon to curtail its destruction was a global policy of “social distancing”, advising people to quarantine at home, closing schools and businesses, and disrupting routine health care. as the pandemic lasted, the need to re-open the economy and health care emerged with precautions placed for masking and social distancing. significant disruptions occurred to breast imaging including deferred screening mammography, triaging diagnostic breast imaging, and changes in breast cancer care algorithms. this article summarizes the effect of the global pandemic – and efforts to curtail its spread – on both breast cancer care and on breast imaging practices including effects on patients, clinical workflow, education and research. ( ) the covid- pandemic starting in the u.s. in has had practice-changing effects on cancer care, clinical workflow, education, research, and radiology finances. ( ) significant volume reductions and delays occurred to breast imaging with screening mammography the hardest hit ( ) long term outcomes from changes in breast cancer management algorithm during the pandemic are yet to be determined. ( ) increased telehealth and telecommuting will likely continue after the pandemic is over in some fashion. on march th , news reports of potential danger to mammography technologists from work exposures were released, with a death in a mammography technologist in georgia from covid- , a possible work exposure . hcws were confirmed to be high risk for covid- infections (up to %) from initial data in early outbreaks in china, italy, and spain . the nccn issued guidelines for health care worker safety early in the pandemic, based on who recommendations . in a study rating different professions' risk of contracting covid- from work, radiology technologists were one of the highest (a score or out of ), and sonographers ( out of ) . mammography technologists likely have an even higher risk, as they are unable to maintain social distancing ( m or feet) during positioning. quickly, breast radiologists and technologists had palpable concerns regarding the need to protect hcws and patients during screening, and firm statements were released by national organizations with the asbrs and acr joint statement on breast screening exams during the covid- pandemic, and the society of breast imaging statement on breast imaging during the covid- pandemic all released later in march, , and recommending to "postpone all breast screening exams (to include screening mammography, ultrasound, and mri) effective immediately" as well as to discontinue routine and non-urgent breast health appointments. , moreover, shortages of ppe existed, and so technologist and radiologists could not uniformly be masked, with only . % ( of ) of radiology practices stating they had an adequate supply, and . % reporting that ppe supplies were low and needed to rationed . be deferred for at least - weeks and suggested triaging the diagnostic cases, deferring ones that were not highly suspicious for cancer . the society of breast imaging followed suit with a statement that was broader and less prescriptive, but also recommended delaying screening by "several weeks or a few months" . other international societies published similar statements , . multidisciplinary care algorithms changed the management of breast cancer during the pandemic in response to need to balance the urgency of care against the risks to patients and hcws secondary to potential covid- exposures. surgeries were postponed both to limit covid- transmission, as well as to preserve resources like ventilators, ppe, and hospital beds. the american college of surgeons (acs) and the society of surgical oncology released triage guidelines recommending an interim cancellation of most routine surgeries, while still performing breast surgeries for those in more urgent cases , . some centers, such as magee-breast cancer program and johns hopkins published multi-disciplinary algorithms of how best to triage breast cancer patients, broken down by sub-types program , . other published tools suggested risk-stratifying patients for breast surgery with the purpose of causing few deleterious effects in patients recommended for postponement . in early april, a multi-disciplinary group of breast cancer experts in the u. . the main goals of the consortium recommendations were to "preserve hospital resources for virus-inflicted patients by deferring bc treatments without significantly compromising long-term outcomes for individual bc patients". patients were placed into categories based on severity of symptoms or illnesses with algorithms for chemotherapy and surgery outlined based on disease process. re-opening of routine care by july , as the pandemic proved lasting and ppe supplies improved nationwide, consensus guidelines shifted to avoid delays in care and focused instead on how to better protect patients and workers . leaders in breast cancer made evidence based pleas to cease labelling patients with cancer as a high risk population in order to avoid delays in their diagnosis and treatment . numerous consensus statements and guidelines regarding how to best balance the risks of covid- transmission to patients and hcws against the risks of delaying care have been published . the european society for medical oncology guidelines include increasing telehealth appointments (noting in person visits are needed for new cancer patients or urgent infections / post-operative complications) and specific guidance for management and advised that the risk/benefit balance for most patients favored continued administration of systemic therapies and chemotherapies, with additional precautions when possible (e.g., choosing less immunosuppressive therapies, regimens requiring fewer appointments) . numerous other guidance documents have emerged fluidly including from asco and an online resource from asco, and others globally , [ ] [ ] [ ] [ ] [ ] [ ] . although the recommendations for the management of breast cancer change the order and timing of breast cancer treatments, the goals have remained to change these algorithms in ways that don't affect long term outcomes or changes for a cure. for example, surgery should remain the primary option for small triple-negative breast cancers that did not require chemotherapy based on pre-covid- algorithms . additionally, patients with progressive disease on medical therapy should have surgery. further patients who are competing their neoadjuvant regimens, or patients who did not respond to neoadjuvant therapy should receive surgery . prophylactic measures were implemented with guidance from the cdc, for protecting patients and hcws, including social distancing where possible, masking both patients and hcws, decreasing the number of scheduled patients, increasing space in waiting areas, and implementing disinfection protocols. nearly all imaging centers implemented pre-appointment screening for symptoms of covid- , most requiring temperature screening at some point during the pandemic, and a few even required covid- negative testing prior to a breast interventional procedure (although many centers required covid- negative testing prior to breast surgeries) . initially, the fda halted inspections of mammography facilities (required by the mammographic quality standards act (mqsa) in mid-march, . additionally, the acr granted automatic extensions and halted in person inspections for sites where accreditation was expiring . as the re-opening phase began, the fda announced that it would restart inspections at facilities in locations that were not as affected by the pandemic on july th, although it did not actually start them then. it recommended that state inspections could start based on individual state guidance at the end of june , guided by an advisory system to take into account the extent of the outbreak in that location combined with how critical the inspection would be . initially, concern existed that patients with breast cancer, especially advanced or metastatic breast cancer, may be more susceptible to severe outcomes with covid- . many of the most common chemotherapy regimens used to treat breast cancer are known to cause immunosuppression. further, patients undergoing cancer care have more visits and therefore more exposures to hcws and patients, potentially making them more at risk of being infected with covid- , . initial studies from wuhan, china showed worse outcomes from covid- in cancer patients and suggested caution with cancer care during the pandemic [ ] [ ] [ ] . in one study of patients from the wuhan outbreak, patients with cancer had more than double the risk of contracting covid- than patients without (odds ratio [or], . ; % ci, . - . ) . in another early study from the wuhan experience, the relative risk of dying or being j o u r n a l p r e -p r o o f admitted to the intensive care unit with covid- in cancer patients was . ( % ci . - . ) . moreover, cancer patients had a higher relative risk of requiring intubation, across all age ranges. the mortality rate of covid- in patients with cancer has ranged from - % in reported studies [ ] [ ] [ ] , compared to the . % mortality rate reported in the general population from the initial wuhan studies . however, not all cancer patients have the same risks, as a patient with an early stage breast cancer may not have the covid- risks as an end of life stage iv breast cancer patient. this was confirmed by one study of patients with cancer and covid- that found that having active cancer that was progressing (as opposed to remission) and having a worse performance status were associated with increased risk of mortality . as the pandemic has unfolded, registries for cancer patients and covid- have been developed in an attempt to better understand the risk to cancer patients, as initial reports on outcomes were limited to single institutional or smaller studies. an international database was established to study the risks of covid- on cancer patients from the us, canada, and spain with underlying cancer (the covid- and cancer consortium database or ccc ) . and asco developed its own registry to be able to share data rapidly and contribute to evidence-based decision making for cancer patients during the pandemic . initial reports from mid-march through mid-april of the ccc , including over cancer patients ( % breast cancer) and covid- found that although the -day all-cause mortality for the entire population with cancer and covid- was high, associated with both general and cancer-specific risk factors, the actual risk in patients with solid tumors (i.e. breast cancer) was not significantly higher . this study also confirmed recent cancer surgery did not impact the mortality rate from concurrent infections with covid- . a large cohort study of cancer patients with covid- in the uk (uk coronavirus cancer monitoring project or ukccmp), at a similar time frame of the pandemic, found that although the mortality rate was %, when adjusted for age and other comorbidities, the presence of cancer alone did not increase the mortality from covid- . importantly, the use of chemotherapy prior to covid- infection did not impact mortality. neither did the use of hormonal, targeted, and, immune therapies, or radiation . thus, although it may be possible that some cancer patients have a propensity towards worse outcomes with covid- , it does not seem likely that cancer treatments such as chemotherapy, hormonal therapy, radiation, and surgery predispose patients to more serious outcomes from covid- . if care is taken for protective measures for the patients and hcws as outlined in different care algorithms, breast cancer treatment should continue during the pandemic, especially in light of the unknown timeframe of the crisis. not only did multidisciplinary care algorithms force patients into delaying care during the pandemic, but patients also self-selected to delay care. nearly out of patients said the economic changes from the pandemic impacted their ability to pay for medical care . a survey by acep demonstrated almost / of patients ( %) delayed or avoided going to the emergency room in march/april in order to avoid covid- exposures . four out of patients were fearful of contracting the virus from a patient or hcw if they did go . over % of survey participants acknowledged practicing social distancing . in an italian study, during the height of the outbreak, there was a significant increase in patients refusing to undergo diagnostic appointments and breast biopsies at a major cancer center . in another breast care patients surveyed, almost % stated they had routine and followup appointments delayed, / had reconstruction surgery delayed, and % had delayed diagnostic imaging . therapies that required in person visits to the hospital (radiation, chemotherapy infusion, and surgical lumpectomies) were more likely to be delayed than those that could be obtained through telehealth appointments or a prescription pick-up . medicare and medicaid services and private insurers expanded telehealth benefits to patients covering increased virtual visits . on average, about % of patients experienced delays in the mainstays of breast cancer treatment including lumpectomies, radiation therapy, and chemotherapy . breast cancer surgeries declined significantly during the early parts of the global pandemic . in data from breast centers in states, it was noted that the average decline in breast surgery clinic appointments over the first few weeks was % with a nadir of % from baseline and a near % decline in new breast cancer surgery consultations in the surgery clinics . similarly, breast cancer genetics appointments declined, by between - % . in one study from wuhan, china, over half of patients receiving radiation therapy were unable to complete their regimens during the lockdowns . the pandemic increased the use of neoadjuvant and hormonal therapies prior to surgery, as well as increased genotypic profiling, secondary to deferrals of surgeries . in another study from the netherlands / of patients noted that the pandemic affected their cancer care, with most of these noting a shift to telehealth consultations . chemotherapy was also affected in about / of these patients . the long term physical and psychosocial ramifications of these delays remain to be determined. one study demonstrated that over half of cancer patients were concerned the delays or discontinuation of care during the pandemic affected their outcomes . oncologic patients noted anxieties regarding whether they were at increased risk of worse outcomes with covid- , as well as anger and worry from delays or interruptions in their care during covid- . some patients even stated that the changes in their care encountered sounded "like a death sentence" or made them "feel like my care and health aren't important to you" . these patient perceptions, whether accurate or not, will need to be addressed as the pandemic unfolds , . the mental health effects of limiting care during this pandemic, and potentially in future crises, on both cancer specialists, and patients, who are used to unlimited resources for health care, may be far reaching. having consensus guidelines to guide fair decision making and developing empathic communication with regards to these issues is important . education and shifts in mindsets to prioritize the maximum health benefit for the community over the individual may j o u r n a l p r e -p r o o f be necessary in a country used to unlimited resources. guidelines have been developed for low resource communities that may prove useful , . it is unclear what effects these covid- provoked changes in cancer screening and management will have on long term cancer outcomes. in the u.s., an estimated additional , deaths occurred in march and most of april compared to the last years, of which % ( , ) were not directly attributable to covid- (and in states, > % of excess deaths frame were not attributable) . almost half ( %) of us people surveyed had a family member who had delayed medical care during the pandemic with % stating that that member's medical condition worsened during the delay . one modeling study of new stage - cancer cases in the uk who were delayed multi-disciplinary work-up during the pandemic suggested that an additional lives and life years would be lost with a conservative estimate of only % of cases backlogged for two months . during the early phases of the pandemic, the number of new cancers diagnosed decreased , . this drop was likely secondary to patients not presenting for care, and not a true drop in incidence. thus, these cancers will come to the radar eventually at a greater size or stage than they would have with earlier detection, which may affect prognosis. a model that assumed only a month disruption of care during the pandemic estimated the potential excess deaths from breast and colorectal cancer secondary to the pandemic disruptions in care demonstrates an excess of over , deaths in the next decade, peaking in the first few years . this model does not account for the increased morbidity with possible more extensive surgeries including more mastectomies or more need for chemotherapy secondary to later presentations of disease. previous studies have demonstrated worsened outcomes during economic downturns, and in times of stress, and so it is likely the effects on breast cancer detection and management combined with the economic and societal effects of the pandemic will lead to effects on long term outcomes . it is also plausible that if there are not measurable deleterious effects from these delays, then reimbursements for care may be renegotiated or guidelines may shift to reduce care. the covid- pandemic has had marked economic effects on the health care system, academic radiology departments, and radiology practices. a survey conducted by acr and the radiology business management association reported that . % of radiology practices (urban, academic, and rural) experienced declines in imaging volume in march/april , with a drop of > % of elective procedures and % of urgent procedures . one third of academic radiology chairs reported a near / decrease in volume with some reporting an % drop in hard hit areas . over % of chairs had at least a % decrease in total radiology volume at the nadir . breast imaging was disproportionately affected by postponed cases. the largest health care system in new york reported a drop of % affecting all modality types, with mammography use plummeting by %, mri %, and ultrasound % . in another study of academic medical centers across the u.s., in regions with lower rates of covid- , radiology volumes declined steeply from calendar week - with a range of - % total volume drop at the lowest drop . of those drops, screening mammography was among the most significant drop, as well as slowest in recovering. the reduction in screening mammography went as far as % in weeks and . diagnostic mammography volumes did not drop as dramatically, however still hit a low of % volume decrease at the nadir in week . upon gradual re-openings of care (in may-july in most centers), a significant backlog of past studies had built. additionally, significant changes in scheduling with increased evening or weekend hours, changes in protocols for shorter mri scan times , off-loading studies from hospitals and cancer centers to protect higher risk patients were required to allow for more spacing. changes to patient registration and check-in, pre-screening for symptoms, ppe requirements, and disinfection protocols were instituted briskly. % of academic radiology departments reported reorganizing the waiting rooms and dressing areas to comply with social distancing mandates . radiology practices restructured reading rooms and implemented home pacs. some practices shifted rapidly to home pacs, moving from % of radiologists onsite to % reading from home within a few weeks . however, for breast imaging, this process is more complicated and expensive due to quality compliance requirements, the need for high resolution monitors, and the need to be on site for diagnostic and interventions, and happened at much lower levels. telehealth increased in general, for patient surgery, oncology, and genetics appointments, as well as for virtual multidisciplinary tumor boards, leading to fewer in person multidisciplinary consults. educational conferences and lectures moved to virtual platforms such as webex, microsoft teams, and zoom , . the effect of increased telecommuting and telehealth remain unclear. telecommuting may increase radiologist morale, flexibility, and even potentially productivity, or alternatively it may decrease collaborations, interfacing with multidisciplinary colleagues, decrease educational value, or decrease productivity . about half of the radiologists surveyed nationwide believed that teleradiology would continue and lead to increased efficiency . the marked reductions in volume have devastating financial implications to practices. half of the health care practices in california furloughed or laid off employees, and almost / reduced staff hours. , in academic practices, a quarter had furloughed or laid off staff . significant reductions to radiologist and staff incomes (in about % of practices in one survey), personal and academic protected time, research endeavors, workload, hours, professional funds, bonuses and financial incentives, and retirement allocations, occurred amidst hiring freezes, and workspaces changes . in a survey of practices from across the country, there were mean reductions in both receipts and gross charges on average about % . and over % of respondents reported applying for some sort of governmental financial relief. although emergency governmental funds for financial relief were dispensed to hospitals and health care organizations through the coronavirus aid, relief, and economic security act and the paycheck protection program and health care enhancement act (on the order of nearly $ billion dollars), these funds are likely not enough to prevent lasting financial implications from the significant disruptions in volume and care , . although practices are recovering, some near fully, as of september , the anticipated time to full recovery remains unknown. effects on radiologists mental health through this crisis have been significant. over % of radiologists in states, rated their anxiety as a out of during the pandemic. in addition to having work and economic worries, some radiologists and staff were redeployed in the early days in hotspots to better serve covid- patient care. additionally, many radiologists have had increased burdens at home with unexpected need to provide childcare and teaching duties for virtual schooling amidst school and childcare care closures. additionally, over / of radiologists felt that they did not have adequate teleradiology capabilities during the pandemic, and about half said they did not have adequate ppe for themselves or their patients. mental stress regarding personal and family health, disruptions to travel and schedule, and family members with lost jobs or decreased income also effect the potential for long term burnout in radiologists to increase and mitigation strategies for burnout should be employed . radiology education has also been significantly disrupted during the covid- pandemic, including the need for redeployment, changes to reading rooms and social distancing, and cessation of in person conferences and didactic learning . some radiologists, especially residents early in training, were redeployed to other areas in particularly hard hit urban environments such as new york and boston, with some medical students even graduating early to join the front lines in caring for covid- infected patients. approximately % of radiologists in one survey felt that the shift to socially distant interpretations and conferences had a deleterious effect on resident and fellow education . hundreds of scientific and medical conferences including dozens of radiology conferences were cancelled or moved to virtual formats. significant impacts on networking, collaboration, committee work, vendor marketing, scientific presentations and sharing of research, are likely that may impact scientific progress as well as career choices. many radiologists were placed on institutional or state travel bans. virtual grand rounds and virtual interviews both for education and for hiring were implemented during the pandemic. the cost and time savings of such virtual practices may prove to be practice changing after the pandemic is over. initially, most academic centers and universities suspended research, especially all trials involving patients or in person interactions . guidance on how best to preserve clinical trials, and maintain integrity for those interrupted, was offered by the senior editorial staff at jama. the fda offered direction for those trials that may be disrupted. additional suggestions on how to avoid overestimation of disease free survival if patients skip assessments, and to report results from data during the pandemic separately from date before the pandemic continues to be offered. , in contrast, the national cancer institute intentionally kept functioning at % and stressed the importance of maintaining research to allow patients to have access to clinical trials and to maintain scientific progress, as well as to study the effects of covid- in cancer patients. the nci showed increased flexibility for prior minor infractions (such tests as a missed blood draw), recognizing that they may be necessary during covid- to help maintain social distancing best practices for the patient. some of the flexibility extended to clinical trials during the pandemic such as virtual instead of in-person visits for enrollment or assessments, the ability to receive tests and lab draws at sites closer to the patient that are not part of the trial sites, and decreases in the administrative tasks required pre-pandemic may carryover to the postpandemic world, perhaps making clinical trials more accessible to the general population. of note, the pandemic led to the creation of unique opportunities for the creation of collaborative, crowdsourced research endeavors and databases, including the covid- and cancer consortium, among others, collecting real time data for observational trials. the final economic costs of the pandemic on the health care industry will likely be colossal. one study proposes the direct medical costs will approach $ billion dollars if only % of the population is infected ( . million symptomatic cases) and would continue to cost up to a total of almost $ billion in indirect costs in the year after discharge. this figure will increase if the percent infected increased above that. nationally, there has been significant deleterious effects on the economy including almost million americans filing for unemployment in a week period over march/april alone, although with claims decreasing continually since that peak. , whether or not covid- will continue to circulate in the population with annual or seasonal outbreaks, or whether this will be an outbreak that has mostly cycled through the population with a return to closer to normal by or so remains unclear and debated yet at the time of this writing. what is clear is that without a vaccine and other treatments, social distancing and personal protective equipment with masks and other protections for hcws are likely to remain the primary weapons against the virus and will likely continue to play a part in daily life and in radiology practices and patient care in breast imaging centers for a while yet to come. what the future looks like on the other side of the pandemic remains unclear, but will involve significant effects on both covid- and non-covid- related health outcomes, mental health outcomes, the national and global economy, radiology practices and breast centers, and on cancer outcomes, screening rates, and cancer management and treatment protocols. characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention first case of novel coronavirus in the united states responding to community spread of covid- : interim guidance framework for healthcare systems providing non-covid- clinical care during the covid- pandemic response to covid- in breast imaging for the rsna covid- task force. special report of the rsna covid- task force: the short-and long-term financial impact of the covid- pandemic on private radiology practices the coronavirus claims two georgia health care workers risk of covid- among front-line health-care workers and the general community: a prospective cohort study safety at the time of the covid- pandemic: how to keep our oncology patients and healthcare workers safe. j natl compr canc netw the front line: visualizing the occupations with the highest covid- risk asbrs and acr joint statement on breast screening exams during the covid- pandemic society of breast imaging statement on breast imaging during the covid- pandemic initial impact of coronavirus disease (covid- ) on radiology practices: an acr/rbma survey canadian society of breast imaging and canadian association of radiologists joint position statement on covid- society of breast imaging statement on screening in a time of social distancing camps herrero j, on behalf of the eusobi executive board. eusobi recommendations for breast imaging and cancer diagnosis during and after the covid- pandemic breast imaging and cancer diagnosis during the covid- pandemic: recommendations from the italian college of breast radiologists by sirm american college of surgeonscovid- : guidance for triage of non-emergent surgical management of cancer surgery cases during the covid- pandemic: considerations breast cancer diagnosis, treatment and follow-up during covid- pandemic management of breast cancer during the covid- pandemic: a stage-and subtype-specific approach a system for risk stratification and prioritization of breast cancer surgeries delayed by the covid- pandemic: preparing for re-entry recommendations for prioritization, treatment, and triage of breast cancer patients during the covid- pandemic the covid- pandemic breast cancer consortium association of perioperative registered nurses managing cancer patients during the covid- pandemic: an esmo multidisciplinary expert consensus covid- and the precautionary principle: prioritizing treatment during a global pandemic the impact of covid- on and recommendations for breast cancer care: the singapore experience recommendations for triage, prioritization and treatment of breast cancer patients during the covid- pandemic esmo management and treatment adapted recommendations in the covid- era a guide to cancer care delivery during the covid- pandemic case - : a -year-old woman with early breast cancer during the covid- pandemic operational radiology recovery in academic radiology departments after the covid- pandemic: moving toward normalcy acr response to covid- update: fda prepares for resumption of domestic inspections with new risk assessment system sars-cov- transmission in patients with cancer at a tertiary care hospital in wuhan cancer patients in sars-cov- infection: a nationwide analysis in china clinical characteristics of covid- -infected cancer patients: a retrospective case study in three hospitals within wuhan, china characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention case fatality rate of cancer patients with covid- in a new york hospital system do patients with cancer have a poorer prognosis of covid- ? an experience in new york city clinical impact of covid- on patients with cancer (ccc ): a cohort study clinical characteristics of coronavirus disease in china covid- mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study when a global pandemic complicates cancer care: although oncologists and their patients are accustomed to fighting tough battles against a lethal disease, coronavirus disease (covid- ) has posed an unprecedented challenge american college of emergency physicianns covid- breast cancer and covid- : the effect of fear on patients' decision-making process patient-reported treatment delays in breast cancer care during the covid- pandemic breast imaging, breast surgery, and cancer genetics in the age of covid- outcomes in radiotherapy-treated patients with cancer during the covid- outbreak in wuhan management of breast cancer during the covid- pandemic: a stage-and subtype-specific approach impact of the coronavirus disease pandemic on cancer treatment: the patients' perspective perspectives on oncology-specific language during the coronavirus disease pandemic: a qualitative study oncology language for the covid- pandemic fair allocation of scarce medical resources in the time of covid- applying lessons learned from low-resource settings to prioritize cancer care in a pandemic the breast health global initiative: clinical practice guidelines for management of breast cancer in low-and middle-income countries excess deaths from covid- and other causes effect of delays in the -week-wait cancer referral pathway during the covid- pandemic on cancer survival in the uk: a modelling study is a delayed cancer diagnosis a consequence of covid- ? changes in the number of us patients with newly identified cancer before and during the coronavirus disease (covid- ) pandemic covid- and cancer economic downturns, universal health coverage, and cancer mortality in high-income and middle-income countries, - : a longitudinal analysis impact of the coronavirus disease (covid- ) pandemic on imaging case volumes early-stage radiology volume effects and considerations with the coronavirus disease (covid- ) pandemic: adaptations, risks, and lessons learned response to the covid- pandemic: practical guide to rapidly deploying home workstations to guarantee radiology services during quarantine, social distancing, and stay home orders j o u r n a l p r e -p r o o f coronavirus has sparked a teleradiology revolution ibm, a pioneer of remote work, calls workers back to the office: big blue says move will improve collaboration and accelerate the pace of work thousands of healthcare workers are laid off or furloughed as coronavirus spreads paycheck protection program and health care enhancement act impacts of the coronavirus disease (covid- ) pandemic on healthcare workers: a nationwide survey of united states radiologists understanding and addressing sources of anxiety among health care professionals during the covid- pandemic burnout and posttraumatic stress disorder in the coronavirus disease (covid- ) pandemic: intersection, impact, and interventions the impact of covid- on radiology trainees adapting scientific conferences to the realities imposed by covid- the impact of a pandemic on professional meetings the impact of the covid- pandemic on the radiology research enterprise: radiology scientific expert panel preserving clinical trial integrity during the coronavirus pandemic fda guidance on conduct of clinical trials of medical products during covid- pandemic: guidance for industry, investigators, and institutional review boards. us food and drug administration covid- update from the nci cancer imaging program rethinking clinical trials reform during the covid- pandemic covid- and cancer consortium registry (ccc ). clinicaltrials.gov identifier: nct . posted the potential health care costs and resource use associated with covid- in the united states. health aff (millwood) the economic impact of the covid- pandemic on radiology practices key: cord- - jbehcb authors: nan title: confronting the pandemic superthreat of climate change and urbanization date: - - journal: orbis doi: . /j.orbis. . . sha: doc_id: cord_uid: jbehcb nan the grand illusion. . . is that the collectivity of states is capable of agreeing upon the taking of decisive action. -colin s. gray uch has been written about climate change and its causes and effects. while some deny that climate change is happening or that humans have any mitigating role to play, most reasonable people would concede that climate change poses real problems that must be addressed. regardless of one's skepticism on the matter of climate change, it is essential to consider its worst-case outcomes when developing u.s. security strategies and policies. as the department of defense (dod) has reported to congress, "the effects of a changing climate are a national security issue with potential impacts to [dod] missions, operational plans, and installations." of the projected negative effects of climate change, from severer storms to more extensive droughts, probably the threat with the most devastating potential is a pandemic. from disrupting trade to decimating populations, a pandemic could potentially cause more destruction than a nuclear strike; thus, it is essential to understand how changing climate could unleash such destruction-with little to no advance warning-and how we can best manage the consequences. most experts agree that the world is heading into a potentially severe warming phase, with average temperatures expected to rise - degrees celsius (c) by the end of this century. as a result, weather events such as heat waves and storms, and the attendant consequences of droughts and floods, are expected to increase in frequency and severity. and due to these climatic and weather changes, a significant increase is expected in the potential for infectious diseases transmitted via insects, rodents, and contaminated water. deadly diseases carried by insects, such as malaria, thrive at higher temperatures and so are expected to be a more active threat in the years ahead. in addition, waterborne infectious diseases, such as cholera, will also likely increase due to poor sanitation caused by water scarcity in times of drought and by "overwhelmed sewage lines or the contamination of water by livestock" during times of flooding. as an example of how bad a cholera epidemic can become, consider the recent outbreak in yemen, which erupted in april and has since led to over one million suspected cases and over , deaths. the ongoing civil war in yemen and the resulting scarcity of water have exacerbated the epidemic. pandemic disasters caused by climate change are not new; there are plenty of examples in world history. one especially tragic example is the "black death" of the mid-fourteenth century, which killed upwards of million people in europe and asia and likely was caused by climatic changes that stimulated the growth of the rodent population. certainly, this example involved a complex interaction of factors over an extended period of decades. a mild climate in eastern kazakhstan and southwest china "fostered plant-food abundance and hence wild rodent proliferation." as a subsequent cooling took place, "plant growth declined" and catastrophic floods "displaced and drowned many people." the environmental changes "likely also displaced wild rodents and increased rodent-human contact." at the same time, in western china "encroaching nomadic mongol pastoralists" and "han chinese farmers" engaged in increased conflict, and this also displaced people and likely increased rodent-human contact. this chain of climatic effects could well have potentiated a deadly plague epidemic. "before long, trade caravans or (more probably) horse-borne mongol armies, with 'companion' black rats, carried the disease westward shuman, "global climate change and infectious diseases." into europe . . . via the black sea port of kaffa." within ten years, europe's population was decimated. this pandemic starkly illustrates the dark side of fourteenth-century globalization. it demonstrates all too clearly that climate changes in one location can result in cascading effects that ripple around the world and eventually wreak havoc far removed from the source of initial disaster. those forces were the same ones that we face today: natural disasters, migrations of people, conflict over scarce resources, and ultimately a pandemic transmitted around the world through trade and war. at present, with billions more people and modern means of transportation, it is clear the same situation today would be exponentially more disastrous. lest one think that modern society is safer due to advanced technology and capabilities, consider that many experts believe the opposite: modern societies, though better resourced and more interconnected, are also more densely populated and infrastructure-dependent, and hence less flexible and more vulnerable to a sudden disastrous shock. one of the starkest differences between now and the mid-fourteenth century is how populated the earth is at present, and how much of that population has crowded itself into urban centers. the current world population is over . billion people, approximately percent of whom live in urban environments. compare that to a world population of approximately million before the onset of the "black death," most of whom lived in rural, sparsely populated areas. looking ahead, the trend to urbanization is only expected to continue: experts estimate that roughly percent of the population will live in dense urban environments by the year . while the movement of rural populations to cities is caused by several factors, including economic and educational opportunities, it is being exacerbated by the increased incidence of droughts, floods, and other consequences associated with climate change. these climate-related disasters hurt agricultural production and serve as "push" factors from rural to urban, just as jobs and education serve as "pull" factors. experts predict that climate-induced migrations potentially will accelerate after . most of the urban growth is projected to occur in asia and africa, where developing countries dominate the landscape and where basic healthcare, sanitation, and other infrastructure is sorely lacking in rural areas. as a result, cities in developing countries that are already at, or near, the limits of the population they can adequately support are being slowly overwhelmed by at-risk migrants who are overtaxing already weak infrastructure and security systems. this problem is exacerbated by the rapid development of megacities, defined as having a population in excess of million. "in , developing nations boasted megacities compared to seven in developed countries." this trend toward expansion in developing countries is set to continue, especially in africa. for example, luanda, predicted to become a megacity by , "is expected to undergo a percent increase in its population between and , placing further strain on housing, transport, public utilities and sanitation." one critical problem with the expanding urban landscape is that the growth is largely uncoordinated. densely populated shanty towns and slums ring the edges of otherwise modern and ordered square blocks of skyscrapers and malls. the uncontrolled development leads to increased human interaction with rats and other rodents, thereby greatly increasing the likelihood of zoonotic infectious diseases. also increasing the potential for zoonotic contagions is that the new populations push cities out into previously undisturbed ecosystems (e.g., adjacent deserts and forests), and as a result contact between animals and humans increases, generally in unsanitary environments. the overcrowded conditions heighten the risk of vector-borne diseases, such as malaria and dengue fever. basic sanitation and water systems become overwhelmed, resulting in contaminated water supplies and increasing the potential for cholera and other water-borne diseases. diseases that were formerly confined to rural areas accompany the migrants into the new urban environment, where they have a much greater chance to thrive. security services are often unable to properly police the expanded slum areas, which can become lawless and less secure. in addition, where order has disappeared, other city services generally will not go. most critically, existing healthcare services cannot properly serve the increased population. if a pandemic takes root in such an environment, chances are high that it will spread rapidly before it can be detected. to understand how severe the problem can become, one can look at mogadishu, somalia. mogadishu's devastation has been caused by many factors, including poverty, violence, and lack of effective governance. climate change has been a significant contributor to all of this. as scholars giovanna kuele and ana cristina miola have noted, "over the past decade climate change-related desertification has expanded in somalia, greatly increasing the vulnerability of the local population." this change has sharpened disputes over scarce water resources and has led to "high rates of malnutrition, disease outbreaks, and food insecurity." cholera epidemics have been recurrent in somalia, the most recent one starting in late , and thousands have died as a result. with disease and violence rampant, over one million somalis have been displaced; with mogadishu in utter chaos, many of them have migrated to nearby kenya, thus putting a strain on kenya's resources. in the yemen cholera outbreak noted above, scientists have determined that the strain causing the outbreak "came from eastern africa and entered yemen with the migration of people in and out of the region." thus, it is likely that somalia's dysfunction has contributed to yemen's. combined, these problems have enabled easier recruitment of warlords, reyes et al., "urbanization and infectious diseases," p. . intent on controlling the capital city mogadishu through violence and terror. mogadishu is the prime example of what richard j. norton has termed "feral cities," where degradation and insecurity create conditions where disease and violence flourish. be realistic. more aggressive action is required to resolve, or at least mitigate, the immediate consequences and near-horizon disasters looming as a result of climate change and increasing urbanization-especially regarding the possibility of a pandemic. several arms of the u.s. government, including the department of state (dos), the u.s. agency for international development (usaid), and the centers for disease control and prevention (cdc), are actively combatting disease and climate change around the world. however, none of these agencies can match the global presence and financial heft of dod. this realization is especially true in the current political environment, as the trump administration seems intent on cutting foreign assistance and health budgets while increasing dod's. for example, president trump's fy budget "requests $ billion for dod, a $ billion or five-percent increase from the enacted level"; at the same time, it "requests $ . billion for the department of state and usaid, a $ . billion or -percent decrease from the estimate." congress is unlikely to agree with the president's overall budget proposal, now or in the future, but it seems safe to predict that military resources will increase. due to its global reach and resources, the u.s. military is better placed than "the relationship between the proliferation of illegal armed groups and the severe droughts in somalia is evident in the case of al-shabaab. the group has been successful in attracting young people who are affected by famine and food insecurity and who face no job prospects; those youth end up joining the armed group in a bid to survive, finding no other option other than to submit to the extremist group. nearly any other organization and should take an aggressive leading role in preventive efforts. unfortunately, to date, the international community has not demonstrated the will to act decisively on climate change. while many nations voluntarily have signed onto international agreements, such as the kyoto protocol and the paris agreement, few of these countries adhere to the agreed standards. and, the agreed standards themselves have been called into question as not being sufficient. in addition, some of the greatest contributors to pollution and environmental degradation flagrantly ignore climate concerns. indeed, both india and china, two of the biggest polluters in the world, were exempted from the kyoto protocol, and the paris agreement contains no formal enforcement mechanisms-one of the glaring weaknesses of internationally engineered solutions to climate change. at the recent climate gathering in katowice, poland, participants agreed to a new rulebook to improve the paris agreement; however, details of the "rulebook" are not clear, and key countries did not support the creation of a global carbon market, seen by many economists as the key to reducing carbon emissions worldwide. the gathering appeared to promise more of the same: heavy polluters will continue to pollute, while certain developed countries will continue voluntarily to reduce emissions (or not). this is not to say that international government organizations (igos) bring no benefit to the discussion. the united nations and other igos serve a useful role in raising awareness, providing a forum for debate, and providing resources in some david g. victor, keigo akimoto, yoichi kaya, mitsutsune yamaguchi, danny cullenward, and cameron hepburn, "prove paris was more than paper promises," nature, aug. , , https://www.nature.com/news/prove-paris-was-more-than-paper-promises- cases. for these reasons alone, the united states should stay actively involved in international efforts to combat climate change and ensure as much as possible that u.s. interests are promoted. however, a realist understands that due to the inefficiencies of international consensus-building, igos' actions generally will be longer-term solutions with slow and clumsy implementation. as divya srikanth has written: "developed states are highly reluctant to voluntarily stunt their economic growth by adhering to the kyoto protocol, and developing states are unwilling to compromise on their new-found economic successes. this has led to a stalemate in terms of tackling the impact of climate change." though the stalemate shows no positive signs of breaking, due to the severity of the stakes involved, america cannot abdicate leadership in this long-term effort. at the same time, it must lead efforts to combat the near-term consequences of climate change. engage partners, including china. fighting pandemics is one issue on which nations should share strategic goals and could therefore use the opportunity to build better relations. the united states should utilize this common interest and leverage alliances and partnerships in the most at-risk locations. for example, one of the current hotspots for a future pandemic to break-out is southeast asia, specifically the sulu-sulawesi sea area. the u.s. military currently works closely with indonesia, malaysia, and the philippines-the countries that ring the sulu-sulawesi sea-on counterterrorism and anti-piracy actions in the area. these relationships could be leveraged to take additional actions to prevent a pandemic from breaking out there, such as increased coordination and construction of research, detection, and healthcare facilities along the sea's edge. sulu-sulawesi sea and the adjacent south china sea, could be pulled into a multilateral partnership to fight against a pandemic. there are multiple challenges to a u.s.-china partnership, including lack of trust and a competition for influence, especially in southeast asia. as author robert kaplan recently wrote, u.s-china differences are "stark and fundamental" and "can barely be managed by negotiations and can never really be assuaged." however, there are opportunities to exploit, one of which is china's experience dealing with its own deadly disease outbreak in - , when severe acute respiratory syndrome (sars) took root in guangdong province and eventually infected over , people and killed more than . according to one chinese public health official, "the sars crisis provided an enormous boost to the development of china's public health system." china is also considered by some to be a likely origin of a future pandemic, especially from h n bird flu, which chinese and western scientists have been studying closely in hopes of preventing a disastrous spread. presumably, china has significant knowledge and resources to contribute in the war against pandemics. china also is keen to build roads, ports, and other facilities as part of its belt and road initiative (bri), especially in developing regions such as africa, and it has significant experience managing the growth of megacities. through effective partnering, china's infrastructure investments and its planning experience could be harnessed toward mitigating the negative consequences of climate change and urbanization. to consider an indirect approach, china is realizing that its rapidly aging population will not accommodate the country's current plan of sustained economic growth as a means to sustain internal stability and increase global influence. as china envisions negative population growth as early as , it will need to partner creatively with other countries and organizations to attain the necessary prosperity to support its changed demographics. the united states should leverage china's changing domestic politics to pull it into constructive partnerships on health and climate-change (and other) matters, and thereby, it is hoped, increase its stake in an international rules-based order. this becomes especially important as china seeks to build-up its navy and spread its influence. as bernard-henri levy has written, "one may hope, though without illusions, that china will send its steel junks in the wake of the fleets of the wise zheng he, china's admiral of the western seas and leader of expeditions bound for glory and not for conquest." active and constructive engagement on human-security problems is one way to help make this happen. research and model. one of the most effective defenses against a future pandemic is to undertake research now in the hopes of discovering the potential pandemic before it discovers us. several governments and ngos are actively engaged in this type of research; however, they often lack adequate resources or cohesion to be truly effective. the u.s. military could fill a serious need by bringing its resources to bear. the naval medical research unit (namru) is an entity that the military could employ to establish laboratory facilities to conduct research and support that of others, and to help develop and maintain an organized database of useful information. usaid's emerging pandemic threats program is one effort that this unit could support more deeply, and an example of an effective component of this program is the predict project, based at the university of california, davis. these organizations and others are researching contagions that potentially could infect humans, especially from animal hosts, and possible vaccines to combat them. researchers perform their work in areas where contagions are most likely to take root, such as the sulu-sulawesi sea described above. it is areas like this where the u.s. military should concentrate its efforts. as part of its research, the u.s. military can engage in predictive modeling, trying to determine based on weather patterns, people movements, socioeconomic factors, and potential contagions-what this author collectively refers to as pandemic intelligence-where the next pandemic might break out. an effective partner would be the national oceanic and atmospheric administration (noaa), which has programs and technology in place to monitor weather patterns and climate activity. the military could harness noaa's capabilities and knowledge, and that of others, to consider the potential cascade effects that would occur should a pandemic take root and spread. as chad michael briggs has noted, "environmental systems often exhibit feedback and multiplier effects, where a smaller change in one area leads to a cascade of impacts with much greater shifts elsewhere." for example, a heatwave in russia caused a food shortage and price spikes in north africa and the middle east and thus likely contributed to the arab spring revolts. cascade predictions could help to predict both near-and long-term consequences and would thus be critical in ensuring up-to-date operational plans to be used by the military when responding to pandemic outbreaks, and for efforts to prevent or contain outbreaks when responding to natural disasters. surveil and detect. it is also critical to conduct surveillance of possible threats from weather events, sudden migrations of people, and detected contagions. many developing countries lack modern and reliable warning systems for incoming severe storms. one of the reasons more than , people died when a tsunami hit sulawesi, indonesia, in september , was that the populations in its path were not properly forewarned of the seriousness of the danger. the u.s. military should help to ensure that essential warning systems are in place at critical spots, especially in southeast asia. in addition to working with local stakeholders to assess critical vulnerabilities, the military should coordinate with agencies such as noaa, which has models and equipment in place to warn of natural disasters. for example, noaa has tsunami detection buoys placed throughout the world's oceans and seas, most heavily in the pacific. however, despite these buoys and noaa's predictive capabilities, indonesia and other countries continue to rely on their own systems, with oftentimes disastrous results. in indonesia's case, its warning system was no longer operational in september due to lack of maintenance. because of its worldwide presence and resulting unique relationships and influence, the u.s. military is well-positioned to ensure coordination between developing countries and u.s. agencies such as noaa, who have capabilities to help but sometimes lack the resources to effectively coordinate. when natural disasters do occur, the u.s. military should maximize its strengths to complement the work of other relief organizations. for example, drone and satellite technology can monitor sudden migrations of people and detect infectious diseases that might be accompanying a group. scientists have experimented with using drones to take samples of mosquitos and other potential carriers of disease, and this could be an effective way to discover contagions before they hit a large city, or to determine which parts of a city might be at risk once a contagion has taken root. in addition, drones could be used to deliver self-spreading vaccines and other countermeasures to remote or highly infected locations. drones and satellites could also be used to monitor at-risk environmental ecosystems. scientists are developing techniques to use these technologies to monitor the health of crops, and the same ideas conceivably could be used to research the potential for zoonotic diseases to take root, especially in areas where human-animal interactions are unexpectedly increasing. the pandemic intelligence that results could be valuable not just for local predicting, but also for the cascade modeling described above. due to its reach and resources, the u.s. military is ideally situated to assist in this type of research and should work with the governments of at-risk nations, other u.s. government agencies, and allies who share common interests in the at-risk areas. as cities greatly expand in the coming decades, many predict that only a small percentage of them will be healthy and properly regulated; most will contain large areas of at-risk populations, where a pandemic could easily take root and spread. many cities in developing countries lack proper sanitation and sewage facilities and have insufficient healthcare infrastructure. to help correct this, the u.s. military should increase its partnering of civil-affairs and engineering resources with at-risk cities and development organizations to upgrade and build necessary infrastructure. because a significant reason for increasing urbanization is migration from rural areas, at-risk governments should take steps to improve rural infrastructure and services as well. again, the u.s. military has reach and resources that others cannot match. it could expand ongoing efforts, such as the pacific environmental security forum, and make them more frequent and routine. it is essential to expand partnerships with and support the world health organization (who), usaid, and others to add facilities, provide training, conduct services in the most vulnerable areas, and help cities better plan for expansion and a proper balance of interaction between humans, animals, and johns hopkins, "technologies to address global catastrophic biological risks," p. . sonia shah, "how cities shape epidemics," the atlantic, feb. , , https://www.theatlantic.com/health/archive/ / /urbanization-pandemicexcerpt/ /. neiderud, "how urbanization affects the epidemiology or emerging infectious diseases," p. . "between and , the group in urban settings which lacked sanitation actually significantly increased from million to million, which could be explained by population growth." based on this author's experience as economic officer in iraq, the u.s. military civil affairs teams were better at enacting effective and pragmatic changes than were usaid and other non-military organizations. this author worked closely with civil affairs team members who had agriculture, finance, and engineering expertise and who effectively shared it with iraqi government officials and business managers to bring about positive change. reyes et al., p. . for a description of the program and ongoing projects, see, "pacific environmental security forum," u.s. indo-pacific command, http://pesforum.org/. delicate eco-systems. as noted earlier, an effective partner could be china, whose focus on public infrastructure could be strengthened by america's traditional focus on policy reform and technical assistance in sectors such as healthcare. the u.s. military should also upgrade its own capacity in line with the new threat environment. while we place a renewed focus on great-power competition with china and russia and continue hedging against terrorism and other intermediate threats, we should also factor in human-security challenges such as pandemics. our force structure should change to reflect this. for example, we should add more hospital ships and invest more heavily in health-related artificial intelligence (ai) capabilities, even if that means cutting warships. in addition to providing essential medical services, the hospital ships could be redesigned and updated to include extensive laboratory facilities and drone and ai platforms to assist with research, surveillance, and detection. the drones could also be used to deliver medical supplies to hard-to-reach locations. some would argue that this change in force structure would cut against the grain of the national defense strategy's emphasis on traditional "lethality" and its focus on great-power competition, diverting money from much-needed warfighting capabilities. however, it is reasonable to argue that the american homeland and overall global security face a deadlier threat from a pandemic than from chinese or russian aggression. as an example, one should consider the spanish flu that broke out in , and by the spring of , it "had sickened an estimated one-third of the world's population and may have killed as many as million people," including approximately , americans. this black swan attacked a world completely unprepared for it, and its death toll was higher than that of the great war that immediately preceded it. a more recent example is the swine flu pandemic of , which, according to cdc, killed an estimated , people. security against this kind of non-traditional threat involves a different kind of lethality, one in which we invest in capabilities that are designed to preempt and destroy contagions rather than people and infrastructure. adding hospital and laboratory ships, and the associated drone and ai capabilities, would greatly improve our ability to provide medical services and research and surveillance support at the most at-risk locations. it would also demonstrate a positive u.s. presence to huge segments of the developing world's population. from a budgetary perspective, consider that "the cost to the global economy of sars is estimated to have been $ billion, according to the world bank, while the organization estimates that a 'severe flu pandemic' could cost over $ trillion, nearly five percent of global gdp." even if a newly designed hospital and laboratory ship carried a price tag of $ billion or so, the potential of catastrophic loss from a pandemic dwarfs the investment in human security that would come with the procurement of a fleet of these ships. when one considers that the majority of the world's growing urban population resides "in a coastal zone or a zone with distinct coastal influence," the argument to update the navy's human-security capabilities becomes even more cogent. as climate change and urbanization progress, pandemics are likely to occur, and american national-security professionals must consider this worst-case scenario as they develop strategies and policies. if we actively pursue preventive and mitigating actions, the outcome of a pandemic could be a disaster that can be managed, contained, and learned from. the alternative will be more mogadishus, or worse. igos play an important role in encouraging international debate and in providing limited resources; however, to address the looming threat of deadly contagion, we must take aggressive and pragmatic action. due to its reach and resources, the u.s. military is well-placed to lead. it should partner with governments and ngos, leveraging existing alliances and building new ones. primary actions should include conducting research and creative predictive modeling; ensuring effective surveillance and detection efforts; and upgrading and building infrastructure in high-risk areas. the military should also revise its capabilities to better address the growing pandemic threat. it is appropriate to close with an overarching statement of purpose from the u.s. national biodefense strategy: "the united states will use all appropriate means to assess, understand, prevent, prepare for, respond to, and recover from biological incidents-whatever their origin-that threaten national or economic security." due to the interconnectedness of today's world, it is hard to imagine a pandemic that would not have potential to threaten american security. we must approach the fight against pandemics aggressively, detecting, containing, and destroying a pandemic when it attacks, and the rest of the time working to prevent and prepare for the next pandemic. as the climate warms and eco-systems change, new and deadlier contagions will enter the fight, and we must stay engaged. groundswell: preparing for internal climate migration here's what you need to know about the megacities of the future here's what you need to know about the megacities of the future urbanization and infectious diseases: general principles, historical perspectives, and contemporary challenges how urbanization affects the epidemiology or emerging infectious diseases suburban sprawl into previously unpopulated areas is also a significant cause of new interaction between humans and other species how urbanization affects the epidemiology or emerging infectious diseases urbanization and infectious diseases: general principles, historical perspectives, and contemporary challenges," p. ; see, also, thayer, darwin and international relations, p. a new cold war has begun outbreak-changed-mainland-china. for infection and death figures, see, anmar frangoul how the sars outbreak changed mainland china is china ground zero for a future pandemic? how china sees the world: han-centrism and the balance of power in international politics one of them is its showcase city, shanghai, with a population of . million. see, sharon omondi china lowered its economic growth target "to between % and . %, bowing to a deepening slowdown that can't be quickly arrested without aggravating already-high debt levels the empire and the five kings: america's abdication and the fate of the world many governments of developing countries do not have the capabilities to organize effective response efforts, and igos, usaid, and others often do not have sufficient resources. "review of the dod-geis influenza programs: strengthening global surveillance and response usaid, emerging pandemic threats for example, see, noaa's following sites on climate and exploration tools: noaa, climate climate security, risk, assessment and military planning climate security, risk, assessment and military planning how urbanization affects the epidemiology or emerging infectious diseases surveillance is of primary importance to monitor the burden of disease and will give both local authorities and the global community a chance for a quick response to public health threats the art of predicting unpredictable tsunamis indonesia tsunami early-detection buoys haven't worked for six years due to 'lack of funding climate security, risk, assessment and military planning the art of predicting unpredictable tsunamis how tsunami early warning systems work, and why indonesia's system failed from self-spreading vaccines to d drugs: the tech that will stop a pandemic for a thorough review of research and technologies that could be used to prevent and respond to pandemics, see how urbanization affects the epidemiology or emerging infectious diseases adequate city planning and surveillance can be powerful tools improve the global health and decrease the burden of communicable diseases navy is considering upgrades to its hospital-ship capability, but the thinking seems too constricted for the human-security challenges, such as pandemics, that we face. the navy's focus is more on care and not enough on research and prevention. megan eckstein with the first line of effort being lethality, the undersecretary said, 'make no doubt about it-we are about warfighting the central challenge to u.s. prosperity and security is the reemergence of long-term, strategic competition by what the national security strategy classifies as revisionist powers why was the influenza pandemic called the 'spanish flu for an analysis of world war i deaths, see, david stevenson, cataclysm: the first world war as political tragedy counting the cost of a global epidemic retire-one-of-its-two-hospital-ships. this author has seen the huge impact that hospital ships can have on u.s. diplomacy. when he served in cambodia, the usns mercy conducted a humanitarian visit as part of pacific partnership . the doctors and nurses on the ship treated thousands of cambodians for health problems. this left an impact that will stay with those people-and their families, friends, and villages-for the rest of their lives. overall, the pacific partnership mission visited six southeast asian countries and treated , patients. for an overview of the mission, see counting the cost of a global epidemic the navy eyes replacing its hospital ships with a fleet of smaller medical vessels megacities and large urban agglomerations in the coastal zone: interactions between atmosphere, land, and marine ecosystems for a good discussion on the need for continuous vigilance, see, gray, fighting talk as noted above, the increased interaction of humans, animals, and previously untouched environmental ecosystems will likely lead to new contagions infecting humans. there are also unknown viruses lurking in the arctic. for a good discussion on the discovery of previously unknown viruses buried beneath permafrost, see key: cord- -w ajpaxo authors: yıldız, erman title: what can be said about lifestyle and psychosocial issues during the coronavirus disease pandemic? first impressions date: - - journal: perspect psychiatr care doi: . /ppc. sha: doc_id: cord_uid: w ajpaxo nan what can be said about lifestyle and psychosocial issues during the coronavirus disease pandemic? first impressions to the editor, the disease caused by the coronavirus disease (covid- ) which shows involvement mainly in the respiratory tract was declared as a pandemic on march by the world health organization (who). everything regarding covid- started with cases detected in the city of wuhan in china and became a public even that concerns the entire world in a short time due to the disease's high contagiousness. , according to the official website of who, it was confirmed globally that more than people had covid- infection by june , and the number of cases is increasing day by day. although the methods used by countries to take the covid- pandemic under control show a diversity, it is seen that the strategy that is common in the world involves calls for staying home. , without a doubt, it is a necessity in terms of slowing down the spreading speed of the pandemic for governments to recommend people to self-isolate and self-quarantine, that is, deliberate social isolation. , nevertheless, these restrictions mean reduced physical activity, and this is known as an unhealthy lifestyle. it is a known fact that regular physical activity helps prevent and treat noncontagious diseases such as cardiac diseases, paralysis, diabetes and breast and colon cancer. regular physical activity not only helps prevent hypertension, overweight and obesity but also has the potential to increase mental health, quality of life and prosperity. , in addition to this, restrictions that have been issued in the period of the covid- pandemic prohibited a large proportion of these open and social activities (eg, going to the gym) and led to a reduction in physical activity. additionally, while people are encouraged to exercise at home during quarantine, there are questions regarding the functionality of this. another important area regarding lifestyle involves changing dietary habits and difficulties experienced in effective weight management in connection with the availability of food products and transition to unhealthy foods. that is, due to the concerns on food availability problems in the future, individuals have a tendency to purchase packaged and long-lasting foods rather than fresh foods. such unhealthy dietary behaviors and ineffective weight management carry the potential of causing several noncontagious diseases, such as obesity, diabetes, cardiovascular disease, cancer, chronic kidney disease and osteoarthritis. furthermore, in the long term, negative effects of some behaviors that may be used in coping with problems in the pandemic process may also be experienced. in this context, usage of cigarettes, alcohol and other addictive substances which is defined among ineffective coping styles may present another unhealthy lifestyle. considering the multifaceted nature of healthy lifestyles, applying transdiagnostic approaches can contribute to achieving pragmatic results. indeed, unhealthy lifestyle behaviors encountered in the pandemic period are not just related to noncontagious diseases, but these behaviors are also closely in interacting with the mental health of individuals. considering that unhealthy lifestyle behaviors due to quarantine, such as physical limitation and ineffective weight management are frequently comorbid with stress, anxiety, and depression, the mental health of individuals should not be neglected. for all these reasons, from the perspectives of public health and protective care, there is an emergent need to provide information and interventions to individuals, communities and healthcare institutions for them to continue the healthiest lifestyle under quarantine. although governments encourage people to work from home in the period of the covid- pandemic, working from home does not seem to be suitable and sufficiently functional for the entire population, especially tradespeople. as this situation will inevitably have serious effects on mental health by increasing unemployment, lack of financial security and poverty, it is clear that pandemic management requires socioeconomic policies. the sense of loss experienced in the society in the pandemic process may be caused by losing direct social contact, and this loss may be in multiple forms (eg, loved ones, employment, education opportunities, recreation, loss of freedoms, and social support). moreover, since the losses experienced are known as important risk factors for depression and suicide, they require more careful observation and approach. under quarantine conditions, individuals not only get away from the sources of social support, but they may also need social support more than ever. if these individuals cannot receive sufficient social support from their children, spouses, relatives or surroundings, it is likely for their psychosocial adaptation to be affected negatively. it seems rational to consider the pandemic as a psychological crisis and accept that the uncertainty and unpredictability in the nature of this crisis will have social, psychological and behavioral effects. , in pandemics, uncertainty and the anxiety related to this have strongly remained since the past. , although it is argued that uncertainty is an experience that is always existent in the world of people, this may be felt more than ever in a period of a pandemic. [ ] [ ] [ ] while the speed of spread of the infection seems fast, it is observed that the uncertainty, fear and anxiety caused by the virus spread more rapidly. especially paranoia feelings related to hygiene may be largely affected by anxiety and show themselves as symptoms of obsessive who characterizes covid- as a pandemic early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia mental health and psychosocial problems of medical health workers during the covid- epidemic in china covid- : surge in cases in italy and south korea makes pandemic look more likely coronavirus disease (covid- ) situation dashboard mental health and psychosocial aspects of coronavirus outbreak in pakistan: psychological intervention for public mental health the psychological impact of quarantine and how to reduce it: rapid review of the evidence quarantine, isolation and the duty of easy rescue in public health considerations for quarantine of individuals in the context of containment for coronavirus disease (covid- lifestyle modification with physical activity promotion on leptin resistance and quality of life in metabolic syndrome-a systematic review with meta-analysis lifestyle indices and cardiovascular disease risk: a meta-analysis lifestyle at time of covid- : how could quarantine affect cardiovascular risk ineffectiveness of commercial weight-loss programs for achieving modest but meaningful weight loss: systematic review and meta-analysis multidisciplinary research priorities for the covid- pandemic: a call for action for mental health science. lancet psychiatry the effects of acceptance and commitment therapy on lifestyle and behavioral changes: a systematic review of randomized controlled trials (article in press) the relation of anxiety, depression, and stress to binge eating behavior lifestyle behaviours during the covid- -time to connect the public health effect of economic crises and alternative policy responses in europe: an empirical analysis managing and reducing uncertainty in an emerging influenza pandemic intolerance of uncertainty, appraisals, coping, and anxiety: the case of the h n pandemic the relationship between uncertainty and affect the novel coronavirus, -ncov, is highly contagious and more infectious than initially estimated covid- and mental health: a review of the existing literature china adopts non-contact free consultation to help the public cope with the psychological pressure caused by new coronavirus pneumonia coronavirus disease (covid- ): reducing stigma stigma in the time of influenza: social and institutional responses to pandemic emergencies influenza stigma during the h n pandemic influenza: the once and future pandemic key: cord- -a r gjc authors: dubb, s.s. title: coronavirus pandemic: applying a whole-of-society model for the whole-of-the world date: - - journal: br j oral maxillofac surg doi: . /j.bjoms. . . sha: doc_id: cord_uid: a r gjc during a pandemic, a national government is often considered solely responsible for dealing with the outbreak with local-based policies. a whole-of-society approach to a pandemic is evidence-based and used successfully in countries with a history of pandemic infections. this collaborative approach assumes that no single entity has the capacity to successfully manage the dynamic, complex problems that arise in a pandemic environment. application of the whole-of-society model globally would provide a more harmonious and concerted response with mutual and synergistic benefits to all affected nations. central entities within the model include; civil society, business and government. these are addressed at the community, local government and sub-national level. nine essential services are also identified including health, defence, law & order, finance, transport, telecommunication, energy, food and water. a continuing cycle of readiness, response and recovery of services encapsulates this model. pandemics affect the whole of the world, a global whole-ofsociety approach is therefore needed to tackle them. fritz described "disaster" as being a concentrated event in time and space in which society undergoes disruption such that essential functions are impaired. this disruption occurs on multiple levels; osterholm describes even in a mild pandemic the catastrophic loss of life and devastating impact on world economy, potentially lasting for several years. the cost of preparedness, an estimated $ . billion per year, is dwarfed by the estimated $ billion annual pandemic costs. such disasters and their inevitable consequences occur as the situation exceeds beyond the protective measures placed to contain it. international cooperation remains * corresponding author. e-mail address: ssd @ic.ac.uk fundamental and despite improved general medical care and institutional plans pandemics continue to overwhelm these public health protocols. as witnessed during this current coronavirus pandemic crisis and past pandemics; although the responsibility of control falls upon the country affected by the outbreak there does not currently exist a foolproof singular response system. . these emerging infection threats are made more potent by the increasing international transportation modalities upon which we have come to depend on. lessons have been learned from past pandemics and an evidence-based plan now exists. the world health organisation (who) first proposed a whole-of-society (wos) preparation plan in with risk management update in based upon lessons learned from the a(h n ) pandemic. , , in this model they describe central entities; government, civil society and business with surrounding essential services such as health, defense and food. these are all managed by a continuum of readiness, response and recovery (fig. ) . on declaring the coronavirus pandemic on march th dr. tedros adhanom ghebreyesus, who director-general stated: "this is not just a public health crisis, it is a crisis that will touch every sector, so every sector and every individual must be involved in the fights" is this too complex of a problem to tackle from a local systems perspective let alone on a world scale? complexity within healthcare systems has been described as individual agents able to act independently and unpredictably, their actions are interconnected and become defined by these same interactions. we are naturally used to working within a well-oiled rigid system with specific targets and outcomes, meeting them allows us to level up in the game of healthcare. complex systems in reality are more akin to the matrix; some rules can be bent, others can be broken with rigid boundaries being more blurred than clear. the features of a pandemic are not dissimilar to the features of complexity within a health system; the rapid pace and changing narrative of spreading infection; decisions based on inadequate, incomplete or debated data and adaptive solutions to fix local problems. is a surgical mask superior to an ffp mask? the roth score is widely used one week only to be discounted the next, does wearing theatre shoe covers have any evidence-based impact on reducing infection? the medical research council (mrc) itself adapted to this challenge evolving from rigid randomised control trials to including non-linear, mixed-method approaches to aid in the answering of these questions. as with the wos approach that utilises a multivariate approach this is reflected in the guidance and approach to dealing with complex problems in healthcare itself. the wos approach aims to utilize the principles of complexity within systems and seeks to improve the global effort against pandemic infections, increase information sharing and further institutionalize pandemic responses. although simple in theory, executing such measures requires national, political and local involvement incorporating the entirety of society, the so-called wos pandemic collaboration. this collaborative approach incorporates public agencies including but not limited to businesses, philanthropic organisations, communities and the entire public as a whole. this collaborative approach assumes that no single entity has the capacity to successfully manage the dynamic, complex problems that arise in a pandemic environment. pan-collaboration allows for responses to local changes and appropriate allocation of resources to meet national requirements. despite this well-versed plan on paper, lockdowns initiated as per the advice from the who protocols initially appeared draconian with many countries still not following recommendations of widespread testing, strict quarantine, contact tracing and social distancing. the now ubiquitous and familiar social distancing protocols, restricted transport and hand-hygiene measures were sluggishly adopted in italy, spain and the usa amongst others which in hindsight appear poorly judged decisions. the uk itself went through several different strategies starting with "contain-delay-mitigate-research", a plan that overlooked the who recommendation of testing and "detect, protect and treat". the new plan now aims to "suppress-shield-treat-palliate". another phrase that comes to mind is "singing from the same hymn sheet", a wos approach applied on a global scale would aim to mitigate the plethora of policy changes adopted with every country effectively trying to re-invent the wheel unnecessarily. italy as a case example went from its' discovery of the first official coronavirus case to the biggest crisis it has faced since world war ii within the space of weeks. many other countries have unfortunately suffered the same fate demonstrating not a lack of available knowledge but failure to efficiently and systematically execute this knowledge. from a political perspective pandemics, with their tendency to start small but exponentially and dramatically increase, represent a tightrope walk. strict and systematic measures are best undertaken early before cases are even officially confirmed. in retrospect, these actions would inevitably appear as overreactions if the interventions are successful. partial solutions, however, have been shown to fail time and again with confirmation bias a significant confounder when making daily objective assessments of infection progression. , from a governing body perspective a unified message of preparedness, not panic, is required with prudence overriding politics. an important aspect of this collaborative approach is trust and situation awareness. during the h n pandemic in taiwan, despite mass production of a vaccine, a negative media story centred around the death of a physicians' son led to a significant loss of trust. not only were vaccinations refused but this lack of trust then also extended to government recommendations and inhibited protective measures. situation awareness, so easily lost on a macro-scale again reflects the dynamic, ever-changing environment that is not dissimilar to an operating room . errors on a local level but magnified on a national and international setting may occur often because of tunnel vision toward achieving a particular action or goal to the exclusion of all other factors. conversely, relevant information may be present yet ignored due to distraction or hierarchy or a combination of these factors. examples of this may include panic-buying items despite no suggestion of shortage in supplies or ability to access, listening to local evidence and policy to the exclusion of globally available information and changing events. a government plea for businesses to help in the manufacture and production of ventilators was met with positive pledges from multiples businesses, related and not, to aid in the production of these vital machines. an important aspect missed in the early rush to produce more physical machines was the awareness of training need, recognising the deployment of healthcare workers from a familiar to an unfamiliar environment and different devices having different operational instructions. this very human and relevant clinical factor applies equally to the rapid production of safe machines that make it easy to use under considerable stress and pressure. to this end, further guidance has been appropriately released for a rapidly manufactured ventilator system specification that is minimally, clinically acceptable. other successful collaborations include that of telecommunication companies. these have recently committed to combined resources to support the government and nhs with broadband and mobile network services to support the almost overnight conversion of physical gp and outpatient appointments to remote and digital consultations. a real-life example of the wos model at work can be seen in the h n influenza pandemic. as the who raised the pandemic alert level the taiwanese government, using the wos model utilized many of the measures across multiple entities that we have started to witness in the uk also. this included mass school closure with public education through mass media, enhanced border controls, enhanced border controls and a mass vaccination programme. retired healthcare workers, volunteers and active members of the workforce were also readily mobilized as part of their preparedness measures. more localized examples of this included containment strategies utilized across cities and the triaging process of patients within the hospital. in the former, the city was segregated into sub-districts and districts led by a mayorappointed official. using six sigma principles of breaking down a complex process into smaller, simpler steps these districts were given allocations based on infection status. a "hot zone" for infection outbreaks, "intermediate zones" as buffers and lastly "cold zones" for no outbreaks. checkpoints limited interzonal traffic and isolated outbreaks within a cold zone were transported to isolated hospitals for treatment. triaging of patients for hospital often took place outside of the hospital environment. clear zones of contamination with confirmed cases, clean zones and disinfection stations in between these clearly marked areas. the starkest example of the effectiveness of these measures when followed and when not is that of lombardy and veneto, neighbouring regions within italy of similar socioeconomic profiles. lombardy has suffered , deaths in its' population of million compared to deaths in veneto's population of million. obvious confounders such as population density have played a part however lombardy and veneto adopted opposing public health strategies. whilst lombardy adopted a more relaxed approach veneto undertook many of the wos measures that included extensive testing, proactive tracing of cases and widespread quarantine. at-risk populations including healthcare workers, pharmacists, supermarket cashiers and other essential exposure-prone workers were specifically targeted. the wos model mobilized on the global canvas has untold potential benefits that we have already started to witness. the who-led solidarity trial is a global, coordinated research effort combining worldwide expertise for the discovery of potential treatments of coronavirus. similarly, unicef, who and the coalition for epidemic preparedness innovations (cepi) have combined their efforts, raising funds to help across multiple levels including protective equipment for health workers, mitigate the considerable societal impacts; education, health and safety among others. these are true examples of facet of the wos model applied across the whole of the world and what can be achieved. the occurrence of any pandemic, by definition, is panic inducing and responsibility is often considered to be solely of the governing body within that country. past pandemics have demonstrated that mobilizing all aspects of society in a collaborative effort has dramatically improved results. the most effective response requires an orchestrated, systematic approach undertaken simultaneously rather in partial measures. a whole-ofsociety-approach applied on the global canvas characterizes the most effective response to a global pandemic; the combined efforts of society undertaking a multitude of effective actions undertaken harmoniously and simultaneously. q [ ] . no conflicts complexity science: the challenge of complexity in health care actor management in the development of health financing reform: health insurance in south africa collaborative governance in theory and practice world health organisation. who guidelines for pandemic preparedness and response in the nonhealth sector offline: covid- and the nhs-"a national scandal lessons from italy's response to coronavirus pandemic risk: how large are the expected losses? mass psychogenic illness in nationwide in-school vaccination for pandemic influenza a(h n ) , taiwan situation awareness in anesthesia: concept and research leading article: what can we do to improve individual and team situational awareness to benefit patient safety? department of health & social care. rapidly manufactured ventilator system specification media & sport and the rt hon oliver dowden cbe mp. industry and government joint statement on telecommunications support for the nhs toward a collaborative model of pandemic preparedness and response: taiwan's changing approach to pandemics from sars in to h n in : lessons learned from taiwan in preparation for the next pandemic world health organisation. who and unicef to partner on pandemic response through covid- solidarity response fund i would like to thank professor trisha greenhalgh, professor of primary care sciences, nuffield department of primary care health sciences for her insight, support and advice in primary care and public health for this paper. i would like to thank professor peter a brennan, consultant maxillofacial surgeon & honorary professor of surgery for his insight, support and advice in clinical human factors. key: cord- -x dcfjm authors: carlos, ruth c. title: defining the recovery date: - - journal: j am coll radiol doi: . /j.jacr. . . sha: doc_id: cord_uid: x dcfjm nan all human wisdom is contained in these two wordswait and hope. the pandemic introduced new phrases, collections of words, that have seeped into our unconscious and define this period. phrases like "flatten the curve," so pervasive that it has its own hashtag, or "shelter in place," which raises images of natural disasters. there are other words and phrases that personally define the pandemic. "hyperlocality," a neologism, emphasizes the unique coronavirus disease (covid- )-related experiences of each of the communities served by our radiology practices and health care institutions. in the state of michigan, the number of deaths in washtenaw county, including the city of ann arbor, is only % of that in neighboring wayne county, including detroit [ ] . intensity and duration of covid- care delivery and the impact on ability to resume elective services vary immensely with downstream consequences on institutional and practice losses, potential reduction in staff, and compensation reduction. although we seek to predict the future, models that project rates of service resumption make key assumptions that individual practices must validate for their own situation before implementing system responses. multiple institutions present their data showing the magnitude and time course for imaging reduction rates that reflect their institution capacity, their local rate of covid- infections, and state-level shelter-in-place regulations [ ] [ ] [ ] [ ] . although the shape of the curve is similar, hyperlocal variables introduce variability. one institution modeled service recovery informed by hyperlocal considerations [ ] . "time is elastic," as elastic as the waistband of my work-from-home pants. stretching out to the horizon without change where we cannot imagine a life after covid- , then snapping forward in our race to reopen. practices convert to a skeleton crew or a lombardy model with teams alternating by weeks to decrease the probability or consequence of an infection. working from home, normally a luxury, puts new demands on our time when coupled with new childcare and homeschooling duties and the need to protect those in our household who are most vulnerable. the situation highlights with uncomfortable clarity the persistent gendered expectations of home work, adding to the risk of burnout that each of us already has. prolonged or repeated exposure to insult can transform that burnout into posttraumatic stress disorder [ ] . some of us ask, what is our ethical obligation to care for the sick and at what point does the risk become too great [ ] ? "patient-centered care" assumed a more urgent meaning as we sought to keep patients away from health care facilities to reduce their risk. the acr provides guidance on safe resumption of routine care as we prepare to welcome patients back [ ] . an expert panel also provides recommendations on management of lung nodules during the pandemic [ , ] . however, as much as we have guidance from professional societies, we have to convince patients to trust in our ability to protect them before elective service volumes will normalize. new communication and scheduling mechanisms as well as restructuring the physical space in the waiting room will go a long way toward reassuring them [ , , ] . less frequently represented in the radiology literature is the impact of covid- on patients. what are the health consequences of delayed or foregone care? economic shocks to the system have left patients even more vulnerable to costs of care and other barriers such as patient trust in the system to protect them. although we can increase capacity, patients may continue to delay to seek imaging. "trust" and "transparency," recurring leadership themes in times of plenty, take a heightened importance in management during a time of great uncertainty. at all levels, we take on risks and make decisions under imperfect conditions in which one or more key variables governing the decision remain unknown or unknowable. leaders who communicate early and often and with great transparency reassure us [ ] . leaders who trust those who work for and with them engender a spirit of camaraderie even under sacrifice. this spirit of camaraderie relies on inclusion; particularly as the venues in which we convene have become virtual, nuance of interaction has become more difficult to detect and communicate [ , ] . as public discourse becomes tenser, how do we maintain the trust in each other to constructively address fraught situations, such as a casual comment about the "asian virus," or engage as allies to diffuse tension? we are relearning methods of communication as technological modes promote depersonalization of others. "rapid" as an adjective as become a benchmark for the adequacy of collective response to the pandemic, with rapid response tests, rapid issuing of shelter-in-place regulations, and rapid reopening of shuttered businesses. much work on covid- has been shared through preprint servers, nonpeer-reviewed hosting services that allow for public comment and vetting of emerging data. the desire to introduce and share research through these services and the apparent success at least with regard to covid- -related data call into question the relevance of the scholarly publication that navigates a sometimes prolonged peer-review process. the jacr has responded quickly to the need for rapid review and dissemination of covid- -related information to help practices manage the acute phase of the pandemic and signpost the coming recovery by using an existing expedited peer-review process for high-impact manuscripts and fast-tracked online publication of preproofs. our time-to-online publication for these manuscripts averaged to days with a capability to publish preproofs online within days of acceptance. at least for the content within our mission, our efforts have resulted in faster data and knowledge dissemination in a rapidly evolving situation. necessarily, these materials appear in print up to months after online publication, because of the publishing production process. information on the acute stage of the pandemic become out of date between online and print publication. what then is the purpose of the print journal? a historical document for posterity? a device for institutional and practice reflection after the normalization? a need for those who rely on print to make science seem "real" or more tangible than onlineonly publication? the move to online-only journal publication has not gained much traction among established imaging journals, although many more discussions have taken place because of climate change. it is unclear if concern over print as a vector for covid- infection will accelerate this change. we wait to see if our prognostications about the recovery are useful. we hope that patient trust in the system overcomes fear so that we can atleast mitigate the inevitable crisis of undiagnosed illness such as stage shift in breast cancer from delayed screening or surveillance and deaths from acute conditions such as heart attacks or strokes. regardless of the v-, l-, w-or any other letter that one thinks is the shape of economic and practice recovery, we will be digesting the consequences of the pandemic for years to come. variables influencing radiology volume recovery during the next phase of the coronavirus disease (covid- ) pandemic impact of the coronavirus disease (covid- ) pandemic on imaging case volumes changes in interventional radiology practice in a tertiary academic center in the-united states during the coronavirus disease (covid- ) pandemic radiology department preparedness in the coronavirus disease (covid- ) post-shutdown environment burnout and posttraumatic stress disorder in the coronavirus disease (covid- ) pandemic: intersection, impact and interventions pandemic: radiologists' ethical and professional responsibilities acr statement on safe resumption of routine radiology care during the coronavirus disease (covid- ) pandemic management of lung nodules and lung cancer screening during the covid- pandemic: chest expert panel report off-site radiology workflow changes due to the coronavirus disease (covid- ) pandemic rescheduling non-urgent care in radiology: implementation during the coronavirus disease- (covid- ) pandemic transparency and trust during the coronavirus disease (covid- ) pandemic together/apart during coronavirus disease (covid- ): inclusion in the time of social distancing coronavirus disease (covid- ), videoconferencing and gender dr carlos is editor-in-chief of jacr and receives salary support key: cord- -ywb krdp authors: barr, margo; raphael, beverley; taylor, melanie; stevens, garry; jorm, louisa; giffin, michael; lujic, sanja title: pandemic influenza in australia: using telephone surveys to measure perceptions of threat and willingness to comply date: - - journal: bmc infect dis doi: . / - - - sha: doc_id: cord_uid: ywb krdp background: baseline data is necessary for monitoring how a population perceives the threat of pandemic influenza, and perceives how it would behave in the event of pandemic influenza. our aim was to develop a module of questions for use in telephone health surveys on perceptions of threat of pandemic influenza, and on preparedness to comply with specific public health behaviours in the event of pandemic influenza. methods: a module of questions was developed and field tested on adults using the new south wales department of health's in-house computer assisted telephone interviewing (cati) facility. the questions were then modified and re field tested on adults. the module was then incorporated into the new south wales population health survey in the first quarter of . a representative sample of , adults completed the module. their responses were weighted against the state population. results: the reliability of the questions was acceptable with kappa ranging between . and . . overall . % of the state population thought pandemic influenza was very or extremely likely to occur; . % were very or extremely concerned that they or their family would be affected by pandemic influenza if it occurred; and . % had made some level of change to the way they live their life because of the possibility of pandemic influenza. in the event of pandemic influenza, the majority of the population were willing to: be vaccinated ( . %), be isolated ( . %), and wear a face mask ( . %). people with higher levels of threat perception are significantly more likely to be willing to comply with specific public health behaviours. conclusion: while only . % of the state population thought pandemic influenza was very or extremely likely to occur, a significantly higher proportion were concerned for self and family should a pandemic actually occur. the baseline data collected in this survey will be useful for monitoring changes over time in the population's perceptions of threat, and preparedness to comply with specific public health behaviours. if an outbreak of pandemic influenza should occur, it is essential that public health authorities are prepared to act. while resources have been prepared to educate the population about the nature of a threat and planned government actions, [ ] it is necessary to understand the potential response of a population. most of the existing information about a population's response to the threat of pandemics comes from research on outbreaks of the sars coronavirus, most notably in hong kong, singapore, and canada, [ ] [ ] [ ] [ ] and on studies of risk perception and anticipated behaviours in a potential pandemic in humans from the avian influenza virus (especially the h n subtype). [ ] [ ] [ ] [ ] to date, australia has been relatively unaffected by sars or h n ; however, some of australia's neighbours have experienced limited outbreaks: for example, sars in hong kong and singapore; and h n in indonesia and hong kong and china. globally, the threat of a pandemic of h n is high. a key component of a population's response is the perception of risk or threat. research shows that in a sars outbreak willingness to comply with risk-reducing behaviours is linked to the perceived immediacy and seriousness of the threat. [ , , ] three risk perception studies on potential avian influenza outbreaks were conducted in . in the first study, lau et al. surveyed residents of hong kong on a potential outbreak of h n . [ ] their study focussed on protective behaviours and likely compliance with them; however, the researchers also asked respondents about the perceived threat of h n and the likelihood of it occurring within the next months. it was found that % of respondents felt the chance of an outbreak was high or very high. lau's study also asked respondents how worried they would be about oneself or a family member contracting the virus in the event of a local outbreak; % said they would be very worried. in the second study, de zwart et al. compared the risk perceptions of european and asian respondents to the threat of avian influenza, [ ] and measured self-efficacy beliefs to assess the likely compliance with protective health measures. overall the study found that % of respondents thought they were likely or very likely to become infected should an outbreak of avian influenza occur. this figure varied from % (denmark and singapore) to % (poland and spain). the researchers took a composite measure of risk perception and found that higher scores were observed in europe rather than asia. they found higher risk perceptions in females and older respondents; while lower self-efficacy beliefs in europe suggested that adherence to protective measures would be lower in europe. in the third study, di giuseppe et al. surveyed the knowledge and attitudes of an italian population to avian influenza. [ ] they found that around % of respondents had a high risk perception and felt very much at risk of contracting avian influenza. in this study lower socioeconomic status and lower education levels were associated with higher risk perception, and those with a higher risk perception were more likely to comply with hygiene practices to avoid the spread of disease. our aim was to develop a module of questions for use in telephone health surveys on perceptions of threat of pandemic influenza, and on preparedness to comply with specific public health behaviours in the event of pandemic influenza. [ ] [ ] [ ] as such, our literature search identified no relevant studies on response to pandemic influenza specifically, although other studies have been published on general threat perception and compliance with protective behaviours in the context of infectious diseases or other emergencies. the primary reference was a study by canadian researchers on anticipated public response to terrorism. [ ] questions on the threat likelihood, effect on family, and behavioural compliance, were adapted with permission by subject matter experts and survey methodologists. each proposed question was considered for clarity, ease of administration, and possible biases. a set of questions was developed for field-testing (table ) , as well as an additional open question: "do you have any comments you would like to make on any of the questions or any other issues?" the pandemic influenza questions were field tested for test-retest reliability using the protocol of the new south wales health survey program. [ ] the questions were then modified based on the results from the field testing and were re field tested. for both field tests the target sample was persons living in the state aged years and over stratified by geographical region. this sample size ensures that a kappa of . (good or excellent) is able to be detected at a significance level of % and a power of % when compared to a kappa of . or less (fair or poor) for response frequencies greater than %. [ ] additional context added before question to provide better context. likelihood of being affected was changed to concern about being affected, to tap a sense of vulnerability rather than probability. responses altered to reflect concern and increase to options. households were contacted using random digit dialling. one person aged years and over from each household was randomly selected for field testing. trained interviewers conducted the interviews. up to calls were made to establish initial contact with a household, and at least calls were made to contact a selected respondent. when the respondent completed the first field test, an appointment was made for a retest at least a week later but within weeks of the initial field test. if a respondent was unable to be contacted during this week window they were deemed to be unavailable and their initial field test was deleted. [ ] test-retest reliability and validity were estimated by cohen's kappa statistic for binary variables, and weighted kappa with cicchetti-allison weights for ordinal variables. unbalanced tables were corrected using the method described by crewson. [ ] since erroneously low values of kappa can arise from skewed data, per cent agreement was also presented for categorical variables, calculated as the proportion of respondents in the same category at test and retest. responses for don't know and refused are also reviewed. [ ] data manipulation and analysis were conducted using sas version . . [ ] the survey the new south wales population health survey is a continuous telephone survey of the health of the state population using the in-house cati facility of the new south wales department of health. [ ] only residential phone numbers were used in the sample, as residential phone coverage in australia still remains high, [ ] and results from persons who only have mobile phones has been shown to be comparable in the united states. [ , ] the pandemic influenza module was administered as part of the survey between january and march . the pandemic influenza questions were submitted to a lead ethics committee for approval prior to use. the survey also includes other modules on health behaviours, health status (including psychological distress, using the kessler k measure, and self-rated health status), and access to health services, as well as the demographics of respondents and households. the target population for the survey is all state residents living in households with private telephones. up to calls were made to establish initial contact with a household, and calls were made in order to contact a selected respondent. response categories were dichotomised into indicators of interest and don't knows and refused were removed. for the hypothetical questions -that is, likelihood of pandemic influenza, likelihood that family or self affected, willingness to comply with vaccination, isolation or wearing a face mask -the responses of extremely likely and very likely were combined into the indicator of interest. for the non-hypothetical question "changed way live because of the possibility of an influenza pandemic" responses a little, moderately, very much and extremely were combined into the indicator of interest: that is, changed life. the survey data were weighted to adjust for probability of selection and for differing non-response rates among males and females and different age groups. [ ] data were manipulated and analysed using sas version . . [ ] the surveyfreq procedure in sas was used to analyse the data and calculate point estimates and per cent confidence intervals for the prevalence estimates. for pairwise comparisons of subgroup estimates, the p-value for a two-tailed test was calculated using the normal distribution probability function probnorm in sas, assuming approximate normal distribution of each individual subgroup estimates with the estimated standard errors, and approximate normal distribution for the estimated difference. in total, residents aged years and over completed the first field test and residents completed the second field test. estimates of test-retest reliability for the first and second field tests are shown in second field test. kappa values for the indicators derived from the questions ranged between . and . in the second field test. there were low don't know response rates ( - . %) and no respondent refused to answer any question. in response to the open question "do you have any comments you would like to make on any of the questions or any other issues?": % made positive comments about the questions, . % found the question wording easy to understand and answer, and . % found the subject matter relevant and interesting. of the respondents who had difficulty answering the questions, the main issues were: the questions were too vague ( . %), response options were not descriptive enough ( . %), or the topic area was difficult ( . %). table shows the responses to each question, including don't know and refused. the percentage of don't know or refused responses was low. table shows the indicators for pandemic influenza likely, concern for self and family, and changed life by sex, age group, demographic characteristics, and the indicators of level of psychological distress and general self-rated health status. overall . % of the population thought pandemic influenza was very or extremely likely, . % were very or extremely concerned that they or their family would be affected by pandemic influenza, and . % had made some (small to extreme) level of change to the way they live their life because of the possibility of pandemic influenza. when the indicators for pandemic influenza likelihood, concern for self and family and changed life were combined, as shown in figure , the greatest proportion of the population ( . %) thought pandemic influenza was unlikely to occur, would not be concerned for themselves or their family, and had not changed the way they lived their life because of the possibility of pandemic influenza. a quarter of the population ( . %) thought pandemic influenza was unlikely to occur and had not made any changes to their lives, but would be concerned for themselves and their family in the event of pandemic influenza. table also shows the combined indicators pandemic influenza likely and concern for self and family as well as pandemic influenza likely and concern for self and family and changed life by sex, age group, demographic characteristics, and the indicators of level of psychological distress and general self-rated health status. table shows the indicators willing to receive vaccination, isolate themselves, or wear a face mask by sex, age group, demographic characteristics, and the indicators of level of psychological distress and general self-rated health status. overall, the majority of the population would be willing to receive vaccination ( . %), willing to be isolated ( . %), and willing to wear a mask ( . %), if pandemic influenza were to occur. when the indicators for willing to receive vaccination, isolate themselves, and wear a face mask were combined, as shown in figure , . % reported being willing to receive vaccination, isolate themselves, and wear a face mask if pandemic influenza were to occur; . % would not be willing to receive vaccination, isolate themselves and wear a face mask; . % would be willing to receive vaccination, isolate themselves but not wear a face mask; and . % would be willing to receive vaccination and wear a face mask but not isolate themselves. table also shows the combined indicator for willing to receive vaccination, isolate themselves, and wear a face mask by sex, age group, demographic characteristics, and the indicators of level of psychological distress and general self-rated health status. table shows the indicators for willing to receive vaccination, isolate themselves, or wear a face mask as well as complying with all the specific public health behaviours: that is, willing to receive vaccination, isolate themselves, and wear a face in people who think a pandemic influenza is very or extremely likely, and who are also very or extremely concerned for themselves and their family. this study shows it is possible to construct a small set of questions about threat perception for a general population, which can be used for health surveillance. field testing identifies improvements that can be made to the questions and the response structure, and highlights the population's interest in surveys of this nature. kappa values for the indicators ranged from . - . , which is acceptable for hypothetical questions. the items had low don't know response rates ( - . %); no respondents refused to answer any of the questions; and the majority of respondents made positive comments about the questions. those reporting the highest levels of threat perception are older people, those with fair or poor self-rated health status, no formal qualifications, low household incomes, and those living in rural areas. perhaps surprisingly, there were no differences noted between the perceptions of men and women, or between those persons with or without children. overall, the majority of the population has taken no action, at this point, to change the way they live their life because of the possibility of pandemic influenza. the only two subgroups reporting moderate changes are those born overseas and those who speak a language other than english in the home. although direct comparisons with other studies are difficult to make, these findings suggest that the threat perceptions of the new south wales population are similar to those reported by residents of hong kong, even though australia has not been exposed directly to sars or h n . willingness to comply with specific public health behaviours is generally high ( - %), with willingness to be vaccinated greater than being willing to be isolated, which in turn is greater than being willing to wear a face mask. there is clearly a lower level of willingness to comply with wearing a face mask, especially in younger people, those living in urban areas, and those who speak a language other than english in the home. current findings on compliance with protective behaviours are comparable with findings from studies con- ducted in hong kong in relation to anticipated sars and h n . [ , ] a study about sars in hong kong indicates that those with higher risk perception and moderate levels of anxiety were more likely to take comprehensive precautionary measures against infection, and younger less educated males were least likely to adopt preventative measures. [ ] our data suggest that younger people are less likely to comply with protective behaviours, while a higher level of formal education (a university degree or equivalent) is associated with higher willingness to comply with all protective behaviours, but especially wearing a face mask. a study of this nature has a number of limitations. first, people are being asked about a hypothetical event of which they have no experience. however, comparisons [ ] and reported mask wearing rising from % in the early stages to % in the later stages of the outbreak. clearly data in that study support the increased likelihood of protective behaviours being adopted with increased risk perception; and, in our study, those with higher levels of threat perception were significantly more likely to be willing to comply with specific public health behaviours. prevalence estimates and % confidence intervals for response combinations to the three questions on health protection behaviours for pandemic influenza willing to be vaccinated, isolated, and wear a face mask willing to be vaccinated and isolated, but not willing to wear a face mask willing to be vaccinated and wear a face mask, but not willing to be isolated willing to be vaccinated, but not willing to be isolated or wear a face mask willing to be isolated and to wear a face mask, but not willing to be vaccinated willing to be isolated, but not willing to be vaccinated or to wear a face mask willing to wear a face mask, but not wiling to be vaccinated or isolated not willing to be vaccinated, isolated, or wear a face mask % our data indicate that while most respondents are very or extremely willing to perform a behaviour; the remaining respondents are expressing varying, but lower, degrees of willingness to perform these behaviours, with - % indicating they would be moderately or a little willing, and - % indicating they would be not at all willing to perform these behaviours. however, evidence such as data indicating very high levels of compliance with quarantine and minimal requirement for enforceable quarantine orders during sars in canada suggests that, in the event of a serious and immediate threat, the majority of those who are indecisive would shift their position and comply. [ ] it is likely, however, that even with such a compliance 'shift' the relative compliance of sub groups within the population noted in our study will be upheld; as these patterns of compliance have been supported consistently by studies of actual protective behaviours. [ , ] this study of the response of the new south wales population to the threat of pandemic influenza is part of a broader study of perceptions and behaviours around adverse events, including terrorism and global warming. as post-disaster studies generally report a lack of baseline data as a major handicap to understanding the trajectory for psychosocial recovery, [ , ] our study takes the first steps in establishing baseline for data vital for emergency planning, against which impact and recovery can be monitored. australian health management plan for pandemic influenza canberra: australian government department of health and ageing infectious disease and risk: lessons from sars london: the nuffield trust the impact of community psychological responses on outbreak control for severe acute respiratory syndrome in hong kong monitoring community psychological responses to the sars epidemic in hong kong: from day to day risk perception and compliance with quarantine during the sars outbreak avian influenza risk perception: hong kong anticipated and current preventative behaviours in response to an anticipated human-to-human h n epidemic in hong kong chinese general population notes: level of statistical significance: * p < ‡ population level frequencies do not agree with table as don't know/ refused responses were excluded from this analysis. § for pairwise comparison testing in subgroups with more than two categories comparisons are made between each subgroup prevalence and the overall population prevalence. ψ psychological distress was measured using the k . values range from - , with 'high' psychological distress considered as being ≥ avian influenza risk perception a survey of knowledge, attitudes and practices towards avian influenza in an adult population of italy national public survey of perceived cbrn terrorism threat and preparedness. in university of ottawa in partnership with health canada and the canadian food inspection agency ottawa: institute of population health nsw population health survey: description of methods australian bureau of statistics: population survey monitor. catalogue no. . canberra: abs estimation issues in dual frame sample of cell and landline numbers surveying households on cell phones: results and lessons. paper presented at the annual conference of the american association for public opinion research nsw population health survey: review of weighting procedures australian bureau of statistics: census of population and housing effects of fear and anger on perceived risks of terrorism: a national field experiment comparison of post-disaster psychiatric disorders after terrorist bombings in nairobi and oklahoma city public health measures to control the spread of the severe acute respiratory syndrome during the outbreak in toronto this study was funded by emergency management australia and the new south wales department of health. the following staff of the centre for epidemiology and research, new south wales department of health, assisted with the study: matthew gorringe, question development and data collection; raymond ferguson, sas programming and infrastructure; frances garden, comparing weighted survey data against census data. the authors declare that they have no competing interests. the authors contributed equally to this work.publish with bio med central and every scientist can read your work free of charge the pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/ - / / /pre pub key: cord- - ocsf authors: amorin‐woods, deisy; fraenkel, peter; mosconi, andrea; nisse, martine; munoz, susana title: family therapy and covid‐ : international reflections during the pandemic from systemic therapists across the globe date: - - journal: aust n z j fam ther doi: . /anzf. sha: doc_id: cord_uid: ocsf the covid‐ pandemic has convulsed human communities across the globe like no previous event in history. family therapists, paradoxically, given the core of their work is with systems, are also experiencing upheaval in professional and personal lives, trying to work amidst a society in chaos. this paper offers a collection of reflections by systemic and family therapists from diverse cultures and contexts penned in the midst of the pandemic. the main intention in distilling these narratives is to preserve the ‘cultural diversity’ and ‘ecological position’ of the contributors, guided by phenomenology, cultural ecology, and systemic worldviews of ‘experiencing.’ the second intention is to ‘unite’ promoting solidarity in this isolating situation by bringing each story together, creating its own metaphor of a family: united, connected, stronger. as a cross‐cultural family practitioner, with a strong mission for collaboration, the lead author acknowledges the importance of context – the nation and location of the experience; culture – the manner in which culture impacts on experience; collaboration – enhancing partnership, enriching knowledge, and mapping the journey’s direction; and connectedness – combating isolation while enhancing unity. since the key transmission of culture is through language, raw reflections were sought initially in the practitioners’ own language, which were translated for an english‐speaking readership. these narratives are honest and rich descriptions of the authors’ lived experiences, diverse and distinctive. the contributors trust colleagues will find these reflections helpful, validating and acknowledging the challenges of this unique period in history. deisy amorin-woods this compilation of reflections, while not a research project per se, is written in an auto-ethnographic style (ellis & bochner, ; rhodes, ) by five systemic therapists from varied cultures and contexts about the covid- pandemic. their narratives, experiences, perceptions, ponderings, and feelings were composed as they were living the experience; unique in their meaning making and in the way they contribute to this collection. as the lead author, i live and practice in perth, australia. reflecting my international and collective soul, my curiosity has given me the impetus to facilitate global exchange and initiate cross-cultural conversations. peter fraenkel, in new york, united states, incorporates his buddhist insight and psycho-musical intervention to provide a message of connection and hope to help others preserve a capacity for joy. andrea mosconi, from padua, italy, provides students and colleagues with a gentle message of wisdom, and insights to stimulate critical thinking and opportunities for new ways forward. martine nisse, from paris, france, delivers a 'mood note' which introduces a sense of 'lightness' in the midst of her complex and challenging work with domestic violence and incest. susana munoz from santiago, chile, with a background as a midwife, uses the metaphor of labour and birth to demonstrate survival. this 'pandemic project' initially arose mid-march as i reached out to colleagues abroad to check how they were navigating through the pandemic chaos. through our 'cross-cultural' conversations, the sense of feeling understood through shared experience and empathic means led to strengthened connection. this gave me the impetus to ask myself: wouldn't it be helpful if we could write something together to find some healing, whilst sharing our stories with others, in order for them to also find healing? i realised this was a global crisis; a collective narrative unfolding daily which has left no one untouched, and we as family therapists had important and individual stories to tell. time was of the essence, the view from this window was unique and so i drafted a brief. given my strong interest in collaboration and collaborative practice, over the years i had fostered relationships and developed partnerships including with family therapists abroad (amorin-woods, ). thus, i reached out to this wide network of colleagues and invited them to join me in telling our stories. most i invited responded enthusiastically to this initiative almost immediately. regrettably, due to the tight deadline, a few were understandably overwhelmed with other priorities. as a cross-cultural family therapist, my mission is to be diverse and inclusive when meeting the varied cultural needs of my clients, developing programs, delivering services, and working with families. this project was no different. as i heard the international collective voices it was thus vital to me that contributions were garnered from a cross-section of nations and continents as i wanted to honour different cultural backgrounds and language representation. i believed that by tackling phase sharing our experiences, we could capture each of our cultural and ecological worldviews and thus unite in this process. then, we could contemplate stepping into phase regenerative process in order to rebuild our own lives post-pandemic. after we are given the space to process the raw and organic heaviness of our own experience, we are able to support our clients to come up with practical responses, but not before. it was critical to put the stories together before the 'immediacy' of the raw accounts was lost. we are in the midst of the experience, in 'situ,' in confinement, confused, hypervigilant. we live in a world where we seem to 'rush' to come up with labels, treatments, and solutions to human distress, often bypassing our lived experience of suffering, loss, and isolation. i felt as if these early collections merged into one, represent the 'holding, healing space' that we as therapists need, before we dare consider what life may look like on the 'other side.' without this, how could we support our clients in putting themselves, their families, and their lives back together, in even contemplating what a world of 'functionality' or 'normality' may look like? while family therapists are aware of the importance of 'unmasking' to remain authentic to our clients and to self-disclose to deepen connection and trust, therapists do not often have the chance to share their accounts as they too travel through challenging life experiences. these reflections provide that opportunity. finally, any conversation about culture must include the element of language. since the key transmission of culture is through language, organic reflections were sought in the practitioner's primary language. as in therapy, authenticity of feelings and vulnerability cannot be truly transmitted except in the primary language (amorin-woods, ). however, since the main demographic of this journal speak english as their primary language, these reflections are translated and offered in english. i am deeply appreciative to each contributor for responding as i reached out. from the bottom of my heart, thank you andrea, peter, martine, and susana. deisy amorin-woods, perth, australia this pandemic is a collective trauma event and its multi-faceted impact cannot be underestimated. this leads us to first acknowledge and respect the interconnectedness and relationship between systems, within our body, between us and our environment, and between one another. this also causes us to question the notion of permanence versus impermanence and certainty versus uncertainty. as a cross-cultural family and systemic therapist, i have developed a thirst for collaboration within programs, across organisations, within communities, and across the globe (lee, thompson, & amorin-woods, ). as a migrant to australia from peru, i have always felt drawn to the idea of collectivism (amorin-woods, ), a sense of 'being together' and of 'joining with the other,' and that notion has never left me. whether working in government, non-government organisations (ngos), in private practice, or in academia, i have ensured i bring my 'collective soul' into my profession in the way i practice and in my teaching. i try to connect with the issues that impact on the lives of our families regardless of where they are located or where they originate (amorin-woods, a , b . the issues are varied and the systems diverse, whether a couple facing grief, families with intergenerational trauma, or refugees who have fled persecution. when the news broke in early about a possible epidemic, i had not conceptualised either the extent or the utter devastation that was to follow. i was due to travel to basel, switzerland in early march to present at the world congress of family global family therapists reflect on covid- ª australian association of family therapy therapy under the international family therapy association (ifta). ironically, my presentation was titled, therapeutic conversations and trauma informed systemic practice: acknowledging meaning making in the backdrop of relentless fear and unpredictability. two days before my departure, the conference was cancelled due to the pandemic, which was rapidly spreading around the globe. in the weeks that followed, the whole world convulsed through a rapid period of change. the need to find refuge from this potent, yet invisible, force left us vulnerable, confused, distressed, fearful, and ambivalent. in my own space, due to the need to isolate, and the closure of state borders, i have not been able to see my daughters or embrace my little 'grandies.' this has left me profoundly sad and nostalgic. having family, friends, and colleagues around the world, many located in the countries worst hit, i was driven to connect, to check-in on how they were navigating through the crisis. i heard directly their accounts of anguish, dread, panic, powerlessness, loss, and grief. this virus was burning, just like the recent ignition of highly combustible dry eucalyptus trees in the australian bush, spreading rapidly like a wildfire, loud and forceful, the echoed thoughts keeping alive the nagging fear. people wondering, will i be next? will i be a carrier and infect my loved ones? families losing parents, grandparents . . . a whole generation seemingly vanishing as in a puff of smoke. listening to these raw and distressing stories became rather confronting. i found myself holding their collective pain in my arms and with a virtual embrace. i was attempting to ease their suffering. personally, these stories transported me back to a similar experience as a child living in peru. this was a time of 'sendero luminoso' (shining path) a guerrilla group, along with 'sinchis' an anti-subversive 'police sub-group,' both of whom were responsible for committing human rights violations, terrorising and decimating over , people, most of whom were indigenous. this led to cases of intergenerational trauma, the stories of fear, sorrow, and confusion passed down as through the 'mother's breast milk' for generations. these painful memories accumulate in one's body becoming a historical site which is transported through time (rueda, ) . i remember my mother distraught as the situation evolved given my sibling was studying at the university at the epicentre. while not directly impacted by the war and the trauma, i felt them indirectly, yet latently, through the suffering of my mother and the stories told by my sibling who witnessed young students being murdered. this brings me back to the present time and leaves me concerned wondering whether we will see stories of pain and sorrow passed down as a result of the covid- war? will this generation transmit trauma to those to follow? professionally, as the epidemic evolved, so did the need to transition my practice from face-to-face to purely tele-health. while australia has been fortunate not having been impacted as heavily as other countries, i have observed among my clients signs of anxiety and hypervigilance related to the fear of transmission, as well as new manifestations of suicidal ideation previously absent. these signs are connected to a number of issues: the stress related to job loss and financial uncertainty; the sadness and loneliness linked to the inability to see family and friends; grandparents' sorrow not seeing their grandchildren, an embrace appearing so distant. children unsettled, mothers feeling stressed and exhausted juggling extra roles, including home-schooling. while some people see isolation ('iso') as simply confinement, others see it as imprisonment, fearing the threat of imminent danger if leaving their safe and familiar bubble. for others the uncertainty, the not knowing, the unpredictable re-organisation of families and communities, is too much to bear and leads to heightened levels of suicidal ideation. people ask themselves: will there be an end to this? are we facing the end of the world? there is documented concern for heightened risk of suicide among communities continuing past the pandemic (gunnell et al., ) . further to this, given my extensive experience working with people with acute mental health issues and with complex trauma, i am aware that people who have experienced trauma are highly impacted by threats about the safety and stability of the world (brown, ; james & mackinnon, ) . i have also observed how vulnerable families (such as families with intergenerational trauma and child abuse survivors) are particularly at high risk, and consequently presenting with clear signs of re-traumatisation. throughout this pandemic transition, i have noticed various community stances rapidly forming. one that blames, with xenophobic undertones, pointing to race and culture as the original cause of the virus, discriminating against certain cultural groups. another that labels, describing people as 'paranoid' or 'hysterical' as people frantically accumulate food supplies or simply voluntarily decide to self-isolate. a third, with traces of denial and avoidance about the existence or magnitude of the situation, that judges and ridicules those taking a more conservative approach. within this stance, there is an underlying expectation and pressure from strangers or loved ones to 'move on' rapidly through the stages of grief (kubler-ross & kessler, ) from shock and denial to acceptance, without recognition that people need to be allowed to 'feel their feelings.' on the other hand, i have also seen demonstrations of kindness, generosity, and solidarity for fellow community members, much of which has been led by children. teddies perched in trees, messages of encouragement and hope written around neighbourhoods to lighten the tone and brighten people's days. boxes of fresh produce or non-perishables left to help others financially disadvantaged. i have observed some people viewing this pandemic as an opportunity to start over and live in a healthier, humble, more acknowledging and respectful way towards self, towards family and their environment. i have seen occasions when cut-off families have re-connected, and couples considering separation have learned to appreciate and not take each other for granted. i have been mindful of being available for my clients, to provide the holding space to acknowledge and validate their feelings and allow them to process their experiences. the need for self-care and self-compassion takes on a new meaning in its recognition of our shared humanity. i thus ponder: are we able to provide clients with a holding space to process things if we are not connecting with ourselves? . . . even though we too are living amidst the chaos. we do not have to abnegate ourselves or our experiences and feelings to show we are capable practitioners, because when we abnegate ourselves we tell our clients to let go of parts of self in order to function, in order to accept themselves, in order to relate. we need to 'be,' before we can 'do.' remaining authentic is key in therapy. i often say to my students and supervisees, authenticity is to a therapist what breath is to life. we need to be authentic with the families who come to us with hope and trust and this includes possessing heightened awareness of ourselves, hence the need to uncover the 'self'. i recall a similar description often during my fellowship at the accademia di psicoterapia della famiglia in rome. andolfi would often make reference to ridding self of the mask and being fully self, fully human (andolfi, ) . it is only through such a process that we arrive to a place of recognition of what is ours and what is theirs. it is crucial that we are able to name and process our experiences in order to support our global family therapists reflect on covid- ª australian association of family therapy clients to do the same, in order to provide the holding space they need, and joining-in with them (minuchin, ) . this then allows us to welcome the rich exchange between each other in order to develop an empathic connection and trusting relationship with them (aponte, ) , because how can we join in with families and trust be elicited without this important element? this also helps not to transfer or project our experiences onto our clients (lum, ) . as systemic therapists we are in a privileged position as collaborators and partners influencing the family system and the environment and context where families are placed. this gives us the opportunity to awaken deeper knowledge and understanding within a given system, within the family who puts their trust in us. we become responsible in co-creating and co-constructing the therapeutic reality and in eliciting change (von foerster, ) . we influence the environment whether we bring empathy, healing, anxiety, or fear. understanding the self and understanding each other becomes the impetus for healing. around the globe, we are all living the experience of the covid- pandemic as a collective trauma. the chaos is real to us all. we are dealing with challenges that are comparable yet distinct. while we are all impacted, the impact is different depending on where we are located, in our culture, our ecological system, and the politics of our day. a frequently used expression suggests we are all in the same boat; however, i would like to use the metaphor, while we may be sailing the same storm, we are in different boats. how robust our ship is, and how we manoeuvre it, may determine how we survive the storm. in writing this i am mindful of families as they navigate through this pandemic. i am interested in supporting them to acknowledge their being 'human,' while rejecting reductionist ideas of 'experiencing' that rush them to numb or bypass their experience. instead, it is time to pause and connect with the basics, our relationships. the lesson from gregory bateson was the importance of the interconnectedness of living things to their natural environment (bateson, ) . this is so relevant to our current situation. we hear loudly the desire of communities to go back to 'normal' . . . however, do we really want to go back to the normal that we knew? or do we want to look at this as an opportunity for social change? for a change in direction? in the way we do things, in the way we relate to self, to other people, to other cultures, to our environment. instead let's nurture families and preserve relationships. let's propose a paradigm shift about the way we think of ourselves not as passive closed-off beings, but as active authors of our life, insightful, creative, purposeful, and connecting. let us use this time to co-create a space for healing and holding the human spirit. coping with covid- : a time to focus on the simple gifts of life peter fraenkel , new york, united states as news of the covid- pandemic quickly grew in march of this year, i immediately found myself re-immersed in the traumatic disorientation of september, . terrorist planes crashing into the world trade center launched new york city and the united states more generally, into what i termed 'the new normal' (fraenkel, b) . yet this is different: an invisible virus with an unpredictable course, unseen yet life threatening. where to go? what to do? the answers to those questions quickly were determined in march by the governor of new york with guidance from federal and state health experts: go home, work at home. on march, i delivered the last in-person workshop at the ackerman institute for the family. attendees spread out across the room as a safety precaution to decrease the likelihood of communicating the virus among us. none of the usual handshakes between newlymet colleagues, none of the usual hugs between old friends, my former students, and professional acquaintances. we carried on, focusing on effective techniques in couple therapy. but we all had a nagging sense, mostly at the periphery of our consciousness, that the world outside was growing increasingly fearsome, and that we were better off in here, held by the warm embrace of what mary pipher has called the 'shelter of each other.' as i wrote in another article after / , we therapists were fortunate to be helped by the act of helping othersto belong to a community of care (fraenkel, ) . i've specialised for many years in work with families traumatised by incest, domestic violence, and homelessness. in my private practice, i've specialised in what i've called 'last chance couples'those who've often seen one or more couple therapists, without much improvement, and who are now on the brink of divorce or its nonmarried equivalent of relationship dissolution (fraenkel, ) . these two areas of my work now overlap: distressed, disengaged partners already strongly considering separating, or already living apart, now stuck together with kids and sometimes their elders and even other families. precipitous layoffs and loss of income, infection with the virus, and in some cases, the known death of relatives, friends, or colleagues, have led to the kind of traumatic effects of living through a tsunami, gathering force every day with no end in sight. at the same time, accurate information, guidance, and leadership from the federal government is sorely lacking, alarming in its own wayno comfort there. my clients are experiencing all the usual symptoms of psychological trauma: intrusive thoughts and nightmares, edginess and hypervigilance, sleeplessness, anxiety, and depression, as well as relational trauma and ruptures between couple partners, and among family members. the factor most clearly correlated with resilience in the face of trauma and other disruptive experiencessocial supportis in short supply, despite inventive use of social media and online meetings, including teletherapy. i have occasionally ventured into a nearby park with my percussion instruments to record myself playing along with inspiring songs about social justice and love, posting these videos on facebook and instagram. the response has been overwhelmingly one of gratitude and unexpected pleasure, and those responses have gratefully been received by me, giving me a slight sense that through my 'out-of-the-box' psycho-musical 'intervention,' i've helped others preserve their energy, hope, and capacity for joy. but i then return to my apartment, to be alone once again, as my kids are now attending college in europe. we're in close touch, as i am with friends and colleagues, but i surely feel isolated; and when i occasionally venture out and on to the streets to shop or bank, there's the uneasy, unreal sense of being on another planet, or at least, a familiar but altered landscape, with fearful masked neighbours strolling six feet apart. coincidentally, just a few weeks prior to news about the coronavirus, i had started writing a book for the general public about lessons to be learned from taoism about love and other relationships (fraenkel & akambe, ) . as a long-time buddhist and taoist, i've practiced noticing the little, familiar things and accustomed events of life that can bring unexpected joy once brought into the gentle gaze of the 'now.' for decades, i've tried to live my life as if inside a haiku poem, taking pleasure just from being sensate, breathing, and alive. musing on the nature of existence, the creator of taoism, th-century b.c. court librarian, philosopher, and social critic lao tzu, writes in the first passage of his classic text, the way of life ( th century bc): existence is beyond the power of words to define terms may be used but are none of them absolute . . . if name be needed, wonder names them both from wonder into wonder existence opens i've been advising all my clientsindividuals, couples, and familiesto use this disorienting time to reflect upon the following taoist suggestions, to look for opportunities to experience wonder, just as i have as a fellow traveller through this time. specifically, i've suggested they: look for pleasure and joy in small, everyday experiences. i took a break from writing this article, went to the kitchen window in my fifth-floor apartment, and watched the rain falling upon the black-painted fire escape. it was beautiful. a few hours later, i took another break, and saw my two kittens, whom i adopted from a shelter in october, cuddled together in my furry chair, sleeping contentedly. it was beautiful. it calmed me down. slow down. our usual life pace in nyc is frenetic, our lives overstuffed with aspiration, achievement, a never-ending quest for riches, possessions, and when we've accumulated enough of those, the relentless search for new experiences (which i've termed 'experience greed'), for unique travel destinations and novel experiences to empty our constantly refilling 'bucket list.' lao tzu ( th century bc) writes: gravity is the root of grace, the mainstay of all speed . . . what lord of countless chariots would ride them in vain, would make himself fool of the realm, with pace beyond rein, speed beyond helm? it's a time to stop, and look closely at what and who we already have in our lives. it's a time to breathe, walk, eat, and talk slowly, compassionately, and patiently with loved onesthose living with us or those whom the virus has separated from us. and while slowed down, take a good long look at your partner, your child, your parent, your friend, your neighbour, your colleague (online, most likely!)listen to their voices, and enjoy their unique aliveness. in the timeless words of songwriter cole porter and a song made famous by frank sinatra ('i get a kick out of you'), let yourselves 'get a kick' out of them (fraenkel, a) . look at them like there's no tomorrow for them, or for you. let go of control. on a related note, we cannot definitively avoid illness, and we cannot insure through our hand-washing and social distancing and mask wearing that we will survive this pandemic, or at least, leave it unscathed health-wise, financially, or emotionally. nor can we avoid the suffering of learning that a family member, a neighbour, a student, a mentor, or a colleague is sick, or has died. radical humility is called for in this troubling, unpredictable time. take precautions, yes, but recognise that this virus is nature, and nature has its way of overcoming even the best-laid plans of mice and men. learn from persons who inhabit oppressed social locations. lao tzu ( th century bc) advocated wisdom over knowledge: leave off find learning! end the nuisance of saying yes to this and perhaps to that, what slightest use are they! if one man leads, another must follow, how silly that is and how false! communities that have experienced generations of oppression due to race, ethnicity, geographic region/country, culture, and economic status have much wisdom to share about surviving and even thriving under hardship, and about how to make do with few resources. one hysterically funny video that circulated around the internet early in the emergence of the coronavirus came from the philippines, in response to privileged westerners' panic about running out of toilet paper. it was a lively music video, with dancing women behind the male lead singer, demonstrating how to use a little colourful plastic pot called the 'tabo' to wash up after defecating. it's high time we erase the terms 'first world' and 'third world' and the power and knowledge hierarchy between the countries and cultures belonging to each politically constructed group. the world must come together to defeat this virus, and to survive, as a unified, mutually respectful people in harmony with the earth and nature itself. my mother mimi bialostolsky fraenkel, who died of cancer in just before / , believed the world might eventually come together in a time she called 'creative chaos.' i think of her now, and whether this worldwide pandemic is enough to unite us in a common effort to live on. i'd like to hope so . . . but i'm not sure. what we are going through is not an ordinary crisis, this is an epochal crisis! it seems to me that it is the most obvious consideration which echoes with many. the question then may be the systemic one: what do we do in each situation for every person who presents to us with a problem? as i often say, a kind of systemic mantra: perfection, what does this allow me to learn? it is now clear that this virus has three aspects that makes it scary: ) it is new and we cannot be immunised; ) it also passes through healthy carriers who, even if they have a lower viral load, are still capable of contagion and therefore cannot be easily controlled; and ) it is not a flu virus like most flu viruses. this virus directly attacks the lungs and therefore gives viral pneumonia; it also attacks many other global family therapists reflect on covid- ª australian association of family therapy systems in our body. from this point of view, respect for the required government measures is essential as the only defence, while there is no effective drug or vaccine. the alternative is to build herd immunity, through a selection of the species. only those with resistance will survive. on the level of interaction between this virus and the social system, the question is: how long will it last? if we take into account the date of government measures, the fact that the need to tighten up has often been felt, and also the fact that it is always difficult both to impose and to accept strict rules and that the incubation time is days, it is not difficult to hypothesise that the so-called 'peak' of the infections is still to be reached. from there, it takes time for the sick to heal and for additional time to pass before the virus is eliminated by the carriers. by putting all this together, i believe that we must accept that the current situation will last a long time. epidemiologists seem to be moving increasingly in this direction, obviously, barring unforeseen events for the better and for the worse. let's have patience! however, let us look wider, at the macrosystem where all this happens. if we take into consideration the relationship between us, 'homo sapiens,' and the natural system into which we are inserted, this story changes some rules of the relationship. it allows us to realise that we are not omnipotent, but that we are part of a system that can destroy us in a short time if we do not take into account the feedback that comes from the interaction with the other elements of the system itself. its 'liberation' is part of this process of inappropriate invasion by us 'sapiens' of natural contexts not coordinated with the human system. from this point of view, this virus is a warning, it is almost a homeostatic mechanism that is produced in a system that is already at the limit of its range of possible interactions and is reaching a possible 'bifurcation point' (prigogine, p. ) . this is a test of a general catastrophe, a global crisis. basically there are other 'covid' around which we do not want to be aware of and which can equally undermine our survival in a global way: global warming, pollution, deforestation, desertification, water consumption, economic imbalances within societies and between different parts of the world. just like the case of 'covid,' we pretend not to see them yet they advance in a hidden and creeping way until they explode. just like covid- ! the 'good' thing we can say about the virus is that, unlike wars which can be taken out on someone who is considered guilty, the same cannot happen as this virus does not discriminate; it is a common enemy of the whole system. the virus applies equally to everyone, just like in the family systems with which we want to work. just as the members of a family system at the end of a session should not be able to say who is right or who is wrong (selvini palazzoli, boscolo, cecchin, & prata, ) , so as humans we are driven to look at each other, to confront each other, to even try to understand and help those, who until yesterday, rejected each other. yes, there are those who, not understanding, continue to wave the flag of personal interest, or hunt the culprit, or act in their own defence, but for now they are exposed and forced to admit or to try to make amends. for now, solidarity prevails, and there is admiration for the commitment and generosity of those on the front line, a sense of being a community. and we see the increasingly clear signs that, where man takes a step back, the natural system of which we are part takes a breath, pollution decreases, and everything seems to show us what we must consider for development and the future. a great opportunity, don't you think? but several times i have said: for now . . . the real question is: will we be able to take this into account? this brings another consideration regarding the social system. in recent years, perhaps blinded by the race for well-being or perhaps because well-being itself had allowed many to take advantage of it incorrectly even in public structures, the focus has been rebalancing national budgets by destroying the network of structures that had functioned as the skeleton, blood, and neurological system of society by supporting and bringing food throughout the social system. i am talking about healthcare, public education, welfare . . . let's consider what it means not to have continued to be aware of the value of these 'elements' of the social system. i say this both for those who have dishonestly taken advantage of it from within and for those who, from their own ideology, have fought them. here, this crisis can help us rearrange the scale of values regarding what is most important to preserve in a social system, counterbalancing the excessive importance given to the production system, to take into due consideration what is at the basis of a possible safe and civil coexistence. even regarding the enormous development of the computer network that is becoming more and more the neuronal network of the planet: on the one hand it allows us to accelerate the feedback between parts of the system facilitating the possibility of co-building solutions; on the other hand tomorrow it will put us in the face of problems such as the enormous possibility of controlling, even more than now, individual lives and determining who and how to manage the enormous power that all this enters . . . and in whose hands? of course, it is always the two polarities of the life of a system that must be balanced: the competitive system and the collaborative one. the same goes for natural selection which is the survival of the fittest and the other towards the idea that the average good of the most is better than the maximum good of the few. but here the question is: will we remember it later? and what does all this say about our systems of daily interaction, to our closest systems? of course, stopping puts us in a position to change our position in the systems of which we are a part and the relationship rules change. we feel distant from those who were close to us, communicating virtually with those we used to touch, look in the face, caress, shake hands, pat on the shoulder, take by the arm. in contrast, we find ourselves living with those who we did not have close to us for so many hours or who we were even in conflict with, seeing him/her every day and maybe having to talk to each other. we can no longer take advantage of dissipative structures, as they are called, which diluted and differentiated, distributed the tensions of the systems: work, travel, school, various activities. maybe if we choose to use the avoidance mechanism that is so useful to delude ourselves that there is a balance in relationships? no, we can't back off now, we're in touch! and then? this is an opportunity to stop and listen to ourselves and others, try to look at them with different eyes, re-appreciate the small gestures, let things arise from building together and patiently look for solutions, not problems. so, in the infinite space we can perhaps rediscover the value of everyday life, of silence, of simple things, of doing together, of allowing our imagination to bring to mind an idea. sometimes it's simpler than it seems! and with our patients . . . 'clients?' here too our position changes. from time to time we may find ourselves inventing different ways of making ourselves feel close, exploring new and different tools for staying in relationship and offering help, believing that, beyond the tool used, the relationship is what matters. cecchin's words echo on us: we all need to feel seen, and to feel seen we are willing to invent all the colors! (cecchin, p. ) . and then of course: hypothesis, circularity, and neutrality! (selvini palazzoli et al., ) . so, our patients will feel us present, even if in a different way, and they will appreciate our sincere and attentive commitment. as milton erickson (erickson & rossi, , p. ) said: there are no difficult or incurable patients, there are only therapists who are able or unable to find a way to communicate with them. another thing comes to mind. let's see how a small virus, which affects the system at a specific point, achieves great effects. this can be a teaching for our therapy. the 'saltology' mentioned by the milan team in the first pages of paradox and counterparadox comes to mind: the results confirmed that, when it is possible to discover and change a fundamental rule of a system, pathological behavior can quickly disappear. this leads us to accept rabkin's proposed idea: that in nature events of radical importance can happen suddenly when a fundamental rule of a system is changed. rabkin proposes the term "saltology", that is saltology (from the latin saltus) for the discipline that should study these phenomena. this finds its correspondence in the general theory of systems whose theorists speak of "p.s." as of that point of the system on which the maximum number of essential functions converges to a system, changing when obtaining the maximum change with a minimum of energy expenditure. (selvini palazzoli, boscolo, cecchin, & prata, , p. ) so, these are my reflections these days which i wanted to share. all this 'allows us to learn' and perhaps finally arrive. it is an opportunity to become aware what this covid virus . . . offers us as systemic therapists. let's go ahead, let's build better times together! small mood note from a french family therapist in times of pandemic (petit billet d'humeur d'une th erapeute familiale franc ßaise en temps de pand emie) the family therapy sessions i conduct are very rarely by videoconference. when they are, they involve my patients who, for one reason or another, have gone abroad to settle temporarily or permanently. but since the arrival of the pandemic in france, one of my patients, herself a psychotherapist and familiar with consultations by videoconference, has pushed me towards this mode of therapy. two days after the announcement of the confinement, i was equipped, and i launched the invitations to my patients. after researching what angle of view for my webcam would symbolically give an open message about the future, i decided to turn my back to my patio, so that the view behind me would lead them towards the sun and the plants. the weather is extraordinarily nice, the pollution in paris has dropped dramatically, the sun is shining without any halo of pollution. birds are heckling in the city. i half draw two curtains, in the colour of my therapy room, which has been abandoned since the confinement, and adjust lights towards my face to gently counterbalance the brightness of the outside. it is, finally, a kind of 'chiaroscuro' (light/dark) that makes my first affected and surprised patients say, keep going . . . it reminds us of vermeer . . . the surprises are mutual, i arrive directly in their living room, or their office, even if they have passed through my 'virtual waiting room' of zoom. i note that some have asked their spouse to use their one-hour right of exit during the consultation to be quiet, others are gathered on the living room sofa, a cup of tea in hand with their pet. sometimes a decorative detail jumps out at me, so 'connected' with the patient's problem that i cannot avoid referring to it. one of these surprised patients says to me, do you want me to show you where i live? i pose and respond, no thanks. or . . . maybe . . . yes, you could ask all your patients to show you their home, you could learn a lot from that? . . . don't you think so? . . . mmm, no, i don't think so. holding the structure is one of the signatures of family therapy. most of my patients have been exposed to violence that has broken into their psyche (nisse, ; nisse & sabourin, ) . re-establishing boundaries or maintaining distance from others requires an ongoing effort. it requires constant therapeutic adjustment. i find that they are grateful for the availability of their therapist. i find that after the first few sessions, i feel as if i am regenerated. despite the shock of this epidemic, i have not forgotten anything about my way of being a therapist with each of them, nor their family history. my abilities as a therapist seem to be naturally at my disposal. the new and artificial proximity of the screen requires me to be attentive to maintain a therapeutic atmosphere (nisse, ) , in conformity with the pre-existing one: that is to say, intimate and respectful at the same time. i also note that since the beginning of the pandemic their psychological work seems to be more productive between sessions. some patients have refused videoconference sessions. they cannot imagine hearing themselves or me talking at home about the violence, especially sexual violence, for which they have consulted; they don't have housing where it's possible to really isolate themselves, or they are single women raising their children. sometimes, a patient who has not responded to the offer checks in with her therapist with a fear of illness. some of them tested positive for covid- . it is nothing too serious, but a great deal of fatigue and fear for the impact on others. i don't have a pre-established bilateral agreement for the therapeutic meeting by videoconferencethis bothers me a little, but i know my patients, i trust them. it will be possible to establish it afterwards for the next sessions. the french or european family therapy societies provide support, stimulate reflection on this subject, offer platforms for exchange with family therapists, or platforms for helping families stressed by covid- or affected by it and also affected by sudden bereavement. a large part of our patient population is made up of children who have been placed in care by the juvenile judges. they come from all over france, and half of the country is currently in the 'red zone,' which means that children are not allowed to go to school or to travel more than kilometres to go to court. as for each of the people living in this 'red zone,' sometimes, as i know from the supervisions i give by videoconference, a certain number of them paradoxically relax knowing they will not receive any more parental visits, mediated at the same time . . . recently, the status of social workers has changed. they are now considered during this time of pandemic as health professionals, and as such they have the right to travel to meet with children. the idea emerges to organise family network therapy sessions by videoconference before the end of the confinement. the centre des buttes-chaumont is again in demand. the conventions established with each of the participants in the network session and the therapeutic tandem usefully frame the new disturbing context for the most vulnerable among them, by calming the fears of abandonment, or on the contrary of dictatorial control through this means of communication. a spontaneous energy flow appears as the homage 'at the windows' is paid every evening at pm to the nursing staff. i too hit something, a shell casing from world war i (empty!)it reminds me of the spanish flu pandemicand as a drumstick, a saharan jewel offeredwell, well, well!by one of my former patients who went to the sahel to offer solidarity to women. it makes a rather high-pitched bell sound, somewhat close to the bells of the tibetan monks . . . everything blends into this positive energy. a neighbour who is ill with cancer is the most alert to beat the call of the neighbours . . . her care continues during this time. the calmness is conducive of reflection. what do i want to change in my life as a therapist? . . . nothing, other than taking more time for myself. sports, baking, tidying up, painting, talking . . . i miss my friends, but the family exchange is nicely intensifying. confinement slogans tirelessly spread their message, one week, two weeks, three weeks, we don't count the weeks anymore, time has changed value, the pace has slowed down. look, why don't i take the time to check my pension rights? no, i'd rather watch a good series . . . humanity in times of pandemic (humanidad en pandemia) therapists and patients living through times of pandemic have evolved in a context of threat and uncertainty. due to the regulations to avoid contagion, family members have been forced to stay in the same space for indefinite times. the personal and group impact of this dynamic unfolds in multiple dimensions and has an unsuspected scope. the experience of physical space has evolved as hours, days, weeks have passed. although at first it could be perceived as a break from the whirlwind of everyday life, the 'forced' stay has turned into a kind of narrowing of the limits; of the physical space, of the psychic/corporal world, relational, bonding. no matter how many people inhabit a place, the members resent the isolation and helplessness on many occasions. in some way, previous forms of relationship, ties and family, group, and social functioning have pointed out the dominant styles of behaviour in this type of closure (muñoz, ) . without external compensatory systems, which operate as sedatives of the sense and deniers of finitude, we observe how the first attachment style appears in a dynamic that goes through different levels depending on the global context and the verbal and non-verbal information that emerges from authority (bowlby, ) . groups with primarily disorganised attachments generate contexts where friction, punishment, and violence emerge quickly as a way to relieve anxiety, fear, and tension. when the primary attachments are associated with anxiety and ambivalence, the group is submerged in fear that spreads through networks infiltrating the psychocorporal world, facilitating extreme care behaviours alternated with reckless risk behaviours that increase fear and anxiety. systems with predominantly anxious-avoidant attachment tend to focus on demand and performance by amplifying effective control systems at the expense of body and emotions. these are subject to the dominance of reason, dissociating body and its messages controlling fear, anxietiy, and uncertainty. on the contrary, groups with predominantly secure attachments creatively and adaptively go through this turbulence at the pole of action, creating and recreating new realities and ways of living. then, the isolation gradually infiltrates the family system, so fear and emptiness take over the bonds, as a melody that silences with consumer products. therefore, an impossible gap associated with the absence of meaning and a deep fear of damage and death is attempted to be filled. so, time becomes a waiting time. simultaneously, we witness an institutional and organisational crisis with the ensuing collapse of credibility and trust. a massive disconnection of people who in this paralysis have lost their jobs confirms those premises about the hope and credibility violated, and although cognitively it is explainable emotionally and affectively, the experience is overwhelming. uncertainty, fear, and the experience of injustice increase in a context that is impossible to decode. on the other hand, teleworking has been a way of maintaining continuity of work and staying on the move. however, in many organisations, this system has forced workers to be permanently available online. for executive women workers, the demand has increased exponentially due to the exercise of multiple roles that overlap and require time, effort, and dedication. uncertainty in an emotional, relational, social, global context reduces security for people; groups, institutions, when faced with the threat, exacerbate control and defence mechanisms. they bring solutions that only increase the problem, generating fear and pain expressed in different ways. they deny mourning in the face of loss at all levels: stability, power, status, the lives of loved ones, and their own lives (sluzki, ) . and the body? often forgotten and uninhabited due to the predominance of the image, it becomes the repository of emotions that, given the context, are impossible to symbolise and integrate. raising these emotions to consciousness reminds us that we hurt ourselves in bonds and heal in them, so that it is possible to agree to feel enough fear for self-care and care for others. holding the bond of intimacy that the therapeutic space provides in this transit that emerges as a new context from the face-to-face to virtual, implies an opening to newness. in turn, group networks that met in transit rituals establishing contact, providing support, direction, and meaning when assisting life and death, have also been impacted and injured. however, the voice and face have enhanced as a contact image and company (sluzki, ) . the question of my being a therapist . . . being also a midwife refers me to processes and learning; my history and its multiple resonances weaved into a systemic psycho-dramatic tapestry that includes myself and humanity. i feel that we cross a threshold similar to labour, being delivered and giving birth, simultaneously, in a channel whose timelessness is felt in our bodies. we are leaving a womb that could no longer contain us. today by force of contractions, we remain at times with fear, compressed by narrow walls that adhere to the personal, group, social and human body, with fears of harm and death. simultaneously and in another polarity, with an unknown force and with the survival instinct to the maximum, we open the virtual space in search of the exit. ª australian association of family therapy where are we going? just like before we were born, it is a mystery; however, from another perspective i know that we will look to another territory, with keys, codes, and ways of survival different from what is known. a place where we will need to put into operation new approaches that, probably without much awareness, we have developed in this previous gestation process. these are bodily, personal, group, social, and of humanity. i feel that, as in any process, we may reach the other side crying, it is also possible that we remain detained in a space 'in-between,' without being able to advance. so, as humanity we are at risk; it is the essential trust, the conscience and bonding that sustains us to arrive someday at that 'other side. ' nowadays, for me to be a therapist is to be a midwife, creating contexts that, in the intimacy of psychotherapy, allow me to accompany in uncertainty, in fear, in the pain of losses, in silence and respect for the expression of grief. i trust that the strength of the bonds will allow us to be born to other unimaginable dimensions from the prisms in which we contact today. i only miss hugging my son and daughter. i carry with me the nostalgia and smell of their bodies. the loneliness of the therapist . . . my being a therapist cuts across the many roles i carry out. with maturity and conscience, the person of the therapist talks and integrates with my entire person. on one level, i feel lonely, but, on another, it is a joy to feel the strength of the bonds of systemic therapists around the world to reach out. this unique practice collection offers readers a glimpse into the professional and personal experiences and reflections of an international group of family and systemic therapists across the globe as they experience the first phase of the covid- pandemic. the world is navigating through unpredictable times. therapists need to 'be,' before they can 'do.' systemic therapists are able to heal and in turn support the healing of the families, couples, and individuals they work with through the process of reaching out to fellow therapists in shared experience. it is only then they can contemplate stepping into a next phase; the 'regenerative process' where they can rebuild their lives post-pandemic. there needs to be time to pose and consider; whether the familiar pre-pandemic 'normal' is the 'normal' that is desperately sought . . . or in fact whether this calls for the creation of new opportunities for social change. the pandemic illustrates the reality that society remains at its essence 'collectivist.' we are all in this together, as a collective humanity. it is evident humans are inter-dependent on one another. there is an inescapable inter-connectedness and relationship between systems, within the body, between one another; humanity cannot separate from the environment, just as therapists cannot separate from their families or fellow therapists. this crisis may assist therapists to rearrange the scale of values regarding what is important. beyond the interventions used, preservation of the relationship is what really matters. it seems ironic that an enforced need to 'stay apart' from one another (in order to stay alive), has birthed an invitation to be more human (in order to stay emotionally and relationally alive), and be closer to each other than ever before. this collection illustrates now more than ever the importance of looking at the 'macro' issues presenting for people and society from a systemic perspective. the more complex the issues, the more important they be considered and addressed through a systemic lens. approaching these complexities from a sequestered, individual perspective is reductionist, invalidating, unrealistic, but also disrespectful to other cultures. this present challenge also causes a questioning of the notion of permanence and certainty to give room to impermanence and uncertainty; while distressing, and unsettling, this provides opportunities. this is an unpredictable and crucial time. if there has ever been a need for systemic therapists and the 'world of systems' to advocate for systems change, this is the time. humanity is part of a system that can destroy it in a short time if it does not listen to the feedback that comes from the interaction with the other elements of that system. as the pathway to the 'other side' is navigated, there is a need to value context, culture, collaboration, and connectedness in order to combat isolation and trauma while enhancing unity. together we can begin to think about some of the implications and recommendations for family therapy practice and research in relation to covid- . first, family and systemic therapists are in a key position to advise stakeholders such as governments and health departments in developing and implementing a response to the covid- pandemic. second, there are numerous advantages to understanding the effects of the pandemic through a systemic lens. it is unrealistic, illogical, and unscientific to imagine that complex issues like covid- can be considered simply by focusing on individuals. third, this suggests an integrated approach to the management of pandemic trauma and suicide prevention utilising 'systemic thinking' as a foundation. future collaborative research could focus on: the collective nature of trauma to consider the consequences of traumatic events shared by a 'social collective,' and how this may differ from 'interpersonal trauma'; mental health consequences that take into account the impact of pre-existing and co-existing mental health issues; the relational consequences of covid- in exploring whether collective traumas create greater resilience given the collective shared experience; further rigorous qualitative and phenomenological studies to capture the experiences of family therapists honouring different cultural backgrounds and languages. associate professor of psychology, subprogram in clinical psychology, department of psychology director of the paduan center of family therapy, academic of the milanese center of family therapy. email: mosconia @gmail.com member ipscan (international society for prevention of child abuse and neglect il multi-linguaggio e il multi-tempo dell'amore: il lavoro con le coppie interculturali (the multi-language and the multi-time of love: work with intercultural couples). paper presented at the convegno residenziale apf 'il processo terapeutico. tempi e fasi della terapia familiare my story, your story: the role of culture and language in emotion expression of cross-cultural couples. the mi culture model reflection on aaft family therapy conference getting together with like minded people': a conference edition habla mi idioma? an exploratory review of working systemically with people from diverse cultures: an australian perspective children in the margins training the person of the therapist in structural family therapy mind and nature: a necessary unity el apego (attachment). barcelona: paid os treating complex traumatic stress disorders: an evidence-based guide revisione dei concetti di ipotizzazione, circolarit a, neutralit a: un invito alla curiosit a (hypothesizing, circularity, and neutrality revisited: an invitation to curiosity) autoethnography, personal narrative, reflexivity: researcher as subject hypnotherapy: an exploratory casework getting a kick out of you: the jazz taoist key to love the new normal: living with a transformed reality the helpers and the helped: viewing the mental health profession through the lens of love in action: an integrative approach to last chance couple therapy the tao of love: life lessons learned from laotzu and the way of life suicide risk and prevention during the covid- pandemic integrating a trauma lens into a family therapy framework: ten principles for family therapists the five stages of grief the way of life one service, many voices: enhancing consumer participation in a primary health service for multicultural women the use of self of the therapist families and family therapy v ınculo, percepci on y conciencia en la coordinaci on grupal: la persona del coordinador (link, perception and consciousness in group coordination: the person of the coordinator) g enogramme et inceste: tempo th erapeutique et tempo judiciaire, in i les g enogrammes aujourd'hui la clinique syst emique en mouvement quand la famille marche sur la tête: inceste, p edophilie, maltraitance (when the family walks on your head: incest, pedophilia, abuse) la fin des certitudes. temps, chaos et lois de la nature (the end of certainties. time, cahos and the laws of nature) how family therapy stole my interiority and was then rescued by open dialogue memory, trauma, and phantasmagoria in claudia llosa's 'la teta asustada paradosso e controparadosso. un nuovo modello nella terapia della famiglia a transazione schizofrenica (paradox and counterparadox. a new model in schizophrenic transaction family therapy) ipotizzazione, circolarit a, neutralit a: tre direttive per la conduzione della seduta (hypothesizing, circularity, neutrality: three guidelines for the conductor of the session) la red social: frontera de la pr actica sist emica observing systems the authors look forward to further systemic themed papers on the family therapy response to covid- such as focusing on the regenerative phase of the pandemic and the reporting of practice and practical responses. lyndon amorin-woods for assistance in preparation of the draft manuscript.